Observational studies to emulate randomized trials: Some real-world barriers.
bias
real-world evidence
trial emulation
Journal
British journal of clinical pharmacology
ISSN: 1365-2125
Titre abrégé: Br J Clin Pharmacol
Pays: England
ID NLM: 7503323
Informations de publication
Date de publication:
15 Jan 2024
15 Jan 2024
Historique:
revised:
19
12
2023
received:
13
11
2023
accepted:
29
12
2023
medline:
16
1
2024
pubmed:
16
1
2024
entrez:
15
1
2024
Statut:
aheadofprint
Résumé
The randomized controlled trial (RCT) forms the basis for drug approval by regulatory agencies. Observational studies using existing data from healthcare databases now also provide real-world evidence (RWE) in regulatory decision-making. Several initiatives are assessing the value of RWE by conducting observational studies that emulate published RCTs. While many RCTs are straightforward to emulate, others are challenging. We describe three RCT design aspects that pose challenges for observational studies. First are trials that enrol already treated subjects who must discontinue these treatments at the time of randomization, which can distort the comparison with observational studies. Second is the inclusion of a run-in phase, especially to exclude non-compliant subjects from the trial. Third are trials that evaluate the effect of weaning off treatment. In conclusion, future randomized trials that aim to be emulated by observational studies could consider study designs that allow emulation and thus provide valid and complementary RWE.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024 The Author. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.
Références
Cefalu WT, Kaul S, Gerstein HC, et al. Cardiovascular outcomes trials in type 2 diabetes: where do we go from here? Reflections from a diabetes care Editors' expert forum. Diabetes Care. 2017;41(1):14-31. doi:10.2337/dci17-0057
Sharma A, Pagidipati NJ, Califf RM, et al. Impact of regulatory guidance on evaluating cardiovascular risk of new glucose-lowering therapies to treat type 2 diabetes mellitus. Circulation. 2020;141(10):843-862. doi:10.1161/CIRCULATIONAHA.119.041022
Peters SP, Bleecker ER, Canonica GW, et al. Serious asthma events with budesonide plus formoterol vs. budesonide alone. N Engl J Med. 2016;375(9):850-860. doi:10.1056/NEJMoa1511190
Stempel DA, Raphiou IH, Kral KM, et al. Serious asthma events with fluticasone plus salmeterol versus fluticasone alone. N Engl J Med. 2016;374(19):1822-1830. doi:10.1056/NEJMoa1511049
Wise RA, Anzueto A, Cotton D, et al. Tiotropium Respimat inhaler and the risk of death in COPD. N Engl J Med. 2013;369(16):1491-1501. doi:10.1056/NEJMoa1303342
Sherman RE, Anderson SA, Dal Pan GJ, et al. Real-world evidence-what is it and what can it tell us? N Engl J Med. 2016;375(23):2293-2297. doi:10.1056/NEJMsb1609216
Frieden TR. Evidence for health decision making - beyond randomized, controlled trials. N Engl J Med. 2017;377(5):465-475. doi:10.1056/NEJMra1614394
Eichler HG, Koenig F, Arlett P, et al. Are novel, nonrandomized analytic methods fit for decision making? The need for prospective, controlled, and transparent validation. Clin Pharmacol Ther. 2020;107(4):773-779. doi:10.1002/cpt.1638
Gershon AS, Lindenauer PK, Wilson KC, et al. Informing healthcare decisions with observational research assessing causal effect. An official American Thoracic Society research Statement. Am J Respir Crit Care Med. 2021;203(1):14-23. doi:10.1164/rccm.202010-3943ST
