How do clinical trials work, and who can participate?

Chris, a Florida resident with autoimmune arthritis who has tried 10 different drugs, was rejected from a clinical trial despite being exactly the patient who might benefit most—those whose previous treatments have failed. This raises a critical ethical and scientific question: why do clinical trials often exclude patients who have exhausted multiple therapies? Dr. Holly Fernandez-Lynch, a bioethicist at the University of Pennsylvania, explains that exclusion criteria are designed to isolate the drug’s effect by minimizing confounding variables—like prior treatments that may have altered disease progression. However, she notes that this approach can create a paradox: the people most in need of new treatments are systematically excluded from trials meant to develop them. The FDA doesn’t require new drugs to outperform existing ones—just to show they work better than nothing. This allows approval based on surrogate endpoints (like plaque reduction in Alzheimer’s) even when clinical benefit isn’t proven, as seen in the controversial approval of Adjuhelm. Meanwhile, oversight of trials comes from both the FDA and Institutional Review Boards (IRBs), whose standards vary widely—especially between academic and commercial IRBs—raising concerns about consistency and transparency. Under the current administration, FDA review timelines have been accelerated through priority vouchers, but this risks compromising thoroughness.