Time to Modernize Cancer Clinical Trial Eligibility Criteria

Time to Modernize Cancer Clinical Trial Eligibility Criteria

How can we make cancer-focused clinical trials more inclusive while also raising the quality of overall research? That sounds like a win-win value proposition. But how would this happen? With several thousand cancer studies competing for less than 5% of the total cancer population in America, the odds aren’t great. Finding ways to reduce barriers to cancer trial participation was the topic of a recent online webinar sponsored by the American Society of Clinical Oncology (ASCO) and the Friends of Cancer Research. Their new recommendations to progress cancer research eligibility were also recently published. With an unprecedented burst of innovation in cancer-focused drug development, from immuno-oncology and cell and gene therapy to precision-based approaches and targeting tumors, never before has the opportunity to in many cases extend life thanks to clinical research been so prevalent. However, challenges persist in ensuring sufficient numbers of participants in these studies. A competitive, dynamic, and unfolding situation—there are many sponsors recruiting for cancer-based trialsfrom biotech and pharma companies to academic medical centers and prominent research institutes—and the existing eligibility criteria make participation all the harder. Out of the approximately 1.8 million people diagnosed with cancer in the United States, only a small fraction will participate in clinical trials—and that’s a problem as this research in many cases helps propel the movement of the clinical research as a care option: that’s where a trial is part of the care regimen. A problem discussed for a long time now, the recent ASCO-sponsored event shared at least one perspective on the trend toward cancer clinical trials modernization, made possible thanks to new and updated protocols, and breakthroughs such as real-world evidence and remote data collection. Perhaps the COVID-19 pandemic forced a trajectory of clinical trial modernization—that is, the industry-wide acceptance of systems, processes and methods leading to greater patient-centricity, advanced use of data and other forward steps.

The Challenge

Given the tremendous breakthroughs with many life science therapies and approaches, such as biomarkers and precision-based medicine, the potential to not only save and extend life but to dramatically boost quality of life becomes more imminent by the year. Hence the importance of this topic, especially for underrepresented populations (ethnic minorities, elderly, rural populations, etc.) that may present cancer at greater rates and benefit even more from research and yet not ever have the chance to even consider.

A brief survey of clinicaltrials.gov reveals that there are at least 10,779 active cancer-focused clinical trials in the United States alone.  If factoring just clinical trials that are presently in the status “actively recruiting” that number adjusts at 8,054. Out of this figure 2,785 studies are in Phase 1, traditionally focused on safety of novel therapies and most often involving less than 100 patient participants. There are 3,155 active cancer trials in Phase 2 and 584 in Phase 3 (the last stage prior to regulatory filings and of course most often the phase needing the most participation). Phase 4 and other not applicable research studies in cancer total 1,530 according to this search criteria.

With about 1.8 million people diagnosed with cancer in America, it has been estimated that only about 5% of the adult cancer patient population (and some estimate less) enroll in cancer clinical trials. Put another way, the vast majority of adult cancer patients, that is at least 95%, do not bother to participate in research, despite the fact that according to various polls, up to 70% of Americans are included or wiling to participate in research studies.

This means that there are only 90,000 cancer patients in America that presently participate in research and, of course, all sorts of barriers impede even efficiently engaging that 5% of the cancer population participating in research. The math doesn’t really add up—its clear that a majority of the studies will struggle with cancer patient clinical trial accrual.

Barriers to Research

In “Role of Clinical Trial Participation in Cancer Research: Barriers, Evidence and Strategies,” an impressive group of authors shared that actual participation rates are less than 5% and that despite the continuous study into the barriers impeding more cancer study participation, nothing in effect ever really changes—meaning lots of purportedly smart people spend lots of time, effort and moneyresearching this problem with no real meaningful outcomes that raise the bar.

Raising the “structural, clinical, and attitudinal” barriers to cancer trial participation, these authors note the importance of barrier by demographic and socioeconomic factors. A “foundational” challenge, the lifting of key barriers represents a fundamental imperative for the authors. Considering local strategies to reduce barriers, they posit that given the “treatment decision-making process” centering on the patient perspective, never before has the urgency for patient-centric research been greater. These barriers include the following:

  • Structural barriers (clinic access & assessment of trial availability)
  • Clinical barriers (eligibility and the topic of the ASCO webinar)
  • Attitudinal barriers (they exist for both physician and the patient)

What follows is a brief breakdown of the ASCO webinar focusing on transforming eligibility criteria for more inclusivity in cancer research.

The ASCO Webinar

Lori Pierce, MD, a radiation oncologist and national leader in breast cancer research, kicked off the event. Highly accomplished herself, Pierce serves as Vice Provost for Academic and Faculty Affairs at the University of Michigan—and directs the Michigan Radiation Oncology Quality Consortium. Dr. Pierce shared that ASCO and a tight group of cancer research stakeholders, including the U.S. Food and Drug Administration (FDA), the National Cancer Institute (NCI), part of the National Institutes of Health (NIH) and others, spent five years working on ways to transcend current challenges in research, including the lack of participation in studies, as well as severe underrepresentation of some groups, such as African Americans, the elderly, rural populations, etc. 

This work led to the second joint research statement called Continuing to Broaden Eligibility Criteria to make Clinical Trials more Representative and InclusiveASCO -Friends of Cancer Research Joint Research Statement published in the Journal of Clinical Cancer Research. These new  recommendations address the eligibility criteria challenges seen today, such as prior therapy, performance status, treatment washout periods, concomitant medication exclusion, laboratory reference ranges and testing intervals.

With an aim to encourage robust inclusivity and representation in clinical trial enrollment, many cancer patients today, perhaps even most, are excluded based on the eligibility criteria promulgated in the study protocol. But these broad-based exclusionary elements—often like contractual “boilerplate”—aren’t necessarily scientifically justified. In fact, they are in many cases representative of outdated thinking and lead to overly restrictive eligibility criteria hurting the research, and the patients. The underrepresented are hurt most.

Back to the Future

The reality is that, apparent in this webinar content, all of the approaches, tactics and technologies currently discussed have been with us for years now. Advocates for patient-centricity in one form or another have called out for years the importance to make research participation easier for the patient. This author, for example, was involved with one of the largest patient recruitment vendors in the United States two decades ago and many of these topics were just as resonant, relative and relevant back then as they are today. Of course, the science and associated therapies have dramatically evolved to the point where in some cases it could be considered gross negligence to not consider a particular study for patients where the match could make the difference between life and death.

But why does so little change with such big stakes—given clinical research can literally in some cases not only save the life of a loved one with cancer, but can also significantly extend that life for a considerable period of time?

Do the identified barriers and trends represent too great a force to surmount? Of course not. But its time to act, and TrialSite’s mission to drive greater transparency and accessibility to research will find ways to shine a spotlight on this topic: the stakes are too big to ignore.

The Tools and Tactics Are Known

Webinar presenters included notable research figures such as FDA acting chief Janet Woodcock, MD, and Norman Sharpless, MD, director of the NCI, and others. The speakers shared the obvious impacts of the pandemic on research. For those trial watchers, the influence of the lockdowns and control measures led to a broader embrace of myriad technologies, processes and approaches that have again in many cases been available for use for years now.   

For example, Dr. Sharpless shared that the NCI often consults with the FDA to discuss what’s feasible, from streamlining informed consent (e.g. by phone) to shipping investigational product to the home in remote or so-called “site less” patient-centered research, sharing some of these efforts have been “wildly successful.”

Kari Oakes, writing for Regulatory Focus™, shared some of the highlights of this recent event, which can be read here. Follow the link to watch this important webinar here

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