Paul Ndebele

Consent and community engagement in diverse research contexts: reviewing and developing research and practice

Consent and community engagement (CE) in health research are two aspects of a single concern—that research is carried out in a respectful manner where social value is maximized. There are important overlaps and interdependencies between consent and CE; for example, CE can provide insights into how best to tailor consent to context and can be an important component of consent processes. Engaging communities can also have intrinsic and instrumental value beyond consent; for example, as a means of showing respect and identifying appropriate ways of working respectfully. In this paper we critically examine how CE and consent processes are characterized, conducted, and evaluated in diverse health research contexts, and propose a preliminary research agenda to support future learning in these critical areas.Consent and community engagement (CE) in health research are two aspects of a single concern-that research is carried out in a respectful manner where social value is maximized. There are important overlaps and interdependencies between consent and CE; for example, CE can provide insights into how best to tailor consent to context and can be an important component of consent processes. Engaging communities can also have intrinsic and instrumental value beyond consent; for example, as a means of showing respect and identifying appropriate ways of working respectfully. In this paper we critically examine how CE and consent processes are characterized, conducted, and evaluated in diverse health research contexts, and propose a preliminary research agenda to support future learning in these critical areas.

The Declaration of Helsinki, 50 Years Later

Fifty years and 7 revisions later, the 2013 version of the Declaration of Helsinki includes several important changes. By changing the format and including several subsections, the revised declaration enhances and improves clarity regarding specific issues. By having specific issues covered under these subsections, the declaration is now “ bolder” in the way it addresses specific issues. The new formatting will also be welcomed by readers because the subsections improve the readability of the document. By so doing, the Declaration of Helsinki is a better and more important authority at what it is aimed at achieving—providing guidance on conducting medical research involving humans. The increase in international studies over the past few decades has contributed to serious debate about the ethics of research conducted in various settings. Most of the debate centered on issues related to limited resources and justice: use of placebo and posttrial access to interventions. Through this and previous revisions, the World Medical Association (WMA) has demonstrated that the declaration is a living document that considers current issues in medical research. Important documents such as the declaration are expected to respond to new areas of need or areas that require revision. The Declaration of Helsinki was born from the history of abuses of human research subjects. Over the years, research oversight has improved but has led to the underrepresentation of certain groups in research investigations.1 This has disadvantaged such groups because they have not benefitted from some advances that others have experienced from the conduct of research. The new version of the declaration addresses this development in paragraph 13 by recommending that access to clinical trials for underrepresented groups needs be increased so these groups also can benefit from research. Instead of excluding groups that have been ordinarily excluded from research, such as minority groups, women, and children, researchers need to clearly justify why these groups have been excluded from research. There are current discussions about compensation and treatment for individuals who are harmed as a result of their participation in research. Some funders of research have been unwilling to address this topic over the years.2 However, India has issued a law that requires all trial participants to receive treatment and financial compensation for trial-related injuries or death. The law has disrupted the conduct of clinical trials supported by one of the major funders of medical research in that country.3 The issues of compensation and access to treatment for research-related injuries are important for limited-resource settings in which the majority of trial participants are not insured. By clearly stating that trial participants need to be treated and compensated for trial-related injuries, the new declaration is likely to lead to further discussions by certain research funders who would like to avoid the cost of insuring trial participants. In the past some important stakeholders in medical research have preferred to adhere to older versions of the declaration as a way of avoiding dealing with certain provisions included in newer versions.4 ThenewversionoftheDeclarationofHelsinki ismore relevant to countries with limited resources because it includes clear terms that address issues of importance in these settings, such as posttrial access to interventions and care for participants from limited-resource settings. In limited-resource countries, there have been concerns that communities may be used for testing interventions that will not be accessible to their citizens because of high costs and other reasons such as logistical challenges in delivering the new interventions outside the research environment. The new version of the declaration is clear on the requirement to have plans for ensuring access to an intervention if it is proven to be effective. This requirement serves to recognize that research can play an additional role of improving access to care in limitedresource settings. In further recognition of the role of research in improving access to care in limited-resource settings, the new version of the declaration also addresses the issue of use of unproven interventions. The 2013 version of the Declaration of Helsinki recommends use of unproven interventions in cases for which proven interventions do not exist, after the physician has sought expert advice as well as the patient’s informed consent. The new version also addresses several issues related to the dissemination of health research information, including registration of trials in publicly accessible databases and publication of negative, inconclusive, and positive results. The nonpublication of research with inconclusive or negative findings is concerning and must be discouraged by all who sanction research. The scientific enterprise must acknowledge openly that science improves through failures and successes. Informed consent is one of the hallmarks of ethical research and ensures that individuals can make decisions that are in their best interests. The new version of the declaration acknowledges that in some cases, such as in close-knit societies, informed consent needs to involve others such as community leaders and significant others. Community leaders can serve as additional layers of protection that researchers need to pass through before they reach the potential participants. By addressing this reality, the new version is emphasizing respect for culture and community norms as part of the research process. With respect to individual participants in research, several studies have illustrated that individuals often agree to participate in clinical trials without full knowledge or understanding of the studies.5 The new version of the decVIEWPOINT

