Network meta-analysis can inform the ethical evaluation of trials that randomise away from standard of care: The case of symptomatic carotid stenosis.
randomisation
standard of care
stroke
trial
Journal
Journal of evaluation in clinical practice
ISSN: 1365-2753
Titre abrégé: J Eval Clin Pract
Pays: England
ID NLM: 9609066
Informations de publication
Date de publication:
07 Dec 2023
07 Dec 2023
Historique:
revised:
27
09
2023
received:
10
05
2023
accepted:
19
10
2023
medline:
7
12
2023
pubmed:
7
12
2023
entrez:
7
12
2023
Statut:
aheadofprint
Résumé
Little guidance exists on the conduct of randomised clinical trials (RCT) that seek to randomise patients away from standard of care. We sought to test the technique of network meta-analysis (NMA) to ascertain best available evidence for the purposes of informing the ethical evaluation of RCTs under these circumstances. We used the example of RCTs for patients with symptomatic, moderate to severe carotid stenosis that seek to compare surgical intervention plus medical therapy (standard of care) versus medical therapy (less than standard of care). Network meta-analysis of RCTs of adults with symptomatic carotid artery stenosis of 50%-99% who were treated with carotid endarterectomy (CEA), carotid artery stenting (CAS), or medical therapy (MT). The primary outcome was any stroke or death until end of follow-up, and secondary outcome was 30-day risk of ipsilateral stroke/death. We analysed eight studies, with 7187 subjects with symptomatic moderate/severe stenosis (50%-99%). CEA was more efficacious than MT (HR = 0.82, 95% credible intervals [95% CrI] = 0.73-0.92) and CAS (HR 0.73, 95% CrI = 0.62-0.85) for the prevention of any stroke/death. At 30 days, the odds of experiencing an ipsilateral stroke/death were significantly lower in the CEA group compared to both MT (OR = 0.58, 95% CrI = 0.47-0.72) and CAS (OR = 0.68, 95% CrI = 0.55-0.83). Our results support the feasibility of using NMA to assess best available evidence to inform the ethical evaluation of RCTs seeking to randomise patients away from standard of care. Our results suggest that a strong argument is required to ethically justify the conduct of RCTs that seek to randomise patients away from standard of care in the setting of symptomatic moderate to severe carotid stenosis.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2023 The Authors. Journal of Evaluation in Clinical Practice published by John Wiley & Sons Ltd.
Références
Ashcroft R. Equipoise, knowledge and ethics in clinical research and practice. Bioethics. 1999;13:314-326.
Fedyk M, Dewar B, Jurkovic L, et al. How are randomized clinical trials ethically justified? A systematic scoping review and thematic analysis of reasons that ethically justify randomized clinical trials. J Clin Epidemiol. 2022;147:160-167.
Shamy M, Dewar B, Fedyk M. Different meanings of equipoise and the four quadrants of uncertainty. J Clin Epidemiol. 2020;127:248-249.
Wein T, Lindsay MP, Côté R, et al. Canadian stroke best practice recommendations: secondary prevention of stroke, sixth edition practice guidelines, update 2017. International Journal of Stroke. 2018;13:420-443.
Randomised trial of endarterectomy for recently symptomatic carotid stenosis: final results of the MRC european carotid surgery trial (ECST). The Lancet. 1998;351:1379-1387.
Barnett HJM, Taylor DW, Eliasziw M, et al. Benefit of carotid endarterectomy in patients with symptomatic moderate or severe stenosis. N Engl J Med. 1998;339:1415-1425.
Brott TG, Hobson RW, Howard G, et al. Stenting versus endarterectomy for treatment of carotid-artery stenosis. N Engl J Med. 2010;363:11-23.
Cheng SF, van Velzen TJ, Gregson J, et al. The 2nd European Carotid Surgery trial (ECST-2): rationale and protocol for a randomised clinical trial comparing immediate revascularisation versus optimised medical therapy alone in patients with symptomatic and asymptomatic carotid stenosis at low to intermediate risk of stroke. Trials. 2022;23:606.
Rothwell P, Eliasziw M, Gutnikov S, et al. Analysis of pooled data from the randomised controlled trials of endarterectomy for symptomatic carotid stenosis. Lancet. 2003;361:107-116.
Lun R, Dhaliwal S, Zitikyte G, Roy DC, Hutton B, Dowlatshahi D. Comparison of ticagrelor vs clopidogrel in addition to aspirin in patients with minor ischemic stroke and transient ischemic attack: a network meta-analysis. JAMA Neurol. 2022;79:141-148.
Bangalore S, Kumar S, Wetterslev J, et al. Carotid artery stenting vs carotid endarterectomy: meta-analysis and diversity-adjusted trial sequential analysis of randomized trials. Arch Neurol. 2011;68:172-184.
Moresoli P, Habib B, Reynier P, Secrest MH, Eisenberg MJ, Filion KB. Carotid stenting versus endarterectomy for asymptomatic carotid artery stenosis: a systematic review and meta-analysis. Stroke. 2017;48:2150-2157.
