OOCCUUVolume 8 Number 11 October 1993

FF A Guide toAIDSResearch and Counseling

SSWomen’s participation in clinical trials

is essential. Factors such as age andweight affect drug metabolism; it is inac-curate to assume that female-specificfactors—hormones, percentage of bodyfat, menstrual cycle changes, and otherless tangible influences—have no impacton drug efficacy.

Women, however, have historically beenunderrepresented in medical researchcohorts and clinical studies, includingseveral major myocardial infarction andhypertension treatment trials of the past10 years. AIDS research has maintainedthis gender imbalance: men have been thefocus of epidemiologic and natural historystudies as well as of clinical drug trials forthe treatment of HIV infection and itsassociated opportunistic infections. Untilrecently, published research has focusedon women only as vectors of infection tochildren and sexual partners, despite thefact that the percentage of women withAIDS has increased steadily from 6.6 per-cent in 1985 to 11.5 percent in 1990.1

Fortunately, this situation is changing as aresult of publicity and political pressureabout the inequity and the realization thatwomen are an important pool of potentialresearch subjects.

Women with HIV disease have much togain from participation in clinical trials.The most obvious advantage is access tothe latest medical treatments. Trials alsooffer concrete psychological advantages.Participants often feel they are maximiz-ing their involvement in controlling thedisease and gain personal satisfactionfrom helping to discover an effectivetreatment. Because research staff oftenbecome involved in education and sup-

port, they establish an important caringrelationship with participants. Patientsfrequently experience reduced anxiety asthey broaden their network of providersand discover that they are valued andimportant to study staff.

This article examines the barriers towomen’s participation in clinical trials andoutlines strategies for medical and mentalhealth practitioners, as well as researchers,to increase this participation.

Barriers to Trial ParticipationBarriers to women’s participation in

research are both blatant and subtle. Theyexist on societal, institutional and person-al levels.

Societal Barriers. Overt sexism allowsresearchers to minimize women’s partici-pation with the contradictory justifica-tions that research done on men can begeneralized to women, and concern thathormonal differences in women will alterstatistical analysis.2 Concerns aboutwomen becoming pregnant during thecourse of a clinical drug trial, the poten-tial of harm to a developing fetus, andresulting liability have led to the exclu-sion of all women of child-bearing poten-tial from some studies.3 However, theNational Institutes of Health (NIH), whichprovides funding for many HIV epidemio-logic studies and drug efficacy trials, isstrongly enforcing its regulations forinclusion of women (and minorities).Compliance with these regulations is now a part of the review process for thefunding of all NIH grants and contracts.

Covert sexism leads to the situationreported at the 1991 International Confer-ence on AIDS by researcher DeborahCotton.4 Cotton found that, in addition togeographic variations in the number ofwomen enrolled in HIV clinical trials, thepresence of a female principal investigatoror coinvestigator resulted in an increase in

Women and HIV Clinical TrialsPatricia J. Kelly, FNP, MPH

the number of women enrolled. This sug-gests female investigators may have dif-ferent approaches to participant recruit-ment and retention.

Socioeconomic problems cause otherimpediments to participation in researchtrials. Poverty, substance abuse, codepen-dency, and the lack of services may makeinvestigators reluctant to work with specif-ic populations or be less willing to expendthe additional effort necessary to recruitand maintain women in a research cohort.Women from inner-city communities arelikely to receive care at community healthcenters or municipal hospitals, and not at the academic medical centers where research trials are most frequently funded.

Institutional Barriers. Although researchersmay decide that they want to enter womeninto clinical trial cohorts, they often areunaware of the necessity to design andimplement recruitment strategies that willattract women. Failure to utilize strategiessuch as meaningful incentives, child care,or patient-centered scheduling (makingappointments available at times conve-nient for patients as well as providers)

means that logistical factors remain asbarriers.

The complex structures of some proto-cols can create a further disincentive forparticipation. Multiple study questions,rigid eligibility criteria, lengthy question-naires and examinations, multi-tube phle-botomy, and inflexible clinic hours can be daunting for the most motivated ofpatients. Women with limited time, symp-tomatic HIV disease, or young childrenwill be particularly discouraged.

