Conflicts of interest in clinical practice: lessons learned from cardiovascular medicine.

Cardiovascular diseases represent a major burden worldwide, and clinical trials are critical to define treatment improvements. Since various conflicts of interest (COIs) may influence trials at multiple levels, cardiovascular research represents a paradigmatic example to analyze their effects and manage them effectively to re-establish the centrality of evidence-based medicine.Despite the manifest role of industry, COIs may differently affect both sponsored and non-sponsored studies in many ways. COIs influence may start from the research question, data collection and adjudication, up to result reporting, including the spin phenomenon. Outcomes and endpoints (especially composite) choice and definitions also represent potential sources for COIs interference. Since large randomized controlled trials significantly influence international guidelines, thus impacting also clinical practice, their critical assessment for COIs is mandatory. Despite specific protocols aimed to mitigate COI influence, even scientific societies and guideline panels may not be totally free from COIs, negatively affecting their accountability and trustworthiness.Shared rules, awareness of COI mechanisms and transparency with external data access may help promoting evidence-based research and mitigate COIs impact. Managing COIs effectively should preserve public trust in the cardiovascular profession without compromising the positive relationships between investigators and industry.

Promoting Data Sharing: The Moral Obligations of Public Funding Agencies.

Sharing research data has great potential to benefit science and society. However, data sharing is still not common practice. Since public research funding agencies have a particular impact on research and researchers, the question arises: Are public funding agencies morally obligated to promote data sharing? We argue from a research ethics perspective that public funding agencies have several pro tanto obligations requiring them to promote data sharing. However, there are also pro tanto obligations that speak against promoting data sharing in general as well as with regard to particular instruments of such promotion. We examine and weigh these obligations and conclude that all things considered funders ought to promote the sharing of data. Even the instrument of mandatory data sharing policies can be justified under certain conditions.

Reporting Conflicts of Interest and Funding in Health Care Guidelines: The RIGHT-COI&F Checklist.

BACKGROUND: Conflicts of interest (COIs) of contributors to a guideline project and the funding of that project can influence the development of the guideline. Comprehensive reporting of information on COIs and funding is essential for the transparency and credibility of guidelines. OBJECTIVE: To develop an extension of the Reporting Items for practice Guidelines in HealThcare (RIGHT) statement for the reporting of COIs and funding in policy documents of guideline organizations and in guidelines: the RIGHT-COI&F checklist. DESIGN: The recommendations of the Enhancing the QUAlity and Transparency Of health Research (EQUATOR) network were followed. The process consisted of registration of the project and setting up working groups, generation of the initial list of items, achieving consensus on the items, and formulating and testing the final checklist. SETTING: International collaboration. PARTICIPANTS: 44 experts. MEASUREMENTS: Consensus on checklist items. RESULTS: The checklist contains 27 items: 18 about the COIs of contributors and 9 about the funding of the guideline project. Of the 27 items, 16 are labeled as policy related because they address the reporting of COI and funding policies that apply across an organization's guideline projects. These items should be described ideally in the organization's policy documents, otherwise in the specific guideline. The remaining 11 items are labeled as implementation related and they address the reporting of COIs and funding of the specific guideline. LIMITATION: The RIGHT-COI&F checklist requires testing in real-life use. CONCLUSION: The RIGHT-COI&F checklist can be used to guide the reporting of COIs and funding in guideline development and to assess the completeness of reporting in published guidelines and policy documents. PRIMARY FUNDING SOURCE: The Fundamental Research Funds for the Central Universities of China.

Accuracy of Disclosed Financial Relationships between Radiologists and Industry at the 2018 RSNA Annual Meeting.

Online supplemental material is available for this article. See also the editorial by Grant in this issue.

How prevalent are financial conflicts of interest in dermatology randomized controlled trials? A cross-sectional study.

