Pragmatic clinical trials
https://doi.org/10.37489/2588-0519-2020-3-52-60
Abstract
Pragmatic clinical trials (PCTs) allow combining the advantages of observational trials in real-world evidence with the scientific rigor of randomized clinical trials (RCTs), and thereby provide more effective answers to questions of real-world evidence.
Aim. Assessment of differences in conducting RCTs and PCTs, as well as analysis of the features related to conducting PCTs at different stages.
Methods. An analysis of publications in the period from 1999 to 2017 was conducted to identify data on PCTs.
Results. There are significant differences in conducting classic RCTs and PCTs. First, PCTs use more flexible inclusion criteria and differ in the approach to choosing an investigator’s site. Also, the procedure for obtaining informed consent has significant differences from that of classical RCTs; alternative options are proposed but a unified approach has not yet been developed. When conducting PCTs, monitor intervention should be minimal in order not to interfere in the routine therapy, which, however, can lead to a violation of reporting. A possible solution may be remote data collection.
Conclusion. PCTs represent a huge potential for studying the effectiveness of drugs in real-world evidence. However, despite a significant increase in the number of such trials, there are still a sufficient number of points that need to be resolved.
About the Authors
O. R. Shevchenko
FSBEI HE I.P. Pavlov SPbSMU MOH Russia
Russian Federation
Russian Federation
Shevchenko Olga R. - Post-graduate student, Department of Clinical Pharmacology and Evidence-Based Medicine
St. Petersburg
A. S. Kolbin
FSBEI HE I.P. Pavlov SPbSMU MOH Russia;
FSBEI HE “Saint-Petersburg State University”
Russian Federation
Russian Federation
Kolbin Alexey S. - D. Sci. in Medicine, Professor, Head of the Department of Clinical Pharmacology and Evidence-Based Medicine, FSBEI HE I.P. Pavlov SPbSMU MOH Russia; Professor of the Department of Pharmacology, Medical Faculty, SPbSU
SPIN code: 7966-0845
St. Petersburg
References
1. Upravlenie klinicheskimi issledovaniyami / pod obshch. red. Belousova DYU, Zyryanova SK, Kolbina AS. — 1-e izd. — M.: Buki Vedi: Izdatel’stvo OKI, 2017. (In Russ).
2. FDA. Framework for FDA’s real-world evidence program. 2018. [cited 2020 Jul 25]. Available from: https://www.fda.gov/media/120060/download
3. Cochrane AL. Effectiveness and efficiency: random reflection on health services. — London: Nuffield Provincial Hospitals Trust. 1972. [cited 2020 Jul 25]. Available from: https://www.nuffieldtrust.org.uk/files/2017-01/effectiveness-and-efficiency-web-final.pdf DOI: 10.1016/S0033-3506(73)80082-4
4. Wang X, et al. Identification and mapping of worldwide sources of generic real-world data. Pharmacoepidemiol Drug Saf. 2019;28(7):899-905. DOI: 10.1002/pds.4782
5. Hemkens LG, Contopoulos-Ioannidis DG, Ioannidis JP. Agreement of treatment effects for mortality from routinely collected data and subsequent randomized trials: meta-epidemiological survey. BMJ. 2016;352:i493. DOI: 10.1136/bmj.i493
6. Zuidgeest MGP, Goetz I, Groenwold RHH, et al. Series: Pragmatic trials and real world evidence: Paper 1. Introduction. Journal of Clinical Epidemiology. 2017;88:7-13. DOI:10.1016/j.jclinepi.2016.12.023
7. Schwartz D, Lellouch J. Explanatory and Pragmatic Attitudes in Therapeutical Trials. J. Chron. Dis. 1967;20:637-648.
8. Zwarenstein M, Treweek S, Gagnier JJ, et al. Improving the reporting of pragmatic trials: an extension of the CONSORT statement. BMJ. 2008;337;a2390. DOI:10.1136/bmj.a2390
9. Thorpe KE, Zwarenstein M, Oxman AD, et al. A pragmatic-explanatory continuum indicator summary (PRECIS): a tool to help trial designers. J Clin Epidemiol. 2009;62(5):464-75. DOI: 10.1016/j.jclinepi.2008.12.011
10. Loudon K, Treweek S, Sullivan F, et al. The PRECIS-2 tool: designing trials that are fit for purpose. BMJ. 2015;350:h2147. DOI: 10.1136/bmj.h2147
11. Worsley SD, Rengerink KO, Irving EA, et al. Series: Pragmatic Trials and Real World Evidence: Paper 2. Setting, Sites, and Investigator Selection. Journal of Clinical Epidemiology. 2017;88:14-20. DOI: 10.1016/j.jclinepi.2017.05.003
12. Donovan JL, Paramasivan S, de Salis I, et al. Clear obstacles and hidden challenges: understanding recruiter perspectives in six pragmatic randomised controlled trials. Trials. 2014; 15:5 [cited 2020 Jul 25]. Available from: https://trialsjournal.biomedcentral.com/track/pdf/10.1186/1745-6215-15-5
13. Kennedy-Martin T, Curtis S, Faries D, et al. A literature review on the representativeness of randomized controlled trial samples and implications for the external validity of trial results. Trials. 2015;16:495. DOI: 10.1186/s13063-015-1023-4