Personal Barriers. Women may not wantto participate in research studies. As theyare likely to be primary caretakers for allfamily members, concrete issues such asscheduling, child care and transportationare real impediments to study participa-tion. Inner-city women may not perceivestudy participation as providing any bene-fits for themselves, their families or theircommunity. Cultural beliefs may runcounter to vigorous medical interventionsin a disease process. Women who areactive drug users are generally unable toparticipate until their addiction is undercontrol. Many people of color in the

FOCUS2 October 1993

The small numbers of womeninvolved in HIV-related clinicaltrials compromises the care ofthis growing population of HIV-infected people. Appropriatecare for women in the futurerequires their involvement inclinical trials today. It is theeffects of clinical trials on cur-rent clients, however, that maybe most important to providers.

As Patricia Kelly points out in her article in this month’sFOCUS, clinical trials providewomen access to quality healthcare, expensive treatments, andpsychological support. Her over-view of the barriers and strate-gies to recruit women can helpclarify the role of mental healthand medical providers in thisprocess. More importantly, it canhelp providers communicate totheir clients and patients how toevaluate specific trials, not interms of treatment protocols butwith regard to the psychosocial

support they should offer.Kelly’s perspective is comple-

mented by Terry McGovern’sexamination of the legal aspectsof the exclusion of women fromtrials. She portrays a world ofso-called facts backed up withlittle evidence and supported bypoor enforcement of govern-ment regulations.

It is rare for me to highlightRecent Reports in this editorial.But, this month we focus on twocommentaries recently publishedin the New England Journal ofMedicine. These articles look atfederal regulations requiring allclinical trials to study subpopu-lations, including women andpeople of color. FOCUS is notable to do justice to the com-plexity of these articles, but Iurge readers to consult them fora clarification of the basic scien-tific and statistical issues at stake.

The issue as a whole providesa comprehensive view of a topic

that is not often discussed intherapy. Providers should notdismiss this topic as removedfrom the treatment challengesthat face most clients. Clinicaltrials continue to be a criticalsource of care, particularly forwomen who are less likely tohave insurance that will financetheir health care.

Getting past discrimination,bureaucracy, and the real com-plications of performing statisti-cally valid medical research is achallenge not to be understated.But, overcoming the challenge,or even attempting to overcomeit, may foster a sense of powerand competence.

Whether they confront admin-istrators of specific clinical trials,advocate through their doctors,local researchers, or the FDA, orquestion insupportable asser-tions in the courtroom, womenmay find more than frustrationwhen they seek inclusion inclinical trials. Physicians andcounselors must be prepared tohelp them face frustration andreap the rewards of assertingtheir rights.

Editorial: Trial and ErrorRobert Marks, Editor

FOCUS3 October 1993

United States have a justifiable distrust ofmedical experimentation as a result of thelegacy of the Tuskegee syphilis study, anddue to abuses in contraceptive studies andsterilization procedures.

Strategies for Recruiting WomenThe idea of a woman-centered approach

can be a guiding principle for what willwork to increasewomen’s participationin HIV-related trials.Studies that have usedthis approach havesuccessfully recruitedwomen who are ethnicminorities, immigrants,drug users, or peoplefrom lower socio-eco-nomic backgrounds.

Responsibility forrecruitment is sharedby both field staff andinvestigators. Whilefield staff must identifysubjects and discussstudy participation withthem, it is the responsi-bility of investigators toprovide the resourcesfor such work. Fieldstaff often feel pres-sured to meet unrealis-tic recruitment goals, inpopulations difficult torecruit into researchprotocols, withouthaving the necessarytools to complete thejob. To do so, investiga-tors must providepatient incentives, time, and office or clinic space.

Successful recruitment activities arefacilitated by an effective organizationalframework. This might mean that onestaff member has overall responsibilityfor coordinating and assessing the successor failure of different recruitment strate-gies. It might also involve using a data-based management system, which allowsrapid, objective feedback about perfor-mance that can be shared with other staffat regular meetings.

Essential to the task of successfulrecruitment of women into clinical trialsis a non-judgmental, supportive staff.Drawing field staff from the community ofthe desired study population further facil-itates recruitment. Bonds of trust resultmore easily when language and cultureare shared, especially when addressing

the historic suspicion of research partici-pation. Staff can create a caring environ-ment by welcoming participants in anopen, non-judgmental manner, both at the time of their scheduled study visitsand when they have physical or emotionalneeds. Study staff frequently report thatone of the most important reasons thatwomen enter clinical trials, and one that is

often unacknowledged, isthe ability of staff to takeextra time with study par-ticipants and provide themwith education and coun-seling about their HIV dis-ease. If sufficient trainedstaff are available, rotatinga beeper for 24 hour on-calltelephone coverage letsstudy participants knowthat someone will be avail-able to them.

