Vol 57: August • Août 2011
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Canadian Family Physician•Le Médecin de famille canadien871
Debates
NO
L
ike any other medical specialty, family medicine needs to engage in research in order to expand its evidence base. With drug companies funding the bulk of clinical research,1 it is natural for family physicians to turn to the pharmaceutical industry for funding—natural, but a serious mistake. There are 3 big reasons for look- ing elsewhere for research dollars: drug companies have a narrow range of interests; many of the postapproval studies that they fund are “seeding trials”; and the results of industry-funded research are often biased.Range of interests
For sound economic reasons, companies are interested in funding research that will increase the sales of their products. At the same time, many of the problems that family medicine deals with have nothing to do with drug therapy (eg, dealing with teenage sexual confusion) and therefore will not be of interest to pharmaceutical com- panies. If family medicine researchers turn to drug com- panies, the range of questions that they will be asking will become more narrow and more commercially ori- ented. Thirty-five percent of life science researchers in American universities who received funding from indus- try reported that they took commercial considerations into account when choosing research topics, compared with 14% who did not have industry support.2
When it comes to problems that have multiple medical approaches, again companies will only be inter- ested in funding research on pharmacotherapy. One good example is osteoarthritis of the knee. General practitioners wanted more research on surgical success rates and on conservative treatments such as educa- tion, and they believed that oral drugs had been over- researched. However, half the studies identified were concerned with oral drug therapy, with pharmaceutical companies funding a quarter of them; conversely, these companies funded only 1 of 33 studies on education and 5 of 238 studies on surgery.3
In a discussion paper, Taylor explored the value of pharmaceutical company–funded clinical research in Canada by surveying 40 key medical figures. Results
indicated that they were happy about the availability of funding from pharmaceutical companies, but they also expressed a number of misgivings about indus- try funding—90% foresaw a likely conflict of interest;
80% deemed clinical pharmaceutical research “me too”
research; 75% saw it as “might as well” research; and 40% were worried about a potential delay in the publica- tion of unfavourable results.4
Seeding trials
Doctors who participate in clinical trials are known to increase their use of trial drugs.5 Companies take advan- tage of this knowledge to sponsor postapproval trials, referred to as seeding trials, whose sole purpose is to get doctors to start and continue to use a product.6
The most widely publicized seeding trial was the ADVANTAGE (Assessment of Differences between Vioxx and Naproxen To Ascertain Gastrointestinal Tolerability and Effectiveness) study,7 undertaken by Merck, to pro- mote the use of rofecoxib (ie, Vioxx). An analysis of Merck internal and external correspondence, reports, and presentations showed that “the trial was designed by Merck’s marketing division to fulfill a marketing objective; Merck’s marketing division handled both the scientific and the marketing data, including collection, analysis, and dissemination; and Merck hid the market- ing nature of the trial from participants, physician inves- tigators, and institutional review board members.”8
Biases in industry-funded research
Whether certain pharmaceuticals are used extensively or not at all is dependent on the outcome of clinical research; because of that, and owing to the intense com- petitive nature of the pharmaceutical industry, there is strong financial pressure to ensure that research results are favourable to the product being studied. A recent qualitative systematic review looked at 19 meta-analy- ses examining the relationship between industry-funded research and outcomes; 17 of them concluded that indus- try funding was more likely to produce positive findings.9
One reason often offered to justify positive industry- funded research results is that drug companies have the resources to mount trials with large numbers of patients that are powered to find statistically significant differences. However, this defence cannot explain the
Does family medicine have a professional
obligation to play a leading role in pharmaceutical industry–sponsored drug research?
Joel Lexchin
MDcontinued on page 873 Cet article se trouve aussi en français à la page 875.
Vol 57: August • Août 2011
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Canadian Family Physician•Le Médecin de famille canadien873
Debates
NO
continued from page 871superiority associated with industry sponsorship in situ- ations in which head-to-head trials of 2 different medi- cations have different outcomes depending on which company is sponsoring the trial. For example, of 9 stud- ies comparing olanzapine and risperidone, 5 were spon- sored by Eli Lilly, the maker of olanzapine, and favoured that drug, whereas 3 of the 4 sponsored by Janssen, the maker of risperidone, favoured that medicine.10 Similarly, randomized controlled head-to-head comparisons of statins were more likely to report conclusions favour- ing the sponsor’s product compared with the other drug being studied.11
Companies systematically do not publish research that is unfavourable to their products, and what is pub- lished frequently has its conclusions dramatically altered.
Out of 74 studies registered with the United States Food and Drug Administration (FDA) dealing with 12 antide- pressants, “a total of 37 studies viewed by the FDA as having positive results were published; 1 study viewed as positive was not published.”12 An additional 11 stud- ies that produced either negative or questionable results were published in a way that conveyed positive out- comes. Although the published material made it appear as though 94% of the trials had positive results, the FDA analysis showed that only 51% had positive outcomes.