Müller MD, Lyrer P, Brown MM, et al. Carotid artery stenting versus endarterectomy for treatment of carotid artery stenosis. Cochrane Database Syst Rev. 2020;2020:748-749.
Hutton B, Salanti G, Caldwell DM, et al. The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations. Ann Intern Med. 2015;162:777-784.
Sterne JAC, Savović J, Page MJ, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366:l4898.
Mayberg MR. Carotid endarterectomy and prevention of cerebral ischemia in symptomatic carotid stenosis. JAMA J Am Med Assoc. 1991;266:3289-3294.
MRC European Carotid Surgery Trial: interim results for symptomatic patients with severe (70-99%) or with mild (0-29%) carotid stenosis. European Carotid Surgery Trialists’ collaborative group. Lancet Lond. Engl. 1991;337:1235-1243.
North American Symptomatic Carotid Endarterectomy Trial Collaborators, Barnett HJM, Taylor DW, et al. Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. N Engl J Med. 1991;325:445-453.
Brooks WH, McClure RR, Jones MR, Coleman TC, Breathitt L. Carotid angioplasty and stenting versus carotid endarterectomy: randomized trial in a community hospital. J Am Coll Cardiol. 2001;38:1589-1595.
Mas J-L, Chatellier G, Beyssen B, et al. Endarterectomy versus stenting in patients with symptomatic severe carotid stenosis. N Engl J Med. 2006;355:1660-1671.
Mas J-L, Trinquart L, Leys D, et al. Endarterectomy versus angioplasty in patients with symptomatic severe carotid stenosis (EVA-3S) trial: results up to 4 years from a randomised, multicentre trial. Lancet Neurol. 2008;7:885-892.
SPACE Collaborative Group, Ringleb PA, Allenberg J, Brückmann H, et al. 30 day results from the SPACE trial of stent-protected angioplasty versus carotid endarterectomy in symptomatic patients: a randomised non-inferiority trial. Lancet. 2006;368:1239-1247.
Eckstein H-H, Ringleb P, Allenberg J-R, et al. Results of the stent-protected angioplasty versus carotid endarterectomy (SPACE) study to treat symptomatic stenoses at 2 years: a multinational, prospective, randomised trial. Lancet Neurol. 2008;7:893-902.
Hoffmann A, Engelter S, Taschner C, et al. Carotid artery stenting versus carotid endarterectomy-a prospective randomised controlled single-centre trial with long-term follow-up (BACASS). Schwiezer Archiv Fur Neurologie Und Psychiatrie. 2008;(159):84-89.
Bonati LH, Dobson J, Featherstone RL, et al. Long-term outcomes after stenting versus endarterectomy for treatment of symptomatic carotid stenosis: the International Carotid Stenting Study (ICSS) randomised trial. Lancet. 2015;385:529-538.
Ederle J, Dobson J, International Carotid Stenting Study investigators. Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial. Lancet. 2010;375:985-997.
Barnett HJM, Taylor DW, North American Symptomatic Carotid Endarterectomy Trial Collaborators. Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. N Engl J Med. 1991;325:445-453.
Kurzrock R, Stewart DJ. Equipoise abandoned? Randomization and clinical trials. Ann Oncol. 2013;24:2471-2474.
De Meulemeester J, Fedyk M, Jurkovic L, et al. Many randomized clinical trials may not be justified: a cross-sectional analysis of the ethics and science of randomized clinical trials. J Clin Epidemiol. 2018;97:20-25.
Haidich AB. Meta-analysis in medical research. Hippokratia. 2010;14:29-37.
Millum J, Grady C. The ethics of placebo-controlled trials: methodological justifications. Contemp Clin Trials. 2013;36:510-514. doi:10.1016/j.cct.2013.09.003
Raymond J, Darsaut TE, Altman DG. Pragmatic trials can be designed as optimal medical care: principles and methods of care trials. J Clin Epidemiol. 2014;67:1150-1156.
Johnston SC, Easton JD, Farrant M, et al. Clopidogrel and aspirin in acute ischemic stroke and high-risk TIA. N Engl J Med. 2018;379:215-225.
Wang Y, Wang Y, Zhao X, et al. Clopidogrel with aspirin in acute minor stroke or transient ischemic attack. N Engl J Med. 2013;369:11-19.
Amarenco P, Bogousslavsky J, Callahan 3rd A, et al. High-Dose atorvastatin after stroke or transient ischemic attack. N Engl J Med. 2006;355:549-559.
PROGRESS Collaborative Group. Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6,105 individuals with previous stroke or transient ischaemic attack. Lancet. 2001;358:1033-1041.
SPS3 Study Group, Benavente OR, Coffey CS, et al. Blood-pressure targets in patients with recent lacunar stroke: the SPS3 randomised trial. Lancet. 2013;382:507-515.