Journal of Hepatology
Volume 51, Issue 4 , Pages 792-797 , October 2009

Ethics in clinical research

References 

  1. Regulation (EC) No. 726/2004 of the European Parliament and of the Council of 31 March 2004 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency (Official Journal L 136, 30/4/2004 p. 1–33). Available on the web: http://ec.europa.eu/enterprise/pharmaceuticals/eudralex/vol-1/reg_2004_726_cons/reg_2004_726_cons_en.pdf (last access February 6, 2009).
  2. Ottolenghi L, Bertele’ V, Garattini S. Limits of add-on trials: antirheumatic drugs. Eur J Clin Pharmacol. 2009;65:33–41
  3. Zinman B, Hoogwerf BJ, Durán Garcı´a S, Milton DR, Giaconia JM, Kim DD, et al. The effect of adding exenatide to a thiazolidinedione in suboptimally controlled type 2 diabetes: a randomized trial. Ann Intern Med. 2007;146:477–485
  4. DHHS Food and Drug Administration. 21 CFR part 312. Human subject protection; foreign clinical studies not conducted under an investigational new drug application. Final rule 28 April 2008, effective, October 27 2008. http://www.regulations.gov/fdmspublic/component/main?main=DocumentDetail&o=0900006480537f08 (last access June 1st, 2009).
  5. Goodyear MD, Lemmens T, Sprumont D, Tangwa G. Does the FDA have the authority to trump the Declaration of Helsinki?. BMJ. 2009;338:1157–1158
  6. Apolone G, Joppi R, Bertele’ V, Garattini S. Ten years of marketing approvals of anticancer drugs in Europe: regulatory policy and guidance documents need to find a balance between different pressures. Br J Cancer. 2005;93:504–509
  7. Splawinski J, Kuzniar J. Clinical trials: active control vs placebo – what is ethical?. Sci Eng Ethics. 2004;10:73–79
  8. Garattini S, Bertele’ V, Li Bassi L. How can research ethics committees protect patients better?. BMJ. 2003;326:1199–1201
  9. Garattini S, Bertele’ V. Non-inferiority trials are unethical because they disregard patients’ interests. Lancet. 2007;370:1875–1877
  10. Barbui C, Violante A, Garattini S. Does placebo help establish equivalence in trials of new antidepressants?. Eur Psychiatry. 2000;15:1–6
  11. Bertele’ V, Torri V, Garattini S. Inconclusive messages from equivalence trials in thrombolysis. Heart. 1999;81:675–676
  12. Moher D, Dulberg CS, Wells GA. Statistical power, sample size, and their reporting in randomized controlled trials. JAMA. 1994;272:122–124
  13. U.S. Food and Drug Administration (2006) US FDA’S noninferiority stance could slow sinusitis approvals. SCRIP – World Pharmaceutical News 3193: 27.
  14. Committee for Medicinal Products for Human Use (CHMP). Guideline on clinical investigation of medicinal products in the treatment of Parkinson’s disease. (CHMP/563/95 Rev.1) http://www.emea.europa.eu/pdfs/human/ewp/056395en.pdf (last access June 1st, 2009).
  15. Committee for Medicinal Products for Human Use (CHMP). Guideline on medicinal products for the treatment of Alzheimer’s disease and other dementias. (CPMP/EWP/553/95 Rev.1) http://www.emea.europa.eu/pdfs/human/ewp/055395en.pdf (last access June 1st, 2009).
  16. Van Spall HG, Toren A, Kiss A, Fowler RA. Eligibility criteria of randomized controlled trials published in high-impact general medical journals: a systematic sampling review. JAMA. 2007;297:1233–1240
  17. Rochon PA, Fortin PR, Dear KB, Minaker KL, Chalmers TC. Reporting of age data in clinical trials of arthritis. Deficiencies and solutions. Arch Intern Med. 1993;153:243–248
  18. Tappenden P, Jones R, Paisley S, Carroll C. Systematic review and economic evaluation of bevacizumab and cetuximab for the treatment of metastatic colorectal cancer. Health Technol Assess. 2007;11:1–128
  19. Pandolfini C, Bonati M. A literature review on off-label drug use in children. Eur J Pediatr. 2005;164:552–558
  20. Psaty BM, Weiss NS. NSAID trials and the choice of comparators–questions of public health importance. N Engl J Med. 2007;356:328–330
  21. Tricontinental Mycophenolate Mofetil Renal Transplantation Study Group. A blinded, randomized clinical trial of mycophenolate mofetil for the prevention of acute rejection in cadaveric renal transplantation. Transplantation 1996; 61: 1029–37.
  22. Remuzzi G, Lesti M, Gotti E, Dimitrov BD, Ene-Iordache B, Gherardi G, et al. Mycophenolate mofetil versus azathioprine for prevention of acute rejection in renal transplantation (MYSS): a randomized trial. Lancet. 2004;364:503–512
  23. Margreiter R. Efficacy and safety of tacrolimus compared with ciclosporin microemulsion in renal transplantation: a randomized multicentre study. Lancet. 2002;359:741–746
  24. Schieppati A, Perico N, Remuzzi G. Tacrolimus and ciclosporin microemulsion in renal transplantation. Lancet. 2002;360:799–800
  25. Geddes J, Freemantle N, Harrison P, Bebbington P. Atypical antipsychotics in the treatment of schizophrenia: systematic overview and meta-regression analysis. BMJ. 2000;321:1371–1376
