Randomize Kontrollü Deneyler

Yıl 2017, Cilt: 4 Sayı: 1, 73 - 92, 18.05.2017

Belgin Akın Deniz Koçoğlu

Öz

Bu derleme kanıta dayalı uygulama bakış açısının gelişmesiyle birlikte önemli bir araştırma türü haline gelen Randomize Kontrollü Deneylerle ilgili temel kavram ve yaklaşımların açıklanması amacıyla yapılmıştır. Randomize Kontrollü Deneylerin başarısı ve kalitesi ölçülen sonucun ortaya çıkmasında uygulanan müdahalenin gerçek etkisinin gösterilmesine bağlıdır. Bu neden-sonuç bağlantısının kurulması Randomize Kontrollü Deneylerin bir protokol çerçevesinde yürütülmesi, random atamanın yapılması, yanlılıkların önlenmesi, iç ve dış geçerliliğin sağlanması, körleme tekniklerinin kullanılması ve uygun istatistiksel değerlendirmenin yapılmasıyla olasıdır. Bu derleme bu aşamalara ilişkin yapılan hataları ve alınabilecek önlemlere ilişkin yaklaşımları içermektedir.

Anahtar Kelimeler

Dış geçerlik, iç geçerlik, nedensellik, randomize kontrollü deneyler, yanlılık

Randomized Controlled Trials

Öz

This review aims to explain the basic concepts and approaches related to randomized controlled trials, which is an important type of research with the development of viewpoint of evidence -based care. The success and quality of randomized controlled trials hinge upon observing the actual effect of the applied intervention on the emergence of the measured result. Establishing this cause-effect relation can be possible if randomized controlled trials are conducted within a protocol, use random assignment, avoid biase, ensure internal and external validity, use blind techniques and appropriate statistical evaluations. This review includes the mistakes made in these stages and the precaution to be taken.

Anahtar Kelimeler

Bias, causality, external validity, internal validity, randomized controlled trial

