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Better Regulation of Industry-Sponsored Clinical Trials is Long Overdue

Published online by Cambridge University Press:  01 January 2021

Matthew Wynia  and
David Boren
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Extract

There is an old saw in health policy that everyone wants health care that is good, fast, and cheap — but it’s impossible to have more than two of these at one time.

A similar bit of folk wisdom seems intuitively true for the development and testing of new pharmaceutical products. The public is in a bind. We want breakthrough drugs, and fast. But we also want these drugs to be affordable, thoroughly tested, safe, and effective. It seems we can’t have it all.

In this paper, we will not claim that one can have it all — but that we can do far better than we are at present. First, we review extensive data on contemporary problems in the design, conduct, and analysis of industry-sponsored clinical trials. Finding major issues that have been solidly documented over more than a decade, we provide many examples of the multifarious ways in which industry-funded trials have been manipulated to raise the likelihood of producing industry-friendly results.

Type
Symposium
Information
Journal of Law, Medicine & Ethics , Volume 37 , Issue 3 , Fall 2009 , pp. 410 - 419
Copyright
Copyright © American Society of Law, Medicine and Ethics 2009

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References

Stossel, T. P., “Regulating Academic-Industrial Research Relationships – Solving Problems or Stifling Progress?” New England Journal of Medicine 353, no. 10 (2005): 1060–1065.CrossRefGoogle Scholar
Lasser, K. E. et al., “Timing of New Black Box Warnings and Withdrawals for Prescription Medications,” JAMA 287, no. 17 (2002): 2215–2220.CrossRefGoogle Scholar
Moore, T. J. et al., “Serious Adverse Drug Events Reported to the Food and Drug Administration, 1998–2005,” Archives of Internal Medicine 167, no. 16 (2007): 1752–1759.CrossRefGoogle Scholar
Collins, J. and Porras, J. I., Built to Last: Successful Habits of Visionary Companies (New York: HarperCollins, 2004).Google Scholar
Wynia, M. K., “Public Health, Public Trust and Lobbying,” American Journal of Bioethics 7, no. 6 (2007): 4–7, at 6.CrossRefGoogle Scholar
Brody, H., Hooked: Ethics, the Medical Profession and the Pharmaceutical Industry (Lanham: Rowman & Littlefield Publishers, Inc.: 2007): at 342.Google Scholar
Ridker, P. M. and Torres, J., “Reported Outcomes in Major Cardiovascular Clinical Trials Funded by For-Profit and Not-for-Profit Organizations: 2000–2005,” JAMA 295, no. 19 (2006): 2270–2276.CrossRefGoogle Scholar
Als-Nielsen, B. et al., “Association of Funding and Conclusions in Randomized Drug Trials”, JAMA 290, no. 7 (2003): 921–928; Djulbegovic, B. et al., “The Uncertainty Principle and Industry-Sponsored Research”, The Lancet 356, no. 9230 (2000): 635-638..CrossRefGoogle Scholar
Bero, L. et al., “Factors Associated with Findings of Published Trials of Drug-Drug Comparisons: Why Some Statins Appear More Efficacious Than Others,” Public Library of Science 4, no. 6 (2007): 1–10.Google Scholar
Id.Google Scholar
Lexchin, J. et al., “Pharmaceutical Industry Sponsorship and Research Outcome and Quality: Systematic Review”, BMJ 326, no. 7400 (2006): 1167–1170.CrossRefGoogle Scholar
Bekelman, J. E. et al., “Scope and Impact of Financial Conflicts of Interest in Biomedical Research”, JAMA 289, no. 4 (2003): 454–456.CrossRefGoogle Scholar
