Proceedings of

The Symposium on

International Health and Medical Ethics

—Harvard SPH Takemi Symposium—

December 1st and 2nd, 2000

Tokyo

Hosted by Japan Medical Association

Harvard School of Public Health

Supported by Japan Pharmaceutical Manufacturers Association

Japan International Cooperation Agency (JICA)

Proceedings of The Symposium onInternational Health and Medical Ethics

—Harvard SPH Takemi Symposium—

CONTENTS

December 1st (Friday), 2000

Greetings:

Eitaka Tsuboi . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5President, Japan Medical AssociationPresident, World Medical Association

Barry R. Bloom . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6Dean, Harvard School of Public Health (HSPH)

Michael R. Reich . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7Professor, Harvard School of Public Health

Special Address:

“Ethical Issues in Global Health Research”

Barry R. Bloom (HSPH) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

December 2nd (Saturday), 2000

Keynote Address:

“Ethical Analysis in Public Health”

Michael R. Reich (HSPH) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

Takemi Fellow Presentations:

First Session —Morning—

“Ethical Issues Raised by Smoking”

Lecturer: Prakash C. Gupta (TF 1984–85, India) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19

Commentator: Luiz Augusto Facchini (TF 1996–97, Brazil) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23

“Health and Medical Ethics in Taiwan:“New Century, New Challenges and New Thinking”

Lecturer: Chung-Fu Lan (TF 1986–87, Taiwan) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24

Commentator: Bimo (TF 1991–92, Indonesia) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28

“Where Shall We Die, In the Hospital or At Home?“—Past, Present and Future Perspectives of Community Medicine in Japan”

Lecturer: Eiji Marui (TF 1986–87, Japan) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29

Commentator: Lola Dare (TF 1999–2000, Nigeria) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32

“Ethical Concerns in the Dietary Supplements Business”

Lecturer: Khor Geok Lin (TF 1988–89, Malaysia) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33

Commentator: Prakasamma Mallavarapu (TF 1992–93, India) . . . . . . . . . . . . . . . . . . . . . . . . . . . 36

Comment for First Session:

Nii Ayite Coleman (TF 1996–97, Ghana) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38

Second Session —Afternoon—

“The Ethics of HIV/AIDS: A South African Case Study”

Lecturer: William M. Pick (TF 1990–91, South Africa) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40

Commentator: Maha El-Adaway (TF 1997–98, Egypt) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42

“Protection of Intellectual Property Vs. Protection of Public Health:“Ethics and Politics”

Lecturer: Sauwakon Ratawijitrasin (TF 1995–96, Thailand) . . . . . . . . . . . . . . . . . . . . . . . . . 44

Commentator: Jin Hyun Kim (TF 1996–97, Korea) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46

“Antimalarial Drugs: Attractive Innovations, Tough Choices”

Lecturer: Allan Schapira (TF 1987–88, Denmark) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47

Commentator: Siripen Supakankunti (TF 1996–97, Thailand) . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53

“Policy on Drug Distribution in Korea—A Challenge to the Welfare State—”

Lecturer: Bong-min Yang (TF 1989–90, 95–96, Korea) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55

Commentator: Kanchanasak Phonboon (TF 1986–87, Thailand) . . . . . . . . . . . . . . . . . . . . . . . . . . 58

Comment for Second Session:

John Bertie Mendis (TF 1991–92, Sri Lanka) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59

General Comment:

Michael R. Reich (HSPH) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60

The Symposium onInternational Health and Medical Ethics

Harvard SPH Takemi Symposium

December 1st and 2nd, 2000Japan Medical Association Office, Tokyo

Main Theme

“International Health and Medical Ethics in the 21st Century”

Hosted by Japan Medical Association (JMA)Harvard School of Public Health (HSPH)

Supported by Japan Pharmaceutical Manufacturers AssociationJapan International Cooperation Agency (JICA)

December 1st (Friday), 2000 at the JMA Auditorium (1F)

Facilitator: Dr. Hokuto Hoshi (Executive Board Member, JMA)

–Special Address and Reception—

18:00�18:05 Greetings . . . . . . . . . . . . . . Dr. Eitaka Tsuboi (President, JMA, WMA)

18:05�18:45 Special Address . . . . . . . . . Dr. Barry R. Bloom (Dean, HSPH)Chair: Dr. Akira Koizumi (Vice-President, JMA)

18:45�19:00 Q&A

19:00� Reception at the JMA Hall (3F)

December 2nd (Saturday), 2000 at the JMA Auditorium (1F)

Facilitator: Dr. Hokuto Hoshi

First Session —Morning—

9:00� 9:10 Opening Remarks . . . . . . . Dr. Eitaka Tsuboi

9:10� 9:20 Welcome Address . . . . . . . . Dr. Barry R. Bloom

9:20�10:00 Keynote Address . . . . . . . . Dr. Michael R. Reich (Professor, HSPH)Chair: Mr. Keizo Takemi (Member, House of Councilors)

10:00�11:00 Presentations . . . . . . . . . . . Takemi Fellows

11:00�12:00 Discussion . . . . . . . . . . . . . Takemi FellowsChair: Dr. Akira Koizumi

12:00�13:00 Lunch

Second Session —Afternoon—

13:00�14:00 Presentations . . . . . . . . . . . Takemi Fellows

14:00�15:00 Discussion . . . . . . . . . . . . . Takemi FellowsChair: Dr. Akira Koizumi

15:00�15:20 Break

15:20�15:40 Comments by Chair Dr. Akira Koizumi

15:40�16:00 Closing Remarks . . . . . . . . Dr. Michael R. Reich

Adjournment

Time Schedule

5

Eitaka Tsuboi

President, Japan Medical AssociationPresident, World Medical Association

On behalf of the Japan Medical Association, I would like to offer my heartfelt appreciation

for the cooperation of the Harvard School of Public Health in organizing this important sympo-

sium on the problems of medical ethics in international health. I would also like to acknowledge

the generous support for this conference offered by the Japan Pharmaceutical Manufacturers’

Association and the Japan International Cooperation Agency.

Takemi Program in International Health was established in 1983 on the basis of an agree-

ment between the late Dr. Taro Takemi and Professor Hiatt, former Dean of the Harvard School

of Public Health. It was designed as an academic and practical program in the United States for

specialists, primarily from developing countries, to conduct research activities on public health

issues related to the development and distribution of scarce medical resources.

This symposium was planned with the grand goal of assembling former Takemi Fellows,

many of whom have great influence in the field of international health, in a place where they can

meet and exchange information about issues in the twenty-first century. I am aware that the role

played in international society by the Program is already widely known. I hope that through this

seminar, it will contribute greatly to international health on a global scale in the 21st century.

I also expect that the Takemi Program, which has a global impact, will be even more

successful, under the excellent leadership of Dean Bloom and Professor Reich, and that the Japan

Medical Association will continue its strong support for the Program.

Greetings

6

Barry R. Bloom

Dean, Harvard School of Public Health

It is my pleasure, on behalf of the Harvard School of Public Health, to express my enormous

appreciation to the Japan Medical Association for hosting this important meeting on ethics and

international health, in collaboration with the Takemi Program in International Health. The

Takemi Program represents an extraordinary partnership in providing a special educational and

research experience for outstanding health professionals who have great potential for leadership

in health around the world. At every international meeting on health that I attend, I meet former

Takemi Fellows, who express their appreciation for their Takemi experience at the Harvard

School of Public Health. It is gratifying that so many of them have achieved positions of leader-

ship in their countries. As Dean of the Harvard School of Public Health, I wish to express my

special appreciation for President Tsuboi and his colleagues at the JMA, who have been so

dedicated in supporting the Takemi Program at Harvard. I am grateful for your generosity in

hosting this meeting that brings together many Takemi Fellows to address a major issue in

medicine and international health.

With the extraordinary advances in medical science, there are unprecedented opportunities

for the development of new drugs, devices and procedures that will improve the health and

quality of life of millions of people around the world. But to learn which of those advances is

promising and safe, there will be a great need for clinical trials with many volunteers in countries

around the world. For the medical community to maintain its respect and credibility, it is essential

that the fundamental ethical principles expressed by the Declaration of Helsinki be honored and

applied to our contemporary world. President Tsuboi is a world leader in placing ethical concerns

at the top of the global health agenda, and this meeting sponsored by the JMA and the Takemi

Program is an important one for all of us. Professor Michael Reich, Director of the Takemi

Program, and I are most grateful for the opportunity for the Harvard School of Public Health to

participate, and we look forward to a stimulating and important meeting.

Greetings

7

Michael R. Reich

Taro Takemi Professor of International Health PolicyChair, Department of Population and International HealthHarvard School of Public Health

As Director of the Takemi Program of International Health, I would like to express my

appreciation to President Tsuboi and all members of the Japan Medical Association who have

made possible this Symposium on International Health and Medical Ethics. The Takemi Program

was established at the Harvard School of Public Health in 1983, and accepted its first group of

Takemi Fellows in 1984–85. Since that time, 140 Takemi Fellows from 42 countries around the

world have participated in the program, including 24 from Japan. The program was initiated with

the vision of Dr. Taro Takemi about the importance of interdisciplinary research to improve the

health of people around the world—through the idea of a partnership between Japan, the United

States, and developing countries.

Remarkably, the Takemi Program has continued for these 17 years, through the dedicated

efforts of many people in Japan. President Tsuboi, as Chairman of the Japan Committee for the

Takemi Program, has provided important support to the Takemi Program and its Takemi Fellows.

In addition, I would like to express my appreciation to Dr. Toshitsugu Oda of the Japan Founda-

tion for the Promotion of International Medical Research Cooperation, and the other members of

the Japan Committee for the Takemi Program. We are grateful for assistance provided by the

Japan Pharmaceutical Manufacturers Association and by the Japanese Ministry of Health and

Welfare, and by many individuals associated with these two organizations. The Honorable Keizo

Takemi and his family have assisted our efforts to assure the continuity of the program named

after his father. In addition, the Takemi Program and Takemi Fellows have received financial

support from many international organizations, private foundations, and private corporations

around the world.

This Symposium marks a special event in the history of the Takemi Program in Inter-

national Health at Harvard. We are pleased that so many Takemi Fellows could attend the

Symposium—through the generous contributions of the Japan Medical Association and the

Japan International Cooperation Agency—to share their thoughts on international health and

ethics. We would like to express our heartfelt appreciation to all who have made possible the

existence and continuity of the Takemi Program.

Greetings

8

Ethical Issues in Global Health Research

Barry R. Bloom

Dean, Harvard School of Public HealthBoston, MA, USA

Special Address

It is an enormous privilege for me to presentan opening speech at this very important sympo-sium. I would like to say that part of the inspira-tion for the subject was the efforts of Dr. Tsuboiand the World Medical Association in reconsider-ing and revising the major ethical guidelines.And it seems like a very appropriate subject toconsider at this time.

Let me begin with a brief history of ethicalconsiderations in biomedical research. It is a sadfact that the first real codification of ethical prin-ciples occurred only after devastating experi-ments were done on human beings during theSecond World War without their knowledge orpermission. As a consequence, at the NurembergWar Crimes Tribunal in 1947, it was not themedical profession, but the juridical profession—three judges, to be precise—that set up thefirst policies for medical research. The frame-work in which the ethical guidelines were devel-oped is illustrated in Article 7 of the Inter-national Covenant on Civil and Political Rights,which states, “No one shall be subjected to tor-ture or to cruel, inhuman or degrading treat-ment or punishment. In particular, no one shallbe subjected without his free consent to medicalor scientific experimentation.” By linking thesetwo sentences, the foundational documents ofmedical ethics associated biomedical researchwith torture, degrading treatment and punish-ment. Thus we are left with the challenge of con-vincing the global public that our work is actu-ally inspired by only the highest motivations.

The realization that this framework was in-adequate began in 1964 with the Declaration ofHelsinki which was designed by physicians andmedical scientists, overseen by the World Medi-cal Association, to try to set meaningful guide-lines for the practice of medical research. Thereare several important principles that underlieall successive guidelines that were originally put

into the Declaration of Helsinki, and this, Ithink, is from the most current revision releasedearlier this year, in the year 2000, which states,“It is the duty of the physician in medicalresearch to protect the life, health, privacy anddignity of the human subject.” And, “In medicalresearch on human subjects, considerationsrelated to the well-being of the human subjectshould take precedence over the interests ofscience and society.” Thus, no matter how im-portant a scientific question is, according tothe current ethical guidelines, it has to be inthe interest of humanity and individuals tojustify putting human subjects at risk for anyexperimentation.

These guidelines were formulated initially in1964, and I know through personal communica-tion with members of that original committeethat the possibility of conducting serious bio-medical research in developing countries wasnever considered. Almost all of the originalguidelines were relevant only to the industrial-ized countries of the time, although the worldwas rapidly changing and evolving. As the econo-mies and educational status of people in develop-ing countries have changed dramatically, theguidelines have been revealed to be inadequateto address all the critical issues faced by bio-medical researchers working with human sub-jects. In 1982, together with the World HealthOrganization, the Council for International Or-ganizations of Medical Science (CIOMS) con-vened to reinterpret or redefine the HelsinkiDeclaration guidelines for human experimenta-tion done in developing countries. It should benoted that this was meant to be a clarification,not a replacement or amendment of the Declara-tion of Helsinki.

In these 15 guidelines and commentaries theaim is to indicate how ethical principles underthe Helsinki Declaration could effectively be

(December 1st, 2000)

9

applied to developing countries. While not themost important of the declarations or reports inconsidering biomedical research ethics, there isone from the United States that in a very suc-cinct way defined the fundamental principlesthat are underlying all of the other reports andguidelines. Since they are so clear, I thought itmight be useful simply to summarize those prin-ciples. The first is respect for persons, that is,respect for autonomy and self-determination. In-dividuals must have the power and the right todetermine whether they will or will not be sub-jects for biomedical research. Secondly, researchshould adhere to the principle of beneficence, orhaving the purpose of doing good, maximizingbenefits and minimizing potential harms experi-enced by the human subjects. And finally, thethird principle in ethical experimentation inhuman subjects is that of justice, particularlywith regard to products or knowledge thatresults from such biomedical research. Thereshould be an equitable distribution of boththe burdens and benefits of participation inresearch. People who do participate in researchshould be entitled to some benefits that derivefrom that and should not simply be used asexperimental subjects to benefit some othergroup of people.

All of the existing guidelines in my judgmenthave had a fundamental limitation until thisyear. They are silent on the issue of the economicand technical capacity of either the trial popula-tion or the host country to implement the recom-mendations. Starting in 1998 the committee thatI chair at the United Nations Joint Program onAIDS (UNAIDS), the Vaccine Advisory Commit-tee, together with the UNAIDS Ethical AdvisoryCommittee held a series of workshops and hear-ings in Geneva, Thailand, Uganda, Brazil, andWashington, sampling the views of 160 partici-pants from 37 countries. At these meetings theparticipants were asked about the issues orproblems that would be presented by the exist-ing guidelines for ethical research if an AIDSvaccine were to undergo clinical trials. Given theassumption that no vaccine has ever workedperfectly in the first trial, there would have to bemultiple trials of the vaccine. It would also meanthat in the early trials it is almost certain thatthe vaccine would not protect some people untilimprovements were made.

The UNAIDS Committee considered fivemajor issues, of which I will touch on only four:the issue of individual informed consent, the

issue of vulnerable populations, the issue of thebest diagnostic and therapeutic method and theissue of reasonable availability in vulnerablepopulations. Until these discussions, the focus ofconcerns in most of the ethical guidelines was on‘underdeveloped countries,’ the language used inthe original Helsinki Declaration. Much of therecent dialogue has dealt with guidelines thatwould be more relevant to the realities andconditions in developing countries than thosein developed countries. In our deliberations,however, we became much more aware that theterm “developing countries” encompasses a verywide spectrum, ranging from extremely poor tomiddle-class or higher in socio-economic status,and, in fact, “developing countries” was not asingle entity but a continuum. Thus, the aspectof research on developing country populationsthat the committee chose to emphasize wasnot on their being developing populations, butrather vulnerable populations; vulnerable toexploitation and vulnerable to harm.

Our discussions revealed that vulnerabilityis defined in a variety of ways. One apparentlevel of vulnerability is in the realm of economiccapacity. To measure this we suggested using theUnited Nations Development Program’s HumanDevelopment Index, which ranks countries ontheir standards of education, development andeconomic status. Second is vulnerability in thecontext of lacking in community and culturalexperience with scientific research. Third is lack-ing in local infrastructure and technical capacityfor producing health care and treatment optionseven if AIDS vaccine trials were done. Finally, forconducting the proposed research, was theretechnical capability and ability to provide genu-inely free informed consent. And finally, did apopulation have the capacity for conducting ethi-cal and scientific review? And if the answer toany of those criteria was no, that suggested thatthe population was by definition a vulnerableone, and special care had to be taken to makesure that the research would be of the highestethical standard.

On the issue of informed consent, we oftenconsider it a certainty that every individual hasthe right and, in fact, necessity for autonomy andability to give individual informed consent as itis in the most advanced industrialized countries.However, in many parts of the world individualinformed consent is not only unimportant, but itcould be harmful to individuals, for instance, insocieties where village leaders are traditionally

10

the decision-makers and should not be under-mined by individuals. As would be expected, westruggled with that criterion, and eventuallycame up with a useful recommendation. In somecommunities it is customary to require authori-zation of a third party, such as a communityelder, to enter the community in order to inviteits individual members to participate in re-search. We recommended that such authoriza-tion may not be used as a substitute for indi-vidual informed consent. What this says is thatin those cultures where a village elder has greatpower, it would be inappropriate for research tobe carried out on any individual without the con-sent of the elder. But if the elder does give con-sent, then the fundamental principle of Helsinkiand all other ethical guidelines must be adheredto and all individuals must be free to choosewhether or not to be subjects of research.

The most contentious issue in the HelsinkiDeclaration in its original formulation had to dowith the standard of care of a subject who be-came ill during the course of the research. Theoriginal wording of Article 23 says that in everymedical study, every patient, including those in acontrol group, if any, should be assured the bestproven diagnostic and therapeutic method.When we considered this in the context of HIV/AIDS in a country in Africa, for example, likeUganda, the best proven treatment became avery huge problem. If one assumes that the sero-prevalence was about 20%, and the per capitaexpenditure on health was about US$6 per per-son per year, and the best proven treatment,which would be high activity anti-retroviraltherapy combination chemotherapy, would costUS$15,000 per person per year, there was nopossibility that this country and many otherdeveloping countries around the world couldafford the best proven treatment. This issue con-tinues to inspire great debate among the medicaland ethical communities all over the world.

