Factors Associated with Findings of Published Trials of Drug–Drug Comparisons: Why Some Statins Appear More Efficacious than Others

Leiden University, Leyden, South Holland, Netherlands
PLoS Medicine (Impact Factor: 14.43). 06/2007; 4(6):e184. DOI: 10.1371/journal.pmed.0040184
Source: PubMed


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.

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    • "El 96% de los autores que apoyaban los bloqueadores de los canales de calcio tenían relaciones económicas con los productores de estos fármacos, comparado con el 60% de los autores que se mostraban " neutrales " y el 37% de los que se mostraban críticos. Con posterioridad, han sido numerosos los estudios que han documentado una asociación entre conflictos de interés y conclusiones " pro-industria " , especialmente en ensayos clínicos aleatorizados (Yaphe y otros, 2001; Kjaergard y Als-Nielsen, 2002; Als- Nielsen y otros, 2003; Montgomery y otros, 2004; 3 Perlis y otros, 2005; Ridker y Torres, 2006; Etter y otros, 2007; Peppercorn y otros, 2007; Tungaraza y Poole, 2007; Bero y otros, 2007). "
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    ABSTRACT: Resumen: Los vínculos profesionales y financieros entre la industria farmacéutica y las personas e instituciones que llevan a cabo investigación, formación y práctica médicas pueden provocar que intereses individuales o corporativos influyan en la toma de decisiones y en el juicio profesional. Esta situación de posible conflicto de intereses amenaza la integridad de la investigación, la objetividad de la educación médica, la calidad de la atención al paciente y, de forma más general, la confianza pública en la medicina. Una estrategia para proteger la integridad de la investigación y mantener la confianza pública es la comunicación de los posibles conflictos de interés de los autores cuando publican los resultados en las revistas científicas. El presente trabajo analiza las políticas editoriales de declaración de conflictos de interés de las 16 revistas de orientación clínica publicadas en España incluidas en el JCR del año 2011. Los resultados ponen de manifiesto que la mayoría de revistas incluyen en sus instrucciones para autores al menos una mención a la necesidad de declarar los conflictos de interés y ofrecen algún tipo de descripción de estas situaciones, si bien se trata de definiciones laxas sobre las relaciones económicas que se deben declarar, y sin que especifiquen el alcance de las relaciones personales. En la mayor parte de los casos no existen formularios estándar de declaración de conflictos de interés, no se determina el tiempo durante el que puede considerarse que una relación es susceptible de generarlo, no se indica quién y cómo evaluará las declaraciones, ni se indica si las declaraciones se publicarán en los artículos. Palabras clave: Biomedicina; conflictos de interés; industria farmacéutica; políticas editoriales; revistas clínicas. Conflict of interest disclosure policies in clinically oriented Spanish biomedical journals Abstract: Professional and financial ties between the pharmaceutical industry and persons and institutions carrying out research, conducting medical training, and practicing medicine can lead to individual or corporate interests influencing decision-making and professional judgment. These conflicts of interest threaten the integrity of research, the objectivity of medical education, the quality of patient care and, more generally, public confidence in medicine. A strategy to protect research integrity and maintain public trust is for authors to communicate their possible conflicts of interest in the studies they publish. This paper analyses the editorial policies of the 16 clinically oriented biomedical journals published in Spain that were included in the JCR in 2011, in relation to authors' conflict of interest declarations. Results show that, in their instructions to authors, most journals mention the need to disclose possible conflicts of interest and offer some sort of description of such situations. However, the definitions are lax concerning which economic relations should be declared and do not specify the extent of personal relationships. In most cases there is no standard form for declaring conflicts of interest; there is no indication of the period of time during which a relationship can be considered likely to generate a conflict; there is no indication of who will evaluate these statements and how they will be evaluated; and there is no indication as to whether these statements will be published in the articles.
    Revista española de Documentación Científica 09/2015; 38(3):e091. DOI:10.3989/redc.2015.3.1231 · 0.57 Impact Factor
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    • "For example, the so-called “publication bias” against untraceable or unpublished papers with non-significant or unfavourable results could be present in some CEA research [6]. Another source of sponsorship bias could be that dragged from efficacy studies, which was shown by Bero and colleagues [8], who reported in a cross-sectional study of 192 randomized trials that comparative trials of statins were more likely to report outcomes favouring the sponsor’s statin compared to the comparator drug. "
