Richard L. Schilsky, MD, FASCO
Nathan A. Pennell, MD, PhD, FASCO
The ripple effects of the coronavirus pandemic have been felt in every area of health care. In our medical specialty, oncology, clinical trials of new treatments were upended by COVID-19. In the early months of the pandemic, widespread interruptions in trial enrollment prevented some patients from receiving experimental cancer therapies that represented their best, or in some cases their only, options for treatment.
Yet in a testament to the strength of the cancer research system, we managed to avert the worst-case scenario—trials shutting down entirely, forcing patients off their treatment protocols. Research sponsors and regulators acted quickly to create more flexible research practices—for example, allowing doctors to monitor patients remotely or to ship study medications to patients’ homes. As a result, most patients were able to continue their treatments, and most trials were able to resume after just a few weeks or months of interruption. In fact, by July 2020, many large clinical research sites have reopened nearly all clinical trials.
As many in health care are discovering, the emergency policies implemented during the pandemic are accelerating positive changes to the health-care delivery system that were long needed. The new, more flexible practices adopted for cancer research seem to be working well and should be made permanent. But we shouldn’t stop there. As we plan ahead for a post-pandemic recovery,1 the clinical cancer research enterprise needs to pursue a broader set of reforms spanning trial design and operations. If we pursue these reforms, we have the potential to emerge from COVID-19 with a cancer research system that is more efficient, more accessible to patients, potentially less costly, and more resilient going forward.
Embracing Flexibility in Day-to-Day Trial Operations
From the moment COVID-19 arrived, protecting patients from infection was a top priority. Because people with cancer are especially vulnerable to coronavirus infection,2 cancer care and research had to change virtually overnight to reduce the risks of patient exposure.
On the one hand, this meant pressing pause on a large portion of clinical research activity. Within the first weeks of the pandemic, some 60% of research institutions had halted patient screening and enrollment for at least some trials,3 according to an ASCO survey. Similar numbers of institutions halted patient visits focused solely on research, blood draws, or tissue collections, prioritizing only those visits that were essential to sustain patients’ health.
To help minimize the impacts of the pandemic and get research moving again, the U.S. Food and Drug Administration and the National Cancer Institute (NCI) worked quickly to issue guidance4 and workarounds5 that gave researchers and trial sponsors new flexibility while preserving the integrity of research. Along with remote patient monitoring and drug administration, the guidance allowed virtual consent using e-signatures; limited collection of biospecimens for research only; and blood draws and imaging scans to be performed by local health-care providers more conveniently located for patients than research sites.
“Some of the emergency measures already taken—such as allowing patients to have lab tests done closer to home— are steps in the right direction.”— Richard L. Schilsky, MD, FASCO, and Nathan A. Pennell, MD, PhD, FASCO
Tweet this quote
Many of these changes had, in fact, been considered for years. Even before the pandemic, ASCO and others had been calling for such steps to increase patients’ access to cancer research. Remote monitoring and drug administration, for example, could make it far easier for patients in rural areas to join a trial without frequent, long-distance travel for research visits.
To determine which reforms should be implemented post-COVID, ASCO established a task force of experts to provide comprehensive recommendations for the clinical oncology field, published in the Road to Recovery Report.1 The task force recommended that the recent flexibility in trial operations should be made permanent in most cases, unless or until evidence emerges to refute their value for patients or the research system.
Increasing Research Access and Efficiency
Our task force also examined lessons from 2020 to determine what other, more fundamental changes are needed to make the research system more accessible and resilient for the future. A first priority is to expand access to research and eliminate racial and ethnic disparities in trial participation.
Long before COVID hit, minority populations were underrepresented in clinical trials.6 Although data are limited, it is probable the pandemic will have exacerbated these disparities. COVID-19 has taken a disproportionate toll in Black and Hispanic communities generally7 and among Black and Hispanic patients with cancer in particular.8 Related barriers to research, such as loss of employment-based insurance coverage,9 have also affected these communities disproportionately.
To help rectify inequities in clinical research post-COVID, -ASCO’s task force calls for better integration of clinical research into day-to-day patient care. Some of the emergency measures already taken—such as allowing patients to have lab tests done closer to home—are steps in the right direction.
However, we can and should take things much further. First, ASCO’s own TAPUR trial,10 for example, is conducting cutting-edge research on targeted cancer treatment, embedded mainly within routine patient care. The NCI’s Community Oncology Research Program is a far larger example, bringing clinical research opportunities to more than a thousand sites where patients already receive routine cancer care, including many in rural areas and urban minority communities. Not surprisingly NCI trials, on the whole, achieve much higher levels of minority participation than other cancer research studies.11
Second, we need to increase flexibility in research operations, to better avoid halting trials in the face of crises. ASCO’s task force recommended, for example, that research programs centralize key functions, including institutional review boards, to help expedite the response to changing circumstances. It also recommended standardizing research procedures and data-collection tools across sponsors, broadening the criteria for clinical trial eligibility, minimizing the amount of data collected, cross-training research staff, and taking other steps to avoid staff shortages and help staff members quickly adapt to workload challenges.