Staff forums can providethe support and supervi-sion necessary for staffwho go to such lengths torecruit women and meettheir needs. Regular discus-sion about roles, overiden-tification, limit setting, andemotional issues raised bytheir work can prevent staffburnout and maximizeeffective relationships withstudy participants.

IncentivesIntegration of clinical

care into the research set-ting is a definite enhance-ment for research partic-ipation. It is important to

attend to aspects of clinical care duringstudy visits or to try to complete all orpart of the study protocol during a regu-larly scheduled clinic visit. An organizedsystem that makes research test resultsavailable to clinicians (with signed con-sent from patients) avoids unnecessaryreplication of costly laboratory tests foragencies and multiple venipunctures forpatients. A drug treatment counseloravailable for emergency situations andongoing counseling, regularly scheduledpsychological support groups, andacupuncture or other complementarytherapies all enhance clinical care andstudy recruitment.

Mental health staff can work togetherwith study staff to ensure that womenresearch participants have their medicaland psychological needs met. These link-

References1. Ellerbrock T, BushT, Chamberland M, etal. Epidemiology ofwomen with AIDS inthe United States,1981 through 1990.Journal of the Ameri-can Medical Associa-tion. 1991; 265(22):2971-2975.

Successfulrecruitment

begins with awoman-

centeredapproach, a

non-judgmental,supportive staff,

and theprovision of

incentives, suchas child careand clinicaltreatment.

2. Cotton P. Is therestill too much extrapo-lation from data onmiddle-aged whitemen? Journal of theAmerican MedicalAssociation. 1990;263(8): 1049-1050.

3. Minkoff H, MorenoJ. Drug prophylaxisfor human immunod-eficiency virus-infect-ed pregnant women:Ethical considerations.American Journal ofObstetrics and Gyne-cology. 1990; 163(4,part 1): 1111-1114.

4. Cotton D, FeinbergJ, Finkelstein D. Par-ticipation of women ina multicenter HIV clin-ical trials program inthe United States. Pre-sentation at the VIIInternational Confer-ence on AIDS, Florence,Italy, June 1991.

AuthorsPatricia J. Kelly, FNP,MPH is the formerDirector of Women’sHIV Research atDownstate MedicalCenter in New York.She currently teachesin the Nurse Practi-tioner program atRush University inChicago.

ages are especially important when researchstudies end and study staff terminate theirrelationships with participants. In suchcases mental health staff may be asked toaddress patient needs that had been previ-ously met by researchers or to work withparticipants who feel abandoned or resent-ful about termination.

Investigators and administrators canencourage participation by creating apositive clinic environment and offeringmeaningful incentives to subjects. Theclinic environment can promote or dis-courage recruitment. Administrators cancreate a welcoming environment by pro-viding a comfortable, congenial space forpatient visits; making literature, videos,and coffee, tea, and snacks freely avail-able; and encouraging a positive staffattitude. Depending on the number ofpatients seen, researchers might makeavailable a volunteer or staff member toprovide child care, or prepare a secure,defined play area equipped with easilycleaned toys. In order to allow patients to get in and out with a minimum of wait-ing time, bother, and paperwork,researchers should ensure that there isflexibility in terms of staff and clinictimes.

Incentives such as transportationstipends, paid in cash at the time of everystudy visit, are essential. Other incentivesmake study participation easier for sub-jects and provide them with a small butconcrete return. Some groups have givenT-shirts, mugs, baby clothes, diapers, babypictures, or tote bags, varying these byvisit. In prospective studies, where thereis a greater investment over time, it is agood idea to make the incentives moreattractive with study longevity. An annualholiday party or summer outing can pro-vide a welcome break for study partici-pants, their families, and staff. Staff can

easily maintain a system for sendingbirthday and holiday cards by using acomputerized data base.

