Evaluating dose response from flexible dose clinical trials

BMC Psychiatry
Ilya LipkovichJ P Houston

Abstract

The true dose effect in flexible-dose clinical trials may be obscured and even reversed because dose and outcome are related. To evaluate dose effect in response on primary efficacy scales from 2 randomized, double-blind, flexible-dose trials of patients with bipolar mania who received olanzapine (N = 234, 5-20 mg/day), or patients with schizophrenia who received olanzapine (N = 172, 10-20 mg/day), we used marginal structural models, inverse probability of treatment weighting (MSM, IPTW) methodology. Dose profiles for mean changes from baseline were evaluated using weighted MSM with a repeated measures model. To adjust for selection bias due to non-random dose assignment and dropouts, patient-specific time-dependent weights were determined as products of (i) stable weights based on inverse probability of receiving the sequence of dose assignments that was actually received by a patient up to given time multiplied by (ii) stable weights based on inverse probability of patient remaining on treatment by that time. Results were compared with those by unweighted analyses. While the observed difference in efficacy scores for dose groups for the unweighted analysis strongly favored lower doses, the weighted analyses showed no strong d...Continue Reading

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Feb 21, 2013·Journal of Clinical Psychopharmacology·Hans RasmussenBirte Glenthøj
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