Is Clinical Trial Diversity the New Patient Centricity?

By Hiren Thakkar, Managing Director, Octalsoft
LinkedIn: Hiren Thakkar
LinkedIn: Octalsoft

Inadequate ethnic diversity in clinical trials, tight eligibility criteria, delayed or missing prescription recommendations for certain communities, and access gaps affecting global health are all hot topics in academia, business, and government. These deficiencies are being filled by outreach activities, regulatory standards, and pragmatic experiments. Transformative progress will need multi stakeholder commitment to responsibly accept variability in intrinsic and extrinsic clinical development aspects, made possible by quantitative translational sciences, a Totality of Evidence mentality, purpose, and trust.

Findings suggest that diversity and inclusion may play a crucial role in the future trajectory of global health. For example, the influence of demographic transitions, migration, and urbanization (e.g., the adoption of Western diets in developing nations) was explored, as was the slower dissemination of medical innovations in impoverished places.

Some future scenarios, for example, indicated a highly diversified ecosystem for drug development and health care, emphasizing the significance of reconsidering our approaches to intrinsic and extrinsic aspects as clinical pharmacologists.

In a paradigm with a Totality of Evidence attitude, we are increasingly adopting population pharmacology models instead of specific clinical pharmacology research. As trust in quantitative translational frameworks and patient-centric diversity grows, it opens the door for us to reconsider how we approach population heterogeneity in drug development, so that we don’t lose out on chances to conduct more varied and accessible clinical trials. The tools and procedures are already in place; all that is required is a refocus through the diversity and inclusion lens.

How Patient-Centricity and Trial Population Diversity go Hand in Hand

A recent study of patient diversity in clinical trials in phase III trials supporting FDA approval of solid tumor anticancer drugs between January 1, 2006, and June 30, 2020, found that Black patients and women were underrepresented in comparison to national cancer epidemiology statistics. Underrepresentation of men (compared to an age-adjusted prevalence of rheumatoid arthritis in men nationally) and minority racial/ethnic groups, as well as the exclusion of elderly with varying upper age limits in over 40% of trials, have been discussed as factors that may impact the generalizability of results in randomized controlled trials in rheumatoid arthritis.

Efforts to extend clinical trial eligibility criteria are increasing, recognizing that the rationale for exclusion criteria may not be scientifically valid. The efforts of organizations such as the American Society of Clinical Oncology, Friends of Cancer Research, and the FDA in recent years have enabled progress towards more inclusive clinical development, with position papers and regulatory guidelines encouraging rational expansion of eligibility criteria—an opportunity for clinical pharmacology.

Clinical trial simulations of more inclusive alternative designs showed that broadening eligibility criteria could have more than doubled the pool of eligible patients, with more women and patients over 75 years old, without affecting the hazard ratio for survival benefit or treatment withdrawals due to adverse events. This example demonstrates how, by combining RWD and sophisticated analytics, data-driven clinical trial designs may increase diversity and inclusion without compromising benefit/risk. The ideas and lessons acquired from widening eligibility criteria in cancer studies using clinical pharmacology principles, we believe, are generally relevant across therapeutic domains.

The International Conference on Harmonisation (ICH) E17 guideline allows for ethnic population-specific dosage in multiregional clinical studies where disparities in dose exposure relationships are present. This option is underutilized, leading to the idea that significant ethnic variations demanding a different dose should always imply the exclusion of an area (e.g., Asia) from phase III studies.

Our respect for variability in intrinsic and extrinsic characteristics has grown exponentially as our ability to harness multidimensional data both cross sectionally and longitudinally has grown dramatically.

In Summation

Human diversity, as well as our ability to thoroughly characterize its multidimensional and spatiotemporal richness, is growing all the time. A patient-centric approach to considering diversity in intrinsic and extrinsic factors in appropriately inclusive clinical development strategies and evidence synthesis provides clinical pharmacologists with opportunities that were not previously available.

Progress will need multi stakeholder trust in a Totality-of-evidence approach combined with a development attitude and willingness to depart from traditional paradigms. This will eventually allow everyone to have faith in and timely access to evidence-based medicine.