Associate Director, Life Sciences, Guidehouse

Liisa M. Eisenlohr

While the scientific conceptual origins of health equity date back to the early 1800s, the global healthcare industry is still striving for ways to help ensure every person can attain their full health potential. One important way manufacturers can help advance the mission is to ensure clinical trials more closely reflect the populations intended for treatment. Scientifically, people of different sexes, gender identifications, ages, races, ethnicities, and health conditions may react differently to certain medical products. Despite this fact, and even though many life sciences companies developing products are making efforts and have come a long way in better representing patient diversity, clinical trials often still do not accurately reflect the populations intended for treatment.

Scientific and technological advances are making it easier than ever to expand clinical trial candidate bases, so, in many cases, companies should be able to more accurately reflect their real-world patient population. This article offers guidance on 5 key considerations for assessing and restructuring your clinical trial design and processes to achieve better representation of target populations.

Consider technology to help expand recruitment

Traditionally, studies often limited the diversity of trial subjects because of scientific and business factors, including the availability, vulnerability, and/or willingness of participants, as well as budgetary and time constraints. For example, as trial sites, the location of hospitals tended to dictate the participant pool, based on proximity and accessibility. People who lived farther away and/or lacked means of transportation were harder to recruit than those who lived nearby—and in general, those who live nearby hospitals or have convenient transport tend toward homogeneity.

However, technological advances have addressed many of these barriers. Nowadays, smart trial technologies are available for design, recruitment, execution and data analysis. This means you can more easily engage, monitor and track participants, and conduct decentralized trials virtually and remotely to broaden the reach and enlist a broader group of patients. For example, some trial activities can be completed through telehealth visits or at a patient’s preferred clinic.

You also can leverage publicly shared online content from patient advocacy, support and fundraising groups as well as patients themselves to identify and reach out to ideal participant candidates to help spread the word about clinical trials. To this end, it also is very helpful to provide trial information in multiple languages and make it available in locations that different ethnic communities frequently visit.

Consider who you’re including or excluding—and why?

For purposes of a clinical trial, diversity should reflect the demographic and clinical factors present in the population targeted by the medical product’s indication and the addressed market. To define a more robust trial participant pool, first identify the population groups you plan to treat and the clinical rationale for targeting that particular group.

For example, in some cases, whether intentionally or inadvertently, companies continue to base their clinical trial recruitment strategy on familiar “tried and true” routines that tend to secure the easiest-to-reach trial candidates. And the easiest-to-reach candidates are those who typically live nearby the designated trial sites, or volunteer to participate. In these cases, manufacturers can proactively choose study sites that have a more diverse patient population and leverage technology to include patients who live farther away.

In addition, many companies adhere to established trial inclusion/exclusion criteria, which can lead to enrollment of a less diverse study population. In some cases, these criteria are applied with the intent to keep a population safe, such as for example not including children or pregnant individuals, even when there is no evidence the medication will be detrimental to those patient segments. In such cases, manufacturers should consider whether the established inclusion/exclusion criteria can be adjusted to allow a broader population to be enrolled without harm to those who are perceived as more vulnerable study subjects.

The needs for diversity and inclusion can vary depending on the clinical trial phase. For example, Phase I clinical trials for medications treating a disease generally are aimed at answering whether a drug is safe and, if so, how much of a drug a patient can tolerate. It remains important to consider diversity and inclusion for these trials, however, patient health will be the highest priority in order to ascertain safety and tolerability of a new drug. As the trials move into later efficacy-testing stages, aligning the diversity of the population with the end-use patient pool becomes increasingly critical to gaining scientific evidence. Indeed, excluding patients based on factors that are not associated with risk can impede your ability to establish an efficient safety profile for the new drug and limit your commercial market potential.

