Keywords
public health
research design
causality
clinical decision-making
How to Cite
Abstract
In press
Background. Evidence-Based Medicine (EBM) integrates the best available research evidence with clinical expertise and patient values. In practice, it may be reduced to a hierarchy in which Randomized Controlled Trials (RCTs) are treated as a universal criterion of validity. Order of the Ministry of Health of Ukraine No.845 of June 19, 2026, updated procedures for sectoral standards and adaptation of clinical guidelines, emphasizing evidence applicability to clinical context.
Aim. To clarify the place of randomized controlled trials in the classical and contemporary understanding of evidence-based medicine, systematize situations in which other study designs are required, and determine the relevance of the resulting methodological conclusions to the new healthcare standardization system in Ukraine.
Materials and Methods. The study employed bibliosemantic and comparative methods and systems analysis. Scientific publications available in the PubMed and Google Scholar databases for 2016–2026, selected fundamental publications from earlier years, as well as Order of the Ministry of Health of Ukraine No.845 of June 19, 2026. and the regulatory and methodological documents on the development of sectoral standards approved by this Order were analyzed. The study was conducted as a private initiative of the authors, without grant support or state registration of the research topic. The article outlines ethical considerations for authors of scientific papers regarding the use of EBM tools.
Research Ethics. The study was conducted without the involvement of patients or animals and therefore did not require approval by an ethics committee.
Results. RCTs are the most reliable design for estimating causal effects of many controlled interventions, but their superiority is not universal. Randomization may be ethically unacceptable, difficult in surgery, infeasible in rare diseases, insufficient for detecting rare or delayed harms, and unsuitable for some population-level and policy interventions. In such situations, observational studies, natural experiments, pragmatic trials, and real-world evidence may be informative. Order No.845 provides for selection, appraisal, and adaptation of clinical guidelines with consideration of evidence quality and applicability.
Conclusions. RCTs should be regarded as a powerful but research-question-dependent tool. Evidence appraisal should consider design appropriateness, quality of conduct, and applicability of findings, integrated with clinical expertise and patient values.
Keywords: epidemiology, public health, research design, causality, clinical decision-making.
References
Evidence-Based Medicine Working Group. Evidence-based medicine. A new approach to teaching the practice of medicine. JAMA. 1992;268(17):2420-5. DOI: 10.1001/jama.1992.03490170092032. PMID: 1404801.
Smith R, Rennie D. Evidence-based medicine – an oral history. JAMA. 2014;311(4):365-7. DOI: 10.1001/jama.2013.286182. PMID: 24449049.
Sackett DL, Rosenberg WMC, Gray JAM, Haynes RB, Richardson WS. Evidence based medicine: what it is and what it isn't. BMJ. 1996;312(7023):71-2. DOI: 10.1136/bmj.312.7023.71. PMID: 8555924.
Ministry of Health of Ukraine. Order No.845 of 19 Jun 2026 "Certain issues concerning the development of sectoral standards in healthcare". Registered with the Ministry of Justice of Ukraine on 30 Jul 2026 with No.1090/46484. In force as of 28 Sep 2026. Verkhovna Rada of Ukraine. Legislation of Ukraine. [Internet]. Available at: https://zakon.rada.gov.ua/laws/show/z1090-26 [in Ukrainian].
Shevchuk RV. Problems of health care system reform in modern Ukraine. Public Management. 2022;(3(31)):95-101. DOI: 10.32689/2617-2224-2022-3(31)-13. [In Ukrainian].
Velychko VI, Lahoda DO, Venher YaI. Introduction of evidence-based medicine in the education of medical students. Medical Education. 2021;(2):11-6. DOI: 10.11603/me.2414-5998.2021.2.11944. [In Ukrainian].
Tonelli MR, Bluhm R. Teaching medical epistemology within an evidence-based medicine curriculum. Teach Learn Med. 2021;33(1):98-105. DOI: 10.1080/10401334.2020.1835666. PMID: 33356585.
Greenhalgh T, Howick J, Maskrey N; Evidence Based Medicine Renaissance Group. Evidence based medicine: a movement in crisis? BMJ. 2014;348:g3725. DOI: 10.1136/bmj.g3725. PMID: 24927763.
