© © Ross,Ross, 20102010

360 Degrees of Human 360 Degrees of Human Subjects Protections (HSP) in Subjects Protections (HSP) in

Community Engagement Community Engagement Research (CEnR)Research (CEnR)

Lainie Friedman Ross, MD, PhDLainie Friedman Ross, MD, PhD

University of ChicagoUniversity of Chicago

© © Ross,Ross, 20102010

Funding/AcknowledgementsFunding/AcknowledgementsFUNDINGFUNDING: This project has been funded in whole : This project has been funded in whole

with Federal funds from the National Center for with Federal funds from the National Center for Research Resources (NCRR), National Institutes of Research Resources (NCRR), National Institutes of Health (NIH), through the Clinical and Translational Health (NIH), through the Clinical and Translational Science Awards Program (CTSA), part of the Science Awards Program (CTSA), part of the Roadmap Initiative, Re-Engineering the Clinical Roadmap Initiative, Re-Engineering the Clinical Research Enterprise, UL1RR024999.  The 3 Research Enterprise, UL1RR024999.  The 3 manuscripts were approved by the CTSA manuscripts were approved by the CTSA Consortium Publications Committee.Consortium Publications Committee.

CO-AUTHORS: CO-AUTHORS: Lainie Friedman Ross, MD, PhD, Lainie Friedman Ross, MD, PhD, Allan Loup, Robert M. Nelson, MD, PhD, Jeffrey R. Allan Loup, Robert M. Nelson, MD, PhD, Jeffrey R. Botkin, MD, MPH, Rhonda Kost, MD, George R Botkin, MD, MPH, Rhonda Kost, MD, George R Smith, Jr, MPH, Sarah Gehlert, PhDSmith, Jr, MPH, Sarah Gehlert, PhD

© © Ross,Ross, 20102010

DISCLOSURESDISCLOSURESI have I have nono relevant financial relationships with relevant financial relationships with

the manufacturer(s) of any commercial the manufacturer(s) of any commercial product(s) and/or provider(s) of commercial product(s) and/or provider(s) of commercial services discussed in this CME activity.services discussed in this CME activity.

I I do notdo not intend to discuss an intend to discuss an unapproved/investigative use of a commercial unapproved/investigative use of a commercial product/device in my presentation.product/device in my presentation.

© © Ross,Ross, 20102010

MethodologyA seven-member writing team to develop a framework for HSP

in CEnROne academic researcher who does community-based participatory

research (CBPR)One community research partner; Four with specialization in human subjects protections (HSP)

3 who self identify as ethicists 1 research subject advocate (RSA);

One research associate with interest in HSP. Two stakeholder meetings were held with numerous academic

researchers, community research partners, community activists and other HSP program personnel. At the first meeting, the stakeholders were asked to give presentations about the

process, challenges and benefits of CEnR from their various perspectives. There were both large group and small group break-out sessions to give all

Over the next 4 months, through iterative collaboration, the writing group developed a taxonomy and framework for the risks presented by CEnR.

At the second stakeholder meeting, some changes in stakeholder participants to increase the diversity of viewpoints. All stakeholders were asked to comment on written drafts and most were asked to give oral presentations regarding strengths and weaknesses of the framework.

© © Ross,Ross, 20102010

Traditional Conception of Traditional Conception of Human Subjects Protection (HSP)Human Subjects Protection (HSP)

Code of Federal Regulations (CFR) Title 45 Part 46 (1981, rev. Code of Federal Regulations (CFR) Title 45 Part 46 (1981, rev. 1991, 2001)1991, 2001) outlines federal policy for the protection of human outlines federal policy for the protection of human subjects in researchsubjects in research

Based on The Belmont Report (written by National Based on The Belmont Report (written by National Commission for the Protection of Human Subjects of Commission for the Protection of Human Subjects of BiomedicalBiomedical and Behavioral Research) Three PrinciplesThree Principles