In addition to this selective publication was the fact that the effect sizes of the published trials were systemati- cally inflated by a mean of 32%.12
Conclusion
Getting research dollars is never easy, especially to fund studies that concern family physicians; it is tempting to turn to pharmaceutical companies for help, but that temptation needs to be resisted. Pharmaceutical com- panies are concerned with the bottom line, and their research efforts are directed toward ensuring that that bottom line is enhanced. Family medicine research needs to put patient needs ahead of private profits.
Dr Lexchin is Professor in the School of Health Policy and Management at York University in Toronto, Ont, an emergency physician with the University Health Network in Toronto, and Associate Professor in the Department of Family and Community Medicine at the University of Toronto.
Competing interests
Dr Lexchin was a consultant to a law firm representing Apotex in 2007. From 2007 to 2008 he was a consultant to the Canadian federal government in its defence against a lawsuit challenging the ban on direct-to-consumer advertis- ing of prescription drugs. In 2010 he was a consultant to a law firm represent- ing the family of a patient who was alleged to have died from a side effect of a drug made by Allergan Inc. He is a current member of the Management Group at Healthy Skepticism and a member of the Association Board at Health Action International Europe.
Correspondence
Dr Joel Lexchin, School of Health Policy and Management, York University, 4700 Keele St, Toronto, ON M3J 1P3; telephone 416 736-2100, extension 22119;
e-mail jlexchin@yorku.ca
References
1. Moses H 3rd, Dorsey ER, Matheson DH, Thier SO. Financial anatomy of bio- medical research. JAMA 2005;294(11):1333-42.
2. Blumenthal D, Campbell EG, Causino N, Louis KS. Participation of life- science faculty in research relationships with industry. N Engl J Med 1996;335(23):1734-9.
3. Tallon D, Chard J, Dieppe P. Relation between agendas of the research com- munity and the research consumer. Lancet 2000;355(9220):2037-40.
4. Taylor KM. The impact of the pharmaceutical industry’s clinical research pro- grams on medical education, practice and researchers in Canada: a discussion paper. In: Canadian pharmaceutical research and development: four short-term studies. Ottawa, ON: Industry, Science and Technology Canada; 1991.
5. Andersen M, Kragstrup J, Søndergaard J. How conducting a clinical trial affects physicians’ guideline adherence and drug preferences. JAMA 2006;295(23):2759-64.
6. Psaty BM, Rennie D. Clinical trial investigators and their prescribing patterns:
another dimension to the relationship between physician investigators and the pharmaceutical industry. JAMA 2006;295(23):2787-90.
7. Lisse JR, Perlman M, Johansson G, Shoemaker JR, Schechtman J, Skalky CS, et al. Gastrointestinal tolerability and effectiveness of rofecoxib versus naproxen in the treatment of osteoarthritis: a randomized, controlled trial.
Ann Intern Med 2003;139(7):539-46.
8. Hill KP, Ross JS, Egilman DS, Krumholz HM. The ADVANTAGE seeding trial: a review of internal documents. Ann Intern Med 2008;149(4):251-8.
9. Sismondo S. Pharmaceutical company funding and its consequences: a qual- itative systematic review. Contemp Clin Trials 2008;29(2):109-13. Epub 2007 Aug 16.
10. Heres S, Davis J, Maino K, Jetzinger E, Kissling W, Leucht S. Why olanzapine beats risperidone, risperidone beats quetiapine, and quetiapine beats olan- zapine: an exploratory analysis of head-to-head comparison studies of sec- ond-generation antipsychotics. Am J Psychiatry 2006;163(2):185-94.
11. Bero L, Oostvogel F, Bacchetti P, Lee K. Factors associated with findings of published trials of drug-drug comparisons: why some statins appear more efficacious than others. PLoS Med 2007;4(6):e184.
12. Turner EH, Matthews AM, Linardatos E, Tell RA, Rosenthal R. Selective pub- lication of antidepressant trials and its influence on apparent efficacy. N Engl J Med 2008;358(3):252-60.
closing arguments
• Pharmaceutical companies fund research studies within a narrow range of interests with more commercial appeal; often the questions being posed by these studies are not relevant to family medicine.
• When physicians participate in pharmaceutical industry–
sponspored clinical trials, their use of the trial drugs often increases; therefore, pharmaceutical companies often fund postapproval trials with the sole purpose of getting family doctors to begin prescribing a certain drug.
• Results of industry-funded research are often biased in favour of the drug being studied; studies with negative outcomes often go unpublished or their conclusions are altered to appear favourable.