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    ABSTRACT: We examined sponsorship of published cost-effectiveness analyses of statin use for cardiovascular (CV) prevention, and determined whether the funding source is associated with study conclusions. We searched PubMed/MEDLINE (up to June 2011) to identify cost-effectiveness analyses of statin use for CV prevention reporting outcomes as incremental costs per quality-adjusted life years (QALY) and/or life years gained (LYG). We examined relationships between the funding source and the study conclusions by means of tests of differences between proportions. Seventy-five studies were included. Forty-eight studies (64.0%) were industry-sponsored. Fifty-two (69.3%) articles compared statins versus non-active alternatives. Secondary CV prevention represented 42.7% of articles, followed by primary CV prevention (38.7%) and both (18.7%). Overall, industry-sponsored studies were much less likely to report unfavourable or neutral conclusions (0% versus 37.1%; p<0.001). For primary CV prevention, the proportion with unfavourable or neutral conclusions was 0% for industry-sponsored studies versus 57.9% for non-sponsored studies (p<0.001). Conversely, no statistically significant differences were identified for studies evaluating secondary CV prevention (0% versus 12.5%; p=0.222). Incremental costs per QALY/LYG estimates reported in industry-sponsored studies were generally more likely to fall below a hypothetical willingness-to-pay threshold of US $50,000. Our systematic analysis suggests that pharmaceutical industry sponsored economic evaluations of statins have generally favored the cost-effectiveness profile of their products particularly in primary CV prevention.
    PLoS ONE 07/2013; 8(7):e69462. DOI:10.1371/journal.pone.0069462 · 3.23 Impact Factor
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    • "This created an important precedent, as everyone can now obtain such access in accordance with the principles on which the EU is founded. Other drug agencies should follow suit, as the traditional secrecy is not in the patients’ interest and cannot be defended ethically [25]. "
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    ABSTRACT: Background Authors of systematic reviews have difficulty obtaining unpublished data for their reviews. This project aimed to provide an in-depth description of the experiences of authors in searching for and gaining access to unpublished data for their systematic reviews, and to give guidance on best practices for identifying, obtaining and using unpublished data. Methods This is a qualitative study analyzing in-depth interviews with authors of systematic reviews who have published Cochrane reviews or published systematic reviews outside of The Cochrane Library. We included participants who 1) were the first or senior author of a published systematic review of a drug intervention, 2) had expertise in conducting systematic reviews, searching for data, and assessing methodological biases, and 3) were able to participate in an interview in English. We used non-random sampling techniques to identify potential participants. Eighteen Cochrane authors were contacted and 16 agreed to be interviewed (89% response rate). Twenty-four non-Cochrane authors were contacted and 16 were interviewed (67% response rate). Results Respondents had different understandings of what was meant by unpublished data, including specific outcomes and methodological details. Contacting study authors was the most common method used to obtain unpublished data and the value of regulatory agencies as a data source was underappreciated. Using the data obtained was time consuming and labor intensive. Respondents described the collaboration with other colleagues and/or students required to organize, manage and use the data in their reviews, generally developing and using templates, spreadsheets and computer programs for data extraction and analysis. Respondents had a shared belief that data should be accessible but some had concerns about sharing their own data. Respondents believed that obtaining unpublished data for reviews has important public health implications. There was widespread support for government intervention to ensure open access to trial data. Conclusions Respondents uniformly agreed that the benefit of identifying unpublished data was worth the effort and was necessary to identify the true harms and benefits of drugs. Recent actions by government, such as increased availability of trial data from the European Medicines Agency, may make it easier to acquire critical drug trial data.
    Systematic Reviews 05/2013; 2(1):31. DOI:10.1186/2046-4053-2-31
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