Reporting bias represents a major problem in the assessment of health care interventions. Several prominent cases have been described in the literature, for example, in the reporting of trials of antidepressants, Class I anti-arrhythmic drugs, and selective COX-2 inhibitors. The aim of this narrative review is to gain an overview of reporting bias in the medical literature, focussing on publication bias and selective outcome reporting. We explore whether these types of bias have been shown in areas beyond the well-known cases noted above, in order to gain an impression of how widespread the problem is. For this purpose, we screened relevant articles on reporting bias that had previously been obtained by the German Institute for Quality and Efficiency in Health Care in the context of its health technology assessment reports and other research work, together with the reference lists of these articles.We identified reporting bias in 40 indications comprising around 50 different pharmacological, surgical (e.g. vacuum-assisted closure therapy), diagnostic (e.g. ultrasound), and preventive (e.g. cancer vaccines) interventions. Regarding pharmacological interventions, cases of reporting bias were, for example, identified in the treatment of the following conditions: depression, bipolar disorder, schizophrenia, anxiety disorder, attention-deficit hyperactivity disorder, Alzheimer's disease, pain, migraine, cardiovascular disease, gastric ulcers, irritable bowel syndrome, urinary incontinence, atopic dermatitis, diabetes mellitus type 2, hypercholesterolaemia, thyroid disorders, menopausal symptoms, various types of cancer (e.g. ovarian cancer and melanoma), various types of infections (e.g. HIV, influenza and Hepatitis B), and acute trauma. Many cases involved the withholding of study data by manufacturers and regulatory agencies or the active attempt by manufacturers to suppress publication. The ascertained effects of reporting bias included the overestimation of efficacy and the underestimation of safety risks of interventions.In conclusion, reporting bias is a widespread phenomenon in the medical literature. Mandatory prospective registration of trials and public access to study data via results databases need to be introduced on a worldwide scale. This will allow for an independent review of research data, help fulfil ethical obligations towards patients, and ensure a basis for fully-informed decision making in the health care system.
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
We all want to base our healthcare decisions on trustworthy evidence. Yet the landmark 2009 Institute of Medicine report identified widespread financial conflicts of interest across medical research, education, and practice. 1 It highlighted that extensive industry influence may be jeopardising "the integrity of scientific investigations, the objectivity of medical education, the quality of patient care, and the public's trust in medicine." 1 Problem of financial dependence Research Financial dependence on commercial companies is common within research, and in the United States almost 60% of medical research is industry funded. 9 It's been shown repeatedly that published outcomes of industry sponsored studies tend to favour sponsors' products, creating a "sponsorship bias" in the evidence base that overplays benefits and underplays harms. 10 In 2013, research by the German Institute for Quality and Efficiency in
Beate Wieseler and colleagues compare the completeness of reporting of patient-relevant clinical trial outcomes between clinical study reports and publicly available data. Please see later in the article for the Editors' Summary
More than half of new drugs entering the German healthcare system have not been shown to add benefit. Beate Wieseler and colleagues argue that international drug development processes and policies are responsible and must be reformed
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