Clinical Trials

  • Desmond G. Julian
  • Stuart Pocock

Abstract

British interest in randomised controlled trials started shortly after the second world war. Indeed, the study of streptomycin in tuberculosis carried out by the Medical Research Council (MRC) is generally credited with being the first clinical trial in the world with a properly randomised control group. The MRC trials of antihistaminic drugs for the treatment of the common cold — possibly the first placebo controlled trials — followed shortly thereafter. Randomised trials of treatment for heart disease did not start until several years later, and Cochrane, the arch proponent of evidence based medicine, was particularly critical of cardiologists for not basing their practice on good science. However, cardiology, perhaps more than any other, is now firmly established as a discipline in which most clinical decision making is rooted in well conducted clinical trials. In this chapter we discuss the British contribution to evidence based advances in various clinical contexts and consider how British experience has advanced the principles and practice of the clinical trial.

Keywords

Placebo Heparin Tuberculosis Cardiol Propranolol 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References and notes

  1. 1.
    Reid DD. A trial of long-term anticoagulant administration after myocardial infarction. In: Council for International Organizations of Medical Sciences, ed. Controlled clinical trials. Oxford: Blackwell, 1960:109–14.Google Scholar
  2. 2.
    Working Party on Anticoagulant Therapy in Coronary Thrombosis. Assessment of short-anticoagulant administration after cardiac infarction. Report of the Working Party on Anticoagulant Therapy in Coronary Thrombosis to the Medical Research Council. BMJ 1969;1:335–42.CrossRefGoogle Scholar
  3. 3.
    Chalmers TC, Matta RJ, Smith H, Kunzler A-M. Evidence favoring the use of anticoagulants in the hospital phase of acute myocardial infarction. N Engl J Med 1977;297:1091–6.PubMedCrossRefGoogle Scholar
  4. 4.
    Pickering GW. Clinical problems and results. In: Council for International Organizations of Medical Sciences, ed. Controlled clinical trials. Blackwell. Oxford, 1960:115–22.Google Scholar
  5. Medical Research Council. Second report of the working party on anticoagulant therapy in coronary thrombosis. BMJ 1964;2:837–43.CrossRefGoogle Scholar
  6. 6.
    ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17 187 cases of suspected acute myocardial infarction: ISIS-2. Lancet 1988;ii:349–60.Google Scholar
  7. 7.
    Elwood PC, Williams WO A randomized controlled trial of aspirin in the prevention of early mortality in myocardial infarction. J R Coll Gen Pract 1979;204:413–6.Google Scholar
  8. 8.
    Elwood PC, Cochrane AL, Burr ML, et al. A randomized controlled trial of acetyl salicylic acid in the secondary prevention of mortality from myocardial infarction. BMJ 1974;95:436–40.CrossRefGoogle Scholar
  9. 9.
    Antiplatelet Trialists’ Collaboration. Collaborative overview of randomised trials of antiplatelet therapy: 1. prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patient. BMJ 1994;308:81–106.Google Scholar
  10. 10.
    Yusuf S, Collins R, Peto R, et al. Intravenous and intracoronary fibrinolytic therapy: overview of results on mortality, reinfarction and side-effects from 33 randomized trials. Eur Heart J 1985;6:556–85.PubMedGoogle Scholar
  11. 11.
    Gruppo Italiano per lo Studio della Streptokinase nell’Infarto Miocardico (GISSI). Effectiveness of intravenous thrombolytic treatment in acute myocardial infarction. Lancet 1986;i:397.Google Scholar
  12. 12.
    AIMS Trial Study Group. Effect of intravenous APS AC on mortality after acute myocardial infarction. Lancet 1988;i:545–9.Google Scholar
  13. 13.
    Wilcox RG, von der Lippe G, Ollson CG et al. Trial of tissue plasminogen activation for mortality reduction in acute myocardial infarction. Anglo-Scandinavian study of early thrombolysis (ASSET). Lancet 1988;ii:525–30.CrossRefGoogle Scholar
  14. 14.
