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Social and Scientific History of Randomized Controlled Trials

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Principles and Practice of Clinical Trials

Abstract

The practice and conceptual foundations of randomized controlled trials have been changed both by societal forces and by generations of investigators committed to applying rigorous research methods to therapeutic evaluation. This chapter briefly discusses the emergence of key trial elements such as control groups, alternate allocation, blinding, placebos, and finally randomization. We then explore how shifting intellectual, social, political, economic, regulatory, ethical, and technological forces have shaped the ways that RCTs have taken form, the types of therapies explored, the ethical standards that have been prioritized, and the populations included in studies. This history has not been a simple, linear march of progress. We also highlight key challenges in the historical use of RCTs and the more recent expansion of concerns regarding competing commercial interests that can influence trial design. As investigators continue to advance the rigor of controlled trials amid these challenges, exploring the influence of historical contexts on clinical trial development can help us to understand the forces that may impact trials today.

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References

  • Barter PJ et al (2007) Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med 357:2109–2112

    Google Scholar 

  • Bothwell LE (2014) The emergence of the randomized controlled trial: origins to 1980. Dissertation, Columbia University

    Google Scholar 

  • Bothwell LE, Jones DS (2019) Innovation and tribulation in the history of randomized controlled trials in surgery. Ann Surg. https://doi.org/10.1097/SLA.0000000000003631

  • Bothwell LE, Podolsky SH (2016) The emergence of the randomized, controlled trial. N Engl J Med 375:501–504

    Google Scholar 

  • Bothwell LE, Greene JA, Podolsky SH, Jones DS (2016) Assessing the gold standard – lessons from the history of RCTs. N Engl J Med 374(22):2175–2181

    Google Scholar 

  • Bourgeois FT, Murthy S, Mandl KD (2010) Outcome reporting among drug trials registered in clinical Trials.gov. Ann Intern Med 153:158–166

    Google Scholar 

  • Calabrese RL, Roberts B (2004) Self-interest and scholarly publication: the dilemma of researchers, reviewers, and editors. Int J Educ Manag 18:335–341

    Google Scholar 

  • Carpenter D (2010) Reputation and power. Princeton University Press, Princeton

    Google Scholar 

  • Chalmers I (2005) Statistical theory was not the reason that randomisation was used in the British Medical Research Council’s clinical trial of streptomycin for pulmonary tuberculosis. In: Jorland G et al (eds) Body counts. McGill-Queen’s University Press, Montreal, pp 309–334

    Google Scholar 

  • Chalmers I, Dukan E, Podolsky S, Smith GD (2012) The advent of fair treatment allocation schedules in clinical trials during the 19th and early 20th centuries. J R Soc Med 105(5). See also JLL Bulletin: Commentaries on the history of treatment evaluation. http://www.jameslindlibrary.org/articles/the-advent-of-fair-treatment-allocation-schedules-in-clinical-trials-during-the-19th-and-early-20th-centuries/. Accessed 17 Mar 2019

  • Chikenkokusaikakenkyukai [Study group on the globalization of clinical trials] (2013) ICH-GCP Nabgeita: Kokusaitekishitenkaranihonnochiken wo kangaeru. (ICH-GCP navigator: considerations of clinical trials in Japan from an international perspective). Jiho, Tokyo

    Google Scholar 

  • Cochrane AL (1972) Effectiveness and efficiency: random reflections on the health services. Nuffield Provincial Hospitals Trust, London

    Google Scholar 

  • Daly J (2005) Evidence-based medicine and the search for a science of clinical care. University of California Press, Berkeley

    Google Scholar 

  • Epstein S (1996) Impure science: AIDS, activism, and the politics of knowledge. University of California Press, Berkeley

    Google Scholar 

  • Fiore L, Lavori P (2016) Integrating randomized comparative effectiveness research with patient care. N Engl J Med 374:2152–2158

    Google Scholar 

  • Ford I, Norrie J (2016) Pragmatic trials. N Engl J Med 375:454–463

    Google Scholar 

  • Freedman B (1987) Equipoise and the ethics of clinical research. N Engl J Med 317:141–145

    Google Scholar 

  • Gabriel JM (2014) The testing of Sanocrysin: science, profit, and innovation in clinical trial design, 1926–1931. J Hist Med Allied Sci 69:604–632

    Google Scholar 

  • Gaudilliere JP, Lowy I (1998) The invisible industrialist: manufactures and the production of scientific knowledge. Macmillan, London

    Google Scholar 

  • Hill AB (1963) Medical ethics and controlled trials. Br Med J 5337:1043–1049

    Google Scholar 

  • Jones DS (2000) Visions of a cure: visualization, clinical trials, and controversies in cardiac therapeutics, 1968–1998. Isis 91:504–541

