多SHOULD WE ACCPET ENRICHMENT DESIGNS IN PSYCHIATRY?. Enriched enrolment designs aim to increase the proportion of responders in a clinical trial population and to decrease the number of patients withdrawing because of intolerable or unmanageable adverse events. This should enhance the average benefit of study drug over placebo (or over an active comparator) where only a subset of the diseased population responds to the intervention. Enriched enrolment strategies were described by Amery and Dony in 1975 and several have been used in medicine, and more frequently in psychiatry and chronic pain trials. Enriched studies are also known by other names: -
Discontinuation Design. Randomized discontinuation design. Study with a qualification period. Enriched enrollment with randomized withdrawal.
The next figure shows an example of a clinical trial using the enrichment design. Enrichment period
Randomized, controlled trial
Response Active (Study Drug). Non response Responders All elegible subjects
Response Non Responders or Non tolerance are excluded
Control (Placebo or other active comparator)
One of the main concerns about enrichment designs is the loss of generalizability (i.e, external validity) in selecting a specific subpopulation in the enrichment phase. The Key difference with randomized controlled trials is that a group of responders rather than all comers are randomized with the enrichment design. An example in psychiatry is maintenance studies of bipolar disorder, where there are two basic study designs: Prophylaxis and relapse prevention. In the prophylaxis design all comers (all participants) are included in the study; in other words, any patient who is euthymic, no matter how that person got well, is eligible to be randomized to drug versus placebo or control. In the relapse prevention design, only those patients who acutely respond to the drug being studied are then eligible to enter the maintenance phase, which is when the study begins. Those who responded to the drug are then randomized to stay on the drug or be switched to placebo or control. (Ghaemi S.Nassir). With this methodology the FDA has approved some medications (especially some atypical antipsychotics) for the treatment of bipolar disorder. ¿To whom do the results of an enriched trial demonstrating a benefit of active therapy over placebo (or over other active medication) apply?. ¿Why not randomized the complete sample from the baseline instead of preselecting a group of patients?. ¿Does this kind of designs have a selection bias?. ¿Why FDA accepts this type of design to approve a new indication for a drug?. Jorge Augusto Franco López. President of the Colombian society of biological psychiatry. firstname.lastname@example.org