Menu
Search BMJ Group Search BMJ Group Journals Jobs Education Decision support Quality improvement Community BMJ Group
From trainee to consultant, BMJ Group offers doctors around the world tailored information, special events, learning resources and recruitment services at every step along their career path.
... by doctors, for doctors, for patients About BMJ Group Customer Service Subscriptions & Sales Working for BMJ Group BMJ Media Centre BMJ Group Awards Advertising & Sponsorship Rights & Licensing Affinity & Society Publishing Online learning BMJ Learning High-quality CME / CPD for doctors and other healthcare professionals. BMJ Learning features hundreds of accredited, peer-reviewed learning modules in text, video, and audio formats. Find out more Courses and Qualifications BMJ Masterclasses BMJ Masterclasses, led by experts, help clinicians to use the latest evidence and recent guidelines in practice and meet their CPD/CME requirements. Find out more Exam Preparation 
The leading provider of online exam preparation, helping over 167,000 healthcare professionals to pass their exams. Find out more BMJ Learning BMJ Portfolio BMJ Masterclasses Clinical Leadership Programme Diabetes Qualifications and Courses onExamination Decision support and clinical reference BMJ Evidence Centre The BMJ Evidence Centre builds evidence into practice, to support improvements in the consistency and quality of health care.
Best Practice Clinical Evidence Evidence Updates Best Health Action Sets
Informatica Systems Informatica Systems delivers performance management systems and innovative software solutions to primary care. Learn more Audit + Contract + Health Checks FrontDesk BMJ Quality 
The latest news, research, events, opinion and guidance related to quality and safety in health care.
The 2013 event will take place in London from 16th- 19th April 2013. Find out more BMJ Quality BMJ Quality and Safety International Forum on Quality and Safety in Healthcare BMJ The flagship general medical journal, published since 1840, updated daily online, weekly in print and on the iPad.
BMJBMJ Journals BMJ Journals division publishes over 40 journals across a broad range of specialties.
BMJ JournalsstudentBMJ An international medical journal written for students by students.
Student BMJ JobsBMJ Careers BMJ Careers makes it easy for you to find the right job with the latest healthcare vacancies, upcoming careers fairs, advice on choosing the right specialty, pay and working conditions.
19-20 October 2012 at the Business Design Centre in Islington, London. Register here BMJ Careers Jobs and vacancies at BMJ Group BMJ Careers Fair Community 
Join the discussions on our community site doc2doc or our social pages
... by doctors, for doctors, for patientsWe are open for entries! doc2doc Follow BMJ Group on Twitter BMJ Group on Facebook BMJ Group Awards Subscribe My account
Update my details
Manage my emails
BMA Members Sign in Username: * Password: * Forgot your sign in details?BMA membersAthens or your organisation BMJ Helping doctors make better decisions Search bmj.com: Advanced search Home Research Education News Comment Multimedia Specialties Archive Search all BMJ research articles: From18401841184218431844184518461847184818491850185118521853185418551856185718581859186018611862186318641865186618671868186918701871187218731874187518761877187818791880188118821883188418851886188718881889189018911892189318941895189618971898189919001901190219031904190519061907190819091910191119121913191419151916191719181919192019211922192319241925192619271928192919301931193219331934193519361937193819391940194119421943194419451946194719481949195019511952195319541955195619571958195919601961196219631964196519661967196819691970197119721973197419751976197719781979198019811982198319841985198619871988198919901991199219931994199519961997199819992000200120022003200420052006200720082009201020112012JanFebMarAprMayJunJulAugSepOctNovDec To18401841184218431844184518461847184818491850185118521853185418551856185718581859186018611862186318641865186618671868186918701871187218731874187518761877187818791880188118821883188418851886188718881889189018911892189318941895189618971898189919001901190219031904190519061907190819091910191119121913191419151916191719181919192019211922192319241925192619271928192919301931193219331934193519361937193819391940194119421943194419451946194719481949195019511952195319541955195619571958195919601961196219631964196519661967196819691970197119721973197419751976197719781979198019811982198319841985198619871988198919901991199219931994199519961997199819992000200120022003200420052006200720082009201020112012JanFebMarAprMayJunJulAugSepOctNovDec Limit by AllResearchMethods and reporting Our online table of contents is updated at least twice each day. Read all articles published in the last 7 days. You can use bmj.com to help you with your continuing medical education. Find out about CME/CPD credits for BMJ articles Keep up to date with cardiology: Access the latest cardiovascular medicine resources from across BMJ Group.OPEN ACCESS: All research articles are freely available online, with no word limit. Find out more about the BMJ's open access policy. Submit your paper. Find out how study types differ in our How to read a paper section. The truth about sports drinks: Find out more about the joint BMJ and BBC Panorama investigation into the evidence base behind many health claims. Research Reporting of conflicts of interest from drug trials in Cochrane reviews: cross sectional study BMJ 2012; 345 doi: 10.1136/bmj.e5155 (Published 21 August 2012) Cite this as: BMJ 2012;345:e5155 Epidemiologic studies Competing interests (ethics) Clinical trials (epidemiology) Article Related content Article metrics Michelle Roseman, master’s student1, Erick H Turner, assistant professor2, Joel Lexchin, professor3, James C Coyne, professor4, Lisa A Bero, professor5, Brett D Thombs, associate professor11Lady Davis Institute for Medical Research, Jewish General Hospital and McGill University, Montreal, Quebec, Canada, H3T 1E42Department of Psychiatry, Oregon Health and Science University and Portland Veterans Affairs Medical Center, Portland, OR, USA3School of Health Policy and Management, York University, Toronto, ON, Canada4Department of Health Science, Health Psychology Section, University Medical Center Groningen, University of Groningen, Netherlands5Department of Clinical Pharmacy, School of Pharmacy and Institute for Health Policy Studies, School of Medicine, University of California, San Francisco, USACorrespondence to: B D Thombs brett.thombs{at}mcgill.caAccepted 12 July 2012AbstractObjectives To investigate the degree to which Cochrane reviews of drug interventions published in 2010 reported conflicts of interest from included trials and, among reviews that reported this information, where it was located in the review documents. Design Cross sectional study.Data sources Cochrane Database of Systematic Reviews.Selection criteria Systematic reviews of drug interventions published in 2010 in the Cochrane Database of Systematic Reviews, with review content classified as up to date in 2008 or later and with results from one or more randomised controlled trials.Results Of 151 included Cochrane reviews, 46 (30%, 95% confidence interval 24% to 38%) reported information on the funding sources of included trials, including 30 (20%, 14% to 27%) that reported information on trial funding for all included trials and 16 (11%, 7% to 17%) that reported for some, but not all, trials. Only 16 of the 151 Cochrane reviews (11%, 7% to 17%) provided any information on trial author-industry financial ties or trial author-industry employment. Information on trial funding and trial author-industry ties was reported in one to seven locations within each review, with no consistent reporting location observed.Conclusions Most Cochrane reviews of drug trials published in 2010 did not provide information on trial funding sources or trial author-industry financial ties or employment. When this information was reported, location of reporting was inconsistent across reviews.IntroductionConcerns are ongoing about the influence on the medical evidence base of conflicts of interest stemming from links between researchers and drug manufacturers.1 2 A conflict of interest has been defined by the Institute of Medicine as “a set of circumstances that creates a risk that professional judgment or actions regarding a primary interest will be unduly influenced by a secondary interest.”3 Conflicts of interest due to research funding and other financial relations can influence how drug trials are designed and carried out,1 4 the likelihood that results will support a sponsor’s drug,5 6 7 8 9 whether or not results will be published,10 11 12 and how results will be interpreted in trial reports and articles about drug trials.10 12 13 14 Similarly, industry support of systematic reviews and meta-analyses, including financial ties of the authors of the reviews, has been associated with conclusions more likely to favour a sponsor’s drug compared with systematic reviews and meta-analyses not linked to industry.15 16 As a result, research reporting guidelines now routinely recommend that study funding and author-industry financial ties be disclosed in published research reports, including reports of systematic reviews and meta-analyses.17 18 19 20 Guidelines for systematic reviews and meta-analyses do not, however, require review authors to report conflicts of interest from trials included in the reviews.19 21 In this context, a recent study found that only two of 29 meta-analyses of drug trials published in high impact biomedical journals reported the funding sources of included drug trials, and none reported author-industry financial ties from included trials.22Systematic reviews and meta-analyses produced by the Cochrane Collaboration are widely recognised as setting the standard for the evaluation of healthcare interventions.23 24 25 26 As evidenced by substantial ongoing funding to the Cochrane Collaboration by major governmental agencies,27 28 29 along with Cochrane’s partnerships with the World Health Organization30 and