Even with an open environment, it isimportant to maintain patient confiden-tiality. HIV-related brochures should bedisplayed only with other health-relatedliterature, questions from casual passers-by or patient family and friends—”Whatkind of clinic is this?” or “What kind ofresearch do you do here?”—answered ingeneral terms, and HIV-related informa-tion about specific patients discussedonly with those whom the patient hasspecified in a written consent. Birthdaycards and other mailings to study partici-pants should omit mention of “AIDS” or“HIV.” In addition, not every staff memberin a multi-service agency needs to knowthat clients are coming in to participate inan HIV clinical trial.

ConclusionEnsuring that women with HIV disease

have knowledge about and access to clini-cal trials is important. Mental healthproviders can assist women to enroll inresearch studies by initiating discussionabout available clinical trials, answeringquestions, and clarifying confusing detailsand technical concepts (for example,“double-blind” and “placebo”).

By maintaining communication withresearch staff, having a general idea ofavailable studies, and knowing what psy-chological and concrete incentives areoffered, mental health staff can provide arealistic picture of the advantages anddisadvantages of study participation.Their most important contribution to theenrollment of more women is to facilitatenon-coercive discussion during whichwomen with HIV disease can work throughthe decision-making process about studyparticipation.

FOCUS4 October 1993

ReferencesAllen MH, Marte C. HIV infection in wo-men: Presentations and protocols. Hospi-tal Practice. March 15, 1992; 113-120.

Carpenter CCJ, Mayer KH, Stein, MD, etal. Human immunodeficiency virusinfection in North American women:Experience with 200 cases and a reviewof the literature. Medicine. 1991; 70(5):307-325.

Currier J, Spino C, Cotton DJ. Womenand power: The impact of accrual ratesof women on the ability to detectgender differences in toxicity andresponse to therapy in clinical trials.Presentation from the VIII InternationalConference on AIDS, Amsterdam,Netherlands, June 1992.

Houle L, Rocheleau S, Lebel P, et al.Response to zidovudine treatment in

women with AIDS: Results from theCanadian open trial. Presentation fromthe VIII International Conference onAIDS, Amsterdam, Netherlands, June1992.

Long IL, Hanna L. The FDA meets withadvocates for women with HIV/AIDS.BETA: Bulletin of ExperimentalTreatments for AIDS. June 1993: 23-24.

Murphy TF. Women and drug users: thechanging face of HIV clinical trials.Quality Review Bulletin. 1991; 17(1):26-32.

Nuckols T. Pregnancy and HIV infection.

Clearinghouse: Women and Trials

HIV-infected women are often unable togain access to the early phases of clinicaltrials. There are numerous obstacles atwork, some of which have to do withthe U.S. Federal Drug Administration’s(FDA) guidelines on the subject andthe specific inclusion and exclusioncriteria of a given protocol. Otherobstacles relate to the general lack ofhealth care and treatment optionsmany HIV-infected women face. Thisarticle outlines federal regulations onthe inclusion of women in clinicaltrials and describes the response ofpharmaceutical companies to theseregulations.

An example: A physician recom-mended that one of his patients par-ticipate in Phase I of the Johns HopkinsUniversity/ Hoffmann-LaRoche tat-inhibitor clinical trial. The protocol’sfirst inclusion criterion was: “Male orfemale of non-childbearing potential(surgically sterile, one year postmeno-pausal).” When one woman attemptedto enroll in this phase, trial administratorstold her that she would have to be surgi-cally sterilized.

The client was willing to undergo preg-nancy tests, use detectable birth control,and sign a waiver and covenant not to sue.She was not, however, willing to undergosurgical sterilization. Even with the HIVLaw Project’s intervention, trial adminis-trators prevented her from enrolling inPhase I of the trial. The question is why. Itseems that what lies at the heart of thecontroversy is the fear of drug companiesthat they will incur huge liability costs byallowing women into trials.

Since the 1970s, which saw successfullitigation in cases involving the drugs DESand thalidomide, pharmaceutical compa-nies have been extremely cautious aboutallowing women into clinical trials.* Al-though a statement releasing the manu-facturer from liability is generally includ-ed in the informed consent agreement,

manufacturers worry that federal andstate laws governing protection fromharm would diminish this legal protec-tion. In reality, drug manufacturers canprotect themselves by having participantsexecute a covenant exempting manufac-turers and medical practitioners fromliability for injuries that may arise fromthe non-negligent, proper performance ofa procedure or use of a drug.1

Federal RegulationsFederal regulations require that the

selection of subjects for all clinical trialsbe equitable: women, as well as minori-

*The three pharma-ceutical corporationscontacted for thepurposes of thisarticle required, at aminimum, that femaleparticipants whoexpected to engage inheterosexual inter-course at any pointduring the trial usean approved methodof birth control. Thecompanies—Bristol-Myers, BurroughsWellcome andHoffman-LaRoche—also uniformlyrequired that femaletrial participantsundergo a baselinepregnancy test.