Since the last assessment of conflicts of interest (COIs) in dermatology randomized controlled trials (RCTs) in 2004, several countries have introduced transparency databases. We assessed the prevalence of financial COIs in dermatology RCTs and quantified payments from study sponsors to academic/clinical authors using transparency databases, which are available in the USA, France, Australia, Belgium and the Netherlands, while the UK has a noncompulsory transparency database. We included RCTs from the top 10 dermatology journals and the top 7 general medical journals published in 2019. The study assessed 83 RCTs, and COIs were identified in 69%. The highest prevalence was in exclusively industry-funded trials (46/47, 98%), which consisted of personal payments to an academic/clinical author (96% of trials) and having authors who were employees/stockholders (96%). Payments were identified for 31/56 (55%) academic/clinical first/final authors (median payment US$28 746, maximum US$597 299, interquartile range US$17 061-146 253), and 24/31 payments (77%) payments were each > US$10 000.

Association between conflicts of interest and favourable recommendations in clinical guidelines, advisory committee reports, opinion pieces, and narrative reviews: systematic review.

OBJECTIVE: To investigate the association between conflicts of interest and favourable recommendations in clinical guidelines, advisory committee reports, opinion pieces, and narrative reviews. DESIGN: Systematic review. ELIGIBILITY CRITERIA: Studies that compared the association between conflicts of interest and favourable recommendations of drugs or devices (eg, recommending a drug) in clinical guidelines, advisory committee reports, opinion pieces (eg, editorials), or narrative reviews. DATA SOURCES: PubMed, Embase, Cochrane Methodology Register (from inception to February 2020), reference lists, Web of Science, and grey literature. DATA EXTRACTION AND ANALYSIS: Two authors independently extracted data and assessed the methodological quality of the studies. Pooled relative risks and 95% confidence intervals were estimated using random effects models (relative risk >1 indicates that documents with conflicts of interest more often had favourable recommendations than documents with no conflicts of interest). Financial and non-financial conflicts of interest were analysed separately, and the four types of documents were analysed separately (preplanned) and combined (post hoc). RESULTS: 21 studies that analysed 106 clinical guidelines, 1809 advisory committee reports, 340 opinion pieces, and 497 narrative reviews were included. Unpublished data were received for 11 studies (eight full datasets and three summary datasets). 15 studies showed risk of confounding because the compared documents could differ in factors other than conflicts of interest (eg, different drugs used for different populations). The relative risk for associations between financial conflicts of interest and favourable recommendations for clinical guidelines was 1.26 (95% confidence interval 0.93 to 1.69; four studies of 86 clinical guidelines), for advisory committee reports was 1.20 (0.99 to 1.45; four studies of 629 advisory committee reports), for opinion pieces was 2.62 (0.91 to 7.55; four studies of 284 opinion pieces), and for narrative reviews was 1.20 (0.97 to 1.49; four studies of 457 narrative reviews). An analysis of all four types of documents combined supported these findings (1.26, 1.09 to 1.44). In one study that investigated specialty interests, the association between including radiologists as authors of guidelines and recommending routine breast cancer was: relative risk 2.10, 95% confidence interval 0.92 to 4.77; 12 clinical guidelines). CONCLUSIONS: We interpret our findings to indicate that financial conflicts of interest are associated with favourable recommendations of drugs and devices in clinical guidelines, advisory committee reports, opinion pieces, and narrative reviews. Limitations of this review were risk of confounding in the included studies and the statistical imprecision of individual analyses of each document type. It is not certain whether non-financial conflicts of interest influence recommendations. SYSTEMATIC REVIEW REGISTRATION: Cochrane Methodology Review Protocol MR000040.

[Participant-funded clinical trials on rare diseases]. / Ensayos clínicos en enfermedades raras financiados por los participantes.

The development of medicines for certain rare diseases can be frustrated by lack of funding. In certain cases the patients themselves, or their relatives, occasionally fund the clinical trial in which they will be treated with the investigational medicine. There are 3models of self-funded research: 2of them, "pay to try" and "pay to participate", have already been put into practice. The third, the "plutocratic" proposal, which has been recently put forward is still a theoretical model. In this work the scientific, social and ethical benefits and risks of the 2clinical research models, "pay to participate" and the "plutocratic" proposal, are reviewed. Patient-funded clinical trials are frequently performed through crowdfunding. The most controversial aspects of this funding modality are also addressed in this article from several perspectives. Finally, a future scenario that would allow the launching of self-funded clinical trials in Spain by the "plutocratic" proposal is proposed.