other key healthcare organisations,31 the Cochrane Collaboration plays an important part in the development of healthcare policies around the world. The Cochrane Collaboration also plays a key part in the training of health researchers27 and influences how both Cochrane and non-Cochrane systematic reviews and meta-analyses are conducted and reported. The Cochrane Handbook for Systematic Reviews of Interventions,21 32 which describes the Cochrane Collaboration’s methodology for review conduct and reporting, is a widely cited source of guidance on systematic review and meta-analysis methodology. The current version of the Cochrane Handbook (March 2011)21 and the previous version (September 2008),32 which guided reviewers until recently, indicate that review authors should extract data on the funding source of included trials and may consider extracting data on trial author-industry financial ties.33 34 Both versions make reporting information on trial funding in reviews optional and indicate that, if reported, it should be included in the table on characteristics of included studies.35 36 Whereas the previous edition (September 2008)32 suggested that potential bias related to study sponsorship could optionally be incorporated into the risk of bias assessment,37 the current version of the handbook (March 2011)21 states that information on conflicts of interest from included trials should not be included in the risk of bias assessment.38We investigated the extent to which systematic reviews of drug treatments published in 2010 in the Cochrane Database of Systematic Reviews reported funding sources, author-industry financial ties, and author-industry employment from included trials. Among reviews that reported such information, we also determined where it was located in the published Cochrane review document.MethodsSelection of systematic reviewsWe searched the Cochrane Database of Systematic Reviews through the Cochrane Library on 28 March 2011, using the MeSH term “drug therapy,” to identify Cochrane reviews of drug interventions published in 2010. Cochrane reviews are published in the Cochrane Database of Systematic Reviews when new and when updates (that is, a new search) or amendments (that is, edited to make corrections or to reflect changes in methodology) are made to previously published reviews. Because reporting standards are evolving, we restricted the search to this one year period to obtain recent systematic reviews, with or without meta-analyses, that reflected relatively current reporting practices.19 20Eligibility criteriaCochrane reviews published in 2010 were eligible if they included a documented systematic review of the literature classified by Cochrane as up to date in 2008 or later,39 included results from at least one randomised controlled trial, and evaluated the efficacy, effectiveness, or harm of a drug or class of drug against an alternative treatment (for example, placebo, alternative drug). We excluded reviews that only assessed different methods for administering a drug or dosage schedules of that drug. Drugs were defined broadly to include biologicals and vaccines but not nutritional supplements (for example, vitamins) or medical devices without a drug component. We included reviews that investigated a combination of drug and non-drug interventions (for example, psychotherapy), or interventions that may or may not involve a drug (for example, amnioinfusion), if a study group was exclusively given a drug intervention or if the review assessed the addition of a drug to a treatment received by both intervention and control groups. Interventions were classified as having a drug component if any form of the active ingredient (for example, dosage, route, strength, compound) was listed as an approved or discontinued brand name, generic drug, or therapeutic biological product by the US Food and Drug Administration.40 For agents not listed in the Drugs@FDA database,40 we determined drug status on the basis of consensus among investigators, using publically available sources that provided information on a particular agent.Two investigators independently reviewed Cochrane reviews for eligibility. If either reviewer deemed a review to be potentially eligible based on review of the title and abstract, then we carried out a review of the full text. Two reviewers also independently carried out full text reviews, with any disagreements resolved by consensus. Cohen’s ? statistic was used to assess agreement between reviewers corrected by chance.Data extractionTwo investigators independently extracted and entered into a standardised spreadsheet data items from the Cochrane reviews, with any discrepancies resolved by consensus. Investigators reviewed all text, tables, figures, appendices, disclosure statements, and acknowledgments from each Cochrane review to record disclosed conflicts of interest from each selected Cochrane review (review funding source and review author-industry financial ties). They also determined whether or not conflicts of interest from included trials (trial funding sources, trial author-industry financial ties, or trial author-industry employment) were reported in the reviews. Data items were extracted only from the included Cochrane reviews and not from any additional sources, such as online Cochrane resources (see supplementary appendix 1 for data extraction forms).We extracted the funding sources for the Cochrane reviews from the sources of support declaration or acknowledgments and classified them as non-industry (for example, public granting agency, private not for profit granting agency), combined pharmaceutical industry and non-industry, or none reported (review not funded or review funding information not disclosed). Financial ties of review authors to industry were defined per the July 2010 version of the International Committee of Medical Journal Editors uniform disclosure form for potential conflicts of interest20 and included current or former board membership, current or former consultancy work, current or former industry employment, expert testimony, industry grants (issued or pending), payment for lectures including service on speakers bureaus, payment for manuscript preparation, patents (planned, pending, or issued), royalties, payment for development of educational presentations, stock or stock options, travel reimbursement, or other relations with industry, as disclosed in the review. If a review did not contain a disclosure statement, we coded review author-industry financial ties as not reported.For each Cochrane review we also recorded whether the review reported information on the following types of conflicts of interest from included trials: trial funding sources, trial author-industry financial ties, and trial author-industry employment. For each of these types of conflicts of interest from included trials, we coded the reviews as reporting fully (reporting for all included trials), partially (reporting for some, but not all, included trials), or not reporting. We coded reviews as not reporting trial funding sources if they included data from pharmaceutical industry databases or noted that trial drugs were supplied by the manufacturers for certain trials but did not make any explicit statement of trial funding sources. For Cochrane reviews that reported information on conflicts of interest from included trials either fully or partially, we recorded where the information was reported. Specifically, we recorded whether the information was reported in the context of the risk of bias assessment (text, figure, or risk of bias table attached to the table showing the characteristics of the included studies) or outside of the context of the risk of bias assessment, including the text, the characteristics of included studies table, other table, the abstract, the plain language summary, in a footnote of a summary of findings table, or in the context of sensitivity analyses. In addition to coding whether conflicts of interest from included trials were reported in the Cochrane reviews, we coded whether the review’s reported data extraction protocol included extracting data on trial funding sources and trial author-industry financial ties or employment (yes, no, could not be determined).A protocol was not published or registered for the present study. However, all methods were determined a priori with two exceptions. Firstly, during data extraction we added the classification of Cochrane reviews as funded by “combined industry and non-industry” sources. This was because, although the Cochrane Handbook states that commercial funding of reviews is prohibited,41 we encountered three Cochrane reviews where industry funding sources, along with non-industry funding sources, were listed. Secondly, our initial review protocol indicated that Cochrane reviews would be coded as either reporting or not reporting conflicts of interest information from included trials. We added the fully and partially reporting classifications because some reviews provided information on some, but not all, included trials. This occurred, for instance, when reviews mentioned a subset of included trials as funded by industry but did not provide information on the funding status of other trials (non-industry funding, no trial funding, not reported).ResultsThe electronic database search yielded 272 unique titles and abstracts for review. Of these, 110 were excluded after review of the title and abstract because, although published in 2010, the review content was not classified as being up to date as of 2008 or later, no randomised controlled trials were included in the review, or the review did not assess the efficacy, effectiveness, or harm of a drug or class of drug against an alternative treatment. Of the 162 Cochrane reviews that underwent review of the full text, 11 were excluded because they were not systematic reviews of the efficacy, effectiveness, or harm of a drug or class of drug against an alternative treatment, leaving 151 eligible systematic reviews (figure?). Chance corrected agreement on inclusion and exclusion decisions between reviewers, as assessed with the Cohen’s ? statistic, was 0.95.
