Challenges in the Design and Interpretation of Noninferiority Trials: Insights From Recent Stent Trials

Journal of the American College of Cardiology

Volumn 70, Issue 7, 2017, Pages 894-903

  Macaya, Fernando ^a   Ryan, Nicola ^a   Salinas, Pablo ^a   Pocock, Stuart J ^b,c  

^a UNIVERSIDAD COMPLUTENSE DE MADRID   (Spain)

^b LONDON SCHOOL OF HYGIENE AND TROPICAL MEDICINE   (United Kingdom)

^c CENTRO NACIONAL DE INVESTIGACIONES CARDIOVASCULARES CNIC   (Spain)

Author keywords

clinical trial; clinical trial design; coronary stent; noninferiority margin; sample size

Indexed keywords

SITAGLIPTIN;

CLINICAL RESEARCH; CORONARY STENT; CRYOABLATION; DRUG EFFICACY; DRUG ELUTING STENT; HUMAN; INTENTION TO TREAT ANALYSIS; MORTALITY; PAROXYSMAL ATRIAL FIBRILLATION; PATIENT SAFETY; PRIORITY JOURNAL; RADIOFREQUENCY ABLATION; REVIEW; RISK ASSESSMENT; STUDY DESIGN; SURGICAL APPROACH; TRANSCATHETER AORTIC VALVE IMPLANTATION; TREATMENT PLANNING; CARDIOLOGY; CLINICAL TRIAL (TOPIC); CORONARY ARTERY DISEASE; HEART MUSCLE REVASCULARIZATION; ORGANIZATION AND MANAGEMENT; PROCEDURES; PROSTHESIS DESIGN; STENT;

CARDIOLOGY; CLINICAL TRIALS AS TOPIC; CORONARY ARTERY DISEASE; HUMANS; MYOCARDIAL REVASCULARIZATION; PROSTHESIS DESIGN; STENTS;

EID: 85028610685     PISSN: 07351097     EISSN: 15583597     Source Type: Journal    
DOI: 10.1016/j.jacc.2017.06.039     Document Type: Review

References (36)

