Applying Research Ethics Guidelines A View from Malawi

Applying Research Ethics Guidelines: A View from Malawi David Blair Mahoney, MD, MBE

Some definitions… • Research Ethics Guidelines • Research Ethics Committee • Clinical Trial Protocol • Informed Consent Process 2

Background • Significant variation in how research guidelines are applied across institutions and countries • With the rise of international research collaborations, Research Ethics Committees (ECs) in developing countries often apply US, UK, or other international regulations – Which to use? 3

Background • Additional local challenges – Limited resources – Proliferation of number and complexity of protocols • Few reports on views of local ECs 4

Background • Malawi National Health Sciences Research Committee – 14 committee members – 40 to 50 protocols reviewed annually • Half of protocols were international collaborations • Conditions most represented – HIV/AIDS – Malaria – Tuberculosis 5

Background • Purpose of interviews – Determine criteria used by the EC to review clinical trial protocols – Better understand the challenges they face – Gain knowledge of their perceptions of international collaborations – Explore how to build successful international relationships 6

Background • Most protocols from US or UK • World Health Organization most often utilized – DHHS, Declaration of Helsinki, CIOMS 7

Background • Topics – Questions about protocol review process • Informed consent, vulnerable populations, risk, benefit • Role of the local EC and relationships with other ethics committees – Influences on independent review – Overall training needs 8

Background • 11 of 14 EC members interviewed • Each interview lasted 1 to 2 hours • Audio-taped and transcribed verbatim 9

Background • Qualitative content analysis – Three authors reviewed all transcripts, identifying broad deductive codes based on study objectives – Identification of main themes that emerged within each code • Approved by the Malawi EC and the Institutional Review Board at the University of North Carolina 10

Informed Consent “… your principles are not working on the ground. ” 11

Informed consent • Doubt expressed about the effectiveness of the current process used to obtain voluntary, informed consent – 80% believed that study participants typically do not fully understand information presented to them 12

Informed consent • Two causes were identified – The length of the consent forms • “You have made it a legal document and nothing more. ” • Who is it meant to protect? – Limited time for explanation 13

Informed consent • Importance of translating the consent forms into the local language, but the need for transferring the meaning of concepts – “The consent form has to be translated into the local language so that people can understand… and it is not just a question of translation, but it has to carry the meaning in the original version. ” 14

Informed consent • Importance of consent forms that stress voluntariness of participation – Fear that subjects agree to research participation simply because they trust researchers to do their best for them or their child 15

Vulnerable Populations “…virtually every person enrolled in studies in Malawi is poor. ” 16

Vulnerable Populations • Traditionally, chiefs made decision for the village – Influence of local leaders over these decision-making processes has moderated in recent years – Leaders must still be informed of impending research in their community • “…people know they have rights now. The chief might say yes, [yet researchers should not] take it for granted that everybody shall say yes. ” 17

Vulnerable Populations • Poverty was cited by every EC member as a sign of vulnerability – “I don’t know how truly autonomous a poor person is in America. Autonomy suggests that you have alternatives… A lot of the difference between the West and Africa does not have to do with what we’re discussing [autonomy]. It has to do with being rich and poor, and…virtually every person enrolled in studies in Malawi is poor. ” 18

Risks “… if a certain vehicle comes, everyone will know it’s the AIDS vehicle. ” 19

Risks • Stigmatization is the primary risk of research participation – “We look at social risks such as [risk to] privacy and confidentiality. Social risk can become a physical risk, for example, if a wife participates in HIV/AIDS research and is identified as having HIV, she could be harmed by her husband. ” 20

Risks • Stigmatization is the primary risk of research participation – “When [study staff go to a participant’s house] to draw blood to test for HIV, what will the community talk about? They will say this person has HIV … so we look at such risks. ” 21

Risks • Social and ethical implications of a vaccine trial – Outside study settings, participants theoretically may not be able to differentiate new infection from vaccine-related seropositivity – Thought-provoking scenarios 22

Risks • EC members spend significant time explaining risks beyond just the physical – “Clearly in the researcher’s best interest because if you stigmatize people, they won’t come or they won’t return. ” 23

Benefits “…first we look at the benefits to the community. ” 24

Benefits • Every EC member emphasized the paramount importance of benefit to the community – Hierarchy of benefits • “First of all we look at the benefits to the community, and not to the individuals. And also we look at how the study is going to benefit the institution doing the study. Finally, we can look at the benefits to the individuals. ” 25

Benefits • In US, oftentimes fundamental difference between why researchers think patients participate in clinical research, and why the participants do so – “While it is recognized that societal benefit, such as construction of a hospital, can also benefit the individual, … usually we discourage [discussing] individual benefits because it is like coercing people into the study. ” 26

Benefits • EC members pay particular attention to whether projects will ‘build capacity. ’ – Sustainability versus ‘Duffle Bag Medicine’ – Computers, trucks, clinics, hospitals, trained local staff, medical supplies, books 27

The Role of the EC in Collaborations • Barrier or facilitator? – Many said they were seen as “police officers” by Western institutions, blocking research and delaying scientific progress 28

The Role of the EC in Collaborations • Role of cultural broker – Help to make the research “culturally feasible. ” – Local investigators are a key component • “if you don’t have local investigators, then you don’t have insight into what is culturally [or logistically] acceptable. ” 29

The Role of the EC in Collaborations • Misunderstandings when researchers proposed to draw blood, causing fear that they would sell it or “play magic” with it – Resulted in emphasis on community education prior to recruitment 30

The Role of the EC in Collaborations • Members expect international collaborators submitting protocols to have them reviewed by their own EC first 31

The Role of the EC in Collaborations • But they also believe that the final decision is theirs – “Clearly people are influenced by what other institutional review boards have said, but the final say is with us. ” • No formal or informal mechanisms for communication between international ECs and the Malawi EC 32

Discussion • Process of obtaining informed consent for research in developing countries is unclear – Inappropriately focuses on written documentation and emphasis on literal translations of consent forms • Consent document should be one written by the local EC in the local language, rather than by the sponsoring country’s EC 33

Discussion • While protection of human research subjects is defined in the regulations as their primary objective, Malawi ECs take various stances vis-à-vis the research enterprise, some collaborative, some more adversarial • Resemblance to ECs in the West? 34

Discussion • Most striking difference is the priority given to evaluating research in terms of community benefits – Reflects the communal nature of African society? – Concerns regarding economic and scientific exploitation that has determined the worldview of many in Africa? – Demands for social justice in research? 35

Discussion • Limited generalizability • Yet many observations and concerns resonate – Kass et al (2007) reports that, in reviewing data on 12 African ECs from 1967 to 2007, committees become more stable, equipped, and better trained over this time • Interviews with members of this EC offer concrete suggestions regarding priorities for change 36

Conclusions • This EC is very familiar with human subjects protection guidelines used in the US and elsewhere • They interpret these guidelines in light of local conditions – Cultural, educational, and economic factors – Benefit to society versus benefit to individual 37

Acknowledgments • Project directed by Gail E. Henderson, UNC Department of Social Medicine • Other investigators: Irving Hoffman, UNC Center for Infectious Disease; Daniel K. Nelson, UNC Office of Human Research Studies; Amy Corneli, Department of Epidemiology, and Charles Mwansambo, Paediatric Department, Kazumu Hospital, Lilongwe, Malawi • Funding: Holderness Fellowship and the UNC Center for AIDS Research 38

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• Questions? 40 40