Unless we can significantly improve the current paltry rate of just 3% adult participation in clinical studies … we will not be able to advance cancer care for all patients in the future.
—Julie M. Vose, MD, MBA, FASCO
A few weeks ago, I read an op-ed1 in The New York Times written by Stan Collender, a patient with Merkel cell carcinoma, a rare and aggressive type of skin cancer. In his article, he described his participation in a clinical trial for a new drug he is hoping will stem progression of his cancer and the need for more patients to enroll in clinical studies so effective new medications can be approved and quickly get into the hands of patients who need them. Without clinical trials, wrote Mr. Collender, promising new drugs won’t be tested, and progress against cancer will be slowed.
Mr. Collender is so right. All new cancer drugs must go through the rigors of clinical trial investigations to ensure their safety and efficacy, but unless we can significantly improve the current paltry rate of just 3% adult participation in clinical studies—participation is even lower among minority patients and patients aged 65 and older—we will not be able to advance cancer care for all patients in the future. In fact, a study of genitourinary cancer clinical trials found that 1 in 10 adult clinical trials ends prematurely due to poor accrual,2 which can unnecessarily doom a potentially effective drug from ever making it to the marketplace.
Barriers to Trial Participation
The barriers to patient participation in clinical trials are many. Patients may fear a reduced quality of life, have concerns about not receiving the experimental drug, worry about potential treatment side effects and loss of control over treatment decisions, and have anxiety about the inconvenience a trial might cause.
Physicians hamper the process, too, by not encouraging patients to join studies or not referring them to appropriate trials. Excessive administrative and regulatory burdens and decreased federal funding for clinical trials are big contributing factors as well.
Federally funded research through the National Institutes of Health (NIH) has played a critical role in every major advance in cancer treatment over the past 50 years. But this funding has remained flat for more than a decade, leaving NIH federal research funds with a 23% loss when adjusted for biomedical inflation. Promising research is now going unfunded, and new studies are being scaled back, leaving fewer patients with the opportunity to participate in clinical trials.
Recently, the U.S. House of Representatives passed the 21st Century Cures Act, which includes more than $9 billion in additional funding for the NIH and the U.S. Food and Drug Administration (FDA). The increased funding will strengthen both agencies and the medical community as a whole. I applaud this effort and urge the Senate to pass the bill.
All of these challenges are occurring at a pivotal point in cancer research, and ASCO is taking steps to help mitigate the problem of low patient participation in clinical studies. In July, ASCO published a position statement, “Improving the Evidence Base for Treating Older Adults With Cancer,” which calls for federal agencies to broaden clinical trials to include older patients,3 and members of ASCO’s Cancer Research Committee published “Modernizing Eligibility Criteria for Molecularly Driven Trials,” which examines the need to redefine eligibility criteria for participation in clinical studies investigating molecularly targeted agents.4
Including Older Patients
Although more than 60% of cancers in the United States occur in people aged 65 and older—a population that is expected to double by midcentury5—the evidence base for treating these patients is lacking because older adults are underrepresented in clinical trials, and trials designed specifically for this age group are rare. The result is that we have less evidence on how to treat this population of patients and less knowledge regarding the risk of toxicity and key endpoints of importance than we do for younger adult and pediatric patients.
To make clinical trials more inclusive and expand the number of older patients in clinical trials, ASCO is proposing five recommendations:
In the paper, ASCO also outlines 16 specific action items to facilitate implementation of its recommendations. These measures include asking regulatory agencies, research funders, and researchers to consider whether evidence exists to support eligibility criteria based on the three primary reasons older adults are excluded from clinical studies: age, performance status, and comorbid health conditions.
Molecularly Driven Trials
In ASCO’s second position paper, members of ASCO’s Cancer Research Committee propose the organization of a public workshop, with input from regulatory bodies and key stakeholders, to develop a streamlined algorithmic approach to determining eligibility criteria for study protocols in this era of molecularly driven therapy. ASCO is working with collaborators, including the FDA and Friends of Cancer Research, toward a meeting in spring 2016.
This is an important first step as trials of molecularly targeted cancer therapies increase in number and our understanding of the molecular drivers of cancer advances. “Although eligibility criteria are necessary to define the population under study and conduct trials safely, excessive requirements may severely restrict the population available for study,” wrote the paper’s authors.
Hopefully, fewer eligibility restrictions will enable more patients to participate in clinical trials and speed our understanding of the risks and benefits of investigational targeted therapies based on the molecular characteristics of cancer.
In addition to the steps ASCO is taking on a national level to boost clinical trial participation, there are also approaches on the community level that can improve patient recruitment and retention. For example, you can budget time during an office visit to provide all eligible patients with clear information about appropriate clinical studies at your institution or refer them to a study at another cancer center. At this time, you can answer any questions patients may have regarding potential risks and benefits, time involved, and any costs associated with the trial.
I commend Mr. Collender for his courage in speaking out about the need for all of us— clinicians, scientists, and public officials—to step up our efforts to encourage more patients to join clinical trials. Our patients are the true heroes of cancer research, and without their participation in clinical studies, we will not make the progress necessary to find cures for cancer.
We owe it to Mr. Collender and to the millions of other patients with cancer to advance scientific discovery into more effective therapies and improved outcomes for all patients. ■
Disclosure: Dr. Vose reported no potential conflicts of interest
1. Collender S: Clinical trials need cancer patients. The New York Times. June 19, 2015. Available at www.nytimes.com/2015/06/19/opinion/clinical-trials-need-cancer-patients.html. Accessed July 28, 2015.
2. Stensland KD, McBride R, Wisnivesky JP, et al: Premature termination of genitourinary cancer clinical trials. 2014 ASCO Annual Meeting. Abstract 288.
3. Hurria A, Levit LA, Dale W, et al: Improving the evidence base for treating older adults with cancer: American Society of Clinical Oncology statement. J Clin Oncol. July 20, 2015 (early release online).
4. Kim ES, Bernstein D, Hilsenbeck SG, et al: Modernizing eligibility criteria for molecularly driven trials. J Clin Oncol. July 20, 2015 (early release online).
5. West LA, Cole S, Goodkind D, et al: 65+ in the United States: 2010. U.S. Census Bureau. June 2014. Available at www.census.gov/content/dam/Census/library/publications/2014/demo/p23-212.pdf. Accessed July 28, 2015.
Dr. Vose is President of ASCO, the Neuman M. and Mildred E. Harris Professional Chair and Chief of the Oncology/Hematology Division in the Department of Internal Medicine at the University of Nebraska Medical Center, and the Associate Director of Clinical Research at the Fred & Pamela Buffett Cancer Center in Omaha.