In a recent draft of the U.S. National Bio-ethics Advisory Committee, “the best proventreatment” was removed and replaced with thewords “established effective treatment” in orderto best convey what is owed to research partici-pants. The recommendations of the UNAIDSethical advisory committee were inspired by thepreamble to the World Health OrganizationCharter or Constitution which says “The enjoy-ment of the highest attainable standard ofhealth is one of the fundamental rights of everyhuman being, without distinction of race, reli-

gion, political belief, economic or social condi-tions.” The concept of “the highest attainablestandard” has also been enshrined in the Eco-nomic and Social Rights Convention, ascribingmeaning to it that is important in the context ofethical biomedical research. As such, the finalwording of the UNAIDS recommendations was“In the ideal case, one should try to provide thebest proven therapy. Where that is not possible,the minimum would be to provide the highestlevel of care that is attainable in the host coun-try.” In essence this means, some level of carebetter than common or routine care for thoseinvolved in the trial, but not necessarily the mostexpensive, best proven treatment anywhere inthe world. In many respects, the simplest formu-lation of this concept, and perhaps the most use-ful, has been articulated in the recent revision ofthe Helsinki Declaration which says that “Inevery medical study every patient, includingthose of the control group, if any, should beassured of proven effective prophylactic, diag-nostic and therapeutic methods.” The word “best”has been replaced with “proven” effective treat-ment for any aspect of the condition. This changeis clearly a recognition, by all of the relevantbodies, of the importance of meeting the prac-tical needs as well as the ideal needs of volun-teers for human experimentation in developingcountries.

The CIOMS guidelines have a very specificphrase that has been long ignored in biomedicalresearch which says that “Externally-sponsoredresearch must be responsive to the health needsof the host country. As a general rule, any prod-uct developed through such research will bemade reasonably available to the inhabitants ofthe host community or country at the completionof successful testing.” This is very seldom done. Atrial is carried out in a developing country, aproduct is either effective or not, and there is noprovision for making that effective treatmentavailable to the population that took the risks ofvolunteering for such a trial. I am very pleasedthat in the current revision of the Declaration ofHelsinki, it says “At the conclusion of the studyevery patient entered into the study should beassured access to the best prophylactic diagnos-tic and therapeutic methods identified by thestudy.” So if there are multiple arms to a study,whichever one has the best results then has to bemade available in an ethical way to the popula-tion that was involved in the study. Here I wouldjust add a thought from the UNAIDS document

11

which says that “Plans should be developed atthe initial stages of HIV vaccine” or, I would sayany “clinical trial, to ensure such availability.” Itis well known that if plans are not made at thebeginning of a study, it is very difficult to guaran-tee availability at the end.

Thus the abiding question is: who is respon-sible for making those products available to thepopulation? The current understanding is thatthe responsibility for providing access to theproven treatment or therapy lies on the manu-facturer or the pharmaceutical company thatcarries out the trial. However, the world ischanging. Very few trials are carried out by onlyone sponsor. Many trials are now being carriedout by people who are not sponsors. These arecontract research organizations that are hiredby companies solely to design and carry outtrials. The UNAIDS document said that tradi-tionally the sponsor has been thought of as asingle corporate entity such as a pharmaceuticalcompany. In modern vaccine development pro-grams there are commonly multiple sponsors,including one or more corporations, one or morenational governments and one or more inter-national agencies. It becomes clear then thatpharmaceutical companies are not solely respon-sible for providing or ensuring the availability ofsuccessful products, rather, in contemporarymedical research this is a responsibility sharedamong all the sponsors.

In that two-year period, I developed a per-spective on the Helsinki and CIOMS ethicalguidelines which I would like to share. The firstis that Helsinki’s and CIOMS guidelines areuniversally respected and should not be changedlightly. But the documents must be living docu-ments that evolve to encompass and provideguidance for changing realities and globalhealth, like the problem of AIDS, and the neces-sity of carrying out trials in countries whereAIDS is most prevalent. Also, the recognitionthat thoughtful people of good will may and oftenwill disagree on ethical judgments. And finally,when those disagreements occur there is cur-rently no forum anywhere in the world for re-viewing independently and providing resolutionfor disputes about international ethical issues,and I believe such an international agreementon how to resolve disputes is urgently needed.

Now these are the kinds of ethical consider-ations that have been undertaken and some ofthe major issues of contention. But the context inwhich biomedical research for trials in develop-

ing countries is changing and worrisome. Theincome gap between the richest and poorestcountries is ten times greater in the year 2000than it was in 1970. There are a hundred millionmore people in the world living in poverty,defined as living on one dollar a day or less. Theaverage salary in the wealthiest 20 countries isabout US$25,000 a year, and the average incomein the 20 poorest countries is 50-fold less. Thedisparities are increasing. I have a thesis, andthe thesis is stated simply as follows. There wasa very famous politician, the Speaker of theHouse of Representatives from my state namedTip O’Neill, and his wonderful philosophicalview of politics was that all politics is local. Itend to agree. I believe that all health care andhealth care systems are national, and thatincludes essential national health research. Andthat leads me to the view that all health researchis global. What do I mean by health research andglobal health research? The first is that globalhealth research is done by individuals and insti-tutions, it is not done by nation-states and is notrestricted within the boundaries of a nation-state. And global health issues are problems,issues and concerns that transcend nationalboundaries and may be best addressed by shar-ing knowledge and cooperative action. That iswhat I mean by global health research.

In that sense, global health research is a pub-lic good. To economists a public good means agood that is not owned by the place or the inven-tor, but is useful for many other people otherthan those who produced the product or knowl-edge. And that is the essence of the knowledgederived from biomedical research. That researchis done in a changing world with increasingglobalization, multinational corporations, inter-national pharmaceutical and vaccine companies,contract research organizations hired to do trialsand health management organizations spreadingaround the world to control the costs of healthcare and to deliver health care in a different waythan traditionally. There are new infectious dis-eases and reemerging infections. There is globaltransfer of toxins, of poisons, of environmentalrisks, and the net result is that the gap betweenthe rich and the poor at the level of health andscience and technology is increasing. All of thatis the context, then, to look at the new advancesand new approaches in biomedical science.

The pinnacle of those new approaches is theHuman Genome Project, probably the mostexciting project in the history of modern biology.

12

But if one looks at the focus of the HumanGenome Project, it is mostly dealing with prob-lems of the rich countries, it deals primarily withnon-communicable diseases—cancer, cardiovas-cular disease and psychiatric disease. On this Iwould make two points. The first is, there is aportion of the Human Genome Project thatis devoted to pathogen genomes, and therehave been 22 pathogen genomes completelysequenced, many of which are pathogens like thetubercle bacillus, other bacterial pathogens thatprimarily afflict people in developing countriesthrough such illnesses as cholera, typhoid feverand leprosy. The second point would be whilethere are big differences between the diseases ofdeveloping countries and industrialized coun-tries, there is a tendency towards convergence,so that 20 years from now chronic diseases willbe the major problem in both sets of countries.The Genome Project is of extraordinary interestbecause if epidemiology has defined the externalrisks to health, the Genome Project is going todefine intrinsic risks that each of us has, uniquerisks for disease. And it will do so using unbeliev-ably sophisticated technologies, such as geneexpression and micro-arrays, and DNA chips.The amount of information is so complex thatthe human mind and the eye simply cannot putthem together intuitively or practically. There-fore, one needs a whole new discipline of bio-informatics, and one needs large populations tolook at subtle differences between individualsthat control the degree of susceptibility.

A DNA chip is smaller than my wristwatchand holds 8,000 genes. A slightly larger chip con-taining 16,000 genes was used to study patternsof genes turned on and off in human cancers. Byusing complex informatics and computer analy-sis, it is possible to group individual tumors anddemonstrate that all the tumors of melanomashave a very consistent pattern, quite differentthan the pattern for lymphomas. And from thiskind of analysis it is possible by using purelymolecular technology to take even a single tumorcell and define the nature of the tumor and dis-tinguish at a molecular level between a mela-noma, a lymphoma, colon cancer, etc. More im-portantly, it is now possible to look at the geneexpression patterns, for example, of breast can-cers, and predict which will survive currenttreatment for more than five years and whichindividuals will die in short times, even with thebest current treatment. And that enables us todetermine which individuals will not succeed in

treatment and should try new and experimentaltreatments. And this is at a level, in the breastcancer case, that no pathologist is able to distin-guish between these two types of tumors.

The possibilities are immense. There willbe many positive outcomes from the HumanGenome Project. There will be the developmentof bio-markers, markers, genes, color tests,enzymes, that indicate the kind of tumor or thekind of circumstance or the kind of disease thatwill lead to a great deal more opportunities fordiagnosis earlier and more definitively. Thedefinition of the structure of the gene predictsthe structure, to an extent, of the protein andwill enable the development of many new drugtargets. A new kind of chemistry is capable ofproducing in a small laboratory 50,000 new com-pounds a week, more than a major drug companywould have been able to produce in a year justfive years ago.

The first two vaccines derived solely from theGenome Project have been developed, where theDNA sequence was read, inferences were madeabout what would be antigenic fragments, pep-tides were synthesized and shown to be protec-tive in mice against Neisseria meningitis andagainst streptococcus pneumonia, two majordiseases in desperate need of vaccines.

I’m very optimistic about stem cell therapy,where it is possible to take early stem cells fromembryos—but five years from now probablyfrom blood or bone marrow without the need forembryos—and to replace damaged tissue, as inthe case of myocardial-infarcted tissue or dam-aged tissues in other organs, for example, in thecase of multiple sclerosis, and produce new cellsthat function in the exact environment. Genetherapies will be developed, they will be devel-oped primarily for single gene defect diseases,inborn errors of metabolism. It will be harder toget them to work than stem cells because thegene will be more difficult to regulate up anddown as it would in a normal cell, but it will bea major advance. And from this, great numbersof new drugs will be developed so that one couldimagine the day a child is born in a rich country,their DNA would be put on a chip and it wouldbe possible in a matter of hours to predict allthe intrinsic risks for susceptibility to disease—cancer, heart disease, Alzheimer’s disease, andthen at day five of life provide a cocktail of drugsto prevent those risks from developing. And onehas the nightmare of every child for the rest ofits entire life taking between 50 and a hundred

13

pills a day to prevent against all of the intrinsicrisks. Whatever that is, that will not be the lifeenvisioned by a child that grows up in a develop-ing country.

But even the power of the genome causesreally extraordinarily interesting problems. Forexample, estimates are that there are about80,000 genes in the human genome. Perhaps allof them or only half of them are functional. Atthe present time, if one looks at all the drugs inthe world for which we know the target of thedrug, there are only 479 defined targets for allthe existing drugs. And we know that 40% of thenew molecular entities or drugs are ‘me-too’drugs that actually work on one of those alreadyexisting targets. So if one assumes that maybe10% of the human genome will represent newtargets for drugs, how will the pharmaceuticalindustry be able to make ten to twenty thousandnew compounds? It is not clear. And if drug costsare the major cost to the health systems, both inJapan and the United States, where drug costsare rising at the rate of 18% a year, what do wedo if we have 10,000 new drugs and how will wecontrol the costs and ration access to new drugs?

Finally, the genome is going to be helpful per-haps in predicting risks for adverse effects.Many of you know that the only drug for treatinginflammatory bowel disease recently has beenremoved from the market because three peopledied. When hundreds of thousands of peoplereceive a drug and only three people die, it maybe that those three people have a special geneticpredisposition for adverse effects. The GenomeProject may make it possible for the pharmaceu-tical industry to predict those people who havethe greatest risk for adverse effects, as well aspredicting who will respond well and who willnot to new drugs.

The Genome Project has predictable risks,however, that have ethical implications. One isthat, as I suggested, with many new targets fordrugs and many new drugs, drugs will be tai-lored to the individual, not to populations. Andthis will lead to what I call “boutique” medicine,individually-tailored pharmaceutical and othermedical interventions. There will be an exploita-tion of populations in developing countries forresearch and clinical trials who may not benefitfrom that research when it is carried out on con-tract. There is a danger when the risks for dis-ease are made available that insurance compa-nies will adjust their risks and exclude peoplefrom the day they’re born because they may have

some genetic predisposition for one disease oranother. There may be discrimination, againbased on genetic risks, in jobs, marriage andhousing. And all of the information on anyone’sgenome poses great threats to privacy andconfidentiality. And finally, with all the good thatthe Genome Project will do, it is almost certain toincrease the gap between the rich and the poorcountries. And it is a major responsibility, I be-lieve, of the medical and scientific communitiesto seek population-based treatments like vac-cines, like drugs such as aspirin that could begiven to people no matter what their economicstatus is, that would have wide application. Butthat is not the current trend.

The next revolution in parallel and succeed-ing the genetic revolution will be in behavioralresearch and the brain itself. We now can show aman thinking, with a positron emission tomo-graph (PET) scan. From the point of publichealth we have an awareness now in the U.S.that 50% of all the annual debts are due to be-havioral problems, that is tobacco, poor diet, lackof exercise and preventable injuries. Fifty per-cent of people who die in the U.S., were they tochange their behavior, would not die in this givenyear.

We have also learned that while we believethat behavior is one’s individual responsibility, itis really not. The advertising industry is verywell aware of that fact. Behavior is socially pat-terned. In the health business, one cannot sim-ply target only high-risk individuals. One has totarget the society and the culture. And there’s aneed to engage better than we do with the mediaand the communications people who know howto reach the public and have a major role in in-creasing tobacco, poor diet and lack of exercise.

Now with the new biology and the newgenetic therapy, what is the best we could hopefor countries that cannot now provide even exist-ing vaccines and essential drugs to their popula-tions? My hope is that it will be possible from theGenome Project to provide better and cheapertools for prevention and treatment, particularlyat the population level. But we have to think atthat level to make it happen. I would hope thatit would stimulate local and regional researchand industry in developing countries them-selves. If there are 10,000 new drug targets,seven or eight major pharmaceutical companiescannot make drugs for all of those targets. Itopens new opportunities for biotechnology andthe pharmaceutical industry in many countries.

14

Finally, I would hope when the opportunitiesbecome available and the gap between their useand the opportunities become clear, it will createa demand and mobilize resources for a globalresponsibility. All of us should take some respon-sibility to see that the advances of science be-come available to the poorest people in the world.To do that is going to be a great challenge. In myview, the way that we have to begin to thinkabout that is not on the basis of national health,but on global health. And that is to create part-nerships on the basis of mutual collaborationwithout exploitation and without imperialism.And reciprocally, those partners, developingcountry partners, must be, as we must be, ac-countable for the use of public funds in theresearch and to see that it is used in a waythat fosters the health of the most people pos-sible. We have a responsibility to learn from thebest and from the worst practices in partner-ships. What makes partnerships succeed andwhy do they fail, even though it would be ineverybody’s interest to succeed. And the hardestpart of any type of collaboration is to sustain itand to make it long lasting and long active.

I want to conclude with a small diversion of asubject that is intrinsic to everything we worryabout, which is the cost of health care and theneed for cost effectiveness and saving money.There’s a debate at Harvard, and perhaps else-where in the world, that is very clear betweenpeople who really care about health and whoreally care about development. And the debateis between people who believe that health isinstrumental for economic development. And Ithink there is a coming consensus that it is veryhard to get economic development in poor coun-tries unless one invests in health and in educa-tion. And I think that’s clear. But there is an-other view articulated by the Nobel laureate oflast year, Amartya Sen, who believes that healthhas an intrinsic value, and it is essential forallowing human beings to fulfill their potentialand their capability. And I would remind youthat the enjoyment of the highest attainablestandard of health is in the Charter of the WorldHealth Organization.

And as we worry about cost effectiveness, letme remind you that there was a very strikingexample of cost effectiveness. It was in 1348when the Black Death devastated Europe. Itkilled 50 to 70% of the urban population ofEurope. But from an economic point of view, itreduced marginal labor, it increased wages, it

opened guilds to wider membership, it stimu-lated technology, because they had to feed morepeople with fewer resources. And they had tocreate the printing press when the scribes diedand were no longer able to copy the bible, it cre-ated great universities when there was greatdisillusionment with the religious orders whocould not protect the population from the dis-ease. In essence, from an economic point of view,it was the Black Death that transformed Europefrom the medieval to a modern state. It onlykilled 50 to 70% of the urban population ofEurope. Be careful of making all judgmentsbased solely on economic considerations.

Finally, if I were to state my vision for wherewe would like to go or I would like to see therelationship between biomedical research in anethical way and developing industrialized part-nerships, it is with partnerships. There’s a ten-dency for pluralism, a thousand organizationseach doing their own good thing. I feel that is notnearly as effective as bringing them together inareas of common interest, in partnerships inwhich the whole is greater than the sum of theindividual parts. The point of these collabora-tions should not just be to produce new knowl-edge, but to use research to create knowledgethat will contribute to global equity, knowledgethat will improve rather than increase the dis-parities between rich and poor in the world. Ithink that can only be done if we understandthat everyone has an interest, a self-interest anda moral interest in taking responsibility forhealth research and generating knowledge thatbenefits everyone in the world. I would argueeach of my visions for essential global healthresearch is epitomized and exemplified by theTakemi Program, which is a true partnershipbetween Harvard University and the HarvardSchool of Public Health and our colleagues at theJapan Medical Association and the generoussponsorship of the Japan Pharmaceutical Manu-facturers Association. This symposium has beena wonderful experience for so many distin-guished people who are now gathering heretogether in Tokyo and with great pride watchingthe success of the Takemi Program, which hasbeen sustained over the years. As you will see,responsibility has been global because theTakemi Fellows have worked in various coun-tries in the world but maintained a network. AndI would say this program has been an inspirationfor me; if it could be generalized, think of how wecould change the face of the earth.