Franklin JM, Pawar A, Martin D, et al. Nonrandomized real-world evidence to support regulatory decision making: process for a randomized trial replication project. Clin Pharmacol Ther. 2020;107(4):817-826. doi:10.1002/cpt.1633
Crown W, Dahabreh IJ, Li X, Toh S, Bierer B. Can observational analyses of routinely collected data emulate randomized trials? Design and feasibility of the observational patient evidence for regulatory approval science and understanding disease project. Value Health. 2023;26(2):176-184. doi:10.1016/j.jval.2022.07.003
Wallach JD, Deng Y, McCoy RG, et al. Real-world cardiovascular outcomes associated with Degarelix vs leuprolide for prostate cancer treatment. JAMA Netw Open. 2021;4(10):e2130587. doi:10.1001/jamanetworkopen.2021.30587
Franklin JM, Patorno E, Desai RJ, et al. Emulating randomized clinical trials with nonrandomized real-world evidence studies: first results from the RCT DUPLICATE initiative. Circulation. 2021;143(10):1002-1013. doi:10.1161/CIRCULATIONAHA.120.051718
Wang SV, Schneeweiss S, Franklin JM, et al. Emulation of randomized clinical trials with nonrandomized database analyses: results of 32 clinical trials. JAMA. 2023;329(16):1376-1385. doi:10.1001/jama.2023.4221
Lipson DA, Barnhart F, Brealey N, et al. Once-daily single-inhaler triple versus dual therapy in patients with COPD. N Engl J Med. 2018;378(18):1671-1680. doi:10.1056/NEJMoa1713901
Suissa S, Drazen JM. Making sense of triple inhaled therapy for COPD. N Engl J Med. 2018;378(18):1723-1724. doi:10.1056/NEJMe1716802
Suissa S, Ariel A. Triple therapy trials in COPD: a precision medicine opportunity. Eur Respir J. 2018;52(6):1801848. doi:10.1183/13993003.01848-2018
Suissa S. Perplexing mortality data from triple therapy trials in COPD. Lancet Respir Med. 2021;9(7):684-685. doi:10.1016/S2213-2600(21)00238-1
Wedzicha J, Banerji D, Kostikas K. Single-inhaler triple versus dual therapy in patients with COPD. N Engl J Med. 2018;379(6):590-593. doi:10.1056/NEJMc1807380
Han MKCG, Dransfield MT, et al. The effect of ICS withdrawal and baseline inhaled treatment on exacerbations in the IMPACT study. Am J Respir Crit Care Med. 2020;202(9):1237-1243. doi:10.1164/rccm.201912-2478OC
Lipson DA, Crim C, Criner GJ, et al. Reduction in all-cause mortality with fluticasone Furoate/Umeclidinium/Vilanterol in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2020;201(12):1508-1516. doi:10.1164/rccm.201911-2207OC
Suissa S, Dell'Aniello S, Ernst P. Single-inhaler triple versus dual bronchodilator therapy in COPD: real-world comparative effectiveness and safety. Int J Chron Obstruct Pulmon Dis. 2022;17:1975-1986. doi:10.2147/COPD.S378486
Brittain E, Wittes J. The run-in period in clinical trials. The effect of misclassification on efficiency. Control Clin Trials. 1990;11(5):327-338. doi:10.1016/0197-2456(90)90174-Z
Laursen DRT, Paludan-Müller AS, Hróbjartsson A. Randomized clinical trials with run-in periods: frequency, characteristics and reporting. Clin Epidemiol. 2019;11:169-184. doi:10.2147/CLEP.S188752
Suissa S. Run-in bias in randomised trials: the case of COPD medications. Eur Respir J. 2017;49(6):1700361. doi:10.1183/13993003.00361-2017
MRC/BHF heart protection study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360(9326):7-22. doi:10.1016/S0140-6736(02)09327-3
McMurray JJ, Packer M, Desai AS, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371(11):993-1004. doi:10.1056/NEJMoa1409077
Rabe KF, Martinez FJ, Ferguson GT, et al. Triple inhaled therapy at two glucocorticoid doses in moderate-to-very-severe COPD. N Engl J Med. 2020;383(1):35-48. doi:10.1056/NEJMoa1916046
