FARMAKOEKONOMIKA. Modern Pharmacoeconomic and Pharmacoepidemiology

Advanced search

History of controlled trials in medicine: real priorities are little-known. Report 1. Basic concepts, terms, and disciplines that use medical experiment: historical and philosophical sources

Full Text:


The three-report review was aimed at describing the historical development of clinical trials, controlled trials (CT) and randomized controlled trials (RCT), and the inclusion of these experimental approaches in disciplines related to both the health of individuals and populations (medicine and epidemiology). In Report 1, the authors consider the terminology issues applied to CT and RCT, the sources of the involved concepts, and relevant disciplines. It was shown that the terms ‘control’ and ‘trial’ appeared in experimental literature only at the end of the 19th century, ‘CT’ appeared in the first third or quarter of the 20th century, and the term ‘RCT’ appeared only in 2000s. It was found that approaches with CT and RCT were often included even in classical epidemiology, and this fact eliminates the specificity of differences between observational and experimental disciplines and blurred the difference between inductive and deductive methodologies. Scientific, philosophical, conceptual, and historical aspects were also considered for three areas that included CT and RCT: epidemiology, clinical epidemiology and evidence-based medicine (EBM). It was concluded that classical epidemiology, using predominantly inductive approaches, was not the scope of real medical experiments, in the first place, and, secondly, its prognosis was not aimed at the individual. At the same time, both clinical epidemiology and EBM, which mainly use deductive approaches, involve experiments, making it possible to make prognosis for a particular patient. The proposed summarizing scheme of the historical origins and philosophical foundations of disciplines aimed at finding and proving health effects using observational and experimental approaches reflects the problems considered and covers individual time milestones, which, as a rule, are not named in modern epidemiology textbooks and textbooks of other disciplines.

About the Authors

A. N. Koterov
Russian State Research Center – Burnasyan Federal Medical Biophysical Center, Federal Medical Biological Agency
Russian Federation

Aleksey N. Koterov – Dr. Biol. Sc., Head of Laboratory, Department of Radiation Epidemiology. RSCI SPIN-code: 1493-2530

46 Zhivopisnaya Str., Moscow 123182

O. A. Tikhonova
Russian State Research Center – Burnasyan Federal Medical Biophysical Center, Federal Medical Biological Agency
Russian Federation

Olga A. Tikhonova – MD, PhD, Head of Laboratory of Multidisciplinary Clinical Studies. RSCI SPIN-code: 5904-4013

46 Zhivopisnaya Str., Moscow 123182

L. N. Ushenkova
Russian State Research Center – Burnasyan Federal Medical Biophysical Center, Federal Medical Biological Agency
Russian Federation

Liliya N. Ushenkova – PhD (Biol.), Leading Researcher, Department of Radiation Epidemiology. RSCI SPIN-code: 1289-9679

46 Zhivopisnaya Str., Moscow 123182

A. P. Biryukov
Russian State Research Center – Burnasyan Federal Medical Biophysical Center, Federal Medical Biological Agency
Russian Federation

Aleksander P. Biryukov – Dr. Med. Sc., Professor, Head of Department of Radiation Epidemiology. RSCI SPIN-code: 5690-5212

46 Zhivopisnaya Str., Moscow 123182


1. Hart J.T. Cochrane Lecture 1997. What evidence do we need for evidence based medicine? J Epidemiol Community Health. 1997; 51(6): 623–9.

2. Hart J.T. The inverse care law. Lancet. 1971; 1 (7696): 405–12.

3. Martsevich S.Yu., Kutishenko N.P. Randomised clinical trials and observational studies: the ratio in the hierarchy of evidence of the efficacy of drugs. Rational Pharmacotherapy in Cardiology. 2016; 12(5): 567–73 (in Russ.).

4. Bull J.P. A study of the history and principles of clinical therapeutic trials. M.D. thesis, University of Cambridge. 1951; 80 p. URL: (дата обращения 15.03.2021).

5. Bull J.P. The historical development of clinical therapeutic trials. J Chronic Dis. 1959; 10 (3): 218–48.

6. Avxentyeva M.V. A controlled trial in medicine. Medical Technologies. Assessment and Choice. 2011; 3: 88–93 (in Russ.).

7. Nellhaus E.M., Davies T.H. Evolution of clinical trials throughout history. Marshall J Med. 2017; 3 (1): 41–8.

8. Torshin I.Yu., Gromova O.A., Kobalava Z.D. Concerning the "repression" of ω-3 polyunsaturated fatty acids by adepts of evidence-based medicine. FARMAKOEKONOMIKA. Modern Pharmacoeconomics and Pharmacoepidemiology. 2019; 12 (2): 91–114 (in Russ.).

