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Regulation of Therapeutic Research is Compromising the Interests of Patients

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Abstract

In this paper, I consider the impact of research regulation on the duty of doctors to help to resolve uncertainties about the effects of treatments; in particular, treatments already in use within ‘normal’ or ‘usual’ clinical practice. After providing examples of ways in which current research regulation is obstructing this professional duty, I consider the influence of “a confused ethical analysis”, the double-standard in informed consent to treatment within and outside of controlled trials, and the failure of research regulators to use their powers to reduce unnecessary research and promote full publication of necessary research. I suggest that these problems should be addressed by more thoughtful ethical analyses, more effective protection of the interests of patients by research regulators and empirical research to inform the future development of research regulation. Because ethicists and research regulators have paid insufficient attention to these issues, I conclude that they have contributed to the avoidable suffering and deaths of millions of people, the vast majority of whom have not been participants in clinical research.

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References

  1. European Forum for Good Clinical Practice Ethics Working Party. The procedure for the ethical review of protocols for clinical research projects in the European Union. Int J Pharm Med 2007; 21 (1): 1–113

    Google Scholar 

  2. Wade DT. Ethics, audit, and research: all shades of grey. BMJ 2005; 330: 468–73

    Article  PubMed  Google Scholar 

  3. Glasziou P, Chalmers I. Ethics review roulette: what can we learn? BMJ 2004; 328: 121–2

    Article  PubMed  Google Scholar 

  4. Griffiths R. On drinking from a poisoned chalice. BMJ 2006; 332: 801

    Google Scholar 

  5. Hey E, Chalmers I. Investigating allegations of research misconduct: the vital need for due process. BMJ 2000 Sep 23; 321 (7263): 752–5

    Article  PubMed  CAS  Google Scholar 

  6. Hey E, Chalmers I. Are any of the criticisms of the CNEP trial true? Lancet 2006; 367: 1032–3

    Article  PubMed  Google Scholar 

  7. Beecher HK. Ethics and clinical research. New Engl J Med 1963; 274: 1354–60

    Article  Google Scholar 

  8. Pappworth MH. Human guinea pigs: experimentation on man. London: Routledge and Kegan Paul, 1967

    Google Scholar 

  9. Ashcroft RE. The ethics and governance of medical research. In: Ashcroft RE, Dawson A, Draper H, et al., editors. Principles of healthcare ethics. 2nd ed. Chichester: Wiley, 2007: 681–7

    Google Scholar 

  10. Candib LM. How turning a QI project into “research” almost sank a great program. Hastings Center Report 2007 Jan–Feb: 26–30

    Google Scholar 

  11. Cohen P. As ethics panels expand grip, no field is off limits. New York Times 2007 Feb 28 [online]. Available from URL: http://www.nytimes.com/2007/02/28/ arts/28board.html?ex=1330405200&en=c85e708083bf4c41&ei= 5124&partner=digg&exprod=dig [Accessed 2007 Sep 13]

    Google Scholar 

  12. General Medical Council. Good medical practice. 2006 [online]. Available from URL: http://www.gmc-uk.org/guidance/good_medical_practice/GMC_GMP. pdf [Accessed 2007 Feb 7]

  13. Chalmers I. Well informed uncertainties about the effects of treatments: how should clinicians and patients respond? BMJ 2004; 328: 475–6

    Article  PubMed  Google Scholar 

  14. Alderson P, Roberts I. Corticosteroids in acute traumatic brain injury: systematic review of randomised controlled trials. BMJ 1997; 314: 1855–9

    Article  PubMed  CAS  Google Scholar 

  15. CRASH Trial Collaborators. Effect of intravenous corticosteroids on death within 14 days in 10 008 adults with clinically significant head injury (MRC CRASH Trial): a randomised placebo-controlled trial. Lancet 2004; 364: 1321–8

    Article  Google Scholar 

  16. Medical ethics: should medicine turn the other cheek? Lancet 1990; 336: 846–7

    Article  Google Scholar 

  17. Salman RS, Brock TM, Dennis MS, et al. Research governance impediments to clinical trials: a retrospective survey. J R Soc Med 2007; 100: 101–4

