Influence of drug company authorship and sponsorship on drug trial outcomes. Association of funding and findings of pharmaceutical research at a meeting of a medical professional society. Association of industry sponsorship to published outcomes in gastrointestinal clinical research. Relationship between drug company funding and outcomes of clinical psychiatric research. Publication bias in the pulmonary/allergy literature: effect of pharmaceutical company sponsorship. Industry sponsorship and authorship of clinical trials over 20 years. The effect of study sponsorship on a systematically evaluated body of evidence of head-to-head trials was modest: secondary analysis of a systematic review. Industry sponsorship and financial conflict of interest in the reporting of clinical trials in psychiatry. Relationship between sponsorship and failure rate of dental implants: a systematic approach. Issues that may determine the outcome of antipsychotic trials: industry sponsorship and extrapyramidal side effect. The quality of drug studies published in symposium proceedings. The uncertainty principle and industry-sponsored research. Association between pharmaceutical involvement and outcomes in breast cancer clinical trials. Association of funding and conclusions in randomized drug trials: a reflection of treatment effect or adverse events? Extent and impact of industry sponsorship conflicts of interest in dermatology research. Factors associated with failure to publish large randomized trials presented at an oncology meeting. Association between industry funding and statistically significant pro-industry findings in medical and surgical randomized trials. Source of funding and outcome of clinical trials. Discrepancy between results and abstract conclusions in industry- vs nonindustry-funded studies comparing topical prostaglandins. An analysis of the effect of funding source in randomized clinical trials of second generation antipsychotics for the treatment of schizophrenia. Factors associated with findings of published trials of drug-drug comparisons: why some statins appear more efficacious than others. Why olanzapine beats risperidone, risperidone beats quetiapine, and quetiapine beats olanzapine: an exploratory analysis of head-to-head comparison studies of second-generation antipsychotics. Association between research sponsorship and study outcome in plastic surgery literature. Outcome reporting among drug trials registered in ClinicalTrials.gov. Epidemiologic studies of adverse effects of anti-retroviral drugs: how well is statistical power reported. Does sponsorship matter in patient satisfaction surveys? A randomized trial. Adverse event reporting in publications compared with sponsor database for cancer clinical trials. Bias from industry trial funding? A framework, a suggested approach, and a negative result. Adverse effects of inhaled corticosteroids in funded and nonfunded studies. Commercially funded and United States-based research is more likely to be published; good-quality studies with negative outcomes are not. Reported outcomes in major cardiovascular clinical trials funded by for-profit and not-for-profit organizations: 2000-2005. Assessment of risk of bias among pediatric randomized controlled trials. Association of trial registration with the results and conclusions of published trials of new oncology drugs. Funding source, trial outcome and reporting quality: are they related? Results of a pilot study. Publication bias: evidence of delayed publication in a cohort study of clinical research projects. The impact of pharmaceutical company funding on results of randomized trials of nicotine replacement therapy for smoking cessation: a meta-analysis. Publication bias in presentations to the Annual Scientific Congress. Publication and non-publication of clinical trials: longitudinal study of applications submitted to a research ethics committee. Factors associated with results and conclusions of trials of thiazolidinediones. Impact of presentation of research results on likelihood of prescribing medications to patients with left ventricular dysfunction. Relation of study quality, concordance, take home message, funding, and impact in studies of influenza vaccines: systematic review. A study of manufacturer-supported trials of nonsteroidal anti-inflammatory drugs in the treatment of arthritis. Do drug-free workplace programs prevent occupational injuries? Evidence from Washington State. Evolution of the randomized controlled trial in oncology over three decades. Association between competing interests and authors' conclusions: epidemiological study of randomised clinical trials published in the BMJ. Bias in reporting clinical trials. Improving drug-therapy decisions through educational outreach. A randomized controlled trial of academically based "detailing".
Studies of drug treatments are more likely to report favourable outcomes when they are funded by the pharmaceutical industry. We compared drug trials reported in three major psychiatric journals to investigate these influences. Independent studies were more likely to report negative findings than industry-funded studies. However, the involvement of a drug company employee had a much greater effect on study outcome than financial sponsorship alone. To evaluate the association between funding and findings of pharmaceutical research presented at an annual meeting of a medical professional society.
                We reviewed the abstracts of all papers and posters presented at the annual meeting of a medical professional society. Two independent raters classified each study of a drug (n = 48) as either positive (favoring the drug studied) or negative, and as either funded by a pharmaceutical company or not. We computed kappa and chi-squared statistics to evaluate the agreement between the raters, as well as the association between the results and the sponsorship of the study.
                Thirty studies of drugs (63%) were supported by pharmaceutical companies, all of which reported positive results. Of the 18 studies (37%) not supported by pharmaceutical companies, 67% reported positive results. The association between pharmaceutical funding and positive findings was statistically significant (P = 0.0007).
                At this scientific meeting, research funding from pharmaceutical companies was associated with study findings that supported the use of drugs marketed by pharmaceutical sponsors. We emphasize further study of this relation and suggest three principles--full disclosure, policies against "outcome bias," and educational opportunities--that may help manage industry-academia conflicts of interest that could otherwise jeopardize the credibility of pharmaceutical research presented at scientific meetings. Recent years have seen an increase in industry sponsorship of clinical trials throughout medicine. We conducted a study to evaluate the association of industry sponsorship to published outcomes in gastrointestinal (GI) clinical research. Our aims were (1) to evaluate the trends in the source of funding for GI clinical research during the period from 1992 to 2002-2003, (2) to determine whether the source of study funding predicted the likelihood that a study would publish results that favor the drug or device being tested, and (3) to determine whether differences exist in the methodologic quality of the investigational study methods used in studies funded by private industry versus other sources.
                We selected all clinical studies evaluating a drug or device from 4 prominent GI journals (Gastroenterology, The American Journal of Gastroenterology, Hepatology, and Gastrointestinal Endoscopy). All studies were abstracted by using a standardized data abstraction form. We evaluated the trends in funding source for studies published during the years 1992, 2002, and 2003. All selected studies were scored for methodologic quality by using a previously validated scoring system. The percentage of studies that reported outcomes that favored the device or drug being tested against the standard therapy or placebo was determined for each funding source. A funnel plot was constructed to assess for the presence of negative publication bias.
                A total of 6326 studies were reviewed. For the 1992 trend data, 1860 studies were reviewed, and 135 were selected for inclusion in the study. Ninety-five studies were studies involving the investigation of drugs, and 40 studies involved the testing of a device. For the 2002-2003 data 4466 studies were reviewed, and 315 were selected for inclusion in the study. Two hundred twenty-two studies were clinical trials involving the investigation of drugs, and 93 were clinical trials involving devices. In comparing 1992 to 2002, the percentage of studies funded by industry sources more than doubled from 10% to greater than 28% of the total studies assessed. There was an associated decline in the proportion of studies with funding from non-industry sources during this period (62% to less than 48%). The percentage of studies that did not disclose a funding source fell modestly from 28% to 24%. We found that 86% of studies funded by private industry reported a result favorable to the study drug or device, and 83% of studies funded by academic sources reported a result favorable to the study drug or device (P=.572). On average, studies funded by private industry had a higher methodology score than studies funded by traditional academic sources (75 of 100 vs 65 of 100; P=.005). Analysis of the funnel plot did not reveal evidence of bias against the publication of small studies with insignificant results.
                The proportion of research funded by industry has more than doubled during the last decade and currently comprises almost half of the funding for GI clinical research. Industry-sponsored studies are, on average, of superior methodologic quality to studies funded by other sources. Industry-sponsored studies in leading GI journals were no more likely than other studies to publish results that favored the study sponsor, although an extremely high percentage of all studies in these journals reported positive results. There has been only a modest decline in studies not acknowledging a funding source. Pharmaceutical industry funding of psychiatric research has increased significantly in recent decades, raising the question of a relationship between pharmaceutical company funding of clinical psychiatric studies and the outcomes of those studies. This study examines this relationship.
                Abstracts of articles from 1992 and 2002 in four peer-reviewed psychiatric journals were examined. Drug outcomes (n=542) for clinical studies were evaluated and then compared across sponsorship source. Outcome raters were blind to source of sponsorship. The percentage of these studies sponsored by drug companies in 2002 v. 1992 was also compared. In a secondary analysis, the contribution of a series of potentially mediating variables to the relationship between sponsorship source and study outcome was assessed via logistic regression.
                The percentage of studies sponsored by drug companies increased from 25% in 1992 to 57% in 2002. Favorable outcomes were significantly more common in studies sponsored by the drug manufacturer (78%) than in studies without industry sponsorship (48%) or sponsored by a competitor (28%). These relationships remained after controlling for the effects of journal, year, drug studied, time since FDA drug approval, diagnosis, sample size, and selected study design variables.
                These data indicate an association between pharmaceutical industry funding of clinical studies and positive outcomes of those studies. Further research is needed to elucidate the mechanisms underlying this relationship. A publication bias exists towards positive results in studies funded by pharmaceutical companies.
