BMJ Confidential: For Review Only Collaboration between academics and industry in clinical trials: cross-sectional study of publications and survey of lead academic authors Journal: BMJ Manuscript ID BMJ.2018.044617 Article Type: Research BMJ Journal: BMJ Date Submitted by the Author: 17-Apr-2018 Complete List of Authors: Rasmussen, Kristine; Nordic Cochrane Centre, Rigshospitalet Dept. 7811 Bero, Lisa; University of Sydney, Charles Perkins Centre / Pharmacy Redberg, Rita; University of California San Francisco, UCSF Division of Cardiology Gøtzsche, Peter; Nordic Cochrane Centre, Rigshospitalet Dept. 7811 Lundh, Andreas; Center for Evidence-Based Medicine, Odense University Hospital and University of Southern Denmark industry, conflicts of interest, funding, academic, authorship, ghost Keywords: authorship https://mc.manuscriptcentral.com/bmj Page 1 of 42 BMJ 1 2 3 4 Collaboration between academics and industry in clinical trials: cross-sectional study of 5 publications and survey of lead academic authors 6 7 8 Word count: 3612 9 10 Kristine Rasmussen1 (researcher, MD, MSc), [email protected] 11 Confidential: For Review Only 12 Lisa Bero2 (professor, PhD), [email protected] 13 14 Rita Redberg3 (professor, MD, MSc, FACC), [email protected] 15 16 Peter C. Gøtzsche1 (professor, MD, DMSci), [email protected] 17 18 Andreas Lundh4 (senior researcher, MD, MSc, PhD), [email protected] 19 20 21 22 1 23 Nordic Cochrane Centre, Rigshospitalet, Copenhagen, Denmark 24 2 25 Charles Perkins Centre and Faculty of Pharmacy, University of Sydney, Australia 26 3 UCSF Division of Cardiology, 505 Parnassus Ave., Suite M-1180, San Francisco, California, USA 27 28 4 Center for Evidence-Based Medicine, Odense University Hospital and University of Southern Denmark, 29 30 Odense, Denmark 31 32 33 34 § Contact information for corresponding author: Kristine Rasmussen Nordic Cochrane Centre, 35 36 Rigshospitalet Dept. 7811, Blegdamsvej 9, DK-2100 Copenhagen Ø, Denmark, 37 38 Phone: +45 35 45 7110, Fax: +45 35 45 7007, E-mail: [email protected] 39 40 41 42 Competing interests: All authors have completed the ICMJE uniform disclosure form 43 at www.icmje.org/coi_disclosure.pdf and declare: no support from any organisation for the 44 45 submitted work; RFR is editor of JAMA Internal Medicine which is included in our sample of 46 journals, but RFR had no role in data extraction or analysis of the results; all authors declare no 47 48 financial relationships with any organisations that might have an interest in the submitted work in 49 the previous three years and no other relationships or activities that could appear to have 50 51 influenced the submitted work. 52 53 Funding: No external funding received. Study was financed by institutional salaries. 54 55 56 57 58 59 60 https://mc.manuscriptcentral.com/bmj BMJ Page 2 of 42 1 2 3 4 BOX: 5 6 Section 1: What is already known on this subject 7 8 The biomedical industry funds most clinical trials. Industry funders may influence how trials are 9 designed and reported, sometimes serving financial rather than public interest. 10 11 SectionConfidential: 2: What this study adds For Review Only 12 13 All aspects of the clinical trial were influenced by the industry funder in most industry-funded trials 14 in high impact medical journals. Lead academic authors involved in industry-funded trials found the 15 collaboration with the funder beneficial, but some reported loss of academic freedom. 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 https://mc.manuscriptcentral.com/bmj Page 3 of 42 BMJ 1 2 3 4 ABSTRACT 5 6 Word count: 291 7 8 Objective: To determine the role of academic authors, funders and contract research 9 organisations in industry-funded vaccine, drug and device trials, and to determine lead academic 10 11 authors’Confidential: experiences with industry funder collaborations.For Review Only 12 13 Design: Cross-sectional analysis of trial publications and survey of lead academic authors. 14 15 Eligibility criteria for selecting studies: We included the most recent 200 phase III and IV 16 17 vaccine, drug and device trials with full industry funding, at least one academic author, published in 18 one of the top seven high impact general medical journals (NEJM, Lancet, JAMA, BMJ, Annals of 19 20 Internal Medicine, JAMA Internal Medicine and PLoS Medicine). 21 22 Results: Employees of industry funders coauthored 173 (87%) of publications. We found 183 23 24 (92%) trials reported funder involvement in design and 167 (84%) academic author involvement. 25 Data analysis involved the funder in 146 (73%) trials and the academic authors in 79 (40%). Trial 26 27 reporting involved the funder in 173 (87%) trials and academic authors in 197 (99%). Contract 28 research organisations were involved in the reporting of 123 (62%) trials. 