    Fibrinolytic Therapy Trialists’ Collaborative Group. Indications for fibrinolytic therapy in suspected myocardial infarction: collaborative overview of early mortality and major morbidity results from all randomised trials of more than 1000 patients. Lancet 1994;343:311–22.Google Scholar
  15. 15.
    Late Study Group. Late efficacy of thrombolysis (LATE) study with alteplase 6–24 hours after onset of acute myocardial infarction. Lancet 1993;342:759–66.CrossRefGoogle Scholar
  16. ISIS-3 (Third International Study of Infarct Survival) Collaborative Group. ISIS-3: a randomised comparison of streptokinase vs tissue plasminogen activator vs anistreplase and of aspirin plus heparin vs aspirin alone among 41 299 cases of suspected acute myocardial infarction. Lancet 1992;339:753–770.CrossRefGoogle Scholar
  17. 17.
    Gruppo Italiano per lo Studio della Soprawivenza nell’Infarto Miocardico (GISSI-2). A factorial randomised trial of alteplase versus streptokinase and heparin versus no heparin among 12 490 patients with acute myocardial infarction. Lancet 1990;336:65–71.Google Scholar
  18. 18.
    The International Study Group. In-hospital mortality and clinical course of 20 891 patients with suspected acute myocardial infarction randomised between alteplase and streptokinase with or without heparin. Lancet 1990;336:71–5.CrossRefGoogle Scholar
  19. 19.
    The GUSTO Investigators. An international randomized trial comprising four thrombolytic strategies for acute myocardial infarction. N Engl J Med 1993;329:673–82.CrossRefGoogle Scholar
  20. 20.
    Snow PJD. Effect of propranolol in acute myocardial infarction. Lancet 1965;ii:551–3.Google Scholar
  21. 21.
    ISIS-1 (First International Study of Infarct Survival) Study Group. Randomised trial of intravenous atenolol among 16 027 cases of suspected acute myocardial infarction. ISIS-1 Lancet 1986;ii:57–66.Google Scholar
  22. 22.
    ISIS-1 (First International Study of Infarct Survival) Collaborative Group. Mechanisms for the early mortality reduction produced by beta-blockade started early in myocardial infarction. ISIS-1. Lancet 1988;i:921–3.Google Scholar
  23. 23.
    Norwegian Multicenter Study Group. Timolol-induced reduction in mortality and reinfarction in patients surviving myocardial infarction. N Engl J Med 1981;304:801–7.CrossRefGoogle Scholar
  24. 24.
    Beta-blocker Heart Attack Study Group (BHAT). A beta-blocker heart attack trial. JAMA 1981;246:2073–4.CrossRefGoogle Scholar
  25. 25.
    Multicentre International Study. Improvement in prognosis of myocardial infarction by long-term β-adrenoceptor blockade using practolol. BMJ 1975;3:735–40.CrossRefGoogle Scholar
  26. 26.
    Baber NS, Wainwright Evans D, Howitt G, et al. A multicentre propranolol post-infarction trial in 49 hospitals in the United Kingdom, Italy and Yugoslavia. Br Heart J 1980;44:96–100.PubMedCrossRefGoogle Scholar
  27. 27.
    Taylor SH, Silke B, Ebbutt A, et al. A long-term prevention study with oxprenolol in coronary heart disease. N Engl J Med 1982;307:1293–301.PubMedCrossRefGoogle Scholar
  28. 28.
    Julian DG, Prescott RJ, Jackson FS, Szekely P. Controlled trial of sotalol for 1 year after myocardial infarction. Lancet 1982;i:l 142–7.Google Scholar
  29. 29.
    Baber NS, Lewis JA. Confidence in results of beta-blocker post-infarction trials. BMJ 1982;284:1749–50.PubMedCrossRefGoogle Scholar
  30. 30.
    Held PH, Yusuf S. Effects of β-blockers and calcium channel blockers in acute myocardial infarction. Eur Heart J 1993;14 (suppl F): 18–25.PubMedGoogle Scholar
  31. 31.
    Wilcox RG. Hampton JR, Banks DC, et al. Trial of early nifedipine in acute myocardial infarction: the TRENT study. BMJ 1986;293:1204–8.PubMedCrossRefGoogle Scholar
  32. 32.
    Yusuf S, Collins R, MacMahon S, Peto R. Effect of intravenous nitrates in acute myocardial infarction. Lancet 1988;i: 1088–92.CrossRefGoogle Scholar
  33. 33.
    Teo KK, Yusuf S, Collins R, Held PH, Peto R. Effects of intravenous magnesium in suspected myocardial infarction: overview of randomised trials. BMJ 1991;303:1499–503.PubMedCrossRefGoogle Scholar
  34. 34.