Kaynakça

• 1. Ciliska D, Cand N, Brian H. Evidence-based nursing, USA: Wiley; 2013. p.15-48
• 2. Persson J, Sahlin NE. A philosophical account of interventions and causal representation in nursing research. International Journal Of Nursing Studies  2009; 46(4): 547-56.
• 3. Cochrane Consumer Network. Levels of evidence. 2016. URL:http://consumers.cochrane.org/levelsevidence: 10.12.2016
• 4. Shah HM, Chung KC. Archie Cochrane and his vision for evidence-based medicine. Plast Reconstr Surg 2009; 124(3): 982–8.
• 5. Johnson MH. The early history of evidence-based reproductive medicine.Reprod Biomed Online  2013;26(3):201-9.
• 6. Peterson MH, Barnason S, Donnelly B, Hıll K, Mıley H, Rıggs L Whiteman K. Choosing the best evidence to guide clinical practice: Application of AACN levels of evidence. Critical Care Nurse 2014; 34(2):58-68.
• 7. Nichol AD, Bailey M, Cooper DJ. Challenging issues in randomised controlled trials. Injury 2010;41: 20–3
• 8. Higgins JPT, Green S. Cochrane handbook for systematic reviews of interventions version 5.1.0. England: The Cochrane Collaboration; 2011.
• 9. Flecha OD, Douglas de Oliveira DW, Marques LS, Gonçalves PF. A commentary on randomized clinical trials: How to produce them with a good level of evidence. Perspect Clin Res 2016;7:75-80.
• 10. Forbes A. Clinical intervention research in nursing. International Journal of Nursing Studies 2009; 46: 557–68
• 11. Richards DA, Hamers JP. RCTs in complex nursing interventions and laboratory experimental studies. International Journal of Nursing Studies 2009;(46): 588–92
• 12. Borglin G, Richards DA. Bias in experimental nursing research: Strategies to improve the qualityand explanatory power of nursing science. International Journal of Nursing Studies 2010;47:123–8
• 13. Fridlund B, Jönsson AC, Andersson EK, Bala SV, Dahlman GB, Forsberg, A, et al. Essentials of nursing care in randomized controlled trials of nurse-led interventionsin somatic care: A Systematic Review. Open Journal of Nursing 2014; 4: 181-97.
• 14. Mantzoukas S. The research evidence published in high impact nursing journals between 2000 and 2006: A quantitative content analysis. International Journal of Nursing Studies. 2009;46; 479–89
• 15. Baldi I, Del Lago E, De Bardi S, Sartor G, Soriani,N, Zanotti, R. Trends in RCT nursing research over 20 years: mind the gap British Journal of Nursing 2014;23(16), 895-99.
• 16. Blackwood B. Methodological issues in evaluating complex healthcare interventions Journal of Advanced Nursing 2006; 54(5): 612–2.
• 17. Thompson C. Fortuito us phenomena: on complexity, pragmatic randomised controlled trials, and knowledge for evidence-based practice. World Views on Evidence-Based Nursing 2004;1: 9–17.
• 18. Glasdam S, Sivberg B, Wihlborg, M. Nurse-led interventions in the concept of randomized controlled trials – critical perspectives on how to handle social contexts. Internatıonal Journal of Multıple Research Approaches 2015; 9(1); 1-23.
• 19. Rolfe G. Complexity and uniqueness in nursing practice: Commentary on Richards and Hamers (2009). International Journal of Nursing Studies 2009:46;1156–8
• 20. Lindsay B. Randomized controlled trials of socially complex nursing interventions: creating bias and unreliability. Journal of Advanced Nursing 2004;45 (1): 84–94.
• 21. Chow, SC. Design and analysis of clinical trials, USA:Wiley; 2013, p.124-98
• 22. Pocock SJ. Clinical trials, USA:Wiley; 2013, p.16-89, p.321-80
• 23. Institute of Medicine Staff. Small clinical trials, NationalAcademies Press; 2001. p.3-89
• 24. Alford L. On differences between explanatory and pragmatic clinical trials. New Zealand Journal of Physiotherapy 2006;35(1):12-6.
• 25. Treweek S, Zwarenstein M. Making trials matter: pragmatic and explanatory trials and the problem of applicability. Trials 2009;10:37
• 26. Lesaffre E. Superiority, equivalence, and non-inferiority trials. Bulletin of the NYU Hospital for Joint Diseases 2008;66:150–4.
