The Food and Drug Administration (FDA) made a recommendation to drugmakers last week stating that they only use placebos in cancer clinical trials in select circumstances.
The government agency said there could be some ethical concerns if alternative therapies were used.
According to an FDA press release, placebos should only be considered in trials to treat oncologic disease or hematologic malignancy “when surveillance is standard of care” or in studies with “certain trial design features (e.g., when the trial uses an add-on design).”
“A placebo-controlled study design may be useful or preferred in maintenance therapy, in add-on trial designs, in trials of adjuvant therapies (for which standard of care is surveillance), and for indications where no treatment is available,” the FDA stated in the press release.
Monica M. Bertagnolli, MD, FACS, FASCO President, American Society of Clinical Oncology, weighed in on the FDA guidance.
"ASCO appreciates the FDA’s draft guidance to sponsors regarding the use of placebos and blinding in randomized controlled clinical trials in development of drugs and biological products for the treatment of hematologic malignancies and oncologic diseases,’’ Bertagnolli wrote in a letter to FDA commissioner Scott Gottlieb. “ASCO agrees with the agency’s thinking that a placebo design can be useful and specific criteria should be applied to determine the appropriate use of the placebos in oncology drug Via Electronic Submission 2 development.’’
Bertagnolli cited a Journal of Clinical Oncology article from 2008 entitled Ethical, Scientific and Regulatory Perspectives Regarding the Use of Placebos in Cancer Clinical Trials, which examines the use of placebos in cancer clinical trials from all three perspectives of ethical, scientific and regulatory to provide considerations and criteria for their appropriate use in cancer development.
"ASCO agrees that there are scenarios, such as add-on trials or when existing therapies are minimally effective or have serious adverse effects, when the use of a placebo can be appropriate, and there should be a rationale for a placebo trial design and blinding,’’ Bertagnolli said. ‘’ASCO supports the guidance to sponsors to provide the rationale, justification, detailed protocol and statistical analysis plan for the use of placebo trial designs and blinding; as well as the circumstances and process for unblinding a study, particularly if unexpected or unexpectedly severe or frequent adverse events are observed. It is also critical that the informed consent document for participants detail the risks and potential disadvantages of a placebo design trial and double-blind randomized trials."
Bertagnolli said that the use of placebos in double-blind randomized trials for the treatment of malignant hematologic and oncologic diseases can present practical and ethical concerns, particularly due to the toxicity profile of the active treatment.
"ASCO believes that the best way to improve access to cancer therapeutics is through well-designed clinical trials that are both ethical and provide clear evidence of the product’s safety and efficacy,’’ Bertagnolli said.
