Conflicts-of-Interest

[Michael Scally MD]

Time [Years] to Publication Among Completed Clinical Trials

Prior studies have shown that 25% to 50% of clinical trials are never published. However, among those published, we know little about the length of time required for publication in the peer-reviewed biomedical literature after study completion. Ioannidis previously demonstrated that a sample of randomized phase 2 and 3 trials conducted between 1986 and 1996 required nearly 2.5 years for publication, while our more recent study of National Institutes of Health (NIH)-funded trials found that the average time to publication was almost 2 years. We sought to determine time to publication for a recent and representative sample of trials published in 2009.

We found, on average, that nearly 2 years had passed between completion and publication of clinical trials, across all trial funders. Moreover, given that our study was necessarily limited to examining time to publication among completed trials that were eventually published, this estimate is conservative. First, we studied trials registered in and linked to ClinicalTrials.gov, a select group of studies. Because of policies in place as of 2005, many may have been registered to ensure compliance with International Committee of Medical Journal Editors requirements for publication and thus more likely to publish in a timely manner. Second, we only studied trials that were published (and indexed via MEDLINE and linked to ClinicalTrials.gov identifiers). Between 50% and 70% of studies registered in ClinicalTrials.gov are eventually published many years after trial completion; 30% to 50% are never published.

We cannot rule out that study findings may have been disseminated through means other than publication, including scientific meeting presentations. However, with the exception of public results reporting, these alternative dissemination strategies lead to limited public awareness of the research. Given the time required to publish results from these clinical trials, our findings support current federal initiatives requiring results reporting of clinical studies within 12 months of trial completion to ensure the timely dissemination of clinical science.


Ross JS, Mocanu M, Lampropulos JF, Tse T, Krumholz HM. Time to Publication Among Completed Clinical Trials. JAMA Intern Med. 2013:1-3. JAMA Network | JAMA Internal Medicine | Time to Publication Among Completed Clinical Trials

 

[Michael Scally MD]

Dollars for Docs Mints a Millionaire
Dollars for Docs Mints a Millionaire - ProPublica

 

[Michael Scally MD]

A Sharp Rise in Retractions Prompts Calls for Reform
http://www.nytimes.com/2012/04/17/s...etractions-prompts-calls-for-reform.html?_r=1

Fang FC, Steen RG, Casadevall A. Misconduct accounts for the majority of retracted scientific publications. Proceedings of the National Academy of Sciences. Misconduct accounts for the majority of retracted scientific publications

A detailed review of all 2,047 biomedical and life-science research articles indexed by PubMed as retracted on May 3, 2012 revealed that only 21.3% of retractions were attributable to error. In contrast, 67.4% of retractions were attributable to misconduct, including fraud or suspected fraud (43.4%), duplicate publication (14.2%), and plagiarism (9.8%). Incomplete, uninformative or misleading retraction announcements have led to a previous underestimation of the role of fraud in the ongoing retraction epidemic. The percentage of scientific articles retracted because of fraud has increased ?10-fold since 1975. Retractions exhibit distinctive temporal and geographic patterns that may reveal underlying causes.

 

[Michael Scally MD]

Trouble at the lab
Scientists like to think of science as self-correcting. To an alarming degree, it is not.
Unreliable research: Trouble at the lab | The Economist

The idea that the same experiments always get the same results, no matter who performs them, is one of the cornerstones of science’s claim to objective truth.

If a systematic campaign of replication does not lead to the same results, then either the original research is flawed (as the replicators claim) or the replications are (as many of the original researchers on priming contend).

Either way, something is awry.

 

[Michael Scally MD]

How science goes wrong
Scientific research has changed the world. Now it needs to change itself
Problems with scientific research: How science goes wrong | The Economist

A SIMPLE idea underpins science: “trust, but verify”. Results should always be subject to challenge from experiment. That simple but powerful idea has generated a vast body of knowledge. Since its birth in the 17th century, modern science has changed the world beyond recognition, and overwhelmingly for the better.

But success can breed complacency. Modern scientists are doing too much trusting and not enough verifying—to the detriment of the whole of science, and of humanity.

 

[Michael Scally MD]

Ioannidis JPA, Greenland S, Hlatky MA, et al. Increasing value and reducing waste in research design, conduct, and analysis. The Lancet 2014;383(9912):166-75. Increasing value and reducing waste in research design, conduct, and analysis : The Lancet

Correctable weaknesses in the design, conduct, and analysis of biomedical and public health research studies can produce misleading results and waste valuable resources. Small effects can be difficult to distinguish from bias introduced by study design and analyses.