    Article  Google Scholar 

  18. Slowther A, Boynton PM, Shaw S. Research governance: ethical issues. J R Soc Med 2006; 99: 65–72

    Article  PubMed  Google Scholar 

  19. Warlow C. A new NHS research strategy. Lancet 2006; 367: 12–3

    Article  PubMed  Google Scholar 

  20. Corrigan OP, Williams-Jones B. Consent is not enough: putting incompetent patients first in clinical trials. Lancet 2003; 361: 2096–7

    Article  PubMed  Google Scholar 

  21. Chalmers I. Provision of consent. Lancet 2003; 362: 663–4

    Article  PubMed  Google Scholar 

  22. CRASH Trial Management Group. Research in emergency situations: with or without relatives consent. Emergency Med J 2004; 21: 703

    Article  Google Scholar 

  23. Schmidt B, Roberts RS, Davis P, et al., and the CAP Investigators. The International Caffeine for Apnea of Prematurity (CAP) Trial: preliminary analysis of outcomes at a corrected age of 182–21 months. [late breaking abstract 5130.1]. Annual Meeting of the American Pediatric Academic Societies; 2007 May 5–7; Toronto

    Google Scholar 

  24. Smithells RW. Iatrogenic hazards and their effects. Postgrad Med J 1975; 15: 39–52

    Google Scholar 

  25. Lantos J. Ethical issues: how can we distinguish clinical research from innovative therapy? Am J Pediatr Hematol Oncol 1994; 16: 72–5

    PubMed  CAS  Google Scholar 

  26. Chalmers I, Silverman WA. Professional and public double standards on clinical experimentation. Control Clin Trials 1987; 8: 388–91

    Article  PubMed  CAS  Google Scholar 

  27. Pappworth MH. Medical ethical committees: a review of their functions. World Med 1978 Feb 22; 13: 19–78

    Google Scholar 

  28. Chalmers I. Medical experimentation. World Med 1978 Apr 5: 18

    Google Scholar 

  29. Pappworth MH. “Human guinea pigs”: a history. BMJ 1990; 301: 1456–60

    Article  PubMed  CAS  Google Scholar 

  30. Chalmers I. Human guinea pigs. BMJ 1991; 302: 411

    Article  Google Scholar 

  31. Stobbart L, Murtagh MJ, Louw SJ, et al. Consent for research in hyperacute stroke. BMJ 2006; 332: 1405–6

    Article  PubMed  Google Scholar 

  32. Silverman WA. Informed consent in customary practice and in clinical trials. In: Goldworth A, Silverman W, Stevenson DK, editors. Ethics and perinatology. New York: Oxford University Press, 1995: 245–62

    Google Scholar 

  33. Oxman AD, Chalmers I, Sackett DL. A practical guide to informed consent to treatment. BMJ 2001; 323: 1464–6 [online]. Available from URL: http://www.bmj.com/cgi/content/full/323/7327/1464

    Article  PubMed  CAS  Google Scholar 

  34. Covert Darbyshire C. Cartoon. The New Yorker 2006 Jul 10

    Google Scholar 

  35. Chalmers I, Lindley R. Double standards on informed consent to treatment. In: Doyal L, Tobias JS, editors. Informed consent in medical research. London: BMJ Publications, 2001: 266–75

    Google Scholar 

  36. Doyal L. The moral importance of informed consent in medical research: concluding reflections. In: Doyal L, Tobias JS, editors. Informed consent in medical research. London: BMJ Publications, 2001: 315

    Google Scholar 

  37. Chalmers I. What do I want from health research and researchers when I am a patient? BMJ 1995; 310: 1315–8

    Article  PubMed  CAS  Google Scholar 

  38. Chalmers I. Better information systems are needed to help patients and clinicians integrate clinical research within everyday clinical practice. Otorhinolaryngology 2007; 137: S69–71

    Google Scholar 

  39. Vist GE, Hagen KB, Devereaux PJ, et al. Outcomes of patients who participate in randomised controlled trials compared to similar patients receiving similar interventions who do not participate. Cochrane Database System Rev 2007 (2). Art. No.: MR000009

