Participating in a cancer clinical trial: a path rife with difficulties

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Swetha Srinivasan

Cancer therapies, like all other medicines, only make their way to patients after the completion of a lengthy process of extensive research studies involving animals and then people to make sure that the benefits of the drug outweigh the risks. These final research studies in people are commonly known as clinical trials and are critical to finding new ways of preventing, diagnosing and treating cancer. Conducting a clinical trial is an inherently challenging process, and recruiting patients for these studies is tricky. However, clinical trials in cancer have become particularly notorious for low recruitment rates. An estimated 32% of adult cancer patients are very willing to participate in cancer trials, and 38% are inclined to participate but have some questions or reservations. Yet, less than 5% of adult cancer patients actually enroll in clinical trials, and this rate has not changed significantly over the years. So what accounts for this big difference in patients willing to participate and patients who actually participate?

It turns out that there a number of barriers to participation in clinical trials for cancer therapies. These barriers could be structural (e.g. lack of an available trial for a subtype), clinical (e.g. not meeting the eligibility criteria for enrollment), or related to the attitudes of the physician and/or the patient towards trial enrollment. While structural and attitudinal barriers are harder to mitigate, clinical barriers may be more easily removed and have thus been the focus of recent work.

The American Society of Clinical Oncology (ASCO), the FDA and Friends of Cancer Research came together in 2016 and launched an initiative to modernize eligibility criteria for clinical trials with the goal of improving clinical trial participation. Currently, clinical trials for cancer have a number of criteria for excluding patients from participation: prior cancer history, receipt of prior cancer treatments, having HIV or other serious medical conditions, required organ function and blood counts, etc. These criteria are driven both by a desire to understand the true effect of therapies for a clinical indication, and by a desire to protect patients from excessive toxicity, and have been held as the standard for decades. However, recent debate has centered around this question:  are these criteria too restrictive and in need of modernization so that patients have expanded opportunities to receive care by participating in clinical trials?

To answer this question, studies examining the evidence and justification for these criteria have emerged in recent years. One such study, published last month, aimed to understand if comorbidities, or the presence of two or more diseases in a patient, impacted participation in cancer clinical trials (Unger, Hershman, Fleury, & Vaidya, 2019). Using a national survey embedded in tools available on cancer-oriented websites that allow patients to arrive at treatment decisions, investigators tracked how patients who received a diagnosis of breast/lung/prostate/colorectal cancer made a decision about pursuing a clinical trial over a 3-month period. They found that the presence of comorbidities (e.g. cardiovascular conditions, kidney disease, diabetes, asthma, etc) in these patients’ medical histories were associated with lower rates of trial discussion (16 out of 18 instances), offer for enrollment into a trial (17 out of 18 instances), and participation in a trial (16 out of 18 instances), after adjusting for any sociodemographic differences that could result in differential rates of participation in clinical trials.

These results suggest that re-examining the current ASCO recommendations for excluding patients from cancer clinical trials based on the presence of comorbidities is necessary. Updating these criteria would allow more patients to be recruited into studies, and using the study sample in this report, the investigators estimated that up to 6317 additional patient trial registrations every year could be generated by removing this criterion. Modifying, instead of completely, removing this criterion would still result in substantial increases in patient trial enrollment. Further, the inclusion of patients with well-managed comorbidities in such trials more closely mirrors the population in which these drugs will ultimately be used, given the number of patients with cancer who have comorbidities. These considerations should outweigh any concerns that including such patients in clinical trials would lead to a lower chance of a successful trial, especially given the current environment where nearly 1 in 5 cancer trials fail to accrue enough patients to draw any valid conclusions about the therapy to be tested.

Clinical trial participation benefits patients by increasing the speed at which new treatments are identified through trials and is also important in the era of precision medicine, where biomarker-stratified treatments result in smaller groups of patients eligible for trials. Reduced mortality and prolonged survival in patients with cancer are also correlated with clinical trial activity. Today, researchers and stakeholders are paying closer attention to barriers for clinical trial participation, heralding a future where the power of innovative, life-saving medicines can be felt by more cancer patients than ever.

References:

Unger, J. M., Hershman, D. L., Fleury, M. E., & Vaidya, R. (2019). Association of patient comorbid conditions with cancer clinical trial participation. JAMA Oncology. doi:10.1001/jamaoncol.2018.5953

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