9. Koterov A.N. A clamorous refutation showed only the verity of the refuted: the article by I.Yu. Torshin, O.A. Gromova, and Zh.D. Kobalava “Repressions of ω-3 polyunsaturated fatty acids by adherents of evidence-based medicine” (2019). FARMAKOEKONOMIKA. Modern Pharmacoeconomics and Pharmacoepidemiology. 2020; 13 (1): 63–4 (in Russ.).

10. Ahrens W., Pigeot I. (Eds.) Handbook of epidemiology. 2nd ed. New York, Heidelberg, Dordrecht, London: Springer; 2014: 2498 p.

11. Melikhov О.G. Clinical trials. 3rd ed. Мoscow: Atmosfera Publ.; 2013: 200 p. (in Russ.)

12. Langton J. A discussion on the treatment of hernia in children. Brit Med J. 1896; 2 (73): 470–2.

13. Lilienfeld A.M. The Fielding H. Garrison lecture: Ceteris paribus: the evolution of the clinical trial. Bull Hist Med. 1982; 56 (1): 1–18.

14. Koterov A.N. Causal criteria in medical and biological disciplines: history, essence and radiation aspect. Report 2. Henle–Koch postulates and criteria for causality of non-communicable pathologies before Hill. Radiation Biology. Radioecology. 2019; 59 (4): 341–75 (in Russ.).

15. Feinstein A.R. Clinical epidemiology: the architecture of clinical research. Philadelphia etc.: W.B. Saunders Company; 1985: 812 p.

16. Edwards M.V. Control and the therapeutic trial, 1918–1948. MD thesis. University of London, 2004; 142 p. URL: (дата обращения 15.03.2021).

17. Edwards M. Control and the therapeutic trial: rhetoric and experimentation in Britain, 1918–1948. Wellcome Series in the History of Medicine, Clio Medica 82. Amsterdam, New York; 2006: 221 p.

18. Williams K.J. British pharmaceutical industry, synthetic drug manufacture and the clinical testing of novel drugs 1895–1939. PhD thesis. University of Manchester. 2005; 484 p. URL: (дата обращения 15.03.2021).

19. Marks H.M. The Kendrick–Eldering-(Frost) pertussis vaccine field trial. J R Soc Med. 2007; 100 (5): 242–7.

20. Trohler U. The introduction of numerical methods to assess the effects of medical interventions during the 18th century: a brief history. J R Soc Med. 2011; 104 (11): 465–74.

21. Day S. The development of clinical trials. In: Textbook of clinical trials. 2nd ed. Chichester; 2006: 3–11.

22. Gallin J.I., Ognibene F.P. (Eds.) Principles and practice of clinical research. 4th ed. 2018: 806 p.

23. Petrenko А. Scraped and borrowed: how the components of a clinical trial came together. Available at: articles/s-miru-po-nitke-kak-soedinilis-komponenty-klinicheskogoissledovaniia (accessed 15.03.2021) (in Russ.).

24. Sollmann T. Experimental therapeutics. J Am Med Assoc. 1912; 58(4): 242–4.

25. Gordis L. Epidemiology. 5th ed. Philadelphia: Saunders, Elsevier Inc.; 2014: 392 p.

26. Sacks H., Chalmers T.C., Smith H. Jr. Randomized versus historical controls for clinical trials. Am J Med. 1982; 72 (2): 233–40.

27. Koterov A.N., Ushenkova L.N., Zubenkova E.S. et al. Strength of association. Report 1. Graduations of relative risk. Medical Radiology and Radiation Safety. 2019; 64 (4): 5–17 (in Russ.).

28. Koterov A.N., Ushenkova L.N., Zubenkova E.S. et al. Strength of association. Report 2. Graduations of correlation size. Medical Radiology and Radiation Safety. 2019; 64 (6): 12–24 (in Russ.).

29. Chalmers I., Dukan E., Podolsky S., Davey Smith G. The advent of fair treatment allocation schedules in clinical trials during the 19th and early 20th centuries. J. R. Soc. Med. 2012; 105 (5): 221–227.

30. Sengupta P. The laboratory rat: relating its age with human’s. Int J Prev Med. 2013; 4 (6): 624–30.

31. Bernard C. An introduction to the study of experimental medicine. (1st ed. 1865). New York: Dover Publications. 1957; 272 p.

32. Hankin E.H. A cure for tetanus and diphtheria. Nature. 1890; 43: 121–3. Reprint. Science. 1891; 43 (413): 1–3.

33. Porter T.M. Control and the therapeutic trial: rhetoric and experimentation in Britain, 1918–1948: review of Edwards M. Control and the therapeutic trial: rhetoric and experimentation in Britain, 1918-1948. Med Hist. 2010; 54 (3): 421–2.

34. Medical Research Council Therapeutic Trials Committee. The serum treatment of lobar pneumonia. Br Med J. 1934; 1 (3814): 241–5.

