Dive Brief:
- The FDA on Thursday released draft guidance that pushes drugmakers to think twice before comparing experimental cancer drugs against placebos in clinical trials, recommending inert controls be used only in certain circumstances.
- Testing cancer drugs poses notable practical and ethical challenges for researchers, particularly for malignancies that have effective therapies available. Maintaining treatment blinding can also be difficult when toxicity makes readily apparent which therapy patients have received.
- The agency did note that placebo controls could be used in studies where an experimental drug is added to standard-of-care medicines or to support a labeling claim that relies on subjective endpoints like patient-reported outcomes.
Dive Insight:
When effective drugs are available, active controls are preferable to placebo, the FDA said, pointing to the practice of permitting doctors to choose standard therapies as comparators.
Another solution is to add the investigational agent to both placebo and an active standard treatment and then compare these two treatment arms in what's known as an add-on trial.
Due to the toxicity of cancer drugs, patients and investigators often can surmise which treatment is active in a placebo-controlled trial — making the blinding ineffective. Continued blinding after adverse events or progression can also pose real dangers for patients. Those who suffer adverse events in the placebo arm may receive unnecessary treatments that could be harmful, while continuing blinding after disease progression can delay the initiation of effective standard therapy.
When there are effective standard therapies, unblinding at the time of disease recurrence or progression is especially crucial, the FDA said.
Drugmakers should also provide a detailed explanation of its plans for blinding in the study protocol. If blinding will be continued after disease progression, patient informed consent documents should specify the risks of this approach, according to the FDA’s draft guidance.
The guidance comes as the FDA is working to revamp its thinking on the use of surrogate endpoints and continuous trials, with the aim of providing greater flexibility for clinical testing.