Respect for personsRespect for personsBeneficenceBeneficenceJusticeJustice

ApplicationApplicationInformed ConsentInformed ConsentAssessment of Risks and BenefitsAssessment of Risks and BenefitsSelection of Subjects Selection of Subjects

Establishes mandate for Institutional Review Boards (IRBs)Establishes mandate for Institutional Review Boards (IRBs) Discusses additional protections for vulnerable populations Discusses additional protections for vulnerable populations

(pregnant women, human fetuses, neonates, prisoners, and (pregnant women, human fetuses, neonates, prisoners, and children)children)

© © Ross,Ross, 20102010

The Limits of the Fed RegsThe Limits of the Fed RegsThe Federal Regulations were designed for clinical The Federal Regulations were designed for clinical

trials…trials…Do not consider risks for communitiesDo not consider risks for communitiesThe regulations also state that “The IRB should not The regulations also state that “The IRB should not

consider possible long-range effects of applying consider possible long-range effects of applying knowledge gained in the research (for example, the knowledge gained in the research (for example, the possible effects of the research on public policy) as possible effects of the research on public policy) as among those research risks that fall within the among those research risks that fall within the purview of its responsibility.” purview of its responsibility.” §46.111 a2§46.111 a2

BUT there are other mechanisms to promote BUT there are other mechanisms to promote HUMAN SUBJECTS PROTECTIONSHUMAN SUBJECTS PROTECTIONS

© © Ross,Ross, 20102010

Seven distinct entities may be Seven distinct entities may be involved in an HSP program*involved in an HSP program*

1.1. The individual investigators*The individual investigators*2.2. The institutional review board (IRB)*The institutional review board (IRB)*3.3. Research ethics consultation (REC)Research ethics consultation (REC)4.4. Research subject advocate (RSA)Research subject advocate (RSA)5.5. Conflict of Interest CommitteeConflict of Interest Committee6.6. Data safety monitoring plan (DSMP)*Data safety monitoring plan (DSMP)*

Data safety monitoring committee (DSMC)Data safety monitoring committee (DSMC)

7.7. Community Advisory BoardCommunity Advisory Board*These are federally regulated*These are federally regulated

Greg Koski will discuss these

© © Ross,Ross, 20102010

The Nine Key FunctionsThe Nine Key Functions1.1. The risks of the research are minimized; The risks of the research are minimized; 2.2. The risks to subjects are reasonable in relation to anticipated The risks to subjects are reasonable in relation to anticipated

benefits; benefits; 3.3. The selection of subjects is fair; The selection of subjects is fair; 4.4. Each participant gives a voluntary and informed consent; Each participant gives a voluntary and informed consent; 5.5. When appropriate, the research plan makes adequate provisions When appropriate, the research plan makes adequate provisions

for monitoring the data collected to ensure the safety of subjects; for monitoring the data collected to ensure the safety of subjects; 6.6. There are adequate provisions to protect the privacy of subjects There are adequate provisions to protect the privacy of subjects

and to maintain the confidentiality of data; and to maintain the confidentiality of data; 7.7. Conflicts of interest are transparent and appropriately managed; Conflicts of interest are transparent and appropriately managed; 8.8. Consideration is given to what additional protections, if any, are Consideration is given to what additional protections, if any, are

needed for vulnerable populations; and needed for vulnerable populations; and 9.9. Proper training in human subjects protections is provided for Proper training in human subjects protections is provided for

research personnel. research personnel. Again, Greg Koski will discuss these

© © Ross,Ross, 20102010

In CEnR, the same 7 entities and the same 9 key functions must be addressed by a HSP

program.

What changes is the greater need to consider the risks to the community that is both research partner and research

participant.

© © Ross,Ross, 20102010

What other HSP issues need to What other HSP issues need to be addressed in CEnR?be addressed in CEnR?

