FDA Pushes for Relaxed Patient Inclusion Criteria for Cancer Trials
[Thursday, March 14, 2019] The clinical trial recruitment criteria must be modernized to accurately reflect measures needed for the safety of the participants, and to diligently evaluate the investigational product. This week FDA published five new Guidance Documents to rebut common exclusion criteria used for all clinical trials, specifically trials in cancer patients. The goal is to eliminate common exclusion criteria that are no longer based on safety of the study participants or the context of the disease. Clinical trial sponsors use several common inclusion and exclusion criteria that have been used over time more so as a caution rather than based on scientific rationale or justified to avoid anticipated safety concerns. Patient accrual is slowed, many patients are denied recruitment and the trial populations are overly sanitized to become very different from those that would use the product in the real world. The most common disqualifiers are age, infectious diseases, organ disfunctions unrelated to the disease being investigated and prior or concurrent malignancies. Two of the new FDA guidance documents discuss ways to include pediatric patients and adolescents in cancer clinical trials. Children as young as 2 years of age can be included in cancer clinical trials if the anticipated risk is justified by the expected benefit, or the benefit of getting the experimental therapy is at least as favorable as the available alternative treatment option. Inclusion of children and adolescents can be justified using natural history data, preliminary clinical data from adults, non-clinical studies, and other scientific justifications. Children can and should be included in late stage trials. For children (age 2-12 years), the sponsor should be prepared to create child-friendly formulations, body weight adjusted doses, and informed consent issues. Children can generally be included after preliminary data from adults has been gathered to extrapolate the safety and efficacy parameters to children. Children and adolescents with cancers untreatable with available therapies can also be included in early stage trials. Another guidance provides criteria for including cancer patients with HIV, Hepatitis B and Hepatitis C infections in clinical trials. Generally, HIV-infected individuals with a CD4 count of greater than 350 cells/ul should be able to participate in most cancer clinical trials; even patients with lower CD4 counts can be included in cancer trials if they have a curable form of cancer. Similar flexibilities are available for patients with hepatitis infections whose disease is well-managed with treatment. An important consideration for including patients with active infection could be the interactions with the drugs that are needed to manage their disease and the investigational drug for cancer. Patients with cardiac, renal and hepatic issues, and brain metastasis can be also be included in clinical trials under several conditions mostly related to the justification of the non-interference of their underlying disease with the biological effects of the investigational product. Almost all the suggestions from FDA are common sense adjustments to the inclusion and exclusion criteria not only for cancer trials but also other indications. However, only time will tell if sponsors are willing to change their habits and be less conservative in their trials, we can be assured that FDA would be pushing them to, at least for cancer trials.
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