FDA Issues Guidance On Chronic Fatigue Syndrome And Myalgic Encephalomyelitis

The Food and Drug Administration (FDA) has issued a guidance document for the pharmaceutical industry entitled, “Chronic Fatigue Syndrome(CFS)/Myalgic Encephalomyelitis(ME): Developing Drug Products for Treatment.” The guidance is a draft only and contains non-binding recommendations. After a comment period, the final guidance will represent the FDA’s current position on drug development for CFS/ME. The guidance assists drug sponsors to focus on specific drugs and trial designs. Sponsors are encouraged to discuss specifics with personnel in the Division of Pulmonary, Allergy, and Rheumatology.

Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) is a complex condition with an unknown cause and no approved therapies. Because there is little known about the origins or treatment of the condition, the FDA considers it a public health concern. Symptoms span multiple systems and include fatigue, muscle and joint pain, cognitive deficits, headaches, and poor sleep. Patients vary in their experience of the disease. Some have mild cases while others are severely disabled.

Diagnostic Criteria

The FDA states that investigators use different criteria to diagnose patients including the Fukuda Criteria, the International Criteria, and the Canadian consensus criteria. The agency recognizes that no diagnostic criteria for CFS/ME is more appropriate than another when establishing clinical enrollment criteria.

However, certain patients should be excluded, including those with congestive heart failure, hepatitis, and cancer.

Efficacy

Under section 505(d) of the Federal Food, Drug, and Cosmetic Act, drug sponsors must design clinical trials that prove efficacy. Drug sponsors should choose primary endpoints in clinical trials that relate to how the patient feels or functions. Patient-reported symptoms, Patient Reported Outcome (PRO) instruments, and objective measures are preferred for clinical trials for CFS/ME. Sponsors are encouraged to use other measures suitable for the drug under investigation.

Trial Design

The FDA recognizes that trial design depends on the type of drug being developed. In general, the agency prefers placebo-controlled, double-blinded, randomized, and parallel-group designs. Placebo use should not deprive patients of usual care treatments. If placebo control raises ethical issues, sponsors may re-evaluate placebo trials. Sponsors should aim for two trials to establish efficacy. Trial duration is subject to data collected from previous trials and may be adjusted after discussions with the FDA. Trials should last at least 24 weeks and may be for much longer.