Improving understanding of clinical trial procedures among low literacy populations: an intervention within a microbicide trial in Malawi.

BackgroundThe intervention reported in this paper was a follow up to an empirical study conducted in Malawi with the aim of assessing trial participants’ understanding of randomisation, double-blinding and placebo use. In the empirical study, the majority of respondents (61.1%; n= 124) obtained low scores (lower than 75%) on understanding of all three concepts under study. Based on these findings, an intervention based on a narrative which included all three concepts and their personal implications was designed. The narrative used daily examples from the field of Agriculture because Malawi has an agro-based economy.MethodsThe intervention was tested using a sample of 36 women who had been identified as low scorers during the empirical study. The 36 low scorers were randomly assigned to control (n=18) and intervention arms (n=18). The control arm went through a session in which they were provided with standard informed consent information for the microbicide trial. The intervention arm went through a session in which they were provided with a narrative in ChiChewa, the local language, with the assistance of a power point presentation which included pictures as well as discussions on justification and personal implications of the concepts under study.ResultsThe findings on the efficacy of the intervention suggest that the 3 scientific concepts and their personal implications can be understood by low literacy populations using simple language and everyday local examples. The findings also suggest that the intervention positively impacted on understanding of trial procedures under study, as 13 of the 18 women in the intervention arm, obtained high scores (above 75%) during the post intervention assessment and none of the 18 in the control arm obtained a high score. Using Fischer’s exact test, it was confirmed that the effect of the intervention on understanding of the three procedures was statistically significant (p=0.0001).ConclusionsPotential trial participants can be assisted to understand key clinical trial procedures, their justification and personal implications by using innovative tailored local narratives.

Trial Participants’ Understanding of Randomization, Double-Blinding, and Placebo Use in Low Literacy Populations Findings From a Study Conducted Within a Microbicide Trial in Malawi

Concerns have been raised about the limits of understanding of consent by clinical trial participants in developing countries. Consequently, this empirical study was conducted in Malawi to assess microbicide trial participants’ understanding of randomization, double-blinding, and placebo use. The study used a combination of quantitative and qualitative methods, including structured questionnaire interviews with a random sample of 203 individual participants, four in-depth interviews with research nurses, and two focus group discussions with 18 study participants. Most respondents earned high scores on questions related to randomization (85%) and placebo use (72%), while a greater proportion of the same respondents obtained low scores on questions related to double-blinding (68%) and personal implications of the study procedures (63%). Overall, most respondents (61%; n = 124) obtained low scores on combined understanding of all the three concepts under study.