35. Medical Research Council. Streptomycin treatment of pulmonary tuberculosis: a Medical Research Council investigation. Brit Med J. 1948; 2 (4582): 769–82.

36. Medical Research Council. Prevention of whooping-cough by vaccination; a Medical Research Council investigation. Br Med J. 1951; 1 (4721): 1463–71.

37. Medical Research Council. Rheumatic Fever Working Party of the Medical Research Council of Great Britain, Subcommittee of Principal Investigators of the American Council on Rheumatic Fever and Congenital Heart Disease, American Heart Association. Treatment of acute rheumatic fever in children a co-operative clinical trial of A.C.T.H., cortisone, and aspirin. Br Med J. 1955; 1 (4913): 555–74.

38. Donaldson I. George Starkey’s 1658 challenge to Galenists to compare their treatment results with his. J R Soc Med. 2017; 110 (7): 292–4.

39. Donaldson I.M. Mesmer’s 1780 proposal for a controlled trial to test his method of treatment using “animal magnetism”. J R Soc Med. 2005; 98 (12): 572–5.

40. Morabia A. P.C.A. Louis and the birth of clinical epidemiology. J Clin Epidemiol. 1996; 49 (12): 1327–33.

41. Neyman J. (1923/1990) Sur les applications de la theorie des probabilites aux experiences agricoles [On the application of probability theory to agricultural experiments: essay on principles (Section 9)]. Stat Sci. 1990; 5 (4): 465–72.

42. Fisher R.A. The arrangement of field experiments. Journal of the Ministry of Agriculture. 1926; 33: 503–513.

43. Kaptchuk T.J. Early use of blind assessment in a homeopathic scientific experiment. JLL Bulletin. 2004. URL: (дата обращения 15.03.2021).

44. Peirce C.S., Jastrow J. On small differences of sensation. National Academy of Sciences Memoirs. 1884; 43 (1): 75–83.

45. Colebrook D. Report of the work at the North Islington Infant Welfare Centre Light Department. 3 March, FD1/5052. National Archive in Kew, London. 1925.

46. Edwards M. Dora Colebrook and the evaluation of light therapy. J R Soc Med. 2011; 104 (2): 84–6.

47. Hill A.B. The clinical trial. Br Med Bull. 1951; 7 (4): 278–82.

48. Altman D.G., Bland J.M. Statistics notes. Treatment allocation in controlled trials: why randomise? Br Med J. 1999; 318 (7192): 1209.

49. Chalmers I. Why the 1948 MRC trial of streptomycin used treatment allocation based on random numbers. J R Soc Med. 2011; 104 (9): 383–6.

50. Armitage P. Randomisation and alternation: a note on Diehl et al. JLL Bulletin. 2002. URL: (accessed March 15, 2021).

51. Waller L.A. A note on Harold S. Diehl, randomization, and clinical trials. Control Clin Trials. 1997; 18 (2): 180–3.

52. Diehl H.S., Baker A.B., Cowan D.W. Cold vaccines; an evaluation based on a controlled study. J Amer Med Assoc. 1938; 111 (13): 1168–73.

53. Ellison J.B. Intensive vitamin therapy in measles. Brit Med J. 1932; 2 (3745): 708–11.

54. Hill A.B. Principles of medical statistics. I. The aim of the statistical method; and General summary and conclusions. Lancet. 1937; 1: 41-3, 883–5.

55. Ferguson R.G., Simes A.B. BCG vaccination of indian Infants in Saskatchewan. Tubercle. 1949; 30 (1): 5–11.

56. Houston C.S. Ferguson’s BCG research – Canada’s first randomized clinical trial? Clin Invest Med. 1993; 16 (1): 89–91.

57. Farewell V., Johnson T. Major Greenwood and clinical trials. J R Soc Med. 2017; 110 (11): 452–7.

58. Hrobjartsson B., Gotzsche P.C., Gluud C. The controlled clinical trial turns 100 years: Fibiger’s trial of serum treatment of diphtheria. Brit Med J. 1998; 317 (7167): 1243–5.

59. Farewell V., Johnson A. The origins of Austin Bradford Hill’s classic textbook of medical statistics. J R Soc Med. 2012; 105 (11): 483–9.

60. Bradford Hill A. Principles oi medical statistics. 6th ed. London: Lancet; 1955.

61. Green F.H. The clinical evaluation of remedies. Lancet. 1954; 267 (6848): 1085–90.

62. Lock S. The randomised controlled trial — a British invention. In: Lawrence G. (Ed.) Technologies of modern medicine. London: Science Museum; 1994: 81–7.

63. Doll R. Controlled trials: the 1948 watershed. Br Med J. 1998; 317 (7167): 1217–20.

64. Jadad A.R., Enkin M.W. Randomized controlled trials. Questions, answers, and musings. 2nd ed. Malden, Oxford, Carlton: BMJ Books; 2007: 136 p.