                To determine whether drug studies in the pulmonary/allergy literature also demonstrate a publication bias towards more favorable results when a pharmaceutical company funds the study.
                We reviewed all original articles published in seven pulmonary and allergy journals between October 2002 and September 2003. Included in the review were studies of inhaled corticosteroids (oral or nasal), long- or short-acting bronchodilators, or leukotriene receptor antagonists. Articles with funding from a pharmaceutical company and/or one or more authors employed by a pharmaceutical company were considered pharmaceutical company-sponsored studies. The remaining studies were considered not sponsored by a pharmaceutical company. Results were compared to ascertain whether positive results were obtained more frequently in the company-sponsored studies.
                Of the 100 articles included in this review 63 were considered pharmaceutical company-sponsored research. Results favorable for the drugs studies were significantly more common in those funded by a pharmaceutical company (98% vs. 32%).
                In the pulmonary and allergy literature, as in other fields, there is a publication bias towards positive results in pharmaceutical company-sponsored research. The pharmaceutical industry has become a major source of funding for biomedical research. Our general observation is that pharmaceutical industry employees are appearing with increasing frequency as coauthors of clinical trial publications.
                To characterize clinical trial funding, reporting, and sources; investigate author-industry affiliation; and describe clinical outcome trends over time.
                We reviewed 500 randomly selected clinical trials published in 5 influential medical journals over a 20-year period (1981-2000).
                Of the 500 clinical trials reviewed, 181 (36%) involved pharmaceutical industry as an independent (n = 104) or joint (n = 77) sponsor and 180 (36%) involved a peer-review funding source; the balance (139; 28%) lacked any declared sponsorship. The percentage of industry-sponsored clinical trials increased to 62% during 1997-2000. The percentage of nonprofit sponsored clinical trials remained constant over time, while the percentage of those without funding declaration declined. Reported author affiliation with industry increased to 66% of clinical trials sponsored only by industry. An increase in the percentage of clinical trials with reported author-industry affiliation was observed for all journals. Regardless of funding source, the majority of clinical trials reported clinical outcomes that favored the study drug.
                Pharmaceutical industry-sponsored and mixed-funding clinical trials are common, and the relative incidence of published trials with these declared funding sources in the 5 journals reviewed has increased. Industry employees are appearing as coauthors of clinical trial publications with increasing frequency. The objective of this study was to determine the effect of industry bias in a systematically reviewed body of evidence of head-to-head trials.
                We limited our analysis to published head-to-head randomized controlled trials of selective serotonin reuptake inhibitors (SSRIs) identified in a comparative effectiveness review. Two reviewers independently determined the status of funding for each trial. We classified drugs into one of two groups: (1) drugs associated with the funding source and (2) drugs not associated with the funding source. To determine the effect of any underlying industry bias, we conducted relative-benefit meta-analyses comparing the response rates of drugs when associated with the funding source with response rates of the same drugs when not associated with the funding source.
                Thirteen out of 20 studies (65%) numerically favored drugs associated with the funding source over drugs used as controls. The pooled response rates of SSRIs, when associated with the funding source, are significantly greater than those of the same SSRIs when not associated with the sponsor (relative benefit=1.07; 95% confidence interval=1.02-1.11). The difference, however, is likely to be not of clinical importance.
                The effect of industry bias in comparative effectiveness reviews might play a lesser role than in systematic reviews of placebo-controlled trials.
                Copyright 2010 Elsevier Inc. All rights reserved. Financial conflict of interest has been reported to be prevalent in clinical trials in general medicine and associated with a greater likelihood of reporting results favorable to the intervention being studied. The extent and implications of industry sponsorship and financial conflict of interest in psychiatric clinical trials have not been investigated, to the authors' knowledge.
                The authors examined funding source and author financial conflict of interest in all clinical trials published in the American Journal of Psychiatry, the Archives of General Psychiatry, the Journal of Clinical Psychopharmacology, and the Journal of Clinical Psychiatry between 2001 and 2003.
                Among 397 clinical trials identified, 239 (60%) reported receiving funding from a pharmaceutical company or other interested party, and 187 studies (47%) included at least one author with a reported financial conflict of interest. Among the 162 randomized, double-blind, placebo-controlled studies examined, those that reported conflict of interest were 4.9 times more likely to report positive results; this association was significant only among the subset of pharmaceutical industry-funded studies.
                Author conflict of interest appears to be prevalent among psychiatric clinical trials and to be associated with a greater likelihood of reporting a drug to be superior to placebo. The number of dental implant treatments increases annually. Dental implants are manufactured by competing companies. Systematic reviews and meta-analysis have shown a clear association between pharmaceutical industry funding of clinical trials and pro-industry results. So far, the impact of industry sponsorship on the outcomes and conclusions of dental implant clinical trials has never been explored. The aim of the present study was to examine financial sponsorship of dental implant trials, and to evaluate whether research funding sources may affect the annual failure rate.
                A systematic approach was used to identify systematic reviews published between January 1993 and December 2008 that specifically deal with the length of survival of dental implants. Primary articles were extracted from these reviews. The failure rate of the dental implants included in the trials was calculated. Data on publication year, Impact Factor, prosthetic design, periodontal status reporting, number of dental implants included in the trials, methodological quality of the studies, presence of a statistical advisor, and financial sponsorship were extracted by two independent reviewers (kappa = 0.90; CI(95%) [0.77-1.00]). Univariate quasi-Poisson regression models and multivariate analysis were used to identify variables that were significantly associated with failure rates. Five systematic reviews were identified from which 41 analyzable trials were extracted. The mean annual failure rate estimate was 1.09%.(CI(95%) [0.84-1.42]). The funding source was not reported in 63% of the trials (26/41). Sixty-six percent of the trials were considered as having a risk of bias (27/41). Given study age, both industry associated (OR = 0.21; CI(95%) [0.12-0.38]) and unknown funding source trials (OR = 0.33; (CI(95%) [0.21-0.51]) had a lower annual failure rates compared with non-industry associated trials. A conflict of interest statement was disclosed in 2 trials.
                When controlling for other factors, the probability of annual failure for industry associated trials is significantly lower compared with non-industry associated trials. This bias may have significant implications on tooth extraction decision making, research on tooth preservation, and governmental health care policies. This study presents a meta-analysis of the influence of several potentially biasing factors (eg industry support, extrapyramidal side effects) on efficacy of studies comparing second-generation antipsychotic (SGA) with first-generation antipsychotic (FGA) medications. We used the dataset from our previously published meta-analysis of 124 randomized controlled trials (RCTs) comparing SGAs with FGAs, to evaluate whether certain possible biases could influence the actual outcome on the total score of the Positive and Negative Syndrome Scale (PANSS), Brief Psychiatric Rating Scale (BPRS), and Clinical Global Impressions (CGI) scores. Industry sponsorship was determined by contact with authors or publication statement. We calculated whether (1) industry sponsorship, (2) study quality, (3) extrapyramidal symptoms (EPS) properties, or (4) prophylactic antiparkinsonian medications influenced SGA vs FGA efficacy for each drug and averaged overall by two Hedges and Olkin-based meta-analyses. The analysis found that none of the factors was significantly associated with a particular outcome. While industry-sponsored articles may conclude their medication to be more favorable than that of a competitor in an RCT, we found that the observed efficacy was not influenced by sponsorship. Many attribute the finding that SGAs appears to be more efficacious than FGAs to be a result of EPS-decreasing efficacy (or its measurement). We were unable to confirm that the drug's EPS properties or antiparkinsonian management altered actual efficacy. To compare the quality, relevance, and structure of drug studies published in symposium proceedings that are sponsored by drug companies with 1) articles from symposia with other sponsors and 2) articles in the peer-reviewed parent journals of symposium proceedings; and to study the relation between drug company sponsorship and study outcome.
                Cross-sectional studies of clinical drug studies published in symposium proceedings or their parent medical journals.
                The proportion of articles with no methods sections (which are necessary to assess quality); methodologic quality and clinical relevance scores; and the proportion of articles with outcomes favoring the drug of interest.
                Symposia sponsored by single drug companies had more articles without methods sections (10%; 108 of 1064) than did symposia that had other sponsors (3%; 58 of 2314) or symposia that had no mentioned sponsor (2%; 29 of 1663) (P < 0.001). The mean methodologic quality and relevance scores of articles were similar both by type of sponsorship and between articles published in symposia sponsored by single drug companies and articles from the parent journals. Significantly more articles with drug company support (98%; 39 of 40) than without drug company support (79%; 89 of 112) had outcomes favoring the drug of interest (P = 0.01).
