Blog >     Do clinical trials have a diversity problem?

 

This initiative has become a moral and scientific responsibility when designing clinical studies in all their research phases; therefore, it is necessary to know about the safety and efficacy of innovative therapies among populations with different conditions such as race, age, sex, culture, region, and comorbidities, since these make the response to those therapies different and make groups underrepresented in the results of the trials, a situation that increases disparities worldwide and implies a risk when deciding a preventive, diagnostic or therapeutic strategy in these minorities.

Underrepresented Populations in Clinical Trials

Populations that are underrepresented in clinical studies can be analyzed from two groups:

1) Demographic characteristics

2) Non-demographic characteristics

1. Demographic characteristics

For this group, variables such as gender, race, ethnicity, and place of residence are the ones that potentially generate differences in clinical studies; for example, according to a publication in The Lancet, Equity in Digestive Health, 12.4% of cases of pancreatic cancer in the USA are diagnosed in African Americans; however, they only represented 8.2% of the participants in clinical trials for pancreatic cancer. Likewise, according to the 2021 report of the FDA Drug Trials Snapshots, the approval of drugs for Alzheimer's disease was made with a participation of 3% of the Hispanic population, when this condition fluctuates between the fourth and tenth cause of death for the Latin population (PharmaBoardroom, InFigures: Latin America 2022).

2. Non-demographic characteristics

This group includes the conditions of patients with specific comorbidities, disabilities, rare diseases, and extreme weight (above or below the body mass index ranges).

In this sense, the FDA published the Guide for the industry Enhancing the Diversity of Clinical Trial Populations, highlighting the importance of applying the recommendations to expand the eligibility criteria for clinical trials of drugs that treat rare diseases, given that these studies pose some specific challenges explained by its limited number of patients, its geographical dispersion, and mobility limitations. Therefore, it is imperative to make the necessary efforts to include the largest number of participants in these studies and keep them adherent to the related activities.

Among the strategies proposed to increase their participation are the inclusion of groups of patients with rare diseases in the initial stages of molecule development and listening to their suggestions; these patients will be more engaged and willing to participate in the studies. In addition, re-enrollment of participants who were in the first and last phases should be considered (as long as there is no potential risk in terms of security and data analysis). Extending the studies with an open-label stage and broader eligibility criteria are also strategies to ensure that all participants have access to the innovative therapy.

Some populations with conditions such as organ dysfunction are usually excluded from clinical studies; this is the case of patients with kidney failure, heart failure, cancer, HIV, and extreme weight. To optimize the participation of these groups, strategies such as defining the stage/grade of the disease in which their inclusion is acceptable, evaluating the metabolism, excretion, and interaction with other drugs from the preclinical phases, as well as proposing eligibility criteria in phase 3 clinical trial that allow to include a higher number of people with various comorbidities, are presented.

Characteristics such as age, ethnicity, and place of residence are often limited in eligibility criteria when extreme age, lack of language proficiency, transportation limitations, or hours of operation are restricted. Although these criteria seek a more suitable population for analysis, many are standardized and may not have an objective justification.

Hispanic population participation in clinical trials

For the 2021 report of the FDA Drug Trials Snapshots, a low sample of the Hispanic population was reported in clinical trials, with approximate participation of 10% for all trials with molecules approved for that year, while for 2020, 2019, and 2018 Hispanic participation was 11%, 18%, and 14% respectively. In this, there is evidence of a tendency to reduce their representation despite the efforts made. It is forecasted that by 2050 the Hispanic population will reach a quarter of the total population of the United States, a situation that draws attention given that, despite this growth, it is not reflected in the participation in the studies of innovative molecules and therefore, they do not represent the population in which those molecules will potentially be used.

The foregoing can be explained from two perspectives: the limitations inherent to the design and execution of the study, such as in-person visits, informed consent on paper, no flexibility in schedules, a medical team that does not manage the culture and language of other populations or the limitations of mobility; and, on the other hand, the non-inclusion of research centers from different regions that can guarantee the approval of molecules that prove to be safe and effective in different races and cultures.

This shows the importance for this region of conducting clinical studies with the highest quality standards, involving research centers with experienced teams, empowered researchers, leading coordinators, and adequate infrastructure. This includes the Contract Research Organizations (CROs), who play a key role in monitoring the studies and in promoting the centers to ensure adequate recruitment, monitoring and compliance with the agreed deadlines. Likewise, it is essential that sponsors standardize the inclusion of research centers in different regions and that regulatory authorities intervene, including local Ethics Committees, ensuring short evaluation and approval times for the research protocols.

If this joint work is achieved, LATAM, as a region, will be more attractive for the execution of clinical trials and will allow its population to be adequately represented.

Roles of the interested parties (Stakeholders)

According to the publication Increasing Diversity in Clinical Trials: Overcoming Critical Barriers from the journal Current Problems in Cardiology, there are several actors that intervene to increase the diversity of populations in clinical trials. In this qualitative research work, 5 main barriers were identified for populations considered to be minorities to enter the study: distrust from participants, lack of comfort with study processes, lack of information, time and resource constraints, and lack of awareness about clinical trials.

With that information, a revision took place regarding who the stakeholders are and what their responsibilities would be to increase the recruitment of this type of population:

1. Referring physicians since it has been proven that if they intervene, it is much more likely that the participant will agree to enter the study because they provide more confidence.

2. Researchers are the ones who can mitigate and clarify the doubts that these communities have, focusing on strategies that cover the five identified barriers.

3. The study coordinators are often the "face of the study", and the adherence of the participants depends a lot on them, since more often than not, they directly address the doubts, problems, and personal situations of each subject and therefore, they can make the subject feel much more comfortable in the study, if their doubts are properly attended.

4. Sponsors have a crucial role when designing the studies, knowing the need t o include populations that are usually underrepresented, as well as training researchers on the importance of the diversity of populations, besides including and listening to patient communities to increase their trust in clinical trials.

Conclusions 

It is widely documented that, despite the efforts, there are still problems of diversity in clinical trials that can lead to serious obstacles [OW1] of safety and efficacy of innovative therapies. Therefore, this issue must be addressed starting by expanding the eligibility criteria to participating in a more significant number of research centers in several regions. Finally, it is crucial that the FDA, the European Medicines Agency (EMA), local regulatory authority, CROs, research centers and, above all, patient communities work together to build trust and foster the means to reduce disparities in health care for the world population.

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