Risks not only of individuals, but also of Risks not only of individuals, but also of groups and communitiesgroups and communitiesPotential risks to non-participant members of the Potential risks to non-participant members of the

groupgroup

What is the significance of the role of the What is the significance of the role of the group (community) as both research partner group (community) as both research partner and research subject?and research subject?

© © Ross,Ross, 20102010

What is Community?What is Community?Group versus CommunityGroup versus Community

Both have shared trait (for example, based on Both have shared trait (for example, based on geography, but also culture, ethnicity, education, geography, but also culture, ethnicity, education, disease)disease)

Community = Structured groupsCommunity = Structured groupsHas its own internal structure and leadershipHas its own internal structure and leadership

Unstructured groupsUnstructured groupsInternal: Can be empowered to create structureInternal: Can be empowered to create structureExternal: By a CBOExternal: By a CBOLegitimacy of the structure may depend on the extent to Legitimacy of the structure may depend on the extent to

which the leadership is inclusive and responsive.which the leadership is inclusive and responsive.

© © Ross,Ross, 20102010

A Taxonomy of RisksLEVEL OF

RISKProcess Risks to

Well-BeingOutcomes Risks to Well-Being

Risks to Agency

Individual

[A]

Clinical and psychosocial risks of the research interaction

Clinical and psychosocial risks of research findings

Risk of undermining personal autonomy/ authority

Individual by group

association [B]

Clinical and psychosocial identity risks of the research interaction

Clinical and psychosocial identity risks of research findings

Risk of group decisions undermining personal autonomy/authority. Risk of individual decisions undermining group autonomy/authority

Community

[C]

Risks to group cohesion or structure because of engagement in research

Risks to group cohesion or structure because of research findings

Risk of undermining the group’s moral and sociopolitical authority

© © Ross,Ross, 20102010

A-Level (Individual Risks)A-Level (Individual Risks) Box A-1Box A-1 : In a research interaction there are physical and psychosocial : In a research interaction there are physical and psychosocial

risks to participating individuals.risks to participating individuals. Blood is drawn for a sample; there is a risk of bruising.Blood is drawn for a sample; there is a risk of bruising. A drug is administered; there is a risk of adverse effects.A drug is administered; there is a risk of adverse effects. A survey is performed; there is a risk of emotional distress.A survey is performed; there is a risk of emotional distress.

Box A-2: Box A-2: When the findings of research conducted on individuals are When the findings of research conducted on individuals are reported, there are clinical and psychosocial risks to those individuals. reported, there are clinical and psychosocial risks to those individuals. A patient experiences adverse clinical effects from a trial and her condition is A patient experiences adverse clinical effects from a trial and her condition is

worsened. There is the risk that she will no longer be able to take a particular worsened. There is the risk that she will no longer be able to take a particular alternative treatment.alternative treatment.

A participant is informed she has tested positive for a genetic predisposition. A participant is informed she has tested positive for a genetic predisposition. There is the risk that she will incur psychological difficulty or damage to her There is the risk that she will incur psychological difficulty or damage to her social relationships. social relationships.

Box A-3: Box A-3: When an individual participates in research, there are risks to the When an individual participates in research, there are risks to the individual’s moral agency. individual’s moral agency. Blood samples are taken as data for a cholesterol study to which the participant Blood samples are taken as data for a cholesterol study to which the participant

has agreed; but the samples are then used as controls for a genetic study on has agreed; but the samples are then used as controls for a genetic study on aggression without her knowledge—an area of genetic study that she does not aggression without her knowledge—an area of genetic study that she does not support.support.

