Specifying interventions in a clinical trial

THE CONSORT STATEMENT is a checklist and flow diagram developed by an international group of clinical triallists, statisticians, epidemiologists and biomedical editors for reporting randomised controlled trials. 1 Item 4 in the checklist relates to interventions (Box 1). The interventions used in a randomised clinical trial should be clearly defined in the protocol and reported in enough detail to be replicated. The control or placebo treatment arms should be described with the same degree of detail as the treatment arms. If the control group receives standard care rather than an intervention, this care must be described in detail, as it may differ between institutions or countries. The characteristics of any placebo (eg, tablet or capsule form, taste) and the way it is administered should be documented. If the study interventions are delivered in a blinded (masked) fashion, details of how the blinding was achieved should be described, including any procedures for unblinding subjects during the study. The use of blinding is desirable to reduce reporting and measurement bias. 1 A study is classified as single-blind when only the study subject is unaware of which treatment has been assigned, and double-blind when the responsible clinician is also unaware of the assigned treatment. Double-blind studies, in which data are presented to the data-monitoring committee in a blinded fashion (ie, as treatments A and B), are sometimes referred to as triple blind. 2 If blinded interventions are not feasible or ethical, blinded assessment of outcomes should be attempted. For example, in a study comparing psychological outcomes after coronary surgery or percutaneous angioplasty for coronary heart disease, the assessor can still be blinded to treatment if patients are carefully gowned to obscure the presence or absence of a surgical scar and trained not to disclose the type of treatment received (assessments can even be videotaped to check that the blinding is preserved). Pharmaceutical interventions Generally, the dose of a drug intervention used in a comparative trial would be the maximum effective tolerated dose determined from earlier-phase trials. The dose may be the same for all patients or modified according to criteria such as body weight or surface area. Alternatively, dose escalation or reduction may be appropriate to achieve a particular degree of response (eg, lowering of cholesterol or raising of haemoglobin levels) or where known side-effects have been reported. In addition to the usual monitoring of patients' details, any special safety investigations required as …