Djulbegovic, B. et al., “The Uncertainty Principle and Industry-Sponsored Research,” The Lancet 356, no. 9230 (2000): 635–638; see Lexchin, , supra note 11; Als-Nielsen, et al., supra note 8; Kjaergard, L. L. and Gluud, C., “Funding, Disease Area, and Internal Validity of Hepatobiliary Randomized Controlled Trials”, American Journal of Gastroenterology 97, no. 11 (2002): 2708-2713.CrossRefGoogle Scholar
See Als-Nielsen, , supra note 8.Google Scholar
Moher, D. et al., “Assessing the Quality of Reports of Randomized Controlled Trials: Implications for the Conduct of MetaAnalyses”, Health Technology Assessment 3, no. 12 (1999), available at <http://www.hta.ac.uk/fullmono/mon312.pdf> (last visited July 2, 2009).CrossRefGoogle Scholar
Chan, A. W. et al., “Empirical Evidence for Selective Reporting of Outcomes in Randomized Trials: Comparison of Protocols to Published Articles,” JAMA 291 (2004): 2457–2465; Rennie, D., “Thyroid Storm”, JAMA 277, no. 15 (1997): 1238-1243.CrossRefGoogle Scholar
Smith, R., “Medical Journals Are an Extension of the Marketing Arm of Pharmaceutical Companies,” Public Library of Science Medicine 2, no. 5 (2005): 364–366.Google Scholar
Laine, C. et al., “Clinical Trial Registration: Looking Back and Moving Ahead,” JAMA 298, no. 3 (2007): 93–94.CrossRefGoogle Scholar
Blumenthal, D. et al., “Withholding Research Results in Academic Life Science: Evidence from a National Survey of Faculty,” JAMA 277, no. 15 (1997): 1224–1228.CrossRefGoogle Scholar
See Lexchin, et al., supra note 11.Google Scholar
Bero, L. A. and Rennie, D., “Influences on the Quality of Published Drug Studies,” International Journal of Technology Assessment in Health Care 12, no. 2 (1996): 209–237; Safer, D. J., “Design and Reporting Modifications in Industry-Sponsored Comparative Psychopharmacology Trials”, Journal of Nervous and Mental Disease 190, no. 9 (2002): 583-592; see Smith, , supra note 17.CrossRefGoogle Scholar
Johansen, H. K. and Gøtzsche, P. C., “Problems in the Design and Reporting of Trials of Antifungal Agents Encountered During Meta-analysis,” JAMA 282, no. 18 (1999): 1752–1759.CrossRefGoogle Scholar
Id.Google Scholar
Psaty, B. M., Weiss, N. S. and Furberg, C. D., “Recent Trials in Hypertention: Compelling Science or Commercial Speech?” JAMA 295, no. 14 (2006): 1704–1706.CrossRefGoogle Scholar
See Safer, , supra note 21.Google Scholar
See Bero, et al., supra note 9.Google Scholar
See Brody, , supra note 6.Google Scholar
Lind, T. et al., “Esomeprazole Provides Improved Acid Control vs. Omeprazole in Patients with Symptoms of Gastro-Oesophageal Reflux Disease,” Alimentary Pharmacology & Therapeutics 14, no. 7 (2000): 861–867.CrossRefGoogle Scholar
See Djulbegovic, et al., supra note 13.Google Scholar
Psaty, B. M. and Rennie, D., “Clinical Trial Investigators and Their Prescribing Patterns,” JAMA 295, no. 23 (2006): 2787–2790.CrossRefGoogle Scholar
Brophy, J. M., “Selling Safety — Lessons from Muraglitazar,” JAMA 294, no. 20 (2005): 2633–2635 at 20.CrossRefGoogle Scholar
Kaul, S. and Diamond, G. A., “Good Enough: A Primer on the Analysis and Interpretation of Noninferiority Trials,” Annals of Internal Medicine 145, no. 1 (2006): 62–69.CrossRefGoogle Scholar
Ross, D. B., “The FDA and the Case of Ketek,” New England Journal of Medicine 356, no. 16 (2007): 1601–1604.CrossRefGoogle Scholar