© © Ross,Ross, 20102010

A Taxonomy of RisksLEVEL OF

RISKProcess Risks to

Well-BeingOutcomes Risks to Well-Being

Risks to Agency

Individual

[A]

Clinical and psychosocial risks of the research interaction

Clinical and psychosocial risks of research findings

Risk of undermining personal autonomy/ authority

Individual by group

association [B]

Clinical and psychosocial identity risks of the research interaction

Clinical and psychosocial identity risks of research findings

Risk of group decisions undermining personal autonomy/authority. Risk of individual decisions undermining group autonomy/authority

Community

[C]

Risks to group cohesion or structure because of engagement in research

Risks to group cohesion or structure because of research findings

Risk of undermining the group’s moral and sociopolitical authority

© © Ross,Ross, 20102010

C-Level (Community Risks)C-Level (Community Risks) Box C-1: Box C-1: When a community engages in the research process, there are risks to the group’s When a community engages in the research process, there are risks to the group’s

cohesiveness and structure.cohesiveness and structure. A community engages in research. Conflict arises within the community’s leadership regarding the A community engages in research. Conflict arises within the community’s leadership regarding the

direction and extent of the group’s participation. One leader loses respect within the group or is direction and extent of the group’s participation. One leader loses respect within the group or is ousted. ousted.

Box C-2: Box C-2: When the findings of research are reported, there are risks to the engaged group itself. When the findings of research are reported, there are risks to the engaged group itself. Havasupai traditionally believed their origin as a people to be the Grand Canyon. Genetics Havasupai traditionally believed their origin as a people to be the Grand Canyon. Genetics

revealed their origins in Asia with migration across the Bering Straight to what is now Arizona. revealed their origins in Asia with migration across the Bering Straight to what is now Arizona. Threat to identity.Threat to identity.

Research found evidence of elder abuse among one Navajo community. The most prevalent form Research found evidence of elder abuse among one Navajo community. The most prevalent form of abuse cited was neglect. The findings spurred self-critique and discord within the community of abuse cited was neglect. The findings spurred self-critique and discord within the community because of its potential adverse impact on group solidarity and social traditions. because of its potential adverse impact on group solidarity and social traditions.

A study of an isolated genetic community in Greece identified community members who were A study of an isolated genetic community in Greece identified community members who were heterozygote carriers for Sickle Cell Disease. The traditional social operation of the community heterozygote carriers for Sickle Cell Disease. The traditional social operation of the community was disrupted.was disrupted.

Box C-3: Box C-3: When an established community (structured group) engages in research, there are risks to When an established community (structured group) engages in research, there are risks to the group’s moral agency. the group’s moral agency. The Havasupai tribe grew concerned about diabetes in their community and sought to participate The Havasupai tribe grew concerned about diabetes in their community and sought to participate

in a research study to address the issue. Unbeknownst to the tribe, the researchers used these in a research study to address the issue. Unbeknownst to the tribe, the researchers used these blood samples to study evolutionary biology and schizophrenia. The data may also have been blood samples to study evolutionary biology and schizophrenia. The data may also have been shared with researchers at other institutions. The group’s agency was harmed because they had shared with researchers at other institutions. The group’s agency was harmed because they had not given consent for these additional uses of its samples.not given consent for these additional uses of its samples.

The Sephardic Jewish Congregation Mikvé Israel-Emanuel (Curaçao) is the oldest synagogue in The Sephardic Jewish Congregation Mikvé Israel-Emanuel (Curaçao) is the oldest synagogue in continuous use in the Western Hemisphere with a few hundred individual members. In the 1960s, continuous use in the Western Hemisphere with a few hundred individual members. In the 1960s, the synagogue’s Board of Directors commissioned Dr. Isaac Emmanuel to write a comprehensive the synagogue’s Board of Directors commissioned Dr. Isaac Emmanuel to write a comprehensive history of the congregation, but retained the right to prevent publication of unfavorable descriptions history of the congregation, but retained the right to prevent publication of unfavorable descriptions to protect the community as a whole and its individual members. to protect the community as a whole and its individual members.

