Top

Published in:

01-12-2007 | Current Opinion

Regulation of Therapeutic Research is Compromising the Interests of Patients

Author: Professor Sir Iain Chalmers

Published in: Pharmaceutical Medicine | Issue 6/2007

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.

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

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

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

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

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

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

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

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

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

10.

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

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]

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: 475–6PubMedCrossRef

14.

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

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: 1321–8CrossRef

16.

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

17.

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

18.

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

19.

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

20.

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

21.

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

22.

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

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

24.

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

25.

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

26.

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

27.

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

28.

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

29.

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

30.

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

31.

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

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

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 PubMedCrossRef

34.

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

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

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

37.

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

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

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

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: 217–24PubMedCrossRef

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: 1295–8PubMedCrossRef

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: 970–8PubMedCrossRef

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

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: 240–8PubMedCrossRef

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

46.

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

47.

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

48.

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

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

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]

51.

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

52.

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

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: 2694–8PubMedCrossRef

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: 1910–6PubMedCrossRef

55.

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

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: 218–32PubMedCrossRef

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

58.

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

59.

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

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: 2457–65PubMedCrossRef

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: 161–6PubMedCrossRef

62.

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

63.

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

64.

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

65.

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

66.

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

67.

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

68.

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

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

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]

71.

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

72.

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

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

74.

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

75.

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

76.

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

77.

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

78.

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

79.

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

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 CrossRef

81.

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

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 31PubMedCrossRef

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: 2742–53PubMedCrossRef

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: 422–7CrossRef

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

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: 98–101CrossRef

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

88.

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

Title: Regulation of Therapeutic Research is Compromising the Interests of Patients
Author: Professor Sir Iain Chalmers
Publication date: 01-12-2007
Publisher: Springer International Publishing
Published in: Pharmaceutical Medicine / Issue 6/2007
Print ISSN: 1178-2595
Electronic ISSN: 1179-1993
DOI: https://doi.org/10.2165/00124363-200721060-00004

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Regulation of Therapeutic Research is Compromising the Interests of Patients

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 6/2007

Forum

Journal Watch

The Pharmaceutical Medicine Year That Was

Major Pharmaceutical Conferences

Informed Consent in Health Research

Acknowledgement