In order to accurately represent the safety and efficacy of drugs, we need clinical trials with a patient population that mirrors real world use, and unfortunately, we have seen that most trials fail to achieve this goal. As regulatory guidance continues to evolve, industry leaders must adopt a bold, proactive approach to increasing representation and involving underserved populations in vital medical research.
By Karla Feghali and Laura Fernandes (reposted from LinkedIn)
Clinical trials are the lynchpin of safe, successful drug development. To develop an accurate picture of how therapeutic agents interact with populations they are intended to treat, trial sponsors must enroll a critical mass of patients – and ideally include individuals who are representative of the real-world demographics of people affected by the target disease.
That’s often easier said than done. It’s extraordinarily difficult to find enough patients to fill the vast majority of proposed clinical trials, and many trials fail to get off the ground due to recruitment. It’s even more difficult to create a diverse, representative, and inclusive patient population for studying diseases that affect us all.
Despite the FDA’s clear endorsement of diversity in clinical trials, most trials do not meet acceptable thresholds of representative participants. For example, African Americans have twice the risk of non-Hispanic whites for presenting with advanced-stage prostate cancer. Yet in the clinical trial for a well-known advanced prostate cancer drug in 2020, only 5% of the patients were African American.
This is not an isolated incident. In 2020, the FDA’s Center for Drug Evaluation and Research (CDER) approved 53 different drugs – of the 32,000 participants in the trials for these therapies, 75% were white. In a pooled analysis of 19 multiple myeloma registrational trials leading to an indication, only 7% of the patients were African American despite there being twice the incidence in African American patients compared to white for multiple myeloma.
We must take swift and comprehensive action to correct this imbalance. By reexamining the current systems in place and leveraging real world data (RWD) to support representative recruitment processes, pharma leaders can put the industry on the path to more effective and informative medical research. Here’s how.
Making diversity a core tenet of the pharma philosophy
Clinical trials are a critical part of the pharma ecosystem, but they are only one component of what we do as a community. To enhance diversity in clinical trials, we must challenge ourselves to reevaluate the larger decision-making processes and organizational operations that surround the research environment.
If we want our clinical trials to be truly diverse and representative, we must empower diverse leaders to develop an industry culture that is authentically inclusive from top to bottom.
A broadly representative perspective from the board of directors, C-suite, and other visible leadership positions can lay the groundwork of fostering inclusion commitments throughout the organization. When operating under an inclusive culture and inclusive talent practices, organizations generate up to 30 percent higher revenue per employee, are more profitable than their competitors, and become eight times more likely to achieve positive business outcomes, according to research by Deloitte.
Meanwhile, review committees, ethics advisors, and external observers can supplement internal activities and ensure that the entire organization remains on track with its shared objectives.
Consider integrating patients and caregivers into the decision-making process to provide a critical perspective that is often lacking in medical research. Patients and their family members are best positioned to identify challenges that limit access to care, perpetuate unintentional biases, or result in poor experiences.
Infusing diversity into clinical trial operations is not limited to internal changes. A pharma company’s vendor partners are also inextricably tied to an organization’s commitment. When choosing a contract research organization (CRO) team, companies can work together to realize a trial design that promotes diverse enrollment from the very beginning. In addition, pharma can assess each data provider, consultant, and other outsourced group for their own commitments to diversity and inclusion.
These activities are part of biopharma’s fundamental responsibility to bring better treatments to all patients, no matter what their racial, ethnic, or socioeconomic background. Without thoroughly examining our overall commitment to diversity and inclusion and making active changes to improve our processes, we will not be able to develop and sustain a clinical trial environment that meets high standards of inclusivity.
Leveraging innovative technologies to jumpstart inclusive clinical trial recruitment
Trial sponsors that rely on existing clinical partnerships and historical data, or those who choose trial sites based on previous successes, are severely limiting their ability to find, recruit, and retain an appropriately representative set of trial participants.
Emerging technologies offer a new road forward. With the rise of artificial intelligence, natural language processing, and other advanced data analytics techniques, pharma companies now have access to tools that take advantage of the rich, largely untapped resources of real-world data (RWD).