View larger version:In a new windowDownload as PowerPoint SlideFlow chart of selection of Cochrane reviews of drug trials published in 2010 with searches up to date as of 2008 or laterThe 151 selected Cochrane reviews evaluated a broad range of drug interventions, including 18 on treatment efficacy or effectiveness, two on harms, and 131 on both efficacy or effectiveness and harms. Between one and 121 trials were included in each systematic review. The content of 27 Cochrane reviews (18%) was classified as up to date in 2008, 59 (39%) in 2009, and 65 (43%) in 2010. The review status of 39 reviews (26%) was listed as “new,” 51 (34%) as “new search” with or without a change to review conclusions, 50 (33%) as “edited” (that is, any modification which does not involve a search for new studies) with or without a change to review conclusions, and 11 (7%) as “stable” (that is, no further changes expected to the review). The 151 selected Cochrane reviews included systematic reviews from 36 of the 53 Cochrane Review Groups that were registered in 2010. (See supplementary appendix 2 for the characteristics of the 151 selected Cochrane reviews.)Review funding and review author-industry financial ties of Cochrane reviewsOf the 151 selected Cochrane reviews, 125 (83%) reported review funding from non-industry sources, three (2%) reported review funding from both pharmaceutical industry and non-industry sources, three (2%) stated that the review was not funded, and 20 (13%) did not include a sources of support declaration (see supplementary appendix 2). Of the three reviews that reported funding from both industry and non-industry sources, we were able to clarify that for two studies this referred to previous funding to the authors unrelated to the review itself (personal communication, Christopher Eccleston, coordinating editor, Cochrane Pain, Palliative, and Supportive Care Review Group, 10 April 2012); for the third study, this reflected a contribution from Merck for a previous version of a review that had been carried out from 1998 to 2000, before the 2004 Cochrane policy that prohibited industry funding of reviews (personal communication, Jackie Price and Gerry Stansby, coordinating editors, Cochrane Peripheral Vascular Diseases Review Group, 4 May 2012). In 42 of the 151 Cochrane reviews (28%, 95% confidence interval 21% to 35%), at least one review author reported one or more financial ties to the pharmaceutical industry (see supplementary appendix 3).Reporting in Cochrane reviews of trial funding sourcesForty six of the 151 selected Cochrane reviews (30%, 95% confidence interval 24% to 38%) reported information on the funding source of least some of the included trials. Thirty reviews (20%, 14% to 27%) reported information on trial funding for all included trials and 16 (11%, 7% to 17%) reported for some, but not all, included trials (table 1?; also see supplementary appendix 4). Four Cochrane reviews did not report or partially reported trial funding sources, but did state that the trial drug was provided by a pharmaceutical company for at least some trials (see supplementary appendix 5). One hundred and five Cochrane reviews did not report trial funding sources (70%, 62% to 76%), including (based on data extraction protocols) 11 reviews (7%) that recorded, but did not report, trial funding sources, 16 (11%) that provided a data extraction protocol that did not list trial funding source information, and 78 (52%) for which it could not be determined whether or not data on trial funding sources had been collected.View this table:View PopupView InlineTable 1 Reporting of trial funding sources, trial author financial ties to the pharmaceutical industry, and trial author employment by the pharmaceutical industry among 151 Cochrane reviews of drug trials published in 2010*Among the 46 Cochrane reviews that reported any trial funding sources, partially or fully, this information was reported in as few as one and as many as seven locations in each review. In all, 22 different reporting patterns (see supplementary appendix 6) were observed. In each of the 46 Cochrane reviews that reported trial funding sources partially or fully, this information was reported in at least one of four locations in the review: in the risk of bias section of the text, in the risk of bias table attached to the characteristics of included studies table, in other text, or in a part of the characteristics of included studies table other than the risk of bias table. Trial funding source was reported in the context of the risk of bias assessment in 28 of the 151 Cochrane reviews (19%), including eight (5%) that reported this information in the risk of bias text only, four (3%) that reported in the risk of bias table only, 14 (9%) that reported in both of these locations, and two (1%) that reported in both of these locations plus the risk of bias figure. Twenty four reviews (16%) reported the sources of trial funding in other text, and 24 (16%) reported the sources of trial funding in the characteristics of included studies table in the “methods” or “notes” fields. Information on trial funding source was reported in other locations less often, including another table (one review, 1%), a footnote in a summary of findings table (five reviews, 3%), the abstract (one review, 1%), the plain language summary (two reviews, 1%), and in the context of sensitivity analyses (six reviews, 4%) (table 2?; see also supplementary appendix 4).View this table:View PopupView InlineTable 2 Summary of reporting patterns of the 46 of 151 Cochrane reviews of drug trials published in 2010 that reported trial funding sources, trial author financial ties to the pharmaceutical industry, and trial author employment by the pharmaceutical industry*Partial or full information on trial funding sources was reported in 16 of 39 reviews with “new” status (41%, 95% confidence interval 27% to 57%) and 30 of 112 reviews with an updated or amended status (27%, 19% to 36%), including 17 of 50 reviews with “edited” status (34%, 22% to 48%), 11 of 51 reviews with “new search” status (22%, 12% to 35%), and two of 11 reviews with “stable” status (18%, 5% to 48%). Trial funding source was partially or fully reported in nine of 27 reviews classified as up to date in 2008 (33%, 19% to 52%), 18 of 59 classified as up to date in 2009 (31%, 20% to 43%), and 19 of 65 classified as up to date in 2010 (29%, 20% to 41%).Reporting in Cochrane reviews of trial author-industry financial ties and trial author-industry employmentSixteen (11%, 95% confidence interval 7% to 17%) of the 151 Cochrane reviews reported trial author-industry financial ties or employment by industry. Eleven reviews (7%, 4% to 11%) reported information on author-industry financial ties from included trials, including two (1%) that reported for all included trials and nine (6%) that reported for some, but not all, included trials. Ten reviews (7%, 4% to 12%) partially reported trial author employment by industry, and none reported this fully. Of the 10 reviews that reported trial author-industry employment for some included trials, five also partially reported other trial author-industry financial ties (table 1; see also supplementary appendix 4). All of the reviews that reported information on trial author-industry financial ties or trial author-industry employment reported information on trial funding sources. All studies that extracted trial author-industry financial ties or employment data reported it in the review. In addition, in 30 reviews (20%) the data extraction protocols indicated that this information was not extracted and 105 (70%) did not provide enough information to determine if this information had been extracted.Trial author-industry financial ties or employment by industry were reported in between one and three locations in each review that reported this information. Information on trial author-industry financial ties or employment was reported in the context of the risk of bias assessment in 15 reviews (10%), including five (3%) that reported this information only in the risk of bias section of the text, seven (5%) only in the risk of bias table, two (1%) in both locations, and one (1%) in both locations plus the risk of bias figure. Trial author-industry financial ties or employment were reported in other review text in three reviews (3%) and in the characteristics of included studies table in one review (1%) (table 2; see also supplementary appendix 4).Reporting in Cochrane reviews of trial funding, trial author-industry financial ties, and trial author-industry employmentOverall, considering either partial or full reporting, 30 Cochrane reviews (20%) reported only information on trial funding sources, six reported on trial funding sources and trial author-industry financial ties (4%), five on trial funding sources and trial author-industry employment (3%), and five on all three (3%). Considering only full reporting, 28 reviews (19%) reported only on trial funding sources and two reviews reported on trial funding sources and trial author-industry financial ties (1%).Of the 42 Cochrane reviews that had at least one review author with disclosed financial ties to industry, 12 (29%) reported information on trial funding sources compared with 34 of 109 reviews (31%) in which no review authors disclosed financial ties to industry. Two of 42 Cochrane reviews (5%) with review author ties to industry reported trial author-industry financial ties or employment by industry from included trials, compared with 14 of 109 Cochrane reviews (13%) without review authors with disclosed financial ties to industry.DiscussionLess than a third of 151 Cochrane reviews of drug trials published in 2010 reported the funding source of any included trials, with only a fifth providing funding information for all included trials. Information on the funding source of any included trials was reported at a somewhat higher rate among new reviews (41%) than updated or amended reviews (27%). About 1 in 10 Cochrane reviews reported on trial author-industry financial ties, including employment of the trial author by the pharmaceutical industry, for at least some included trials. When Cochrane reviews did report on conflicts of interest from included trials, the location where this information was reported was inconsistent across reviews. The 46 Cochrane reviews that provided partial or full information on trial funding