65. Aschengrau A., Seage G.R. III. Epidemiology in public health. 4th ed. Burlington: Jones & Bartlett Learning, LLC; 2020: 528 p.

66. Chalmers I. Why transition from alternation to randomisation in clinical trials? Br Med J. 1999; 319: (7221): 1372.

67. Vandenbroucke J.P. When are observational studies as credible as randomised trials? Lancet. 2004; 363 (9422): 1728–31.

68. Yoshioka A. Use of randomisation in the Medical Research Council’s clinical trial of streptomycin in pulmonary tuberculosis in the 1940s. Br Med J. 1998; 317 (7167): 1220–3.

69. Chalmers I. UK Medical Research Council and multicentre clinical trials: from a damning report to international recognition. J R Soc Med. 2013; 106 (12): 498–509.

70. Armitage P. Bradford Hill and the randomized controlled trial. Pharm Med. 1992; 6: 23–37.

71. Hill A.B. Suspended judgment. Memories of the British streptomycin trial in tuberculosis: the first randomized clinical trial. Control Clin Trials. 1990; 11 (2): 77–9.

72. Hill B.A. The environment and disease: association or causation? Proc R Soc Med. 1965; 58 (5): 295–300.

73. Bell J.A. Pertussis prophylaxis with two doses of alum-precipitated vaccine. Public Health Rep. 1941; 56 (31): 1535–46.

74. Bhatt A. Evolution of clinical research: a history before and beyond James Lind. Perspect Clin Res. 2010; 1 (1): 6–10.

75. Wiedermann W., von Eye A. (Eds.) Statistics and causality: methods for applied empirical research. Hoboken, New Jersey: John Wiley & Sons, Inc.; 2016: 438 p.

76. Meldrum M.L. A brief history of the randomized controlled trial. From oranges and lemons to the gold standard. Hematol Oncol Clin North Am. 2000; 14 (4): 745–60.

77. Armitage P. The role of randomization in clinical trials. Stat Med. 1982; 1 (4): 345–52.

78. Cox-Maximov D. The making of the clinical trial in Britain, 1910-1945: expertise, the state and the public. PhD thesis. University of Cambridge; 1997: 395 p. URL: (дата обращения 15.03.2021).

79. Kulkarni K., Harrison J., Baguneid M., B. Prendergast B. (Eds.) Oxford handbook of key clinical evidence. 2nd ed. Oxford: Oxford University Press; 2016: 949 p.

80. Mayer D. Essential evidence-based medicine. 2nd ed. Cambridge University Press; 2010: 442 p. URL: (дата обращения 15.03.2021).

81. Morabia A. The controversial controversy of a passionate controversialist. J Clin Epidemiol. 2002; 55 (12): 1207–13.

82. Piantadosi S. Clinical trials: a methodologic perspective. 2nd ed. Hoboken, New Jersey: John Wiley & Sons, Inc; 2005: 687 p.

83. Sackett D.L., Haynes R.B., Gibson E.S., et al. Randomised clinical trial of strategies for improving medication compliance in primary hypertension. Lancet. 1975; 1 (7918): 1205–7.

84. Hill A.B. Reflections on the controlled trial. Ann Rheum Dis. 1966; 25 (2): 107–13.

85. Guyatt G., Sackett D., Adachi J., et al. A clinician’s guide for conducting randomized trials in individual patients. CMAJ. 1988; 139 (6): 497–503.

86. Shavelson R.J., Towne L. (Eds.) National Research Council. Committee on Scientific Principles for Educational Research. Scientific research in education. Washington, DC: National Academy Press; 2002: 204 p.

87. Brass C.T., Nunez-Neto B., Williams E.D. Congress and program evaluation: an overview of randomized controlled trials (RCTs) and related issues. CRS Report for Congress. Order Code RL33301. Congressional Research Service. The Library of Congress; 2006. URL: (дата обращения 15.03.2021).

88. Bloom H.S. The core analytics of randomized experiments for social research. In: Alasuutari P., Bickman L., Brannen J. (Eds.) The SAGE handbook of social research methods. London, England: SAGE; 2008: 115–33.

89. Stephenson J, Imrie J. Why do we need randomised controlled trials to assess behavioural interventions? Brit. Med. J. 1998. 316; (7131): 611–613.

90. Ahmed I., Soares K.V., Seifas R., Adams C.E. Randomized controlled trials in Archives of General Psychiatry (1959–1995): a prevalence study. Arch Gen Psychiatry. 1998; 55 (8): 754–5.

91. O’Cathain A. A practical guide qualitative research with randomized controlled trials. Oxford: Oxford University Press; 2018: 224 p.

92. Jones D.S., Podolsky S.H. The art of medicine. The history and fate of the gold standard. Lancet. 2015; 385 (9977): 1502–3.