15

Ethical Analysis in Public Health

Michael R. Reich

Taro Takemi Professor of International Health PolicyChair, Department of Population and International HealthHarvard School of Public Health, USA

Keynote Address

I would like to begin with two citations fromDr. Taro Takemi on ethics. First, in 1977, hewrote, “According to a new medical ethics I havein mind, the protection of the life of an individualis the responsibility of society as a whole, and itis in such a society that the physician offers histechnology and spiritual service.” Then in 1981he wrote, “Medical ethics of the future must bebased on a global and human viewpoint. It mustbe one in which there is a meaningful relation-ship between each individual human being andthe physician at all times. I believe that we mustclearly recognize that the concept of medicalethics today is expanding to a global scale.” Thatwas nearly 20 years ago. And today I think weare witnessing the value of Dr. Takemi’s ideas aswe sit here today to talk about ethics and itsimplications globally for physicians, for publichealth, for Japan, for the United States, for thedeveloping world and for all of us.

I would like in my presentation to cover threepoints. First, I would like to speak with youabout a conceptual approach to ethics. Second,I will discuss three main categories of ethical

argument. And then third, I will present someimplications for international health policy.

Let me begin with some of the broad con-ceptual approaches. Why do we need ethicalanalysis for health policy? First, public healthproblems are not just technical problems. Tech-nical analysis alone will not give us answers tothe most important public health problems oftoday. Second, how do we decide which problemsto address? We have limited resources. It’s notpossible to address all problems at once. We needto set priorities. And third, once we’ve defined aproblem, once we have a set of solutions, how dowe decide which solution is the best one? All ofthese issues drive us to the need for ethicalanalysis. In this symposium today we’ll be talk-ing about many specific cases that requireethical analysis. We’ll talk about smoking andtobacco, we’ll talk about how the end of life isdealt with, we’ll speak about AIDS treatment indeveloping countries, pharmaceutical policy invarious aspects and we’ll talk about dietarysupplements. Each of the public health problemshere requires ethical analysis and reflection.

(December 2nd, 2000)

Fig. 1 Fig. 2

Harvard SPH Takemi Symposium Harvard SPH Takemi Symposium

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At the Harvard School of Public Health wehave had a required course in ethical analysisand public health for the past 10 years. Ethicalanalysis is considered a core competency for any-one who wants to be a public health professional.Indeed, I taught that course, along with Pro-fessor Marc Roberts, and in order to attend thissymposium I had to ask Dr. Roberts to teach twoof my classes. The course at Harvard providesthe basis for my talk today. I would like to giveyou a synopsis of some of the main ideas that wepresent in the course.

If we think about ethical analysis in publichealth it moves us beyond the doctor-patientrelationship, which is typically considered thebasis for medical ethics. If we think about publichealth we have to think about how individualsand societies confront patterns of illness in theworld. And we have to think about how individu-als and societies confront the determinants andthe consequences of those patterns. I think that,as reflected in the quotations from Dr. Takemi,he was in many ways expressing the importanceof considering public health. In doing this, how-ever, ethical theory alone is not sufficient. Why?First of all, philosophical terms often are notclearly defined. Secondly, if you want to use ethi-cal analysis to make real decisions about policyit requires practice in applying ethical theory.And thirdly, in our approach, we believe that youhave to go back and forth between ethical theoryand practical cases to understand how to useethical theory in guiding decisions about allocat-ing resources for public health policy.

There are three main categories that we usein ethical analysis. First is to say the best deci-sion is defined by the consequences of a policy onsociety. That is typically considered utilitarian-ism. The second approach says that the rightdecision depends on rights and opportunities forpeople, not on consequences. This is typically thebasis for liberalism, for rights-based thinking.The third says the right decision is defined bythe virtues of a community, by the values heldin a particular community, and this is calledcommunitarianism. I’d like to give you someexamples for these three categories of ethicalthinking. They all believe that moral truthexists, and that there is a right way to do things.They have very different ideas about what thatright way is.

In addition, each perspective has problems.Each perspective has questions that are notanswered. For utilitarians the question is how do

you measure consequences? Which conse-quences should you be concerned about? Forliberals the question is which rights do citizenshave? Which rights take priority? And forcommunitarians the question is who defines thecommunity and how are the virtues defined inthe community?

I think these three perspectives are allrelevant to Japan for several reasons. Japan isbecoming increasingly internationalized. Japanis in the process of constructing policies for inter-national health, as part of its policies for inter-national assistance. And Japanese organiza-tions, including the Japan Medical Association,including the Japan Pharmaceutical Manufac-turers Association, including non-governmentalorganizations, are all increasingly involved ininternational health.

What are the key principles for these threeperspectives? Remember, utilitarians are con-cerned about consequences. The right policy isthe policy that does the most good. What mattersis well being of people. In seeking to increasewell being, each individual counts equally, andthe best action is decided by adding up the gainsand the losses in well-being for the differentpeople. There are two broad ways to measureutility. The first says the best way to measureconsequences is to let each person decide ontheir preferences about well-being. So each per-son in the audience would say, I think that whatmatters most to me is X. This is called subjectiveutilitarianism. The second approach says weneed some experts to devise a scale and an indexto measure everyone’s well-being, these arecalled objective utilitarians, and then decide onwhat the best policy is according to conse-quences. So a health policy for a subjective utili-tarian would ask consumers about their willing-ness to pay to avoid death or disability, and thenuse the data to calculate the costs and thebenefits and the policy that has the greatestbenefits and the least costs is the one to follow.An example from the presentations today mightbe if the costs of smoking outweigh the benefits,then health professionals should try to helppeople to avoid or stop smoking. Dr. PrakashGupta will talk about this in his presentation.

Objective utilitarians might construct anindex or a scale. One of these scales is calleddisability-adjusted life years (DALYs) to mea-sure health, and it is used to calculate the impactof different policies on health. This measure isused to calculate which policy has the greatest

17

impact in saving a certain amount of health, andpriorities are then based on the cost effective-ness of different interventions. An example inthe presentations today is if certain pharmaceu-tical products will improve health at low cost,then national policy measures are justified toassure access to those drugs. This issue will bediscussed by Dr. Sauwakon in her presentationon intellectual property and public health.

Liberalism takes a totally different approach.It says each individual has the capacity to makemoral choices about life. Each individual, there-fore, is entitled to respect and each individualhas a right to certain preconditions to make thebest choices in life. This perspective emphasizesrights. And again, there are two approaches torights. One approach says the only rights thatmatter are the rights to be left alone, to be free tochoose, to be able to speak, to be able to buy andsell. This is typically called liberatarianism, rep-resented by national leaders like Ronald Reaganand Margaret Thatcher. The second approachsays that people have rights to those resourcesneeded for a reasonable range of opportunity.People have rights to a minimum standard ofliving, which is similar to the notion of thewelfare state. So a libertarian would say, forexample, that people have the right to buy andsell human organs for transplants. People havethe right to suicide and euthanasia, the rightto abortion. The priority is given to the marketand to the individual to decide what constitutesthe best life, with minimal intervention by thestate. So an example here from the presentationstoday is to what extent should governmentsintervene in the private market of dietarysupplements? This is the presentation by Dr.Geok Lin Khor. And a libertarian would say keepthe state out and let the market work. An egali-tarian liberal concerned with positive rightswould have a very different perspective. Theywould say each individual has a right to a basicpackage of health services for all citizens. Thegovernment’s responsibility is to assure thateveryone has universal access to a minimumstandard of packages of health. So, for example,they would say there’s a right to drugs for treat-ment of AIDS for the worst-off citizens of society.The role of the state here is totally different.The role of the state is to redistribute resourcesto assure fairness and to assure justice. Anexample from the presentations today is ananalysis of the rights that exist to pharmaceuti-cal products, and how the state can assure access

without excessive expenditure. Dr. Bong-minYang from Korea will talk about efforts tochange the drug distribution system in Koreaand its implications for different kinds of rights.

The third main category of ethical thinking iscommunitarianism. This approach says peoplelive in a society not in isolation. If you focus onrights too much you will disrupt social cohesion.A good society requires citizens with virtuouscharacter, and the role of society and the role ofgovernment is to instill the right virtues andpreserve a desirable social order. The questionhere is, who decides on what is virtuous? Andagain, two approaches exist. Relative communi-tarians say each society, each community shoulddecide for itself what the true virtues are, andthere will necessarily be different virtues fordifferent communities. The universal communi-tarians say no, there is one right definition, oneright set of values that apply to all people in theworld, and we can use coercion to get people toaccept our notion of the good. So, a relativecommunitarian would say local culture deter-mines local practice, even if the practice hurtshealth. So, for example, in Japan you could saythe rules for organ transplants are decided bythe Japanese community’s cultural beliefs, and ifthose practices differ from the United States, sobe it. Dr. Eiji Marui will discuss these issues inhis presentation on where to die in Japan. Howdoes a country shape its values on the place todie, and what’s the role of the community andthe role of community medicine in shaping theright policy? A universal communitarian wouldsay there is a single set of international normsfor healthy behavior, regardless of local culture.This approach does not tolerate health practicesrooted in local culture. It says there is one rightway. Similar issues are raised in the presenta-tion by Dr. William Pick on South Africa andAIDS treatment. To what extent should inter-national norms constrain national policy onaccess to drugs for AIDS in South Africa?

Now let’s turn to the implications of thisapproach to ethical analysis for internationalhealth policy. Senator Keizo Takemi told me ear-lier today that the role of an academic is to talkabout complicated theory and the role of a politi-cian is to talk about simple choices and mattersthat people can understand. I hope that some ofthese complicated ideas can be connected to realdecisions and real questions in the last part ofthis presentation.

The first implication is that you cannot do

18

international health without ethics. Indeed, youcannot do public health without ethics. Valuesare implicit in all health policy decisions, and inall policies for international health. In addition,we believe that it is important to address thosevalue choices explicitly.

The second is that conflicts in values oftenoccur in debates about the right policy. It’s notonly that values are part of decisions, but thereare conflicts in values. These conflicts occurwithin a single category as well as betweencategories. Does local culture take precedenceover rights? What happens if trying to maximizehealth violates certain rights? When do youignore the consequences to certain groups intrying to maximize the consequence for an entiresociety?

The third point is that ethical analysis canhelp to resolve these conflicts. We believe thatethical analysis is just as important as epidemio-logical analysis, economic analysis, and politicalanalysis. It is a core training for both publichealth and medicine.

I wanted to conclude with three questions

that I think will be discussed in the papers thatare presented today. The first question is what isthe appropriate role for the market in health?When is it appropriate to use the market? Whenand how should the market be regulated? Whichproducts is it appropriate to sell? Which prod-ucts should the government provide? The secondquestion is how can we respect local culture asglobalization makes the world smaller and moreconnected? Sometimes local culture conflictswith global efforts to improve welfare. Whodecides when local culture takes precedence andhow? The third question concerns the obligationsof the rich to the poor. When there are so manygaps in welfare and health between the richcountries and the poor countries what are theobligations of the rich countries like Japan andthe United States to poor countries, and how canthose obligations best be met?

I hope that these questions will be relevant tothe presentations and commentaries we heartoday on the role of ethical analysis in publichealth and international health.

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Ethical Issues Raised by Smoking

Prakash C. Gupta (Takemi Fellow 1984–85, India)

Tata Institute of Fundamental ResearchNational Centre of the Government of Indiafor Nuclear Science and MathematicsINDIA

Takemi Fellow Presentation

I have chosen the topic of smoking becauseglobally we know that adult deaths are increas-ing largely due to two causes, HIV and smoking.Just about a week ago the World Health Organi-zation estimated that this year there are going tobe three million deaths from HIV, and four mil-lion deaths from smoking. And by 2030 on thebasis of current patterns of smoking, the numberof deaths is going to be 10 million. So we aredealing with a very serious public health prob-lem. We understand quite well that smoking isthe most preventable cause of serious diseaseand death among adults in the world today. Andthis is something that is no longer disputed byanyone, not even by cigarette companies. Forinstance, on the Phillip Morris web site we findthe statement: “We agree with the overwhelmingmedical and scientific consensus that cigarettesmoking causes lung cancer, heart disease, em-physema and other serious diseases in smokers.Smokers are far more likely to develop seriousdiseases like lung cancer than non-smokers.”Similarly, on the British-American Tobacco web-site we find: “With cigarette smoking come realrisks of serious diseases such as lung disease,respiratory disease and heart disease. Also formany people it is difficult to stop smoking.”These statements are not from any medical asso-ciation but from two of the largest tobacco com-panies in the world.

So there is no disagreement today about thehealth consequences of smoking. But it was notalways like this. In advertisements from the1950s, you can read that “Dentist Ed Wisesmokes Lucky Strikes,” “Leading doctors stillsmoke Lucky Strikes,” “Eminent doctors provePhilip Morris to be less irritating,” and one veryfamous advertisement, “More doctors smokeCamels than any other cigarettes.” So this was

the way in which cigarettes were advertised.Since then, of course, we have progressed quite abit, and such advertisements are not allowedanywhere, even if cigarette advertisements areallowed.

So we have made a lot of progress. But thereare also many points where we need to makemore progress. I will, in my presentation, con-trast the two situations. For example, in the1940s or 50s it would not have been uncommonin a hospital for a doctor to offer a cigarette to apatient. But today it would be a completely unac-ceptable behavior. Smoking in front of a patientmight have been the norm 40 or 50 years back,but it is a completely unacceptable behaviortoday. We all understand that smoking by healthprofessionals is something that is highly unde-sirable. We also understand that smoke-freehealth care facilities are highly desirable. Andwe also know that doctors themselves have ledanti-smoking campaigns, and they were the firstgroups to drastically reduce their own smoking.And we have data on these trends.

For example, during the late 40s and early50s the smoking prevalence among physicians inthe U.S.A. was the same or slightly more than inthe general population. But by the time the firstSurgeon General’s report came out, it was downto 30%. By the early 1980s it was less than 10%,and in the early 1990s, only 6% were classifiedas daily smokers. Many of them had smokedat some point, but most have given up theirtobacco habits. Unfortunately, this decrease isnot matched by other categories of health profes-sionals, nurses and staff at medical colleges or inall countries. What about the initiation of smok-ing? For that we should look at the medicalcollege students.

These data are available from studies at

(December 2nd, 2000)

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Johns Hopkins University where they have beenmonitoring the smoking habits of medical collegestudents (Fig. 1). In the late 1940s and early1950s smoking prevalence among medical stu-dents was 65%, the same as, or slightly higherthan, in the general population. But again by the60s it decreased to 40%, and during the 1980s itwas less than 3%. So the initiation of smoking inmedical college students, at least in the UnitedStates, has gone down tremendously. Unfortu-nately, this has not happened everywhere. Forexample, I looked at some studies in India.Smoking and tobacco use among medical collegestudents in India is still very high. I am notaware of much data from other countries.

Considering this extensive knowledge aboutsmoking, it should be logical that all the medicaland health conferences that take place aroundthe world ought to be smoke-free. There shouldbe no smoking in those conferences. But as far as

I know the only agency that has qualified andprovided guidelines for a smoke-free conferenceis the International Union Against Cancer basedin Geneva. They have provided mandatory anddesirable guidelines for declaring a non-smokingevent, including all venues that are attached tothe conference, and applying to all attendees,whether they are delegates, advertisers or vol-unteers. Further, the guidelines stipulate thatthe conference should not have any associationwith any tobacco company. Among desirable con-ditions, there should be smoke-free facilities forall attendees, such as hotels, restaurants, trans-port, shopping. If this is not feasible, there shouldat least be a separation of smoking and non-smoking areas. The executive committee of theInternational Union Against Cancer acceptedthese guidelines, which I wrote, and now, inorder to have the sponsorship of the Inter-national Union Against Cancer it is a require-

Fig. 1

Johns Hopkins8 Medical SchoolsNo data

100

80

60

40

20

0

Smoking prevalence among medical students

Cur

rent

Sm

oker

s (P

erce

ntag

e)

1950 1955 1960 1965 1970 1975 1980 1985 1990

Sources: Derived from unpublished data, Precursors Study and Preventive Cardiology Series.

Class (Year)

Smoking Prevalence among MedicalStudents

Johns Hopkins—65.4% during 1948-51By 1965 decreased to 40%During 1980s in 8 med schools�3%

21

ment to follow them.Also, we understand that in any health care

facility the direct advertising and the promotionof smoking would be unacceptable. I suppose noone would actually do that but it should be notedthat there is a lot of indirect advertising andpromotion that is still tolerated. For example,there are magazines that are left around inpatient waiting areas. These magazines oftencontain many cigarette and tobacco advertise-ments. There is one suggestion from an organiza-

tion called “Doctors Ought to Care” in the UnitedStates to tackle this problem. They suggestcrossing out every tobacco advertisement with athick black marker and displaying the followingnotice: “Many of the ads in this publication aremisleading and are a rip-off. For example, Smok-ing does not make one glamorous, macho, suc-cessful or athletic. It does make one sick, poorand dead. We care about you and your health.”

Physicians should be expected to inquireabout every patient’s tobacco habit and offer

Fig. 2

Fig. 3

Sources: 1974, 1976, 1987 National Health Interview Surveys; 1986 Adult Use of Tobacco Survey.

Physician advice, as reported bycurrent and former smokers

Former SmokersCurrent Smokers

Per

cent

age

Rep

ortin

g A

dvic

e

Survey Year1974 1976 1986 1987

60

50

40

30

20

10

0

Current smokers advised to quit, by time period anddemographic characteristics

1974 to 1976 1986 to 1987(n�16,033) (n�10,403) Ratio

Percentage (Standard Error)

Overall 27.3% (0.4) 49.7% (0.5) 1.8

SexMale 25.8 (0.5) 45.8 (0.7) 1.8Female 28.9 (0.5) 53.3 (0.7) 1.8

Age20 to 29 yr 19.4 (0.7) 41.9 (1.1) 2.230 to 44 26.7 (0.6) 49.6 (0.8) 1.945 to 64 33.0 (0.9) 55.1 (1.1) 1.7�65 33.4 (1.2) 54.5 (1.4) 1.6

RaceWhite 28.5 (0.4) 51.5 (0.5) 1.8Black 18.4 (0.9) 39.4 (1.3) 2.1Other 15.9 (3.1) 44.1 (3.0) 2.8

Education�12 yr 27.2 (0.6) 47.9 (1.0) 1.812 25.2 (0.6) 48.5 (0.8) 1.913 to 15 28.5 (0.6) 52.1 (0.9) 1.8�16 30.8 (1.3) 53.4 (1.5) 1.7

Sources: 1976, 1984, 1987 National Health Interview Surveys,Sources: 1986 Adult Use of Tobacco Survey.