FOCUS5 October 1993

As a direct result of theFDA’s failure to monitor

these results and the FDAapplication process, trial

sponsors have been able toexclude women on the

basis of fetal toxicity whenin fact there is no evidence

of such toxicity.

BETA: Bulletin of Experimental Treat-ments for AIDS. March 1993: 10-14.

Selected open clinical trials forHIV/AIDS Treatments. BETA: Bulletin ofExperimental Treatments for AIDS. June1993: 39-40.

Smeltzer SC. Women and AIDS:sociopolitical issues. Nursing Outlook.1992; 40(4); 152-157.

Sperling RS, Stratton P, O’Sullivan MJ,et al. A survey of zidovudine use inpregnant women with human immun-odeficiency virus. New England Journalof Medicine. 1992; 326(13): 857-861.

Sperling RS, Stratton P. Treatmentoptions for human immunodeficiencyvirus-infected women. Obstetrics andGynecology. 1992; 79(3): 443-448.

ContactsAIDS Clinical Trials InformationService, 800-874-2572. AmFARTreatment Directory, 212-682-7440.Regional directories of clinical trialsinclude: San Francisco Bay Area, 415-476-9554; Middle Atlantic States, 212-682-7440; Northern Georgia andAlabama, 404-874-7926; Canada, 604-631-5327.

Jennifer Burroughs, NP, Bay AreaConsortium on Women and AIDS, 400 Parnassus Street, Room AC16, San Francisco, CA 94143-1352, 415-476-6018.

Patricia Kelly, FNP, MPH, RushUniversity College of Nursing, 1743West Harrision Street, Room 519,Chicago, IL 60612, 312-942-5808.

Terry McGovern, JD, HIV Law Project,80 Fifth Avenue, Suite 1505, New York,NY 10011, 212-645-8863.

See also references cited in articles in this issue.

Clinical Trial RegulationsTerry McGovern, JD

ties, children and hemophiliacs, are to beincluded in clinical research.2 On theother hand, the federal regulations severe-ly limit research on pregnant women orfetuses.3 For example, FDA guidelines forthe clinical evaluation of drugs recom-mend that women of childbearing poten-tial should be excluded from clinical trialsuntil FDA animal reproduction guidelineshave been completed, except in the caseof life-threatening illness. The NationalInstitutes of Health (NIH) has recentlyestablished policies and procedures de-signed to enroll more women and peopleof color in HIV-related clinical trials.†

Unfortunately, these policies apply only toAIDS Clinical Trials Group (ACTG) studiesand not to studies initiated by privatedrug companies.

In summary, where a drug is intendedto address the effects of a life-threateningdisease (including HIV infection), men andwomen who have that disease may partici-pate in the drug trial regardless of theoutcome of animal reproduction studies,provided that researchers fully explain theresults and implications of these studiesand treatment alternatives.

Scientific RationaleAlthough the FDA guidelines appear to

be straightforward, drug companies con-tinue to use more restrictive policies. Forexample, the woman who wanted to jointhe tat-inhibitor trial was still deniedentry. Hoffmann-LaRoche explained that it had not yet finished animal reproduc-tion studies and therefore was excludingwomen. Under the FDA guidelines, how-ever, she should have been included sinceshe suffers from a life-threatening illness.

According to at least one pharmacolo-gist aware of the clinical trial, the tat-inhibitor is a diazepine derivative, a classof drugs that has been well-studied byHoffmann-LaRoche prior to its applicationto HIV infection. These studies show noevidence of long-term negative effects onwomen’s reproductive systems. Moreover,if, despite these studies, the drug wasthought to be capable of inflicting long-term damage upon the reproductive sys-tem, then men might also risk such damage.Yet there is no requirement that menparticipating in the trial be surgicallysterilized.