93. Feinstein A.R., Horwitz R.I. Double standards, scientific methods, and epidemiologic research. N Engl J Med. 1982; 307 (260): 1611–7.

94. Worrall J. Why randomize? Evidence and ethics in clinical trials. In: Gonzalez W.J., Alcolea J. (Eds.) Contemporary perspectives in philosophy and methodology of science. Netbiblo; 2006: 65–82.

95. Worrall J. Evidence: philosophy of science meets medicine. J Eval Clin Pract. 2010; 16 (2): 356–62.

96. Cartwright N. Are RCTs the gold standard? Biosocieties. 2007; 2(1): 11–20.

97. Kaptchuk T.J. The double-blind, randomized, placebo-controlled trial: gold standard or golden calf? J Clin Epidemiol. 2001; 54 (6): 541–49.

98. Bondemark L., Ruf S. Randomized controlled trial: the gold standard or an unobtainable fallacy? Eur J Orthod. 2015; 37 (5): 57–61.

99. Bickman L., Reich S.M. Randomized controlled trials: a gold standard or gold plated? In: Christie C.A., Donaldson S.I., Mark M.M. (Eds.) Credible and actionable evidence: the foundation for rigorous and influential evaluations. 2nd ed. Los Angeles: SAGE Publ.; 2015: 83–113.

100. Grossman J., Mackenzie F. The randomized controlled trial: gold standard, or merely standard? Perspect Biol Med. 2005; 48 (4): 516–34.

101. Bothwell L.E., Greene J.A., Podolsky S.H., Jones D.S. Assessing the gold standard — lessons from the history of RCTs. N Engl J Med. 2016; 374 (22): 2175–81.

102. Szklo M., Nieto F.J. Epidemiology. Beyond the Basics. 4th ed. Burlington: Jones & Bartlett Learning; 2019: 577 p.

103. Rebrova О.Yu. Evidence-based medicine. Concept and practice. Osteoporosis and Bone Diseases. 2001; 3: 6 (in Russ.).

104. Howick J. The philosophy of evidence-based medicine. Chichester: Wiley-Blackwell; 2011: 248 p.

105. Opren. Hansard 1803–2005. HC. Deb 20 July 1987, vol. 120. cc. 183–8. Available at: (дата обращения 15.03.2021).

106. Last J.M. (Ed.) A dictionary of epidemiology. Oxford University Press; 2001.

107. Lilienfeld D.E. Definitions of epidemiology. Am J Epidemiol. 1978; 107 (2): 87–90.

108. Susser M. Epidemiology in the United States after World War II: the evolution of technique. Epidemiol Rev. 1985; 7: 147–77.

109. Porta M. (Ed.) A dictionary of epidemiology. 6th ed. New York: Oxford University Press; 2014: 344 p.

110. Katz D.L., Elmore J.G., Wild D.M.G., Lucan S.C. Jekel’s epidemiology, biostatistics, preventive medicine, and public health. 4th ed. Philadelphia: Elsevier Inc.; 2014: 453 p.

111. Ahlbom A., Norell S. Introduction to modern epidemiology. 1st. ed. Chestnut Hill, MA: Epidemiology Resources; 1984.

112. Bruce N., Pope D., Stanistreet D. Quantitative methods for health research. A practical interactive guide to epidemiology and statistics. 2nd ed. Oxford: John Wiley & Sons; 2019: 545 p.

113. MacMahon B., Pugh T.F., Ipsen J. Epidemiologic methods. Boston: Little, Brown: 1960: 302 p.

114. MacMahon B., Pugh T.F. Epidemiology: principles and methods. Boston: Little, Brown & Co.; 1970: 376 p.

115. Taylor I. Epidemiology 1866–1966. Public Health. 1967; 82; (1): 31–7.

116. Morris J.N. Uses of epidemiology. Br Med J. 1955; 2 (4936): 395–401. Reprint: Int J Epidemiol. 2007; 36 (6): 1165–72.

117. Grimes D.A. Clinical research in ancient Babylon: methodologic insights from the book of Daniel. Obstet Gynecol. 1995; 86 (6): 1031–4.

118. Sankaranarayanan К. Estimation of genetic risks of exposure to ionizing radiation: status in the year 2000. Radiation Biology. Radioecology. 2000; 40 (5): 621–6.

119. UNSCEAR 2001. Report to the General Assembly, with Scientific Annexes. Annex “Hereditary effects of radiation”. United Nations. New York. 2001. Available at: (дата обращения 15.03.2021).

120. Schneider D., Lilienfeld D.E. (Eds.) Lilienfeld’s Foundations of Epidemiology. 4th ed. New York: Oxford University Press; 2015: 333 p.