RWD allows us to build better trials from the ground up. For example, our growing digital data assets can inform protocol design by ensuring we are identifying the most appropriate inclusion criteria and clinical endpoints for new studies.
Instead of relying on spotty historical data to develop protocols, researchers can now access deeply curated, longitudinal clinical records on thousands of patients to gain insight into current standards of care, develop external control arms (ECAs), and construct proxy cohorts that can be much more diverse and representative than those based on a limited pool of locally available participants.
As a result, clinical trial sponsors can validate their study design more effectively and gain confidence that they are starting off on the right path.
RWD also opens the door to less centralized, more distributed trials/decentralized trials, enabling researchers to connect with the optimal participant pool without the traditional constraints of geographical location and anticipation of more diverse trial participants.
Take the fully virtual Duke Hearts of Athletes Study, for example. Duke University is recruiting 500 amateur and professional athletes from across the country to take part in a study about the potential relationship between COVID-19 vaccination and myocarditis without disrupting the participants’ daily lives.
With the trial built on a next-generation platform, researchers will be able to manage recruitment and consent, collect clinical information and patient-reported data, and monitor participants in a fully decentralized manner. If necessary, participants can complete imaging studies at their local healthcare providers and securely send the results to Duke researchers without ever setting foot on the North Carolina campus.
This type of decentralized, RWD-driven trial is just getting started, but the technique holds enormous potential for increasing participation from underserved and disadvantaged communities. Someday soon, patients may even be able to stop in at trial sites located at their neighborhood pharmacy, clinic, or grocery store, eliminating the need to live near a premier academic medical center to get access to life-altering care.
Urging on regulators and peers to enact industry-wide change
The FDA is increasingly offering industry guidance on diversity and inclusion and has established of the Oncology Center of Excellence (OCE) Rare Cancers Program, however pharma leaders don’t have to – and can’t afford to – wait for regulators to weigh in on a topic that is universally considered a moral imperative.
Even more pragmatically for the business-minded, diversity in clinical trials can be a powerful competitive differentiator. By studying the impact on therapeutic patients on a broader range of individuals, pharma stakeholders can gain a deeper, more thorough understanding of how their offerings may act in a highly variable real-world environment. That is a very strong competitive advantage. Forward-thinking stakeholders need to start acting like it.
We will need to establish ambitious but attainable goals for clinical trial diversity. Commit to time-bound deadlines and create accountability mechanisms to ensure continued progress toward these targets. We should publicly announce and celebrate these efforts, such as the BMS Foundation’s $300 million effort to improve health equity through clinical trial diversity. And let’s challenge our colleagues and competitors to do the same.
A recent study by Deloitte and PhRMA found that no one stakeholder can change the clinical trial paradigm alone. Partnering to build scalable and sustainable relationships and solutions, embedded within underrepresented communities and that extend beyond any one clinical trial can be key elements to help ensure success. Patients can benefit from solutions cultivated by the clinical trial ecosystem coming together and developing long-term strategies across multiple disease areas.
Doing this requires collaboration across the industry, integrated clinical care providers, patients, and caregivers into the conversation. Providers in community care settings, in particular, need to be at the table. These clinicians understand their patients deeply and can share insights into effective outreach and retention strategies for their unique patient populations.
Lastly, we must continue to demonstrate the effectiveness of new technologies and data sources for identifying participants and speeding up the completion of safe, informative clinical research. Regulatory entities need real-world use cases to inform their guidance, so we must take a proactive role in providing evidence and feedback to build the guardrails of the future.
Biopharma organizations that embrace these principles and lean into their social responsibility to create diverse, inclusive, and representative clinical trials will be better positioned for success in the modern research environment.
We must move past the outdated recruitment techniques of the past and rise to the challenges of reinventing the clinical trial ecosystem.
With the aid of cutting-edge data technologies and commitment from inclusive and innovative stakeholders across the life sciences industry, we can achieve our shared goals to provide life-changing therapies for all the diverse patients under our care.
Contributors: We would like to thank our contributors Emma Mei, Viraj Narayanan, Jaimee Ryan for their input, review and support of this article.