Patient-reported outcomes are key to approval in this challenging indication, say regulators.

The lowdown: Between 1 million and 4 million people in the United States have chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME), but there are no approved therapies for this indication. To help bridge this gap, the US Food and Drug Administration (FDA) published a first CFS draft guidance, with guidelines around various aspects of trial designs.

Efficacy end points “should include patient-reported symptoms using well-defined and reliable [patient-reported outcome] instruments”, says the agency. It lists CFS symptoms as including fatigue, unrefreshing sleep, weakness, muscle and joint pain, impaired memory or mental concentration, tender lymph nodes, sore throat, headaches and sleep dysfunction. “The FDA is not aware of existing [patient-reported outcome] instruments or sets of instruments optimal for measurement of fatigue or other symptoms of CFS/ME,” it adds, but will consider proposals. Increased exercise capacity and reduced post-exertional malaise are also included as possible treatment benefits that may be measurable through either patient-reported outcomes or objective outcomes. The agency says it will consider the use of instruments that measure health-related quality of life as well.

The agency recommends that sponsors carry out two 24-week placebo-controlled trials to generate approvable, pivotal efficacy data. Because patients are likely to use treatments over prolonged periods, the FDA advises sponsors to collect long-term safety data, including, when efficacy trials are substantially less than 1 year, separate long-term safety trials.

The draft guidance document stemmed from the FDA's patient-focused drug development programme, through which the FDA is meeting with patient communities to get input on drug development priorities (Nature Rev. Drug Discov. 12, 651–652; 2013). CFS patients and their advocates were the first community to meet with the FDA, in April 2013. The agency is due to hold a total of 20 meetings with patients from different disease areas by the end of 2017.