It is also common to treat all patients with placebo during the run-in. The case against using placebo during the run-in has been argued strongly by Senn.14,15 He points out that this stratagem involves the treating physician deceiving the patient, whereas in more conventional uses of placebo both are in the same state of ignorance. As far as the subsequent comparison of randomized treatment arms is concerned, it would be just as acceptable to have a runin without treatment: it does no harm to the main objective of the study. The onus to prove their case lies squarely on those who believe that placebo treatment

Inhibitors,research,lifescience,medical is necessary during a run-in. Losses of patients from clinical trials The incidence of dropout from clinical trials in schizophrenia is high. This is one of the factors that make these trials particularly difficult to interpret because the biases introduced by dropouts

are difficult to assess. All possible steps should be taken to minimize the number of dropouts and to shed light on the potential bias Inhibitors,research,lifescience,medical they induce. The reasons for dropout should be carefully documented. After stopping their trial CHIR-98014 price medication, dropouts should Inhibitors,research,lifescience,medical still be followed up as fully as possible as planned in the protocol. Key measurements should also be made at the time of stopping treatment. The primary analysis of a placebo-controlled comparison should include all randomized patients

Inhibitors,research,lifescience,medical regardless of dropout. A “per protocol” analysis should support the primary analysis. There should be a full exploration of the sensitivity of the main results of the trial to the influence of the dropouts, taking into account the reasons for dropout, and the corresponding potential biases that they might, cause. Short-term trials The efficacy of a neuroleptic agent can generally be established in a short-term trial lasting about 6 weeks, studying acute exacerbations of the disease. A dose-ranging study might, Inhibitors,research,lifescience,medical include three or more doses, placebo (ethically justified, as described earlier), and a standard during treatment arm, making five treatment arms in all, to establish the optimal dose and the lower end of the dose range. A phase 3 confirmatory study would use the dosing regimen intended for licensing and would also ideally include placebo and active control. Long-term studies The difficulties inherent in schizophrenia trials make it imperative that licensing decisions are made on the basis of controlled trial data. It is not sufficient to monitor a group of patients exposed to long-term therapy and record their progress. The data from such a study would probably be supportive, especially for safety purposes, but would not establish a regulatory claim. The duration of controlled data adequate to establish use as maintenance therapy is of the order of 1 year.