An absence of detailed written protocols and poor documentation of research is common. Information obtained might not be useful or important, and statistical precision or power is often too low or used in a misleading way. Insufficient consideration might be given to both previous and continuing studies. Arbitrary choice of analyses and an overemphasis on random extremes might affect the reported findings.

Several problems relate to the research workforce, including failure to involve experienced statisticians and methodologists, failure to train clinical researchers and laboratory scientists in research methods and design, and the involvement of stakeholders with conflicts of interest. Inadequate emphasis is placed on recording of research decisions and on reproducibility of research. Finally, reward systems incentivise quantity more than quality, and novelty more than reliability.

We propose potential solutions for these problems, including improvements in protocols and documentation, consideration of evidence from studies in progress, standardisation of research efforts, optimisation and training of an experienced and non-conflicted scientific workforce, and reconsideration of scientific reward systems.

 

[Michael Scally MD]

van Assen MALM, van Aert RCM, Nuijten MlB, Wicherts JM. Why Publishing Everything Is More Effective than Selective Publishing of Statistically Significant Results. PLoS ONE 2014;9(1):e84896. PLOS ONE: Why Publishing Everything Is More Effective than Selective Publishing of Statistically Significant Results

Background - De Winter and Happee examined whether science based on selective publishing of significant results may be effective in accurate estimation of population effects, and whether this is even more effective than a science in which all results are published (i.e., a science without publication bias). Based on their simulation study they concluded that “selective publishing yields a more accurate meta-analytic estimation of the true effect than publishing everything, (and that) publishing nonreplicable results while placing null results in the file drawer can be beneficial for the scientific collective” (p.4).

Methods and Findings - Using their scenario with a small to medium population effect size, we show that publishing everything is more effective for the scientific collective than selective publishing of significant results. Additionally, we examined a scenario with a null effect, which provides a more dramatic illustration of the superiority of publishing everything over selective publishing.

Conclusion - Publishing everything is more effective than only reporting significant outcomes.

 

[Michael Scally MD]

Pham-Kanter G. Revisiting Financial Conflicts of Interest in FDA Advisory Committees. Milbank Quarterly 2014;92(3):446-70. http://www.milbank.org/uploads/docu...ts_of_Interest_in_FDA_Advisory_Committees.pdf

Policy Points:
· FDA Center for Drug Evaluation and Research advisory committee members who have financial ties solely to the firm sponsoring the drug under review are more likely to vote in ways favorable to the sponsor.
· Committee members who serve on advisory boards for sponsoring firms show particularly strong pro-sponsor bias.
· Contrary to conventional wisdom, committee members who have financial ties to many different firms do not, on average, show pro-industry bias in their voting behavior.

Context The Food and Drug Administration (FDA) Safety and Innovation Act has recently relaxed conflict-of-interest rules for FDA advisory committee members, but concerns remain about the influence of members’ financial relationships on the FDA's drug approval process. Using a large newly available data set, this study carefully examined the relationship between the financial interests of FDA Center for Drug Evaluation and Research (CDER) advisory committee members and whether members voted in a way favorable to these interests.

Methods The study used a data set of voting behavior and reported financial interests of 1,379 FDA advisory committee members who voted in CDER committee meetings that were convened during the 15-year period of 1997–2011. Data on 1,168 questions and 15,739 question-votes from 379 meetings were used in the analyses. Multivariable logit models were used to estimate the relationship between committee members’ financial interests and their voting behavior.

Findings Individuals with financial interests solely in the sponsoring firm were more likely to vote in favor of the sponsor than members with no financial ties (OR = 1.49, p = 0.03). Members with interests in both the sponsoring firm and its competitors were no more likely to vote in favor of the sponsor than those with no financial ties to any potentially affected firm (OR = 1.16, p = 0.48). Members who served on advisory boards solely for the sponsor were significantly more likely to vote in favor of the sponsor (OR = 4.97, p = 0.005).

Conclusions There appears to be a pro-sponsor voting bias among advisory committee members who have exclusive financial relationships with the sponsoring firm but not among members who have nonexclusive financial relationships (ie, those with ties to both the sponsor and its competitors). These findings point to important heterogeneities in financial ties and suggest that policymakers will need to be nuanced in their management of financial relationships of FDA advisory committee members.