121. Vlasov V.V. Epidemiology: a textbook. 2nd ed. Мoscow: GEOTARMedia; 2006: 464 p. (in Russ.)

122. Okasha S. Experiment, observation, and the confirmation of laws. Analysis. 2011; 71 (2): 222–32.

123. Hofmann B., Holm S., Iversen J.G. Philosophy of Science. In: Laake P., Benestad H.B., Olsen B.R. (Eds.) Research methodology in the medical and biological sciences. London etc.: Academic Press, Elsevier; 2007: 1–32.

124. Susser M. The logic of Sir Karl Popper and the practice of epidemiology. Am J Epidemiol. 1986; 124 (5): 711–8.

125. Hume D. Essays: in 2 vol. 2nd ed. Vol. 1. Moscow: Mysl’; 1996: 733 p. (in Russ.)

126. Rothman K.J. Inferring causal connection – habit, faith or logic? In: Rothman K.J. (Ed.) Causal inference. Mass., USA: Epidemiology Resources Inc.; 1988: 3–12.

127. Popper K.R. The logic of scientific discovery. London and New York: Routledge Classics; 2002: 513 p.

128. Rothman K.J., Greenland S., Poole C., Lash T.L. Causation and causal inference. In: Rothman K.J., Greenland S., Lash T.L. (Eds.) Modern epidemiology. 3rd ed. Philadelphia (PA): Wolters Kluwer; 2008: 5–31.

129. Van den Broeck J., Brestoff J.R. (Eds.) Epidemiology: principles and practical guidelines. Dordrecht: Springer; 2013: 621 p.

130. Maldonado G., Greenland S. Estimating causal effects. Int J Epidemiol. 2002; 31 (2): 422–9.

131. Guyatt G.H., Keller J.L., Jaeschke R., et al. The N-of-1 randomized controlled trial: clinical usefulness. Our three-year experience. Ann Intern Med. 1990; 112: 293–9.

132. Weed D.L. Epidemiologic evidence and causal inference. Hematol Oncol Clin North Am. 2000; 14 (4): 797–807.

133. Vandenbroucke J.P. What is the best evidence for determining harms of medical treatment? CMAJ. 2006; 174 (5): 645–6.

134. Glasziou P., Chalmers I., Rawlins M., McCulloch P. When are randomised trials unnecessary? Picking signal from noise. Brit Med J. 2007; 334 (7589): 349–51.

135. Rimm A.A., Bortin M. Clinical trials as a religion. Biomedicine. 1978; 28 (Spec No): 60–3.

136. Favaloro R.G. Critical analysis of coronary artery bypass graft surgery: a 30-year journey. J Am Coll Cardiol. 1998; 31 (4 Suppl B): 1B–63B.

137. Olsen J., Greene N., Saracci R., Trichopoulos D. (Eds.) Teaching epidemiology. A guide for teachers in epidemiology, public health, and clinical medicine. 4th ed. New York: Oxford University Press; 2015: 555 p.

138. Feinstein A.R. Clinical epidemiology. I. The populational experiments of nature and of man in human illness. Ann Intern Med. 1968; 69 (4): 807–20.

139. Fletcher R.H., Fletcher S.W., Wagner E.H. Clinical epidemiology: the essentials. 3rd ed. Philadelphia: Lippincott Williams & Wilkins; 1996: 276 p.

140. Sackett D.L. Clinical epidemiology. What, who, and whither. J Clin Epidemiol. 2002; 55 (12): 1161–6.

141. Bonita R., Beaglehole R., Kjellstrom T. Basic epidemiology. 2nd ed. World Health Organization; 2006: 212 p.

142. Saracci R. Epidemiology. A very short introduction. New York: Oxford University Press, Inc.; 2010: 171 p.

143. Holmes L.J. Applied epidemiologic principles and concepts. Clinicians’ guide to study design and conduct. New York: Taylor & Francis; 2018: 316 p.

144. Kincaid H. Causal modelling, mechanism, and probability in epidemiology. In: Illari P.M., Russo F., Williamson J. (Eds.) Causality in the sciences. New York: Oxford University Press; 2011: 20 p.

145. Bhopal R.S. Concepts of epidemiology: integrated the ideas, theories, principles and methods of epidemiology. 3rd ed. Oxford: University Press; 2016: 442 p.

146. Coughlin S.S. Causal inference and scientific paradigms in epidemiology. Bentham E-book; 2010: 70 p.

147. Lagiou P., Adami H.O., Trichopoulos D. Causality in cancer epidemiology. Eur J Epidemiol. 2005; 20 (7): 565–74.

148. Karhausen L.R. The poverty of Popperian epidemiology. Int J Epidemiol. 1995; 24 (5): 869–74.

149. Susser M. Falsification, verification and causal inference in epidemiology: reconsiderations in the light of sir Karl Popper’s philosophy. In: Rothman K.J. (Ed.) Causal inference. Chestnut Hill, MS: Epidemiologic Resources; 1988: 33–57.