Further, while the Investigational NewDrug (IND) application process mandatesthat trial sponsors report on efficacy andtoxicity, there is no requirement that theyreport on or even file with the IND appli-cation, the results of animal reproduction

studies, or any evidence of fetal toxicity.As a direct result of the FDA’s failure tomonitor these results and the applicationprocess, trial sponsors have been able toexclude women on the basis of fetal toxic-ity when in fact there is no evidence ofsuch toxicity. Thus, the animal studieswhich the FDA requires as a precursor towomen’s participation in clinical trialsmay never be conducted or may be con-ducted parallel to, not in advance of,clinical trials.

The FDA has recently announced that it is rescinding the discriminatory 1977guideline, which restricts the access ofwomen of childbearing potential to theearly phases of clinical trials. Instead, itleaves this decision to the discretion oftrial sponsors. The FDA does not propose,however, any regulatory changes thatwould require the completion of animalreproduction studies prior to humantesting. It remains unclear whether theuse of gender-discriminating protocolcriteria will cease, especially since the FDA does not actively monitor the process.

ConclusionWithout studies proving danger to

women’s reproduction, the current drugdevelopment process results in womenusing approved drugs that have not beenadequately tested for them, and it deniesmany woman the health care availableonly through drug trials. The failure ofpharmaceutical companies to follow FDAguidelines and the failure of the FDA toenforce these guidelines means thatwomen will continue to suffer discrimina-tion related to clinical trials. To battle thisdiscrimination and deliver appropriatetreatment to women, health providers aswell as activists—and men as well aswomen—must challenge drug companyphobia regarding liability and FDA reti-cence regarding enforcement.

FOCUS6 October 1993

†Additionally, for alltrials conductedthrough the AIDSClinical Trial Groupsystem, NIH policyrequires that a com-pelling scientificrationale be submit-ted for any trial thatdoes not includewomen. See “NIH/ADAMHA Policy Con-cerning Inclusion ofWomen in StudyPopulations,” NIHGuide for Grants andContracts. (First pub-lished October 24,1986, most recentlypublished February 8,1991.) Similar policyhas been issued thatseeks to redress theabsence of people ofcolor in clinical trials.

References1. Colton v. New YorkHospital, 414 N.Y.S.2d 866 (1979).

2. 42 USC 300cc-16.

3. 45 CFR 46.206-7.

AuthorsTerry McGovern, JD isDirector of the HIVLaw Project, whichprovides legal servicesto HIV-infected peopleliving in New York.

Women and HIV ConferenceThe Second Annual Women and HIV

Conference will be held on Saturday,October 23 at the University ofCalifornia Irvine Student Center.Conference admission is $10 for full-time students, $15 for the generalpublic, and $30 for health care profes-sionals. To register, or for furtherinformation, phone South CoastMedical Center at 714-499-7205.

Two Perspectives on Women in TrialsBennet JC. Inclusion of women in clinical trials—Policies for population subgroups. New EnglandJournal of Medicine. 1993; 329(4): 288-292.(National Academy of Sciences.) Merkatz RB,Temple R, Sobel S, et al. Women in clinical trials ofnew drugs. New England Journal of Medicine. 1993;329(4): 292-296. (Food and Drug Administration.)

In response to proposed NationalInstitute of Health (NIH) and Food andDrug Administration (FDA) guidelines forall clinical trials (including HIV-relatedones), two commentaries examine theeffects of the underrepresentation ofsubgroups in medical research.

The first focuses on possible conse-quences of mandatory inclusion of under-represented groups in clinical trials andemphasizes the statistical challenges ofstudying subgroups. Despite the validityof arguments to include women in researchsamples, statistical considerations requirefactoring the biological plausibility of sex-related differences with the time andmoney needed to pursue meaningful

research. Nonetheless, cost shouldnot be a consideration in determin-ing whether to include members ofsubgroups in trials.

In designing a study, researchersmust balance conflicting desiresbetween the homogeneity and het-erogeneity of a study cohort. Thestudy cohort must be homogeneousenough to yield a low level of vari-ability and diverse enough to allowany findings to be generalizablebeyond narrow subgroups. Toachieve these ends, a common strat-egy is to gather cohorts that mirrorthe composition of the general popu-lation that would receive the treat-ment. But clinical trials are rarelylarge enough to test reliably thetreatment effect within subgroups,and extremely large samples may beneeded to detect significant differ-ences among subgroups. The highcost and complexity of large-grouptrials, however, prohibit their devel-opment except in the cases of the

most common diseases.In conclusion, when researchers

exclude women entirely, they cannot gaineven a hint about differential response.Merely including some women, however,is not sufficient to learn how to treatwomen, and even including women in the

same proportion as they appear in diseaseprevalence statistics may not providereliable information.