    Google Scholar 

  • Jones DS (2018) Surgery and clinical trials: the history and controversies of surgical evidence. In: Schlich T (ed) The Palgrave handbook of the history of the surgery. Palgrave Macmillan, London, pp 479–501

    Google Scholar 

  • Jones DS, Podolsky SH (2015) The history and fate of the gold standard. Lancet 9977:1502–1503

    Google Scholar 

  • Jones DS, Grady C, Lederer SE (2016) ‘Ethics and clinical research’ – the 50th anniversary of Beecher’s bombshell. N Engl J Med 374:2393–2398

    Google Scholar 

  • Kaptchuk TJ (1998) Intentional ignorance: a history of blind assessment and placebo controls in medicine. Bull Hist Med 72:389–433

    Google Scholar 

  • Keating P, Cambrosio A (2012) Cancer on trial. University of Chicago Press, Chicago

    Google Scholar 

  • Kesselheim AS, Avorn J (2017) New ‘21st century cures’ legislation: speed and ease vs science. J Am Med Assoc 317:581–582

    Google Scholar 

  • Kuo W-H (2005) Japan and Taiwan in the wake of bio-globalization: drugs, race and standards. Dissertation, MIT

    Google Scholar 

  • Kuo W-H (2008) Understanding race at the frontier of pharmaceutical regulation: an analysis of the racial difference debate at the ICH. J Law Med Ethics 36:498–505

    Google Scholar 

  • Kuo W-H (2009) The voice on the bridge: Taiwan’s regulatory engagement with global pharmaceuticals. East Asian Science, Technology and Society: an International Journal 3:51–72

    Google Scholar 

  • Kuo (2012) Transforming states in the era of global pharmaceuticals: visioning clinical research in Japan, Taiwan, and Singapore. In: Rajan KS (ed) Lively capital: biotechnologies, ethics, and governance in global market. Duke University Press, Durham, pp 279–305

    Google Scholar 

  • Lewontin RC (2008) The socialization of research and the transformation of the academy. In: Hannaway C (ed) Biomedicine in the twentieth century: practices, policies, and politics. IOS Press, Amsterdam, pp 19–25

    Google Scholar 

  • Lilienfeld L (1982) The fielding H. Garrison lecture: ceteris paribus: the evolution of the clinical trial. Bull Hist Med 56:1–18

    Google Scholar 

  • Marks HM (1997) The progress of experiment: science and therapeutic reform in the United States, 1900–1990. Cambridge Univ Press, Cambridge

    Google Scholar 

  • Marks HM (2000) Trust and mistrust in the marketplace: statistics and clinical research, 1945–1960. Hist Sci 38:343–355

    Google Scholar 

  • Marks HM (2006) ‘Until the sun of science … the true Apollo of medicine has risen’: collective investigation in Britain and America, 1880–1910. Med Hist 50:147–166

    Google Scholar 

  • Matheson A (2017) Marketing trials, marketing tricks – how to spot them and how to stop them. Trials 18:105

    Google Scholar 

  • Meldrum ML (1998) A calculated risk: the Salk polio vaccine field trials of 1954. Br Med J 7167:1233–1236

    Google Scholar 

  • Milne I (2012) Who was James Lind, and what exactly did he achieve? J R Soc Med 105:503–508. See also JLL Bulletin: Commentaries on the history of treatment evaluation, (2011). http://www.jameslindlibrary.org/articles/who-was-james-lind-and-what-exactly-did-he-achieve/. Accessed 30 Jan 2019

    Google Scholar 

  • Ostroff SM (2015) ‘Responding to changing regulatory needs with care and due diligence’ – remarks to the regulatory affairs professional society. United States Food and Drug Administration, Baltimore

    Google Scholar 

  • Petryna AP (2009) When experiments travel: clinical trials and the global search for human subjects. Princeton University Press, Princeton

    Google Scholar 

  • Podolsky SH (2006) Pneumonia before antibiotics: therapeutic evolution and evaluation in twentieth-century America. Johns Hopkins University Press, Baltimore

    Google Scholar 

  • Podolsky SH (2009) Jesse Bullowa, specific treatment for pneumonia, and the development of the controlled clinical trial. J R Soc Med 102:203–207. See also JLL Bulletin: Commentaries on the history of treatment evaluation, (2008). http://www.jameslindlibrary.org/articles/jesse-bullowa-specific-treatment-for-pneumonia-and-the-development-of-the-controlled-clinical-trial/. Accessed 17 Mar 2019

    Google Scholar 

  • Podolsky SH (2015) The antibiotic era: reform, resistance, and the pursuit of a rational therapeutics. Johns Hopkins University Press, Baltimore

    Google Scholar 

  • Podolsky SH, Jones DS, Kaptchuk TJ (2016) From trials to trials: blinding, medicine, and honest adjudication. In: Robertson CT, Kesselheim AS (eds) Blinding as a solution to bias: strengthening biomedical science, forensic science, and law. Academic Press, London, pp 45–58

