Improving Diversity in Clinical Trials: Strategies for Inclusive and Ethical Research
Clinical research aims to produce knowledge in the service of treating diseases and improving human health. In a just and well-functioning society, the benefits of research would ideally be shared equitably among all social groups, regardless of race, age, gender, or ethnicity. This gives the research community (e.g., sponsors, investigators, and institutional review boards [IRBs]) strong reasons to improve research participation access. It also challenges the community to learn how to improve diversity in clinical trials for historically under-represented groups, such as women, children, cognitively impaired individuals, elderly people, and racial and ethnic minorities.
Unpacking why Groups are Historically Under-represented in Research
Historically, clinical research has failed to adequately include certain groups of people. In some cases, this is at least partly because these groups have been deemed vulnerable and in need of protection.
For example, women and individuals of child-bearing potential have tended to be excluded out of concerns about the potential effects of an investigational product on a developing fetus. People with mental illness and individuals who are cognitively impaired have been excluded because of a perceived inability to consent for themselves. Similarly for children. The elderly have also been excluded out of concern of potential co-morbidities and polypharmacy potentially increasing the risks of research or confound the interpretation of the data.
In other cases, the explanation for why groups are under-represented in research is more complex. Racial and ethnic minorities have suffered a long history of exploitation at the hands of researchers, resulting in high rates of mistrust in the research enterprise. Lower enrollment rates among racial and ethnic minority groups may reflect this fact and should come as no surprise.
Ethical Concerns with Research Under-representation
There are at least two ethical concerns with these disparities.
First, when certain groups are not included in research, it can make it difficult to apply the results of research to them. For example, just because a drug is safe or effective in a narrowly defined study population does not automatically mean it is safe or effective in a wider group of individuals who might include people with comorbidities or on various other types of medications. When these and other groups are excluded from research, it hinders them from sharing in the primary benefits of research – the advances in disease diagnosis, treatment, and prevention research yields – and promotes longer term health inequities, with these groups being “left behind” from a public health standpoint.
Second, when certain groups are not included in research, they do not have access to the potential direct benefits of research participation. While the primary aim of research is the production of knowledge, research participation often yields access to promising new therapies. In disease conditions for which there currently exists no cure or standard of care, enrolling in a research study of an investigational new therapy may be the best option for many patients. All individuals should have equitable and fair access to these opportunities.
Addressing Ethical Issues with Clinical Research Disparities
What can the research community do to address these concerns and learn how to improve diversity in clinical trials? The first thing to recognize is restoring trust among groups who have suffered at the hands of research will take time, a commitment from the research community to listen to what these groups are saying, and a willingness to take their experiences to heart and let them shape us. There are no quick fixes for public mistrust in research.
While we as a research community work to build trust, there are things we can do to promote the inclusion of under-represented groups. While these are simple and commonsense actions, they are unfortunately often overlooked and not put into practice.
While the responsibility of implementing many of the following points begins with sponsors and researchers, the role of the IRB should not be overlooked. Indeed, empirical research has shown IRBs see themselves as having a role to play in promoting inclusion and good work has been done to outline a roadmap for the role of IRBs in enhancing the diversity of clinical research populations.
Here are some practical strategies on how to improve diversity in clinical trials while addressing ethical concerns:
- Design careful study eligibility criteria without unnecessarily excluding certain groups, including women and individuals of child-bearing potential, children, the mentally ill and cognitively impaired, non-English speakers, the elderly, and racial and ethnic minorities.
- Institute thoughtful, protective measures addressing concerns with potentially vulnerable groups participating in research, short of exclusion. Such measures can include contraception measures for individuals of child-bearing potential, legally authorized representatives to consent on behalf of cognitively impaired people, and thoughtfully designed eligibility and individual withdrawal criteria for older people with comorbidities.
- Translate documents into languages other than English for non-English speakers. This is basic, and translation costs are minimal enough for this to be a no-brainer for most sponsors. Subject materials should at least be translated into Spanish and other prominent non-English languages in the relevant geographical area.
- Offer robust reimbursement plans for out-of-pocket costs related to participation, including travel and childcare. Such expenses are among the biggest barriers to research participation among economically vulnerable groups (which often include, unfortunately, racial and ethnic minorities). Additionally, consider offering fair compensation to participants for their time and the burdens they undertake. Determining what counts as “fair” compensation will vary depending on various factors, including the nature of the study and what is being asked of participants, the time commitment involved, and local cost of living.
- Sponsors, sites, and IRBs should strive to diversify their members and staff. This allows the research world to learn and benefit from historically neglected perspectives and standpoints, which may in turn help under-represented groups feel more comfortable in research contexts.
These points are achievable short-term goals. They can move the research community in the right direction while we do the difficult work of building trust in the wider society, and with historically marginalized and exploited groups in particular.