Laura Fernandes, PhD, is the Senior Statistical Director, COTA, Inc.

Laura Fernandes, PhD

Laura Fernandes, PhD, Senior Statistical Director, COTA, Inc.

Clinical trials are continually pushing the envelope of what is possible with therapeutic interventions. These research partnerships are responsible for radically altering the way physicians have learned to treat cancers, rare diseases, and other conditions over the last several decades.

It’s no surprise that the way investigators conduct these trials is constantly evolving as well. The randomized clinical trial (RCT) remains the gold standard for establishing safety and effectiveness, but new trial designs are being developed as experts reintegrate lessons learned over time into the process of conducting reliable and reproducible research.

The advent of digital real-world data (RWD) and real-world evidence (RWE), as well as an explosion of advanced analytical tools, have revolutionized the way life sciences stakeholders interact with information and have made it possible to synthesize enormous volumes of data to generate deeper, and more actionable insights into patient experiences and outcomes.

As investigators become more adept at using RWD and RWE as a fundamental component of clinical trials, these resources have the potential to improve the way they enroll patients in research, conduct effective trials, follow patients over time, and ensure the safety and efficacy of new therapeutics.

Here are 4 top predictions for how clinical trials will evolve to better serve patients in 2023 and beyond.

A stronger focus on cumulative toxicity research

Many early-phase clinical trials typically only follow patients for a limited amount of time. For example, phase 1 trials that work to identify the most appropriate dose of a new therapy can last for only a month or 2, restricting researchers’ insight into what happens when a patient takes multiple cycles of a drug to treat their condition over time.

There is a need for more information about the cumulative toxicity of emerging therapies, especially as new drugs diverge from the “hit it as hard and fast as possible” mentality of traditional chemotherapy. For some targeted therapies, more might not be better. But researchers will never know unless they conduct the right research into the issue.

The FDA has launched Project Optimus to pursue this area of investigation with the goal of refining approaches to dose finding so as to avoid the need for dose modifications in the latter trials.

 In the near future, I anticipate the FDA will become more interested in these factors earlier in the clinical trial process, so trial sponsors will need to rethink their strategies accordingly.

More structured approaches to ensuring diversity and inclusion in clinical trials

Increasing clinical trial diversity has been on the industry’s radar for some time, and for good reason. The composition of most clinical trials remains woefully homogenous, with white men still comprising the vast majority of participants in research globally.

This poses risks to patients who are not represented in the research cohort and may alter the real-world safety and efficacy profile of therapies once they hit the market.

Clinical trial sponsors will need to prioritize integrating racial and ethnic minorities into the research ecosystem in the coming months and years. Not only will they face increasing market pressures to do so, but the FDA is also urging sponsors to take a more proactive approach to broadening the participant pool.

In the spring of 2022, the agency released draft guidance for developing plans to enroll more participants from underrepresented racial and ethnic populations in the United States.

 The draft guidance recommends that sponsors develop and submit a Race and Ethnicity Diversity Plan to the FDA at the front end of clinical development and provides a framework for doing so.

Although there is no regulatory mandate for diversity plans yet, trial sponsors would be wise to consider how they will address any upcoming requirements, and in the process, benefit from more equitable and reliable research.

“Tokenizing” patients to aid in aggregating and applying RWD to research

As RWD flows into the clinical trial environment from multiple locations, researchers will need better ways to track patients and their unique records.

In the continued absence of a national patient identifier to ensure that patients are appropriately matched with their data—and only their data—researchers risk double-counting or inappropriately merging patients as they collect and analyze RWD from disparate sources.

To truly maximize the potential of RWD, they will need to collaborate on a private and secure method for tokenizing patients. This will have to happen sooner rather than later, and the project must go beyond the life sciences community to include clinical care providers, payers, and intermediaries.

I hope to see a neutral, trusted stakeholder, such as a non-profit organization or government entity, take on the challenge to avoid any competing business incentives that may cloud the utility, privacy, and security of a proposed methodology.

New requirements for including RWD in every FDA submission

RWD and RWE are quickly showing their value for broadening the scope of knowledge and supporting more comprehensive, longitudinal research. Several new therapies have successfully included RWD and RWE in their FDA submissions, and the FDA is keenly interested in integrating RWD and RWE even more closely into the standard clinical research process to inform regulatory decisions.

New draft guidance released in fall 2021 helped further establish the agency’s vision for an RWD-enabled future, which includes the broader use of external control arms and even synthetic control armsto augment RCTs and other foundational research assets.

I predict that RWD will eventually become a required component of regulatory decision making in some capacity. There is simply too much value in RWD to do otherwise.

Of course, it will take some time and a great deal of collaborative effort for investigators to refine their approach to collecting and using RWD in submissions at scale. Actual mandates are likely some years away, but that doesn’t mean they shouldn’t start preparing for them.

Clinical trial sponsors should embrace the opportunity to learn more about integrating RWD into research initiatives and actively contribute to the discussion around how, when, why, and where RWD should be used to support therapeutic development and regulatory approvals.

With the clinical trial ecosystem changing so rapidly, there are many promising developments on the horizon. By working together and embracing the exciting potential of RWD and RWE, we can quickly move toward our shared goals of developing and distributing safe, effective, and life-changing therapies to all patients who can benefit from the efforts of our research.

1. Project Optimus: reforming the dose optimization and dose selection paradigm in oncology. FDA. Updated May 31, 2022. Accessed December 12, 2022. https://bit.ly/3PmbQ5U

2. Sharma A, Palaniappan L. Improving diversity in medical research. 

. 2021;7(1):74. doi:10.1038/s41572-021-00316-8

3. FDA takes important steps to increase racial and ethnic diversity in clinical trials. FDA. April 13, 2022. Accessed December 12, 2022. https://bit.ly/3VSIo9Z

4. Concato J, ElZarrad MK. FDA issues draft guidances on real-world evidence, prepares to publish more in future. FDA. January 31, 2022. Accessed December 12, 2022. https://bit.ly/3FpczyH

5. Real-world evidence. FDA. Updated October 19, 2022. Accessed December 12, 2022. https://bit.ly/2IVBGhx

Articles

Laura Fernandes, PhD, Senior Statistical Director of COTA, Inc, gives 4 predictions of upcoming trends that will change how clinical trials are performed. 

Laura Fernandes, PhD | Authors

Articles

Predicting the Clinical Trials of the Future: Top 4 Trends to Watch