22

cessation advice where necessary, as it is thelargest determinant of adult ill health. In fact,there have been several randomized clinicaltrials which show that a three-minute counsel-ing session with a patient can substantially in-crease cessation rates and lead to improvementsin public health. Clearly, not every patient wouldend their tobacco habit or quit smoking, but asubstantially high percentage would, whichwould lead to a significant improvement in pub-lic health. The clinical test guidelines in relationto tobacco use are available from varioussources; the most recent one is from the U.S.Department of Health and Human Services,which came out in June 2000.

But how far is this advice followed by thephysicians? Again, we have data from the UnitedStates (Fig. 2). In the mid 1970s about 25% ofthe current smokers were advised about theirtobacco habit. In the 1980s it has gone up to 50%.So there is progress. Again, one does not knowabout other parts of the world, and the progressis not uniform if you look at the data (Fig. 3).More women than men are advised, youngerpersons are advised less, non-whites are advised

less compared to whites and, less educated areadvised less than highly educated. So there arethese kind of demographic differences.

It is also well-established that one of the con-sequences of smoking during pregnancy is lowbirth weight, and other adverse outcomes. Thisis a well-known fact to attending physicians andall attending physicians and obstetrics /gyne-cology specialists do inquire about smoking topregnant women and offer cessation advice, par-ticularly where smoking among women is com-mon. But another fact is that exposure of chil-dren to environmental tobacco smoke causesspecific diseases like middle ear infection and itexacerbates asthma. And there is a recentexhaustive review and many background papersthat were commissioned by the World HealthOrganization. All of the background papers andconsensus statements are available at the WHOweb site. Yet, it has not become a common prac-tice for physicians who are attending parents ofchildren to inquire about smoking habits of par-ents and offer cessation advice and warningthem that this is injurious to the children.

23

— Comment for the Presentation —

Ethical Issues Raised by Smoking

Luiz Augusto Facchini (Takemi Fellow 1996–97, Brazil)

Program DirectorDegree in EpidemiologyFederal University of PelotasBRAZIL

I would congratulate Dr. Gupta for his excep-tional presentation about one of the most impor-tant problems in public health, with a lot of in-terest to the discussion on international healthand medical ethics.

In my comments I want to emphasize twoaspects, the smoking habits among childrenwhen they start, when people start to smoke, andthe role of the health professional in the cam-paign against smoking. In Brazil the anti-tobaccocampaign is advancing positively. For the firsttime we have a federal law regulating the smok-ing advertisements in TV and other media. How-ever, cigarette smoking remains a serious publichealth problem, and the attitudes of health pro-fessionals are very important to change thisproblem. The prevalence is declining only in moreaffluent population groups, remaining around40% among the workers and the poorer. Further-more, the smoking prevalence is increasingamong women and teens, and it’s also a problemamong children, especially if they work. In astudy of around 5,000 children between 6 and17 years old in more than 3,000 households inPelotas in southern Brazil, a mid-sized city with300,000 inhabitants, I have found a close rela-tionship between child labor and smoking. Thesmoking prevalence was 12% among the workersand 3.3% among the non-workers. To calculatethis prevalence, the WHO criteria for adultswere used, that is, if the respondent was smok-ing on the day of the interview and had at leastone cigarette per day during the past six monthsor more. Controlling for age, the prevalence wassignificantly higher among workers than non-

workers. From 6 to 9 years old, 3.3% of thesmokers among workers and 0.1% among non-workers. From 10 to 14 years old, 4.1% amongworkers and 1.5% among non-workers. And from15 to 17 years old, 18% among workers and 13%among non-workers. These findings call atten-tion to two interactive problems, work and smok-ing. In a common perception the kids think thatif they can work they can smoke. Many paperscall attention to some family and social charac-teristics that increase the smoking prevalence inkids of parents and friends who are smokers.And the adults’ behavior is also a strong in-fluence in the work environment.

Further, access to money and the possibilityto buy cigarettes freely are concurrent problems.In many countries around the world, anotherrelationship between child labor and tobacco isthe significant presence of children working ontobacco plantations and selling tobacco in thestreets. In Brazil we also find health profession-als smoking in public buildings like the head-quarters of the Health Department in Pelotas orin the classroom or in the health centers. Tochange this attitude will be one of my prioritiesin my mandate as Secretary of Heath for thecity of Pelotas, which starts on January 1, 2001.We need more campaigns, collaborative studies,restrictive policies and well-designed educationprograms to carry out at schools, work environ-ments, health centers and communities. But weneed also strong leadership against smokingfrom health professionals, politicians and deci-sion-makers. Tobacco control needs to reach allchildren, workers and health professionals.

(December 2nd, 2000)

24

Takemi Fellow Presentation

Today my talk will address health and medi-cal ethics in Taiwan. My approach is to giveyou a brief introduction about recent develop-ments in Taiwan, and then to provide some stra-tegic thinking about the future of health care inTaiwan.

Taiwan is now the only nation in the worldthat is not a member of the United Nations andis also not affiliated with the WHO. But people inTaiwan, particularly in the medical society, arestill working very hard trying to catch up. We areunder great pressure from China, but we try tohelp China too. There is a drastic change in Tai-wan. Since 1995 our national health insuranceprogram has been implemented. Since then thechanges have reached every sector of healthcare, particularly the medical society and thehospital sectors. For example, there’s a greatchange in the health care environment in hospi-tals. The hospital is now getting larger andlarger. Some hospitals now reach 7,000 beds inone system, and they can see the patients, thenumber of out-patients, reach 18,000 patientsper day just in one hospital. The demand forhealth care professionals, particularly physi-cians, is under very great financial pressure,particularly from market-driven health carereforms. The public expectation is much higherthan before, and the relationships between doc-tors and patients, hospitals and insurers arequite poor now. As for the medical schools or aca-demic medical centers there’s also a trade-offbetween the academic duties and their relation-ship with the communities and how to achieveclinical excellence.

So, there are many examples of ethical dilem-mas happening in Taiwan now, specific to eachsector of the health care system. For example, at

some community hospitals they have birthdayparties or anniversary parties for the test tubebabies. One single community hospital delivered2,000 test tube babies in the last few years. AndCaesarean sections are also quite prevalent.This kind of overuse of diagnostic tests or exami-nations or therapeutic care is quite common inTaiwan’s medical practice now. Some other ethi-cal dilemmas we are faced with include a veryhigh hemodialysis rate and teen pregnancy, andit also quite common for teen mothers to haveabortions. In terms of end of life care such assustaining life using high-tech equipment andthe use of hospice care, we have some debateover whether we should just give them care andcontinue to sustain their life or just end theirlife. Although, by law, the Medical Care Act isquite strict about organ transplantation afterbrain death, there is some doubt in general prac-tice. In human subject experimentation, becauseof pressure for faculty to get promotions or forhospitals to be accredited, clinical research getsmore funding but they are also quite loose in theregulation on human subject experimentation.Now we are just trying to strengthen this kind ofregulation.

I think there is some major force andinfluence for health and medical ethics in Tai-wan. First I think there is a value change withregard to life and society. The whole culture, par-ticularly the Chinese, Confucius-based culture,has changed a lot. Also, people are living longerand there is a change in the population struc-ture. The younger generation, they do not alwaysobey or follow all the rules and their thinkinghas changed a lot too. Even the expanding of thegovernment, the law of the government throughfinancing and regulation has had a great impact

Health and Medical Ethics in Taiwan:New Century, New Challenges and New Thinking

Chung-Fu Lan (Takemi Fellow 1986–87, Taiwan)

President, Tzu Chi UniversityTAIWAN

(December 2nd, 2000)

25

on health care. And, of course, the technicaladvancement in medicine and information tech-nology has also had a great impact. With theinvolvement of the financial industry and evenreligious organizations, medicine is being runjust like a business now.

The public is now more knowledgeable andquestioning about the practice of medicine. Theychallenge the traditional medical care practitio-ners and their interests. And there is alsoconflict over the difference in thinking aboutmedical practice and health care reform.

In Taiwan traditional medicine still has someimpact and now almost have 4,000 studentsstudy Chinese medicine in China today. Japan’sinfluence is gradually reducing, but the Ameri-can influence is increasing. And Taiwan just triesto balance that. We now send more physiciansout of Taiwan to study in Europe.

Now I would like to mention a little bit aboutthe change of Taiwan’s health care system, par-ticularly physicians’ behavior and hospitals’

behavior. Currently in Taiwan, the governmentrun national health insurance scheme domi-nates almost everything in health care. So thehighly regulated situation under the govern-ment encouraged managed competition. Thereare too many physicians, but some medical spe-cialties seem to be fading now. For example, somesurgical specialties cannot find any new resi-dents to enter the surgical training programnow. Also, continuing medical education is nowcompulsory, and the government just tried toenforce a policy that physicians have to renewtheir license every five years. Clinical practiceguidelines are like a fever and everybody, everyphysician, is talking about evidence-based medi-cine, the clinical path, case management, and soon. Post-graduate training in health policy andmanagement and law is also available for physi-cians now. Many medical graduates who arealready working as the director of the hospital orin some other administrative position, try to getinto a school of public health or law school to get

Fig. 1

Fig. 2 Fig. 3

26

another degree. Strengthening the law of themedical society is also being debated now,particularly the law of the medical association.Now they are divided between the private hospi-tals and the public hospitals as well as betweenthe primary care physician and tertiary carephysician.

Hospital behavior is also changing a lot now.They are talking about appropriate size, becauseas the hospitals are getting larger and larger, thesmaller or medium-sized hospitals are phasingout. And they use all kinds of management strat-egies such as diversification, integration or stra-tegic alliance. Capital investment is also cominginto the health care system. Very few hospitalsare doing Total Quality Management or TotalQuality Improvement, and when they do, theytry to do cost containment and quality improve-ment at the same time. In addition, hospitalaccreditation has gotten tighter and tighter, andthe National Health Insurance Bureau is chang-ing both physician and hospital payments.

So in just a month we are going into the 21stcentury, and I would like to predict some sce-narios for the future. First, the medicine ofhealth care will start to change from personal-ized medicine or socialized medicine; maybe toconcentrate more on population based care, suchas focusing on a specific disease and then con-sidering the nation as a whole before doingsomething about it. The second scenario perhapswill start from conventional medicine, such asprimary or specialty-based medicine or hospital-based medicine, and then expand that or inte-grate it into more IDS or IDN such as horizon-tally and vertically integrated systems. So fromprevention to medical care to rehabilitation ofsocial services we are linked together. And nowTaiwan is also running the system just like theUnited States. We try to copy everything fromthe United States now. In the third scenario, Ithink that medicine in Taiwan will be organizedso that the manager will be running the hospitalor the system, keeping professional autonomy

Fig. 5 Fig. 6

Fig. 4

27

down and raising manager’s capabilities. Thefourth scenario I predict is for the fee-for-servicesystem to gradually change to case payment andperhaps next year Taiwan’s physicians and hos-pitals will fall under the global budget due to theconstraints of the NHI budget. In this scenario,everyone, including the physicians, will have ahuge database in Taiwan, because all medicalcare or insurance claims will be recorded andthere will be profiles of hospitals, physicians andpatients. With this kind of huge database or databank they can achieve evidence-based reim-bursement together. And this might be a hugedata bank for the public health professional, butit will affect all the physicians and the hospitalsand even the citizens. We might concentratemore on the future based on the advancement ofthe Genome Project. Yesterday Dean Bloom toldus of the profound impact of the Genome Project.I also predict this will be a genomic medicine,and there are also several groups in Taiwan try-ing to work on that now. And the last scenario Ipredict will be e-medicine because Taiwan is nowquite good in information technology. As you allknow, we provide a lot of computers to the world,and we also try to use that technology in thehospital information system through hospitalautomation, using the chip to do medical recordsand insurance cards. So everyone will hold a chipjust to record his or her medical care. In fact, thiskind of e-medicine is already quite prevalent inTaiwan’s medical system now.

So finally I would like to offer some options orfundamental thinking about Taiwan’s healthcare system. I personally believe rethinking ofthe values in health and medicine is very impor-tant. Every medical student is now required totake a course called “Medical Ethics.” And notonly for medical students, but dental, nursingand other allied health professional educationall require it. And the philosophy of objective and

medical and allied health professional educationmust be rethought as well. The rights and re-sponsibilities of clinical decision-makers are alsovery important. Now when the physicians seethe patient, it’s not judged by them only, theinsurer will interfere. And the management inthe hospital also has some word to say abouttheir clinical decision-making. So physicians arevery dissatisfied with the current system in Tai-wan. The duty to the patients and to the societyalso needs to be reevaluated. I personally alsothink to review the morality in medicine andhealth care is very important. If the doctor is nothappy, I don’t think anyone else will be happywith his or her treatment. So the health caredelivery and finance is a very important topicnow, and in Taiwan we have just a five-year his-tory with national health insurance, but we arealready talking about the health care reform. Aswe are trying to reform or rethink delivery andfinance systems, the trust among the consumerand provider and the insurer in health care mustalso be rebuilt.

Finally, I personally think the balance be-tween public expectations and limited resourcesis very important. The balance between scientificadvancement and clinical excellence is also veryimportant as well as the balance in quality andcost in health care. Almost every physician orhospital administrator likes to go to seminars ortake courses or workshops to try to learn aboutthe specific techniques to manage this imbal-ance. The health education and informationdilemma is also very important, and we must tryto take advantage of new areas in informationtechnology. So clinical and managerial decision-making must be rebalanced. The role of the doc-tor and the role of this new health care managerhave to reach some kind of new balance, andmedical ethics has to catch up with the new tech-nology progress.

28

— Comment for the Presentation —

Health and Medical Ethics in Taiwan:New Century, New Challenges and New Thinking

Bimo (Takemi Fellow 1991–92, Indonesia)

Indonesia Country RepresentativeJohns Hopkins Program for InternationalEducation in Reproductive HealthINDONESIA

In his presentation, Dr. Lan made an excel-lent description of the changes that Taiwan hasfaced and the challenges that they have to dealwith in the future. In my comments, I would liketo mention that Indonesia is also facing similarchanges in the health care environment. Butthere are some differences because of differentsystems and culture. For example, the domi-nance of the health insurance program is not soprominent yet in Indonesia, because Indonesia isstill in the very early stage of developing itsinsurance system, and managed care works asthe model now. But I would like to mention onechallenge that we face in Indonesia that was notmentioned by Dr. Lan. That is the challenge ofglobalization, and the prospect of having a free-trade agreement in a few years. The impact ofthat in Indonesia would be a large influx of for-eign physicians to work in the health care ser-vices in Indonesia. It poses a major challenge tothe medical profession in Indonesia, that is, howto ensure the quality of services providedthroughout the country. The Medical Associationin Indonesia now has the big task of preparing

the necessary infrastructure in meeting the glo-bal standard for that.

I would like to point out here that changesare happening not just in Indonesia or Taiwan,but also in other countries as well. The changesand the challenges would be unique and specificto each country. And each country has to find itsown way how to deal with the challenges posedby the changes. Unfortunately, there are no com-prehensive models that exist to which a countrycan refer on how to deal with those situations. Iwould like to raise a challenge for all of us herefor further discussion in the symposium. Arethere some common themes of issues that cutacross countries, despite the differences, that wecould collectively find a solution for? I am surethere are lessons learned in one country thatwould be useful for other countries in dealingwith those challenges. And also there is a chal-lenge for all of us as members of the inter-national health community to foster the develop-ment of a network of communication betweencountries to share the lessons learned and towork together for a common arena.

(December 2nd, 2000)

29

Where Shall We Die, In the Hospital or At Home?—Past, Present and Future Perspectives—of Community Medicine in Japan

Eiji Marui (Takemi Fellow 1986–87, Japan)

Department of Public HealthJuntendo University School of Medicine, ProfessorJAPAN

Takemi Fellow Presentation

Today I will talk about where we die inJapan. After 50 years of so-called “progress” ofthe medical sciences in Japan, what has hap-pened? This is in some senses a natural experi-ment in Japan; I can say it is before and after theexperiment. Usually we think about “when shallwe die?” That is a very important thing. Howlong can we live? Length of life is our concern.And then our concern changes to, “how we die,”and in that sense, the cause of death is veryimportant: acute death or chronic death. In someareas we will die with medical care and in otherswithout any medical care. And then today,finally, we come to, “where shall we die?” It is justthe beginning, but it leads to further issues. Forexample, the quality of life for each patient and,

at the same time, we have to think about thequality of medical care. But still, today, I will justtouch upon the major issues.

In 1951 just around 15 or 16 percent of alldeaths occurred at hospitals or clinics, and morethan 80 percent at home (Fig. 1). But after 50years, less than 20 percent happened at home,and more than 80 percent of deaths occurred inhospitals or clinics, in medical facilities. So, dra-matic changes have happened in the last 50years. For example, in 1961 in Japan we com-pleted universal health insurance, but that didnot influence this pattern. Fifty years ago ourbelief was that if we have better medical care,that we will get a better death, or that moderntechnologies mean good care, or the people

(December 2nd, 2000)

Fig. 1

Trends in Deathsby Place of Occurrence: Japan

HospitalizedHome

Others

1951 1956 1961 1966 1971 1976 1981 1986 1991 1996

800000

700000

600000

500000

400000

300000

200000

100000

0

30

wanted to stay and die in hospitals with moremedical instruments or facilities. And especiallythe earlier stage in the last 50 years the realitywas that poor people had to die at home. And atthat time, fewer physicians, but many medicalpractitioners worked in the community. Andthen after the 50 years experiment of “progress”of medical science in Japan, we consider moremedicalized care to be associated with less qual-ity of life. Or many people believe that poorpeople have to die in the hospital and others feelthe need for more humanistic medical care. As abackground, fewer medical practitioners areworking in the community, and some people feelthat we need more home care seriously. Andsome rich people are willing to pay for death athome.

At first I felt that ‘where to die’ might not bethe best ethical issue to discuss, but I believe itis a good example of ethical issues in Japanbecause death is one of the ultimate forms of ourhealth. And quality of life in the final stage of lifeis very important. The right to decide where todie is very important. Many people have pointedout the “spaghetti syndrome” in hospital. That’squite a miserable picture. We have the very well-known folklore in Japan called the oba-sute-yama story that says at some stage of old age,family members take the elderly deep into themountain and leave them there. So it’s a kind ofnatural nursing home. We have to make theeffort to seek a better solution, and that should

be a solution that is socially acceptable. Thereare many problems—what is the role of hospi-tals, what is the role of medical care, and, ofcourse, the background changes of family situa-tion are there, and finally, who decides the placeof death.