 

[Michael Scally MD]

Doctors’Magical Thinking About Conflicts of Interest
http://www.nytimes.com/2014/09/09/u...out-conflicts-of-interest.html?abt=0002&abg=0

 

[Michael Scally MD]

Hidden Conflicts of Interest Found Throughout Medicine
Hidden Conflicts of Interest Found Throughout Medicine

Less obvious places for potential pharmaceutical industry conflicts-of-interest -- patient advocacy groups, physician twitter feeds, and comments submitted to federal agencies -- should be disclosed more regularly, researchers urged.

At the same time, medicine is still falling short on traditional financial disclosures, such as in major clinical practice guidelines, researchers reported in a special issue of JAMA Internal Medicine dedicated to financial conflicts.


Jefferson AA, Pearson SD. Conflict of Interest in Seminal Hepatitis C Virus and Cholesterol Management Guidelines. JAMA Intern Med. Published online January 17, 2017. Conflict of Interest in Seminal Hepatitis C Virus and Cholesterol Management

Importance Little is known regarding whether Institute of Medicine (IOM) standards for managing conflicts of interest (COI) have been met in the development of recent important clinical guidelines.

Objective To evaluate adherence to the IOM standards for limits on commercial COI, guideline development, and evaluation of evidence by the 2013 American College of Cardiology and American Heart Association cholesterol management guideline and the 2014 American Association for the Study of Liver Diseases and Infectious Diseases Society of America hepatitis C virus management guideline.

Design, Setting, and Participants This study was a retrospective document review of the June 2014 print version of the cholesterol guideline and the final September 2015 print version of the hepatitis C virus guideline. Each guideline was assessed for adherence to the IOM standards for commercial COI published in the 2011 special report Clinical Practice Guidelines We Can Trust.

Main Outcomes and Measures The IOM standards call for no commercial COI among guideline committee chairs and cochairs and for less than 50% of committee members to have commercial COI. Guideline and contemporaneous article disclosure statements were used to evaluate adherence to these standards. Each guideline was also reviewed for adherence to other IOM standards for guideline development and evidence review.

Results Among the 16 cholesterol guideline committee members, 7 (44%) disclosed commercial COI, all 7 reported industry-sponsored research, and 6 (38%) also reported consultancy. Of 3 guideline chairs and cochairs, 1 (33%) disclosed commercial COI. Review of contemporaneous articles identified additional commercial COI. Among the 29 hepatitis C virus guideline committee members, 21 (72%) reported commercial COI. Eighteen (62%) disclosed industry-sponsored research, 10 (34%) served on advisory boards, 5 (17%) served on data safety monitoring boards, 3 (10%) were consultants, and 3 (10%) reported other honoraria. Of 6 guideline cochairs, 4 (67%) disclosed commercial COI. All 4 disclosed additional COI in other publications that were not listed in their guideline disclosures. Contemporaneous literature review revealed an additional cochair with commercial COI. Of the 9 IOM guideline development and evidence standards, the cholesterol guideline met 5 (56%), and the hepatitis C virus guideline met them all.

Conclusions and Relevance Neither the cholesterol guideline nor the hepatitis C virus guideline fully met the IOM standards for commercial COI management, and discordance between committee leader guideline disclosures and those in contemporaneous articles was common. Adherence to additional IOM standards for guideline development and evidence review was mixed. Adoption of consistent COI frameworks across specialty societies may help ensure that clinical guidelines are developed in a transparent and trustworthy manner.


Rose SL, Highland J, Karafa MT, Joffe S. Patient Advocacy Organizations, Industry Funding, and Conflicts of Interest. JAMA Intern Med. Published online January 17, 2017. Advocacy Organizations, Industry Funding, and Conflicts of Interest

Importance Patient advocacy organizations (PAOs) are influential health care stakeholders that provide direct counseling and education for patients, engage in policy advocacy, and shape research agendas. Many PAOs report having financial relationships with for-profit industry, yet little is known about the nature of these relationships.

Objective To describe the nature of industry funding and partnerships between PAOs and for-profit companies in the United States.

Design, Setting, and Participants A survey was conducted from September 1, 2013, to June 30, 2014, of a nationally representative random sample of 439 PAO leaders, representing 5.6% of 7865 PAOs identified in the United States. Survey questions addressed the nature of their activities, their financial relationships with industry, and the perceived effectiveness of their conflict of interest policies.

Main Outcomes and Measures Amount and sources of revenue as well as organizational experiences with and policies regarding financial conflict of interest.