29 30 Eighty of 200 lead academic authors (40%) responded to the survey. Twenty-nine (33%) of the 80 31 32 responders reported that academics had final say on the design. Ten responders described 33 34 involvement of an unnamed funder and/or CRO employee in the data analysis and/or 35 reporting. Most academic authors found the collaboration with industry funder beneficial, but 3 36 37 (4%) experienced delay in publication due to the industry funder and 9 (11%) reported 38 disagreements with the industry funder mostly concerning trial design and reporting. 39 40 41 Conclusions: Industry employees and academic authors are involved in the design, conduct, and 42 reporting of most industry-funded trials in high impact journals. However, data analysis is often 43 44 conducted without academic involvement. Academics view the collaboration as beneficial, but 45 some report loss of academic freedom. 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 https://mc.manuscriptcentral.com/bmj BMJ Page 4 of 42 1 2 3 4 INTRODUCTION 5 6 Collaboration between industry and academics is common in vaccine, drug and device 7 8 development, as it can be mutually beneficial. The academics provide access to trial participants 9 and clinical and methodological expertise, and industry provides funding and expertise. The degree 10 11 of independenceConfidential: and roles of academics and For industry Review varies across trials. OnlyTrials may be 12 completely run by academic trial units with unrestricted industry funding or solely provision of study 13 medication.1, 2 Alternatively, academics are involved in trials as honorary authors in order to give a 14 15 trial scientific credibility and downplay the role of industry funder.3, 4 16 17 Based on previous work and examples, collaboration between academics and industry may result 18 19 in commercial considerations outweighing science and constraints on academic freedom. For 20 example, previous studies have found some trial agreements permit funders to block publication.5-8 21 22 Furthermore, academics have reported problems with stalling of publications, restriction of 23 publication rights and threats to never fund their institution again due to reporting of negative 24 9 25 results or harms. A survey of Canadian trial investigators found problems in relation to industry 26 control over study design, data ownership, data access and analysis.10 27 28 Although most clinical drug and device trials are industry funded, the nature of the collaboration 29 30 between industry and academics has received little attention.11 Previous studies have addressed 31 the issue on a general level.5-10, 12 To our knowledge, no contemporary studies have surveyed the 32 33 role and practices of academics, industry, and contract research organisations (CROs) when 34 collaborating in clinical vaccine, drug or device trials. 35 36 37 38 39 Objective 40 41 • To determine the role of academic authors, funders and CROs in industry-funded vaccine, 42 43 drug and device trials. 44 • To determine lead academic authors’ experiences with industry funder collaborations. 45 46 47 48 METHODS 49 50 51 This study was in two parts: 1) a cross-sectional study of trial publications and 2) a survey of the 52 lead academic authors of the 200 most recent industry-funded vaccine, drug and device trials 53 published in one of the top seven high impact general medical journals. 54 55 56 57 58 59 60 https://mc.manuscriptcentral.com/bmj Page 5 of 42 BMJ 1 2 3 4 5 6 Cross-sectional Study 7 8 Search 9 10 11 One authorConfidential: (KR) manually searched the top For seven general Review and internal medical Only journals according 12 to the impact factor of the 2015 Journal Citation Report (New England Journal of Medicine (NEJM), 13 14 Lancet, JAMA, BMJ, Annals of Internal Medicine, JAMA Internal Medicine and PLoS Medicine) for 15 the most recent trial publications meeting our inclusion criteria.13 16 17 18 19 20 Inclusion criteria 21 22 We included publications of phase III and IV trials with one or more academic authors (determined 23 using the institutional address) that disclosed full industry funding. We defined full industry funding 24 25 as any trial with funding exclusively from one or more vaccine, pharmaceutical or device 26 companies. We included industry-supported trials described as investigator-initiated if the only 27 14 28 funding was from industry sources. 29 30 We defined academic authors as authors whose affiliation in the publication was a clinic, hospital, 31 32 university or nonprofit academic research centre. The lead academic author was selected 33 according to the following rank: corresponding author, first author, last author, second author, third 34 35 author, etc. If there were more than one academic corresponding author, the lead academic would 36 be deemed according to the following rank: first author, last author, second author, third author, 37 38 etc.