Abstract
The FDA recently released a final guidance that outlines the specific situations in which placebos can be used in oncology clinical trials—and in which patients and investigators should be unblinded. Oncologists consider the guidance useful, but note that it largely aligns with how oncology trials are already conducted.
The FDA recently released a final guidance on placebos and blinding in oncology clinical trials that outlines specific situations in which placebos can be used, and those in which patients and investigators should be unblinded. Although the information is helpful, it's not necessarily new for oncologists.
“It's useful for FDA to provide written guidelines for placebo-controlled trials, but I think experienced investigators in oncology would already be designing these trials as the FDA guidance recommends,” says Mario Sznol, MD, of Yale Cancer Center in New Haven, CT.
The guidance notes that “using a placebo in randomized controlled clinical trials of therapies to treat hematologic malignancy and oncologic disease for which there is known effective therapy is ethically unacceptable.” Thus, a placebo should be used only in certain situations—namely when surveillance is the standard of care or when the placebo is added to an active therapy. Moreover, trial sponsors should provide rationale for using a placebo, particularly when it would involve an invasive procedure, when medication is required to prevent an adverse reaction, when a non-placebo therapy is available, or when the placebo is given as a monotherapy.
“I've been involved in oncology drug development since I finished my fellowship in 1987,” Sznol says, and even back then “I believe it would've been considered unacceptable to treat with a placebo when there was an active standard-of-care treatment known to provide clinical benefit with a reasonable risk–benefit profile.”
The FDA guidance also recommends that the patient and investigator be unblinded if a patient's disease recurs or worsens, or if a patient experiences serious side effects related to the experimental therapy. These measures, Sznol says, ensure that the investigator and patient can make an informed decision about what might be the best subsequent treatment—whether that involves crossing over to the experimental therapy, receiving a different standard drug, considering another investigational agent, or discontinuing treatment—and that a patient receives appropriate care for side effects.
Although the guidance largely outlines the status quo in oncology trials, Sznol considers it a positive development that may be especially helpful for anyone moving into oncology from a field in which diseases are not life-threatening, and thus using placebos may be more common and acceptable. “Sometimes stating the obvious is very useful,” he says. –Catherine Caruso