Results Of the 439 surveys mailed to PAO leaders, 289 (65.8%) were returned with at least 80% of the questions answered. The PAOs varied widely in terms of size, funding, activities, and disease focus. The median total revenue among responding organizations was $299 140 (interquartile range, $70 000-$1 200 000). A total of 165 of 245 PAOs (67.3%) reported receiving industry funding, with 19 of 160 PAOs (11.9%) receiving more than half of their funding from industry. Among the subset of PAOs that received industry funding, the median amount was $50 000 (interquartile range, $15 000-$200 000); the median proportion of industry support derived from the pharmaceutical, device, and/or biotechnology sectors was 45% (interquartile range, 0%-100%). A total of 220 of 269 respondents (81.8%) indicated that conflicts of interest are very or moderately relevant to PAOs, and 94 of 171 (55.0%) believed that their organizations’ conflict of interest policies were very good. A total of 22 of 285 PAO leaders (7.7%) perceived pressure to conform their positions to the interests of corporate donors.

Conclusions and Relevance Patient advocacy organizations engage in wide-ranging health activities. Although most PAOs receive modest funding from industry, a minority receive substantial industry support, raising added concerns about independence. Many respondents report a need to improve their conflict of interest policies to help maintain public trust.


Tao DL, Boothby A, McLouth J, Prasad V. Financial Conflicts of Interest Among Hematologist-Oncologists on Twitter. JAMA Intern Med. Published online January 17, 2017. Financial Conflicts of Interest of Hematologist-Oncologists on Twitter

Twitter, the social media service that permits 140-character posts or “tweets,” is undergoing rapid uptake by physicians.1 Twitter allows physicians to communicate, interpret, highlight, and curate information as well as engage in discussion or debate with other physicians, patients, patient advocates, researchers, investors, and industry employees. More than 60% of tweets authored by medical professionals in the United States are health-related, and approximately 14% mention commercial products or services.2 Yet, to our knowledge, there has been no investigation of the prevalence of financial conflict of interest (FCOI) among these users.


Lin DH, Lucas E, Murimi IB, Kolodny A, Alexander GC. Financial Conflicts of Interest and the Centers for Disease Control and Prevention’s 2016 Guideline for Prescribing Opioids for Chronic Pain. JAMA Intern Med. Published online January 17, 2017. http://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2598092


Moynihan R, Bero L. Toward a Healthier Patient Voice - More Independence, Less Industry Funding. JAMA Intern Med. Published online January 17, 2017. Toward a Healthier Patient Voice

 

[Michael Scally MD]

From Twitter To Treatment Guidelines, Industry Influence Permeates Medicine
From Twitter To Treatment Guidelines, Industry Influence Permeates Medicine

The long arm of the pharmaceutical industry continues to pervade practically every area of medicine, reaching those who write guidelines that shape doctors' practices, patient advocacy organizations, letter writers to the Centers for Disease Control and Prevention and even oncologists on Twitter, according to a series of papers on money and influence published Tuesday in JAMA Internal Medicine.

The findings of the papers provide further evidence showing how conflicts of interest help shape health care, a subject ProPublica has explored through its Dollars for Docs series since 2010. (Check whether your physician receives money from drug or device companies through ProPublica's search tool.)

"The very way we all think about disease—and the best ways to research, define, prevent, and treat it—is being subtly distorted because so many of the ostensibly independent players, including patient advocacy groups, are largely singing tunes acceptable to companies seeking to maximize markets for drugs and devices," researchers Ray Moynihan and Lisa Bero wrote in an accompanying commentary.

The papers published in the journal cover a variety of issues.

…

 

[Michael Scally MD]

How to spot a “citation cartel”
http://retractionwatch.com/2017/01/18/spot-citation-cartel/ (How to spot a “citation cartel” - Retraction Watch)

Do you know the difference between a group of researchers in the same field who cite each other’s related work, and a group of authors who purposefully cite each other in order to boost their own profiles?

It’s not easy to do, say researchers in a new article about so-called “Citation cartels.”

In Frontiers in Physics, Matjaz Perc and two Iztok Fisters (Senior and Junior) from the University of Maribor in Slovenia present an algorithm to help identify groups of researchers citing each other for overly collegial reasons. Toward the Discovery of Citation Cartels in Citation Networks

(For more on the phenomenon, see a recent column in STAT by our co-founders. “Gaming the system, scientific ‘cartels’ band together to cite each others’ work” Scientific 'cartels' band together to cite each others' work )

We spoke with first author Iztok Fister Jr.

…

 

[Michael Scally MD]

[OA] [Significant] Financial Conflicts of Interest Among Authors of Endocrine Society Clinical Practice Guidelines

Context - There has been a proliferation of clinical practice guidelines in endocrinology and a coincident increased interest in transparency regarding relationships between physicians and industry.