Suissa S. Triple therapy in COPD: understanding the data. ERJ Open Research. 2023;9(1):00615-02022. doi:10.1183/23120541.00615-2022
Papi A, Vestbo J, Fabbri L, et al. Extrafine inhaled triple therapy versus dual bronchodilator therapy in chronic obstructive pulmonary disease (TRIBUTE): a double-blind, parallel group, randomised controlled trial. The Lancet. 2018;391(10125):1076-1084. doi:10.1016/S0140-6736(18)30206-X
Grede N, Kuss K, Staudt I, Donner-Banzhoff N, Viniol A. Mapping the methodological diversity of published drug discontinuation studies-a scoping review of study topics, objectives, and designs. Trials. 2023;24(1):58. doi:10.1186/s13063-023-07105-6
Randomised study of antiepileptic drug withdrawal in patients in remission. Medical Research Council antiepileptic drug withdrawal study group. Lancet. 1991;337(8751):1175-1180. doi:10.1016/0140-6736(91)92856-W
Hawthorne AB, Logan RF, Hawkey CJ, et al. Randomised controlled trial of azathioprine withdrawal in ulcerative colitis. BMJ. 1992;305(6844):20-22. doi:10.1136/bmj.305.6844.20
Packer M, Gheorghiade M, Young JB, et al. Withdrawal of digoxin from patients with chronic heart failure treated with angiotensin-converting-enzyme inhibitors. RADIANCE study. N Engl J Med. 1993;329(1):1-7. doi:10.1056/NEJM199307013290101
Magnussen H, Disse B, Rodriguez-Roisin R, et al. Withdrawal of inhaled glucocorticoids and exacerbations of COPD. N Engl J Med. 2014;371(14):1285-1294. doi:10.1056/NEJMoa1407154
Roussel R, Duran-García S, Zhang Y, et al. Double-blind, randomized clinical trial comparing the efficacy and safety of continuing or discontinuing the dipeptidyl peptidase-4 inhibitor sitagliptin when initiating insulin glargine therapy in patients with type 2 diabetes: the CompoSIT-I study. Diabetes Obes Metab. 2019;21(4):781-790. doi:10.1111/dom.13574
Mathian A, Pha M, Haroche J, et al. Withdrawal of low-dose prednisone in SLE patients with a clinically quiescent disease for more than 1 year: a randomised clinical trial. Ann Rheum Dis. 2020;79(3):339-346. doi:10.1136/annrheumdis-2019-216303
Krumme AA, Glynn RJ, Schneeweiss S, Choudhry NK, Tong AY, Gagne JJ. Defining exposure in observational studies comparing outcomes of treatment discontinuation. Circ Cardiovasc Qual Outcomes. 2018;11(7):e004684. doi:10.1161/CIRCOUTCOMES.118.004684
Suissa S, Dell'Aniello S, Ernst P. Discontinuation of inhaled corticosteroids from triple therapy in COPD: effects on major outcomes in real world clinical practice. COPD. 2022;19(1):133-141. doi:10.1080/15412555.2022.2045265
Secemsky EA, Shen C, Yeh RW. Exposure misclassification in observational studies. Circ Cardiovasc Qual Outcomes. 2018;11(7):e004939. doi:10.1161/CIRCOUTCOMES.118.004939
Suissa S, Moodie EE, Dell'Aniello S. Prevalent new-user cohort designs for comparative drug effect studies by time-conditional propensity scores. Pharmacoepidemiol Drug Saf. 2017;26(4):459-468. doi:10.1002/pds.4107
Tran T, Suissa S. Comparing new-user cohort designs: the example of proton pump inhibitor effectiveness in idiopathic pulmonary fibrosis. Am J Epidemiol. 2021;190(5):928-938. doi:10.1093/aje/kwaa242
Suissa S, Dell'Aniello S, Renoux C. The prevalent new-user Design for Studies with no active comparator: the example of statins and cancer. Epidemiology. 2023;34(5):681-689. doi:10.1097/EDE.0000000000001628
Suissa S. Triple therapy in COPD: time for adaptive selection trials. COPD. 2021;18(6):597-601. doi:10.1080/15412555.2021.1982886