Maintaining respect and fairness in the usage of stored shared specimens

BackgroundEvery year, research specimens are shipped from one institution to another as well as across national boundaries. A significant proportion of specimens move from poor to rich countries. Concerns are always raised on the future usage of the stored specimens shipped to research insitutions from developing countries. Creating awareness of the processes is required in all sectors involved in biomedical research. To maintain fairness and respect in sharing biomedical specimens and reserch products requires safeguarding by Ethics Review Committees in both provider and recepient institutions. Training in basic ethical principles in research is required to all sectors involved in biomedical research so as to level up the research playing field.DiscussionBy agreeing to provide specimens, individuals and communities from whom samples are collected would have placed their trust and all ensuing up-keep of the specimens to the researchers. In most collaborative set-up, laid down material transfer agreements are negotiated and signed before the shipment of specimens. Researchers, research ethics committees (RECs) and institutions in the countries of origin are supposed to serve as overseers of the specimens. There is need to advocate for honesty in sample handling and sharing, and also need to oversee any written commitments by researchers, RECs and institutions at source as well as in recipient institution. Commitments from source RECs and Institutional Review Boards (IRBs) and in the receiving institution on overseeing the future usage of stored specimens are required; including the ultimate confirmation abiding by the agreement. Training in ethical issues pertaining to sample handling and biomedical research in general is essential at all levels of academic pursuit. While sharing of biological specimens and research data demands honesty and oversight by ethical regulatory agents from both institutions in developing country and recepient institutions in developed countries.Concluding summaryArchiving of biological specimens requires reconsideration for the future of biomedical findings and scientific break-throughs. Biomedical ethical regulations still need to established clear viable regulations that have vision for the future of science through shared and archived samples. This discussion covers and proposes essential points that need to be considered in view of future generations and scientific break-throughs. The discussion is based on the experience of working in resource-limited settings, the local regulatory laws and the need to refine research regulations governing sharing and storage of specimens for the future of science.

Protections for clinical trials in low and middle income countries need strengthening not weakening

The latest revision of the Declaration of Helsinki weakens protections for trial participants in low and middle income countries. Rafael Dal-Ré and colleagues argue that this is a step in the wrong direction

Testing the waters: Ethical considerations for including PrEP in a phase IIb HIV vaccine efficacy trial

Background: The field of HIV prevention research has recently experienced some mixed results in efficacy trials of pre-exposure prophylaxis, vaginal microbicides, and HIV vaccines. While there have been positive trial results in some studies, in the near term, no single method will be sufficient to quell the epidemic. Improved HIV prevention methods, choices among methods, and coverage for all at-risk populations will be needed. The emergence of partially effective prevention methods that are not uniformly available raises complex ethical and scientific questions regarding the design of ongoing prevention trials. Methods: We present here an ethical analysis regarding inclusion of pre-exposure prophylaxis in an ongoing phase IIb vaccine efficacy trial, HVTN 505. This is the first large vaccine efficacy trial to address the issue of pre-exposure prophylaxis, and the decisions made by the protocol team were informed by extensive stakeholder consultations. The key ethical concerns are analyzed here, and the process of stakeholder engagement and decision-making described. Discussion: This discussion and analysis will be useful as current and future research teams grapple with ethical and scientific study design questions emerging with the rapidly expanding evidence base for HIV prevention.

Open data sharing and the Global South—Who benefits?

Limited capacity, deep mistrust pose challenges to sharing A growing number of government agencies, funding organizations, and publishers are endorsing the call for increased data sharing, especially in biomedical research, many with an ultimate goal of open data. Open data is among the least restrictive forms of data sharing, in contrast to managed access mechanisms, which typically have terms of use and in some cases oversight by the data generators themselves. But despite an ethically sound rationale and growing support for open data sharing in many parts of the world, concerns remain, particularly among researchers in low- and middle-income countries (LMICs) in Africa, Latin America, and parts of Asia and the Middle East that comprise the Global South. Drawing on our perspective as researchers and ethicists working in the Global South, we see opportunities to improve community engagement, raise awareness, and build capacity, all toward improving research and data sharing involving researchers in LMICs.

Strengthening stakeholder engagement through ethics review in biomedical HIV prevention trials: opportunities and complexities

Clinical trials of biomedical HIV prevention modalities require the cooperation of multiple stakeholders. Key stakeholders, such as community members, may have stark vulnerabilities. Consequently, calls for HIV prevention researchers to implement “stakeholder engagement” are increasingly common. Such engagement is held to benefit inter‐stakeholder relations, stakeholders themselves and the research itself. The ethics review process presents a unique opportunity to strengthen stakeholder engagement practices in HIV prevention trials. However, this is not necessarily straightforward. In this article, we consider several complexities. First, is stakeholder engagement a legitimate component of what Research Ethics Committees (RECs) should review for HIV prevention trials? Second, what are the core features of engagement that should be under ethics review? Third, what are the key practices that should be highlighted in ethics review?

