Placebo-controlled drug trials must continue, says EMEA/CPMP

Placebo-controlled drug trials must continue to be available in orderto satisfy public health needs, according to a position paper published this month on the European Medicines Evaluation Agency's web site. The paper, a joint statement by the EMEA and its scientific advisory body, the Committee for Proprietary Medicinal Products, has been issued in response to the World Medical Association's revised Declaration of Helsinki (Marketletter October 16, 2000), and describes the Declaration as "a vital expression of medical ethics whose aims deserve unanimous support."

Specifically, the EMEA/CPMP comments that Section 29 of the Declaration states that "the benefits, risks and effectiveness of a new method should be tested against those of the best current prophylactic, diagnostic and therapeutic methods. This does not preclude the use of placebo, or no treatment in studies where no proven prophylactic, diagnostic or therapeutic method exists." The EMEA/CPMP notes that a strict interpretation of the Declaration seems to rule out clinical trials that use a placebo control arm whenever authorized therapeutic methods already exist, preferring active controls.

Some new products' efficacy can be shown satisfactorily without use of a placebo but, for others, such judicious use remains essential, says the agency. Where products exist for a given indication, active controlled trials are encouraged, if a methodologically-acceptable demonstration of efficacy and safety is possible. However, trials seeking to prove that a new agent and an active control have similar efficacy are inherently less reliable than those seeking to prove a new agent's superiority to a comparator, whether inactive or active, and increasing trial sizes does not alleviate this problem, it says. In some areas, this means that convincing evidence of efficacy can be obtained only through superiority trials, and use of an active control would mean that a new product would always have to demonstrate improved efficacy over a currently-authorized product. This may be too restrictive, eg granting a Marketing Authorization to a new product with similar efficacy and improved safety may be in the best interest of patients, it says.