© © Ross,Ross, 20102010

A Taxonomy of RisksLEVEL OF

RISKProcess Risks to

Well-BeingOutcomes Risks to Well-Being

Risks to Agency

Individual

[A]

Clinical and psychosocial risks of the research interaction

Clinical and psychosocial risks of research findings

Risk of undermining personal autonomy/ authority

Individual by group

association [B]

Clinical and psychosocial identity risks of the research interaction

Clinical and psychosocial identity risks of research findings

Risk of group decisions undermining personal autonomy/authority. Risk of individual decisions undermining group autonomy/authority

Community

[C]

Risks to group cohesion or structure because of engagement in research

Risks to group cohesion or structure because of research findings

Risk of undermining the group’s moral and sociopolitical authority

© © Ross,Ross, 20102010

B-Level (Individual [participant and non-B-Level (Individual [participant and non-participant] by Group Association Risks)participant] by Group Association Risks) Box B-1: Box B-1: When an individual or group participates in research, there may be risks to an individual When an individual or group participates in research, there may be risks to an individual

who can be associated with a group—both participating and non-participating individuals. who can be associated with a group—both participating and non-participating individuals. In Native Hawaiian culture, blood is correlated with power. If blood samples are taken for a research study, In Native Hawaiian culture, blood is correlated with power. If blood samples are taken for a research study,

participants may be at risk for being stigmatized by their cultural community.participants may be at risk for being stigmatized by their cultural community. A study is underway exploring the high occurrence of Sexually Transmitted Infections in North St. Louis. A study is underway exploring the high occurrence of Sexually Transmitted Infections in North St. Louis.

The individual resident of North St. Louis might be associated with the STI-likelihood trait to his detriment, The individual resident of North St. Louis might be associated with the STI-likelihood trait to his detriment, whether or not he participates.whether or not he participates.

Box B-2: Box B-2: When the findings of research are reported and traits are ascribed to a group, there are When the findings of research are reported and traits are ascribed to a group, there are risks to individuals who can be associated with the group whether or not they participate. risks to individuals who can be associated with the group whether or not they participate. Studies showed a prevalence of the BRCA1 and BRCA2 genes, genes linked to breast cancer, in persons Studies showed a prevalence of the BRCA1 and BRCA2 genes, genes linked to breast cancer, in persons

of Ashkenazi Jewish heritage. The increased risk is ascribed to any woman who self-describes as of Ashkenazi Jewish heritage. The increased risk is ascribed to any woman who self-describes as Ashekanazi Jewish, whether or not she participated in the research, and this may result in higher insurance Ashekanazi Jewish, whether or not she participated in the research, and this may result in higher insurance premiums. premiums.

Expatriate Native Americans maintain group association by their biological heritage. Any study of genetic Expatriate Native Americans maintain group association by their biological heritage. Any study of genetic factors that enrolls these individuals can produce findings that, once ascribed to the genetic group, are factors that enrolls these individuals can produce findings that, once ascribed to the genetic group, are ascribed to all associated individuals of that group, both on- and off-reservation and in- and out-of-study.ascribed to all associated individuals of that group, both on- and off-reservation and in- and out-of-study.

Box B-3: Box B-3: When a group chooses to engage or not to engage in research, there are risks of the When a group chooses to engage or not to engage in research, there are risks of the associated individual’s moral agency being undermined. associated individual’s moral agency being undermined. The leader of an established community has established ongoing relationships with a research institution. The leader of an established community has established ongoing relationships with a research institution.

He hears about a project and thinks it would be great if his community participated. Members hear about He hears about a project and thinks it would be great if his community participated. Members hear about the project and are not interested as they believe that there are more important health priorities. However, the project and are not interested as they believe that there are more important health priorities. However, they feel pressured to participate given that the leader has promised the cooperation of the community.they feel pressured to participate given that the leader has promised the cooperation of the community.

The leader of a disease group has a bad personal experience with a researcher. The researcher now The leader of a disease group has a bad personal experience with a researcher. The researcher now proposes a research project that may be of significant benefit to the group. The leader claims it is too proposes a research project that may be of significant benefit to the group. The leader claims it is too dangerous and refuses to provide access. The other members of the disease group are unaware of the dangerous and refuses to provide access. The other members of the disease group are unaware of the opportunity.opportunity.