• 27. Christensen E. Methodology of superiority vs. equivalence trials and non-inferiority trials. Journal of Hepatology 2007; 46:947–54.
• 28. Gonzalez CD, Bolaños R, de Sereday M. Editorial on hypothesis and objectives in clinical trials: superiority, equivalence and non-inferiority. Thrombosis Journal 2009; 7(1):3.
• 29. Fayers PM, Machin D. Randomized clinical trials. Incorporated: Wiley&Sons, 2010.
• 30. Chan AW, Tetzlaff JM, Gøtzsche PC, Altman DG, Mann H, Berlin JA, et al. SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials. BMJ 2013;346:75-86.
• 31. Chan AW, Tetzlaff JM, Altman DG, Laupacis A, Gøtzsche PC, Krleža-Jerić, K. et al. SPIRIT 2013 statement: defining standard protocol items for clinical trials. Annals of Internal Medicine  2013;158(3): 200-7.
• 32. Gray R, Badnapurkar A, Thomas D. Reporting of clinical trials in nursing journals: how are we doing? JAN 2016; Editorial:1
• 33. Attia A. Bias in RCTs: Confounders, selection bias and allocation concealment. Middle East Fertility Society Journal 2005; 3(10): 258-61.
• 34. Research and Innovation . Randomization in clinical trials, England: University of the West of England ; 2011.
• 35. Xiao L, Lavori PW, Wilson SR, Ma J. Comparison of dynamic block randomization and minimization in randomized trials: A simulation study. Clin Trials 2011;8:59-69.
• 36. Field A. Discovering statistic using IBM SPSS statistics, 4th Edition. Los Angels: SAGE Publication; 2009
• 37. Shively WP. Causal thinking and design of research the craft of political research. 8th edition. New Jersey: Copyright © by Pearson Education Upper Saddle River; 2009.
• 38. Çağatay P, Şenocak M, Baykal İE. A proposal for scoring of the evaluation of randomized clinical trials. Cerrahpaşa J Med 2000; 31 (1): 49-55.
• 39. Dziura JD, Post LA, Zhao Q, Fu Z, Peduzzi P. Strategies for dealing with missing data in clinical trials: From design to Analysis. Yale Journal of Biology and Medıcıne 2013; 86:343-58.
• 40. Pannucci CJ, Wilkins EG. Identifying and avoiding bias in research. Plast Reconstr Surg 2010;126:619– 25.
• 41. Ron K, Faltin F, Ruggeri F. Statistical methods in healthcare, edited by Ron Kenett. USA:Wiley; 2012.
• 42. European Network for Health Technology Assessment (EUnetHTA). Guideline - levels of evidence - internalvalidity of randomizedcontrolledtrials, Final version; 2013 URL:https://eunethta.fedimbo. belgium.be/sites/5026.fedimbo.belgium.be/files/Internal_Validity.pdf ,29.11.2016
• 43. Machin D, Fayers PM. Randomized clinical trials. USA:John Wiley&Sons; 2010
• 44. Borenstein M, Hedges LV, Higgins JPT, Rothstein HR. Introduction to meta-analysis, publication bias USA: John Wiley & Sons, Ltd; 2009
• 45. Song F, Hooper L, Loke YK. Publication bias: what is it? How do we measure it? How do we avoid it? Open Access Journal of Clinical Trials 2013:5; 71–81
• 46. International Committee Medical Journal Editors-ICMJE. Clinical Trials Registration 2008 URL:: http://www.icmje.org/about-icmje/faqs/clinical-trials-registration/ 04.12.2016
• 47. Tse T, Williams RJ, Zarin DA. Reporting “basic results” in Clinicaltrials. CHEST Journal 2009; 136(1):295-303.
• 48. WHO. International standards for clinical trial registries 2012. URL: http://apps.who.int/iris/ bitstream/10665/76705/1/9789241504294_eng.pdf?ua=1&ua=1. 04.12.216
• 49. Food and Drug Administration. Amendments act (FDAAA) 2007 URL: https://www.gpo.gov/fdsys/ pkg/PLAW-110publ85/pdf/PLAW-110publ85.pdf#page=82 Erişim tarihi: 04.12.216
• 50. Moher D, Hopewell S, Schulz KF, Montori V, Gotzsche PC, Devereaux PJ et al. CONSORT 2010 explanation and elaboration: Updated guidelines for reporting parallel group randomised trials. J Clin Epidemiol 2010;63:2237.
• 51. Jull A, Aye PS. Endorsement of the CONSORT guidelines, trial registration,and the quality of reporting randomised controlled trials in leading nursing journals: A cross-sectional analysis. International Journal of Nursing Studies 2015;
• 52(6): 1071–1079 52. Guo JW, Sward KA, Beck SL, Staggers N. Quality of reporting randomized controlled trials in cancer nursing research. Nursing Research 2014; 63(1): 26–35.
