Unnecessary exclusions shut patients out of clinical trials

Not long ago, I examined an otherwise healthy and active man in his 50s with newly diagnosed metastatic lung cancer. He had no heart disease, no kidney disease, no liver disease. He came to my practice at UT Southwestern Medical Center specifically for clinical trial options.

Disappointingly, one detail in his medical history excluded him from all of our available trials. Four years earlier, he had been treated for stage 1 prostate cancer, a disease so prevalent and nonaggressive that the U.S. government no longer recommends routine screening for it. I couldn’t think of a single way in which the patient’s prior experience with cancer would interfere with treatments or assessments on a lung cancer trial. And yet I couldn’t enroll him.

Unfortunately, many sick patients are being denied the opportunity to test new drugs that might save their lives. It’s time for this to change.

The Food and Drug Administration will hold a public meeting this month in Washington to discuss issues related to clinical trial eligibility criteria. Researchers, study sponsors, patients, and the general public will have an opportunity to share their experiences and tell our regulators why it’s time to revisit the guidelines.

Despite repeated calls in recent years to simplify clinical trial criteria, they continue to grow more complex. In a study my colleagues and I published last year, we found that over the past 30 years, the average number of eligibility criteria in lung cancer trials sponsored by the National Cancer Institute grew by 50 percent to an average of more than 25.

Why is this occurring? As treatments for cancer become more targeted, the protocol for selecting participants must be refined by the trial’s investigators and sponsors, who are often academic researchers or pharmaceutical companies. Still, every exclusion criterion must be evaluated critically and justified as being directly relevant to preserving patient safety or producing a quality scientific outcome.

In our study, we found many clinical trials add restrictions related to the risks of new treatments, but often fail to remove those that are no longer relevant. For instance, trials for immunotherapy have introduced new criteria related to pre-existing autoimmune disease and use of immune suppressants. However, most of these trials continue to require that patients meet strict minimum white blood cell, hemoglobin, and platelet counts, a holdover from chemotherapy studies that aren’t necessarily relevant to immunotherapy.

The growing number of exclusions are shrinking the pool of candidates who can participate in trials and causing delays in drug development. Currently, fewer than 2 percent of adult cancer patients in the United States are treated in clinical trials. And my research shows that patients with a history of cancer are excluded in more than 80 percent of lung cancer trials.

If clinical trials enroll only a highly select minority of patients, we may not be able to generalize their results to a broader population of individuals who have the disease. For example, two patients of mine were recently excluded from lung cancer trials due to chronic hepatitis C, which is quite common and may not interfere with treatment.

Running clinical trials effectively and efficiently is critical to medical progress, not just in cancer care but across disciplines. Allowing more patients to be enrolled in trials will speed the medical innovation process, allow more sick people to access potentially beneficial therapies, and produce more generalized results. Spurred by this month’s FDA meeting, lead researchers, sponsors, and regulators must rethink their approach to clinical trial eligibility.

David Gerber, M.D., is associate director for clinical research at the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern Medical Center in Dallas. He reports consulting for and receiving research funds from several pharmaceutical and biotech companies, including Eli Lilly, Pfizer, Boehringer-Ingelheim, Celgene, and AstraZeneca.