Farahani, P. et al., “Clinical Data Gap between Phase III Clinical Trials (Pre-Marketing) and Phase IV (Post-Marketing) Studies: Evaluation of Etanercept in Rheumatoid Arthritis,” Canadian Journal of Clinical Pharmacology, 12, no. 3 (2005).Google Scholar
See Brophy, , supra note 31.Google Scholar
Zinman, et al., “The Effect of Adding Exenatide to a Thiazolidinedione in Suboptimally Controlled Type 2 Diabetes,” Annals of Internal Medicine 146, no. 7 (2007): 477–485. (cited in Malozowski, S., “Exenatide in Combination Therapy: Small Study, Big Market, and Many Unanswered Questions”, Annals of Internal Medicine 146, no. 7 [2007]: 477-485).CrossRefGoogle Scholar
See Psaty, and Rennie, , supra note 30.Google Scholar
Curfman, G. D., Morrisey, S. and Drazen, J. M., “Expression of Concern Reaffirmed,” New England Journal of Medicine 354, no. 11 (2006): 1193.CrossRefGoogle Scholar
Hrachovec, J. B. and Mora, M., “Reporting of 6-month vs 12-month Data in a Clinical Trial of Celecoxib,” JAMA 286, no. 19 (2001): 2398–2399; Malhotra, S. et al., “COX-2 Inhibitors: A CLASS Act or Just VIGORously Promoted?” MedGenMed 6 (2004), available at <http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=15208519#r25> (last visited June 22, 2009).Google Scholar
Reid, I. R. et al., “Addition of Monofluorophosphate to Estrogen Therapy in Postmenopausal Osteoporosis: A randomized Controlled trial”, Journal of Clinical Endocrinology and Metabolism 92, no. 7 (2007): 2446–2452.CrossRefGoogle Scholar
Rossouw, J. E. et al., “Risks and Benefits of Estrogen Plus Progestin in Healthy Postmenopausal Women: Principal Results From the Women's Health Initiative Randomized Controlled Trial,” JAMA 288, no. 3 (2002): 321–333.Google Scholar
Epstein, A. E. et al., “Mortality Following Ventricular Arrhythmia Suppression by Encainide, Flecainide, and Moricizine after Myocardial Infarction: The Original Design Concept of the Cardiac Arrhythmia Suppression Trial (CAST),” JAMA 270, no. 20 (1993): 2451–2455.CrossRefGoogle Scholar
Lago, R. M., Singh, P. P. and Nesto, R. W., “Congestive Heart Failure and Cardiovascular Death in Patients with Prediabetes and Type 2 Diabetes Given Thiazolidinediones: A Meta-Analysis of Randomised Clinical Trials,” The Lancet 370, no. 9593 (2007): 1129–1136.CrossRefGoogle Scholar
Kessler, D. A. et al., “Therapeutic-Class Wars — Drug Promotion in a Competitive Marketplace,” New England Journal of Medicine 331, no. 20 (1994): 1350–1353.CrossRefGoogle Scholar
See Psaty, and Rennie, , supra note 30.Google Scholar
See Kessler, et al., supra note 44.Google Scholar
Caulfield, T. A., “Legal and Ethical Issues Associated with Patient Recruitment in Clinical Trials: The Case of Competitive Environment,” Health Law Review 13, nos. 2–3 (2005): 58–61.Google Scholar
See Brody, , supra note 6, at 120.Google Scholar
Eichenwald, K. and Kolata, G., “Drug Trials Hide Conflicts for Doctors,” New York Times, May 16, 1999, available at <http://www.nytimes.com/1999/05/16/business/drug-trials-hide-conflicts-for-doctors.html> (last visited July 2, 2009).+(last+visited+July+2,+2009).>Google Scholar
Rennie, D. and Flanagin, A. “Authorship! Authorship! Guests, Ghosts, Grafters, and the Two-Sided Coin,” JAMA 271, no. 6 (1994): 469–471.CrossRefGoogle Scholar
See Eichenwald, and Kolata, , supra note 49.Google Scholar
See Ross, , supra note 33.Google Scholar
See Eichenwald, and Kolata, , supra note 49; Harris, G. and Roberts, J., “After Sanctions, Doctors Get Drug Company Pay,” New York Times, June 3, 2007, available at <http://www.nytimes.com/2007/06/03/health/03docs.html> (last visited July 2, 2009); Ross, , supra note 33.+(last+visited+July+2,+2009);+Ross,+,+supra+note+33.>Google Scholar