Reporting of drug trial funding sources and author financial conflicts of interest in Cochrane and non-Cochrane meta-analyses: a cross-sectional study.

OBJECTIVE: To (1) investigate the extent to which recently published meta-analyses report trial funding, author-industry financial ties and author-industry employment from included randomised controlled trials (RCTs), comparing Cochrane and non-Cochrane meta-analyses; (2) examine characteristics of meta-analyses independently associated with reporting funding sources of included RCTs; and (3) compare reporting among recently published Cochrane meta-analyses to Cochrane reviews published in 2010. DESIGN: Review of consecutive sample of recently published meta-analyses. DATA SOURCES: MEDLINE database via PubMed searched on 19 October 2018. ELIGIBILITY CRITERIA FOR SELECTING ARTICLES: We selected the 250 most recent meta-analyses listed in PubMed that included a documented search of at least one database, statistically combined results from ≥2 RCTs and evaluated the effects of a drug or class of drugs. RESULTS: 90 of 107 (84%) Cochrane meta-analyses reported funding sources for some or all included trials compared with 21 of 143 (15%) non-Cochrane meta-analyses, a difference of 69% (95% CI 59% to 77%). Percent reporting was also higher for Cochrane meta-analyses compared with non-Cochrane meta-analyses for trial author-industry financial ties (44% versus 1%; 95% CI for difference 33% to 52%) and employment (17% versus 1%; 95% CI for difference 9% to 24%). In multivariable analysis, compared with Cochrane meta-analyses, the odds ratio (OR) for reporting trial funding was ≤0.11 for all other journal category and impact factor combinations. Compared with Cochrane reviews from 2010, reporting of funding sources of included RCTs among recently published Cochrane meta-analyses improved by 54% (95% CI 42% to 63%), and reporting of trial author-industry financial ties and employment improved by 37% (95% CI 26% to 47%) and 10% (95% CI 2% to 19%). CONCLUSIONS: Reporting of trial funding sources, trial author-industry financial ties and trial author-industry employment in Cochrane meta-analyses has improved since 2010 and is higher than in non-Cochrane meta-analyses.

Pushing partnerships: corporate influence on research and policy via the International Life Sciences Institute.

OBJECTIVE: There are concerns that some non-profit organisations, financed by the food industry, promote industry positions in research and policy materials. Using Freedom of Information (FOI) requests, we test the proposition that the International Life Sciences Institute (ILSI), one prominent non-for profit in international health and nutrition research, promotes industry positions. DESIGN: U.S. Right to Know filed five FOI from 2015 to 2018 covering communications with researchers at four US institutions: Texas A&M, University of Illinois, University of Colorado and North Carolina State University. It received 15 078 pages, which were uploaded to the University of California San Francisco's Industry Documents Library. We searched the Library exploring it thematically for instances of: (1) funding research activity that supports industry interests; (2) publishing and promoting industry-sponsored positions or literature; (3) disseminating favourable material to decision makers and the public and (4) suppressing views that do not support industry. RESULTS: Available emails confirmed that ILSI's funding by corporate entities leads to industry influence over some of ILSI activities. Emails reveal a pattern of activity in which ILSI sought to exploit the credibility of scientists and academics to bolster industry positions and promote industry-devised content in its meetings, journal and other activities. ILSI also actively seeks to marginalise unfavourable positions. CONCLUSIONS: We conclude that undue influence of industry through third-party entities like ILSI requires enhanced management of conflicts of interest by researchers. We call for ILSI to be recognised as a private sector entity rather than an independent scientific non-profit, to allow for more appropriate appraisal of its outputs and those it funds.

Ethics and Industry Interactions: Impact on Specialty Training, Clinical Practice, and Research.

Physicians in training and their mentors must be cognizant of ethical concerns related to industry interactions. Mentors perceived to have conflicts of interest or to be engaging in misconduct can unconsciously and profoundly affect the learning and academic environment by implying certain values and expectations. Despite increased awareness of ethical concerns related to industry interactions in clinical practice and research, there remains a need for interventions to prevent ethical transgressions. Ethics education is essential and a move in the right direction, but it alone is likely inadequate in preventing unethical behavior. Education should be supplemented with ethical environments at institutions.