Identifying and Managing Non-Financial Conflicts of Interest

1. Identifying and Managing Non-Financial Conflicts of Interest Meera Viswanathan PhD Tim Carey MD MPH September 2012

2. AHRQ NFCOI Workgroup Members • Eric Bass • Suzanne Belinson • Elise Berliner • Tim Carey • Stephanie Chang • Donna Dryden • Elaine Graham • Jeanne-Marie Guise • Stanley Ip • Margaret Maglione • Doug McCrory • Melissa McPheeters • Sydne Newberry • Susan Norris • Sara Ratichek • David Samson • Paul Shekelle • Priyanka Sista • Meera Viswanathan • Michael White

3. Overview • Nonfinancial Conflict of Interest (NFCOI) • Why it matters • Concerns regarding NFCOI • Definitions • Identifying the Context • Measuring and Disclosing NFCOI • Judging the Risk of Bias from NFCOI • Managing NFCOI • Monitoring and Reporting NFCOI • Next Steps

4. Why COI Matters • Increasing public skepticism regarding validity of science • Research and researchers coming under increasing scrutiny • COI policies rapidly evolving • New (2011) DHHS guidance for financial COI • No current guidance with DHHS or many universities for NFCOI • Need to reconcile conflicting policies where guidance does exist

6. Concerns about Conflicts of Interest • Bias in study conduct or results is the fundamental concern regarding COI • Researchers may feel accused of 'bias' or COI in circumstances where risk is very low. • We cannot assume that any individual professional will necessarily let financial or other gain influence his/her judgment. • Policies are in place for prevention and management; not punishment • The COI issues for CER and PCOR may be more sensitive, a ‘lower bar’ for investigators

7. Defining Nonfinancial Conflict of Interest Should the definition of NFCOI account for • Financial versus nonfinancial conflicts? • Individual versus institutional conflicts? • Real versus perceived conflicts? • Nonfinancial conflict refers to a set of circumstances that creates a risk that the primary interest, the systematic review, will be unduly influenced by a secondary or competing interest that is not mainly financial.

8. Steps to Identifying and Managing NFCOI • Identify context-specific issues • Identify and disclose NFCOI • Assess the degree to which the potential for undue influence from NFCOI exists • Manage NFCOI that has the potential to unduly influence the systematic review • Monitor and report NFCOI regularly

9. Context Matters! Consider the potential consequences for NFCOI in each of these cases • Strong advocacy positions or active policy debate  • Inter-specialty variations in practice  • Few clinical experts 

10. Examples of NFCOI • Personal Beliefs  • Personal Relationships • Institutional Relationships • Career Advancement  

11. Measures of Disclosure • Direct measures: do you consider yourself at risk of NFCOI? • Proxy measures: what activities are you currently involved that may be a NFCOI? • How comprehensive a list is needed?

12. Judging the Risk of Bias from NFCOI • No formula • Three considerations (IOM): • The value of the secondary interest • The scope of the relationship • The extent of discretion on the part of the reviewer Institute of Medicine. Conflict of Interest in Medical Research, Education, and Practice. Washington, DC: The National Academies Press; 2009.

13. Managing NFCOI: It’s not just disclosure • Exclusion from review • Exclusion from some tasks (e.g., rating the risk of bias of individual studies or grading the strength of evidence) • Inclusion and balance with other viewpoints • Disclosure only

14. Monitoring and Reporting NFCOI • Whose responsibility? Funder or PI? • Frequency of reporting? • One time vs ongoing? • Report to funder or on report?

15. NFCOI and Context: Case Examples

16. Advocacy/Policy Positions • A state neurology society has a position statement saying that medications for restless leg syndrome are ineffective and have no place in therapy. Dr. Archibald is the president-elect for the society but not an author of their position paper. He is asked to be a SR team member on a project looking into the comparative effectiveness of medications for restless leg syndrome versus supportive care alone. Dr. Archibald does not hold a strong personal opinion about the benefits and risks of medications for restless leg syndrome, but becoming president is the culmination of several years of hard work.

17. Inter-Specialty Variations in Practice • Patients with low back pain may seek care from a variety of providers, including allopathic specialists (orthopedic surgeons, physical medicine and rehabilitation, neurologic surgeons, rheumatologists), osteopathic physicians, doctors of chiropractic, and physical therapists. Descriptive research has shown that the types of treatments, and their associated costs, vary substantially across these specialties. Multiple studies, including large cohort studies, secondary data analyses, and some trials, have examined both cost and functional status outcomes. The review question is to compare the clinical outcomes in acute and sub-acute back pain when treatment is initiated with one of the above providers.

18. Few Clinical Experts • A systematic review of a condition that affects fewer than 4000 individuals in the country is conducted. The condition is debilitating if not treated and a new drug has been approved, based on two fairly small RCTs. Other drugs are in the pipeline and early research is available on some compounds. The pharmaceutical company that produced the drug funds almost all research in the field and their scientists are major players at scientific meetings, etc. All patients are treated at a limited number of specialist clinics, mostly at academic centers. All clinics are engaged at some level of research, at the very least by enrolling patients in the drug trials. The SR team includes a nurse who runs a clinic caring for patients with the condition. She is the only team member with direct clinical experience, but because all clinics are enrolling patients in the drug trials, she is actively enrolling patients.

