Statistical controversies in clinical research: comparison of primary outcomes in protocols, public clinical-trial registries and publications: the example of oncology trials.

Background: Protocols are often unavailable to peer-reviewers and readers. To detect outcome reporting bias (ORB), readers usually have to resort to publicly available descriptions of study design such as public clinical trial registries. We compared primary outcomes in protocols, ClinicalTrials.gov and publications of oncology trials and evaluated the use of ClinicalTrials.gov as compared with protocols in detecting discrepancies between planned and published outcomes. Method: We searched for phase III oncology trials registered in ClinicalTrials.gov and published in the Journal of Clinical Oncology and New England Journal of Medicine between January 2014 and June 2015. We extracted primary outcomes reported in the protocol, ClinicalTrials.gov and the publication. First, we assessed the quality of primary outcome descriptions by using a published framework. Second, we evaluated modifications of primary outcomes between each source. Finally, we evaluated the agreement, specificity and sensitivity of detecting modifications between planned and published outcomes by using protocols or ClinicalTrials.gov. Results: We included 65 trials, with 81 primary outcomes common among the 3 sources. The proportion of primary outcomes reporting all items from the framework was 73%, 22%, and 75% for protocols, ClinicalTrials.gov and publications, respectively. Eight (12%) trials presented a discrepancy between primary outcomes reported in the protocol and in the publication. Twelve (18.5%) trials presented a discrepancy between primary outcomes registered at ClinicalTrials.gov and in publications. We found a moderate agreement in detecting discrepant reporting of outcomes by using protocols or ClinicalTrials.gov [κ = 0.53, 95% confidence interval (0.25-0.81)]. Using ClinicalTrials.gov to detect discrepant reporting of outcomes showed high specificity (89.5%) but lacked sensitivity (75%) as compared with use of protocols. Conclusion: In oncology trials, primary outcome descriptions in ClinicalTrials.gov are often of low quality and may not reflect what is in the protocol, thus limiting the detection of modifications between planned and published outcomes.

Factors predictive of ten-year mortality in severe anorexia nervosa patients.

OBJECTIVE: Little is known concerning mortality and predictive factors for anorexia nervosa in-patients. This study aimed to establish mortality rates and identify predictors in a large sample of adults through a 10-year post in-patient treatment follow-up. METHOD: Vital status was established for 601 anorexia nervosa (DSM-IV) consecutive in-patients with initial evaluation at admission. Standardized mortality ratio (SMR) was calculated. Cox analyses for hypothesized predictors of mortality were performed. RESULTS: Forty deaths were recorded. SMR was 10.6 [CI 95% (7.6-14.4)]. Six factors at admission were associated with death: older age, longer eating disorder duration, history of suicide attempt, diuretic use, intensity of eating disorder symptoms, and desired body mass index at admission. CONCLUSION: Anorexia nervosa in-patients are at high risk of death. This risk can be predicted by both chronicity and seriousness of illness at hospitalization. These elements should be considered as warnings to adapt care provision and could be targeted by treatment.

Inclusion of patients with acute leukemia in clinical trials: a prospective multicenter survey of 1066 cases.

BACKGROUND: to estimate the prevalence of adults and children with acute leukemia (AL) included in clinical trials and to determine factors associated with noninclusion. PATIENTS AND METHODS: all patients with AL admitted to the 17 departments managing AL in Paris area from 2005 to 2007 were prospectively included. Clinical data, therapeutic decisions, and enrollment in trials were recorded. Reasons that prevented accrual were identified. RESULTS: a total of 1066 admissions with AL (85% of adults) were recorded, and 34 trials were open. In adults, the rate of inclusion in a trial was 25% [95% confidence interval (CI) 21% to 28%] for acute myeloid leukemia (AML) and 23% (95% CI 17% to 29%) for acute lymphoid leukemia (ALL). In children, the rate of inclusion was 58% (95% CI 41% to 73%) for AML and 64% (95% CI 55% to 72%) for ALL. The rate of inclusion varied across centers, with a significant increase when they were involved in clinical research. Patients included in trials differed significantly from those not included according to age, primary/secondary AL, leukemia type, results of cytogenetic analyses, and stage of disease. CONCLUSIONS: the rate of inclusion is higher than in oncology. This difference may be explained by management in specialized centers often involved in clinical research.