    Google Scholar 

  40. Braunholtz D, Edwards SJ, Lilford RJ. Are randomized clinical trials good for us (in the short term)? Evidence for a “trial effect”. J Clin Epidemiol 2001; 54: 217–24

    Article  PubMed  CAS  Google Scholar 

  41. Kumar A, Soares H, Wells R, et al. What is the probability that a new treatment for cancer in children will be superior to an established treatment? BMJ 2005; 331: 1295–8

    Article  PubMed  Google Scholar 

  42. Soares HP, Kumar A, Daniels S, et al. Evaluation of new treatments in radiation oncology: are they better than standard treatments? JAMA 2005; 293: 970–8

    Article  PubMed  CAS  Google Scholar 

  43. Clarke M. The ethical requirement for systematic reviews for randomized trials. In: Ashcroft RE, Dawson A, Draper H, et al., editors. Principles of healthcare ethics. 2nd ed. Chichester: Wiley, 2007: 697–701

    Google Scholar 

  44. Antman EM, Lau J, Kupelnick B, et al. A comparison of results of meta-analyses of randomized control trials and recommendations of clinical experts. JAMA 1992; 268: 240–8

    Article  PubMed  CAS  Google Scholar 

  45. Chalmers I. The lethal consequences of failing to make use of all relevant evidence about the effects of medical treatments: the need for systematic reviews. In: Rothwell P, editor. Treating individuals. London: Lancet, 2007: 37–58

    Google Scholar 

  46. Evans I, Thornton H, Chalmers I. Testing treatments: better research for better healthcare. London: British Library, 2006

    Google Scholar 

  47. Savulescu J, Chalmers I, Blunt J. Are research ethics committees behaving unethically? Some suggestions for improving performance and accountability. BMJ 1996; 313: 1390–3

    Article  PubMed  CAS  Google Scholar 

  48. Chalmers I. Current controlled trials: an opportunity to help improve the quality of clinical research. Curr Control Trials Cardiovasc Med 2000; 1: 3–8

    Article  PubMed  Google Scholar 

  49. Danish Research Ethics Committee System. Recommendation No. 20. Controlled clinical trials: the influence of existing and newly acquired scientific results on the research ethical evaluation. Copenhagen: Danish Research Ethics Committee System, 1997

    Google Scholar 

  50. Department of Health. Governance arrangements for NHS Research Ethics Committees, 2001 July [online]. Available from URL: http://www.dh.gov.uk/ prod_consum_dh/groups/dh_digitalassets/@dh/@en/documents/digitalasset/ dh_4058609.pdf [Accessed 2007 Sep 18]

    Google Scholar 

  51. Teo KK, Yusuf S, Furberg CD. Effects of prophylactic anti-arrhythmic drug therapy in acute myocardial infarction. JAMA 1993; 270: 1589–95

    Article  PubMed  CAS  Google Scholar 

  52. Furberg CD. Effect of antiarrhythmic drugs on mortality after myocardial infarction. Am J Cardiol 1983; 52: 32C–6C

    Article  PubMed  CAS  Google Scholar 

  53. Hine LK, Laird N, Hewitt P, et al. Meta-analytic evidence against prophylactic use of lidocaine in acute myocardial infarction. Arch Intern Med 1989; 149: 2694–8

    Article  PubMed  CAS  Google Scholar 

  54. MacMahon S, Collins R, Peto R, et al. Effects of prophylactic lidocaine in suspected acute myocardial infarction: an overview of results from the randomized, controlled trials. JAMA 1988; 260: 1910–6

    Article  PubMed  CAS  Google Scholar 

  55. Chalmers I. The scandalous failure of science to cumulate evidence scientifically. Clin Trials 2005; 2: 229–31

    Google Scholar 

  56. Fergusson D, Glass KC, Hutton B, et al. Randomized controlled trials of aprotinin in cardiac surgery: using clinical equipoise to stop the bleeding. Clin Trials 2005; 2: 218–32