                Articles in symposia sponsored by single drug companies were similar in quality and clinical relevance to articles with other sponsors and to articles published in the parent journals. Articles with drug company support are more likely than articles without drug company support to have outcomes favoring the drug of interest. Reporting of pharmaceutical-industry-sponsored randomised clinical trials often result in biased findings, either due to selective reporting of studies with non-equivalent arms or publication of low-quality papers, wherein unfavourable results are incompletely described. A randomised trial should be conducted only if there is substantial uncertainty about the relative value of one treatment versus another. Studies in which intervention and control are thought to be non-equivalent violates the uncertainty principle.
                We examined the quality of 136 published randomised trials that focused on one disease category (multiple myeloma) and adherence to the uncertainty principle. To evaluate whether the uncertainty principle was upheld, we compared the number of studies favouring experimental treatments over standard ones. We analysed data according to the source of funding.
                Trials funded solely or in part by 35 profit-making organisations had a trend toward higher quality scores (mean 2.94 [SD 1.3]; median 3) than randomised trials supported by 95 governmental or other non-profit organisations (2.4 [0.8]; 2; p=0.06). Overall, the uncertainty principle was upheld, with 44% of randomised trials favouring standard treatments and 56% innovative treatments (p=0.17); mean and median preference evaluation scores were 3.7 (1.0) and 4. However, when the analysis was done according to the source of funding, studies funded by non-profit organisations maintained equipoise favouring new therapies over standard ones (47% vs 53%; p=0.608) to a greater extent than randomised trials supported solely or in part by profit-making organisations (74% vs 26%; p=0.004).
                The reported bias in research sponsored by the pharmaceutical industry may be a consequence of violations of the uncertainty principle. Sponsors of clinical trials should be encouraged to report all results and to choose appropriate comparative controls. Since 1992, pharmaceutical industry support has surpassed National Institutes of Health funding for clinical research in the United States. In this study, the authors sought to evaluate the impact of this shift in funding from public to private sponsors on the nature of published breast cancer clinical research.
                All published breast cancer clinical trials from 2003, 1998, and 1993 were reviewed from 10 select English-language medical journals to evaluate pharmaceutical involvement over time and the association between sponsorship, trial design, and results. Clinical studies that reported disease-specific outcomes from medical therapy for breast cancer were eligible for analysis. Pharmaceutical involvement was defined as reported pharmaceutical industry funding, provision of drug, and/or authorship for each publication.
                In total, 140 eligible studies were identified, including 45 studies that were published in 1993, 39 studies that were published in 1998, and 56 studies that were published in 2003. Among those, 67 publications (48%) reported pharmaceutical industry involvement, 36 publications (26%) had at least >/=1 pharmaceutical industry author, And 100 publications (71%) were considered positive. Pharmaceutical involvement was identified in 44% of the studies published in 1993, in 38% of the studies published in 1998, and in 58% of the studies published in 2003. Pharmaceutical authorship was reported in 22% of the 1993 studies, in 21% of the 1998 studies, and in 34% of the 2003 studies. For studies that were published in 2003, those that reported pharmaceutical involvement were more likely to be positive (84% vs 54%; P = .02; Fisher exact test), to be single-arm studies (66% vs 33%; P = .03), and to evaluate metastatic disease (72% vs 46%; P = .06).
                Pharmaceutical involvement in published clinical breast cancer research may affect study design, focus, and results. Further research is warranted, including analysis of unpublished studies, to evaluate the impact of increasing pharmaceutical industry involvement on clinical research.
                (c) 2007 American Cancer Society. Previous studies indicate that industry-sponsored trials tend to draw proindustry conclusions.
                To explore whether the association between funding and conclusions in randomized drug trials reflects treatment effects or adverse events.
                Observational study of 370 randomized drug trials included in meta-analyses from Cochrane reviews selected from the Cochrane Library, May 2001. From a random sample of 167 Cochrane reviews, 25 contained eligible meta-analyses (assessed a binary outcome; pooled at least 5 full-paper trials of which at least 1 reported adequate and 1 reported inadequate allocation concealment). The primary binary outcome from each meta-analysis was considered the primary outcome for all trials included in each meta-analysis. The association between funding and conclusions was analyzed by logistic regression with adjustment for treatment effect, adverse events, and additional confounding factors (methodological quality, control intervention, sample size, publication year, and place of publication).
                Conclusions in trials, classified into whether the experimental drug was recommended as the treatment of choice or not.
                The experimental drug was recommended as treatment of choice in 16% of trials funded by nonprofit organizations, 30% of trials not reporting funding, 35% of trials funded by both nonprofit and for-profit organizations, and 51% of trials funded by for-profit organizations (P<.001; chi2 test). Logistic regression analyses indicated that funding, treatment effect, and double blinding were the only significant predictors of conclusions. Adjusted analyses showed that trials funded by for-profit organizations were significantly more likely to recommend the experimental drug as treatment of choice (odds ratio, 5.3; 95% confidence interval, 2.0-14.4) compared with trials funded by nonprofit organizations. This association did not appear to reflect treatment effect or adverse events.
                Conclusions in trials funded by for-profit organizations may be more positive due to biased interpretation of trial results. Readers should carefully evaluate whether conclusions in randomized trials are supported by data. Many published clinical trials are authored by investigators with financial conflicts of interest. The general medical literature documents the pervasive extent and sometimes problematic impact of these conflicts. Accordingly, there is renewed discussion about author disclosure and clinical trial registry to minimize publication bias from financial conflicts of interest. Despite this evolving discussion in the general medical literature, little is known about the extent or role of financial conflicts of interest in dermatology research.
                Our purpose was to determine the extent and impact of industry sponsorship conflicts of interest in dermatology research.
                We recorded potential financial conflicts of interest, study design, and study outcome in 179 clinical trials published between Oct 1, 2000 and Oct 1, 2003 in four leading dermatology journals.
                Forty-three percent of analyzed studies included at least one author with a reported conflict of interest. These studies were more likely to report a positive result, demonstrate higher methodological quality, and include a larger sample size.
                Conflict of interest in clinical investigations in dermatology appears to be prevalent and associated with potentially significant differences in study methodology and reporting. Large clinical trials are the criterion standard for making treatment decisions, and nonpublication of the results of such trials can lead to bias in the literature and contribute to inappropriate medical decisions.
                To determine the rate of full publication of large randomized trials presented at annual meetings of the American Society of Clinical Oncology (ASCO), quantify bias against publishing nonsignificant results, and identify factors associated with time to publication.
                Survey of 510 abstracts from large (sample size, > or =200), phase 3, randomized controlled trials presented at ASCO meetings between 1989 and 1998. Trial results were classified as significant (P< or =.05 for the primary outcome measure) or nonsignificant (P>.05 or not reported), and the type of presentation and sponsorship were identified. Subsequent full publication was identified using a search of MEDLINE and EMBASE, completed November 1, 2001; the search was updated in November 2002, using the Cochrane Register of Controlled Trials. Authors were contacted if the searches did not find evidence of publication.
                Publication rate at 5 years; time from presentation to full publication.
                Of 510 randomized trials, 26% were not published in full within 5 years after presentation at the meeting. Eighty-one percent of the studies with significant results had been published by this time compared with 68% of the studies with nonsignificant results (P<.001). Studies with oral or plenary presentation were published sooner than those not presented (P =.002), and studies with pharmaceutical sponsorship were published sooner than studies with cooperative group sponsorship or studies for which sponsorship was not specified (P =.02). These factors remained significant in a multivariable model. The most frequent reason cited by authors for not publishing was lack of time, funds, or other resources.
                A substantial number of large phase 3 trials presented at an international oncology meeting remain unpublished 5 years after presentation. Bias against publishing nonsignificant results is a problem even for large randomized trials. Nonpublication breaks the contract that investigators make with trial participants, funding agencies, and ethics boards. Conflicting reports exist in the medical literature regarding the association between industry funding and published research findings. In this study, we examine the association between industry funding and the statistical significance of results in recently published medical and surgical trials.
                We examined a consecutive series of 332 randomized trials published between January 1999 and June 2001 in 8 leading surgical journals and 5 medical journals. Each eligible study was independently reviewed for methodological quality using a 21-point index with 5 domains: randomization, outcomes, eligibility criteria, interventions and statistical issues. Our primary analysis included studies that explicitly identified the primary outcome and reported it as statistically significant. For studies that did not explicitly identify a primary outcome, we defined a "positive" study as one with at least 1 statistically significant outcome measure. We used multivariable regression analysis to determine whether there was an association between reported industry funding and trial results, while controlling for study quality and sample size.
                Among the 332 randomized trials, there were 158 drug trials, 87 surgical trials and 87 trials of other therapies. In 122 (37%) of the trials, authors declared industry funding. An unadjusted analysis of this sample of trials revealed that industry funding was associated with a statistically significant result in favour of the new industry product (odds ratio [OR] 1.9, 95% confidence interval [CI] 1.3-3.5). The association remained significant after adjustment for study quality and sample size (adjusted OR 1.8, 95% CI 1.1-3.0). There was a nonsignificant difference between surgical trials (OR 8.0, 95% CI 1.1-53.2) and drug trials (OR 1.6, 95% CI 1.1-2.8), both of which were likely to have a pro-industry result (relative OR 5.0, 95% CI 0.7-37.5, p = 0.14).