sources did so in between one and seven locations within each review, with more than 20 different patterns observed for reporting this information. Only one Cochrane review reported information on conflicts of interest from included trials in the review abstract.Comparison with other studiesTransparent disclosure of conflicts of interest is increasingly emphasised as an important component in the reporting of results from both clinical trials and systematic reviews, including meta-analyses.17 18 19 20 However, a recent study found that only 7% of meta-analyses of drug trials published in high impact biomedical journals included information on trial funding disclosed in original trials, and none reported on trial author-industry financial ties or employment disclosed in the original trial publications.22 The results of the present study show that, although Cochrane reviews reported trial funding sources and trial author-industry financial ties or employment at a higher rate than non-Cochrane reviews published in high impact journals, information on conflicts of interest from included trials was absent from most Cochrane reviews. This gap in the reporting of conflicts of interest from included trials in Cochrane reviews is important because systematic reviews and meta-analyses of drug efficacy or effectiveness and safety are relied on by clinicians and policy makers,42 43 and Cochrane reviews have been found to be a high quality source of evidence on which to base decisions about healthcare interventions.23 24 25 26 Furthermore, the Cochrane Collaboration is an international leader in setting standards for the conduct and reporting of systematic reviews, including meta-analyses, of healthcare evidence.Policy implicationsAuthors of systematic reviews and meta-analyses are guided by the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement, which does not address the reporting of trial funding and author-industry financial ties from included trials.19 44 Authors of Cochrane reviews are additionally expected to adhere to practice recommendations described in the Cochrane Handbook for Systematic Reviews of Interventions,21 32 which is widely used in practice by authors of both Cochrane and non-Cochrane reviews as a primary source of systematic review and meta-analysis methodology.21 32 Both the current version of the handbook (March 2011),21 which presently guides reviewers, and the previous version (September 2008),32 which served as the standard setter at the time the included Cochrane reviews were done, updated, or amended, state that data on trial funding should be collected in all reviews.33 34 However, neither requires that trial funding sources be reported. Both versions of the handbook suggest that the authors of reviews may optionally include trial funding source as an additional field in the characteristics of included studies table.35 36 The 2008 edition of the handbook suggested that potential bias related to the influence of trial sponsors could be considered in an optional “other sources of bias” domain of the risk of bias tool.37 In contrast, the 2011 edition specifies that this information should not be incorporated in the risk of bias assessment.38 Both versions of the handbook mention that review authors may consider extracting data on trial author-industry financial ties but do not specify if and where this information should be reported.33 34The results of the present study suggest that, without a more explicit reporting policy, conflicts of interest from included trials will not be reported in most Cochrane reviews. Given the well documented influence of industry funding of drug trials on their conduct, interpretation, and reporting,1 4 5 6 7 8 9 10 12 the Cochrane handbook and the PRISMA statement should be updated to require authors of systematic reviews and meta-analyses to report the funding sources of all included trials or to report that trial funding sources were not disclosed. Some Cochrane reviews indicated that a subset of trials in the reviews were funded by industry, but did not report the funding status of other trials (non-industry funding, no trial funding, not reported). As noted previously,22 if the funding source of included trials is only partially reported, readers might assume that the funding sources of other trials were available but not recorded, leaving them unsure as to how to interpret potential bias related to the funding sources of those trials. Alternatively, readers might assume that review authors indeed recorded the funding sources of all included trials, but only reported those with industry funding. This assumption may not be correct, and the potential for conflicts of interest related bias may be different for trials that did not report their funding source compared with trials that reported non-industry funding or trials that were not funded.Beyond study funding, consumers of research consider conflicts of interest from trial author-industry financial ties and employment as relevant to appraising the likelihood of bias in trials.45 46 47 Authors of the Cochrane handbook and the PRISMA statement should also consider recommending that review authors record and report information on trial author-industry financial ties or employment as disclosed in the original trials (for example, number of trial authors with disclosed industry financial ties or employment, or that there was no disclosure statement).Cochrane reviews that do report information on conflicts of interest in trials do not consistently do so in the same location of the review document. Thus, along with an explicit recommendation for reporting conflicts of interest from all included trials, greater emphasis should be placed on ensuring that this information can be easily found without readers having to inspect the entirety of the (typically lengthy) review document. The Cochrane handbook suggests that authors of Cochrane reviews may optionally add up to three extra fields to the characteristics of included studies table, including one to report information on trial funding.35 36 When the source of trial funding was reported in the characteristics of included studies table, however, this information was always reported in either the “methods” or “notes” fields of the table, both of which are required fields. The inclusion of “study funding” and “author-industry financial ties or employment” fields as required fields of the characteristics of included studies table would encourage more consistent reporting.Finally, we recommend that the Cochrane Collaboration reconsider its position that trial funding and trial author-industry financial ties not be included in the risk of bias assessment. The 2008 version of the Cochrane handbook listed “inappropriate influence of funders” (section 8.14.1.6) (for example, data owned by industry sponsor) as a potential source of bias that review authors could optionally incorporate in the “other sources of bias” domain of the Cochrane risk of bias tool.37 The 2011 version of the handbook, however, argues that “vested interests” should not be included in the risk of bias assessment, which “should be used to assess specific aspects of methodology that might be been influenced by vested interests and which may lead directly to a risk of bias” (section 8.15.1.5).38 As previously noted,22 empirical criteria are generally used to select items (for example, sequence generation, blinding) that are included in assessments of risk of bias,38 48 including evidence of a mechanism, direction, and likely magnitude of bias. Empirical data show that trial funding by pharmaceutical companies and trial author-industry financial ties are associated with a bias towards positive results even when controlling for other study characteristics6 8 49 50 and, thus, meet these criteria. One concern might be that including conflicts of interest from included trials in the risk of bias assessment could result in “double counting” of potential sources of bias. However, ratings in the risk of bias table are not summed to a single score, and inclusion of risk of bias from conflicts of interest could reflect mechanisms through which industry involvement can influence study outcomes6 that are not fully captured by the current domains of the risk of bias tool (random sequence generation, allocation concealment, blinding of participants and staff, blinding of outcome assessment, incomplete outcome data, selective reporting, and other sources of bias). Furthermore, even if all relevant mechanisms were to be assessed, the degree of their influence may not be fully captured when reviewers only have access to the relatively brief descriptions of trial methods that are provided in most published reports. Inclusion of conflicts of interest from included trials in the risk of bias assessment would encourage a transparent assessment of whether industry funded trials and independently conducted trials reach similar conclusions. It would also make it explicit when an entire area of research has been funded by industry and would benefit from outside scrutiny.Coding trial funding sources can be complex, and it may not always be clear to what degree different funders played a part in a given study. There are other examples, however, where risk of bias is coded even though the degree of potential bias may not be easily assessed from information available in trial reports. For instance, the degree to which trial participants and outcome assessors are successfully blinded is not always easily determined by review authors, but is rated as accurately as possible on the basis of available information. A reasonably simple system would be to code trial funding as pharmaceutical industry, non-industry (for example, public granting agency, private not for profit granting agency), combined pharmaceutical industry and non-industry, non-industry with study drug supplied by pharmaceutical industry, no study funding, or not reported.22Limitations of the studyLimitations should be considered in interpreting results from this study. Firstly, most (74%) of the included Cochrane reviews published in 2010 were either updates or amendments (that is, review status of “new search,” “edited,” or “stable”), for which it is not known which version of the Cochrane handbook review authors might have consulted. However, the 39 reviews with “new” status reported trial funding sources (partially or fully) at only