63 The presence of comorbid medical conditions or abnormal laboratory tests has also become an increasing concern given the potentially high rates of metabolic syndrome, smoking, etc. among people with schizophrenia. Randomization strategies Most RCTs use even randomization strategies, which assign equal numbers of patients to each treatment arm. This makes sense since the smallest arm will determine Inhibitors,research,lifescience,medical the statistical power involved in the comparison between treatments. However, there are some situations

where equal randomization might not be appropriate. Equipoise randomization64 has been used in some trials and can provide patient and physician input into the potential options involved in the treatment assignment without doing away with randomization altogether. Adaptive design is another strategy which entails the use of data already collected to influence Inhibitors,research,lifescience,medical subsequent randomization of treatment groups.65 This can be particularly useful in studies involving dose-finding; however, it can also lead to premature closure of a study arm or an entire study based on relatively small amounts of data. Sequential design allows pairing of individuals who are assigned to alternate treatments

with the results of each subsequent pair contributing to an ongoing analysis of the Inhibitors,research,lifescience,medical odds of reaching a significant effect or not.65 This can provide statistical significance with a small number of patients if Inhibitors,research,lifescience,medical the treatment effect is substantial, or it can provide an initial confirmation of the null hypothesis. Such a design has rarely been used in RCTs in schizophrenia,66 but should be considered. Stratified randomization is an WP1130 chemical structure important tool to ensure that the treatment arms are balanced

on a small Inhibitors,research,lifescience,medical number of potentially important mediating or moderating variables. The number of such variables will be determined by the overall sample size. Crossover studies are also conducted in some situations, Carnitine palmitoyltransferase II but given potential medication carryover effects and uncertainty as to how vulnerable patients are to returning to their baseline state make placebo-controlled crossover trials less informative in psychiatry than they might be in some medical conditions. So-called “switch” studies are often done in psychiatry, but unless there is a control group they cannot be considered RCTs. Switch studies are obviously much more informative if patients are randomized to be switched or to stay on the original treatment, in a double-blind fashion. Blinding While blinding/masking is an important feature to minimize expectation biases, blinding patients and providers to the treatment does not match clinical practice.