    Article  PubMed  Google Scholar 

  57. Smith R, Chalmers I. Ethics and medical publishing. In: Ashcroft R, Dawson A, Draper H, et al., editors. Principles of health care ethics. Chichester: John Wiley, 2007: 751–8

    Google Scholar 

  58. Lock S, Wells F. Fraud and misconduct in medical research, 2nd ed. London: BMJ, 1996

    Google Scholar 

  59. Faculty of Pharmaceutical Medicine. Ethical Issues Working Group: ethics in pharmaceutical medicine. Int J Pharm Med 1998; 12: 193–8

    Google Scholar 

  60. Chan A-W, Hrobjartsson A, Haahr M, et al. Empirical evidence for selective reporting of outcomes in randomized trials: comparison of protocols to publications. JAMA 2004; 291: 2457–65

    Article  PubMed  CAS  Google Scholar 

  61. Cowley AJ, Skene A, Stainer K, et al. The effect of lorcainide on arrhythmias and survival in patients with acute myocardial infarction: an example of publication bias. Int J Cardiol 1993; 40: 161–6

    Article  PubMed  CAS  Google Scholar 

  62. Moore T. Deadly medicine. New York: Simon and Schuster, 1995

    Google Scholar 

  63. Antes G, Chalmers I. Under-reporting clinical trials is unethical. Lancet 2003; 361: 978–9

    Article  PubMed  Google Scholar 

  64. Chalmers I. Under-reporting research is scientific misconduct. JAMA 1990; 263: 1405–8

    Article  PubMed  CAS  Google Scholar 

  65. Mann H. Research ethics committees and public dissemination of clinical trial results. Lancet 2002, 8

    Google Scholar 

  66. Emanuel EJ, Wendler D, Grady C. What makes clinical research ethical? JAMA 2000; 283: 2701–11

    Article  PubMed  CAS  Google Scholar 

  67. Ashcroft R. Giving medicine a fair trial. BMJ 2000; 320: 1686

    Article  PubMed  CAS  Google Scholar 

  68. Hope T. Medical ethics: a very short introduction. Oxford: Oxford University Press, 2004

    Google Scholar 

  69. Miller PB, Weijer C. Evaluating benefits and harms in clinical research. In: Ashcroft RE, Dawson A, Draper H, et al., editors. Principles of healthcare ethics. 2nd ed. Chichester: Wiley, 2007: 711–7

    Google Scholar 

  70. Dixon-Woods M, Ashcroft R. ESRC Science in Society workshop on “Governing medical research and medical practice: what’s the difference?” Goodenough College; 2007 Jan 18; London [online]. Available from URL: http:// www2.le.ac.uk/departments/health-sciences/extranet/SSSE/social-sciences/re- search/info/childhood-cancer-tissue-donations/Science%20in%20Society [Accessed 2007 Sep 13]

    Google Scholar 

  71. Rhodes R. Rethinking research ethics. Am J Bioethics 2005; 5: 7–28

    Article  Google Scholar 

  72. Harris J. Scientific research is a moral duty. J Med Ethics 2005; 31: 242–8

    Article  PubMed  Google Scholar 

  73. Woods S. Patients’ obligations? In: Ashcroft RE, Dawson A, Draper H, et al., editors. Principles of healthcare ethics. 2nd ed. Chichester: Wiley, 2007: 719–27

    Google Scholar 

  74. Evans HM. Should patients be allowed to veto their participation in clinical research? J Med Ethics 2004; 30: 198–203

    Article  PubMed  CAS  Google Scholar 

  75. Orentlicher D. Making research a requirement of treatment. Hastings Center Report 2005; 35: 20–8

    Article  PubMed  Google Scholar 

  76. Pearson SD, Miller FG, Emanuel EJ. Medicare’s requirement for research participation as a condition of coverage: is it ethical? JAMA 2006; 296: 988–91

    Article  PubMed  CAS  Google Scholar 

  77. Angell M. The truth about the drug companies: how they deceive us, and what to do about it. New York: Random House, 2004

    Google Scholar 

  78. Kassirer J. On the take: how medicine’s complicity with big business can endanger your health. New York: Oxford University Press, 2004