The number of hospitals increased, but in thelast 10 years it has been decreasing. The numberof total beds is the same, while the number ofphysicians and nurses is still increasing and themedical expenditure, it’s greatly increasing now.In the last 25 years single households andnuclear families have been increasing, so thehousehold composition has changed. And espe-cially the households with members over 65

Fig. 2

Fig. 3

Deceased subjects preferred placesto die and actual places of death

actual placeof death

deceasedsubjects whoexpressed apreference ofa place todie (preferredplaces to die)

deceasedsubjects whoexpressed nopreference ofplace to die

unknown

number ofdeceasedsubjects

Total

own home

hospital·clinic

other

total

4755

Percentage distribution (%)

1313

ownhome

Hospital·clinic

other

1473 121 39 2713 569

20.0 33.130.1 5.8 7.7 15.9 13.5

100.0 100.0100.0 100.0 100.0 100.0 100.0

78.7 66.369.1 94.2 84.6 82.9 83.3

1.3 0.60.7 7.7 1.1 3.2

31

Fig. 4

Fig. 5 Fig. 6

years old has increased lately, and especiallysingle elderly people and elderly couples. Thismakes it very difficult for one to stay at homewith a bad physical situation.

Next, I will introduce the survey on the deathof the aged from 1995 (Fig. 2). This shows that of1,473 people surveyed, nearly 90 percent of theaged people wanted to die in their own home,and less than 10 percent wanted to die at hospi-tal (Figs. 3 & 4). But actually, only one-third ofthe people die at home, and two-thirds of thepeople who wanted to die at home ended updying in the hospital (Fig. 5). People who wantedto die in the hospital could actually die there(Fig. 6). So where is the good place to die? Ourown home, hospital, clinic, or nursing home,hospice or maybe some other place? So, finally Ithink that we cannot go back to the good old daysbecause the medical environment has changed,family structure has changed, so even if all the

people wanted to die at home, the family struc-ture has changed so much that they have noplace to die at home. So the places will be quitediversified. Some people try to go home to die,community physicians try to set up a home carehospice, so that maybe we may have moreoptions. We will set up facilities for dying peoplein nursing home or some other kind of place. Andhow can the preference be realized? If you wantto die somewhere in particular, how could thatwish be realized? And, of course, we need tochange the attitudes of patients and physicians.And the role of medical practitioner in commu-nity is very important and could be the key.Many medical professionals are trying to changehospital and clinical settings for death. And so,we have to seek new ways in the 21st century.That is my report on the 50 years of naturalexperiment in Japan.

hospital·clinic8%

other3%

own home89%

other2.6%

hospital·clinic8.2%

own home89.2%

own home 29.6%

other0.5%

hospital·clinic59.1%

own home 89.4%other2.6%

hospital·clinic8.0%

hospital·clinic7.5%

own home 0.5%

32

— Comment for the Presentation —

Where Shall We Die, In the Hospital or At Home?—Past, Present and Future Perspectives—of Community Medicine in Japan

Lola Dare (Takemi Fellow 1999–2000, Nigeria)

Chief Executive Officer, Centre for Health Sciences TrainingResearch and DevelopmentNIGERIA

Dr. Marui’s paper has raised several issuesrelated to quality of care and quality of life atdeath in Japan. This includes the fact that mostJapanese are not dying where they wish to die,death has become medicalized as technology isinterpreted as good care, and there exists anethical dilemma in relation to quality of care,quality of life and access to health care services.This reversal in place of death is also observed inmany developing countries, including Nigeriawhere I live and work. Besides the changingepidemiology of diseases from communicablediseases to non-communicable diseases, we havealso observed other reasons for this reversal inplace of death. In the first place hospitals, onaccount of poor patient satisfaction, lack ofequipment and poor provider attitudes, are per-ceived as places not to be cured but to die. Sopeople just don’t go there anymore. In addition,the increasing cost of health care services meansthat people can’t afford the care anyway, so theywait at home until they are terminal, and thenthey seek health care services for technologythat can no longer help them. There is a hugeemphasis in public health policy on technologyand curative care at the expense of simple home-based care that can improve health. And sopeople do not have access to care.

Culturally, dying at home in Nigeria impliesold age, peaceful, painless death. And mostpeople, even the educated, want to die at home.When you die at the hospital, which implies thatyou have a disease, you’ve had trauma, andthere’s discomfort associated with that kind of

death. This, of course, raises several issues inethics and public health. I would like to raisesome of these issues, not because I have answersto them, but for continuing the dialogue. In thefirst place, place of death has implications forquality of care and public health practice.

Secondly, the ethical analysis presented byProfessor Michael Reich needs to be consideredin defining packages of quality of care. Whosereality counts, the reality of the physician, thereality of the politician or the reality of the enduser of the health service? Thirdly, there are verybig ethical issues in terms of access to healthcare and the distribution of health resources—the number of beds, what kind of manpower isneeded. Do we train more specialists or morecommunity-based providers? Finally, if you lookat the principles of utilitarianism, liberalismand communitarianism that Professor Reich hastalked about, and you look at the various prac-tices of both public health, international healthand private practice in many parts of the world,including Nigeria, you would find that this con-cept of ethics often does not come into definingcare for many communities that we work in.

Finally, I would like to thank Dr. Taro Takemifor his foresight in supporting the Takemi Pro-gram, the contribution the Program has made tobroadening my own perspective of internationaland public health, Professor Reich for his com-mitment and professional development of allFellows and the opportunity to be here providedby JICA.

(December 2nd, 2000)

33

Ethical Concerns in the Dietary Supplements Business

Khor Geok Lin (Takemi Fellow 1988–89, Malaysia)

Department of Nutrition & Health SciencesFaculty of Medicine & Health Sciences, Professor, PhDUniversity PutraMALAYSIA

Takemi Fellow Presentation

As a nutritionist I have chosen to speak onsome ethical concerns in the dietary supple-ments business. The dietary supplements busi-ness involves many billions of dollars. Accordingto the Nutrition Business Journal, in 1998 thedietary supplements industry involved 23 billiondollars in the United States alone. And it in-cludes a wide array of nutrition products, natu-ral foods like the neutraceuticals, functionalfoods, dietary supplements and also nutritionsupplements used in cosmetics. I will be focusingon the dietary supplements.

What is a dietary supplement is actually well-defined by the FDA, according to the DietarySupplements Health and Education Act of 1994:“A dietary supplement is taken by mouth, in-tended to supplement the diet, it contains one ormore of the following dietary ingredients: vita-mins, minerals, etc., and the dietary supple-ments can be the form of pills, tablets and so on,and its label must clearly state that it is adietary supplement.” Now there is increasingdemand for dietary supplements worldwide. Iwould like to propose some reasons that peopleare getting greater access to this complementaryand alternative medicine, including traditionalmedicine and dietary supplements. Also peopleare getting perhaps more disenchanted withthe conventional health care, including its in-creasing cost. There is a worldwide epidemiologi-cal shift from infectious to non-communicablechronic diseases, which requires consumers toseek alternative medicine. The demographicshift increases proportions of all segments of thepopulation, but it is the middle-aged and theolder population that create demand for more ofthese alternative medicines. It is very importantto note the aggressive and effective distribution

and sales channels for dietary supplements. Andif you look at the last point, in the United Statesthey are sold in retail stores, in the mass mar-kets, including supermarkets, and also directsales. And this is the scenario in many ThirdWorld countries, too.

Now I will address some ethical concerns,starting with the regulatory issues, specificallythe lack of legal control regulations even in coun-tries like mine, Malaysia. We have regulationsfor the use of nutrients to be included in foods,but there are no regulations for dietary supple-ments. Even in countries where there are regula-tions there may be poor enforcement of theseregulations. And there are loopholes and ambi-guity in relations. For this I can show the UnitedStates itself as an example. And now in theage of e-commerce we can order nutrients anddietary supplements over the Internet. So who isregulating these sales? I take the example ofUnited States because data are more easilyavailable. Now with regard to the regulation ofdietary supplements in United States, there is aspecific act of 1994 that provides the legal frame-work for dietary supplements. And yet there areambiguities, as I highlight here, a regulatorydilemma. Under the DSHEA (Dietary Supple-ments and Health and Education Act), no claimcan be made for a dietary supplement to treat,cure or mitigate a disease. However, a dietarysupplement can make claims that it affects ormaintains the structure or function of the body.And you know the dietary supplement industry,they’re very clever and skirt this issue, and youget all kinds of claims on the products. So arethese health claims or are they structure func-tion claims? Well, it depends. For instance, ‘helpsmood disorders’ is allowed, and if you’re feeling

(December 2nd, 2000)

34

depressed, that becomes a health claim perhaps.Or ‘helps to rejuvenate and repair cartilage’ so ifyou have arthritis, perhaps you look at it as ahealth claim. And so on. So there’s ambiguity inthis regulation.

The second ethical concern is misleading andunsubstantiated health claims. That is veryprevalent despite the fact that a health claim isactually well defined, again by the FDA: “Ahealth claim characterizes the relationship ofany food, nutrient or substance to a disease orhealth-related condition.” However, again, youhave loopholes and misleading claims. And Itake with you here a very specific example. Avery important dietary supplement that is usedworldwide is Omega 3 Fatty Acids. It is adver-tised widely that Omega 3 Fatty Acids can helpto reduce the risk of coronary heart disease.However, the FDA, having critically reviewedthe evidence from studies, including clinicalstudies, as recent as October 2000, has taken astand that there is no significant scientific agree-ment among experts that such evidence sup-ported a health claim for Omega 3 Fatty Acidsand coronary heart disease. Thus the healthclaim stating that Omega 3 Fatty Acids mayreduce the risk of CHD is misleading. However,there are studies to show that if you take lessthan three grams of Omega 3 Fatty Acids a dayit may be helpful. And so, FDA does allow label-ing that says not more than two grams per day ofOmega 3 Fatty Acids can be taken. This will pro-vide an added safety margin for consumers toremain below the three grams per day safetylevel. This is for the United States, but I assureyou, in countries like Malaysia what you get isadvertisement that you have more Omega 3 inevery capsule you buy, so the more the better.And this is allowed.

The third ethical concern that I would like toaddress here is, of course, very important, andthat relates to safety. The emergence of herbs orbotanicals worldwide is becoming an issue ofconcern from the safety perspective. The WorldHealth Organization estimates that 65 to 80% ofthe world’s population use traditional medicine—Chinese medicine or botanical medicine, astheir primary form of health care. And the use ofherbal medicine, the dominant form of medicaltreatment in developing countries, has beenincreasing and in developed countries in recentyears as well. And the regulations vary even

among the developed countries. For example, inBritain certain specific forms of herbal medicineare exempt from medicine’s license, and inFrance it’s different; in Germany, Denmark, Hol-land and Sweden herbal remedies are sold asfood supplements. And in Australia herbal medi-cine accounts for 26% of the complementary andalternative medicine, and it involved one billiondollars in 1999; 57% of Australians are usingthis form of alternative medicine. I can give oneexample of a herbal product that was in useworldwide, and then, recently, it was found to beunsafe, and that aristolochic acids were found tobe potent carcinogenics and nephrotoxins, andover a hundred cases of nephropathy reported inU.S., Canada and Europe in this year alone.Although small amounts ingested may have noadverse symptoms for years, this has chronicimplications, for example, leading to renal fail-ure. There are over 600 species of plants thatcontain this toxin, and many originate fromChina, and are used widely in Chinese medicine.

So, should more control be introduced? Well,if you take the case of Australia, under theTherapeutic Goods Act of 1989, “Alternativemedicines can be listed for a small fee withoutevaluation provided that no specific claim ismade for efficacy and there is no available evi-dence of problems with quality or safety.” Somany of these alternative medicines are listedfor a small fee without scientific evaluation, evenin a country like Australia. And, in fact, there aremore than 4,500 herbal preparations on this listand less than five are registered as a result offull evaluation of safety and efficacy. Again, I usemodels from the U.S. and Australia to show that,despite the developed status in these countries,despite regulations that they have in these coun-tries, there are problems, and these are alsoproblems in the Third World countries wherethere are no regulations at all.

The fourth concern that I would like toaddress in this forum is health care providers’conflict of interest. Here is a citation from DavidKessler, former FDA commissioner: “Don’t thesepharmacists look and see what you are selling?Maybe they are no longer in control of the store.Maybe they are just behind the counter and any-thing in front of the counter goes.” But it’s timefor that profession to take responsibility forwhat it is selling, while the same goes for othermedical and health professionals—dietitians,

35

nutritionists, even doctors who are involvedin the sale of dietary supplements and herbalproducts. I think they need to be sensitive to thisneed to control and take an ethical stand. TheAmerican Dietary Association recently took theposition that ensuring consumer access to safedietary supplements that are truthful and notmisleading, fully-labeled, should be the over-

arching goal of FDA’s dietary supplement strat-egy. This should apply to other countries, withseparate categories for dietary supplements,which are vitamins and minerals, which areestablished for a long time, separate them fromthe botanicals, the herbals. The latter will re-quire more scrutiny or limits.

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— Comment for the Presentation —

Ethical Concerns in the Dietary Supplements Business

Prakasamma Mallavarapu (Takemi Fellow 1992–93, India)

Director, Academy for Nursing StudiesINDIA

I congratulate Dr. Geok Lin Khor for a verysuccinct presentation. I would like to concen-trate on two aspects of this presentation relatedto dietary supplements. One is from the inter-national public health point of view, wheredietary supplementation is done on a large scaleas part of public health programs in severaldeveloping countries, where it is thought to be anessential requirement as part of public health.And secondly, I would like to concentrate on thewide marketing of dietary supplements and therelated public health implications and ethicalissues.

Firstly, dietary supplements as public healthprograms. We are aware that in different devel-oping countries dietary supplementation is takenup as a large-scale public health program. Wehave examples of dietary supplementation of ironand folic acid for pregnant women, of dietarysupplementation of vitamin A for children underfive, of iodized salts, of various examples acrossseveral countries where dietary supplementa-tion is a national program, where is it done,where millions of dollars are poured into thesepublic health initiatives, where research goes onto see how many micrograms are required tocorrect the imbalance and to make it safe for thepregnant woman, for the child, or for those livingin areas where iodine is to be made as a supple-ment. For those risk groups where, without thesupplementation, it would lead to lifelong dis-ability or even death, these programs are usuallytaken up as campaigns on a war footing, asnational programs and missions, and a lot ofthe national budget is allocated to this. And wealso see international agencies involved. Wehave the example of rich countries pouringmoney into poor developing countries where this

food supplementation becomes a major program.One example is the USAID-sponsored programof food supplementation in several countries.

On one side we know that this is necessary. Itis an essential requirement. And there are publichealth programs for this. But who regulates theprograms? Who regulates and sees whether theamount of input, if we see from the utilitarianpoint of view, the costs incurred, do they reallylead to gains? And what are the implications ofsuch large-scale programs? Across nations wehave seen examples where iron supplementationor world food programs have not really improvedthe nutritional status of people over the years.They would have improved the status at thatpoint of time for those small groups whobenefited from the program, but have not reallybrought about a lasting impact. And for this wehave to look into the ethical issues, was this thebest program for that country at that point oftime? Did it not lead to complacency? Did it notdivert resources and block the problem? And wasit not only a short-term strategy where long-term impact is clouded? Would it not have beenmuch more cost effective to give information tomake food accessible and available? In the wordsof Hippocrates: “If they had made food be themedicine, maybe it would have been a muchmore long-term strategy.” And therefore we cometo the issue of who regulates these national pro-grams, and how does ethics and how do publichealth professionals get into the decisions aboutwho regulates international food aid programsor food supplementation programs?

My second point is about the market and theavailability and marketing of vitamins, miner-als, herbs, medical cures, alternative remedies. Iwould like to quote one or two examples of herbs,

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which are widely used in several countries fordiabetes treatment, that people really believewill reduce their blood sugar levels. I have oneconcrete example of a fish medicine for asthmain India where millions of people come on oneparticular day in a year, and this fish medicine isgiven only one day in the entire year. And nowwe have many people from other countries,South Asian countries and even from the Westcoming to take this fish medicine, really believ-ing that it cures them of asthma if they take it onthat day. The medicine is put into the mouth of alittle fish, and the fish is put into the mouth ofthe patient. And recently we had even our chiefminister lining up for this medicine on that day.So the messages that we give to people are thatthese are effective, and this is a medicine to betaken up by those who have the problem.

In a society with a well-informed publicmaybe choices can be made, because regulationand information on the packets and on the bro-chures would say how effective it is. But in a

society with scarce information, with poor lit-eracy, what is the role of the government orhealth professionals in providing such informa-tion? We see public health issues, for example,where there are vitamins and minerals whichare sold over the counter are taken up by peoplewith very low income levels, and I can put theexample of injections taken as shots to feelbetter by poor people all over the world. I can putthe example of IV fluids when a person is feelingweak, obviously because he worked hard andwould like to take a bottle of IV fluid to feelbetter. And so this is where we cannot stop thepublic with marketing and say, it’s a free market.It is there for people to choose and use. Some-where public health ethics has to come in andpublic health professionals have to take the leadin making information available and ensuringthat adequate research, systematic researchgoes into these unsubstantiated claims of drugsand vitamins and minerals.

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Nii Ayite Coleman (Takemi Fellow 1996–97, Ghana)

Lecturer, School of Public HealthUniversity of GhanaGHANA

Comment for First Session

I’m very honored to have this opportunity tomake a few comments. This morning I have lis-tened to four very good presentations and theirrespective comments on cases that illustratesome of the ethical issues in public health prac-tice and medicine. The wide variation in thecases that we’ve listened to illustrates the com-plexity of international health issues. I wouldlike to make comments that are global. I will nottake the individual cases. I would like to makethree points.

The first point is that the conception andembodiment of medical ethics, as shown in thepresentations, are inadequate to deal with issuesof public health and international health prac-tice. The second point is that I would like to lookat some of the approaches for developing a newframework for international health ethics. Andfinally, I would like to raise a few issues forconsideration in developing this framework forinternational ethics.

