The Case for Diversity in Clinical Trials

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Recruiting and retaining participants in clinical trials is a key factor of clinical research success, and the diversity of participants plays a prominent role. Inclusion of broad patient populations—for example, people of different races, ethnic groups, sex/genders, ages or those with rare conditions—help provide evidence that the study drug or medical device will be safe and effective in the wider target patient pool if the drug or device is approved.

Clinical trial recruitment follows a defined methodology where people who want to volunteer must meet a set of eligibility criteria and provide their informed consent for participation. These criteria are set to minimize the chance of side effects, comorbidity interactions and early withdrawal from the trial. Therefore, eligibility criteria help researchers achieve more accurate research findings. However, at times, they also result in the enrollment of participants who do not fully represent the diversity of the intended patient population.

Diversity and COVID-19 Trials

Without adequate research across diverse patient populations, trial results may give rise to doubt, which is what happened with AstraZeneca and its trial of a COVID-19 vaccine candidate (AZD1222). The preliminary trial results put the vaccine’s overall efficacy rate at 70%. A higher 90% rate was achieved in a subgroup of trial participants who, by an accident, received a half dose followed by a full dose. However, that subgroup did not include any participants over the age of 55. This prompted concerns from the research community about the robustness of the efficacy data, since the half dose/full dose regimen had not been tested in older participants, who are especially vulnerable to COVID-19. AstraZeneca has since said that it would consider running additional global trial to further investigate the efficacy of its vaccine candidate using a lower dosage.

When Moderna presented the interim results from their trial of a COVID-19 vaccine candidate (mRNA-1273), they also signaled achieving diversity in their trial population. The 30,000 trial population included participants over the age of 65; those under the age of 65 with high-risk chronic diseases that put them at increased risk of severe COVID-19; and participants from the communities that have historically been underrepresented in clinical research and have been disproportionately impacted by COVID-19.

Why Diversity Matters

When a clinical trial population is homogenous (for example, consisting of a single race or ethnicity), research findings may be skewed and result in clinical data that would not be generalizable to a wider patient population for which the study drug or medical device is intended. This outcome could result in the drug or medical device being less beneficial or, more so, unsuitable for some patient subgroups.

Even in times of global health emergencies, like the COVID-19 pandemic, recruiting participants from diverse backgrounds remains an important consideration, particularly for the clinical trials studying diseases or conditions that disproportionately affect certain populations. As is the case with COVID-19, research data shows that its severity and mortality rates vary according to age, sex and ethnicity, with higher rates of hospital admissions, critical-care admissions, and death in older individuals, men, and individuals of Black, Asian and minority ethnic groups.

Ultimately, diverse clinical trials support more informed regulatory decisions and product labelling. The inclusion of information relevant to patient subgroups in the product labelling can help better inform healthcare providers and patients about the use of a drug or medical device. This step improves the ability of patients, caregivers and healthcare providers to make more informed decisions regarding their treatment options.

Patient and Public Perspectives

Historically, the public’s feeling towards clinical research, especially among those from the racial and ethnic minority communities, was that of a distrust. This has been mainly attributed to past abuses in clinical research, perceived discrimination in health care and the lack of awareness about clinical research. Thanks to the strong regulatory and ethical oversight of clinical trials and growing transparency about trial conduct over the past decades, this feeling has diminished, but it has not gone away completely.

These feelings are somewhat reflected in the results from a recent perceptions and insights survey by the Centre for Information and Study on Clinical Research Participation (CISCRP). In April, the center surveyed 500 respondents from across the U.S., UK, France, Germany and Italy to assess the impact of the COVID-19 pandemic on levels of public’s understanding, perceptions and experiences related to clinical research. The results of the survey showed that most respondents (58%) had not heard of specific clinical research studies for COVID-19 and that, overall, trust in pharmaceutical companies ranks lower than other research stakeholders.

Although the lack of trust is thought to be one of the most significant factors associated with low participation of minority communities in clinical trials, there are also other, more tangible, barriers. These may include the lack of suitable transportation to the study site, negative financial implications due to time away from work to attend study visits, health insurance barriers, caregiver responsibilities and language barriers. Any or all of these barriers may lead to the patient deciding against their participation in a trial.

Improving Industry Practices

Within the clinical research industry, there is a general acknowledgment that achieving diversity in clinical trials presents a challenge. However, the industry has been taking positive steps towards improving relevant approaches and practices.

In November, the U.S. Food and Drug Administration (FDA) published its final guidance on enhancing the diversity of clinical trial populations, which provides sponsors with the recommendations that can help increase enrollment of underrepresented populations in clinical trials that support a new drug application or a biologics license application. Distinct attention has been given to the strategies for broadening clinical trial eligibility criteria for the participants in clinical trials in rare diseases.

Likewise, the FDA’s guidance on the evaluation and reporting of age-, race-, and ethnicity-specific data in medical device clinical studies calls for sponsors to develop enrollment strategies that include representative proportions of relevant age, racial and ethnic subgroups, which are consistent with the intended users of the device, and includes recommendations for developing such strategies.

The roadmap to improve trial delivery for underserved groups, recently commissioned by the UK National Institute for Health Research Clinical Research Network (NIHR CRN), sets out a methodological framework to help researchers work with underrepresented (“underserved”) groups and to improve their access to clinical research.

A new industry consortium was launched last year to address the critical need to improve patient diversity in clinical trials. A partnership between the CISCRP and leading pharmaceutical companies and clinical research service providers (Merck, IQVIA, Biogen, Otsuka, CSL Behring, Janssen, WCG, Boston Scientific, EMD Serono and Pfizer), the consortium will focus its activities on supporting community-based education to increase general knowledge about the clinical research process among minority communities.

Bridging the Diversity Gap in Clinical Trials

Numerous regulatory guidance and scientific papers provide trial sponsors an abundance of information that can help in defining and operationalizing their strategies related to patient diversity and inclusion. Equally valuable are the industry’s practical case studies and lessons learned, which can offer insights into how to find the right balance between the need to enroll diverse patient groups and conducting research in a timely and cost-effective manner.

The application of adaptive trial designs; emerging technologies for the collection and analysis of clinical outcome data based on various demographic characteristics; and use of novel web-based platforms that facilitate patient participation in clinical trials from the comfort of their homes are just a handful of examples of approaches that can enhance patient centricity and diversity in clinical trials.

Still, among the methodological considerations and technical details, there is a simple fact that stands out. Clinical trials are conducted with human volunteers—people. People learn about things, connect with other people and build stronger relationships through communication and transparency. Clinical trials are no exception to this. Patient engagement and outreach developed in partnership with the target communities; appreciation, and removal, of barriers to trial participation that those communities may face; comprehensive, culturally sensitive education on medical product development; and meaningful communication of research findings to those who participated remain key prerequisites to building trust and fostering diversity in clinical trials.