    Google Scholar 

  79. Saunders J. Research ethics committees: time for a change? Clin Med 2002; 2: 534–8

    PubMed  Google Scholar 

  80. Sokol D. Time to get streetwise: why medical ethics needs doctors. BMJ 2006; 333: 1226 [online]. Available from URL: http://www.bmj.com/cgi/content/full/333/7580/1226?ck=nck

    Article  Google Scholar 

  81. Akkad A, Jackson C, Kenyon S, et al. Informed consent for elective and emergency surgery: questionnaire study. BJOG 2004 Oct; 111 (10): 1133–8

    Article  PubMed  Google Scholar 

  82. Akkad A, Jackson C, Kenyon S, et al. Patients’ perceptions of written consent: questionnaire study. BMJ 2006 Sep 9; 333 (7567): 528. Epub 2006 Jul 31

    Article  PubMed  Google Scholar 

  83. Dixon-Woods M, Williams SJ, Jackson CJ, et al. Why do women consent to surgery, even when they do not want to? An interactionist and Bourdieusian analysis. Soc Sci Med 2006; 62: 2742–53

    Article  PubMed  Google Scholar 

  84. Habiba M, Jackson C, Akkad A, et al. Women’s accounts of consenting to surgery: is consent a quality problem. Quality Saf Health Care 2004; 13: 422–7

    Article  CAS  Google Scholar 

  85. Kenyon S, Dixon-Woods M. What do they know? A content analysis of women’s perceptions of trial information. BJOG 2004; 111: 341–1345

    Google Scholar 

  86. Kenyon S, Dixon-Woods M, Jackson CJ, et al. Participating in a trial in a critical situation: a qualitative study in pregnancy. Quality Saf Health Care 1 2006; 5: 98–101

    Article  Google Scholar 

  87. Flory J, Wendler D, Emanuel E. Informed consent for research. In: Ashcroft RE, Dawson A, Draper H, et al., editors. Principles of healthcare ethics. 2nd ed. Chichester: Wiley, 2007: 703–10

    Google Scholar 

  88. Chalmers I. Lessons for research ethics committees. Lancet 2002; 359: 174

    Article  PubMed  Google Scholar 

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Acknowledgements

I am grateful to Frank Wells and the European Forum for Good Clinical Practice for the invitation to give the 2007 Joseph Hoet Lecture, and to Richard Ashcroft, Frank Davidoff, Hugh Davies, Mary Dixon-Woods, Benjamin Djulbegovic, Imogen Evans, Paul Glasziou, Martin Goller, David Healy, Elina Hemminki, Edmund Hey, Tony Hope, Margaret McCartney, Howard Mann, Andy Oxman, Ching Ling Pang, Michael Parker, Sophie Petit-Zeman, Helen Roberts, Ian Roberts, David Sackett, John Saunders, Hazel Thornton, Andrew Trehearne, Charles Warlow, Frank Wells, Peter Wrobel and two anonymous commentators for helpful comments on an earlier draft of this paper. Readers should not assume that any of these people endorse the current version of this paper.

I declare that I have no conflicts of interest, other than a wish for more relevant and valid evaluation of the effects of the treatments I and other patients may be offered. No sources of funding were used to assist in the preparation of this paper; however, I am grateful to the Medical Research Council and Department of Health for my salary.

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  1. James Lind Library, James Lind Initiative, Summertown Pavilion, Middle Way, Oxford, OX2 7LG, UK

    Iain Chalmers

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1 This paper is based on issues addressed in the Joseph Hoet Memorial Lecture, delivered at a meeting of the European Forum for Good Clinical Practice, Brussels, Belgium on 30 January 2007; an account of the Joseph Hoet Lecture, as delivered, has been published in the Newsletter of the European Forum for Good Clinical Practice, Spring/Summer 2007, pages 3–5.

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Chalmers, I. Regulation of Therapeutic Research is Compromising the Interests of Patients. Int J Pharm Med 21, 395–404 (2007). https://doi.org/10.2165/00124363-200721060-00004

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