150. Jacobsen M. Inference in epidemiology. In: Rothman K.J. (Ed.) Causal inference. Chestnut Hill, MS: Epidemiologic Resources; 1988: 105–17.

151. Buck C. Popper’s philosophy for epidemiologists. Int J Epidemiol. 1975; 4 (3): 159–68.

152. Frost W.H. Risk of persons in familial contact with pulmonary tuberculosis. Am J Public Health Nations Health. 1933; 23 (5): 426–32.

153. Doll R. Cohort studies: history of the method. I. Prospective cohort studies. Soz Praventivmed. 2001; 46 (2): 75–86.

154. Frost W.H. Snow on cholera: being a reprint of two papers by John Snow, M.D. together with a biographical memoir by B.W. Richardson and an introduction by Wade Hampton Frost, M.D. The Commonwealth Fund. New York; 1936: 15.

155. Labarthe D.M., Stallones R.A. Epidemiologic inference. In: Rothman K.J. (Ed.) Causal Inference. Chestnut Hill, MS: Epidemiologic Resources; 1988: 119–29.

156. UNSCEAR 2006. Report to the General Assembly, with Scientific Annexes. Annex A. Epidemiological studies of radiation and cancer. United Nations. New York; 2008: 17–322. URL: (дата обращения 15.03.2021).

157. Webb P., Bain C. Essential epidemiology. An introduction for students and health professionals. 2nd ed. Cambridge etc.: Cambridge University Press; 2011: 445 p.

158. Merrill R.M. Introduction to epidemiology. 7th ed. Burlington: Jones & Bartlett Learning; 2017: 339 p.

159. Koterov A.N., Biryukov A.P. Role of radiobiology for radiation epidemiology using for radiation protection. Int J Low Radiation (Paris). 2010; 7 (6); 473–99.

160. Maclure M. Popperian refutation in epidemiology. Am J Epidemiol. 1985; 121 (3): 343–50.

161. Parascandola M. Epidemiology: second-rate science? Public Health Rep. 1998; 113 (4): 312–20.

162. Rothman K.J. What is causation. In: Rothman K.J. (Ed.) Epidemiology, an introduction. New York: Oxford University Press; 2002: 8–24.

163. Venables K.M. (Ed.) Current topics in occupational epidemiology. New York: Oxford University Press; 2013: 270 p.

164. Susser M., Stein Z. Eras in epidemiology: the evolution of ideas. New York: Oxford University Press; 2009: 368 p.

165. Pokrovskiy V.I., Briko N.I. (Ed.) General epidemiology with the basics of evidence-based medicine: a guide to practical exercises. 2nd ed. Мoscow: GEOTAR-Media; 2012: 496 с. (in Russ.)

166. Gregg M.B. (Ed.) Field epidemiology. 3rd ed. Oxford University Press; 2008: 572 p.

167. Paul J.R. President’s address clinical epidemiology. J Clin Invest. 1938 ; 17 (5): 539–41.

168. Louis P.C.A. Researches on the effects of bloodletting in some inflammatory diseases and on the influence of tartarked antimony and vesication in pneumonitis. Boston: Hilliard & Gray; 1836: 208 p.

169. Sackett D.L., Winkelstein W. Jr. The relationship between cigarette usage and aortic atherosclerosis. Am J Epidemiol. 1967; 86 (1): 264–70.

170. Sackett D.L. Clinical epidemiology. Am J Epidemiol. 1969; 89 (2): 125–8.

171. Feinstein A.R. Clinical judgement. Baltimore: Williams 8 Wilkins; 1967: 414 p.

172. Briko N.I., Polibin R.V., Mindlina А.Ya. Clinical epidemiology: history of formation and prospects of development. Medical Almanac. 2012; (3): 28–31 (in Russ.).

173. Parfrey P.S., Barrett B.J. (Eds.) Clinical epidemiology. Practice and methods. 2nd ed. New York: Humana Press; 2015: 533 p.

174. Strom B.L. (Ed.) Pharmacoepidemiology. 3rd ed. Baffins Lane, Chichester, West Sussex: John Wiley & Sons Ltd.; 2000: 858 p.

175. Worrall J. Evidence in medicine. Compass. 2007; 2 (6): 981-1022.

176. Krauss A. Why all randomised controlled trials produce biased results. Ann Med. 2018; 50 (4): 312–22.

177. Wartolowska K., Beard D.J., Carr A.J. The use of placebos in controlled trials of surgical interventions: a brief history. J R Soc Med. 2018; 111 (5): 177–82.

178. Charlton B.G. The Zombie science of evidence-based medicine: a personal retrospective. A commentary on Djulbegovic, B., Guyatt, G.H. & Ashcroft, R.E. (2009). Cancer Control, 16, 158–168. J Eval Clin Pract. 2009; 15 (60); 930–4.

