Alternatives to placebo-controlled trials in psychiatry

Patients receiving placebo do not merely receive an inert substance but als o receive support, concern, and reassurance that assists the therapeutic al liance and encourages the positive attitude that forms the basis of cogniti ve treatment. Response to non-specific factors is seen in all fields of med icine but is particularly potent in psychiatry. The placebo response is var iable across settings and across time and is unpredictable. Historical data cannot therefore provide an adequate control for treatment effects in stud ies of new drugs. The scientific position is clear that a comparison agains t placebo is required for the unequivocal demonstration of the efficacy of a treatment. Evidence from at least two positive well designed and conducted placebo-con trolled studies is generally accepted as appropriate to establish the effic acy of a drug. Attention to diagnosis, severity of illness, and to possible comorbid condi tions is needed in the design and conduct of placebo-controlled studies in order to optimise the chance of obtaining valid data. The use of all data obtained, including dropouts due to lack of efficacy, s hould be maximised. The use of placebo may not be possible in some conditio ns that represent medical emergencies or may be difficult to justify in ser ious disorders where an effective treatment has already been established. A lternative designs to placebo-controlled studies can be considered. Consistent superior efficacy compared with a well accepted, effective treat ment, given in an easily defended dose, is considered to be good evidence o f efficacy provided that the studies are well designed and well conducted. Evidence of superior efficacy to an established effective comparator treatm ent may be regarded as evidence of efficacy. The demonstration of a dose-response relationship where one dose is found t o be significantly better than another, can be taken as evidence for effica cy, particularly where there is already placebo-controlled evidence of the efficacy of the identified dose. Where a new treatment is found, under controlled conditions, to be equivale nt to an existing well accepted comparator treatment, given at a clearly ef fective dose, this may be taken as evidence of efficacy, but only if the co mparator is consistently superior to placebo and if equivalence has been de fined beforehand. The claims for efficacy based on results from equivalence studies are less easily sustained than the evidence from placebo-controlle d studies or studies demonstrating superior efficacy, due to the fact that those studies have no internal validation. (C) 1999 Elsevier Science BN./EC NP. All rights reserved.