The Development of Study Exit Criteria for Evaluating Antimanic Compounds

Background: There is increasing intereston the part of investigators and the public at large in findingways to study and improve treatments for the seriously mentallyill without exposing such individuals to unnecessary risks. Onegroup of particular interest in this regard are patientssuffering from acute mania. We set out to define “exit”criteria or novel clinical endpoints that might help to assessthe efficacy of antimanic compounds. We sought a method thatwould be safer, more economical, and less sensitive tononspecific factors in the clinical environment while stillallowing unambiguous assessment of efficacy.

Method: From a pool of subjects being screenedfor or already participating in intervention studies, weretrospectively identified 76 admissions of patients with a manicor mixed episode according to DSM-IV. We fit a mixed-effectsregression model to all available data obtained using theBech-Rafaelsen Mania Scale from admission to day 28 of treatment.Using the estimated model coefficients, we obtained empiricalBayes (EB) estimates of each subject’s trend coefficients basedon (1) all available data and (2) data through day 11 oftreatment for mania.

Results: We found a high correlation (r =.67) between EB estimates of final response at day 28 and actualday 28 scores on the Bech-Rafaelsen scale based on scores throughday 11. When subjects were categorized as full, partial, ornonresponders according to their final Bech-Rafaelsen score, wewere able to show that only 2 of the 23 predicted nonrespondersbecame full responders, 27 of the 31 predicted full respondersbecame full responders, and 16 of the 22 predicted partialresponders became partial or full responders.

Conclusion: We conclude on the basis of thischart review study that it should be possible to define exitcriteria for trials assessing the efficacy of antimanic compoundson the basis of relatively short duration exposure toexperimental treatment.