Evidence Acquisition - We collected self-reported disclosures and Open Payments data for 169 authors of 26 clinical practice guidelines published between 2010 and 2017 by the Endocrine Society. Conflicts of interest in which pharmaceutical and device companies manufactured drugs or products pertinent to an author’s specific clinical practice guideline(s) were deemed relevant. Open Payments data were grouped into research and nonresearch (consultancies, honoraria, travel, food) categories.

Evidence Synthesis - We compared the policies of the Endocrine Society regarding seven conflict of interest recommendations issued by the National Academy of Medicine in 2011.

Conclusion - Relevant nonresearch financial conflicts of interest were self-reported by 42% of authors of clinical practice guidelines. Open Payments were recorded for 74% (84 of 113) of US authors between 2013 and 2016. Payments to 84 US authors totaled $5.5 million for nonresearch activities and $30.9 million for research. The nonresearch payments were divided into consulting (46%), honoraria (26%), travel (25%), and food (3%).

The Endocrine Society partially follows the National Academy of Medicine recommendations to limit conflicts of interest. Readers should be aware of how clinical practice guidelines are developed and the policies of the organizations and journals that publish them. Professional societies and journal editors should strive to ensure that their policies and practices promote objective and unbiased clinical practice guidelines.

Irwig MS, Kyinn M, Shefa MC. Financial Conflicts of Interest Among Authors of Endocrine Society Clinical Practice Guidelines*. The Journal of Clinical Endocrinology & Metabolism 2018:jc.2018-00526-jc.2018-. Financial Conflicts of Interest Among Authors of Endocrine Society Clinical Practice Guidelines* | The Journal of Clinical Endocrinology & Metabolism | Oxford Academic

 

[Michael Scally MD]

[OA] Conflicts of Interest in Clinical Practice Guidelines: Accelerating an Evolution

An analysis of the Endocrine Society’s clinical practice guidelines (CPGs) published from 2010 to 2017—presented by Irwig et al. in the current issue of The Journal of Endocrinology and Metabolism—suggested that the Endocrine Society met five of seven National Academy of Medicine (NAM) standards concerning financial conflicts of interest in CPGs.

As current contributors to the Endocrine Society’s CPG efforts, we offer additional context related to the 2011 NAM standards and the current environment concerning industry support in medicine, and we comment on the nature of industry support received by the Society’s CPG authors according to Irwig and colleagues’ analysis of the Centers for Medicare and Medicaid Services’ Open Payments database.

Perhaps most importantly, we outline the Society’s recent and ongoing efforts to enhance the value of its CPGs. Such efforts include a 2016 revision of CPG author conflict of interest rules—a change that was invisible to the investigatory methods used by Irwig et al.—in addition to other processes designed to enhance CPG objectivity.

We conclude our commentary by recognizing that good-faith attempts to enhance transparency and to reduce conflicts of interest (real or apparent) in CPGs will ultimately serve the best interests of patients and providers; we confirm the Endocrine Society’s resolute commitment to providing high-quality, evidence-based clinical guidance via a CPG development process that faithfully accords with current CPG best practices

McCartney CR, Rosen CJ. Conflicts of Interest in Clinical Practice Guidelines: Accelerating an Evolution*. The Journal of Clinical Endocrinology & Metabolism 2018:jc.2018-01878-jc.2018-. Conflicts of Interest in Clinical Practice Guidelines: Accelerating an Evolution* | The Journal of Clinical Endocrinology & Metabolism | Oxford Academic

 

[Michael Scally MD]

Torgerson T, Wayant C, Cosgrove L, et al. Ten years later: a review of the US 2009 institute of medicine report on conflicts of interest and solutions for further reform. BMJ Evid Based Med. 2020 Nov 11:bmjebm-2020-111503. doi: 10.1136/bmjebm-2020-111503. Epub ahead of print. PMID: 33177167. Ten years later: a review of the US 2009 institute of medicine report on conflicts of interest and solutions for further reform | BMJ Evidence-Based Medicine

Conflicts of interest (COIs) in healthcare are increasingly discussed in the literature, yet these relationships continue to influence healthcare. Research has consistently shown that financial COIs shape prescribing practices, medical education and guideline recommendations. In 2009, the Institute of Medicine (IOM, now the National Academy of Medicine) published Conflicts of Interest in Medical Research, Practice, and Education-one of the most comprehensive reviews of empirical research on COIs in medicine. Ten years after publication of theIOM's report, we review the current state of COIs within medicine. We also provide specific recommendations for enhancing scientific integrity in medical research, practice, education and editorial practices.