a somewhat higher rate (41%) than updated or amended (for example, status of “new search,” “edited,” or “stable”) reviews (27%), and most of the “new” reviews did not report this information. Secondly, the small number of reviews from each of the Cochrane Review Groups, which support review authors who carry out reviews in a particular content area, did not allow us to assess whether there may be differences across groups in reporting of conflicts of interest from included trials. Thirdly, we did not review the original reports of drug trials included in the Cochrane reviews to determine how many of these included disclosures of trial funding source or trial author-industry financial ties. However, we previously found that 63% of randomised controlled trials included in meta-analyses published in high impact biomedical journals reported the trial funding source in the original published reports, and 26% of the randomised controlled trial reports included financial disclosures by the trial authors.22 Regardless of the actual rate of original disclosure, systematic reviews and meta-analyses should transparently report whether, in each original trial, conflicts of interest are present, absent, or not disclosed. Finally, we searched the Cochrane Database of Systematic Reviews through the Cochrane Library using the MeSH term “drug therapy,” to identify Cochrane reviews of drug trials. It is possible that our search strategy may have missed potentially eligible reviews. However, we have no reason to believe that this would have biased our findings on the proportion of Cochrane reviews reporting conflicts of interest information from included trials.ConclusionsIn summary, the Cochrane Collaboration is a recognised leader in the establishment of methodology for the conduct and reporting of evidence based reviews. This study, however, found that most Cochrane reviews of drug trials did not report information on trial funding sources or trial author-industry financial ties, including employment, from included trials. When this information was reported, patterns of reporting were inconsistent across Cochrane reviews. Cochrane and the PRISMA statement should require the reporting of conflicts of interest from included trials in systematic reviews and meta-analyses. Cochrane should ensure that this information is reported in the same way across reviews, including in the abstract, which would be consistent with the consolidated standards of reporting trials (CONSORT) recommendation that funding information be reported in the abstracts of journal articles.17 18 Cochrane should also give consideration to including conflicts of interest from trial funding and trial author-industry financial ties as part of the risk of bias tool and assessment.What is already known on this topicGuidelines for systematic reviews and meta-analyses do not require authors to describe conflicts of interest from included trialsA study found that meta-analyses of drug trials published in high impact biomedical journals rarely reported the funding sources of included trials, and none noted trial author-industry financial tiesIt is not known to what degree this information is reported in Cochrane reviews, which set the standard for the conduct and reporting of high quality evidence based reviewsWhat this study addsMost Cochrane reviews of drug trials published in 2010 did not report information on trial funding sources or trial author-industry financial ties, including employment, from included trialsWhen information was reported, it was not consistently reported in the same location across Cochrane reviewsCochrane and the PRISMA statement should require reviews to report conflicts of interest from included trials in a way that is consistent across reviews, and Cochrane should include this information as part of risk of bias assessmentNotesCite this as: BMJ 2012;345:e5155FootnotesContributors: MR contributed to the study design, reviewed articles for inclusion, carried out the data extraction, contributed to the analysis, interpretation, and presentation of the data, and drafted the manuscript with the input of BDT and the other authors. EHT, JL, JCC, and LAB contributed to the study design and contributed a critical revision of the manuscript. BDT was responsible for the study concept and design, reviewed articles for inclusion, carried out the data extraction, contributed to the analysis, interpretation, and presentation of the data, consulted with MR on the drafting of the manuscript, and contributed a critical revision of the manuscript. He is the guarantor. All authors had full access to all of the data (including statistical reports and tables) in the study and can take responsibility for the integrity of the data and the accuracy of the data analysis.Funding: MR was supported by a Frederick Banting and Charles Best Canadian graduate scholarship-master’s award from the Canadian Institutes of Health Research, a master’s training award from the Fonds de la Recherche en Santé Québec, a McGill University provost’s graduate fellowship, and a McGill University principal’s graduate fellowship. BDT was supported by a new investigator award from the Canadian Institutes of Health Research and an Établissement de Jeunes Chercheurs award from the Fonds de la Recherche en Santé Québec. This study received no funding, and no funding body had any input into any aspect of the study.Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare that: no authors had any financial support for the submitted work; JL was a consultant to a law firm representing Apotex in 2007, a consultant to the Canadian federal government in a lawsuit challenging the Canadian ban on direct to consumer advertising of prescription drugs in 2007-08, and a consultant to a law firm representing a plaintiff in a case against Allergan in 2010; LAB has received a grant from the Cochrane Collaboration Methodological Fund to examine how systematic reviewers identify unpublished drug trial data, and is an active member of the Cochrane Collaboration.Ethical approval: Not required.Data sharing: No additional data available.This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/2.0/ and http://creativecommons.org/licenses/by-nc/2.0/legalcode.References?Lexchin J. Those who have the gold make the evidence: how the pharmaceutical industry biases the outcomes of clinical trials of medications. Sci Eng Ethics2011: published online 15 February.?Moynihan R. It’s time to rebuild the evidence base. BMJ2011;342:d3004.OpenUrlFREE Full Text?Lo B, Field MJ, eds. Conflict of interest in medical research, education, and practice. National Academies Press, 2009. ?Sismondo S. How pharmaceutical industry funding affects trial outcomes: causal structures and responses. Soc Sci Med2008;66:1909-14.OpenUrlCrossRefMedlineWeb of Science?Sismondo S. Pharmaceutical company funding and its consequences: a qualitative systematic review. Contemp Clin Trials2008;29:109-13.OpenUrlCrossRefMedlineWeb of Science?Lexchin J, Bero LA, Djulbegovic B, Clark O. Pharmaceutical industry sponsorship and research outcome and quality: systematic review. BMJ2003;326:1167-70.OpenUrlFREE Full Text?Bekelman JE, Li Y, Gross CP. Scope and impact of financial conflicts of interest in biomedical research: a systematic review. JAMA2003;289:454-65.OpenUrlCrossRefMedlineWeb of Science?Bero L, Oostvogel F, Bacchetti P, Lee K. Factors associated with findings of published trials of drug-drug comparisons: why some statins appear more efficacious than others. PLoS Med2007;4:e184.OpenUrlCrossRefMedline?Rattinger G, Bero L. Factors associated with results and conclusions of trials of thiazolidinediones. PLoS ONE2009;4:e5826.OpenUrlCrossRefMedline?Turner EH, Matthews AM, Linardatos E, Tell RA, Rosenthal R. Selective publication of antidepressant trials and its influence on apparent efficacy. N Engl J Med2008;358:252-60.OpenUrlCrossRefMedline?Melander H, Ahlqvist-Rastad J, Meijer G, Beermann B. Evidence b(i)ased medicine—selective reporting from studies sponsored by pharmaceutical industry: review of studies in new drug applications. BMJ2003;326:1171-3.OpenUrlFREE Full Text?Rising K, Bacchetti P, Bero L. Reporting bias in drug trials submitted to the Food and Drug Administration: review of publication and presentation. PLoS Med2008;5:e217.OpenUrlCrossRefMedline?Wang AT, McCoy CP, Murad MH, Montori VM. Association between industry affiliation and position on cardiovascular risk with rosiglitazone: cross sectional systematic review. BMJ2010;340:c1344.OpenUrlFREE Full Text?Tatsioni A, Siontis GCM, Ioannidis JPA. Partisan perspectives in the medical literature: a study of high frequency editorialists favoring hormone replacement therapy. J Gen Intern Med2010;25:914-9.OpenUrlCrossRefMedlineWeb of Science?Yank V, Rennie D, Bero LA. Financial ties and concordance between results and conclusions in meta-analyses: retrospective cohort study. BMJ2007;335:1202-5.OpenUrlFREE Full Text?Jørgensen AW, Hilden J, Gøtzsche PC. Cochrane reviews compared with industry supported meta-analyses and other meta-analyses of the same drugs: systematic review. BMJ2006;333:782.OpenUrlFREE Full Text?Moher D, Hopewell S, Schulz KF, Montori V, Gøtzsche PC, Devereaux PJ, et al. CONSORT 2010 explanation and elaboration: updated guidelines for reporting parallel group randomised trials. BMJ2010;340:c869.OpenUrlFREE Full Text?Hopewell S, Clarke M, Moher D, Wager E, Middleton P, Altman DG, et al. CONSORT for reporting randomised trials in journal and conference abstracts. Lancet2008;371:281-3.OpenUrlCrossRefMedlineWeb of Science?Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ2009;339:b2535.OpenUrlFREE Full Text?Drazen JM, de Leeuw PW, Laine C, Mulrow C, DeAngelis CD, Frizelle FA, et al. Toward more uniform conflict disclosures. JAMA2010;304:212-3.OpenUrlCrossRefMedline?Higgins JPT, Green S, eds. Cochrane handbook for systematic reviews of interventions. Version 5.1.0. The Cochrane Collaboration, 2011. ?Roseman M, Milette K, Bero LA, Coyne JC, Lexchin J, Turner EH, et al. Reporting of conflicts of interest in meta-analyses of trials of pharmacological treatments. JAMA2011;305:1008-17.OpenUrlCrossRefMedline?Kirkham JJ, Dwan KM, Altman DG, Gamble C, Dodd S, Smyth R, et al. The impact of outcome reporting bias in randomised controlled trials on a cohort of systematic reviews. BMJ2010;340:c365.OpenUrlFREE Full Text?Moher D, Tetzlaff J, Tricco AC, Sampson M, Altman DG. Epidemiology and reporting characteristics of systematic reviews. PLoS Med2007;4:e78.OpenUrlCrossRefMedline?Wen J, Ren Y, Wang L, Li Y, Liu Y, Zhou M, et al. The reporting quality of meta-analyses improves: a random sampling study. J Clin Epidemiol2008;61:770-5.OpenUrlCrossRefMedlineWeb of Science?Moja LP, Telaro E, D’Amico R, Moschetti I, Coe L, Liberati A. Assessment of methodological quality of primary studies by systematic reviews: results of the metaquality cross sectional study. BMJ2005;330:1053.OpenUrlFREE Full Text?Canadian Institutes of Health Research. Cochrane Canada receives $9.6 million in funding from the Canadian Institutes of Health Research. 