14. Welch MJ, Larry RC, Miller JE, et al. The ethics and regulatory landscape of including vulnerable populations in pragmatic clinical trials. Clinical trials. 2015;12:503-510. DOI: 10.1177/1740774515597701
15. Council for International Organizations of Medical Sciences. International Ethical Guidelines for Biomedical Research Involving Human Subjects. CIOMS, Geneva, Switzerland, 2002 [cited 2020 Jul 25]. Available at: https://cioms.ch/wp-content/uploads/2017/01/WEB-CIOMS-EthicalGuidelines.pdf
16. Schwartz D, Lellouch J. Explanatory and pragmatic attitudes in therapeutical trials. J Clin Epidemiol. 2009;62(5):499-505. DOI: 10.1016/j.jclinepi.2009.01.012
17. Zuidgeest MGP, Welsing PMJ, G JMW van Thiel, et al. Series: Pragmatic trials and real world evidence: Paper 5. Usual care and real life comparators. Journal of Clinical Epidemiology. 2017;90;92-98. DOI: 10.1016/j.jclinepi.2017.07.001
18. Ross S, Grant A, Counsell CE, et al. Barriers to participation in randomised controlled trials: a systematic review. J Clin Epidemiol. 1999;52(12):1143-1156. DOI: 10.1016/S0895-4356(99)00141-9
19. T-P van Staa, Goldacre B, Gulliford M, et al. Pragmatic randomised trials using routine electronic health records: putting them to the test. BMJ. 2012;344:e55. DOI: 10.1136/bmj.e55
20. McKinney RE, Beskow LM, Ford DE. Use of altered informed consent in pragmatic clinical research. Clin Trials. 2015;12(5):494-502. DOI:10.1177/1740774515597688
21. Kim SYH, Miller FG. Informed consent for pragmatic trials — the integrated consent model. N Engl J Med. 2014;370(8):769-772. DOI: 10.1056/NEJMhle1312508
22. Wendler D. “Targeted” Consent for Pragmatic Clinical Trials. JGIM. 2015;30;679-682. DOI: 10.1007/s11606-014-3169-2
23. Kalkman S, GJMW van Thiel, Zuidgeest M, et al. Series: Pragmatic trials and real world evidence: Paper 4. Informed consent. Journal of clinical epidemiology. 2017;89:181-187. DOI: 10.1016/j.jclinepi.2017.03.019
24. Faden R, Kass N, Whicher D, et al. Ethics and informed consent for comparative effectiveness research with prospective electronic clinical data. Med Care. 2013;51(8 Suppl 3):S53-S57. DOI: 10.1097/MLR.0b013e31829b1e4b
25. Truog RD, Robinson W, Randolph A, et al. Is informed consent always necessary for randomized, controlled trials? N Engl J Med. 1999;340:804-807. DOI: 10.1056/NEJM199903113401013
26. Irving E et al. Series: Pragmatic trials and real world evidence: Paper 7. Safety, quality and monitoring. Journal of clinical epidemiology. 2017;91;6-12. DOI: 10.1016/j.jclinepi.2017.05.004
27. JAMA Deputy Editor Edward Livingston, MD, discusses Pragmatic Trials: Practical Answers to «Real-world» Questions with Harold C. Sox, MD, of PCORI [cited 2020 Jul 25]. Available from: https://edhub.ama-assn.org/jn-learning/audio-player/18519479?utm_source=fbpage&utm_medium=social_jama&utm_term=3448260363&utm_campaign=article_alert&linkId=91852989
28. van Staa T-P, Dyson L, McCann G, et al. The opportunities and challenges of pragmatic point-of-care randomised trials using routinely collected electronic records: evaluations of two exemplar trials. Southampton (UK): NIHR Journals Library. Health Technol Assess. 2014 Jul;18(43):1-146. DOI: 10.3310/hta18430
29. Uren SC, Kirkman MB, Dalton B, et al. Reducing clinical trial monitoring resource allocation and costs through remote access to electronic medical records. Journal of oncology practice. 2013;9(1):e13-6. DOI: 10.1200/ JOP.2012.000666
30. Coronado GD, Vollmer WM, Petrik A, et al. Strategies and Opportunities to STOP Colon Cancer in Priority Populations: design of a cluster-randomized pragmatic trial. Contemp Clin Trials. 2014;38(2):344-9. DOI: 10.1016/j.cct.2014.06.006
31. 2019 Annual Report: A Pragmatic Approach to Benefit an Understudied Population [cited 2020 Jul 25]. Available from: https://dcri.org/2019-annual-report-a-pragmatic-approach-to-benefit-an-understudied-population/
32. Datta S. HEARTLINE: A 180,000 Patient-Strong, Pragmatic, Real World Randomized Trial Assesses the Prowess of Apple Technology in Afib Diagnosis and Improvement of Hard Outcomes. Cardiology now. 2019 March [cited 2020 Jul 25]. Available from: https://cardiologynownews.org/ heartline-a-180000-patient-strong-pragmatic-real-world-trial-assess-the-prowess-of-apple-technology-in-afib-diagnosis-and-improvement-of-hard-outcomes/
Review
For citations:
Shevchenko O.R., Kolbin A.S. Pragmatic clinical trials. Kachestvennaya Klinicheskaya Praktika = Good Clinical Practice. 2020;(3):52-60. (In Russ.) https://doi.org/10.37489/2588-0519-2020-3-52-60
Views:
3181
Email this article 