Why am I saying that medical ethics areinadequate to deal with the challenges of inter-national health? The second presenter alluded tothe changing health care environment. Thischanging health care environment has made itincreasingly difficult for the concept and embodi-ment of medical ethics to deal with the chal-lenges that are arising. We have heard of callsfrom several medical quarters for a new medicalethic. In fact, the American Medical Associationhas come up with a draft medical ethic that waspublished in 1999 for discussion. So even withinthe field of medical practice there’s clearly inad-equacy in the code as we know it. Again, changesin the health care environment, such as man-aged care, have shifted decision-making from thephysician to other people. And so it is not onlythe physician who ought to be held accountablenow, but we have to find ways of holding organi-zations accountable. This fact has also beenacknowledged by the American Medical Associa-

tion, and there is a committee to look at how tomake organizations accountable. So I thinkthese points clearly illustrate the inadequacy ofmedical ethics in dealing with these issues.

When we talk about international healththen it becomes obvious that the model of medi-cal ethics has broken down completely. Thatmodel, which relates to actors, the physician andthe patient, breaks down because in inter-national health we are talking about so manyactors, so that model definitely cannot work. So Ibelieve that it is clear and one would not doubtthat medical ethics as we know it cannot reallybe adequate in dealing with the complex issuesthat happen, as analyzed in the presentationsthis morning.

As a call is made for the development of a newmedical ethic, I think that it is also appropriateto call for the development of an ethical frame-work for international health practice. I wouldlike to say that there are two ways one can lookat the development of this new framework. Wecan decide to have analogues of the principles inmedical ethics as we know it, or we can decide todevelop a new framework altogether. I think thatthe analysis that I made about the inadequacy ofmedical ethics and the model breaking downmakes it obvious that developing a new frame-work based on analogues from the old medicalethics will not be very suitable. And therefore thecall will be for a de novo development of a frame-work for ethics and international health prac-tice. This assumes that international health isclearly defined, but obviously this is not so. Inthe past decades we have witnessed an evolvingdefinition of international health. Many centu-ries ago, it started with the quarantine move-ment, and then it went on to the treatment oftropical diseases, and we have areas in whichinternational health has been thought of as deal-ing with problems or health issues of poor peopleall over the world. Quite recently it has been

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viewed as sort of a north-south dialogue. I thinkthat Dean Bloom’s speech yesterday clearlyillustrates the new dimensions of this collabora-tion. We should move from thinking of resourcesbeing moved from north to south and rather intopartnership between north and south, betweendeveloping countries and developed countries.

So if we want to develop this new frameworkwhat are some of the issues we should consider?I would like to mention just four of them. I wouldlike us to remember the motivation for inter-national health all along. What motivates us toengage in the practice of international health? Ithink we will remind ourselves that throughoutthe changing phases of definition of inter-national health, humanitarian service has beena key issue. The second point I would like us to

consider in developing a new framework is the1948 Universal Declaration of Human Rights.The third one is about globalization, the phe-nomenon of globalization. Several people havereferred to it here. And the last one is one of anew concept of human security that is evolving.If we consider these four points in developing anew framework, then I think we will all agreethat a good guiding principle is one offered bythe American philosopher John Rawls whostated that such decisions should be made basedon principles derived under a “veil of ignorance.”So that just in case we happen to be the oneswho are less fortunate or the least fortunate,we are at least cared for by a certain minimumstandard.

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Takemi Fellow Presentation

I will start by thanking the organizers of thesymposium for making it possible for me to behere and to address you on a subject which is ofgreat importance to South Africa. I want to talkto you today about the dilemma we face in SouthAfrica as we try to address one of the biggestcatastrophes that has struck mankind for a longtime.

By way of introduction, I would like to remindyou that South Africa is a country on thesouthernmost tip of the African continent. It hasa population of 40 million people, and a popula-tion growth rate of 1.8 percent, which is low forAfrican countries. It has a GDP per capita of twoand a half thousand U.S. dollars per annum,which is reasonable for an African country. But itdoes have a very unequal society, as reflected bythe GINI coefficient of 0.62. The infant mortalityrate is high, and the country spends about 8.5%of its GDP on health care, most of it in the pri-vate sector. The AIDS epidemic in South Africahas been explosive. Evidence from blood samplestaken at antenatal clinics reflect a dramaticincrease in seroprevalence from 0.8% in 1990 to24% in 1999, which means that every fourthwoman presenting for antenatal care in the pub-lic sector is HIV-infected. The government doeshave an AIDS plan which is led by the President,premised on a multi-faceted approach involvingboth private and public sectors. And the Presi-dent’s involvement in HIV/AIDS in South Africastems from the fact that while he was Deputy heled the Partnerships Against AIDS Initiative inour country. This has been a mixed blessing, andthose of you who have read the media will beaware that there is considerable controversy inour country at the present time. After manyyears of apathy the new government has beenquite desperate in trying to do something about

the AIDS epidemic, and in so doing inevitablyencountered a range of ethical dilemmas. Someof these dilemmas were, in fact, addressed veryeloquently yesterday by Dean Bloom, the issue ofinformed consent, particularly in the ethical con-text where the definition of individual is cap-tured in the ethical philosophy of buntu, whichsays the individual is a person through otherpeople. And so, the issue of community consentbecomes a major consideration in our context.

I’d like to focus on two areas, the area of vac-cine development and the area of reduction oftransmission from mother to child. In 1998 itwas decided that South Africa would in fact de-velop her own vaccine. One might ask whether acountry that faces a lot of poverty can justifiablyinvest resources in developing its own vaccine.This clearly is a dilemma which was confrontingscientists and government two years ago. And ifSouth Africa were to develop its own vaccine,which clade subtype was it going to be develop-ing it against? The decision was then to developa vaccine against clade C, and given the fact thatwe suspect that there is some cross-protectionbetween clade C and B, that decision was quite acritical one. What it meant was that any vaccinedevelopment in South Africa would take two tothree years longer than if she had adopted theclade D vaccine which had been developed inmany other parts of the world. And the reasonfor the clade C preference was, of course, 90% ofinfections in poor countries are caused by thisclade.

The question we ask ourselves is should wego to vaccine trials? Are we able to amelioratethe physical risks that are involved? Can SouthAfrica really overcome or reduce the psycho-social risks of those who would participate inthis vaccine trial? The issue of stigma is a major

The Ethics of HIV/AIDS: A South African Case Study

William M. Pick (Takemi Fellow 1990–91, South Africa)

Professor and Head, Dept. of Community HealthUniversity of the WitwatersrandSOUTH AFRICA

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consideration. And just to illustrate the point, Iwant to share with you a story of a young person,whose name was Gugu Dlamini. As part of anational campaign to de-stigmatize HIV/AIDS,she declared her seropositive status to hercommunity. But a week later she was killed byvillagers who felt that she had brought shameupon the village. That is the nature of thestigma. And it’s in that context that we face enor-mous dilemmas as we try to address the problemof HIV/AIDS.

Other issues are the desire or the need forgovernment to compensate people for the socialand economic harm they might suffer as a conse-quence of participation in the HIV/AIDS trials.For example, a person that’s come to their trialHIV-negative gets the vaccine, becomes positive,and then finds him or herself unable to get insur-ance. Does South Africa have the capacity toreally involve communities at all levels of re-search given the complexity of our country, thevastness of the terrain, and the lack of literacy inmany parts of the population?

As you know, anybody participating in a vac-cine trial that does become positive, that doesbecome infected, in the arm of non-intervention,needs to have access to treatment. The big de-bate is how intensely do we treat? Do we con-tinue to treat way beyond the duration of thevaccine trial? And is it not true that if one doestreat, one is producing some inducement forpeople to participate in a new trial?

The other major challenge is in the area ofreduction of mother-to-child transmission of thevirus. We anticipate that South Africa will have70,000 HIV-infected births per year. And the evi-dence is overwhelming that using short-courseanti-retroviral therapy is cost-effective and doesreduce mortality. Government policy, on theother hand, says that we will not provide any ofthese drugs to mothers who are pregnant withHIV. And so, we are condemning thousands ofchildren to death. The argument used there wasthe equity argument. Is it reasonable to provide

anti-retroviral therapy to pregnant motherswith HIV when they only account for 10% of allthe HIV infections we will have in our country?In other words, we are excluding 90% of the HIV-infected population, mainly adults, from accessto the drugs.

I think underlying Africa’s reluctance to com-mit itself to providing these drugs is a largerethical dilemma that I think faces most coun-tries in the world today. And that is the issue ofintellectual property rights. The World TradeOrganization, as you know, has some ruling ontrade-related intellectual property and protec-tion of those rights, which does allow countriesunder circumstances of emergency to parallelimport cheaper drugs and to have compulsoryregistration. A lot of pressure has been put onSouth Africa currently not to go that route. Infact, there is an act of Parliament that is now atthe high court being challenged which wouldenable government to do parallel importing andregister drugs compulsorily. The pressure hastaken a range of forms. South Africa is on awatch-list in the United States as a potentialproperty rights violator. And shortly after thiswatch-list two months later, preferential tarifftreatment was withdrawn for four imports fromSouth Africa to the United States. And so there’sa real challenge here to understand globallywhat are the ethics, how are they going to ensurethat poor people have access to cheaper drugs inthe presence of these kind of pressures?

Let me conclude by saying I’ve tried to dem-onstrate that the ethical issues around the HIV/AIDS epidemic are of global importance. I’ve alsotried to show that there is a real potential forconflict between researchers, individuals, com-munities, health care workers, patients, pharma-ceutical companies and governments. And itis my hope that as we confront these ethicaldilemmas we will not only begin to understandthem better, but we will, in fact, be able to mounta global response to what is indeed a humantragedy.

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— Comment for the Presentation —

The Ethics of HIV/AIDS: A South African Case Study

Maha El-Adaway (Takemi Fellow 1997–98, Egypt)

Program Officer, Human Development and Reproductive HealthFord FoundationEGYPT

I would like to thank Professor William Pickfor the excellent presentation, which tackledmany of the issues that we are dealing with inAfrica, especially the epidemic of AIDS and itsexplosion.

Although I come from the other side of Africa,where the epidemic takes a different picture, weare in touch with what is happening, because wewant also to know and to learn from what’s hap-pening in the sub-Saharan part of the continent,because it is going to affect us in the future. Wehave to learn from the experiences.

Professor Pick tackled a number of subjects,including confidentiality and consent, ethicalissues related to vaccine development in a devel-oping country where finances should be allo-cated to other areas, such as in treatment, andthe ethics of treating pregnant mothers who areHIV-positive and may transmit the infection totheir children. When looking at all of this, itraises many questions about how priorities areset. Is it more important to develop a vaccinewhen other countries are developing it, or isit more important to treat patients with HIV-positive in general, or to treat mothers becausetheir unborn children are still free of infectionand we can really save them? So it raises notonly ethical issues, mainly in the form of equity,but also about affordability and financialresource allocation. And more importantly, itshows us how the political environment canshape the agenda for HIV/AIDS and treatmentin the country.

One of the ideas that Professor Pick dis-cussed which seems to be particularly relevantto me in Egypt was whether we should focus our

efforts on preventing HIV/AIDS or on treat-ment. And what would be the role of donors andforeign funders in shaping this interest? If Italk about the experience in Egypt, we are nowin the beginning of the health sector reform pro-cess where a basic benefits package is beingdeveloped. And, unfortunately, HIV/AIDS is notpart of it, not even as a preventive measure. Andwhen we ask why this is not part of it, we say,well, we are a low-prevalence country where HIVis not really a serious matter. But, unfortunately,our Ministry of Health is not giving any atten-tion to HIV/AIDS. All the cases that are takencare of are actually done through foreign-fundedprojects. Even though it is called the NationalAIDS Control Program, the fact is it is onlyfunded through UNICEF and other interna-tional agencies.

So what can we do? What can we do for pre-vention purposes? And what can be our issues?How can we set our priorities? I thought when Iwas listening to Dr. Pick maybe it would be nicefor South Africa to produce a vaccine or producea drug that can be used in countries like Egyptand in other countries, because surely theywould provide it at a better price. But looking atthe intellectual property rights, would it be pos-sible? And when would that be possible? I knowthat many of us would not have an answer orwould be confused to give an answer to this. Is ityes or no? Should we look at affordability andour resources and how we allocate them, orshould we look another way on what is fair andwhat’s equitable? I had most difficulty with thecase about the children, the unborn babies. Is itreally not fair that we do not give treatment for

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the mothers, especially in other developing coun-tries? In Thailand like you showed us, the shortcourses proved to be useful and to prevent theinfection from going to children. We can savechildren who have are infected for no reason, itwas not their fault that they are getting sick orthey are becoming HIV-positive. And I actuallydiscussed this with Professor Pick, and he toldme that some studies were done, on a very smallscale, but these studies showed that giving treat-ment to mothers and preventing the infection

from going to children is actually very cost-effective. So why don’t we take the argument andat least treat the mothers? But it also is not fairto treat the mothers and not give the drugs to theother people who are sick in the community. Butlook at it from the viewpoint of the children whoare born without an infection if their mothersare treated. For children to be sick or not to besick should be their own choice, and surely theywould not want to be born into this world withthis infection.

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Takemi Fellow Presentation

I would like to discuss issues surroundingtwo contradictory pharmaceutical policies. Oneis when a drug is considered a public health tool,then we want the policy goal to be to make itavailable and affordable to the entire population.So we want to increase access. Now, if a drug isconsidered a different object, as an object whichis intellectual property, then the policy argumentis that it is the property of someone, then theright to the property needs to be protected andthen monopoly is given. So, these two are contra-dictory in terms of policy decisions on a specificcase. I will present two cases in Thailand to showthe dilemma surrounding these two policies.

But first let me discuss the Trade-RelatedAspect of Intellectual Property Rights Agree-ment (TRIPS). Basically, the main point ofTRIPS is that it requires member states to set upa system for patents that will protect intellectualproperty rights which would be valid protectionfor 20 years. But TRIPS also allows some excep-tions. In the case of necessity for public healthand nutrition in a country, the government canadopt some measures to stop patents for a while,to address the public health concern. One ofthese measures is compulsory licensing, which isthe authorization of someone else, a third party,to be able to manufacture and sell, in the case ofpharmaceuticals, the product without the con-sent of the patent holder.

In Thailand in the past decade there havebeen two big controversies surrounding patents.The first one was the revision of our earlierpatent law to adopt product patents. Earlier wehad only process patents. In 1992, Thailanddecided to adopt product patents, even thoughTRIPS allows a transition period for developingcountries, and we are a developing country. So

we actually can adopt it this year, or maybe infive more years. However, Thailand did it veryearly. It wasn’t because we were very quick, butbecause we were pressured to be quick, becauseat that time the United States and Europeancountries pressured Thailand to adopt patents,to revise our patent law in exchange for someincrease in export quota. The increase in exportquotas was temporary, but the change in the lawis more permanent. Although it did not seem tobe smart to do it, the Thai government did itanyway.

A new case happened last year and continueduntil the earlier part of this year, which had to dowith a drug called DDI or didanosine. This is adrug to treat HIV/AIDS, and there was a processpatent issued for this drug in January 1998. Thepatent holder is Bristol-Myers Squibb. The issuearose last year when NGOs discovered thataffordability is a problem, because each tablet ofDDI costs about a dollar or a little bit more, andyou have to take four tablets a day. So the costper day is about 178 baht. It’s quite difficult fora large number of low-income people with HIV/AIDS who need this drug. Their minimum wage,which is the legal minimum wage, per day is 120baht. They go without food and other things justto buy drugs and still find themselves withoutenough money to buy just this one kind of drug.So affordability is clearly a big problem here.

Thailand has a strong AIDS group led by oneof the new senators; and health NGOs for thelocal people; and some international NGOs, suchas Doctors Without Borders, MSF. All thesegroups participated in the campaign to requestthat the government do something about DDI.What they proposed was compulsory licensing toauthorize a government pharmaceutical organi-

Protection of Intellectual PropertyVs. Protection of Public Health: Ethics and Politics

Sauwakon Ratawijitrasin (Takemi Fellow 1995–96, Thailand)

Department of Social PharmacyFaculty of Pharmaceutical SciencesChulalongkorn UniversityTHAILAND

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zation to manufacture this product. However,the Ministry of Health chose to do two things.First, they negotiated with the drug company toreduce the price. After several months of nego-tiation and campaign, the result was that thecompany agreed to reduce the price about 30%,and then the government allowed the Govern-ment Pharmaceutical Organization, the GPO, toproduce the drug, not in tablet form, but in pow-der form. The powder is added to antacid andthen you mix it with water and you take it. It ismore inconvenient, but it doesn’t have anythingto do with the patent because the patent is aprocess patent. So the patent is intact, and theright is intact. There are some other means,although more inconvenient, but some othermeans to reduce the price and increase afford-ability, and the Government PharmaceuticalOrganization product costs about 50% of theoriginal price of the tablet.

For these two cases there are dilemmas onethical principles or political concerns that canbe raised. First, there is something about privateincentive or private reward to promote protec-tion of intellectual property rights for innovationin the future, versus public interest that willhelp to increase access for health needs immedi-ately. So there is something about private andfuture versus public and now that must beweighted in making a policy decision. The secondissue is to what extent will multi-national corpo-rations and governments from other countries beable to charge high prices in developing coun-tries. How much do developing countries’ poorpeople need to pay for the price of innovation in

another country, which may be excessive interms of cost of living, which is very different?

However, from the observation of these twocases we may ask whether ethical issues weredebated at all during the decision to adopt prod-uct patents or during the decision not to do com-pulsory licensing. Apparently the answer is no.Ethical issues were not considered when thepolicy-makers or the government made decisionson these two particular cases. It was politicalconcerns that led them to make such a decision.And I think the reason is probably very simple,because the benefit of public health is basicallydispersed and accrued to the powerless. How-ever, the profit of trade is concentrated andawarded to the powerful. So it’s very clear forpolicy-makers. When there was pressure fromoutside, other governments, it’s the pressure ofthe real power and lobby from the pharmaceuti-cal textile and other industries, which allowedsacrificing health and pharmaceutical patents,in exchange for increased export rights. Then inthe second case there are two pressures, so thegovernment adopted compromise measures.

So, I think in conclusion I would like to saythat ethical analysis needs to be made veryclear in every policy debate. Price negotiationsbetween governments and pharmaceutical com-panies may be practical, but it’s very difficult forthe public to really understand or accept. Inaddition, in order to make ethical analysis clearthere needs to be political analysis and politicalstrategies to implement the analysis, so that theconclusions from the ethical analysis can reallywork in the real work.