    Google Scholar 

  • Porter TM (1996) Trust in numbers: the pursuit of objectivity in science and public life. Princeton University Press, Ewing

    Google Scholar 

  • Ross OB (1951) Use of controls in medical research. J Am Med Assoc 145:72–75

    Google Scholar 

  • Shapiro AK, Shapiro E (1997) The powerful placebo: from ancient priest to modern physician. Johns Hopkins University Press, Baltimore

    Google Scholar 

  • Stark L (2011) Behind closed doors: irbs and the making of ethical research. Univ of Chicago Press, Chicago

    Google Scholar 

  • Tibi S (2006) Al-Razi and Islamic medicine in the 9th century. J R Soc Med 99:206–207. See also James Lind Library Bulletin: Commentaries on the History of Treatment Evaluation, (2005). http://www.jameslindlibrary.org/articles/al-razi-and-islamic-medicine-in-the-9th-century/. Accessed 17 Mar 2019

    Google Scholar 

  • Timmermann C (2008) Clinical research in post-war Britain: the role of the Medical Research Council. In: Hannaway C (ed) Biomedicine in the twentieth century: practices, policies, and politics. IOS Press, Amsterdam, pp 231–254

    Google Scholar 

  • Timmermans S, Berg M (2003) The gold standard: the challenges of evidence-based medicine and standardization in health care. Temple University Press, Philadelphia

    Google Scholar 

  • Tröhler U (2000) To improve the evidence of medicine: the 18th century British origins of a critical approach. Royal College of Physicians of Edinburgh, Edinburgh

    Google Scholar 

  • United States Food and Drug Administration (1963) Proceedings of the FDA conference on the Kefauver-Harris drug amendments and proposed regulations. United States Department of Health, Education, and Welfare, Washington, DC

    Google Scholar 

  • United States Food and Drug Administration, Center for Drug Evaluation and Research, Center for Biologics Evaluation and Research (2018) Adaptive design clinical trials of drugs and biologics: guidance for industry (draft guidance). In: United States Department of Health. Education, and Welfare, Rockville

    Google Scholar 

  • Warner JH (1986) The therapeutic perspective: medical practice, knowledge, and identity in America, 1820–1885. Harvard University Press, Cambridge, MA

    Google Scholar 

  • Warner JH (1991) Ideals of science and their discontents in late nineteenth-century American medicine. Isis 82:454–478

    Google Scholar 

Download references

Permission

Segments of this chapter are also published in Bothwell, L., and Podolsky, S. “Controlled Clinical Trials and Evidence-Based Medicine,” in Oxford Handbook of American Medical History, ed. J. Schafer, R. Mizelle, and H. Valier. Oxford: Oxford University Press, forthcoming. With kind permission of Oxford University Press, date TBA. All Rights Reserved.

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Authors and Affiliations

  1. Worcester State University, Worcester, MA, USA

    Laura E. Bothwell

  2. National Yang-Ming University, Taipei City, Taiwan

    Wen-Hua Kuo

  3. Harvard University, Cambridge, MA, USA

    David S. Jones

  4. Harvard Medical School, Boston, MA, USA

    Scott H. Podolsky

Authors
  1. Laura E. Bothwell
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  2. Wen-Hua Kuo
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  3. David S. Jones
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  4. Scott H. Podolsky
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Corresponding author

Correspondence to Laura E. Bothwell .

Editor information

Editors and Affiliations

  1. Samuel Oschin Comprehensive Cancer Insti, WEST HOLLYWOOD, CA, USA

    Steven Piantadosi

  2. Bloomberg School of Public Health, Johns Hopkins Center for Clinical Trials Bloomberg School of Public Health, Baltimore, MD, USA

    Curtis L. Meinert

Section Editor information

  1. Professor of Epidemiology & Population Health, and Medicine, Stanford University School of Medicine, Stanford, CA, USA

    Steven N. Goodman

  2. School of Medicine, The Johns Hopkins University, Baltimore, MD, USA

    Karen A Robinson

  3. The Johns Hopkins Center for Clinical Trials and Evidence Synthesis, Johns Hopkins University, Baltimore, MD, USA

    Curtis L. Meinert

  4. Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Steven Piantadosi

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Bothwell, L.E., Kuo, WH., Jones, D.S., Podolsky, S.H. (2020). Social and Scientific History of Randomized Controlled Trials. In: Piantadosi, S., Meinert, C. (eds) Principles and Practice of Clinical Trials. Springer, Cham. https://doi.org/10.1007/978-3-319-52677-5_196-1

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  • DOI: https://doi.org/10.1007/978-3-319-52677-5_196-1

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-52677-5

  • Online ISBN: 978-3-319-52677-5

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