                Industry-funded trials are more likely to be associated with statistically significant pro-industry findings, both in medical trials and surgical interventions. Because of recent concerns about conflicts of interest and published research, the author analyzed 107 controlled clinical trials. Studies were classified as favoring either a new therapy or a traditional therapy, and as being supported by a pharmaceutical manufacturer or as being generally supported. Seventy-one per cent of the trials favored new therapies; 43% of these were funded by pharmaceutical firms. Of the 31 trials favoring traditional therapy, only four (13%) were supported by a pharmaceutical firm. There was a statistically significant association between the source of funding and the outcome of the study (p = 0.002). Few trials supported by pharmaceutical manufacturers favored traditional therapy; some reasons for this finding may include selection of drugs likely to be proven efficacious, Type II errors (false-negative studies), and fear of discontinuation of funding should such studies be submitted. Important clinical information may be lost if negative studies are not published. To investigate the relationship between industry- vs nonindustry-funded publications comparing the efficacy of topical prostaglandin analogs by evaluating the correspondence between the statistical significance of the publication's main outcome measure and its abstract conclusions.
                Retrospective, observational cohort study.
                English publications comparing the ocular hypotensive efficacy between any or all of latanoprost, travoprost, and bimatoprost were searched from the MEDLINE database. Each article was reviewed by three independent observers and was evaluated for source of funding, study quality, statistically significant main outcome measure, correspondence between results of main outcome measure and abstract conclusion, number of intraocular pressure outcomes compared, and journal impact factor. Funding was determined by published disclosure or, in cases of no documented disclosure, the corresponding author was contacted directly to confirm industry funding. Discrepancies were resolved by consensus. The main outcome measure was correspondence between abstract conclusion and reported statistical significance of the publications' main outcome measure.
                Thirty-nine publications were included, of which 29 were industry funded and 10 were nonindustry funded. The published abstract conclusion was not consistent with the results of the main outcome measure in 18 (62%) of 29 of the industry-funded studies compared with zero (0%) of 10 of the nonindustry-funded studies (P = .0006). Twenty-six (90%) of the industry-funded studies had proindustry abstract conclusions.
                Twenty-four percent of the industry-funded publications had a statistically significant main outcome measure; however, 90% of the industry-funded studies had proindustry abstract conclusions. Both readers and reviewers should scrutinize publications carefully to ensure that data support the authors' conclusions. The effect of funding source on the outcome of randomized controlled trials has been investigated in several medical disciplines; however, psychiatry has been largely excluded from such analyses. In this article, randomized controlled trials of second generation antipsychotics in schizophrenia are reviewed and analyzed with respect to funding source (industry vs. non-industry funding).
                A literature search was conducted for randomized, double-blind trials in which at least one of the tested treatments was a second generation antipsychotic. In each study, design quality and study outcome were assessed quantitatively according to rating scales. Mean quality and outcome scores were compared in the industry-funded studies and non-industry-funded studies. An analysis of the primary author's affiliation with industry was similarly performed.
                Results of industry-funded studies significantly favored second generation over first generation antipsychotics when compared to non-industry-funded studies. Non-industry-funded studies showed a trend toward higher quality than industry-funded studies; however, the difference between the two was not significant. Also, within the industry-funded studies, outcomes of trials involving first authors employed by industry sponsors demonstrated a trend toward second generation over first generation antipsychotics to a greater degree than did trials involving first authors employed outside the industry (p=0.05).
                While the retrospective design of the study limits the strength of the findings, the data suggest that industry bias may occur in randomized controlled trials in schizophrenia. There appears to be several sources by which bias may enter clinical research, including trial design, control of data analysis and multiplicity/redundancy of trials. Published pharmaceutical industry-sponsored trials are more likely than non-industry-sponsored trials to report results and conclusions that favor drug over placebo. Little is known about potential biases in drug-drug comparisons. This study examined associations between research funding source, study design characteristics aimed at reducing bias, and other factors that potentially influence results and conclusions in randomized controlled trials (RCTs) of statin-drug comparisons.
                This is a cross-sectional study of 192 published RCTs comparing a statin drug to another statin drug or non-statin drug. Data on concealment of allocation, selection bias, blinding, sample size, disclosed funding source, financial ties of authors, results for primary outcomes, and author conclusions were extracted by two coders (weighted kappa 0.80 to 0.97). Univariate and multivariate logistic regression identified associations between independent variables and favorable results and conclusions. Of the RCTs, 50% (95/192) were funded by industry, and 37% (70/192) did not disclose any funding source. Looking at the totality of available evidence, we found that almost all studies (98%, 189/192) used only surrogate outcome measures. Moreover, study design weaknesses common to published statin-drug comparisons included inadequate blinding, lack of concealment of allocation, poor follow-up, and lack of intention-to-treat analyses. In multivariate analysis of the full sample, trials with adequate blinding were less likely to report results favoring the test drug, and sample size was associated with favorable conclusions when controlling for other factors. In multivariate analysis of industry-funded RCTs, funding from the test drug company was associated with results (odds ratio = 20.16 [95% confidence interval 4.37-92.98], p < 0.001) and conclusions (odds ratio = 34.55 [95% confidence interval 7.09-168.4], p < 0.001) that favor the test drug when controlling for other factors. Studies with adequate blinding were less likely to report statistically significant results favoring the test drug.
                RCTs of head-to-head comparisons of statins with other drugs are more likely to report results and conclusions favoring the sponsor's product compared to the comparator drug. This bias in drug-drug comparison trials should be considered when making decisions regarding drug choice. In many parts of the world, second-generation antipsychotics have largely replaced typical antipsychotics as the treatment of choice for schizophrenia. Consequently, trials comparing two drugs of this class--so-called head-to-head studies--are gaining in relevance. The authors reviewed results of head-to-head studies of second-generation antipsychotics funded by pharmaceutical companies to determine if a relationship existed between the sponsor of the trial and the drug favored in the study's overall outcome.
                The authors identified head-to-head comparison studies of second-generation antipsychotics through a MEDLINE search for the period from 1966 to September 2003 and identified additional head-to-head studies from selected conference proceedings for the period from 1999 to February 2004. The abstracts of all studies fully or partly funded by pharmaceutical companies were modified to mask the names and doses of the drugs used in the trial, and two physicians blinded to the study sponsor reviewed the abstracts and independently rated which drug was favored by the overall outcome measures. Two authors who were not blinded to the study sponsor reviewed the entire report of each study for sources of bias that could have affected the results in favor of the sponsor's drug.
                Of the 42 reports identified by the authors, 33 were sponsored by a pharmaceutical company. In 90.0% of the studies, the reported overall outcome was in favor of the sponsor's drug. This pattern resulted in contradictory conclusions across studies when the findings of studies of the same drugs but with different sponsors were compared. Potential sources of bias occurred in the areas of doses and dose escalation, study entry criteria and study populations, statistics and methods, and reporting of results and wording of findings.
                Some sources of bias may limit the validity of head-to-head comparison studies of second-generation antipsychotics. Because most of the sources of bias identified in this review were subtle rather than compelling, the clinical usefulness of future trials may benefit from minor modifications to help avoid bias. The authors make a number of concrete suggestions for ways in which potential sources of bias can be addressed by study initiators, peer reviewers of studies under consideration for publication, and readers of published studies. Financial and other competing interests have recently received increasing attention. In particular clinical research in plastic surgery attracts for-profit organizations, thus, explaining the increasing number of financial sponsorships. However, research articles often lack sufficient description of study design as well as disclosure of the source of funding. Furthermore, debate exists whether industry funding influences research findings and is leading to pro-industry results. A hand search was conducted identifying all randomized controlled (RCT) and controlled clinical trials (CCT) in 4 plastic surgery journals (Plastic and Reconstructive Surgery, British Journal of Plastic Surgery, Annals of Plastic Surgery, and Aesthetic Plastic Surgery) between 1990 and 2005. Subsequently, the influence of financial support on study outcome was analyzed. A total of 10,476 original articles were analyzed, resulting in the identification of 346 clinical trials which meet the Cochrane criteria for RCTs and CCTs. One hundred eighty-three trials and 163 studies were found to be RCTs and CCTs, respectively. Hereof, only 70 trials (20.2%) reported on grant support. Of these, 42 trials (60%) were supported by the industry. Depending on the topic addressed marked differences were detected regarding grant support. Studies with a focus on reconstructive plastic surgery were supported by the industry and by public institutions in almost equal shares (18 trials vs. 15 trials), whereas aesthetic surgical topics were predominantly funded by the industry (13 trials vs. 6 trials). Industry-funded trials reported more often statistically significant differences between treatment arms (28 trials vs. 16 trials). Authors' conclusions were found to be positively associated with financial competing interests. However, trial funding is rarely declared in the plastic surgery literature. Thus, the quality of reporting needs to be improved to be able to investigate these relationships in greater detail and draw more representative conclusions. Clinical trial registries are in widespread use to promote transparency around trials and their results.
