The history of clinical research accounts for the high ethical, scientific, and regulatory standards represented in current practice. In this review, we aim to describe the advances that grew from failures and provide a comprehensive view of how the current gold standard of clinical practice was born. This discussion of the evolution of clinical trials considers the length of time and efforts that were made in order to designate the primary objective, which is providing better care for our patients. A gradual, historic progression of scientific methods such as comparison of interventions, randomization, blinding, and placebos in clinical trials demonstrates how these techniques are collectively responsible for a continuous advancement of clinical care. Developments over the years have been ethical as well as clinical. The Belmont Report, which many investigators lack appreciation due to time constraints, represents the pinnacle of ethical standards and was developed due to significant misconduct. Understanding the history of clinical research may help investigators appreciate the responsibility of conducting human subjects’ research.
Conflict(s) of Interest
References with DOI
1. Modjarrad K. A changing paradigm for medical research: The evolution of the clinical trial. Hektoen International Journal. 2016;8(Summer 2016).
2. Bhatt A. Evolution of clinical research: a history before and beyond james lind. Perspectives in clinical research. 2010;1(1):6-10.
3. Machin D, Day, S., & Green, S. Textbook of Clinical Trials. Second ed. Chichester, West Sussex, England: John Wiley & Sons, Ltd; 2007.
4. Gordis L. Epidemiology. 5th ed. Philadelphia, PA: Elsevier/Saunders; 2014.
5. Chalmers I. Comparing like with like: some historical milestones in the evolution of methods to create unbiased comparison groups in therapeutic experiments. International journal of epidemiology. 2001;30(5):1156-64. https://doi.org/10.1093/ije/30.5.1156
6. Trohler U. Lind and scurvy: 1747 to 1795. Journal of the Royal Society of Medicine. 2005;98(11):519-22. https://doi.org/10.1258/jrsm.98.11.519
7. Lind J. A treatise on the scurvy. 3d ed. London,: S. Crowder etc.; 1772. xiv, 2, 559, 1 p. p.
8. Bernard C. An introduction to the study of experimental medicine. New York,: Dover Publications; 1957. 226 p. p.
9. Kaptchuck T. A brief history of the volution of methods to control observer biases in tests of treatments 2011 [Available from: http://www.jameslindlibrary.org/articles/a-brief-history-of-the-evolution-ofmethods- to-control-of-observer-biases-in-tests-of-treatments/.
10. Clarke M. The 1944 patulin trial of the British Medical Research Council. Journal of the Royal Society of Medicine. 2006;99(9):478-80. https://doi.org/10.1258/jrsm.99.9.478
11. Chalmers I, Clarke M. Commentary: the 1944 patulin trial: the first properly controlled multicentre trial conducted under the aegis of the British Medical Research Council. International journal of epidemiology. 2004;33(2):253-60. https://doi.org/10.1093/ije/dyh162
12. Fda.gov. FDA and Clinical Drug Trials: A Short History 2016 [Available from: http://www.fda.gov/AboutFDA/WhatWeDo/History/Overviews/ucm304485.htm - _ednref29.
13. Alabama TUo. Research Compliance: Brief History 2007 [Available from: http://osp.ua.edu/site/PRCO_History.html.
14. Benedict S, Georges JM. Nurses and the sterilization experiments of Auschwitz: a postmodernist perspective. Nursing inquiry. 2006;13(4):277-88. https://doi.org/10.1111/j.1440-1800.2006.00330.x
15. Jotkowitz A. The Holocaust and medical ethics: the voices of the victims. Journal of medical ethics. 2008;34(12):869-70. https://doi.org/10.1136/jme.2008.024687
16. Capron AM. Henry Knowles Beecher, Jay Katz, and the Transformation of Research with Human Beings. Perspectives in biology and medicine. 2016;59(1):55-77. https://doi.org/10.1353/pbm.2016.0025
17. Baker SM, Brawley OW, Marks LS. Effects of untreated syphilis in the negro male, 1932 to 1972: a closure comes to the Tuskegee study, 2004. Urology. 2005;65(6):1259-62. https://doi.org/10.1016/j.urology.2004.10.023
18. University CG. History of Ethics. 2016.
19. Services USDoHH. The Belmont Report 2010 [Available from: http://www.hhs.gov/ohrp/regulations-andpolicy/ belmont-report/.
20. Chen R, Desai NR, Ross JS, Zhang W, Chau KH, Wayda B, et al. Publication and reporting of clinical trial results: cross sectional analysis across academic medical centers. BMJ (Clinical research ed). 2016;352:i637. https://doi.org/10.1136/bmj.i637
21. Bothwell LE, Greene JA, Podolsky SH, Jones DS. Assessing the Gold Standard--Lessons from the History of RCTs. N Engl J Med. 2016;374(22):2175-81. https://doi.org/10.1056/nejmms1604593
Nellhaus, Emma M. and Davies, Todd H.
"Evolution of Clinical Trials throughout History,"
Marshall Journal of Medicine:
1, Article 9.
Available at: https://mds.marshall.edu/mjm/vol3/iss1/9