2010. www.cihr-irsc.gc.ca/e/41767.html. ?Cochrane Collaboration. The Collaboration’s funders. 2012. www.cochrane.org/about-us/funding-support. ?National Institute for Health Research. Embedding health research: National Institute for Health Research annual report 2009/2010. NIHR, 2010. ?Cochrane Collaboration. Relations with the World Health Organization. 2012. www.cochrane.org/about-us/relations-world-health-organization. ?Canadian Cochrane Centre. Partners. 2012.http://ccnc.cochrane.org/partners. ?Higgins JPT, Green S, eds. Cochrane handbook for systematic reviews of interventions. Version 5.0.1. Wiley, 2008.?Higgins JPT, Deeks JJ. Selecting studies and collecting data. In: Higgins JPT, Green S, eds. Cochrane handbook for systematic reviews of interventions. Version 5.0.1. Wiley, 2008.?Higgins JPT, Deeks JJ, eds. Chapter 7: Selecting studies and collecting data. In: Higgins JPT, Green S, eds. Cochrane handbook for systematic reviews of interventions. Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. 2012. www.cochrane-handbook.org.?Schünemann HJ, Oxman AD, Higgins JPT, Vist GE, Glasziou P, Guyatt GH. Presenting results and “summary of findings” tables. In: Higgins JPT, Green S, eds. Cochrane handbook for systematic reviews of interventions. Version 5.0.1. Wiley, 2008.?Schünemann HJ, Oxman AD, Higgins JPT, Vist GE, Glasziou P, Guyatt GH. Chapter 11: Presenting results and ‘Summary of findings’ tables. In: Higgins JPT, Green S, editors. Cochrane handbook for systematic reviews of interventions. Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. 2012. www.cochrane-handbook.org.?Higgins JPT, Altman DG. Assessing risk of bias in included studies. In: Higgins JPT, Green S, eds. Cochrane handbook for systematic reviews of interventions. Version 5.0.1. Wiley, 2008.?Higgins JPT, Altman DG, Sterne JAC, eds. Chapter 8: assessing risk of bias in included studies. In: Higgins JPT, Green S, eds. Cochrane handbook for systematic reviews of interventions. Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. 2012. www.cochrane-handbook.org.?Higgins JPT, Green S, Scholten RJPM. Maintaining reviews: updates, amendments and feedback. In: Higgins JPT, Green S, eds. Cochrane handbook for systematic reviews of interventions. Version 5.1.0. The Cochrane Collaboration, 2011. ?US Food and Drug Administration. Drugs@FDA. 2012. www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm.?Green S, Higgins JPT. Preparing a Cochrane review. In: Higgins JPT, Green S, eds. Cochrane handbook for systematic reviews of interventions. Version 5.1.0 .The Cochrane Collaboration, 2011. ?Patsopoulos NA, Analatos AA, Ioannidis JP. Relative citation impact of various study designs in the health sciences. JAMA2005;293:2362-6.OpenUrlCrossRefMedlineWeb of Science?Harbour R, Miller J. A new system for grading recommendations in evidence based guidelines. BMJ2001;323:334-6.OpenUrlFREE Full Text?Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JPA, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ2009;339:b2700.OpenUrlFREE Full Text?Licurse A, Barber E, Joffe S, Gross C. The impact of disclosing financial ties in research and clinical care: a systematic review. Arch Intern Med2010;170:675-82.OpenUrlCrossRefMedline?Chaudhry S, Schroter S, Smith R, Morris J. Does declaration of competing interests affect readers’ perceptions? A randomised trial. BMJ2002;325:1391-2.OpenUrlFREE Full Text?Schroter S, Morris J, Chaudhry S, Smith R, Barratt H. Does the type of competing interest statement affect readers’ perceptions of the credibility of research? Randomised trial. BMJ2004;328:742-3.OpenUrlFREE Full Text?West S, King V, Carey T, Lohr KN, McKoy N, Sutton SF, et al. Systems to rate the strength of scientific evidence. Evidence report/technology assessment 47. Agency for Healthcare Research and Quality, 2002.?Kjaergard LL, Als-Nielsen B. Association between competing interests and authors’ conclusions: epidemiological study of randomised clinical trials published in the BMJ. BMJ2002;325:249.OpenUrlFREE Full Text?Cho MK, Bero LA. The quality of drug studies published in symposium proceedings. Ann Intern Med1996;124:485-9.OpenUrlMedlineWeb of Science Open access PDFEasy ReadData supplementRespond to this article Tweet Services Email to friendDownload to citation managerAdd article to BMJ portfolioRequest permission Citations Find similar articles in PubMedArticles by Michelle RosemanArticles by Erick H TurnerArticles by Joel LexchinArticles by James C CoyneArticles by Lisa A BeroArticles by Brett D ThombsCiting articles via Web of ScienceCiting articles via Scopus Social bookmarking 
CiteULike
Connotea
Del.icio.us
Digg
Facebook
Mendeley
Reddit
Twitter
Stumbleupon Latest jobsUK jobsInternational jobsUK jobs AXESS LTD, EU MEDICAL ADVISER. (23 Aug 2012)SOLENT NHS TRUST SPECIALTY DOCTOR COMMUNITY SEXUAL AND REPRODUCTIVE HEALTHCARE (23 Aug 2012)Sessional roles for Doctors Scotland: (23 Aug 2012)UNIVERSITY OF LIVERPOOL SENIOR LECTURER (CLINICAL) IN NEONATOLOGY (23 Aug 2012) show me all jobs >> International jobs DOCTORS - ENJOY THE GREAT LIFESTYLE in Australia and New Zealand. SHO/ Registrar/ Consultant and GP openings. (6 Jul 2012)International Medical Recruitment - Medical Jobs in Australia and New Zealand (24 Aug 2012)Saudi Arabia - UAE - Kuwait On behalf of clients Shamco International Recruitment would like to invite applicants for various positions (24 Aug 2012)The Eureka Medical and Bougainvillea Clinic Consultants in General Internal Medicine and Paediatrics required in the British Virgin Islands (23 Aug 2012) show me all jobs >> Rapid responses Latest ResponsesMost responsesLatest Responses Re: Roy Simpson Published 24 August 2012 Why corporate power is a public health priority Published 24 August 2012 Cervical Intraepithelial Neoplasia and Pregnancy Management Published 24 August 2012 Incentives Published 24 August 2012 Re: Unhappy pills Published 24 August 2012 more Most responses Unhappy pills (11 responses) Published 10 August 2012
Transcatheter aortic valve implantation (TAVI): risky and costly (8 responses)Published 31 July 2012
We should not let families stop organ donation from their dead relatives (8 responses)Published 7 August 2012
Diagnosis and management of cellulitis (8 responses)Published 7 August 2012
Association between psychological distress and mortality: individual participant pooled analysis of 10 prospective cohort studies (7 responses)Published 31 July 2012
more THIS WEEK'S POLLRead related article
See previous polls
Recent blogs and podcastsBlogsPodcastsBlogs Domhnall MacAuley: Santa Claus and Lance Armstrong (24 Aug 2012)Tiago Villanueva: Does it matter where you do your medical training? (23 Aug 2012)James Drife: Doctors on the Fringe (22 Aug 2012)Steve Yentis: Infamous names in anaesthesia—part two (21 Aug 2012)Tessa Richards: Personal information empowers and its shift to the people makes sense (20 Aug 2012) more >> Podcasts Ecological public health (24 Aug 2012)Fighting the food giants (17 Aug 2012)Is the drug pipeline really drying up? (10 Aug 2012)Renal patient records (3 Aug 2012)Shift workers' health and assessing risk of violence (27 Jul 2012) more >> BMJ most popular Most sharedMost searchedMost shared Sample size calculations: should the emperor’s clothes be off the peg or made to measure? (804 views)The truth about sports drinks (696 views)When financial incentives do more good than harm: a checklist (650 views)Cochrane review finds no proved benefit in drug treatment for patients with mild hypertension (598 views)Myalgia while taking statins (589 views) Most searched Kathleen Hilditchguyattchronic liver diseasehow to read a paperFrance Follow BMJ Ontwitter.com/bmj_latestfacebook.com/bmjdotcomyoutube.com/user/BMJmedia Content Links Last 7 daysResearchEducationNewsCommentArchiveBlogsVideoPrint Issue My Account Email alertsActivate subscription Resources AuthorsReviewersBMA membersReadersSubscribersAdvertisers and sponsorsMedia Information Contact usFeedback BMJ About usEditorial staffAdvisersPoliciesComplaintsPartnershipsSubmit your paper Explore BMJ About BMJ GroupJunior Doctors: Agents for ChangeOlympics portalStudent BMJdoc2docPandemic FluBMJ Group BMJ Group Privacy and Cookie Policy Website T & Cs Revenue Sources HighWire Press Feedback Help © 2012 BMJ Publishing Group Ltd window.fbAsyncInit = function() {FB.init({appId: '154318714596620', status: true, cookie: true,xfbml: true});};(function() {var e = document.createElement('script'); e.async = true;e.src = document.location.protocol + '//connect.facebook.net/en_US/all.js';document.getElementById('fb-root').appendChild(e);}());View the original article here
This post was made using the Auto Blogging Software from WebMagnates.org This line will not appear when posts are made after activating the software to full version.
View larger version:In a new windowDownload as PowerPoint SlideFig 2 Proportion of patients prescribed cholesterol lowering drugs and mean cholesterol concentration of treated and untreated patientsThe proportion of men and women prescribed antihypertensive drugs was similar in all age groups apart from those aged 65-69 and 75-79, in whom prescriptions were more common in women (39% (610/1562) in women v 34 % (454/1331) in men for ages 65-69; 55% (634/1152) v 48 % (367/757), respectively, for ages 75-79; fig 3?). Overall, women were 10% more likely to receive antihypertensive drugs than men (P<0.001). Statin prescriptions were more common in men than women in those aged under 60 (6% (663/11?078) in women v 8% (947/11?892) in men for ages 40-59) but higher in women aged over 75 (28% (537/1949) in women v 22% (272/1213) in men, for ages 75-84). Overall, men were more likely to receive statin prescriptions than women (odds ratio 1.1, 1.1 to 1.2; P<0.001).