Rothwell PM. External validity of randomised controlled trials: "to whom do the results of this trial apply?" Lancet. 2005;365(9453):82-93. DOI: 10.1016/S0140-6736(04)17670-8. PMID: 15639683.
Ohniev VA. Course of lectures on the discipline "Social Medicine, Public Health". Kharkiv: Kharkiv National Medical University; 2026. 383 p. [In Ukrainian].
Shevchenko AS, Brown GW. What evidence-based medicine can oppose to falsifications in science. Bull KhRIPHS. 2020;96(4):24-35. DOI: 10.5281/zenodo.5076629. [In Ukrainian].
Wallace SS, Barak G, Truong G, Parker MW. Hierarchy of evidence within the medical literature. Hosp Pediatr. 2022;12(8):745-50. DOI: 10.1542/hpeds.2022-006690. PMID: 35909178.
Balshem H, Helfand M, Schünemann HJ, Oxman AD, Kunz R, Brozek J, et al. GRADE guidelines: 3. Rating the quality of evidence. J Clin Epidemiol. 2011;64(4):401-6. DOI: 10.1016/j.jclinepi.2010.07.015. PMID: 21208779.
Kostis JB, Dobrzynski JM. Limitations of randomized clinical trials. Am J Cardiol. 2020;129:109-15. DOI: 10.1016/j.amjcard.2020.05.011. PMID: 32560898.
Concato J, Shah N, Horwitz RI. Randomized, controlled trials, observational studies, and the hierarchy of research designs. N Engl J Med. 2000;342(25):1887-92. DOI: 10.1056/NEJM200006223422507. PMID: 10861325.
Benson K, Hartz AJ. A comparison of observational studies and randomized, controlled trials. N Engl J Med. 2000;342(25):1878-86. DOI: 10.1056/NEJM200006223422506. PMID: 10861324.
Borgerson K. Valuing evidence: bias and the evidence hierarchy of evidence-based medicine. Perspect Biol Med. 2009;52(2):218-33. DOI: 10.1353/pbm.0.0086. PMID: 19395821.
World Medical Association. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human participants. JAMA. 2025;333(1):71-4. DOI: 10.1001/jama.2024.21972. PMID: 39425955.
Smith GCS, Pell JP. Parachute use to prevent death and major trauma related to gravitational challenge: systematic review of randomised controlled trials. BMJ. 2003;327(7429):1459-61. DOI: 10.1136/bmj.327.7429.1459. PMID: 14684649.
Yeh RW, Valsdottir LR, Yeh MW, Shen C, Kramer DB, Strom JB, et al. Parachute use to prevent death and major trauma when jumping from aircraft: randomized controlled trial. BMJ. 2018;363:k5094. DOI: 10.1136/bmj.k5094. PMID: 30545967.
Gaudino M, Chikwe J, Bagiella E, Fremes S, Jones DR, Meyers B, et al. Challenges to randomized trials in adult and congenital cardiac and thoracic surgery. Ann Thorac Surg. 2022;113(5):1409-18. DOI: 10.1016/j.athoracsur.2020.11.042. PMID: 33412133.
Robinson NB, Fremes S, Hameed I, Rahouma M, Weidenmann V, Demetres M, et al. Characteristics of randomized clinical trials in surgery from 2008 to 2020: a systematic review. JAMA Netw Open. 2021;4(6):e2114494. DOI: 10.1001/jamanetworkopen.2021.14494. PMID: 34190996.
Hetzler PT 3rd, Berger LE, Huffman SS, Lee M, Park R, Song DH, Dugdale LS. The characteristics and ethics of sham surgeries: a systematic review of randomized controlled trials. Ann Surg. 2023;278(2):153-8. DOI: 10.1097/SLA.0000000000005882. PMID: 37066793.
Kempf L, Goldsmith JC, Temple R. Challenges of developing and conducting clinical trials in rare disorders. Am J Med Genet A. 2018;176(4):773-83. DOI: 10.1002/ajmg.a.38413. PMID: 28815894.