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— Comment for the Presentation —

Protection of Intellectual PropertyVs. Protection of Public Health: Ethics and Politics

Jin Hyun Kim (Takemi Fellow 1996–97, Korea)

Professor, Department of Health Policy and ManagementInje UniversityKOREA

Dr. Sauwakon pointed out the public choiceproblem between an innovator’s private profitsand the public health. But I would like to see thisissue from a slightly different point of view. Inother words, I’d like to touch on trade imbalancebetween advanced countries and developingcountries in the pharmaceutical industry. In aninternational perspective the point is: who getsthe benefits from the protection of intellectualproperty rights? And who bears the burden?Most drugs, including essential drugs widelyused in developing countries, are developed bymulti-national drug companies. Most of themare based in the U.S. or European countries, notmuch in Japan. It is very interesting that, as faras I know, Japanese pharmaceutical companiesare mostly focused on domestic markets. Theydon’t export as much as the U.S. or Europeancountries. I don’t know why exactly.

Multi-national drug companies in the U.S. orEurope have comparative advantage in technol-ogy, research and development and worldwidedistribution channels in the pharmaceutical in-dustry. As a result, there are few original brandsin developing countries, which means that devel-oping countries have to pay many royalties for

the use of intellectual property rights. But thedilemma that developing countries have is thatthey cannot afford to pay for it. The prices ofbrand drugs are usually very high in developingcountries compared with production costs. Thisimplies that the enforcement of intellectualproperty protection will give a strong economicincentive to make multiple imitations of originalbrands in developing countries. In this situationdeveloping countries will be reluctant to sign theTRIPS agreement. This may bring about legal,political and ethical problems among majorstakeholders, both in developing countries andadvanced countries. In this regard, the TRIPSagreement in the WTO system should be recon-sidered, I think, in such a way that the protec-tion of intellectual property rights does not jeop-ardize the public health in developing countries.For example, the protection periods applied todeveloping countries could be reduced to, say, 10or 15 years from the current 20 years. And theprice should be flexible. Otherwise, essentialdrugs, as well as new effective drugs, will not beavailable in developing countries under theTRIPS agreement.

(December 2nd, 2000)

47

Antimalarial Drugs:Attractive Innovations, Tough Choices

Allan Schapira (Takemi Fellow 1987–88, Denmark)

Regional Advisor in MalariaWHO/Western Pacific Regional OfficeDENMARK

Takemi Fellow Presentation

This presentation follows very much on whathas already been said about the ethical issuesrelated to drugs in developing countries. Al-though we always hear that the malaria situa-tion has gotten worse, the number of malariadeaths has actually gone down overall, but goneup again in the last two decades (Fig. 1). Thedecline in malaria deaths is due to improve-ments in the situation in Asia, with access todrugs and destruction of forests probably beingthe two major factors. In recent years China hasbeen one of the countries most impressive inreducing the malaria burden. North Americaand Europe, of course, have been very low formany years. In Central and South America, thefigures are relatively low. The reason for theincrease during the last two decades, then, isthat the situation has not improved in Africa. Infact, the situation has become worse in Africa,and one of the major factors in making thesituation worse in Africa is worsening drugresistance, particularly chloroquine resistance.

We have chloroquine resistance practicallyeverywhere now (Fig. 2), and fansidar resistanceis spreading and has during the last five yearsbecome quite important in some parts of Africa.We have had resistance to the more recentdrug mefloquine for the last 10 years in Thailandand neighboring countries. And there is alsomefloquine resistance in some areas in SouthAmerica.

The traditional view about antimalarial drugpolicies has been that you get resistance to onedrug, then you change to another one. Countrieshave changed from chloroquine, to amodiaquine,which is only a little bit more expensive, tosulfadoxin-pyrimethamine, better known asfansidar, which is also quite inexpensive. Butthen, the logical choice after that in terms of easeof use and effectiveness, mefloquine, becomesquite expensive. And then if mefloquine resis-tance occurs, as has been the case in Thailand,you will use something like quinine and tetracy-cline combined, somewhat expensive, but with

(December 2nd, 2000)

Fig. 1

48

the much worse problem than the price which isthat the regimen usually lasts for one week. Andit’s very unpleasant to take quinine three timesa day. Actually nobody does it because it doesn’treally work. People don’t get cured by quininetetracycline.

Then in the 1980s the world realized thatthere was a treasure in China that was beingrediscovered, so-called qing hao-su, traditional

medicine going back several thousand years,used for treatment of fever, possibly also used fortreatment of malaria in China. Data wereworked up in China during the 1980s. Effective-ness and efficacy were shown, and safety wasalso shown in China. And there are a lot ofderivatives in the first generation which arerather similar. There are small price variationsthat make it interesting to play around between

Fig. 2

Fig. 3

Effective Regimen Cost range (US$)°Options againststrains (daily doses� (adult RX course)

resistant to days)Chloroquine (CQ) None 1�3 0.06–0.22

Amodiaquine CQ 1�3 0.17Sulfa-pyrimethamine CQ 1�1 0.06–0.10

Mefloquine (15mg/kg) CQ, SP 1�1 1.55–3.18Mefloquine (25mg/kg) CQ, SP 1�2 2.33–4.77

Artesunate-Mefloquine CQ, SP, Q. M (1�3)�1 2.25–3.85(15mg/kg)

Quinine7 CQ, SP 3�7 1.22–1.63Quinine3-Tetracycline5 CQ, SP (3�3)�(4�5) 0.66–1.16

Quinine3-SP CQ, SP (3�3)�1 0.58–0.8Quinine7-Tetracycline7 CQ, SP, Q (3�7)�(4�7) 1.42–2.27

Chloroquine-SP CQ, SP ? 1�(1�3) 0.12–0.32

° -International Drug Price Indicator Guide 1999 (except artesunate)

Options for 1st and 2nd treatment of malaria

49

these derivatives. And then there’s a secondgeneration of semi-synthetic compounds, whichare compounded with fluorine that are consider-ably more expensive and are all still in the devel-oping stages.

What is so special about these artemisinindrugs? One, the action is very rapid, more rapidthan any anti-malarial drugs. Two, the mecha-nism of action, although it is not completelyunderstood, seems to be different from themechanism of action of other classes of anti-malarial drugs, and by and large it seems thatthere is no cross-resistance between thesecompounds and other antimalarial drugs. Safetyso far is excellent. The disadvantage is that ifyou use these drugs as monotherapy to be fullyeffective they must be given for seven days. Viet-nam adopted the use of artemisinin derivativesaround 1990. There was a terrible malaria situ-ation in Vietnam during the 1980s, and deathswent up, malaria cases went up, the Slide Posi-tivity Rate went up, all of this due to social deg-radation. The economy was going terribly, andthe Soviet Union was withdrawing the DDT thatthey had provided for the country. But whenthings go bad quickly then they can also improvequickly. There was a really dramatic improve-ment in the malaria situation in Vietnam, andsince the mid 1990s the number of malariadeaths per year have been lower than ever beforein Vietnam when reasonably good data havebeen collected (Fig. 4).

It was at this time that the artemisinin drugs

were introduced. Some people have made a lotof the association between artemisinin drugsand the reduction of mortality. We’ve tried to doa very careful evaluation district by district,seeing how vector control was introduced, howthe artemisinin drugs were introduced, how thehealth services improved, and how peoplestopped migrating so much. The conclusion ofthis very careful evaluation was that thesefactors were all so interrelated that no clearconclusions could be drawn. But probably theartemisinin drugs played a role in obtaining thevery low mortality that we have now.

We can move to a country not so far fromVietnam, which is Thailand, which has not hadthese fluctuations in its malaria situation, butit’s famous for very good monitoring of resistanceto antimalarial drugs. Many years ago chloro-quine just went down and become useless, andSP fansidar went up very quickly. Then theystarted using quinine, but that went downslowly. Since people don’t take quinine theyadopted mefloquine, but after a few yearsmefloquine also started going down. Things inThailand looked extremely bad about sevenyears ago. Then in came the artemisinin, whichin Thailand from the beginning was combinedwith mefloquine, in contrast to Vietnam andChina where they used these drugs as mono-therapy. And what was detected in Thailand wasthat when combining artemisinin and meflo-quine the efficacy of this treatment was pre-served to an extent which has not been seen with

Fig. 4

Malaria situation in Vietnam (1958–1999)

SPR

SPRDeath due to malariaMalaria cases

Malaria cases (1000)Death (10)

50

any other antimalarial treatment before. Fur-thermore, the susceptibility of parasites tomefloquine has started to improve in the areaswhere the combination was used systematically.So, it looks very much as if the principle of apply-ing a combination to stop drug resistance isworking in that particular situation in Thailand.

Since this was discovered a lot of theoreticalwork has been done. The theory behind combina-tion treatment is that if you give two treatments,then you kill all the parasites, so there are nosurvivors. This would then lead to a delay in theemergence of resistance. I have to say that thereis a raging debate about the validity of thesemodels and these theories, and there are variousways of looking at it. From a theoretical view-point, it is not very well proven that the combi-nation therapy principle will lead to delay ofresistance, but empirically the observation inThailand does suggest that it works. Now, inpractice people who are working with malariachemotherapy are advocating combinationtherapy more and more these days, includingartemisinin drugs. Why? These regimens last foronly three days, which is reasonably acceptablefrom a compliance viewpoint. One or two dayswould be better. But some empirical studies haveshown that many patients can, when they areproperly educated, comply with a three-day regi-men. These regimens are well-tolerated. There-fore, we can expect to see high compliance, notonly in Thailand, where people are very disci-pline in taking the right treatment. If we havehigh compliance with high efficacy we will havehigh effectiveness. The high effectiveness meansthat patients will be satisfied because the treat-ment works. They will go on accepting the treat-

ment and take it correctly, which means againthat in practice, more for these practical reasons,we could expect the principle of combinationtherapy to work in the sense that a given countrycan for a relatively long period, 10 to 15 years,have only one antimalarial standard treatmentthat will remain effective. This will relieve coun-tries of these frequent changes that they have tomake. Especially African countries now have todo like Asian countries did 10 years ago—movefrom chloriquine to fansidar, from fansidar toamodiaquine. This will bring enormous diffi-culty, confusion and frustration on the parts ofpatients, and enormous costs for the publichealth systems to make these changes.

Cambodia is one of the countries with a verydifficult drug-resistance situation. Cambodia isa country where people get antimalarial treat-ment almost anywhere. They get it from drugsellers in the market, which is completely differ-ent from the neighboring country Thailand. Wehave tried to work with the Cambodians to de-velop a drug policy which differentiated threestrata in the country. Where it was worst peoplewould get mefloquine, in other areas quininetetrocycline, and up in the northeast, which isvery backward and still chloroquine sensitive,they would get chloroquine. This has now beenchanged to one regimen, combination of meflo-quine and artesunate, given for three days. Sinceit works universally, training and public educa-tion is much easier. Since we do not have malariaclinics like in Thailand that can give the drug tothe people, we have worked with the Cambodi-ans in developing pre-packaged formulations sothat people can get one package based on theirage group, take this one for three days and that’s

Fig. 5

51

Fig. 6

it. Operational studies so far indicate that itworks, but it’s on a pilot basis so far.

In the meantime, Vietnam, which is muchless dependent than Cambodia on foreign aid,has adopted similar principles. It has had a simi-lar situation of differentiated drug policy inthe whole country according to drug-resistancepatterns, and is now moving in the directionof one combination treatment, which is a com-pletely new treatment, developed by Chineseand Vietnamese scientists somehow out of thepurview of international cooperation from othercountries. It is a very exciting development thatthere is something developed very empiricallybetween China and Vietnam, not with the samerequirements for clinical testing as in othercountries, but the results so far look very prom-ising, and this combination is cheaper.

There was a review done recently on what acombination treatment would cost if used inAfrican countries (Fig. 6). There’s a dramatic dif-ference between the classical treatments, chloro-quine, amodiaquine, fansidar, and so on, and whatit is expected that a combination treatment wouldcost per adult dose. Even the cheapest combi-nation treatment, which is fansidar artesunate,is estimated to cost more than two dollars peradult treatment. It can probably be cut downto something like 1.5 dollars. But because arte-sunate is not a synthetic drug, because thefarmers in China and Vietnam where it’s grownwant a certain minimum for growing theirplants, and the extraction costs something, these

combination treatments will cost more thanone and a half dollars per adult dose, even inthe best of circumstances, even if there are nomultinational drug companies making profitsfrom them.

Even in Asia, for some combinations that areexpensive, the question of whether we should dotrials does come up in the decision-making. Whathas to be said in this respect is that until now inThailand and Vietnam, when trials were done itwas very difficult to project what the actual costsof the treatments would be. And the scientists,who have been quite daring in some cases fromChina, Vietnam, and Thailand, who have testeddifferent drugs and combinations, they havedone the international community a great ser-vice. The knowledge that has been gained bygoing ahead and doing clinical trials in the faceof uncertainty is now benefiting these countriesand is benefiting the international community.

Can we use non-GMP drugs when GMP is notavailable? If you stand with your back againstthe wall, what else can you do? We have to. Thereare Chinese and Vietnamese artemisinin formu-lations available. They have been checked forquality and they have been used to good effect.But what about when European and Americancompanies pick up and produce the same drugsat GMP standards? Here, now suddenly thedecision-making process is getting more compli-cated because there are choices. How much isquality worth? Some people take an absolutistviewpoint and say there that quality is essential,

52

absolute, but if it costs too much, then it’s toomuch, because the affordability may not bethere.

What about treatments that have not under-gone Phase IV clinical trials? This is a very im-portant question. And I think here we have to bevery careful, because there is now commercialpressure from some producers that have combi-nations that have been well-validated by clinicaltrials. But if we are talking about release as first-line treatment in Asian or African countries withmany hundreds of thousands of malaria casesper year, millions of malaria cases per year, thenI think we need to be very careful not just to goahead and say this is the standard treatmentbecause it has been gone through clinical trials.We need phase four safety testing before releas-ing drugs on a very large scale.

The situation in Africa is far more dramaticthan in Asia, because, by and large, in tropicalAfrican countries we can assess that there is upto one fever episode per person per year thatneeds an antimalarial treatment. Combinationtreatment costs more than one U.S. dollar peradult. There is no reason to expect that the pureproduction costs are going to get below the onedollar threshold ever. Can the governments pay?When we ask them they say no. If they have to,can they? I think it will be very difficult. And Ithink one has to be realistic, not beat the drumor talk about morality or weapons and so on. Ithink one has to accept that it’s a reality. It’s veryunlikely that African governments can raise therevenue, in most cases, to pay for such treat-ments. Can the patients afford it? Patients canprobably often afford much more than we thinkthey can afford.

The Asian experience with these drugs is thatif the patients have to pay for treatment thatthey can just afford, then they are not going topay, because there are cheaper alternatives. A

cheaper alternative is to take just half the treat-ment or to mix with something that’s cheaper orto use something that’s cheaper. And if things goin that direction, the patients are allowed thechoice between cheaper and not so good, versusmore expensive and better, too many patientsare going to take cheaper and not so good. Andwe are not going to get anywhere in the drug-resistance problem. We’re going to continue inthe same morass of rapidly developing drug re-sistance, need for changing treatment, and con-fusion about what is effective and not effective.

If combination treatment at this cost is goingto do the job of securing highly effective treat-ment for people in Asia, Africa and SouthAmerica, then there have to be subsidies so thatprice-wise it becomes a very attractive alterna-tive to monotherapies which are less effective.Public-private partnerships may be very inter-esting, but may also have drawbacks. And Ithink there is no way to avoid the decision on thepart of the international community. There willhave to be enormous public investments by theinternational community or we are not going tomake substantial progress in this field.

It should also be said that combination treat-ments are not “the” final solution to the problemof malaria treatment. They will make thingsmuch better for a long period. We still need newdrugs, and I would like again to say that thepublic investments which we are seeing now inthe various initiatives for discovery of new anti-malarial drugs are needed, because in 10 to 15,maybe 20, years, we will need new antimalarialdrugs. There are international initiatives, there’sa special initiative between Japan’s Ministry ofHealth, the Japanese Pharmaceutical Industry,and the WHO TDR Program for discovery of newdrugs. We need these initiatives to be certain ofhaving effective treatments in 10 to 20 years.

53

— Comment for the Presentation —

Antimalarial Drugs:Attractive Innovations, Tough Choices

Siripen Supakankunti (Takemi Fellow 1996–97, Thailand)

Director, Centre for Health Economics, WHO CollaborationAssistant Professor, Faculty of Economics, Chulalonokorn UniversityTHAILAND

I would like to congratulate Dr. Schapira forhis wonderful presentation on antimalarialdrugs, attractive innovations, and top choices.Dr. Schapira illustrated the dynamic problems ofantimalarial drug resistance, drug availability,quality of drugs, prices and market competition,drug resistance problems and drug use patternsin Asia and Africa. I would like to make twoadditional points for our common understandingon this issue.

First, the problem of drug resistance due toquality of drugs and quality of drug producersversus market competition and price. Second,what choices are available for policy makers,especially in the poor countries. The problem ofdrug resistance has a long history in anti-malarial drug development. There are variousfactors related to this problem. For example,quality of drug on producer’s side and proper useof drug on patient’s side.

Dr. Schapira did illustrate well the problemsof drug quality, including the problem of drugresistance. What choices do we have or in otherwords, what choices do we not have, especiallyfor the poor countries in Asia and Africa. If goodmanufacturing practice (GMP), which is a westernconcept, needs to be inexpensive and as Dr.Schapira discussed in his paper, the increasedprice of GMP products is offset by the necessaryquality control of non-GMP products we arefaced with a hard choice and need for furtherclarity. All drug producers in both developingcountries, like Thailand, and developed coun-tries, like Japan, need to have quality controlprocesses. However, each country has its own

system. GMP lays out the minimum require-ments for quality assurance and again, eachcountry has its own ethical guidelines. For ex-ample, in Thailand, GMP is for private producersonly. Why does the GPO (Government Pharma-ceutical Organization) in Thailand have its ownguidelines? We need to reinforce the importanceof quality assurance, but the question is how.Quality assurance is especially important forinternational drug markets, when we face theproblem of drug resistance due to poor quality ofdrug. Therefore, we should agree upon criteria orguidelines that every country can accept. More-over, we need to reinforce these guidelines with agood monitoring system in the country.