Third, we need to finally and fully embrace innovative trial designs that achieve faster, higher-quality results in an era of highly complex genomic cancer medicine. Many oncology leaders have been pressing for these innovations for years, with only limited success. Now, with the COVID-19 pandemic having delayed study results and consumed valuable resources, there is ample reason to move ahead in this regard. The task force recommended trial sponsors embrace an array of approaches, including adaptive trial designs,12 common control groups, and master protocols to move toward this ideal.
For decades, we have been concerned about the slow pace of trial enrollment and the lack of diversity among participants in trials, but the research community has been reluctant to move away from established procedures that are proven to deliver high-quality data. However, the COVID-19 experience has demonstrated we can embrace flexibility, serve patients, and sustain high-quality research without compromising research integrity. In fact, to see the value of flexible research approaches, we only have to look at the rapid launch of COVID-19 vaccine and treatment research. Hundreds of trials have been launched under far-from-ideal circumstances,13 promising to put the end of the pandemic within reach. We can draw lessons and inspiration from this real-world experience.
As oncologists and researchers, we need to work with industry and regulators to advance change and to closely monitor the impact on patients. People with cancer have faced tremendous difficulties because of COVID-19, on top of their cancer diagnosis and treatment. For them, and for tomorrow’s patients, we have a responsibility to emerge from this crisis stronger than we went into it.
Dr. Schilsky recently retired as ASCO Chief Medical Officer and Executive Vice President of ASCO. Dr. Pennell is Director of the Lung Cancer Medical Oncology Program at the Cleveland Clinic Foundation and Professor of Medicine at Cleveland Clinic Lerner College of Medicine of Case Western Reserve University.
DISCLOSURE: Dr. Schilsky has received institutional research funding from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Genentech/Roche, Lilly, Merck, and Pfizer. Dr. Pennell has served as a consultant or advisor to Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Cota Healthcare, G1 Therapeutics, Genentech, Inivata, Lilly, Merck, Pfizer, Viosera, and Xencor and has received institutional research funding from Altor BioScience, AstraZeneca, Bristol Myers Squibb, Celgene, Genentech, Heat Biologics, Jounce Therapeutics, Loxo, -Merck, Mirati Therapeutics, Pfizer, Spectrum Pharmaceuticals, and WindMIL.
REFERENCES
1. Pennell NA, Dillmon M, Levit LA, et al: American Society of Clinical Oncology Road to Recovery Report: Learning from the COVID-19 experience to improve clinical research and cancer care. J Clin Oncol 39:155-169, 2021.
2. Kuderer NM, Choueiri TK, Shah DP, et al: Clinical impact of COVID-19 on patients with cancer (CCC19): A cohort study. Lancet 395:1907-1918, 2020.
3. Waterhouse D, Harvey R, Hurley P, et al: Early impact of COVID-19 on the conduct of oncology clinical trials and long-term opportunities for
transformation: Findings from an American Society of Clinical Oncology survey. JCO Oncol Pract 16:417-421, 2020.
4. U.S. Department of Health and Human Services Food and Drug Administration: Conduct of clinical trials of medical products during the COVID-19 public health emergency: Guidance for industry, investigators, and institutional review boards. March 2020, updated December 4, 2020. Available at fda.gov. Accessed January 27, 2021.
5. National Institutes of Health: Additional guidance regarding alternative procedures for clinical trials supported by the NCI Cancer Therapy Evaluation Program and NCI Community Oncology Research Program affected by the spread of the novel coronavirus. March 23, 2020. Available at ctep.cancer.gov. Accessed January 27, 2021.
6. Duma N, Aguilera JV, Paludo J, et al: Representation of minorities and women in oncology clinical trials: Review of the past 14 years. JCO Oncol Pract 14:e1-e10, 2018.
7. The Atlantic Monthly Group: The COVID Racial Data Tracker. COVID-19 is affecting Black, Indigenous, Latinx, and other people of color the most. Available at covidtracking.com. Accessed January 27, 2021.
8. Potter D, Riffon M, Kakamada S, et al: Disproportionate impact of COVID-19 disease among racial and ethnic minorities in the U.S. cancer population as seen in CancerLinQ Discovery data. 2020 ASCO Quality Care Symposium. Abstract 84.
9. Avalere: COVID-19 projected to worsen racial disparities in health coverage. September 16, 2020. Available at avalere.com. Accessed January 27, 2021.
10. ASCO TAPUR: About the TAPUR study. Available at tapur.org. Accessed January 27, 2021.
11. Unger JM, Hershman DL, Osarogiagbon RU, et al: Representativeness of Black patients in cancer clinical trials sponsored by the National Cancer Institute compared with pharmaceutical companies. JNCI Cancer Spectr 4:pkaa034, 2020.
12. Bhatt DL, Mehta C: Adaptive designs for clinical trials. N Engl J Med 375:65-74, 2016.
13. Shah A, Kadakia KT, Marks P, et al: FDA initiatives to accelerate the development of COVID-19 therapeutics. August 18, 2020. Health Affairs Blog. Available at healthaffairs.org. Accessed January 27, 2021.
Disclaimer: This commentary represents the views of the author and
may not necessarily reflect the views of ASCO or The ASCO Post.
