Nothing Special   »   [go: up one dir, main page]
Skip to main content
Springer Nature Link
Log in

Introduction to Clinical Trials

  • Chapter
  • First Online:
Fundamentals of Clinical Trials

Abstract

The evolution of the modern clinical trial dates back to the eighteenth century [1, 2]. Lind, in his classical study on board the Salisbury, evaluated six treatments for scurvy in 12 patients. One of the two who was given oranges and lemons recovered quickly and was fit for duty after 6 days. The second was the best recovered of the others and was assigned the role of nurse to the remaining ten patients. Several other comparative studies were also conducted in the eighteenth and nineteenth centuries. The comparison groups comprised literature controls, other historical controls, and concurrent controls [2].

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

eBook
USD 15.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Bull JP. The historical development of clinical therapeutic trials. J Chronic Dis 1959;10:218–248.

    Google Scholar 

  2. Lilienfeld AM. Ceteris paribus: the evolution of the clinical trial. Bull Hist Med 1982;56:1–18.

    Google Scholar 

  3. Box JF. R. A. Fisher and the design of experiments, 1922–1926. Am Stat 1980;34:1–7.

    MATH  MathSciNet  Google Scholar 

  4. Amberson JB, Jr, McMahon BT, Pinner M. A clinical trial of sanocrysin in pulmonary tuberculosis. Am Rev Tuberc 1931;24:401–435.

    Google Scholar 

  5. Medical Research Council. Streptomycin treatment of pulmonary tuberculosis. Br Med J 1948;2:769–782.

    Google Scholar 

  6. Hart PD. Letter to the editor: Randomised controlled clinical trials. Br Med J 1991;302:1271–1272.

    Google Scholar 

  7. Diehl HS, Baker AB, Cowan DW. Cold vaccines; an evaluation based on a controlled study. JAMA 1938;111:1168–1173.

    Google Scholar 

  8. Freireich EJ, Frei E, III, Holland JF, et al. Evaluation of a new chemotherapeutic agent in patients with “advanced refractory” acute leukemia: studies of 6-azauracil. Blood 1960;16:1268–1278.

    Google Scholar 

  9. Hill AB. The clinical trial. Br Med Bull 1951;7:278–282.

    Google Scholar 

  10. Hill AB. The clinical trial. N Engl J Med 1952;247:113–119.

    Google Scholar 

  11. Hill AB. Statistical Methods of Clinical and Preventive Medicine. 1962; Oxford University Press, New York.

    Google Scholar 

  12. Doll R. Clinical trials: retrospect and prospect. Stat Med 1982;1:337–344.

    Google Scholar 

  13. Chalmers I. Comparing like with like: some historical milestones in the evolution of methods to create unbiased comparison groups in therapeutic experiments. Int J Epidemiol 2001;30:1156–1164.

    Google Scholar 

  14. Gehan EA, Schneiderman MA. Historical and methodological developments in clinical trials at the National Cancer Institute. Stat Med 1990;9:871–880.

    Google Scholar 

  15. Halperin M, DeMets DL, Ware JH. Early methodological developments for clinical trials at the National Heart, Lung, and Blood Institute. Stat Med 1990; 9:881–892.

    Google Scholar 

  16. Greenhouse SW. Some historical and methodological developments in early clinical trials at the National Institutes of Health. Stat Med 1990;9:893–901.

    Google Scholar 

  17. Byar DP. Discussion of papers on “historical and methodological developments in clinical trials at the National Institutes of Health.” Stat Med 1990;9:903–906.

    Google Scholar 

  18. Organization, Review, and Administration of Cooperative Studies (Greenberg Report). A report from the Heart Special Project Committee to the National Advisory Heart Council, May 1967. Control Clin Trials 1988;9:137–148.

    Google Scholar 

  19. OPRR Reports. Code of Federal Regulations: (45 CFR 46) Protection of Human Subjects. National Institutes of Health, Department of Health and Human Services. Revised June 23, 2005. http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm.

  20. National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research. Fed Regist 1979;44:23192–23197. http://www.hhs.gov/ohrp/humansubjects/guidance/belmont.htm.

    Google Scholar 

  21. Nuremburg Code. http://www.hhs.gov/ohrp/references/nurcode.htm.

  22. World Medical Association Declaration of Helsinki. http://www.wma.net/e/policy/b3.htm.

  23. International Harmonised Tripartite Guideline: General Considerations for Clinical Trials: E8. December 17, 1997. http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM129510.pdf.

