Financial Conflict of Interest and Medical Research Stephen R. Marder, M.D. Disclosure Information for Stephen R. Marder, MD • Advisory board – Abbott; Amgen; Roche; Shire; Otsuka America Pharmaceutical, Inc.; Wyeth; Pfizer, • Research Support – Novartis; Glaxo Smith Kline; Sunovion; Psychogenics Overview • More than ever, there is an incentive for academic researchers to work with industry – NIH is not equipped to develop drugs and bring them to market – Industry researchers seldom translate the newest biological findings into new pharmacological approaches • Ethical Concerns have led many to mistrust research emerging from industry Research Budget (billions): Top 5 Pharmaceutical Companies 5 4.5 4 3.5 3 2.5 2 1.5 1 0.5 0 billion PFE GLX MRK A/Zen BM/Sq NIMH Drug Development’s Major Challenge: Improving Technical Success Candidate Selection 100% 100% 1 year Phase I First Human Dose 80% 1 ½ years 55% 50% Phase II First Efficacy Dose 2 years 10% 2001 CMR Data 0 Development time - years 1 2 1/2 Phase III First Registration Dose Submission 20% Launch 3 years 11% 1 year 9% 4 1/2 8 1/2 Definition A conflict of interest is 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. Institute of Medicine Report, 2009 Cases example 1 • Nancy Fern Olivieri is a hematologist from Toronto who participated in multi-site study of a drug for thalassaemia. • She became concerned about toxicity of the drug and a lack of efficacy. She informed the ethics board of the hospital and the company. The board instructed her to notify study participants. • The company informed her that her confidentiality agreement prevented from notifying subjects. She did anyway. Case example 2 • A prominent psychiatrist-researcher wrote a review in a very prominent journal that focused on new experimental approaches to treating depression. • It turned out that the author had significant COI’s for some of the approaches. These were not disclosed in the article. Is there evidence of bias in research? • Research funded by industry is more likely to report positive findings (Sismondo, 2008) • Examination of comparisons of antipsychotics found the funder’s drug superior 90% of the time. (Heres, 2006) • Sponsors can control when and where results are published. Neuman et al 2011 • Reviewed 14 practice guidelines • Among members of panels writing clinical practice guidelines, 52% had financial conflicts. • 138 were declared; 12 were not declared A high proportion of Committee Chairs (81%) and Committee members (55%) had conflicts. Appelbaum and Gold • Describe the Principal-Agent Problem where the physician or investigator is engaged as an agent of the drug company. • Other principals may be the scientific community, research subjects, the patients who may benefit from study results Approaches • Disclosure of Financial conflicts • Management of conflicts • Eliminating conflicts Approaches to Disclosure • The 2010 Affordable Care and Patient Protection Act contains sweeping sunshine provisions including the development of a searchable public Web site that will list payments from drug, device, biological, and medical products companies to physicians by name. Limitations of Disclosure • Unclear if readers pay attention • The details of the conflict are not reported • Seldom included in abstracts People can never be trusted to be unbiased. The mind doesn’t work like that “And thou shalt take no bribe; for a bribe blinds the eye of the wise; and perverts the words of the righteous” Gold and Appelbaum Raba stated: What is the reason for [the prohibition against taking] a gift? Because as soon as a man receives a gift from another he becomes so well disposed towards him that [the other person] becomes like his own person, and no man sees himself in the wrong. Managing Investigator COI • AAMC recommends that researchers with financial interests related to study results should not participate or should give up the interests. IOM Recommendation • Academic medical centers and other research institutions should establish a policy that individuals generally may not conduct research with human participants if they have a significant financial interest in an existing or potential product or a company that could be affected by the outcome of the research. IOM Recommendation (cont) • Exceptions to the policy should be made public and should be permitted only if the conflict of interest committee (a) determines that an individual’s participation is essential for the conduct of the research and (b) establishes an effective mechanism for managing the conflict and protecting the integrity of the research. Summary • Concerns about the public’s confidence in medical research should be taken seriously • Vital components of a study design, data analysis, and interpretation should be reviewed by individuals who are unconflicted. • Academic scientists should have all agreements with industry reviewed by their institutions to assure that a company does not infringe on the timely publication of all information.