                To describe characteristics of drug trials listed in ClinicalTrials.gov and examine whether the funding source of these trials is associated with favorable published outcomes.
                An observational study of safety and efficacy trials for anticholesteremics, antidepressants, antipsychotics, proton-pump inhibitors, and vasodilators conducted between 2000 and 2006.
                ClinicalTrials.gov, a Web-based registry of clinical trials launched in 1999.
                Publications resulting from the trials for the 5 drug categories of interest were identified, and data were abstracted on the trial record and publication, including timing of registration, elements of the study design, funding source, publication date, and study outcomes. Assessments were based on the primary funding categories of industry, government agencies, and nonprofit or nonfederal organizations.
                Among 546 drug trials, 346 (63%) were primarily funded by industry, 74 (14%) by government sources, and 126 (23%) by nonprofit or nonfederal organizations. Trials funded by industry were more likely to be phase 3 or 4 trials (88.7%; P < 0.001 across groups), to use an active comparator in controlled trials (36.8%; P = 0.010 across groups), to be multicenter (89.0%; P < 0.001 across groups), and to enroll more participants (median sample size, 306 participants; P < 0.001 across groups). Overall, 362 (66.3%) trials had published results. Industry-funded trials reported positive outcomes in 85.4% of publications, compared with 50.0% for government-funded trials and 71.9% for nonprofit or nonfederal organization-funded trials (P < 0.001). Trials funded by nonprofit or nonfederal sources with industry contributions were also more likely to report positive outcomes than those without industry funding (85.0% vs. 61.2%; P = 0.013). Rates of trial publication within 24 months of study completion ranged from 32.4% among industry-funded trials to 56.2% among nonprofit or nonfederal organization-funded trials without industry contributions (P = 0.005 across groups).
                The publication status of a trial could not always be confirmed, which could result in misclassification. Additional information on study protocols and comprehensive trial results were not available to further explore underlying factors for the association between funding source and outcome reporting.
                In this sample of registered drug trials, those funded by industry were less likely to be published within 2 years of study completion and were more likely to report positive outcomes than were trials funded by other sources.
                National Library of Medicine and National Institute of Child Health and Human Development, National Institutes of Health. To determine whether there is a difference in average statistical power between pharmacoepidemiologic studies of anti-retroviral adverse drug effects (ADEs) sponsored by for-profit versus non-profit organizations.
                We studied all published pharmacoepidemiologic studies of ADEs associated with the 15 anti-retroviral drugs approved through the end of 1999. A priori, the primary outcome was the power of each study to detect a clinically important difference in the risk for an adverse effect among patients exposed to the study drug(s). We could not evaluate this outcome because of the infrequent reporting of power calculations. We instead report the distribution of studies across a 5-tiered measure of adequacy of reporting of statistical power, as well as the sponsorship of these studies.
                Of 48 studies meeting our inclusion criteria, only 1 (2%) reported either a completed, a priori power calculation or sufficient details for readers to calculate the power to detect a pre-defined, clinically important effect. Thirty-five studies (73%) reported the minimum information required for sophisticated readers to determine the power to detect an event rate of interest to them; 6 additional studies (13%) reported confidence intervals around at least one summary effect measure and 6 (13%) provided no indication of power or uncertainty. Of the 41 studies for which sponsorship was determined, only 3 (7%) were sponsored by for-profit organizations.
                The poor reporting of statistical power in this sample suggests a need for guidelines to improve the reporting of pharmacoepidemiologic studies of ADEs. Future research is needed to determine whether the observed paucity of industry-sponsored observational studies of anti-retroviral ADEs extends to other clinical areas, and if so, to identify the causes of this phenomenon.
                Copyright 2004 John Wiley & Sons, Ltd. The purpose of this study was to assess the impact of sponsorship of a mailed satisfaction survey on response patterns and patient satisfaction ratings, and to establish whether satisfaction ratings depend on the timing of response. The study was part of a patient satisfaction survey conducted in a medical group practice in Geneva, Switzerland. All persons who had received an outpatient visit at the medical practice in the last week of September 1993 were assigned randomly to receiving the survey package either on university letterhead or on the medical practice letterhead. Participation rates were 80.5% and 80.4% in the two groups, respectively. The sponsorship of the survey had no detectable impact on response speed or response completeness. Six out of seven satisfaction scores were higher in the "medical practice" group, but the differences were not statistically significant. As data collection progressed, the cumulative satisfaction rating decreased gradually. This association was statistically significant but moderate. Whether a satisfaction survey is sponsored by a university or a health care provider does not seem to affect survey results. However, low survey response rates may moderately bias satisfaction estimates toward higher values. Prospectively planned collection and analysis of adverse event (AE) data are essential parts of well-conducted clinical trials. The AE data in a trial sponsor's database should be comparable with what is stipulated in the protocol and with the AE data published. We examined whether the published AE data differ from those in the sponsor's database and from the data collection requirements stated in study protocols.
                We searched the National Cancer Institute (NCI) Clinical Data Update System (CDUS) for studies that used the Common Toxicity Criteria version 2.0 and for which a final study publication was available. We extracted from the protocols information pertaining to AE collection and reporting methods and compared it with the methods cited in the article. We also compared the AE data in the trial publication with the AE data submitted by the investigators to CDUS.
                We identified 22 studies meeting the criteria for this review. There was considerable inconsistency between AE collection and reporting methods cited in the protocols versus final publications. AE data in the article and CDUS were not identical. Twenty-seven percent of article high-grade AEs could not be matched to agent-attributable AEs in the CDUS. Twenty-eight percent of CDUS high-grade AEs could not be matched to AEs in the corresponding article. In 14 of 22 articles, the number of high-grade AEs in CDUS differed from the number in the articles by 20% or more.
                Lack of consistency in and reporting of AEs are associated with NCI database and trial publication AE data discrepancy. Bias from funding sources of trials would threaten their validity. Meta-analyses of high quality acute pain and migraine trials were used to explore the hypothesis that industry funding of clinical trials produced more favourable results than non-profit sponsorship. Analyses were planned to evaluate whether industry-sponsored trials had different results from trials funded by academic or other non-profit sources, but of 176 trials, only two were supported by non-profit sources, while 31 provided no statement of support. An alternative method is proposed within industry-sponsored trials, looking at conflicting industry interests for the same drug, used either as test or comparator treatment. Fifty-three trials used an analgesic as test and 90 as comparator, allowing comparisons to be made for aspirin 600/650 mg, ibuprofen 400 mg, paracetamol (acetaminophen) 1000 mg, rofecoxib 50 mg and sumatriptan 50 and 100 mg. Only for sumatriptan 50 and 100 mg, with the outcome of headache response at 2 h, was there any significant difference between the drug used as a test or as a comparator. The direction was for higher (worse) NNTs with sumatriptan as comparator. Investigating potential industry bias through the funding source of trials is unlikely to be adequate because of a dearth of trials funded by non-profit organisations. We propose a method based on potential conflict of interest within industry-sponsored trials. Using this method, established clinical trial results in acute pain and migraine appear to be unbiased. Evidence regarding the safety profile of drugs may vary depending on study sponsorship. We aimed to evaluate differences between studies funded by the pharmaceutical manufacturer of the drug (PF) and those with no pharmaceutical funding (NoPF) regarding the finding and interpretation of adverse effects of inhaled corticosteroids.
                We assessed the safety reporting of inhaled corticosteroids in 275 PF and 229 NoPF studies identified by a MEDLINE search using prespecified criteria.
                Overall, the finding of statistically significant differences for adverse effects was significantly less frequent in PF (34.5%) than in NoPF (65.1%) studies (prevalence ratio, 0.53; 95% confidence interval, 0.44-0.64). This association became nonsignificant (prevalence ratio, 0.94; 95% confidence interval, 0.77-1.15) after controlling for design features (such as dose or use of parallel groups) that tended to be associated with less frequent finding of adverse effects and were more common in PF studies. Among studies finding a statistically significant increase in adverse effects associated with the study drug, the authors of PF articles concluded that the drug was "safe" more frequently than the authors of NoPF studies (prevalence ratio, 3.68; 95% confidence interval, 2.14-6.33).
                The type of funding may have determinant effects on the design of studies and on the interpretation of findings: funding by the industry is associated with design features less likely to lead to finding statistically significant adverse effects and with a more favorable clinical interpretation of such findings. Disclosure of conflicts of interest should be strengthened for a more balanced opinion on the safety of drugs. Prior studies implying associations between receipt of commercial funding and positive (significant and/or pro-industry) research outcomes have analyzed only published papers, which is an insufficiently robust approach for assessing publication bias. In this study, we tested the following hypotheses regarding orthopaedic manuscripts submitted for review: (1) nonscientific variables, including receipt of commercial funding, affect the likelihood that a peer-reviewed submission will conclude with a report of a positive study outcome, and (2) positive outcomes and other, nonscientific variables are associated with acceptance for publication.
