The use of real-world data (RWD) to help design clinical trials is nothing new but increasingly it is being used early in the process to boost trial diversity and inclusion.
“Data really is the bedrock of how we’re able to increase representativeness in clinical trials as we go forward,” said Christina Mack, PhD, Chief Scientific Officer of IQVIA Real World Solutions, a company providing analytics and technology solutions to the life sciences industry.
Conversations around diversity planning in clinical trials can start too late, Mack explained, with issues coming up after trial sites have already been selected. She noted that enrolled sites may not have patients that reflect the disease population. But recent guidance from the US Food and Drug Administration (FDA) around diversity, equity and inclusion planning is nudging drug sponsors to begin looking at enrollment goals and the rationale behind them earlier in trial planning, and ultimately providing a diversity plan to the FDA around these goals.
“Understanding the epidemiology of disease and understanding the share of disease burden across different sub-populations is absolutely critical. That’s where real-world evidence can put us in the right place at the right time,” she said.
FDA pushes diversity plans
In April 2022, the FDA issued draft guidance on developing formal diversity plans to improve enrollment of participants from underrepresented racial and ethnic populations in clinical trials. The guidance suggests that diversity plans begin with an assessment of any data that may show the potential for a product to have “differential safety or effectiveness associated with race or ethnicity.” The diversity plan guidance encourages sponsors to leverage a variety of data source – including published literature and RWD – to set enrollment goals. (RELATED: FDA recommends sponsors plan to include race, ethnicity in clinical trial design, Regulatory Focus 13 April 2022)
The draft guidance builds on guidance issued in October 2016 that outlined how to collect and present race and ethnicity data in submissions to the FDA and in November 2020 that outlined ways to expand eligibility criteria and enrollment practices to enhance diversity. (RELATED: FDA updates guidance on collecting race, ethnicity data in clinical trials, Regulatory Focus 1 November 2016; FDA lays out strategies for promoting diversity in clinical trial enrollment, Regulatory Focus 9 November 2020)
RWD that is collected through point-of-care clinical trials, in which the clinical study is integrated into routine health care delivery, also has the potential to increase trial diversity by reaching patients with less access to research facilities, FDA’s Office of Medical Policy told Focus.
Compared to the data obtained in traditional clinical trials, RWD sources typically include more diverse study populations. However, RWD collected during routine clinical care – such as in electronic health records (EHRs) or medical claims data — may not be “fit-for-purpose” when evaluating drug-outcome associations from a regulatory perspective, according to FDA. “The goal for all stakeholders is generating reliable evidence, and RWD, in and of itself, does not fill that gap. Rather, using relevant and reliable RWD in a well-designed study can generate trustworthy real-world evidence (RWE) that is diverse regarding the study populations involved,” FDA’s Office of Medical Policy said in a statement.
Recommendations for cancer trials
At the same time as FDA urged industry to move forward with diversity plans as part of clinical trial design, the cancer research community issued recommendations for researchers to improve equity, diversity and inclusion in cancer clinical trials. In April 2022, the American Society of Clinical Oncology (ASCO) and the Association of Community Cancer Centers (ACCC) issued a research statement that spelled out ways to increased diversity, including forming partnerships with patient advocacy groups and community leaders, providing bias training to clinical trialists and reporting data on racial and ethnic diversity of trials participants when reporting trial results.
RWD is one tool to help achieve these clinical trial diversity goals, said Randall A. Oyer, MD, one of the authors of the research statement and executive medical director of the University of Pennsylvania Ann B. Barshinger Cancer Institute in Lancaster, Pennsylvania. “Real-world data could be used to place trials more expeditiously in communities, where populations reside and get their care, where it’s possible to expeditiously complete a trial,” said Oyer, who is also a past president of ACCC.
Another positive of RWD is that it includes outcomes data that matters most to patients, including symptom relief, quality of life, and ability to access treatment, Oyer said.
Data challenges
A first step to improving RWD for use in increasing trial diversity is widespread adoption of a minimal set of definitions around certain health equity data, Oyer said. Additionally, there should be a standardized way of collecting that data in EHRs and making it searchable for researchers, he said.
The lack of completeness and granularity of clinical data by race and ethnicity is a challenge in setting diversity goals early in clinical trial planning, Mack said. In many cases, a single source of RWD on race and ethnicity is not sufficient either because of missing and incomplete data or inherent biases that may be due to how or why the data was originally collected. For example, data extracted from a hospital EHR system has the potential to show worse disease outcomes for certain populations while primary care data could underestimate the prevalence of disease due to the patterns of care at those points of care, Mack said.
Overlaying multiple RWD data sources can help to account for those shortcomings, Mack said, but even then, it is important that the data is interpreted by epidemiologists and clinicians who understand the nuances and limitations of RWD.
“We need to look across enough sources to really give ourselves a good start in our goal setting and in our diversity goals and make sure that we arrive at a reasonably valid and attainable target or target range,” Mack said. “The power of creating a diversity plan is that sponsors are equipped with the evidence to make careful choices, moving the needle towards a more representative population earlier in clinical development and closing the current gap between test subjects and real-world populations. And while it may go beyond race and ethnicity, it is a good place to start.”