  26. Leucht S, Corves C, Arbter D, Engel RR, Li C, Davis JM. Second-generation versus first-generation antipsychotic drugs for schizophrenia: a meta-analysis. Lancet. 2009;373:31–41
  27. Tyrer P, Kendall T. The spurious advance of antipsychotic drug therapy. Lancet. 2009;373:4–5
  28. Epstein AE, Hallstrom AP, Rogers WJ, Liebson PR, Seals AA, Anderson JL, 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. 1993;270:2451–2455
  29. Bush TL, Barrett-Connor E, Cowan LD, Criqui MH, Wallace RB, Suchindran CM, et al. Cardiovascular mortality and noncontraceptive use of estrogen in women: results from the lipid research clinics program follow-up study. Circulation. 1987;75:1102–1109
  30. The Women’s Health Initiative Steering Committee. Effects of Conjugated Equine Estrogen in Postmenopausal Women With Hysterectomy. The Women’s Health Initiative Randomized Controlled Trial, JAMA. 2004; 291: 1701–12.
  31. Barter PJ, Caulfield M, Eriksson M, Grundy SM, Kastelein JJ, Komajda M, et al. Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med. 2007;357:2109–2122
  32. Klimt CR, Knatterud GL, Meinert CL, Prout TE. A study of the effects of hypoglycemic agents on vascular complications in patients with adult-onset diabetes (UGDP). Diabetes. 1970;19:747–830
  33. Freemantle N, Calvert N. Composite and surrogate outcomes in randomised controlled trials. BMJ. 2007;334:756–775
  34. Lapostolle F, Catineau J, Lapandry C, Adnet F. Endpoints in studies on myocardial infarction. Lancet. 2007;369:1430
  35. Ferreira-Gonzalez I, Busse JW, Heels-Ansdell D, Montori VM, Akl EA, Bryant DM, et al. Problems with use of composite end points in cardiovascular trials: systematic review of randomised controlled trials. BMJ. 2007;334:786–792
  36. DREAM (Diabetes REduction Assessment with ramipril and rosiglitazone Medication) Gerstein HC, Yusuf S, Bosch J, Pogue J, Sheridan P, Dinccag N, et al. Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomized controlled trial. Lancet. 2006;368:1096–1105
  37. Stern JM, Simes RJ. Publication bias: evidence of delayed publication in a cohort study of clinical research projects. BMJ. 1997;315:640–645
  38. Melander H, Ahlqvist-Rastad J, Meijer G, Beermann B. Evidence b(i)ased medicine–selective reporting from studies sponsored by pharmaceutical industry: review of studies in new drug applications. BMJ. 2003;326:1171–1173
  39. Kirsch I, Deacon BJ, Huedo-Medina TB, Scoboria A, Moore TJ, Johnson BT. Initial severity and antidepressant benefits: a meta-analysis of data submitted to the food and drug administration. PLoS Med. 2008;5:e45
  40. Chan AW, Hrobjartsson A, Haahr MT, Gotzsche PC, Altman DG. Empirical evidence for selective reporting of outcomes in randomized trials: comparison of protocols to published articles. JAMA. 2004;291:2457–2465
  41. Lieberman JA, Stroup TS, McEvoy JP, Swartz MS, Rosenheck RA, Perkins DO, et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med. 2005;353:1209–1223
  42. Bombardier C, Laine L, Reicin A, Shapiro D, Burgos-Vargas R, Davis B, et al. Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group. N Engl J Med. 2000;343:1520–1528
  43. Juni P, Nartey L, Reichenbach S, Sterchi R, Dieppe PA, Egger M. Risk of cardiovascular events and rofecoxib: cumulative meta-analysis. Lancet. 2004;364:2021–2029
  44. Kjaergard LL, Als-Nielsen B. Association between competing interests and authors’ conclusions: epidemiological study of randomised clinical trials published in the BMJ. BMJ. 2002;325:249–252
  45. Cho MK, Bero LA. The quality of drug studies published in symposium proceedings. Ann Intern Med. 1996;124:485–489
  46. Baker CB, Johnsrud MT, Crismon ML, Rosenheck RA, Woods SW. Quantitative analysis of sponsorship bias in economic studies of antidepressants. Br J Psychiatry. 2003;183:498–506
  47. Wilcock G, Howe I, Coles H, Lilienfeld S, Truyen L, Zhu Y, et al. A long-term comparison of galantamine and donepezil in the treatment of Alzheimer’s disease. Drugs Aging. 2003;20:777–789
  48. Jones RW, Soininen H, Hager K, Aarsland D, Passmore P, Murthy A, et al. A multinational, randomised, 12-week study comparing the effects of donepezil and galantamine in patients with mild to moderate Alzheimer’s disease. Int J Geriatr Psychiatry. 2004;19:5 8–67
  49. Courtney C, Farrell D, Gray R, Hills R, Lynch L, Sellwood E, et al. Long-term donepezil treatment in 565 patients with Alzheimer’s disease (AD2000): randomised double-blind trial. Lancet. 2004;363:2105–2115
  50. ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin converting enzyme inhibitor or calcium-channel blocker vs. diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA 2002; 288: 2981–97.
  51. Godlee F. Can we tame the monster?. BMJ. 2006;333:7558

 The authors who have taken part in this study declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.

PII: S0168-8278(09)00465-6

doi: 10.1016/j.jhep.2009.07.005

Journal of Hepatology
Volume 51, Issue 4 , Pages 792-797 , October 2009