Recruitment Issues with Cancer Trials Lead to Innovative Regulatory Scenarios
​[Posted on: Thursday, August 17, 2017]

An article in the New York Times this week discusses something that all sponsors of cancer trials know too well; there are not enough patients in the US for clinical trials with new drugs. One out of three active clinical trials or about 6300 trials currently recruiting patients in the US are for anti-cancer drugs. And for the last several years, oncology drugs have dominated the number of new drugs approved by the FDA making it hard to find cancer patients who do not respond to any drug in the market and hence willing to try out an experimental drug. Trials which test sub-sets of patient population with specific mutations, or other characteristics making such patients not respond to approved drugs are able to recruit those patients, however, trials with me-too drugs that offer limited advantages over available therapies find it hard to recruit. Clinical sites have also become very selective in which trials to participate in. Most clinical trials are conducted at large oncology centers but tough competition between multiple trials looking for similar patients allows sites to decline trials, or not be able to find patients for. Add another complexity; many cancer patients in the US are treated by doctors who do not participate in clinical trials, making those patients not available for trials. Even companies that go to other countries to find patients, are unable to recruit many patients as the same drugs approved in the US are likely available in other countries creating similar logjam as the US to find patients for trials. Taking that into account, FDA no longer insists on large controlled clinical trials to approve new cancer drugs. Rather the Agency looks for drugs where the significant response is unequivocal. Most new cancer drugs are approved for second or third-line treatments. More drugs for cancer, than any other indication, are approved under special programs such as breakthrough therapy and accelerated approval that require smaller trial sizes and surrogate endpoints based on protein and/or genetic biomarkers. So for a company developing a new cancer drug, the path to success goes through the ability to identify a smaller patient population distinguished by a biomarker, and with sub-optimal response to available therapies. Being able to claim that your drug fills an unmet medical need is the most critical aspect for not only FDA incentives but also support from patients and doctors alike. Expanding the trial to multiple countries could be useful but only to a limited extent. The article highlights a critical aspect of clinical trial recruitment that could be extrapolated to most other diseases. That is the reason, developing a treatment for rare orphan disease is more appealing to companies than developing one for a large blockbuster indication. Lessons for cancer trials are being applied to all other diseases and should be.