  24. Buoen C, Bjerrum OJ, Thomsen MS. How first-time-in-human studies are being performed: a survey of phase 1 dose-escalation trials in healthy volunteers published between 1995 and 2004. J Clin Pharmacol 2005;45:1123–1136.

    Google Scholar 

  25. Carbone PP, Krant MJ, Miller SP, et al. The feasibility of using randomization schemes early in the clinical trials of new chemotherapeutic agents:hydroxyurea (NSC-32065). Clin Pharmacol Ther 1965;6:17–24.

    Google Scholar 

  26. Anbar D. Stochastic approximation methods and their use in bioassay and phase I clinical trials. Commun Stat Ser A 1984;13:2451–2467.

    Google Scholar 

  27. Williams DA. Interval estimation of the median lethal dose. Biometrics 1986;42:641–645; correction in: Biometrics 1987;43:1035.

    MATH  MathSciNet  Google Scholar 

  28. Storer B, DeMets D. Current phase I/II designs: are they adequate? J Clin Res Drug Dev 1987;1:121–130.

    Google Scholar 

  29. Storer B. Design and analysis of phase I clinical trials. Biometrics 1989;45:925–937.

    MATH  MathSciNet  Google Scholar 

  30. Gordon NH, Willson JK. Using toxicity grades in the design and analysis of cancer phase I clinical trials. Stat Med 1992;11:2063–2075.

    Google Scholar 

  31. Schneiderman MA. Mouse to man: statistical problems in bringing a drug to clinical trial. Proceedings of the 5th Berkeley Symposium of Math and Statistical Problems, University of California 1967;4:855–866.

    Google Scholar 

  32. O’Quigley J, Pepe M, Fisher L. Continual reassessment method: a practical design for phase I clinical trials in cancer. Biometrics 1990;46:33–48.

    MATH  MathSciNet  Google Scholar 

  33. O’Quigley J, Chevret S. Methods for dose finding studies in cancer clinical trials: a review and results of a Monte Carlo Study. Stat Med 1991;10:1647–1664.

    Google Scholar 

  34. Wang O, Faries DE. A two-stage dose selection strategy in phase 1 trials with wide dose ranges. J Biopharm Stat 2000;10:319–333.

    Google Scholar 

  35. Babb J, Rogatko A. Bayesian methods for cancer phase I clinical trials. In: N. Geller (Ed.), Advances in Clinical Trial Biostatistics. New York: Marcel Dekker, 2004, pages 1–39.

    Google Scholar 

  36. Biswas S, Liu DD, Lee JJ, Berry DA. Bayesian clinical trials at the University of Texas M. D. Anderson Cancer Center. Clin Trials 2009;6:205–216.

    Google Scholar 

  37. Garrett-Mayer E. The continual reassessment method for dose-finding studies: a tutorial. Clin Trials 2006;3:57–71.

    Google Scholar 

  38. Babb J, Rogatko A, Zacks S. Cancer phase I clinical trials: efficient dose escalation with overdose control. Stat Med 1998;17:1103–1120.

    Google Scholar 

  39. Thall PF, Millikan RE, Mueller P, Lee S-J. Dose-finding with two agents in phase I oncology trials. Biometrics 2003;59:487–496.

    MATH  MathSciNet  Google Scholar 

  40. Cheung YK, Chappell R. Sequential designs for phase I clinical trials with late-onset toxicities. Biometrics 2000;56:1177–1182.

    MATH  MathSciNet  Google Scholar 

  41. Crowley J, Ankerst DP (Eds.), Handbook of Statistics in Clinical Oncology (Second ed.). Boca Raton, FL: Chapman and Hall/CRC, 2006.

    MATH  Google Scholar 

  42. Ting N (Ed.), Dose Finding in Drug Development. New York: Springer, 2006.

    MATH  Google Scholar 

  43. Gehan EA. The determination of the number of patients required in a follow-up trial of a new chemotherapeutic agent. J Chron Dis 1961;13:346–353.

    Google Scholar 

  44. Fleming TR. One-sample multiple testing procedures for phase II clinical trials. Biometrics 1982;38:143–151.

    MATH  Google Scholar 

  45. Herson J. Predictive probability early termination plans for phase II clinical trials. Biometrics 1979;35:775–783.

    MATH  Google Scholar 

  46. Geller NL. Design of phase I and II clinical trials in cancer: a statistician’s view. Cancer Invest 1984;2:483–491.

    Google Scholar 

  47. Whitehead J. Sample sizes for phase II and phase III clinical trials: an integrated approach. Stat Med 1986;5:459–464.