                All manuscripts about hip or knee arthroplasty that were submitted to The Journal of Bone and Joint Surgery, American Volume, over seventeen months were evaluated to determine the study design, quality, and outcome. Analyses were carried out to identify associations between scientific factors (sample size, study quality, and level of evidence) and study outcome as well as between non-scientific factors (funding source and country of origin) and study outcome. Analyses were also performed to determine whether outcome, scientific factors, or nonscientific variables were associated with acceptance for publication.
                Two hundred and nine manuscripts were reviewed. Commercial funding was not found to be associated with a positive study outcome (p = 0.668). Studies with a positive outcome were no more likely to be published than were those with a negative outcome (p = 0.410). Studies with a negative outcome were of higher quality (p = 0.003) and included larger sample sizes (p = 0.05). Commercially funded (p = 0.027) and United States-based (p = 0.020) studies were more likely to be published, even though those studies were not associated with higher quality, larger sample sizes, or lower levels of evidence (p = 0.24 to 0.79).
                Commercially funded studies submitted for review were not more likely to conclude with a positive outcome than were nonfunded studies, and studies with a positive outcome were no more likely to be published than were studies with a negative outcome. These findings contradict those of most previous analyses of published (rather than submitted) research. Commercial funding and the country of origin predict publication following peer review beyond what would be expected on the basis of study quality. Studies with a negative outcome, although seemingly superior in quality, fared no better than studies with a positive outcome in the peer-review process; this may result in inflation of apparent treatment effects when the published literature is subjected to meta-analysis. In surveys based on data available prior to 2000, clinical trials funded by for-profit organizations appeared more likely to report positive findings than those funded by not-for-profit organizations. Whether this situation has changed over the past 5 years or whether similar effects are present among jointly funded trials is unknown.
                To determine in contemporary randomized cardiovascular trials the association between funding source and the likelihood of reporting positive findings.
                We reviewed 324 consecutive superiority trials of cardiovascular medicine published between January 1, 2000, and July 30, 2005, in JAMA, The Lancet, and the New England Journal of Medicine.
                The proportion of trials favoring newer treatments over the standard of care was evaluated by funding source.
                Of the 324 superiority trials, 21 cited no funding source. Of the 104 trials funded solely by not-for-profit organizations, 51 (49%) reported evidence significantly favoring newer treatments over the standard of care, whereas 53 (51%) did not (P = .80). By contrast, 92 (67.2%) of 137 trials funded solely by for-profit organizations favored newer treatments over standard of care (P<.001). Among 62 jointly funded trials, 35 (56.5%), an intermediate proportion, favored newer treatments. For 205 randomized trials evaluating drugs, the proportions favoring newer treatments were 39.5%, not-for-profit; 54.4%, jointly funded; and 65.5%, for-profit trials (P for trend across groups = .002). For the 39 randomized trials evaluating cardiovascular devices, the proportions favoring newer treatments were 50.0%, not-for-profit; 69.2%, jointly funded; and 82.4%, for-profit trials (P for trend across groups = .07). Regardless of funding source, trials using surrogate end points, such as quantitative angiography, intravascular ultrasound, plasma biomarkers, and functional measures were more likely to report positive findings (67%) than trials using clinical end points (54.1%; P = .02).
                Recent cardiovascular trials funded by for-profit organizations are more likely to report positive findings than trials funded by not-for-profit organizations, as are trials using surrogate rather than clinical end points. Trials jointly funded by not-for-profit and for-profit organizations appear to report positive findings at a rate approximately midway between rates observed in trials supported solely by one or the other of these entities. The goal was to assess the risk of bias among pediatric, randomized, controlled trials (RCTs) reported in 8 high-impact journals.
                We searched PubMed for all pediatric RCTs reported between July 1, 2007, and June 30, 2008, in 8 journals with high impact factors. Using Cochrane Collaboration methods for risk assessment, we evaluated all reports for risk of bias according to domain (ie, randomized sequence generation, allocation concealment, masking, incomplete outcome data, selective outcome reporting, and other). We used multiple logistic regression to test for associations between the presence of a high risk of bias according to domain and funding source, intervention type, trial registration, and multicenter status.
                Industry-funded RCTs were more likely to show a high risk of bias for sequence generation, compared with government-funded RCTs (adjusted odds ratio [aOR]: 6.1 [95% confidence interval [CI]: 1.70- 21.89]), and behavioral/educational trials were more likely to show a high risk of bias for sequence generation (aOR: 2.8 [95% CI: 1.06-7.36]) and allocation concealment (aOR: 4.09 [95% CI: 1.69-9.90]), compared with drug trials. Registered trials were less likely to have a high risk of bias for sequence generation, compared with nonregistered trials (aOR: 0.33 [95% CI: 0.15-0.71]).
                Overall, we found a large proportion of pediatric RCT reports with a high risk of bias for sequence generation and allocation concealment. Factors associated with a high risk of bias included industry funding and assessment of behavioral/educational interventions, whereas trial registration was associated with a lower risk of bias. Registration of clinical trials has been introduced largely to reduce bias toward statistically significant results in the trial literature. Doubts remain about whether advance registration alone is an adequate measure to reduce selective publication, selective outcome reporting, and biased design. One of the first areas of medicine in which registration was widely adopted was oncology, although the bulk of registered oncology trials remain unpublished. The net influence of registration on the literature remains untested. This study compares the prevalence of favorable results and conclusions among published reports of registered and unregistered randomized controlled trials of new oncology drugs.
                We conducted a cross-sectional study of published original research articles reporting clinical trials evaluating the efficacy of drugs newly approved for antimalignancy indications by the United States Food and Drug Administration (FDA) from 2000 through 2005. Drugs receiving first-time approval for indications in oncology were identified using the FDA web site and Thomson Centerwatch. Relevant trial reports were identified using PubMed and the Cochrane Library. Evidence of advance trial registration was obtained by a search of clinicaltrials.gov, WHO, ISRCTN, NCI-PDQ trial databases and corporate trial registries, as well as articles themselves. Data on blinding, results for primary outcomes, and author conclusions were extracted independently by two coders. Univariate and multivariate logistic regression identified associations between favorable results and conclusions and independent variables including advance registration, study design characteristics, and industry sponsorship.
                Of 137 original research reports from 115 distinct randomized trials assessing 25 newly approved drugs for treating cancer, the 54 publications describing data from trials registered prior to publication were as likely to report statistically significant efficacy results and reach conclusions favoring the test drug (for results, OR = 1.77; 95% CI = 0.87 to 3.61) as reports of trials not registered in advance. In multivariate analysis, reports of prior registered trials were again as likely to favor the test drug (OR = 1.29; 95% CI = 0.54 to 3.08); large sample sizes and surrogate outcome measures were statistically significant predictors of favorable efficacy results at p < 0.05. Subgroup analysis of the main reports from each trial (n = 115) similarly indicated that registered trials were as likely to report results favoring the test drug as trials not registered in advance (OR = 1.11; 95% CI = 0.44 to 2.80), and also that large trials and trials with nonstringent blinding were significantly more likely to report results favoring the test drug.
                Trial registration alone, without a requirement for full reporting of research results, does not appear to reduce a bias toward results and conclusions favoring new drugs in the clinical trials literature. Our findings support the inclusion of full results reporting in trial registers, as well as protocols to allow assessment of whether results have been completely reported. There has been increasing concern regarding the potential effects of the commercialization of research.
                In order to examine the relationships between funding source, trial outcome and reporting quality, recent issues of five peer-reviewed, high impact factor, general medical journals were hand-searched to identify a sample of 100 randomized controlled trials (20 trials/journal). Relevant data, including funding source (industry/not-for-profit/mixed/not reported) and statistical significance of primary outcome (favouring new treatment/favouring conventional treatment/neutral/unclear), were abstracted. Quality scores were assigned using the Jadad scale and the adequacy of allocation concealment.
                Sixty-six percent of trials received some industry funding. Trial outcome was not associated with funding source (p=.461). There was a preponderance of favourable statistical conclusions among published trials with 67% reporting results that favored a new treatment whereas 6% favoured the conventional treatment. Quality scores were not associated with funding source or trial outcome.
                It is not known whether the absence of significant associations between funding source, trial outcome and reporting quality reflects a true absence of an association or is an artefact of inadequate statistical power, reliance on voluntary disclosure of funding information, a focus on trials recently published in the top medical journals, or some combination thereof. Continued and expanded monitoring of potential conflicts is recommended, particularly in light of new guidelines for disclosure that have been endorsed by the ICMJE. To determine the extent to which publication is influenced by study outcome.
                A cohort of studies submitted to a hospital ethics committee over 10 years were examined retrospectively by reviewing the protocols and by questionnaire. The primary method of analysis was Cox's proportional hazards model.
                University hospital, Sydney, Australia.
                748 eligible studies submitted to Royal Prince Alfred Hospital Ethics Committee between 1979 and 1988.