1. Gopal, A.D., Desai, N.R., Tse, T., Ross, J.S., Reporting of noninferiority trials in ClinicalTrials.gov and corresponding publications. JAMA 313 (2015), 1163–1165.
2. Vaduganathan, M., Patel, R.B., Samman-Tahhan, A., et al. Cardiovascular clinical trials with noninferiority or equivalence designs from 2001 to 2012. Int J Cardiol 214 (2016), 16–18.
3. Head, S.J., Kaul, S., Bogers, A.J.J.C., Kappetein, A.P., Non-inferiority study design: lessons to be learned from cardiovascular trials. Eur Heart J 33 (2012), 1318–1324.
4. Garattini, S., Bertele, V., Non-inferiority trials are unethical because they disregard patients’ interests. Lancet 370 (2007), 1875–1877.
5. Kaul, S., Diamond, G.A., Good enough: a primer on the analysis and interpretation of noninferiority trials. Ann Intern Med 145 (2006), 62–69.
6. Pocock, S.J., Clayton, T.C., Stone, G.W., Challenging issues in clinical trial design: part 4 of a 4-part series on statistics for clinical trials. J Am Coll Cardiol 66 (2015), 2886–2898.
7. Collier, T.J., Tools & techniques—statistics: non-inferiority trials. EuroIntervention 10 (2014), 526–527.
8. Leon, M.B., Smith, C.R., Mack, M., et al., for the PARTNER Trial Investigators. Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery. N Engl J Med 363 (2010), 1597–1607.
9. Smith, C.R., Leon, M.B., Mack, M.J., et al., for the PARTNER Trial Investigators. Transcatheter versus surgical aortic-valve replacement in high-risk patients. N Engl J Med 364 (2011), 2187–2198.
10. Leon, M.B., Smith, C.R., Mack, M.J., et al., for the PARTNER 2 Investigators. Transcatheter or surgical aortic-valve replacement in intermediate-risk patients. N Engl J Med 374 (2016), 1609–1620.
11. Marso, S.P., Daniels, G.H., Brown-Frandsen, K., et al. for the LEADER Steering Committee, LEADER Trial Investigators. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med 375 (2016), 311–322.
12. Ellis, S.G., Kereiakes, D.J., Metzger, D.C., et al., for the ABSORB III Investigators. Everolimus-eluting bioresorbable scaffolds for coronary artery disease. N Engl J Med 373 (2015), 1905–1915.
13. Serruys, P.W., Onuma, Y., Ormiston, J.A., et al. Evaluation of the second generation of a bioresorbable everolimus drug-eluting vascular scaffold for treatment of de novo coronary artery stenosis: six-month clinical and imaging outcomes. Circulation 122 (2010), 2301–2312.
14. Fifth Organization to Assess Strategies in Acute Ischemic Syndromes Investigators. Comparison of fondaparinux and enoxaparin in acute coronary syndromes. N Engl J Med 354 (2006), 1464–1476.
15. Green, J.B., Bethel, M.A., Armstrong, P.W., et al., for the TECOS Study Group. Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes. [Published correction appears in N Engl J Med 2015;373:586] N Engl J Med 373 (2015), 232–242.
16. Kuck, K.H., Fürnkranz, A., Chun, K.R.J., et al., for the FIRE AND ICE Investigators. Cryoballoon or radiofrequency ablation for symptomatic paroxysmal atrial fibrillation: reintervention, rehospitalization, and quality-of-life outcomes in the FIRE AND ICE trial. Eur Heart J 37 (2016), 2858–2865.
17. Kimura, T., Kozuma, K., Tanabe, K., et al., for the ABSORB Japan Investigators. A randomized trial evaluating everolimus-eluting Absorb bioresorbable scaffolds vs. everolimus-eluting metallic stents in patients with coronary artery disease: ABSORB Japan. Eur Heart J 36 (2015), 3332–3342.
18. Raungaard, B., Jensen, L.O., Tilsted, H.H., et al., for the Scandinavian Organization for Randomized Trials with Clinical Outcome (SORT OUT). Zotarolimus-eluting durable-polymer-coated stent versus a biolimus-eluting biodegradable-polymer-coated stent in unselected patients undergoing percutaneous coronary intervention (SORT OUT VI): a randomised non-inferiority trial. Lancet 385 (2015), 1527–1535.
19. von Birgelen, C., Sen, H., Lam, M.K., et al. Third-generation zotarolimus-eluting and everolimus-eluting stents in all-comer patients requiring a percutaneous coronary intervention (DUTCH PEERS): a randomised, single-blind, multicentre, non-inferiority trial. Lancet 383 (2014), 413–423.
20. Pilgrim, T., Heg, D., Roffi, M., et al. Ultrathin strut biodegradable polymer sirolimus-eluting stent versus durable polymer everolimus-eluting stent for percutaneous coronary revascularisation (BIOSCIENCE): a randomised, single-blind, non-inferiority trial. Lancet 384 (2014), 2111–2122.
21. Saito, S., Valdes-Chavarri, M., Richardt, G., et al., for the CENTURY II Investigators. A randomized, prospective, intercontinental evaluation of a bioresorbable polymer sirolimus-eluting coronary stent system: the CENTURY II (Clinical Evaluation of New Terumo Drug-Eluting Coronary Stent System in the Treatment of Patients with Coronary Artery Disease) trial. Eur Heart J 35 (2014), 2021–2031.
22. Smits, P.C., Hofma, S., Togni, M., et al. Abluminal biodegradable polymer biolimus-eluting stent versus durable polymer everolimus-eluting stent (COMPARE II): a randomised, controlled, non-inferiority trial. Lancet 381 (2013), 651–660.
23. Stone, G.W., Teirstein, P.S., Meredith, I.T., et al., for the PLATINUM Trial Investigators. A prospective, randomized evaluation of a novel everolimus-eluting coronary stent: The PLATINUM (A Prospective, Randomized, Multicenter Trial to Assess an Everolimus-Eluting Coronary Stent System [PROMUS Element] for the Treatment of up to Two De Novo Coronary Artery Lesions). Trial. J Am Coll Cardiol 57 (2011), 1700–1708.
24. Serruys, P.W., Silber, S., Garg, S., et al. Comparison of zotarolimus-eluting and everolimus-eluting coronary stents. N Engl J Med 363 (2010), 136–146.
25. D'Agostino, R.B. Sr., Massaro, J.M., Sullivan, L.M., Non-inferiority trials: design concepts and issues - the encounters of academic consultants in statistics. Stat Med 22 (2003), 169–186.
26. Adams, D.H., Popma, J.J., Reardon, M.J., et al., for the U.S. CoreValve Clinical Investigators. Transcatheter aortic-valve replacement with a self-expanding prosthesis. N Engl J Med 370 (2014), 1790–1798.
27. Ardehali, A., Esmailian, F., Deng, M., et al., for the PROCEED II Trial Investigators. Ex-vivo perfusion of donor hearts for human heart transplantation (PROCEED II): a prospective, open-label, multicentre, randomised non-inferiority trial. Lancet 385 (2015), 2577–2584.
28. Piaggio, G., Elbourne, D.R., Pocock, S.J., Evans, S.J., Altman, D.G., for the CONSORT Group. Reporting of noninferiority and equivalence randomized trials: extension of the CONSORT 2010 statement. JAMA 308 (2012), 2594–2604.
29. Office of Biostatistics and the Office of New Drugs in the Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER), Food and Drug Administration. Non-inferiority clinical trials to establish effectiveness. Guidance for industry. November 2016. Available at: https://www.fda.gov/downloads/Drugs/Guidances/UCM202140.pdf. Accessed June 13, 2017.
30. European Medicines Agency, Committee for Medicinal Products for Human Use (CHMP). Guideline on the choice of the non-inferiority margin. July 2005. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003636.pdf. Accessed June 13, 2017.
31. Le Henanff, A., Giraudeau, B., Baron, G., Ravaud, P., Quality of reporting of noninferiority and equivalence randomized trials. JAMA 295 (2006), 1147–1151.
32. Schiller, P., Burchardi, N., Niestroj, M., Kieser, M., Quality of reporting of clinical non-inferiority and equivalence randomised trials-update and extension. Trials, 13, 2012, 214.
33. Byrne, R.A., Kastrati, A., Drug-eluting stent trials: too much non-inferiority, too little progress?. Lancet 383 (2014), 386–388.
34. Byrne, R.A., Serruys, P.W., Baumbach, A., et al. Report of a European Society of Cardiology-European Association of Percutaneous Cardiovascular Interventions Task Force on the Evaluation of Coronary Stents in Europe: executive summary. Eur Heart J 36 (2015), 2608–2620.
35. Pocock, S.J., Stone, G.W., The primary outcome is positive—is that good enough?. N Engl J Med 375 (2016), 971–979.
36. Pocock, S.J., Stone, G.W., The primary outcome fails—what next?. N Engl J Med 375 (2016), 861–870.