See Eichenwald, and Kolata, , supra note 49.Google Scholar
See Harris, and Roberts, , supra note 53.Google Scholar
See Als-Nielsen, et al., supra note 8.Google Scholar
Holmes, D. R. et al., “Conflict of Interest,” American Heart Journal 147, no. 2 (2004): 228–237.CrossRefGoogle Scholar
See Brody, , supra note 6, at 2.Google Scholar
Melander, H. et al., “Evidence B(i)ased Medicine — Selective Reporting from Studies Sponsored by Pharmaceutical Industry: Review of Studies in New Drug Applications,” BMJ 326, no. 7400 (2003): 1171–1173.CrossRefGoogle Scholar
Knox, K. S. et al., “Reporting and Disseminatino of Industry versus Non-Profit Sponsored Economic Analyses of Six Novel Drugs Used in Oncology,” Annals of Oncology 11, no. 12 (2000): 1591–1595.CrossRefGoogle Scholar
See Brody, , supra note 6, at 119.Google Scholar
Schafer, A, “Biomedical Conflicts of Interest: A Defence of the Sequestration Thesis-Learning from the Cases of Nancy Olivieri and David Healy,” Journal of Medical Ethics 30, no. 1 (2004): 8–24.CrossRefGoogle Scholar
See Rennie, and Flanagin, , supra note 50.Google Scholar
Puckner, W. A. and Leech, P., “The Introduction of New Drugs,” JAMA 93, no. 21 (1929): 1627–1630.Google Scholar
Ross, J. S. et al., “Guest Authorship and Ghostwriting in Publications Related to Rofecoxib,” JAMA 299, no. 15 (2008): 1800–1812.CrossRefGoogle Scholar
See Brody, , supra note 6, at 138.Google Scholar
PricewaterhouseCoopers' Health Research Institute, “Recapturing the Vision: Integrity Driven Performance in the Pharmaceutical Industry,” 2005, available at <http://www.pwc.com/extweb/pwcpublications.nsf/docid/ee74bacb-6de454768525702a00630cff> (last visited June 22, 2009). (last visited June 22, 2009).' href=https://scholar.google.com/scholar?q=PricewaterhouseCoopers'+Health+Research+Institute,+“Recapturing+the+Vision:+Integrity+Driven+Performance+in+the+Pharmaceutical+Industry,”+2005,+available+at++(last+visited+June+22,+2009).>Google Scholar
Lenzer, J., “Scandals Have Eroded US Public's Confidence in Drug Industry,” BMJ 329, no. 7460 (2004): 247; Dolliver, M., “Mark Dolliver's Takes: Big Pharma Is Shifty”, May 28, 2007, available at <http://www.adweek.com/aw/magazine/article_display.jsp?vnu_content_id=1003590894> (last visited June 22, 2009).Google Scholar
See Blumenthal, et al. supra note 19.Google Scholar
See Laine, et al. supra note 18.Google Scholar
For a recent example of an apparent post-hoc, selective analysis, see “Clinical Trial Registry of What?” posted anonymously, available at <http://clinpsyc.blogspot.com/2007/10/clinical-trial-registry-of-what.html> (last visited June 22, 2009).+(last+visited+June+22,+2009).>Google Scholar
Wood, A., Grady, C. and Emanuel, E. J., “Regional Ethics Organizations for Protection of Human Research Participants,” Nature Medicine 10, no. 12 (2004): 1283–1288.CrossRefGoogle Scholar
Brody, , supra note 6; Krimsky, S., Science in the Private Interest: Has the Lure of Profits Corrupted Biomedical Research? (Lanham, MD: Rowman and Littlefield, 2003).Google Scholar
Wilensky, G. R., “Developing a Center for Comparative Effectiveness,” The Commonwealth Fund, available at <http://www.commonwealthfund.org/usr_doc/Wilensky_develctrcompareffect_967_itl.pdf?section=4039> (last visited June 22, 2009).+(last+visited+June+22,+2009).>Google Scholar