Ethical Issues in Health Systems Research in Low and Middle-Income Countries

Health Systems Research (HSR) is necessary to ensure health systems are strengthened and that quality of care is improved; and is an important tool for guiding health policy. HSR is increasingly being performed in low and middle-income countries (LMIC) out of the realization that a significant proportion of the disease burden in those settings can be addressed by focusing on system wide issues as opposed to disease-specific actions. In fact, weaknesses in health systems in many LMIC have been cited as major impediments to the achievement of the previous Millennium Development Goals. HSR has been defined as research to generate new knowledge to improve the performance of health systems; and encompasses forms of research such as health services research, operations research, and implementation research. HSR addresses various areas including health planning, health management, service delivery, quality of care, human resources for health; among others. The broad goals of HSR are to improve the operations and efficiency of health systems leading to improved access, enhanced utilization of services, reduced inequities, and rational use of available resources. As with any type of research, HSR is bound to present some ethical challenges in terms of proposing, reviewing, conducting, supervising and reporting its findings; some of which may be common to other types of research. However, given that HSR is somewhat unique from other types of studies in terms of aims, approaches, and methods, the ethical issues present in HSR may be particularly nuanced. While a lot of work has gone into understanding ethical issues in health research in general such as clinical trials, little work has been done to support the growing amount of HSR being conducted in LMICs aimed at clarifying the field’s ethical dimensions. Recent work on ethical issues in HSR has suggested that it has distinctive features (for example relative to clinical research) that may limit the applicability and usefulness of existing ethical guidance on research. By focusing on systems, institutions, and populations much of HSR often differs from clinical research that mainly focuses on individual participant in efforts to address diseases affecting populations. The diversity of methods, nature of interventions being studied, focus on populations, strong emphasis on translating results to policy and practice, and focus on systems rather than specific diseases makes HSR quite unique. Due to these features therefore, the ethical issues that arise in the conduct of HSR may be different or nuanced relative to those that arise in the conduct of other types (such as clinical) research. In view of the limited work that has been done to understand the ethical issues inherent in HSR, this special issue of Developing World Bioethics is a response to the need for conceptual and empirical work in this area. It aims to help identify the types of ethical issues pertinent to HSR, how they might be addressed by researchers, Institutional Review Boards, and sponsors; and defines their impact on communities and research participants. The special issue consists of six papers that focus on various issues ranging from ethical guidelines, to the role of HSR in promoting health equity, and implications of HSR for health systems changes. A paper by Bachani, Rattani & Hyder, presents a review of available peer reviewed literature on the ethics of HSR; followed by a selected review of existing and easily available guidance and tools to facilitate the ethical review of HSR. This paper identifies examples of commonly available guidance and tools for the ethical review of HSR studies and provides insights into appropriate review processes for HSR study protocols and suggestions for future ethical guidance for review of HSR proposals. It serves as an important resource for researchers involved in HSR, as well as research ethics committees that review HSR proposals. One of the important contributions in the ethics of clinical research was a paper by Emanuel, Wendler, and Grady who presented a framework that can be utilized for reviewing clinical trial protocols in LMIC. One of the papers in this issue authored by Wassenaar & Rattani discusses the usefulness of the Emanuel et al framework in guiding the conduct of HSR. The authors conclude that despite the unique features of HSR, the criteria by Emanuel, Wendler and Grady can be usefully applied to the review of HSR to supplement the framework by Hyder, Hyder, Rattani, Manuscripts that include Adnan A. Hyder as author in this Special Issue were peer reviewed independent of the authors involvement as guest editor. 1 Remme, J. H., Adam, T., Becerra-Posada, F., D’Arcangues, C., Devlin, M., Gardner, C., & Mbizvo, M. T. Defining research to improve health systems. PLoS Med 2010; 7(11): e1001000; Travis, P., S. Bennett, A. Haines, T. Pang, Z. Bhutta, A. A. Hyder, et al. Overcoming healthsystems constraints to achieve the Millennium Development Goals. The Lancet 2004; 364(9437): 900-906. 2 Remme et al., ibid. 3 Hyder, A. A., B. Pratt, J. Ali, N. Kass, & N. Sewankambo. The ethics of health systems research in low-and middle-income countries: a call to action. Global Public Health 2014; 9(9): 1008-1022. 4 Pratt, B., & A. A. Hyder. Reinterpreting Responsiveness for Health Systems Research in Low and Middle-Income Countries. Bioethics 2015; 29 (6): 379-388. 5 Emanuel, E. J., D. Wendler, & C. Grady. What makes clinical research ethical? JAMA 2000; 283(20): 2701-2711.