The second article concentrates onreasons why formal guidelines are neededto ensure that the effects of drugs onwomen are specifically studied. Despitethe fact that many trials have includedlarge numbers of women, a 1988 GeneralAccounting Office study found that onlyabout half contained analyses of datarelated to subgroups.

The new FDA guidelines urge the inclu-sion of “reasonable numbers” of women inclinical trials. This is important because ofpharmacokinetic (the concentration of adrug in the blood or other tissue over time)and pharmacodynamic (the body’s responseto a given concentration of a drug) differ-ences between men and women.

These differences are related primarilyto variations in body size and composi-tion and the effects of hormones. Fourhormonal factors seem to be relevant: thelevels of gonadotrophins and circulatingsteroidal hormones during menstruation;the differences between pre- and post-menopausal women, including those whoreceive hormone-replacement therapy; thedrastically different hormone levels dur-ing pregnancy and the metabolic conse-quences of pregnancy; and the relation-ship between steroidal contraceptives andmetabolism of drugs in terms of drug andcontraceptive efficacy.

The article calls for inclusion of womenwith childbearing potential in all phasesof clinical trials. It states that women havethe ethical right to make personal choicesabout participation and notes that it ispossible to design protocols to reducefetal exposure to drugs.

Psychological Effects of Clinical TrialsRobiner WN, Melroe NH, Campbell S, et al.Psychological effects of participation and nonpartici-pation in a placebo-controlled zidovudine clinicaltrial with asymptomatic human immunodeficiencyvirus-infected individuals. Journal of AcquiredImmune Deficiency Syndromes. 1993; 6(7): 795-808.(University of Minnesota and Georgetown University.)

Participation in a clinical trial for zidovu-dine (ZDV; AZT) did not have any adversepsychological effects on asymptomatic HIV-infected subjects, according to a smallMinneapolis study. In fact, participationmay have actually reduced factors that leadto stress, anxiety, and depression.

Forty-six study subjects and 27 controlsubjects completed a questionnaire con-sisting of several standardized psychologi-cal surveys when they entered the trial,

FOCUS7 October 1993

Clinicaltrial

participantsreported

significantlylower levels

of stress,anxiety, and

depressionthan peoplewho did notparticipate.

Recent Reports

FOCUS8 October 1993

after two months, and after six months.The surveys were designed to measurelevels of hopelessness, anxiety, depression,and well-being. All but one of the subjectswas male, and their average age was 34.

Study subjects reported significantlylower levels of stress, anxiety, and depres-sion at the end of the six-month period.Control subjects also reported a decreasein depression, but no significant change instress or anxiety. Subjects who had clini-cally high levels of stress, anxiety, anddepression prior to the study reported nosignificant changes during this period.Researchers attributed beneficial effectsto feelings of altruism and emotionalsupport gained through participation inthe clinical trial.

HIV in Pregnant Women Stratton P, Mofenson LM, Willoughby AD. Humanimmunodeficiency virus in pregnant women undercare at AIDS clinical trials centers in the UnitedStates. Obstetrics and Gynecology. 1992; 79(3):364-368. (National Institute of Child Health andHuman Development.)

A survey of obstetricians at AIDS clinicaltrials centers around the United Statesestablished a bank of knowledge about theclinical and immunologic status of HIV-infected women and found that new strate-gies are needed to care for these womenand combat the progress of their illness.

Forty-five obstetricians from the 49federally supported AIDS clinical trialscenters provided information about thehealth of HIV-infected pregnant womenunder their care. They estimated that1,000 to 1,800 HIV-infected women hadgiven birth at these centers during theyear prior to December 1989. Eighty-twopercent of these women were asympto-matic, 12 percent were symptomatic, and6 percent had AIDS. While 43 of the cen-ters (96 percent) had established formalprenatal HIV antibody testing, only 30 (67percent) performed T-helper cell testing asa standard procedure. Seventy-six percentof the physicians had referred a patient toan AIDS clinical trial.