© © Ross,Ross, 20102010

A Taxonomy of RisksLEVEL OF

RISKProcess Risks to

Well-BeingOutcomes Risks to Well-Being

Risks to Agency

Individual

[A]

Clinical and psychosocial risks of the research interaction

Clinical and psychosocial risks of research findings

Risk of undermining personal autonomy/ authority

Individual by group

association [B]

Clinical and psychosocial identity risks of the research interaction

Clinical and psychosocial identity risks of research findings

Risk of group decisions undermining personal autonomy/authority. Risk of individual decisions undermining group autonomy/authority

Community

[C]

Risks to group cohesion or structure because of engagement in research

Risks to group cohesion or structure because of research findings

Risk of undermining the group’s moral and sociopolitical authority

© © Ross,Ross, 20102010

Interpreting Risk & Agency in CBPRInterpreting Risk & Agency in CBPR RISKRISK

Incommensurability of Risks (esp. between A-level and C-level)Incommensurability of Risks (esp. between A-level and C-level) Benefit: Risk RatioBenefit: Risk RatioNon-Participant Third Parties (B-type harms)Non-Participant Third Parties (B-type harms)

AGENCYAGENCYThe Complexity of Relationships and Agency in CBPRThe Complexity of Relationships and Agency in CBPR

A-level process concerns are addressed by informed consent A-level process concerns are addressed by informed consent and respect privacy/confidentialityand respect privacy/confidentiality

Agency tension between individual and groupAgency tension between individual and groupStructured versus Unstructured GroupsStructured versus Unstructured Groups

Structure is a necessary but not sufficient condition for group Structure is a necessary but not sufficient condition for group agencyagency

Only structured groups can have C-level risksOnly structured groups can have C-level risks PARTNERSHIPSPARTNERSHIPS

Memorandum of understandingMemorandum of understanding

© © Ross,Ross, 20102010

In CEnR, the 9 functions of Human In CEnR, the 9 functions of Human Subjects Protections (HSP) must still Subjects Protections (HSP) must still be fulfilled, but a HSP program must be fulfilled, but a HSP program must

take into account group and individual take into account group and individual risks [process and outcome risks]; risks [process and outcome risks]; …and the additional risks that occur …and the additional risks that occur

when the Community is both research when the Community is both research partner and research subject (threats partner and research subject (threats

to individual and group agency).to individual and group agency).

© © Ross,Ross, 20102010

Who provides the HSP?Who provides the HSP?In traditional research, HSP emanated from the In traditional research, HSP emanated from the

Academic Medical Center (AMC)Academic Medical Center (AMC)In CEnR, 360 degrees of Human Subjects Protections In CEnR, 360 degrees of Human Subjects Protections

emanates from both the AMC (IRB*, REC, COIC) and emanates from both the AMC (IRB*, REC, COIC) and from the community (CAB)from the community (CAB)Other HSP may be joint efforts of AMC and community (role Other HSP may be joint efforts of AMC and community (role

of individual investigators, the establishment of a DSMP, and of individual investigators, the establishment of a DSMP, and possibly the RSA functions)possibly the RSA functions)

Human subjects protection training must be developed Human subjects protection training must be developed that is culturally sensitive and linguistically appropriate that is culturally sensitive and linguistically appropriate for non-health care professionals.for non-health care professionals.

*community members are encouraged to serve on IRBs.*community members are encouraged to serve on IRBs.

© © Ross,Ross, 20102010

Concluding RemarksConcluding RemarksCommunity Engagement Research (CEnR) Community Engagement Research (CEnR)

requires a broader conception of human requires a broader conception of human subjects protections.subjects protections.

We need to train those who provide HSP We need to train those who provide HSP about how CEnR is different from traditional about how CEnR is different from traditional research.research.

In CEnR, HSP, like the research itself, ought In CEnR, HSP, like the research itself, ought to use a collaborative methodology. to use a collaborative methodology.