Técnicas de randomização e alocação para estudos clínicos
Techniques for randomization and allocation for clinical trials
Anna Carolina Miola; Ana Cláudia Cavalcante Espósito; Hélio Amante Miot
Resumo
Palavras-chave
Abstract
Intervention studies require all participants to originate from the same population, with random allocation to intervention groups to ensure comparability. Randomization is crucial for minimizing confounding factors, allowing differences in outcomes to be attributed to the intervention. Simple randomization performs well for large samples (>100 per group), but smaller samples may require block or stratified randomization to balance group sizes and covariates. When randomization isn't feasible, quasi-randomized methods (e.g., based on dates or enrollment order) can help but must compensate with multivariate adjustments. Moreover, blinding and allocation concealment enhance internal validity and reproducibility. Allocation concealment (e.g., sealed envelopes) prevents bias during participant assignment while blinding mitigates detection and performance biases. Precise methodological descriptions in clinical trial registrations and publications enhance study reliability and reproducibility, highlighting the importance of rigorous planning and transparent reporting in intervention research. This article reviews the key concepts of randomization, blinding, and allocation concealment in interventional studies
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References
1 Altman DG, Bland JM. Statistics notes. Treatment allocation in controlled trials: why randomise? BMJ. 1999;318(7192):1209.
2 Sacks H, Chalmers TC, Smith H Jr. Randomized versus historical controls for clinical trials. Am J Med. 1982;72(2):233-40.
3 Roberts C, Torgerson D. Understanding controlled trials: randomisation methods in controlled trials. BMJ. 1998;317(7168):1301-10.
4 Miola AC, Miot HA. P-value and effect-size in clinical and experimental studies. J Vasc Bras. 2021;20:e20210038.
5 Zhao W. Selection bias, allocation concealment and randomization design in clinical trials. Contemp Clin Trials. 2013;36(1):263-5.
6 Coelho F No, Araujo WJB, Belczak S, et al. Influence of compression therapy following varicose vein surgery: a prospective randomized study. J Vasc Bras. 2023;22:e20220052.
7 Hulley SB, Cummings SR, Browner WS. Designing clinical research. 3rd ed. New York: Lippincott Williams & Wilkins; 2006.
8 Garcia EL, Pereira AH, Menezes MG, et al. Effects of aerobic and combined training on pain-free walking distance and health-related quality of life in patients with peripheral artery disease: a randomized clinical trial. J Vasc Bras. 2023;22:e20230024.
9 GraphPad [site na Internet]. 2024 [citado 2024 abr 7].
10 Research Randomizer [site na Internet]. 2024 [citado 2024 abr 7].
11 Moher D, Hopewell S, Schulz KF, et al. CONSORT 2010 explanation and elaboration: updated guidelines for reporting parallel group randomised trials. BMJ. 2010;340(1):c869.
12 Ference BA, Holmes MV, Smith GD. Using Mendelian randomization to improve the design of randomized trials. Cold Spring Harb Perspect Med. 2021;11(7):a040980.
13 Davey Smith G, Hemani G. Mendelian randomization: genetic anchors for causal inference in epidemiological studies. Hum Mol Genet. 2014;23(R1):R89-98.
14 Kang M, Ragan BG, Park JH. Issues in outcomes research: an overview of randomization techniques for clinical trials. J Athl Train. 2008;43(2):215-21.
15 Pocock SJ, Simon R. Sequential treatment assignment with balancing for prognostic factors in the controlled clinical trial. Biometrics. 1975;31(1):103-15.
16 Taves DR. Minimization: a new method of assigning patients to treatment and control groups. Clin Pharmacol Ther. 1974;15(5):443-53.
17 Treasure T, MacRae KD. Minimisation: the platinum standard for trials? Randomisation doesn’t guarantee similarity of groups; minimisation does. BMJ. 1998;317(7155):362-3.
18 Schulz KF, Grimes DA. Generation of allocation sequences in randomised trials: chance, not choice. Lancet. 2002;359(9305):515-9.
19 Purssell E, Drey N, Chudleigh J, Creedon S, Gould DJ. The Hawthorne effect on adherence to hand hygiene in patient care. J Hosp Infect. 2020;106(2):311-7.
20 Chalmers TC, Celano P, Sacks HS, Smith H Jr. Bias in treatment assignment in controlled clinical trials. N Engl J Med. 1983;309(22):1358-61.
21 Forder PM, Gebski VJ, Keech AC. Allocation concealment and blinding: when ignorance is bliss. Med J Aust. 2005;182(2):87-9.
22 Berger VW, Do AC. Allocation concealment continues to be misunderstood. J Clin Epidemiol. 2010;63(4):468-9.
23 Pildal J, Chan AW, Hrobjartsson A, Forfang E, Altman DG, Gotzsche PC. Comparison of descriptions of allocation concealment in trial protocols and the published reports: cohort study. BMJ. 2005;330(7499):1049.
24 Schulz KF, Grimes DA. Allocation concealment in randomised trials: defending against deciphering. Lancet. 2002;359(9306):614-8.
25 Kennedy CE, Fonner VA, Armstrong KA, et al. The Evidence Project risk of bias tool: assessing study rigor for both randomized and non-randomized intervention studies. Syst Rev. 2019;8(1):3.
26 Deeks JJ, Dinnes J, D’Amico R, et al. Evaluating non-randomised intervention studies. Health Technol Assess. 2003;7(27):iii-x.
27 Popp L, Schneider S. Attention placebo control in randomized controlled trials of psychosocial interventions: theory and practice. Trials. 2015;16(1):150.
28 Linde K, Fassler M, Meissner K. Placebo interventions, placebo effects and clinical practice. Philos Trans R Soc Lond B Biol Sci. 2011;366(1572):1905-12.
29 Fregni F, Imamura M, Chien HF, et al. Challenges and recommendations for placebo controls in randomized trials in physical and rehabilitation medicine: a report of the international placebo symposium working group. Am J Phys Med Rehabil. 2010;89(2):160-72.
30 Homer CS. Using the Zelen design in randomized controlled trials: debates and controversies. J Adv Nurs. 2002;38(2):200-7.
31 Simon GE, Shortreed SM, DeBar LL. Zelen design clinical trials: why, when, and how. Trials. 2021;22(1):541.
32 Torgerson DJ, Roland M. Understanding controlled trials: What is Zelen’s design? BMJ. 1998;316(7131):606.
33 Lai D, Wang D, McGillivray M, Baajour S, Raja AS, He S. Assessing the quality of randomization methods in randomized control trials. Healthc (Amst). 2021;9(4):100570.
Submitted date:
04/07/2024
Accepted date:
09/02/2024
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