View larger version:In a new windowDownload as PowerPoint SlideFig 3 Proportion of patients prescribed primary preventive drug treatment in each age group by sexDiscussionSummary of findingsThis study assessed current rates of prescription of primary prevention across a typical primary care population with no previous history of cardiovascular disease. As expected, blood pressure increased with age but while antihypertensive treatment also increased, many older people did not receive blood pressure lowering drugs and most people of all ages were not prescribed statins. This was particularly an issue in the oldest age groups where, despite reasonable recording of risk factors, statins were prescribed in only a fraction of those eligible assuming an absolute cardiovascular disease risk of >20% for most of those aged over 75.30 This increasingly important cohort of older individuals has been largely ignored by current primary prevention programmes, which focus on people under the age of 75. As the population ages, both statins and antihypertensive drugs offer the prospect of further reducing mortality and cardiovascular disease events, but only if they are prescribed.10 31Strengths and weaknesses of the studyIn this large study we used routine data from practices across the West Midlands and included all registered patients over the age of 40. For the purposes of this study, the West Midlands is representative of the national picture, having similar mortality rates in people aged =75 compared with the national picture (death rates in people aged 75-84 and in people aged =85 are 56.6 per 1000 and 152.7 per 1000, respectively, in England and Wales compared with 58.5 per 1000 and 157.6 per 1000 in the West Midlands).32 The advantage of using this cohort over data from the Health Survey for England33 is that the entire population from the study area was sampled and bias from differential response rates was not possible. In addition, we captured accurate data on all prescribed drugs over the preceding 90 days rather than having to rely on self reported accounts from participating patients, as was the case in the Health Survey for England.33We included all patients in this analysis, regardless of their calculated cardiovascular risk. Given that age is the most significant factor in cardiovascular risk scores,22 30 if we had done the analysis taking account of risk, the association of older age with non-use of preventive drugs would have been more marked. We did not do this as the risk calculators have been less well validated for people over the age of 75,27 29 and true denominators would be difficult to establish as treatment with antihypertensive drugs and statins will lower calculated risk.In estimating the proportion of patients receiving treatment, we could not account for contraindications to drug treatment, the general practitioner’s judgment in individual cases, or patients’ choice.34 In addition, we could not distinguish between people who had never been offered primary preventive treatment and those in whom drug treatment was stopped, perhaps because of side effects or because of increasing age or frailty.Study findings in the context of previous researchThe “treatment-risk” paradox we observed, particularly for lipid lowering drugs, has been identified before in elderly patients eligible for secondary prevention.11 12 13 14 The evidence supporting prescription of antihypertensive drugs in elderly patients is relatively well established. The HYVET study showed that antihypertensive treatment in independently living patients over the age of 80 with or without previous cardiovascular disease reduces risk of cardiovascular events and increases life expectancy.31 Patients recruited to this trial were healthier than people of similar ages within the general population because of the strict exclusion criteria that restricted patients with multiple co-existing illnesses from participation.35 Nevertheless, antihypertensive drugs are generally considered safe and effective in elderly patients, as reflected in guidelines in which recommendations on prescription of antihypertensive drugs are not restricted by age.26The evidence for use of statins in the elderly is less clear.36 The Heart Protection Study showed that treatment of people at high risk of cardiovascular disease of all ages (40-80) with simvastatin 40 mg results in a decreased risk of mortality from cardiovascular disease, coronary events, strokes, and revascularisations with no increased risk of mortality from non-cardiovascular disease or haemorrhagic stroke.10 This effect was independent of age. The MEGA trial found a 33% risk reduction for coronary heart disease with no increase in non-cardiovascular disease mortality or other adverse events, and this effect was independent of age up to 80.8 The ASCOT-LLA trial (in patients aged 40-79) found that statins reduce the risk of cardiovascular disease events and procedures (including fatal and non-fatal stroke),9 and this effect was again independent of age.37 The PROSPER trial, however, showed that while pravastatin given for three years reduced the risk of coronary disease in elderly individuals (aged 70-82), it had no effect on the risk of stroke.38Despite evidence that supports the use of statins in patients up to the age of 80,8 9 10 37 38 our findings suggest that general practitioners are choosing to follow guidelines3 that recommend their use only up to age 74. Beyond 80, it is not clear whether statins are effective for primary prevention. This ambiguity exists not because of conflicting trial results, but because trials have not been conducted in this population.39 There is no evidence to suggest that prescribing statins in elderly patients causes any increased side effects or adverse effects. The JUPITER trial found that (in patients aged 50-97), although adverse events were increased in older patients, there was no significant difference in such events between those taking statins and those taking placebo.40 41In the absence of evidence from trials, guidelines rely on expert opinion.3 Currently, while these guidelines note that statins are likely to be beneficial, they fall short of explicitly recommending them for the over 80s, and our findings suggest that general practitioners are not using them in most people of this age. Given the underlying risk associated with age30 42 and that the protective effects of primary prevention drugs can be realised within just one year,43 a case can be made for offering primary prevention to a larger proportion of people aged 80 and over than are currently receive it.In contrast with previous research on secondary prevention15 16 we found minimal clinically significant differences in prescription rates between men and women. This is perhaps surprising given that at any age men are at greater risk of a cardiovascular disease event than women.30 42Implications for policy, research, and clinical practiceIt is difficult to interpret whether the low use of preventive treatments (particularly statins) in older people reflects appropriate or inappropriate care. The non-use of these drugs might reflect a considered decision that has taken into account factors associated with age that might deter doctors from prescribing such as multiple comorbidity, polypharmacy, and cognitive decline as well as the patient’s choice. There is only limited evidence of effectiveness, for statins at least, in people over the age of 80. Nevertheless, there is a striking contrast between use of statins and use of antihypertensive drugs in older people, which does point to possible underuse of statins. To better understand the clinical implications of our findings, more research is needed to determine why general practitioners refrain from prescribing primary preventive treatment in elderly people, the attitudes of older people towards preventive drugs, and the costs and benefits of prescribing in this age group. These are important questions to answer. The number of people aged 80 and over is projected to rise rapidly,44 and greater use of these drugs might reduce disability and prolong healthy life expectancy in this age group.Ultimately, evidence is needed to inform new guidelines that offer more precise recommendations on primary prevention for older people. In particular, consideration needs to be given to whether to continue to use an absolute risk based approach to guide treatment, whether there is a role for novel biomarkers to differentiate people who would benefit from treatment, or whether the optimal strategy might be to offer treatment to all people over a given age with fixed combination low dose multiple preventive drugs, otherwise known as the polypill approach.22 It has been estimated that this could reduce the incidence of cardiovascular disease events by up to 80%.22 The original polypill proposal suggested treating everyone over the age of 55, regardless of their absolute risk of cardiovascular disease.22 Use of this strategy in people aged =75 could be an appropriate place to start, with a simple drug regimen that could reduce absolute risk with few adverse effects.45ConclusionsCurrent guidelines3 and screening strategies46 for primary prevention of cardiovascular disease focus on people aged 40-74. Our study suggests that this is having an effect on the care of elderly patients aged =75. With continuing advances in healthcare, the elderly population is increasing and people are living to an older age.44 They should therefore not be ignored by clinical trials and guidelines or overlooked in strategies for primary prevention of cardiovascular disease.More research is needed to inform practice in primary prevention to deal with developing age inequalities and offer more specific advice about how best to treat elderly patients. Future research should test whether innovative treatment strategies, such as use of a polypill, could reverse these age inequalities in treatment of absolute risk of cardiovascular disease. There is a case for a simple trial of use of statins in people over the age of 80.What is already known on this topicAntihypertensive drugs and statins are safe and effective treatments for absolute risk of cardiovascular disease Age inequalities exist in prescription of statins for elderly patients with existing cardiovascular diseaseWhat this study addsAge inequalities also exist in those eligible for primary preventive treatmentPrescribing trends for statins seem to closely follow guidelines, which do not offer clear guidance for elderly patientsNotesCite this as: BMJ 2012;345:e4535FootnotesWe thank the following general practices for their participation and cooperation with this study; Greenridge Surgery, West Heath Surgery, Dudley Park Medical Centre, Selly Park Surgery, 112 Weoley Park Road Surgery, Sutton Park Surgery, Bellevue Medical Centre, Druids Heath Surgery, Jiggins Lane Medical Centre, River Brook Medical Centre, Bournville Surgery, 192 Charles Road Surgery, 75-77 Cotterills Lane Surgery, Mere Green Surgery, Parkfield Medical Centre, Arden Medical Centre, The Jacey Practice, Hampton Surgery, and Broadway Health Centre.Contributors: JM and RJMcM had the original idea and gained the funding. KF was responsible for the data collection. JPS undertook the analyses and wrote the first draft with RJMcM and SS. All authors subsequently refined the manuscript and approved the final version. JM is guarantor.Funding: This work forms part of a larger programme on stroke prevention in primary care supported by the National Institute for Health Research (RP-PG-0606-1153). JPS and SS are funded by the National Institute for Health Research Birmingham and Black Country Collaboration for Leadership in Applied Health Research and Care. RJMcM holds an NIHR career development fellowship. The views and opinions expressed are those of the authors and do not necessarily reflect those of the NHS, NIHR, or the Department of Health.Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.Ethical approval: All data collection was approved by the Birmingham East North and Solihull research ethics committee in June 2008 (No 08/H1206/91).Study sponsor: The University of Birmingham acted as the study sponsor. They were responsible for the overall conduct of the study and ensured the relevant contracts, insurance and approvals were in place prior to the start of the study. They had no active role in the study design, data collection, analysis or dissemination.Data sharing: Proposals for data sharing should be sent to the corresponding author.This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/2.0/ and http://creativecommons.org/licenses/by-nc/2.0/legalcode.References?World Health Organization. Prevention of cardiovascular disease: guidelines for assessment and management of cardiovascular risk. WHO Press, 2007.?National Institute for Health and Clinical Excellence. Hypertension: clinical management of primary hypertension in adults. CG127, 2011.?National Institute for Health and Clinical Excellence. Lipid modification: Cardiovascular risk assessment and the modification of blood lipids for the primary and secondary prevention of cardiovascular disease. CG067, 2008. www.nice.org.uk/CG067.?British Medical Association, NHS Employers. Quality and outcomes framework guidance for GMS contract 2009/10: delivering investment in general practice. EGUI05501, 2009.?Colhoun HM, Betteridge DJ, Durrington PN, Hitman GA, Neil HAW, Livingstone SJ, et al. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet2004;364:685-96.OpenUrlCrossRefMedlineWeb of Science?Dahlof B, Sever PS, Poulter NR, Wedel H, Beevers DG, Caulfield M, et al. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled trial. Lancet2005;366:895-906.OpenUrlCrossRefMedlineWeb of Science?Hansson L, Zanchetti A, Carruthers SG, Dahlof B, Elmfeldt D, Julius S, et al. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the hypertension optimal treatment (HOT) randomised trial. Lancet1998;351:1755-62.OpenUrlCrossRefMedlineWeb of Science?Nakamura H, Arakawa K, Itakura H, Kitabatake A, Goto Y, Toyota T, et al. Primary prevention of cardiovascular disease with pravastatin in Japan (MEGA Study): a prospective randomised controlled trial. Lancet2006;368:1155-63.OpenUrlCrossRefMedline?Sever PS, Dahlof B, Poulter NR, Wedel H, Beevers G, Caulfield M, et al. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet2003;361:1149-58.OpenUrlCrossRefMedlineWeb of Science?Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet2002;360:7-22.OpenUrlCrossRefMedlineWeb of Science?Lemaitre RN, Furberg CD, Newman AB, Hulley SB, Gordon DJ, Gottdiener JS, et al. Time trends in the use of cholesterol-lowering agents in older adults—the Cardiovascular Health Study. Arch Intern Med1998;158:1761-8.OpenUrlCrossRefMedlineWeb of Science?Whincup PH, Emberson JR, Lennon L, Walker M, Papacosta O, Thomson A. Low prevalence of lipid lowering drug use in older men with established coronary heart disease. Heart2002;88:25-9.OpenUrlFREE Full Text?Gnavi R, Migliardi A, Demaria M, Petrelli A, Caprioglio A, Costa G. Statins prescribing for the secondary prevention of ischaemic heart disease in Torino, Italy. A case of ageism and social inequalities. Eur J Public Health2007;17:492-6.OpenUrlFREE Full Text?Ko DT, Mamdani M, Alter DA. Lipid-lowering therapy with statins in high-risk elderly patients—the treatment-risk paradox. JAMA2004;291:1864-70.OpenUrlCrossRefMedlineWeb of Science?Driscoll A, Beauchamp A, Lyubomirsky G, Demos L, McNeil J, Tonkin A. Suboptimal management of cardiovascular risk factors in coronary heart disease patients in primary care occurs particularly in females. Intern Med J2011;41:730-6.OpenUrlCrossRefMedline?Vulic D, Lee BT, Dede J, Lopez VA, Wong ND. Extent of control of cardiovascular risk factors and adherence to recommended therapies in US multiethnic adults with coronary heart disease: from a 2005-2006 national survey. Am J Cardiovasc Drugs2010;10:109-14.OpenUrlCrossRefMedlineWeb of Science?De Ruijter W, de Waal MW, Gussekloo J, Assendelft WJ, Blom JW. Time trends in preventive drug treatment after myocardial infarction in older patients. Br J Gen Pract2010;60:47-9.OpenUrlCrossRefMedline?Marshall T. The use of cardiovascular risk factor information in practice databases: making the best of patient data. Br J Gen Pract2006;56:600-5.OpenUrlMedlineWeb of Science?Holt TA, Thorogood M, Griffiths F, Munday S, Stables D. Identifying individuals for primary cardiovascular disease prevention in UK general practice: priorities and resource implications. Br J Gen Pract2008;58:495-8.OpenUrlCrossRefMedline?Lawson KD, Fenwick EAL, Pell ACH, Pell JP. Comparison of mass and targeted screening strategies for cardiovascular risk: simulation of the effectiveness, cost-effectiveness and coverage using a cross-sectional survey of 3921 people. Heart2010;96:208-12.OpenUrlFREE Full Text?Chamnan P, Simmons RK, Khaw KT, Wareham NJ, Giffin SJ. Estimating the population impact of screening strategies for identifying and treating people at high risk of cardiovascular disease: modelling study. BMJ2010;340:c1693.OpenUrlFREE Full Text?Wald NJ, Law MR. A strategy to reduce cardiovascular disease by more than 80%. BMJ2003;326:1419-23.OpenUrlFREE Full Text?NHS Health Check Programme. Putting Prevention First—NHS Health Check: vascular risk assessment and management best practice guidance. NHS, 2009.?Khunti K, Walker N, Sattar N, Davies M. Unanswered questions over NHS health checks. BMJ2011;342:c6312.OpenUrl?Reckless JP. Primary prevention of cardiovascular disease. BMJ2011;342:d201.OpenUrlFREE Full Text?National Institute for Health and Clinical Excellence. Hypertension: management of hypertension in adults in primary care. CG034, 2006. www.nice.org.uk/CG034.?Anderson KM, Odell PM, Wilson PWF, Kannel WB. Cardiovascular-disease risk profiles. Am Heart J1991;121:293-8.OpenUrlCrossRefMedlineWeb of Science?Collins GS, Altman DG. An independent and external validation of QRISK2 cardiovascular disease risk score: a prospective open cohort study. BMJ2010;340:c2442.OpenUrlFREE Full Text?Hippisley-Cox J, Coupland C, Vinogradova Y, Robson J, Minhas R, Sheikh A, et al. Predicting cardiovascular risk in England and Wales: prospective derivation and validation of QRISK2. BMJ2008;336:1475-82.OpenUrlFREE Full Text?Wood DA, Wray R, Poulter N, Williams B, Kirby M, Patel V. JBS 2: Joint British Societies’ guidelines on prevention of cardiovascular disease in clinical practice. Heart2005;91(suppl 5):v1-52.OpenUrlFREE Full Text?Beckett NS, Peters R, Fletcher AE, Staessen JA, Liu LS, Dumitrascu D, et al. Treatment of hypertension in patients 80 years of age or older. N Engl J Med2008;358:1887-98.OpenUrlCrossRefMedline?Office for National Statistics. Mortality statistics: deaths registered in England and Wales. 2010. Series DR 10-5-2012. www.ons.gov.uk/ons/publications/re-reference-tables.html?edition=tcm%3A77-230730.?Aresu M, Chaudhury M, Diment E, Fuller E, Gordon-Dseagu V, Gunning N, et al. Health Survey for England 2009. Vol 1: health and lifestyles. Health and Social Care Information Centre, 2010.?Aarabi M, Skinner J, Price CE, Jackson PR. Patients’ acceptance of antihypertensive therapy to prevent cardiovascular disease: a comparison between South Asians and Caucasians in the United Kingdom. Eur J Cardiovasc Prev Rehabil2008;15:59-66.OpenUrlCrossRefMedlineWeb of Science?Messerli FH, Sulicka J, Gryglewska B. Treatment of hypertension in the elderly. N Engl J Med2008;359:972-3.OpenUrlMedlineWeb of Science?Robinson JG. Lipid-lowering therapy for the primary prevention of cardiovascular disease in the elderly: opportunities and challenges. Drugs Aging2009;26:917-31.OpenUrlCrossRefMedlineWeb of Science?Collier DJ, Poulter NR, Dahlof B, Sever PS, Wedel H, Buch J, et al. Impact of atorvastatin among older and younger patients in the Anglo-Scandinavian Cardiac Outcomes Trial Lipid-Lowering Arm. J Hypertens2011;29:592-9.OpenUrlCrossRefMedlineWeb of Science?Shepherd J, Blauw GJ, Murphy MB, Bollen ELEM, Buckley BM, Cobbe SM, et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet2002;360:1623-30.OpenUrlCrossRefMedlineWeb of Science?Robinson JG, Bakris G, Torner J, Stone NJ, Wallace R. Is it time for a cardiovascular primary prevention trial in the elderly? Stroke2007;38:441-50.OpenUrlFREE Full Text?Ridker PM, Danielson E, Fonseca FAH, Genest J, Gotto AM, Kastelein JJP, et al. Rosuvastatin to prevent vascular events in men and women with elevated c-reactive protein. N Engl J Med2008;359:2195-207.OpenUrlCrossRefMedlineWeb of Science?Glynn RJ, Koenig W, Nordestgaard BG, Shepherd J, Ridker PM. Rosuvastatin for primary prevention in older persons with elevated C-reactive protein and low to average low-density lipoprotein cholesterol levels: exploratory analysis of a randomized trial. Ann Intern Med2010;152:488-96.OpenUrlFREE Full Text?Rothwell PM, Coull AJ, Silver LE, Fairhead JF, Giles MF, Lovelock CE, et al. Population-based study of event-rate, incidence, case fatality, and mortality for all acute vascular events in all arterial territories (Oxford Vascular Study). Lancet2005;366:1773-83.OpenUrlCrossRefMedlineWeb of Science?Baigent C, Keech A, Kearney PM, Blackwell L, Buck G, Pollicino C, et al. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet2005;366:1267-78.OpenUrlCrossRefMedlineWeb of Science?Office for National Statistics. Mid-year populations estimates: aging, fastest increase in the “oldest old.” 2010. www.ons.gov.uk.?Yusuf S, Pais P, Afzal R, Xavier D, Teo K, Eikelboom J, et al. Effects of a polypill (Polycap) on risk factors in middle-aged individuals without cardiovascular disease (TIPS): a phase II, double-blind, randomised trial. Lancet2009;373:1341-51.OpenUrlCrossRefMedlineWeb of Science?Department of Health. Putting prevention first. Vascular checks: risk assessment and management. Impact assessment. Central Office of Information, 2008.