179. Guyatt G., Cairns J., Churchill D., et al. Evidence-Based Medicine Working Group. Evidence-based medicine. A new approach to teaching the practice of medicine. J Am Med Assoc. 1992; 268 (17): 2420–5.

180. Guyatt G.H. Evidence-based medicine. ACP J Club. 1991; 114 (2): A16.

181. Oxman A.D., Sackett D.L., Guyatt G.H. Users’ guides to the medical literature. I. How to get started. The evidence-based medicine working group. J Am Med Assoc. 1993; 270 (17): 2093–5.

182. Greenhalgh T. How to read a paper: the basics of evidence based medicine. 1st ed. BMJ Books; 1997:196 p.

183. Sackett D.L., Rosenberg W.M., Gray J.A., et al. Evidence based medicine: what it is and what it isn’t. Brit Med J. 1996; 312 (7023): 71–2.

184. Straus S.E., Glasziou P., Richardson W.S., et al. Evidence-based medicine: how to practice and teach EBM. 5th ed. Edinburgh, etc.: Elsevier; 2019: 406 p.

185. Canadian Task Force on the Periodic Health Examination. The periodic health examination. Can Med Assoc J. 1979; 121 (9): 1193–254.

186. Andreeva N.S., Rebrova O.Y., Zorin N.A. et al. Systems for assessing the reliability of scientific evidence and the soundness of guidelines: comparison and prospects for unification. Medical Technologies. Assessment and Choice. 2012; 4: 10–24 (in Russ.).

187. Vandenbroucke J.P. Observational research, randomised trials, and two views of medical science. PLoS Med. 2008; 5 (3): e67.

188. Sturmberg J.P. Evidence-based medicine – not a panacea for the problems of a complex adaptive world. J Eval Clin Pract. 2019; 25 (5): 706–16.

189. Kuhn T.S. Objectivity, value judgment, and theory choice. In: Kuhn T.S. (Ed.) The Essential tension. Chicago: University Chicago Press; 1977: 320–43 (in Russ.).

190. Scheutz F., Poulsen S. Determining causation in epidemiology. Community Dent Oral Epidemiol. 1999; 27 (3): 161–70.

191. Baker G. An essay concerning the cause of the endemial colic of Devonshire. London: Printed by J. Hughs; 1767 (reprint: New York: Delta Omega Society; 1958).

192. Guy W.A. Contributions to the knowledge of the influence of employments upon health. J Roy Stat Soc. 1843; 6: 197–211.

193. Vineis P. History of bias. Soz Praventivmed. 2002; 47 (3): 156–61.

194. Lane-Claypon J.E. A further report on cancer of the breast, with special reference to its associated antecedent conditions. Reports on Public Health and Medical Subjects No. 32. Ministry of Health. London: Published by His Majesty´s Stationary Office; 1926.

195. Paneth N., Susser E., Susser M. Origins and early development of the case-control study: part 2. The case-control study from Lane-Claypon to 1950. Soz Praventivmed. 2002; 47 (6): 359–65.

196. Doll R., Hill A.B. The mortality of doctors in relation to their smoking habits; a preliminary report. Br Med J. 1954; 1 (4877): 1451–5.

197. Doll R., Hill A.B. Mortality in relation to smoking: ten years’ observations of British doctors. Br Med J. 1964; 1 (5395): 1399–410.

198. Senn S.J. Falsificationism and the clinical trials. Stat Med. 1991; 10 (11): 1679–92.

199. Bonell C., Moore G., Warren E., Moore L. Are randomised controlled trials positivist? Reviewing the social science and philosophy literature to assess positivist tendencies of trials of social interventions in public health and health services. Trials. 2018; 19 (1): 238.

200. Rothman K.J. (Ed.) Causal inference. Mass., USA: Epidemiology Resources Inc.; 1988: 207 p.

201. Boice J.D. Jr. Ionizing radiation. In: Schottenfeld D., Fraumeni J.F. (Eds.) Schottenfeld and Fraumeni cancer epidemiology and prevention. 3rd ed. New York: Oxford University Press: 2006: 259–93.

202. Susser M. Rational science versus a system of logic. In: Rothman K.J. (Ed.) Causal inference. Chestnut Hill, MS: Epidemiologic Resources; 1988: 189–99.

For citation:

Koterov A.N., Tikhonova O.A., Ushenkova L.N., Biryukov A.P. History of controlled trials in medicine: real priorities are little-known. Report 1. Basic concepts, terms, and disciplines that use medical experiment: historical and philosophical sources. FARMAKOEKONOMIKA. Modern Pharmacoeconomic and Pharmacoepidemiology. 2021;14(1):72-98. (In Russ.)

Views: 126

ISSN 2070-4909 (Print)
ISSN 2070-4933 (Online)