19. Questions for Funders and PIs to Assess the Context for NFCOI for Systematic Reviews • Is the topic the subject of advocacy or policy change? • If yes, consider asking additional questions on NFCOI for individual team members •  Does the topic have inter-specialty variations in diagnostic or treatment approaches? • If yes, consider asking additional questions on NFCOI for individual team members • Is there a limited pool of experts with knowledge in this field? • If yes, consider management strategies other than exclusion of team members with COI to ensure adequate expertise on the team.

20. When Context Matters: Questions for Systematic Review Team Members to Disclose NFCOI (1) Advocacy/policy positions • To the best of your knowledge, do you work for, or are you a member of an organization with a stated position (e.g., position statement, blog, editorial, legislature or legal testimony, or related document) related to the topic area of this comparative effectiveness review? • If yes, are you involved in formulating/voting for positions? • If you are involved in formulating or voting for positions, could positive or negative findings of this evidence report conflict with policies you have promoted or are obliged to follow?

21. When Context Matters: Questions for Systematic Review Team Members to Disclose NFCOI (2) Inter-specialty variations in practice: There are no correct answers to these questions. Responses to these questions are intended to ensure adequate disclosure • What is your primary clinical specialty or subspecialty? •  Do you prescribe or otherwise recommend the test or treatment to be examined in this review? 

22. Types of NFCOI: Case Examples

23. Personal Beliefs • Progressive Brain Disorder (PBD) is rare, not currently treatable and devastating • A novel procedure, heavily promoted by a biotech company (Ferretech) claims promising preliminary results through the injection of ferret stem cells into the corpus callosum. • Your institution fortunately has on faculty 3 neurologists with some experience in PBD, its natural history and outcomes. You approach each of them regarding participating as a core team member in a funded systematic review. This will involve content expertise, participating in some article reviews and co-authorship.

24. Professor Brown • Extensive experience treating PBD. He has been a co-author on several case series describing the natural history of the disease as well as narrative reviews and discussions of pathogenesis. No ties to Ferretch. After the review starts, one of younger research assistants sends you screen shots of a blog that Dr Brown participates in. He wrote that “ferret stem cells will certainly result in dramatic improvement in function and longevity.’

25. Professor Black • She has written a few articles on the complications of PBD; no industry ties, and is interested in collaborating. One Saturday you see her coming out of a local church, the “Congregation of human purity”. This congregation, you recall, has doctrines that ban human-ferret tissue exchange.

26. Personal Relationships • Joe Schneider is working on a comparative effectiveness review on treatments for breast cancer. Joe is friends with Stuart, an old college roommate who owns a startup company that manufactures Wonderdrug, a new medication to treat breast cancer. Wonderdrug has received substantial media coverage and their commercial business is brisk. Neither Joe nor anyone in his family has financial investments in the company. Studies of Wonderdrug report favorable remission rates, but one study reports myocardial infarction among women taking Wonderdrug. Studies of other drugs and comparator groups found no similar events

27. Institutional Relationships • University A holds a patent for a medical device included in a CER being conducted by the university-affiliated EPC. Members of the review staff are aware of the university-held patent. The lead investigator on the CER knows that the early literature (prior to the year 2000) on the device highlighted some potential adverse effects. The device developers made some modifications and later studies did not report adverse effects.

28. Career Advancement • A widely held belief is that saturated fat is bad for cardiovascular health. Dr. Smith has been asked to conduct a CER comparing Drug X with Drug Y to prevent primary myocardial infarctions in US populations. The participants’ dietary intake of saturated fat in the various studies is also analyzed. The findings showed that Drug X is more effective than Drug Y in preventing myocardial infarctions. The CER also found that high dietary intake of saturated fat is associated with a decreased risk of myocardial infarctions independent of Drug X or Drug Y. Dr. Smith, an assistant professor, is being considered for promotion to associate professor. A number of his mentors and peers built their academic careers reporting the harms of saturated fat.

29. Questions for Systematic Review Team Members to Disclose NFCOI (1) • Please answer the following questions to the best of your existing knowledge. The questions are not intended to require additional research or time-intensive inquiry beyond your current awareness. Personal beliefs • Do you have strongly held beliefs related to the topic area that would make it difficult for you to consider alternative conclusions on this comparative effectiveness review in an unbiased manner? • If Yes, please explain Previously published opinions • Have you ever authored, coauthored, or publicly provided an opinion related to the topic area of this comparative effectiveness review?   • If yes, what were those views and where were they made?

30. Questions for Systematic Review Team Members to Disclose NFCOI (2) Institutional relationships • Could your institution benefit or be harmed based on whether this review finds benefit, harm, or no difference in outcomes? • If yes, please explain. Career advancement • How would you characterize the support you would receive from your primary mentor, institution, or other entities, if your work generated a strong negative reaction from peers outside your institution?

31. AHRQ Draft Report on Nonfinancial Conflicts of Interest • http://effectivehealthcare.ahrq.gov/research-available-for-comment/comment-draft-reports/?pageaction=displayDraftCommentForm&topicid=467&productID=1245 • We welcome your comments!

32. Next Steps • Incidence and impact of NFCOI • Utility of the proposed NFCOI guidance • For funders • For researchers • For the public • Burden and variation in interpretation of the questions relating to identifying NFCOI • Effect of NFCOI policies and their implementation on the credibility of CER research