Among subjects who were symptomaticor who had AIDS, 35 women had Pneumo-cystis carinii pneumonia (PCP), the mostcommon illness reported, 17 had activetuberculosis, and 15 had candidiasis. Fiftywomen had sexually transmitted diseasesassociated with ulcers. Zidovudine (ZDV;AZT) was the most commonly used AIDSdrug but was administered to only 29women, since its safety during pregnancyis still being evaluated. PCP prophylaxis—which is not recommended for pregnant

women—was used in only 40 cases. Theauthors suggest that more routine T-helper cell testing could identify thosepregnant women for whom PCP prophylax-is might be warranted.

Minority Recruitment for Clinical TrialsEl-Sadr W, Capps L. The challenge of minorityrecruitment in clinical trials for AIDS. Journal of theAmerican Medical Association. 1992; 267(7): 954-957. (Harlem Hospital Center and ColumbiaUniversity.)

A commentary on minority recruitmentfor AIDS clinical trials suggests that strate-gies to increase participation must respondto the lack of social and educational sup-port services available to minority partici-pants and to their historical distrust of theprocess of medical research.

An analysis of past AIDS trials reveals aconsistent trend of low minority enroll-ment. African Americans and Hispanicshave constituted between 18 and 35 per-cent of the population in zidovudine (ZDV;AZT) efficacy studies, despite the fact thatthey make up 45 percent of reported AIDScases. Minorities have also been underrep-resented in studies of the natural historyof HIV. Because of the inability of researchersto draw statistical conclusions from smallsamples of minority participants, thesestudies have led to inconclusive resultsabout the effectiveness of ZDV in thispopulation.

Next MonthFamily interactions can confound an

already complicated psychosocial situ-ation for people with HIV disease. Infamilies that are poor and where morethan one family member may beinfected, these dynamics are all themore confusing. In the November issueof FOCUS, Robert Tufel, MSW, MPH,Program Director of Family SpecialServices, and Geri Brooks, PhD, Exec-utive Director of Sunburst Projects,both in San Francisco, outline the psy-chosocial issues poor, HIV-affectedfamilies face and the impact theseissues have on family dynamics.

Psychotherapy may be useful to helpfamilies deal with the stresses of HIVdisease. Also in the November issue,Gillian Walker, MSW, Co-Director ofthe AIDS and Families Project of theAckerman Institute in New York, dis-cusses approaches to family therapyfor poor, HIV-affected families.

Executive Editor; Director,AIDS Health ProjectJames W. Dilley, MD

EditorRobert Marks

Staff WritersJohn Tighe

Founding Editor; AdvisorMichael Helquist

Medical AdvisorStephen Follansbee, MD

MarketingJoanna Rinaldi

DesignSaul Rosenfield

ProductionJoseph WilsonStephan PeuraLeslie SamuelsRoger Scroggs

CirculationSandra Kriletich

InternsGregory RubinTamara Simon

FOCUS is a monthly pub-lication of the AIDSHealth Project, affiliatedwith the University ofCalifornia San Francisco.

Twelve issues of FOCUSare $36 for U.S. residents,$24 for those with limitedincomes, $48 for individu-als in other countries, $90for U.S. institutions, and$110 for institutions inother countries. Makechecks payable to “UCRegents.” Address sub-scription requests and cor-respondence to: FOCUS,UCSF AIDS HealthProject, Box 0884, SanFrancisco, CA 94143-0884. Back issues are $3each: for a list, write to theabove address or call(415) 476-6430.

To ensure uninterrupteddelivery, send your newaddress four weeks beforeyou move.

Linotronic plates partiallydonated by Design & Type,San Francisco. Printed onrecycled paper.

© 1993 UC Regents: All rights reserved.

ISSN 1047-0719

FOCUSA Guide toAIDSResearch and Counseling

U C S F

AIDSHEALTHPROJECT

DID YOU KNOW?FREE searchable archive

You can access a FREE searchable archive of back issues of this publication online! Visit http://www.ucsf-ahp.org/HTML2/archivesearch.html.

You can also receive this and other AHP journals FREE, at the moment of publication, by becoming an e-subscriber. Visit http://ucsf-ahp.org/epubs_registration.php for more information and to register!

ABOUT UCSF AIDS HeAlTH PrOjeCT PUBlICATIOnS

The AIDS Health Project produces periodicals and books that blend research and practice to help front-line mental

health and health care providers deliver the highest quality HIV-related counseling and mental health care. For more

information about this program, visit http://ucsf-ahp.org/HTML2/services_providers_publications.html.