    Woods KL, Fletcher S, Roffe C, Haider Y. Intravenous magnesium sulphate in suspected myocardial infarction: results of the second Leicester intravenous magnesium intervention trial (LIMIT-2). Lancet 1992;339:1553–8.PubMedCrossRefGoogle Scholar
  35. 35.
    Hamilton M, Thompson EN, Wisniewski TKM. The role of blood pressure control in preventing complications of hypertension. Lancet 1964;i:235–8.CrossRefGoogle Scholar
  36. 36.
    Coope J, Warrender TS. Randomised trial of treatment of hypertension in elderly patients in primary care. BMJ 1986;293:1145–51.PubMedCrossRefGoogle Scholar
  37. 37.
    Medical Research Council Working Party. MRC trial of treatment of mild hypertension. BMJ 1985;291:97–104.CrossRefGoogle Scholar
  38. 38.
    Medical Research Council Working Party. Medical Research Council trial of treatment in older adults. BMJ 1992;304:405–12.CrossRefGoogle Scholar
  39. 39.
    The Xamoterol in Severe Heart Failure Study Group. Xamoterol in severe heart failure. Lancet 1990;336:1–6.CrossRefGoogle Scholar
  40. 40.
    The Acute Infarction Ramipril Efficacy (AIRE) Study Investigators. Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure. Lancet 1993;342:821–8.Google Scholar
  41. 41.
    Oliver MF, Julian DG, Donald KW. Problems in evaluating coronary care units. Am J Cardiol 1967;20:465–74.PubMedCrossRefGoogle Scholar
  42. 42.
    Mather HG, Morgan DC, Pearson NG, et al. Myocardial infarction: a comparison between home and hospital care for patients. BMJ 1976;i:925–9.CrossRefGoogle Scholar
  43. 43.
    Hill JD, Hampton JR, Mitchell JRA. A randomised trial of home versus hospital management for patients with suspected myocardial infarction. Lancet 1978;i:837–41.CrossRefGoogle Scholar
  44. 44.
    European Coronary Surgery Study Group. Coronary artery bypass surgery in stable angina pectoris: survival at two years. Lancet 1979;ii:889–93.Google Scholar
  45. 45.
    CASS Principal Investigators and their Associates. Coronary artery surgery study (CASS): a randomized trial of coronary artery bypass surgery. Circulation 1983;68:939–50.CrossRefGoogle Scholar
  46. 46.
    RITA Trial Participants. Coronary angioplasty versus coronary artery bypass surgery. The randomised intervention treatment of angina. Lancet 1993;341:573–80.CrossRefGoogle Scholar
  47. 47.
    CABRI Trial Participants. First year results of CABRI (coronary angioplasty vs bypass revascularization). Lancet 1995;346:1179–84.CrossRefGoogle Scholar
  48. 48.
    The RITA-2 participants. Coronary angioplasty versus medical therapy for angina: the second randomised intervention treatment of angina (RITA-2). Lancet 1997;350:461–8.CrossRefGoogle Scholar
  49. 49.
    World Health Organisation European Collaborative Group. European collaborative trial of multifactorial prevention of coronary heart disease. Lancet 1986;i:869–72.Google Scholar
  50. 50.
    Research Committee of the Medical Research Council. Controlled trial of soya-bean oil in myocardial infarction. Lancet 1968;ii:693–700.Google Scholar
  51. 51.
    Burr ML, Fehily AM, Gilbert JF, et al. Effects of changes in fat, fish and fibre intakes on death and myocardial infarction (DART). Lancet 1989;ii:757–61.CrossRefGoogle Scholar
  52. 52.
    Committee of Principal Investigators. A cooperative trial in the primary prevention of ischaemic heart disease using clofibrate. Br Heart J 1978;401:1–118.Google Scholar
  53. 53.
    Roussouw JE. Lipid-lowering agents. In: Pitt B, Julian DG, Pocock SJ, eds Clinical trials in cardiology. London: Saunders, 1997:88.Google Scholar
  54. 54.
    Shepherd J, Cobbe SM, Ford I, et al. for the West of Scotland Coronary Prevention Study Group. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N Engl J Med 1995;333:1301–7.PubMedCrossRefGoogle Scholar
  55. 55.
    Hill AB. Statistical methods in clinical and preventive medicine. Edinburgh: Livingstone, 1962.Google Scholar
  56. 56.
    Pocock SJ. When to stop a clinical trial. BMJ 1992:305; 235–240.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag London Limited 2000

Authors and Affiliations

  • Desmond G. Julian
  • Stuart Pocock

There are no affiliations available

Personalised recommendations