    Google Scholar 

  48. Chang MN, Therneau TM, Wieand HS, Cha SS. Designs for group sequential phase II clinical trials. Biometrics 1987;43:865–874.

    MATH  Google Scholar 

  49. Simon R, Wittes RE, Ellenberg SS. Randomized phase II clinical trials. Cancer Treat Rep 1985;69:1375–1381.

    Google Scholar 

  50. Jung S, Carey M, Kim K. Graphical search for two-stage designs for phase II clinical trials. Control Clin Trials 2001;22:367–372.

    Google Scholar 

  51. Case LD, Morgan TM. Duration of accrual and follow-up for two-stage clinical trials. Lifetime Data Anal 2001;7:21–37.

    MATH  MathSciNet  Google Scholar 

  52. Thall P, Simon R. Recent developments in the design of phase II clinical trials. In: P. Thall, (Ed.), Recent Advances in Clinical Trial Design and Analysis. Norwell, MA: Kluwer, 1995, pages 49–72.

    Google Scholar 

  53. Grieve AP, Krams M. ASTIN: a Bayesian adaptive dose-response trial in acute stroke. Clin Trials 2005;2:340–351.

    Google Scholar 

  54. Lee YJ, Staquet M, Simon R, et al. Two-stage plans for patient accrual in phase II cancer clinical trials. Cancer Treat Rep 1979;63:1721–1726.

    Google Scholar 

  55. Schaid DJ, Ingle JN, Wieand S, Ahmann DL. A design for phase II testing of anticancer agents within a phase III clinical trial. Control Clin Trials 1988;9:107–118.

    Google Scholar 

  56. Simon R. Optimal two-stage designs for phase II clinical trials. Control Clin Trials 1989;10:1–10.

    Google Scholar 

  57. Thall PF, Simon R. Incorporating historical control data in planning phase II clinical trials. Stat Med 1990;9:215–228.

    Google Scholar 

  58. Schmidli H, Bretz F, Racine-Poon A. Bayesian predictive power for interim adaptation in seamless phase II/III trials where the endpoint is survival up to some specified timepoint. Stat Med 2007;26:4925–4938.

    MathSciNet  Google Scholar 

  59. Sylvester RJ, Staquet MJ. Design of phase II clinical trials in cancer using decision theory. Cancer Treat Rep 1980;64:519–524.

    Google Scholar 

  60. Berry D. Decision anlaysis and Bayesian methods in clinical trials. In: P. Thall (Ed.), Recent Advances in Clinical Trial Design and Analysis. Norwell, MA: Kluwer, 1995, pages 125–154.

    Google Scholar 

  61. Solomon SD, McMurray JJV, Pfeffer MA, et al. Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. N Engl J Med 2005;352:1071–1080.

    Google Scholar 

  62. Psaty BM, Furberg CD. COX-2 inhibitors – lessons in drug safety. N Engl J Med 2005;352:1133–1135.

    Google Scholar 

  63. Bolen S, Feldman L, Vassy J, et al. Systematic review: comparative effectiveness and safety of oral medications for type 2 diabetes mellitus. Ann Intern Med 2007;147:386–399.

    Google Scholar 

  64. The Digitalis Investigation Group. The effect of digoxin on mortality and morbidity in patients with heart failure. N Engl J Med 1997;336:525–533.

    Google Scholar 

  65. The Intermittent Positive Pressure Breathing Trial Group. Intermittent positive pressure breathing therapy of chronic obstructive pulmonary disease – a clinical trial. Ann Intern Med 1983;99:612–620.

    Google Scholar 

  66. Silverman WA. The lesson of retrolental fibroplasia. Sci Am 1977;236:100–107.

    Google Scholar 

  67. Echt DS, Liebson PR, Mitchell LB, et al. Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial. N Engl J Med 1991;324:781–788.

    Google Scholar 

  68. Alderson P, Roberts I. Corticosteroids for acute traumatic brain injury. Cochrane Database Syst Rev 2000;(2):CD000196.

    Google Scholar 

  69. Roberts I, Yates D, Sandercock P, et al. Effect of intravenous corticosteroids on death within 14 days in 10008 adults with clinically significant head injury (MRC CRASH trial): randomised placebo-controlled trial. Lancet 2004;364:1321–1328.

    Google Scholar 

  70. Edwards P, Arango M, Balica L, et al. Final results of MRC CRASH, a randomised placebo-controlled trial of intravenous corticosteroid in adults with head injury – outcomes at 6 months. Lancet 2005;365:1957–1959.

