Conflicts of interest among authors of medical guidelines: an analysis of guidelines produced by German specialist societies.

BACKGROUND: Conflicts of interest can bias the recommendations of clinical guidelines. In 2010, the Association of Scientific Medical Societies in Germany (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften, AWMF) revised its rules about how conflicts of interest in guidelines should be managed. METHODS: All S2 and S3 guidelines in the AWMF database that were created in the years 2009-2011 were independently examined by two reviewers each (TL, MG, SC, BW, LF, SS). Information on conflicts of interest was extracted and descriptively analyzed. The effects of the new AWMF rules were studied with a before-and-after comparison. RESULTS: 60 (20%) of the 297 guidelines studied contained explicit declarations of conflict of interest by their authors. 680 authors (49%) stated that they had financial relationships that constituted a conflict of interest; 86% declared conflicts arising from membership in specialty societies or professional associations. From 2009 to 2011, there was a substantial rise in the frequency of conflict-of-interest declarations in guidelines (8% of 256 guidelines that were created before the AWMF revised its rules in 2010 and 95% of 41 guidelines created afterward). The percentage of persons declaring financial conflicts of interest rose after the new rules were introduced, while the mode of documentation of conflict-of-interest evaluation and of any measures that might have been taken as a result remained unchanged. CONCLUSION: From 2011 onward, all conflict-of-interest declarations by guideline authors have been published in the AWMF database. There is no current standard for the evaluation and management of conflicts of interest in guideline-creating groups, and this situation urgently needs to be remedied.

Reboxetine for acute treatment of major depression: systematic review and meta-analysis of published and unpublished placebo and selective serotonin reuptake inhibitor controlled trials.

OBJECTIVES: To assess the benefits and harms of reboxetine versus placebo or selective serotonin reuptake inhibitors (SSRIs) in the acute treatment of depression, and to measure the impact of potential publication bias in trials of reboxetine. DESIGN: Systematic review and meta-analysis including unpublished data. DATA SOURCES: Bibliographic databases (Medline, Embase, PsycINFO, BIOSIS, and Cochrane Library), clinical trial registries, trial results databases, and regulatory authority websites up until February 2009, as well as unpublished data from the manufacturer of reboxetine (Pfizer, Berlin). ELIGIBILITY CRITERIA: Double blind, randomised, controlled trials of acute treatment (six weeks or more) with reboxetine versus placebo or SSRIs in adults with major depression. OUTCOME MEASURES: Remission and response rates (benefit outcomes), as well as rates of patients with at least one adverse event and withdrawals owing to adverse events (harm outcomes). DATA EXTRACTION AND DATA SYNTHESIS: The procedures for data extraction and assessment of risk of bias were always conducted by one person and checked by another. If feasible, data were pooled by meta-analyses (random effects model). Publication bias was measured by comparing results of published and unpublished trials. RESULTS: We analysed 13 acute treatment trials that were placebo controlled, SSRI controlled, or both, which included 4098 patients. Data on 74% (3033/4098) of these patients were unpublished. In the reboxetine versus placebo comparison, no significant differences in remission rates were shown (odds ratio 1.17, 95% confidence interval 0.91 to 1.51; P=0.216). Substantial heterogeneity (I(2)=67.3%) was shown in the meta-analysis of the eight trials that investigated response rates for reboxetine versus placebo. A sensitivity analysis that excluded a small inpatient trial showed no significant difference in response rates between patients receiving reboxetine and those receiving placebo (OR 1.24, 95% CI 0.98 to 1.56; P=0.071; I(2)=42.1%). Reboxetine was inferior to SSRIs (fluoxetine, paroxetine, and citalopram) for remission rates (OR 0.80, 95% CI 0.67 to 0.96; P=0.015) and response rates (OR 0.80, 95% CI 0.67 to 0.95; P=0.01). Reboxetine was inferior to placebo for both harm outcomes (P<0.001 for both), and to fluoxetine for withdrawals owing to adverse events (OR 1.79, 95% CI 1.06 to 3.05; P=0.031). Published data overestimated the benefit of reboxetine versus placebo by up to 115% and reboxetine versus SSRIs by up to 23%, and also underestimated harm. CONCLUSIONS: Reboxetine is, overall, an ineffective and potentially harmful antidepressant. Published evidence is affected by publication bias, underlining the urgent need for mandatory publication of trial data.