                Time to publication.
                Response to the questionnaire was received for 520 (70%) of the eligible studies. Of the 218 studies analysed with tests of significance, those with positive results (P < 0.05) were much more likely to be published than those with negative results (P > or = 0.10) (hazard ratio 2.32 (95% confidence interval 1.47 to 3.66), P = 0.0003), with a significantly shorter time to publication (median 4.8 v 8.0 years). This finding was even stronger for the group of 130 clinical trials (hazard ratio 3.13 (1.76 to 5.58). P = 0.0001), with median times to publication of 4.7 and 8.0 years respectively. These results were not materially changed after adjusting for other significant predictors of publication. Studies with indefinite conclusions (0.05 < or = P < 0.10) tended to have an even lower publication rate and longer time to publication than studies with negative results (hazard ratio 0.39 (0.13 to 1.12), P = 0.08). For the 103 studies in which outcome was rated qualitatively, there was no clear cut evidence of publication bias, although the number of studies in this group was not large.
                This study confirms the evidence of publication bias found in other studies and identifies delay in publication as an additional important factor. The study results support the need for prospective registration of trials to avoid publication bias and also support restricting the selection of trials to those started before a common date in undertaking systematic reviews. To assess whether source of funding affected the results of trials of nicotine replacement therapy (NRT) for smoking cessation.
                We reviewed all randomized controlled trials included in the Cochrane review. There were insufficient non-industry trials of the newer products for these to be included. We included 90 trials of either the nicotine gum (52) or nicotine patch (38). They comprised 18 238 treatment and 16 235 control participants. Forty-nine showed evidence of industry support (18 gum, 31 patch).
                Industry (31 of 49, 63%) compared with non-industry (seven of 41, 17%, P < 0.001) supported a higher proportion of nicotine patch studies and had larger sample sizes (479 versus 268, P = 0.04). Twenty-five (51%) industry trials reported statistically significant (P < 0.05) results, compared with nine (22%) non-industry trials (OR = 3.70, 95% CI = 1.46-9.35). This difference was not explained by trial characteristics. Industry-supported trials had a pooled odds ratio of 1.90 (1.67-2.16), compared with 1.61 (1.43-1.80) for other studies (chi(2) = 3.6, P = 0.058). There was evidence of funnel-plot asymmetry among industry trials (t = 4.35, P < 0.001), but not among other trials, indicating that several small null-effect industry trials may not have reached publication. After imputation adjustment, the odds ratio for industry trials reduced to 1.64 (1.43-1.89) and the overall NRT odds ratio reduced from 1.73 (1.60-1.90) to 1.62 (1.49-1.77).
                Compared with independent trials, industry-supported trials were more likely to produce statistically significant results and larger odds ratios. These differences persisted after adjustment for basic trial characteristics. Although we had no data on the amount of funding for each trial, it is possible that more resources led to higher treatment compliance and therefore greater efficacy in industry-supported trials. Differences can also possibly be explained by publication bias with several small, null-effect industry studies not having reached publication. After adjustment for this possible bias, results for industry trials were lower and similar to non-industry results. Similarly, the overall estimate of the net effect for these products reduces to about 5% attributable 1-year successes. This remains of considerable public health benefit. Registration of clinical trials has become mandatory in many countries since most of the trials considered here were conducted, and this should reduce the potential for publication bias in future. Free papers presented to the Annual Scientific Congress (ASC) of the Royal Australasian College of Surgeons (RACS) were reviewed for the years 1994, 1995 and 1996. Reports were examined for evidence of publication bias.
                Suitable free papers were identified from the proceedings of the meetings and authors were contacted to obtain information about the research reported and any publications resulting from it.
                Responses were obtained from 302 of 576 presentations considered suitable. A total of 55% of responding authors reported publication of their paper. Basic science papers were most likely to be published. There was a significant bias in favour of publication of positive results (98 of 139 positive vs 76 of 159 inconclusive or negative reports; P < 0.01). Retrospective data were as likely to be published as prospective (51% and 57%, respectively). Reports describing studies of high-level evidence were more likely to be published in journals with a high impact factor.
                The ASC is a comprehensive meeting that attracts a wide range of free papers from most sections of the RACS. There appears to be no evidence of bias in selection of papers for inclusion in the meeting but there is bias in the subsequent publication, which favours positive reports. Not all clinical trials are published, which may distort the evidence that is available in the literature. We studied the publication rate of a cohort of clinical trials and identified factors associated with publication and nonpublication of results.
                We analysed the protocols of randomized clinical trials of drug interventions submitted to the research ethics committee of University Hospital (Inselspital) Bern, Switzerland from 1988 to 1998. We identified full articles published up to 2006 by searching the Cochrane CENTRAL database (issue 02/2006) and by contacting investigators. We analyzed factors associated with the publication of trials using descriptive statistics and logistic regression models.
                451 study protocols and 375 corresponding articles were analyzed. 233 protocols resulted in at least one publication, a publication rate of 52%. A total of 366 (81%) trials were commercially funded, 47 (10%) had non-commercial funding. 346 trials (77%) were multi-centre studies and 272 of these (79%) were international collaborations. In the adjusted logistic regression model non-commercial funding (Odds Ratio [OR] 2.42, 95% CI 1.14-5.17), multi-centre status (OR 2.09, 95% CI 1.03-4.24), international collaboration (OR 1.87, 95% CI 0.99-3.55) and a sample size above the median of 236 participants (OR 2.04, 95% CI 1.23-3.39) were associated with full publication.
                In this cohort of applications to an ethics committee in Switzerland, only about half of clinical drug trials were published. Large multi-centre trials with non-commercial funding were more likely to be published than other trials, but most trials were funded by industry. When a sponsor funds a study of two competing drugs in a head-to-head comparison, the results and conclusions are likely to favor the sponsor's drug. Thiazolidinediones, oral medications used for the treatment of type 2 diabetes, are one of the most costly choices of oral anti-diabetic medications, yet they do not demonstrate clinically relevant differences in achieving lower glycosylated hemoglobin levels compared to other oral antidiabetic drugs. Our aim is to examine associations between research funding source, study design characteristics aimed at reducing bias, and other factors with the results and conclusions of randomized controlled trials (RCTs) of thiazolidinediones compared to other oral hypoglycemic agents.
                This is a cross-sectional study of 61 published RCTs comparing a thiazolidinedione (glitazone) to another anti-diabetic drug or placebo for treatment of type 2 diabetes. Data on study design characteristics, funding source, author's financial ties, results for primary outcomes, and author conclusions were extracted. Univariate logistic regression identified associations between independent variables and results and conclusions that favored the glitazone. Of the RCTs, 59% (36/61) were funded by industry, 39% (24/61) did not disclose any funding. Common study design weaknesses included inadequate blinding and lack of concealment of allocation. Trials that reported favorable glycemic control results for the glitazone were more likely to have adequate blinding (OR (95% CI) = 5.42 (1.46, 21.19), p = 0.008) and have a corresponding author with financial ties to the glitazone manufacturer (OR (95% CI) = 4.12 (1.05, 19.53); p = 0.04). Trials with conclusions favoring the glitazone were less likely to be funded by a comparator drug company than a glitazone company (OR (95% CI) = 0.026 (0, 0.40), p = 0.003) and less likely to be published in journals with higher impact factors (OR (95% CI) = 0.79 (0.62, 0.97), p = 0.011). One limitation of our study is that we categorized studies as funded by industry based on each article's disclosure which could underestimate the number of industry sponsored studies and personal ties of investigators. Additionally, our study did not include any head-to-head comparisons of one glitazone to another.
                Published RCT comparisons of glitazones with other anti-diabetic drugs or placebo are predominantly industry supported and this support, as well as the financial ties of study authors, appears to be associated with favorable findings. This study was conducted to evaluate willingness to prescribe medication based on identical data presented in different outcome terms to health professionals of varied discipline, geographic location, and level of training. Cross-sectional survey using a self-administered questionnaire was performed in 400 health professionals (physicians, pharmacists, physicians-in-training, and pharmacy students) in the United States and Europe. Data reflecting a clinical trial were presented in 6 outcome terms: 3 terms describing identical mortality (relative risk reduction, absolute risk reduction, and number of patients needed to be treated to prevent 1 death); and 3 distractors (increased life expectancy, decreased hospitalization rate, and decreased cost). Willingness to prescribe and rank order of medication preference assuming willingness to prescribe were measured. The results of the study showed that willingness to prescribe and first choice preference were significantly greater when study results were presented as relative risk reduction than when identical mortality data were presented as absolute risk reduction or number of patients needed to be treated to avoid 1 death (p <0.001). Increase in life expectancy was the most influential distractor. In conclusion, this study, performed in the era of "evidence-based medicine," demonstrates that the method of reporting research trial results has significant influence on health professionals' willingness to prescribe. The high numerical value of relative risk reduction and the concrete and tangible quality of increased life expectancy exert greater influence on health professionals than other standard outcome terms. To explore the relation between study concordance, take home message, funding, and dissemination of comparative studies assessing the effects of influenza vaccines.