The second point is the choices for policymakers to assure affordability of drugs. This is aserious problem in making choices for variouscombination treatments. Each country has itsown health care financing system. Some mightoffer what we call a benefit package. Again,should antimalarial drugs be included in thepackage or not. In other words, who pays fordrugs: the patient or the government? This con-cerns the ethical issues that Dr. Michael Reichaddressed in the morning. There should besufficient evidence to show the cost effectivenessof each alternative treatment. However, this isnot an easy thing, since there are problemsbetween efficacy and effectiveness. Therefore,comparative studies among countries are essen-tial. We need to consider the methodology of eachstudy carefully, especially studies done in onecountry with different situations than othercountries, such as studies on drug availability,

(December 2nd, 2000)

54

patient behavior, preventive policy such as cover-age or vector control and improvement of healthsystem. We still have the conflict between donorand recipient countries policy on antimalarialdrugs, and the problems of price setting. To

create an information base is important, and itcan be shared among countries to make a betterchoice for the poor patients who have no choiceat all.

55

Takemi Fellow Presentation

There have been two major health care re-forms in Korea in the last five years. One is thehealth insurance reform that has changed oursystem from a multiple fund system like Japan’sto a single payer system. That change is nowcomplete and presently we are in the process ofgoing through a second reform, which is on thedrug distribution system.

The new drug policy started implementationfrom July 2000. This means that we alreadyhave a new policy in effect. But now there areproblems that have arisen as a result of this newpolicy implementation. And so, let me go intodetails of this new policy. I will tell you what thecurrent state is and what we can expect fromthis new policy.

There are a few interesting features attachedto this new drug policy. The first is that we hadunprecedented physician strikes four times inthe last six months. The second interestingfeature is that this drug reform policy is drivenby consumer organizations. It is not driven bythe government, not by the medical groups, notby the pharmacists, it is driven by consumergroups. Although we need further refinement ofthis new policy, fortunately the physicians areback to work fully, 100% now. The physicianscame back to clinics and hospitals, and theconsumers, although they have some inconve-niences because of this new policy, they go alongwith this new rule. So, in a word, the new policyis in place.

Now, there are many ways to look at this newpolicy. I’m trying to look at this policy in terms ofchanged economic incentives. And I would like totell you why we needed this policy change and

what we expect from this new policy.In Korea, we have assured quality drugs.

They are available, we can afford them, but theyare not used rationally. This is the problem wehad. It is the typical middle-high income countryproblem of drug consumption. And another prob-lem we had is we did not have adequate regula-tory capacity in drug dispensing. It is a dual dis-tribution system, so all drugs are sold either bypharmacists without prescriptions or by physi-cians in their own clinics and hospitals. So thereis no division of roles between physicians andpharmacists. On top of that, if you sell drugs youhave, on average, 50% profit margins. So if yousell drugs worth of $1,000 per month, you gain$500 as profit margins. Because of this strongprofit incentive, and since there is no division ofroles between physicians and pharmacists, bothphysicians and pharmacists have a very strongincentive to prescribe, to dispense more drugsthan necessary. That was the problem we had.Under this situation there is no way that con-sumers can use drugs rationally.

In summary, I could say that Korea had alack of safety monitoring in dispensing, whichmeans that there is no cross-checking in drugdispensing. Physician and pharmacist drug dis-pensing and prescriptions are not checked byother agencies. The result is the misuse andexcessive use of drugs. Another result is exces-sive expenditure on pharmaceuticals. I think thetotal level of expenditure in total health careexpenditure is slightly higher than the case ofJapan.

Another problem we had was that since thepharmaceutical companies spent a lot of money

Policy on Drug Distribution in Korea— A Challenge to the Welfare State —

Bong-min Yang, Ph.D. (Takemi Fellow 1989–90, 95–96, Korea)

Professor of Health EconomicsSeoul National UniversitySeoul, KOREA

(December 2nd, 2000)

56

for product promotion, we have very little moneyleft for research and development. That meansKorean pharmaceutical companies did not havea competitive edge in the international market.So, we introduced a reform where, prescribingand dispensing of drugs are done in a linear way.I call it a separation policy in that under thispolicy, physicians only prescribe, pharmacistsonly dispense based on prescriptions, and sepa-ration is mandatory for all outpatient services.Outpatients in general hospitals, hospitals, uni-versity hospitals are all subject to this newpolicy. You have to give the prescription to thepatient, and the patient takes the prescription toa pharmacist outside the hospital. It’s manda-tory. There is no way you can buy a drug withina hospital. That is what I mean by separationpolicy.

Because of this new system, physicians havelittle margins left by selling drugs. And for phar-macists, the margins from arbitrarily dispensinghas diminished as a result of this new policy. Andso, both physicians and the pharmacists haveless incentive for excessive prescription and dis-pensing. From this changed situation, we expectimprovement in public health and that misuseand excessive use of drugs will be reduced. Wealso expect an improvement in drug safety. Itmeans that pharmacists now review the physi-cians’ prescriptions, and medication errors canbe reduced as a result of this new single system.The financial implications are the following.Although in the short run we expect an increasedfinancial burden on consumers, in the long runas consumption on drugs falls, we expect peopleto spend less on drugs.

Another benefit we expect is consumer rights.In the past consumers did not know anythingabout the drugs they consumed. On prescriptioncharts the language the physician used wereonly between physician and the dispenser withinthe clinics, who were generally nurses, includingsome part-time nurses. But that languageshould now be common to everybody, a languagethat’s known. So consumers now know what theyconsume to treat the health problems they have.

There is also an enhanced transparency inhealth delivery. In the past 20 years or so,fraudulent claims by physicians, pharmacistsand Oriental medicine doctors had been a verybig problem for health insurance financing. Butnow those false claims can be reduced a lot.

Fraudulent claims can now be reduced becausenow for a single patient who gets a prescriptionfrom a physician and gives this prescription tothe outside pharmacist, both the pharmacist andthe physician claim for reimbursement sepa-rately. So if these two claims are compared, youcan check whether the claims made are true ornot. So we expect a significant reduction ininsurance reimbursements. That is what thegovernment says is an important benefit of thisnew policy.

Another benefit that we could expect fromthis new policy is that we can enhance theefficiency of the pharmaceutical industry. As Imentioned, Korean pharmaceutical firms arespending a lot of money on product promotion.Now with generic substitution possible underthe new system, that product promotion bypharmaceutical firms can be much less. Thesaved money can now be used for research anddevelopment for these pharmaceutical firms sothat they can have a competitive edge in inter-national and domestic markets.

The new policy has caused controversy, suchas the physicians striking four times. But now,they have come back to work and the new policyis fully in force. But still, there are some unre-solved issues that are under negotiation such asthe extent of generic substitution, and the limi-tations on pharmacists’ arbitrary dispensing.Twice in the last six months there has been anincrease in the insurance fee, which is the mainreason physicians came back to work. And thegovernment has promised another increase inJanuary of next year, which is just a month away.But that is another issue still under negotiationbecause consumer groups, labor unions and thefarmers now challenge this government feeincrease. And in the last four weeks these con-sumer groups and labor unions are refusing topay those fee increases that already happened.So it is a problem for the government to handle.They already promised provider groups to in-crease fees, but consumers refuse to pay thoseincreases.

Finally, I would like to make the conclusionthat both retrospectively and prospectively, thereform policy was the right choice. We have hada lot of problems and controversies so far, whichI believe are due to a government that was notprepared in time. Right before I came to Japan Imet a top decision-maker in government, and I

57

told him that now you’re facing problems, chal-lenges from consumer groups, challenges fromphysician groups, challenges from pharmacists.The only way you can solve this complex problemis to have your own position fixed based on publichealth ethics. That is what I meant by philoso-phy. Otherwise, the problems will continue.

I am asking the government to have the rightethics, at least from now on. I told them that isthe only way to restore consumer trust. The

problem is that the providers—the physiciansand the pharmacists—as well as the consumersdo not trust the government. That’s a big prob-lem for them. The government is moving back-ward, forward, right, left. They are drifting. I toldthe government to decide on its position accord-ing to clearly stated public health ethics. I keepasking what is your ethics, what is your philo-sophy about public health?

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— Comment for the Presentation —

Policy on Drug Distribution in Korea— A Challenge to the Welfare State —

Kanchanasak Phonboon (Takemi Fellow 1986–87, Thailand)

Research Manager, Environment and Health ProgramHealth Systems Research InstituteTHAILAND

First of all I would like to thank Dr. Yang forthe very useful and valuable lessons for Thai-land, because we plan in the near future toundertake the same policy reform. The lessonsfrom Korea would provide a very good exampleon how to plan in such a case. Along the spec-trum that Professor Michael Reich talked aboutthis morning, I think I am in the utilitariancamp, and a little in the communitarian camp, somy point of discussion will be based on suchpositions.

From the excellent presentation by Dr. Yang,we can look at many dimensions. Because Dr.Sauwakon has presented her very useful ethicaldilemma on drugs, I will focus instead on the roleof physicians. I would like to focus on two pointsafter Dr. Yang. First, the personal freedom andmarket incentive versus patients’ and publicinterest. If the medical professional has personalfreedom to do anything, I believe that he or shemust do the best that one can do to serve the bestinterest of the patient and the public. In thiscase, I think it would be best for the interests ofthe patients and the public to have a separaterole between physicians and the pharmacists indispensing drugs to the patient, because withouta separate check and balance system it would be

very hard to see whether a doctor might try toencourage patients to take some kind of treat-ment that maximize his or her benefit or incomeinstead of maximize the patient’s benefit atthe end.

The second point is about prevention versuscurative care. In this case also substantial re-sources might be spent for curative care insteadof prevention to improve overall health of thecommunity. There are already many approachesfor prevention that Dean Barry Bloom presentedwhich encouraged people to change or maintainwhat they have. One aspect of prevention that Ithink is very important is on risk management,because in most middle and high-income coun-tries most of the health problems are chronicdiseases. And clinical decisions for both patientsand doctors are complex, and there are manytrade-offs, for example, in decisions aboutwhether one should take aspirin to preventheart disease or whether a woman should takeestrogen therapy after menopause. These deci-sions need more time to discuss and communi-cate between doctors and patients. And this alsowould be better to spend time with, instead offocusing only on the curative aspect.

(December 2nd, 2000)

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John Bertie Mendis (Takemi Fellow 1991–92, Sri Lanka)

Representative: Yangon, UNICEFSRI LANKA

Comment for Second Session

The four papers presented this afternoon andthe respective commentaries that followedhighlighted a number of ethical dilemmas facedby policy-makers and decision-makers. Thesedilemmas emerge when they are confronted withthe need to ensure both the protection of intellec-tual property rights and human rights of indi-viduals to survival and enjoyment of the highestattainable standard of health and for the treat-ment of illness and rehabilitation. If ethics canbe viewed as a set of principles that guide moraldecision-making and behavior, the papers dem-onstrate that the principles to guide decision-making, to defend intellectual property rightsare not only well-formulated but are also backedsolidly by political, legislative and adminis-trative means, for example, the WTO arrange-ments. However, the principles to defend indi-vidual rights to health care, though equally wellformulated, in human rights instruments, sufferfrom a lack of or weak political, legislative, andadministrative commitment for their effectiveimplementation. What needs to be done to levelthis playing field? How many more million livesmust be lost due to malaria and HIV/AIDS, forexample, before acceptable compromises arefound to protect both intellectual property rightsas well as the rights of individuals to the highestattainable standard of health?

The authors suggested a number of solutionsthis afternoon—long-term purchase agreementsto seek price reductions for essential drugs, sub-sidies for essential drugs through international

financing, and generating public pressure toleverage political commitments and actions, aspossible strategies to level this playing field.These are pragmatic solutions. But are theyadequate? I doubt it. But we who believe inequity and social justice must continue thesearch for the compromises that will truly levelthe playing field for the benefit of all.

Professor Reich, if I may paraphrase, saidthat there is a right way to do things out there.The idea of a global forum suggested by mycolleague, Dr. Coleman, possibly organized bythe Harvard School of Public Health and JMA, tohelp further clarify the understanding of inter-national health and contribute towards thedevelopment of processes and methods thatcould be applied at national and internationallevels to resolve ethical conflicts, deserve seriousconsideration. As a U.S. multilateralist, HarlanCleveland once wrote in an essay on humanrights, “We may be living, even if we are notnoticing and articulating, through one of theprofound shifts in human values that comesalong once in a millennium. The idea of humanrights, the notion that societies should be man-aged as if people mattered is so fundamental, sonatural, so obvious once revealed that it may bejust the first revolution to achieve global reach.”

Finally, I wish to thank the Takemi Programand the Harvard School of Public Health for myown professional growth and the Japan MedicalAssociation for making it possible for me to behere today.

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Michael R. Reich

Taro Takemi Professor of International Health PolicyChair, Department of Population and International HealthHarvard School of Public Health

General Comment

I would like to begin by expressing my appre-ciation to all of the Takemi Fellows who havemade presentations and comments at this Sym-posium. From my heart, I want to express myappreciation that you are here and for your con-tributions. I would like to finish today with threethoughts about ethics and public health, and toillustrate those thoughts with some statementsfrom the presentations.

The first point is that ethical issues are every-where in public health. You cannot approach apublic health question without confronting ethi-cal questions. We know that there are limitedresources, we know that there are life and deathquestions, we know that you have to makedifficult decisions, especially in poor countries.One thing I was reminded of today is that a basicproblem is that there are technological changes,new technologies and organizational changeshappening in our health systems faster thanchanges in our ethics. The ethical codes can’tkeep up with the changes in the health systems.As Dr. Nishida said, “What kinds of ethics do weneed for managed care?” As Dr. Marui said,“Where do we die?” This is a question that isrelevant not just for Japan but for many coun-tries. How do we assure the quality of life whilewe are dying? What is a good death and whodecides what a good death is? And in Taiwan, asthe health system is changing, a series of ethicalproblems are arising—conflicts among differentschools of medicine, conflicts in an aging societyand health reform efforts that have put values atthe center of the political agenda. Ethical ques-tions were also raised in the presentation aboutdietary supplements by Geok Lin Khor. How dowe regulate sales of dietary supplements on theInternet? What should we be regulating? Shouldwe be regulating misleading claims? Should webe regulating health claims? How do we dealwith the question of should we limit what peoplewant? So, ethical issues appear throughout pub-lic health, and medicine, almost everywhere we

look.The second point is there are no simple or

single ethical answers. This relates to a broaderset of questions in philosophy which says there isno moral truth out there, that the utilitarians,the liberals, and the communitarians, are alllooking for something that doesn’t exist. Thisposition argues that moral truth is not dis-covered, it is created. This is the school ofthought known as post-modernism. They saythat you can’t find moral truth the way that youfind scientific truth, because moral truth doesn’texist, we have to create moral truth, that there isno single moral truth, there are multiple ideasabout what is good and what is right, and thatwe need to combine these in new ways that makesense for us. I was reminded of this point in Dr.Lan’s presentation on Taiwan. He said, “We needto rethink values in health and medicine, and weneed to rebuild trust in new health systems.” InThailand how do we balance the protection ofpublic health with the protection of intellectualproperty, and how do we know it’s in balance? AsDr. Bimo said about health reform, “There is nosingle comprehensive health reform that willwork everywhere. There is no one model. It hasto be constructed within the realties of eachcountry.” Similar issues arose in Prakasamma’scomments about people who believe that asthmacan be treated if on a certain day you take amedicine in a fish and swallow it. Should we beregulating this? Are these beliefs wrong? How dowe decide?

My third point is that we need to constructnew moral agreements. If moral truths are cre-ated, then we have to be better at learning howto construct moral truths, moral agreementsthat will work, that will be effective. The paperspresented today showed that this can be done.Dr. Gupta talked about the ways in which doc-tors have become agents of change on tobacco.Lola Dare asked a pointed question, “Whosereality counts?” The point is that we have the

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potential to shape the answer. We have thepotential to shape whose reality does count.

Dr. Sauwakon, in talking about Thailand,said, “Ethical issues have not been raised effec-tively. It’s all been based on politics.” And thenshe said, “We need to find political strategiesthat can introduce ethical questions more effec-tively into policy decisions.” She stated that thishas happened with tobacco in Thailand. SenatorTakemi is trying to do the same here in Japan, tointroduce ethical issues through the tax code ontobacco.

Two last examples come from AllanSchapira’s presentation on malaria. He arguedthat there is a need for a commitment from richcountries both to make available existing thera-pies for malaria and to invest in new technolo-gies for malaria. To make this happen effectivelyrequires a new moral agreement which recog-nizes the connection between rich countries andpoor countries and puts significant resourcesinto making that happen.

Finally there is an example from Korea. Thequestion of separating prescribing from dispens-

ing is a very sensitive issue in many countries inAsia, including Japan. Korea is a case of “bigbang” policy reform. They’ve done a sudden sepa-ration, mandatory, and it has had all sorts ofconsequences. What Dr. Yang did not tell you, inhis modesty, is that not only has he been study-ing this process, he has been participating, facili-tating and leading this process. He has beeninstrumental in helping to create a new moralagreement about how pharmaceuticals will beused, dispensed and paid for in Korea. He’s notjust an observer, but very much someone whohas crafted and constructed the new moralagreement.

I think this leaves us on a positive note thatit is possible to construct ethical arguments andmoral agreements for public health reforms.Indeed, it is something that we must do in eachof our own societies and globally to realize thepotential that exists for improving the health ofeveryone, for making societies more just and fair,and for giving people a sense of real substantiveparticipation in improving the quality of theirlives.

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Organizing Committee

Chair: Hokuto Hoshi (TF 1996–97)Executive Member, Board of TrusteesJapan Medical Association

Eiji Marui (TF 1986–87)Professor, Department of Public HealthJuntendo University School of Medicine

Yasuki Kobayashi (TF 1989–90)Professor, Department of Health Economics and PolicyGraduate School of Medicine, University of Tokyo

Keizo TakemiMember, House of Councilors

Facilitator: Dr. Hokuto Hoshi(Executive Board Member, JMA)

Chair: Dr. Akira Koizumi(Vice-President, JMA)

Chair: Mr. Keizo Takemi(Member, House of Councilors)