    Google Scholar 

  71. Alderson P, Roberts I. Corticosteroids for acute traumatic brain injury. Cochrane Database Syst Rev 2005;(1):CD000196.

    Google Scholar 

  72. Stone GW, Lansky AJ, Pocock SJ, et al. Paclitaxel-eluting stents versus bare-metal stents in acute myocardial infarction. N Engl J Med 2009;360:1946–1959.

    Google Scholar 

  73. James SK, Stenestrand U, Lindbäck J, et al. Long-term safety and efficacy of drug-eluting versus bare-metal stents in Sweden. N Engl J Med 2009;360:1933–1945.

    Google Scholar 

  74. Byar DP, Schoenfeld DA, Green SB, et al. Design considerations for AIDS trials. N Engl J Med 1990;323:1343–1348.

    Google Scholar 

  75. Levine C, Dubler NN, Levine RJ. Building a new consensus: ethical principles and policies for clinical research on HIV/AIDS. IRB 1991;13:1–17.

    Google Scholar 

  76. Spiers HR. Community consultation and AIDS clinical trials, part I. IRB 1991;13:7–10.

    Google Scholar 

  77. Emanuel EJ, Grady C. Four paradigms of clinical research and research oversight. In: E.J. Emamuel, C. Grady, R.A. Crouch, R.K. Lie, F.G. Miller, D. Wendler (Eds.), The Oxford Textbook of Clinical Research Ethics. Oxford: Oxford University Press, 2008, pages 222–230.

    Google Scholar 

  78. Abigail Alliance for Better Access to Developmental Drugs. www.abigail-alliance.org.

  79. Furberg CD. The impact of clinical trials on clinical practice. Arzneim-Forsch./Drug Res 1989;39:986–988.

    Google Scholar 

  80. Lamas GA, Pfeffer MA, Hamm P, et al. Do the results of randomized clinical trials of cardiovascular drugs influence medical practice? N Engl J Med 1992;327:241–247.

    Google Scholar 

  81. Friedman L, Wenger NK, Knatterud GL. Impact of the Coronary Drug Project findings on clinical practice. Control Clin Trials 1983;4:513–522.

    Google Scholar 

  82. Boissel JP. Impact of randomized clinical trials on medical practices. Control Clin Trials 1989;10:120S–134S.

    Google Scholar 

  83. Rosenberg Y, Schron E, Parker A. How clinical trial results are disseminated: use and influence of different sources of information in a survey of US physicians. Control Clin Trials 1994;15:16S.

    Google Scholar 

  84. Schron E, Rosenberg Y, Parker A, Stylianou M. Awareness of clinical trials results and influence on prescription behavior: a survey of US physicians. Control Clin Trials 1994;15:108S.

    Google Scholar 

  85. Ayanian JZ, Haustman PJ, Guadagnoli E, et al. Knowledge and practices of generalist and specialist physicians regarding drug therapy for acute myocardial infarction. N Engl J Med 1994;331:1136–1142.

    Google Scholar 

  86. Ford ES, Ajani UA, Croft JB, et al. Explaining the decrease in U.S. deaths from coronary disease, 1980–2000. N Engl J Med 2007;356:2388–2398.

    Google Scholar 

  87. Casper M, Wing S, Strogatz D, Davis CE, Tyroler HA. Antihypertensive treatment and US trends in stroke mortality, 1962–1980. Am J Public Health 1992;82:1600–1606.

    Google Scholar 

  88. Benson K, Hartz AJ. A comparison of observational studies and randomized, controlled trials. N Engl J Med 2000;342:1878–1886.

    Google Scholar 

  89. Concato J, Shah N, Horwitz RI. Randomized, controlled trials, observational studies, and the hierarchy of research designs. N Engl J Med 2000;342:1887–1892.

    Google Scholar 

  90. Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C. Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis. JAMA 2007;297:842–857.

    Google Scholar 

  91. Hulley S, Grady D, Bush T, et al. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. JAMA 1998;280:605–613.

    Google Scholar 

  92. Writing Group for the Women’s Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women. JAMA 2002;288:321–333.

    Google Scholar 

  93. The Women’s Health Initiative Steering Committee. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy. JAMA 2004;291:1701–1712.

    Google Scholar 

  94. Furberg BD, Furberg CD. Evaluating Clinical Research: All that Glitters is not Gold. (Second ed.). New York: Springer, 2007.