Many clinical trials exclude pregnant individuals without necessarily having evidence the therapy could negatively affect the health of the individual or fetus. While this can seem prudent, it may have unintended consequences for the excluded population. Case in point: The development trials of vaccines for COVID-19 at first largely skipped over individuals who were pregnant or breastfeeding. However, early test results within these populations show positive benefits, including good tolerability and reduced risk of infection for the individual. If researchers had continued excluding this population from trials, pregnant individuals interested in vaccination but ineligible to be vaccinated would have continued at higher risk of infection and transmission.

Consider the regulatory landscape and your target market(s)

Naturally, it is critical to review the regulatory approval processes and requirements of your target region(s). Beyond regulatory complexities and intricacies, also consider how current and anticipated regulatory trends could potentially impact your trials, especially later stage ones, as well as the product approval process and timeline for your launch.

Keep in mind, pressure from regulatory bodies and patient advocacy groups is growing for life sciences companies to enhance clinical trial diversity and inclusivity to strengthen the safety and efficacy of treatment options:

FDA has already started requiring more diversity in clinical trials;

EMA is evaluating the impact of excluding certain populations from clinical trials; and

Other agencies like Japan’s Pharmaceuticals and Medical Devices Agency that historically have required in-country trials to ensure their populations have been fairly considered are relaxing these requirements when representative populations are leveraged out-of-country.

Meanwhile, agencies globally also are pushing for post-market surveillance of treatment options to help ensure new therapies work outside trials as intended across populations.

This confluence of pressure points likely is a strong signal as to where forward-thinking manufacturers with global market ambitions should be headed.

It also is important to assess if any discrepancies exist among your target markets that could inform your trial design or change your results. Usually, the best bet is to design the trials so the clinical evidence reflects the genetic and clinical profiles of the patient segments in your target markets. Even territories that seem to share many demographic, socioeconomic, structural or clinical commonalities can present significant underlying differences that must be addressed. For instance, standard of care therapies, typically used as the control treatment (i.e., the therapy against which an experimental drug is tested) in clinical trials, may differ from region to region. Submitted data from clinical trials in which therapies not typically used in a specific country or region were used as control treatments can even cause significant delays in getting marketing approval in those regions or countries.

For example, with the aim to eventually launch a rare disease therapeutic in the United States and European Union, a specialty pharmaceutical company prepared to begin Phase III trials. Phase I and Phase II were conducted exclusively with US patients, and the company based its Phase III trial design on previous study designs with plans to again rely exclusively on U.S. study sites. However, an analysis of the clinical unmet needs, asset feasibility, and commercial attractiveness revealed significant differences in the average age of target patient candidates in the US vs. the EU that correlated to differences in care standards. With this insight, the company redesigned its Phase III trials to meet the needs of both regions.

Without the market analysis, the company would have attempted to enter the EU market and most likely been required to conduct a separate Phase III trial with patients based in Europe and/or of the appropriate age range, delaying the product launch and incurring more costs.

Disparities between trial population and market population will remain—but the more committed life sciences companies are to clinical diversity, the better treatment options they will be able to offer, while at the same time increasing health equity. Depending on your current trial design practices, therapy options in development, and target markets, you may need to overhaul your approach, tweak a few factors, or something in between. By reevaluating your study design and study site locations as well as relying on scientific and medical justification for exclusion and inclusion criteria and decision-making, you can launch therapies that provide safe, efficacious treatment options to a broader patient segment.

, Associate Director, Life Sciences, and 

, Associate Director, Life Sciences; all with Guidehouse

Flores, L.E.; Frontera, W.R.; Michele P. Andrasik, M.P.; et al.. Assessment of the inclusion of racial/ethnic minority, female, and older individuals in vaccine clinical trials. JAMA Netw Open. 2021;4(2):e2037640. doi:10.1001/jamanetworkopen.2020.37640

Jensen, N., Kelly, A.H. & Avendano, M. The COVID-19 pandemic underscores the need for an equity-focused global health agenda. Humanit Soc Sci Commun 8, 15 (2021). 

https://doi.org/10.1057/s41599-020-00700-x

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