Ethical Considerations for Increased Transparency and Reproducibility in the Retrospective Analysis of Health Care Data.

In the field of health care, researchers and decision makers are increasingly turning toward retrospective observational studies of administrative claims and electronic health record databases to improve outcomes for patients. For many important questions, randomized studies have not been conducted, and even when they have been, such studies often inadequately reflect the realities of patients' lives or care. However, use of retrospective studies not only increases methodological complexity but also requires more subjectivity for those attempting to perform statistical analysis. The hurdles for establishing the reproducibility of such research to ensure accuracy and generalizability are therefore also higher, as are the requirements for transparency to limit the impact of bias. The ethical statistical practitioner will therefore need to take additional steps to enable results to be interpreted and acted upon with confidence. These include increased transparency regarding the impact of database selection, database quality, database content, and design decisions on the robustness of statistical conclusions. A number of approaches to increase the reproducibility of retrospective health care research are also presented, along with some discussion regarding responsibilities of data owners, statistical practitioners, publishers, and users of results.

Initial symptoms of manic relapse in manic or mixed-manic bipolar disorder: post hoc analysis of patients treated with olanzapine or lithium.

UNLABELLED: A post hoc analysis of Young Mania Rating Scale (YMRS) item scores was conducted to identify symptoms that may predict impending relapse using prospectively collected data from a double-blind, randomized relapse prevention study of patients treated with olanzapine (N=200, 5-20 mg/d) versus lithium (N=201, 300-1800 mg/d). METHODS: Relapses (YMRS > or = 15, or hospitalization) included in this analysis occurred 3-52 weeks after randomization. Repeated measures logistic regression of increases (> or = 1) in YMRS item scores prior to the visit that preceded relapse was used to estimate the odds of relapse. RESULTS: A total of 31 patients relapsed during the first 3-16 weeks of the study (olanzapine, n=12; lithium, n=19). YMRS items that increased most frequently within a 2-week period preceding relapse were (olanzapine vs. lithium, respectively): increased motor activity/energy (58.3%, 21.1%), irritability (33.3%, 31.6%), decreased need for sleep (25.0%, 10.5%), increased speech (25.0%, 10.5%), and elevated mood (25.0%, 15.8%). YMRS items with significant odds ratios (OR) that predicted relapse in patients treated with olanzapine or lithium, respectively, were: increased motor activity/energy (OR, 35.7; OR, 7.8), irritability (OR, 9.5; OR, 7.8), elevated mood (OR, 8.1; OR, 4.2), and increased sexual interest (OR, 13.7; OR, 7.7). CONCLUSIONS: Early recognition of symptom exacerbation in bipolar mania, particularly increased motor activity-energy may permit clinical interventions to help avert relapse.

Association between early and rapid weight gain and change in weight over one year of olanzapine therapy in patients with schizophrenia and related disorders.

Weight gain is an important issue in the use of atypical antipsychotics, including olanzapine. A retrospective analysis of patterns of weight gain and possible covariates was performed for 1191 patients diagnosed with schizophrenia or schizoaffective disorder who were treated with olanzapine for up to 52 weeks. Patients were dichotomized into 2 main groups according to the percentage of body weight gained during the first 6 weeks of treatment with olanzapine: (1) patients who gained > or =7% of their body weight (Rapid Weight Gain Group [RWG]), and (2) patients who lost weight, gained no weight, or gained <7% of their body weight (Nonrapid Weight Gain Group [NRWG]). Results demonstrated that approximately 15% of the patient population showed rapid increases in weight (RWG group), whereas 85% of patients gained weight more slowly or not at all (NRWG group). Patients in the RWG group gained an average of 4% of their body weight (approximately 4-7 lb) within the first 2 weeks of treatment with olanzapine. Furthermore, patients in the RWG group were younger, had a lower baseline body mass index, were more likely to report an increase in appetite, and showed a more robust clinical response compared with patients in the NRWG group. Over the course of 52 weeks, patients in the RWG group gained significantly more weight and reached a higher plateau for mean weight increase at 38 weeks compared with the mean increase observed for patients in the NRWG group. By measuring the weight of patients during the first few weeks of olanzapine treatment and by assessing changes in appetite, clinicians may be able to identify those patients at risk for substantial weight gain.

Efficacy of accelerated dose titration of olanzapine with adjunctive lorazepam to treat acute agitation in schizophrenia.

We conducted a prospective double-blind study of accelerated dose titration of olanzapine in the treatment of newly admitted acutely agitated patients with schizophrenia. Patients were randomized to either oral olanzapine (10 mg per day) or oral haloperidol (10 mg per day), plus lorazepam as needed (up to 12 mg per day). Antipsychotic dosage was increased to 20 mg per day as early as day 3. Patients were evaluated with the Positive and Negative Syndrome Scale (PANSS) Agitation subscale during the first 24 hours of treatment, daily for the first week, then weekly until study completion. Significant within-group improvement was demonstrated in PANSS Agitation scores for both groups as early as 1 hour after initiating therapy (-5.79 +/- 6.30 for olanzapine and -4.89 +/- 6.05 for haloperidol, P <.001). This study demonstrated that accelerated dose titration of oral olanzapine is as efficacious as oral haloperidol in reducing acute agitation in patients with schizophrenia.