    Google Scholar 

  95. Chalmers TC. Randomization of the first patient. Med Clin North Am 1975;59:1035–1038.

    Google Scholar 

  96. Spodick DH. Randomize the first patient: scientific, ethical, and behavioral bases. Am J Cardiol 1983;51:916–917.

    Google Scholar 

  97. Bonchek LI. Sounding board: are randomized trials appropriate for evaluating new operations? N Engl J Med 1979;301:44–45.

    Google Scholar 

  98. Van der Linden W. Pitfalls in randomized surgical trials. Surgery 1980;87:258–262.

    Google Scholar 

  99. Rudicel S, Esdail J. The randomized clinical trial in orthopaedics: obligation or option? J Bone Joint Surg 1985;67:1284–1293.

    Google Scholar 

  100. Murphy ML, Hultgren HN, Detre K, et al. Treatment of chronic stable angina – a preliminary report of survival data of the randomized Veterans Administration cooperative study. N Engl J Med 1977;297:621–627.

    Google Scholar 

  101. Takaro T, Hultgren HN, Lipton MJ, Detre KM. The VA cooperative randomized study of surgery for coronary arterial occlusive disease. 11. Subgroup with significant left main lesions. Circulation 1976;54:111–107.

    Google Scholar 

  102. Detre K, Peduzzi P, Murphy M, et al. Effect of bypass surgery on survival in patients in low- and high-risk subgroups delineated by the use of simple clinical variables. Circulation 1981;63:1329–1338.

    Google Scholar 

  103. Proudfit WL. Criticisms of the VA randomized study of coronary bypass surgery. Clin Res 1978;26:236–240.

    Google Scholar 

  104. Chalmers TC, Smith H Jr, Ambroz A, et al. In defense of the VA randomized control trial of coronary artery surgery. Clin Res 1978;26:230–235.

    Google Scholar 

  105. CASS Principal Investigators and Their Associates. Myocardial infarction and mortality in the Coronary Artery Surgery Study (CASS) randomized trial. N Engl J Med 1984;310:750–758.

    Google Scholar 

  106. Strachan CJL, Oates GD. Surgical trials. In: F.N. Johnson, S. Johnson (Eds.), Clinical Trials. Oxford: Blackwell Scientific, 1977.

    Google Scholar 

  107. Bunker JP, Hinkley D, McDermott WV. Surgical innovation and its evaluation. Science 1978;200:937–941.

    Google Scholar 

  108. Weil RJ. The future of surgical research. PLoS Med 2004;1:e13. doi:10.1371/journal.pmed.0010013.

    Google Scholar 

  109. Cook JA. The challenges faced in the design, conduct and analysis of surgical randomised controlled trials. Trials 2009. 10:9. doi:10.1186/1745-6215-10-9.

    Google Scholar 

  110. Chalmers TC, Sacks H. Letter to the editor: randomized clinical trials in surgery. N Engl J Med 1979;301:1182.

    Google Scholar 

  111. Greene HL, Roden DM, Katz RJ, et al. The cardiac arrhythmia suppression trial: first CAST…then CAST-II. J Am Coll Cardiol 1992;19:894–898.

    Google Scholar 

  112. ClinicalTrials.gov. http://clinicaltrials.gov/.

  113. WHO International Clinical Trials Registry Platform. http://www.who.int/ictrp/network/en/.

  114. Clinical Trials Registration in ClinicalTrials.gov (Public Law 110-85): Competing Applications and Non-Competing Progress Reports. http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-023.html.

  115. Notice of public process for the expansion of the Clinical Trials.gov registry and availability of a basic results database. Fed Regist 73(99). May 21, 2008. http://edocket.access.gpo.gov/2008/E8-11042.htm.

Download references

Author information

Authors and Affiliations

  1. Bethesda, MD, USA

    Lawrence M. Friedman

  2. School of Medicine, Wake Forest University, Winston-Salem, NC, USA

    Curt D. Furberg

  3. Department of Biostatistics & Medical Informatics, University of Wisconsin, Madison, WI, USA

    David L. DeMets

Authors
  1. Lawrence M. Friedman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Curt D. Furberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. David L. DeMets
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lawrence M. Friedman .

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer New York

About this chapter

Cite this chapter

Friedman, L.M., Furberg, C.D., DeMets, D.L. (2010). Introduction to Clinical Trials. In: Fundamentals of Clinical Trials. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-1586-3_1

Download citation

Publish with us

Policies and ethics

Search

Navigation