• 53. Jadad AR, Enkin MW. Bias in randomized controlled trials in Randomized controlled trials: Questions, answers and musings. 2nd Edition. USA: Blackwell Publishing 2007.
• 54. Turlik M. Evaluating the internal validity of a randomized controlled trial. The Foot and Ankle Online Journal 2009; 2 (3): 5-9
• 55. Armijo-Olivo S, Fuentes J, Ospina M, Saltaji H, Hartling L. Inconsistency in the items included in tools used in general health research and physical therapy to evaluate the methodological quality of randomized controlled trials: a descriptive analysis. BMC Medical Research Methodology 2013; 13(1): 116.
• 56. Smith AS, Oldman A, McQuay H, Moore R. Teasing apart quality and validity in systematic reviews: an example from acupuncture trials in chronic neck and back pain. Pain 2000;86:119-32
• 57. Zeng X, Zhang Y, Kwong JS, Zhang C, Li S, Sun F et al. The methodological quality assessment tools for preclinical and clinical studies, systematic review and meta-analysis, and clinical practice guideline: a systematic review. Journal of Evidence-Based Medicine  2015; 8(1): 2-10.
• 58. Zhang J, Wang J, Han L, Cao X, Shields L. Tools to assess risk of bias in systematic reviews of nursing intervention in China: Global implications of the findings. Nursing Outlook; 2016
• 59. Schulz KF. Randomised trials, human nature, and reporting guidelines. Lancet 1996;348:5968.
• 60. Karanicolas PJ, Farrokhyar F, Bhandari M, Blinding: Who, what, when, why, how? Can J Surg 2010;53(5):345-8.
• 61. Bagiella E. Randomization in handbbok for clinical research. Medical Publishing ; 2014.
• 62. Schulz F, Grimes DA. Blinding in randomised trials: hiding who got what. The Lancet 2002;359(9307):696700.
• 63. Hróbjartsson A, Thomsen ASS, Emanuelsson F, Tendal B, Hilden J, Boutron I, et al. Observer bias in randomized clinical trials with measurement scale outcomes: a systematic review of trials with both blinded and nonblinded assessors. Canadian Medical Association Journal 2013;1: 185:279
• 64. King, KM, Thompson DR. Guest editorial: Pragmatic trials: is this a useful method in nursing research?. Journal of Clinical Nursing 2008; 17(11): 1401-2
• 65. .Hrobjartsson A. What are the main methodological problems in the estimation of placebo effects. Journal of Clinical Epidemiology 2002;55: 430-5
• 66. Macefield R. Usability studies and the Hawthorne effect. Journal of Usability Studies 2007; 2(3): 145-54.
• 67. Polit DF. Blinding during the analysis of research data. International Journal of Nursing Studies 2011; 48(5): 636-41.
• 68. Hallberg IR. Moving nursing research forward towards a stronger impact on health care practice? International Journal of Nursing Studies 2009; 46(4): 407-12
• 69. Armijo-Olivo S,Warren S, Magee D. Intention to treat analysis, compliance,drop-outs and how to deal with missing data in clinical research: a review. Physical Therapy Reviews 2009;14 (1):36-49.
• 70. Fergusson D, Aaron SD, Guyatt G, Hebert P. Post randomisation exclusions: the intention to treatprinciple and excluding patients from analysis.BMJ 2002;325:652–4.
• 71. Gupta SK. Intention-to-treatconcept: A review. Perspect Clin Res 2011; 2(3): 109–12.
• 72. Silva Filho CR, Saconato H, Conterno LO, Marques I, Atallah AN. Assessment of clinical trial quality and its impact on meta-analyses. Rev Saude Publica 2005;39:865–73.
• 73. Montori VM, Guyatt GH. Intention-to-treat principle. CMAJ 2001;165:1339–41.
• 74. Cheema JR. Some general guidelines for choosing missing data handling methods in educational research. Journal of Modern Applied Statistical Methods. 2014;13(2): 3.
• 75. Akl EA, Shawwa K, Kahale LA, Agoritsas T, Brignardello-Petersen R, Busse JW. et al. Reporting missing participant data in randomised trials: systematic survey of the methodological literatüre and a proposed guide. BMJ 2015;5(12): 8431.