                Systematic review without meta-analysis.
                Search of the Cochrane Library, PubMed, Embase, and the web, without language restriction, for any studies comparing the effects of influenza vaccines against placebo or no intervention. Abstraction and assessment of quality of methods were carried out.
                We identified 259 primary studies (274 datasets). Higher quality studies were significantly more likely to show concordance between data presented and conclusions (odds ratio 16.35, 95% confidence interval 4.24 to 63.04) and less likely to favour effectiveness of vaccines (0.04, 0.02 to 0.09). Government funded studies were less likely to have conclusions favouring the vaccines (0.45, 0.26 to 0.90). A higher mean journal impact factor was associated with complete or partial industry funding compared with government or private funding and no funding (differences between means 5.04). Study size was not associated with concordance, content of take home message, funding, and study quality. Higher citation index factor was associated with partial or complete industry funding. This was sensitive to the exclusion from the analysis of studies with undeclared funding.
                Publication in prestigious journals is associated with partial or total industry funding, and this association is not explained by study quality or size. To study the relation between reported drug performance in published trials and support of the trials by the manufacturer of the drug under evaluation, we studied a sample of trials of nonsteroidal anti-inflammatory drugs (NSAIDs) used in the treatment of arthritis.
                All randomized control trials of NSAIDs published between September 1987 and May 1990 identified by MEDLINE were reviewed. If an article met the following criteria (n = 61), it was selected: trials involving adult patients with osteoarthritis or rheumatoid arthritis (n = 180), use of nonsalicylate NSAIDs marketed in the United States (n = 101), randomized control trial (n = 81), duration of the trial 4 or more days (n = 78), and use of an efficacy outcome measure (n = 61). Reviewers, "blinded" to manufacturer status, evaluated the narrative interpretation of results and extracted numeric data on efficacy and toxicity. Manufacturer-associated trials were defined as those that acknowledged an association with a pharmaceutical manufacturer. Because of the scarcity of non-manufacturer-associated trials (n = 9), we report only on the manufacturer-associated articles.
                Fifty-two publications (85.2%) representing 56 trials were associated with a manufacturer. The manufacturer-associated drug was reported as comparable with (71.4%) or superior to (28.6%) the comparison drug in all 56 trials. These narrative claims of superiority were usually justified with trial data. Of the trials identifying one drug as less toxic (n = 22), the manufacturer-associated drug's safety was reported as superior to the comparison drug in 86.4% of cases. Justification for the narrative interpretation of the trial findings regarding less toxicity was provided in only 12 (54.5%) of 22 trials.
                The manufacturer-associated NSAID is almost always reported as being equal or superior in efficacy and toxicity to the comparison drug. These claims of superiority, especially in regard to side effect profiles, are often not supported by trial data. These data raise concerns about selective publication or biased interpretation of results in manufacturer-associated trials. To evaluate the effect of a publicly sponsored drug-free workplace program on reducing the risk of occupational injuries.
                Workers' compensation claims data from the Washington State Department of Labor and Industries covering the period 1994 through 2000 and work-hours data reported by employers served as the data sources for the analysis.
                We used a pre-post design with a nonequivalent comparison group to assess the impact of the intervention on injury risk, measured in terms of differences in injury incidence rates. Two hundred and sixty-one companies that enrolled in the drug-free workplace program during the latter half of 1996 were compared with approximately 20,500 nonintervention companies. We tested autoregressive, integrated moving-average (ARIMA) models to assess the robustness of our findings.
                The drug-free workplace intervention was associated (p < .05) with a statistically significant decrease in injury rates for three industry groups: construction, manufacturing, and services. It was associated (p < .05) with a reduction in the incidence rate of more serious injuries involving four or more days of lost work time for two industry groups: construction and services. The ARIMA analysis supported
                The drug-free workplace program we studied was associated with a selective, industry-specific preventive effect. The strongest evidence of an intervention effect was for the construction industry. Estimated net cost savings for this industry were positive though small in magnitude. The randomized controlled trial (RCT) is the gold standard for establishing new therapies in clinical oncology. Here we document changes with time in design, sponsorship, and outcomes of oncology RCTs.
                Reports of RCTs evaluating systemic therapy for breast, colorectal (CRC), and non-small-cell lung cancer (NSCLC) published 1975 to 2004 in six major journals were reviewed. Two authors abstracted data regarding trial design, results, and conclusions. Conclusions of authors were graded using a 7-point Likert scale. For each study the effect size for the primary end point was converted to a summary measure.
                A total of 321 eligible RCTs were included (48% breast, 24% CRC, 28% NSCLC). Over time, the number and size of RCTs increased considerably. For-profit/mixed sponsorship increased substantially during the study period (4% to 57%; P < .001). There was increasing use of time-to-event measures (39% to 78%) and decreasing use of response rate (54% to 14%) as primary end point (P < .001). Effect size remained stable over the study period. Authors have become more likely to strongly endorse the experimental arm (P = .017). A significant P value for the primary end point and industry sponsorship were each independently associated with endorsement of the experimental agent (odds ratio [OR] = 19.6, 95% CI, 8.9 to 43.1, and OR = 3.5, 95% CI, 1.6 to 7.5, respectively).
                RCTs in oncology have become larger and are more likely to be sponsored by industry. Authors of modern RCTs are more likely to strongly endorse novel therapies. For-profit sponsorship and statistically significant results are independently associated with endorsement of the experimental arm. To assess the association between competing interests and authors' conclusions in randomised clinical trials.
                Epidemiological study of randomised clinical trials published in the BMJ from January 1997 to June 2001. Financial competing interests were defined as funding by for profit organisations and other competing interests as personal, academic, or political. Studies: 159 trials from 12 medical specialties.
                Authors' conclusions defined as interpretation of extent to which overall results favoured experimental intervention. Conclusions appraised on 6 point scale; higher scores favour experimental intervention.
                Authors' conclusions were significantly more positive towards the experimental intervention in trials funded by for profit organisations alone compared with trials without competing interests (mean difference 0.48 (SE 0.13), P=0.014), trials funded by both for profit and non-profit organisations (0.30 (SE 0.10), P=0.003), and trials with other competing interests (0.45 (SE 0.13), P=0.006). Other competing interests and funding from both for profit and non-profit organisations were not significantly associated with authors' conclusions. The association between financial competing interests and authors' conclusions was not explained by methodological quality, statistical power, type of experimental intervention (pharmacological or non-pharmacological), type of control intervention (for example, placebo or active drug), or medical specialty.
                Authors' conclusions in randomised clinical trials significantly favoured experimental interventions if financial competing interests were declared. Other competing interests were not significantly associated with authors' conclusions. The primary aim of the present study was to identify possible occurrence of selective reporting of the results of clinical trials to the Finnish National Agency for Medicines. Selective reporting may lead to poorly informed action or inaction by regulatory authorities.
                In 1987, 274 clinical drug trials were notified to the Finnish National Agency for Medicines. By December 1993, final reports had been received from 68 of these trials and statements that the trial had been suspended from 24 trials. The sponsors of the non-reported trials were requested to report the outcome. The outcomes, if any, of all reported and non-reported trials were classified as positive, inconclusive or negative.
                The total number of trials with positive, inconclusive or negative outcome were 111, 33 and 44, respectively; the outcomes of 86 trials could not be assessed. Final reports were received from 42/111 (38%) trials with positive, 6/33 (18%) with inconclusive and 9/44 (20%) with negative outcomes.
                Substantial evidence of selective reporting was detected, since trials with positive outcome resulted more often in submission of final report to regulatory authority than those with inconclusive or negative outcomes. Improving precision and economy in the prescribing of drugs is a goal whose importance has increased with the proliferation of new and potent agents and with growing economic pressures to contain health-care costs. We implemented an office-based physician education program to reduce the excessive use of three drug groups: cerebral and peripheral vasodilators, an oral cephalosporin, and propoxyphene. A four-state sample of 435 prescribers of these drugs was identified through Medicaid records and randomly assigned to one of three groups. Physicians who were offered personal educational visits by clinical pharmacists along with a series of mailed "unadvertisements" reduced their prescribing of the target drugs by 14 per cent as compared with controls (P = 0.0001). A comparable reduction in the number of dollars reimbursed for these drugs was also seen between the two groups, resulting in substantial cost savings. No such change was seen in physicians who received mailed print materials only. The effect persisted for at least nine months after the start of the intervention, and no significant increase in the use of expensive substitute drugs was found. Academically based "detailing" may represent a useful and cost-effective way to improve the quality of drug-therapy decisions and reduce unnecessary expenditures.
Sponsorship of drug and device studies by the manufacturing company leads to more favorable results and conclusions than sponsorship by other sources. Our analyses suggest the existence of an industry bias that cannot be explained by standard 'Risk of bias' assessments.