Li Y, Izem R. Novel clinical trial design and analytic methods to tackle challenges in therapeutic development in rare diseases. Ann Transl Med. 2022;10(18):1034. DOI: 10.21037/atm-21-5496. PMID: 36267797.
Páez A, Rovers M, Hutchison K, Rogers W, Vasey B, McCulloch P; IDEAL Collaboration. Beyond the RCT: when are randomized trials unnecessary for new therapeutic devices, and what should we do instead? Ann Surg. 2022;275(2):324-31. DOI: 10.1097/SLA.0000000000005053. PMID: 34238815.
Sawchik J, Hamdani J, Vanhaeverbeek M. Randomized clinical trials and observational studies in the assessment of drug safety. Rev Epidemiol Sante Publique. 2018;66(3):217-25. DOI: 10.1016/j.respe.2018.03.133. PMID: 29685700.
Phillips R, Hazell L, Sauzet O, Cornelius V. Analysis and reporting of adverse events in randomised controlled trials: a review. BMJ Open. 2019;9(2):e024537. DOI: 10.1136/bmjopen-2018-024537. PMID: 30826796.
Hong H, Wang C, Rosner GL. Meta-analysis of rare adverse events in randomized clinical trials: Bayesian and frequentist methods. Clin Trials. 2021;18(1):3-16. DOI: 10.1177/1740774520969136. PMID: 33258698.
Ogilvie D, Adams J, Bauman A, Gregg EW, Panter J, Siegel KR, et al. Using natural experimental studies to guide public health action: turning the evidence-based medicine paradigm on its head. J Epidemiol Community Health. 2020;74(2):203-8. DOI: 10.1136/jech-2019-213085. PMID: 31744848.
Crane M, Bohn-Goldbaum E, Grunseit A, Bauman A. Using natural experiments to improve public health evidence: a review of context and utility for obesity prevention. Health Res Policy Syst. 2020;18(1):48. DOI: 10.1186/s12961-020-00564-2. PMID: 32423438.
Craig P, Campbell M, Deidda M, Dundas R, Green J, Katikireddi SV, et al. Using natural experiments to evaluate population health interventions: a framework for producers and users of evidence. Public Health Res (Southampt). 2025;13(3):1-59. DOI: 10.3310/JTYW6582. PMID: 40163348.
Zuidgeest MGP, Goetz I, Groenwold RHH, Irving E, van Thiel GJMW, Grobbee DE; GetReal Work Package 3. Series: pragmatic trials and real world evidence: Paper 1. Introduction. J Clin Epidemiol. 2017;88:7-13. DOI: 10.1016/j.jclinepi.2016.12.023. PMID: 28549929.
Bilinski A, Emanuel N, Ciaranello A. Sins of omission: model-based estimates of the health effects of excluding pregnant participants from randomized controlled trials. Ann Intern Med. 2025;178(6):868-77. DOI: 10.7326/ANNALS-24-00689. PMID: 40294421.
Djulbegovic B, Razavi M, Hozo I. When are randomized trials unnecessary? A signal detection theory approach to approving new treatments based on non-randomized studies. J Eval Clin Pract. 2021;27(4):735-42. DOI: 10.1111/jep.13497. PMID: 33103322.
Terman SW, Speiser JL, Eliasziw M, Kurth T, Schneider ALC. Target trial emulation: a primer on improving observational research in neurology. Neurology. 2025;105(10):e214269. DOI: 10.1212/WNL.0000000000214269. PMID: 41151003.
Cashin AG, Hansford HJ, Hernán MA, Swanson SA, Lee H, Jones MD, et al. Transparent reporting of observational studies emulating a target trial: the TARGET Statement. BMJ. 2025;390:e087179. DOI: 10.1136/bmj-2025-087179. PMID: 40903028.
Stavytskyi VV. Evidence as myth: cognitive traps of evidence-based medicine in the age of scientific absolutism. Reflections of a clinician. Ukrainian Medical Journal. 2026. DOI: 10.32471/umj.1680-3051.273809. [In Ukrainian].
Stavytskyi VV. Evidence-based medicine: Sackett and Guyatt – the schism at the outset. Ukrainian Medical Journal. 2026;4(178):4р. DOI: 10.32471/umj.1680-3051.278401. [In Ukrainian].
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.