By Christoph Koenen, chief medical officer, Otsuka
I attended medical school in Heidelberg, Germany, in the 1990s. The concept of diversity and inclusion in the discovery of new treatments for patients, as well as the disparities that existed within the public health system as whole, did not consume much of my attention. It was not until I studied a semester abroad at Witwatersrand University in Johannesburg, South Africa, and took clinical electives at a very small hospital near Mozambique, that my eyes were opened to the racial injustices that plague our society. This is especially true in the practice of medicine. That experience, at a time when Nelson Mandela was sworn in as the first Black president of South Africa, made a long-lasting impression that has driven my desire to promote diversity of all types in healthcare, and specifically within clinical trials.
On Nov. 9, 2020, the FDA released a final version of its guidance Enhancing the Diversity of Clinical Trial Populations — Eligibility Criteria, Enrollment Practices, and Trial Designs. The guidance, a result of the FDA’s initiative to promote diversity in clinical study samples, was created to more accurately reflect the real-world patient populations that will ultimately use the products being researched and to obtain relevant safety and efficacy data that is specific to those populations.
A week later, Pharmaceutical Research and Manufacturers of America (PhRMA), the pharmaceutical industry’s largest lobbying organization, issued PhRMA’s Principles on Conduct of Clinical Trials and Communication of Clinical Trial Results to enhance racial and ethnic diversity among participants in clinical trials run by the drug makers that are members of the organization. The principles have four main areas of focus — build trust through outreach, acknowledge past wrongdoings, reduce barriers to access and monitor the effectiveness of treatments in diverse populations once on the market, and maintain transparency in efforts to increase diversity and inclusion in clinical trials.
In many ways, the new industry guidelines reflect the FDA’s final guidance. However, PhRMA’s principles reference only demographic diversity — race, ethnicity, gender, and age. The FDA guidance also stresses the need for diversity in terms of non-demographic characteristics such as organ dysfunction, rare diseases, weight, and comorbidities.
Is this a step in the right direction? Absolutely. However, both the FDA and PhRMA guidance are voluntary and lack a mechanism of accountability and enforcement, including insight into who will pay for implementing the infrastructure to achieve these guidelines. The FDA acknowledges that, despite years of effort to increase trial diversity, challenges continue. Part of the lag in trial diversity could be attributable to the fact that nearly two-thirds of drug trials conducted in the past five years were outside the U.S., with many of those trials being conducted in countries with less diverse populations.
It is paramount therefore that pharmaceutical and biotechnology companies, along with regulatory bodies and site sponsors, be unwavering in their commitment to adhere to and incorporate all appropriate guidelines into their clinical trials. Advancements of the protocols, tools, and technologies that were highly leveraged during the COVID-19 pandemic are the key to breaking down the barriers that perpetuate clinical trial disparities.
As a company dedicated to serving those with unmet medical needs, Otsuka continues to innovate and defy limitations by taking risks to overcome the complexities of treating mental health. Respecting the value of every mind and understanding that central nervous system conditions -- such as schizophrenia, major depressive disorder, and bipolar disorder — don’t discriminate based on a patient’s ethnic or cultural background are important. As we embark on designing a completely virtual clinical trial, these are priorities that will break the current selective infrastructure chain. By getting out of our comfort zone and embracing new ways of doing things, we have the potential to help so many more people who need access to appropriate treatment and services.
Democratizing Clinical Trials And Real-World Data
Brick and mortar clinical sites will always be useful and necessary. However, the virtualization of clinical trials and the technologies that make them possible can help to broaden the number and types of medical centers with which we engage. Specifically, this will enable us to democratize clinical trials by training and attracting investigators with diverse backgrounds and conduct trials inclusive of traditionally underrepresented populations and in underserved communities.
As an example, Otsuka has digitized trials over the last five years by leveraging tools such as eConsent, eSource, and eScanning of clinical supplies to provide real-time insight to trial activities. Through collaborations with industry leaders such as Verily Life Sciences, we have developed innovative solutions to virtualize clinical trials that drive greater patient-centric research, while being committed to ensuring patient safety, data integrity, and trial optimization. We do this to meet patients where they are in their wellness journeys.
Real-world data (RWD) is another area that will bolster democratizing clinical trials. The final FDA guidelines include broadening subject eligibility criteria by using RWD to actively find participants versus relying on randomized clinical trials (RCTs). While the gold standard in safety and efficacy of therapies and vaccines, RCTs tend to exclude patient subgroups and do not reflect diversity by race, ethnicity, age, gender, socio-economic status, and specific comorbidities. The end results of the trial will not adequately represent how the new therapy is likely to perform among diverse patient groups in the real world.
By incorporating RWD into trial protocols, pharmaceutical and biotechnology companies can develop broader insights related to the clinical and safety impact of a given therapy within specific patient subgroups that may have been underrepresented otherwise. This would allow us to gain insights into outcomes in real-world scenarios, while achieving a larger, more equitable, and diverse data set.
Beyond Clinical Trials
As mentioned earlier, advocating for and delivering on diversity and inclusion in clinical trials is a step in the right direction, but access to these beneficial medications is critical. Lack of access will only further drive health disparities. As researchers and developers of these therapies, we must address the systemic inequities within our healthcare system that limit access after product commercialization.
To begin to solve for this, we need to simplify the journey for both patients and providers, making it easier for them to learn about, enroll in, and participate fully through patient access services. Digital innovation will be a key factor in bringing this to fruition, while still incorporating the human touch throughout the journey to provide personalized support when and where it is needed.
Only by infusing inclusion into every aspect of the healthcare continuum will we truly be successful in meeting the needs of people around the world who rely on our medicines.
About The Author:
Christoph Koenen, MD, is EVP and chief medical officer at Otsuka, where he leads the company’s global R&D strategy that includes the entire clinical development process from first in human to late-stage development. He also oversees Medical Affairs, which consists of medical strategy and field medical teams, bridging the research and commercial organizations. Before joining Otsuka in 2019, Koenen was head of Cardiovascular Medicine and Development at Bristol-Meyers Squibb (BMS), helping to develop its next generation of cardiovascular medicines. He received his medical degree from Ruprecht-Karls University School of Medicine, holds an MBA from Schiller International University, and is board certified in internal medicine and diabetology.