• 76. Weinstein JN,  Lurie JD,  Tosteson TD,  Skinner JS,  Hanscom B,  Tosteson AN et al. Surgical vs nonoperative treatment for lumbar disk herniation: The Spine Patient Outcomes Research Trial (SPORT): a randomized trial. JAMA 2006;296:2441- 50.
• 77. Abraha I, Montedori A. Modified intention to treat reporting in randomised controlled trials: systematic review. BMJ 2010:3; 40
• 78. Sainani KL. Making sense of Intention-to-Treat, American Academy of Physical Medicine and Rehabilitation 2010; 2:209-213.
• 79. Bell ML, Fiero M, Horton NJ, Hsu CH. Handling missing data in RCTs; a review of the top medical journals. BMC medical research methodology, 2014;14(1): 118.
• 80. Polit DF, Gillespie BM. The use of the intention-to-treat principle in nursing clinical trials. Nursing Research 2009; 58(6); 391-9.
• 81. Gewandter JS, McDermott MP, McKeown A, Smith SM, Pawlowski JR, Poli JJ et al. Reporting of intentionto-treatanalyses in recent analgesic clinical trials: ACTTION systematic review and recommendations, Pain, 2014;155(12):2714-19.
• 82. Joseph R, Sim J, Ogollah R, Lewis, M. A systematic review finds variable use of the intention-to-treat principle in musculoskeletal randomized controlled trials with missing data. Journal of Clinical Epidemiology 2015; 68(1): 15-24.
• 83. Gravel J, Opatrny L, Shapiro S. The intention-to-treat approach in randomized controlled trials: are authors saying what they do and doing what they say?.Clinical Trials 2007; 4(4): 350-6.
• 84. Fernandez A, Sturmberg J, Lukersmith S, Madden R, Torkfar G, Colagiuri R et al. Evidence-based medicine: is it a bridge too far? Health Research Policy and Systems 2015; 13(1):66.
• 85. Shuttleworth M. External Validity. (Aug 7, 2009) URL: https://explorable.com/external-validity. 14.01.2017
• 86. Avelar SA, Thomas J, Kleinman R, Sama-Miller E, Woodruff SE, Coughlin R et al. External validity. The next step for systematic reviews? Evaluation Review 2016; 1:43.
• 87. Khorsan R, Crawford C. External validity and model validity: A conceptual approach for systematic review methodology. Evidence Based Complementary and Alternative Medicine 2014; 1: 12 -15
• 88. Partridge SR, Juan S J-H, McGeechan K, Bauman A, Allman-Farinelli M. Poor quality of external validity reporting limits generalizability of overweight and/or obesity lifestyle prevention interventions in young adults: a systematic review. Obesity Reviews 2015; 1(6):13–31.
• 89. Rothwell PM. Factors that can affect the external validity of randomized controlled trials. PLoS Clin Trials 2006; 1(1):e9
• 90. Buntrock C, Ebert D, Lehr D, Riper H, Smit F, Cuijpers P et al. Effectiveness of a web-based cognitive behavioural intervention for subthreshold depression: Pragmatic Randomised Controlled Trial. Psychother Psychosom 2015; 84:348–58.
• 91. Steckler A, McLeroy KR. (Editorial) The Importance of external validity. American Journal of Public Health. 2008; 98(1): 9-10.
• 92. Donald F, Kilpatrick K, Reid K, Carter N, Martin-Misener R, Bryant-Lukosius D et al. A Systematic review of the cost-effectiveness of nurse practitioners and clinical nurse specialists: What is the quality of the evidence? Nursing Research and Practice 2014;1:28
• 93. Sigurdardottir KR, Oldervoll L, Hjermstad MJ, Kaasa S, Knudsen AK, Lohre ET et al. How are palliative care cancer populations characterized in Randomized Controlled Trials? A Literature Review. Journal of Pain and Symptom Management 2014; (47) 5: 906-14.
• 94. Ferreira JC, Patino CM,3 What does the p value really mean? J Bras Pneumol 2015;41(5):485
• 95. Alpar R. Spor, Sağlık ve eğitim bilimlerinden örneklerle uygulamalı istatistik ve geçerlik-güvenirlik. Ankara: Detay Yayıncılık. 7. Baskı. 2016. S.227-233, s.232-233, s.314
• 96. Borenstein M, Hedges LV, Higgins JPT, Rothstein HR. Meta analizi giriş. Ankara: Anı Yayıncılık.2013. s.17-60
• 97. West A, Spring B.Randomized controlled trials.URL: http://www.ebbp.org/course_outlines/ randomized_controlled_trials/ 14.01.2017
• 98. Peduzzi P, Henderson W, Hartigan P, Lavori P. Analysis of randomized controlled trials. Epidemiologic Reviews 2002; 24(1):12-5