Methodological standards in non-inferiority AIDS trials: Moving from adherence to compliance

被引：21
作者：
Parienti J.-J. [1 ,2 ,3 ]
Verdon R. [4 ]
Massari V. [1 ,2 ]
机构：
[1] Inserm UMR-S 707, Paris
[2] Université Pierre et Marie Curie-Paris6, UMR-S 707, Paris
[3] Department of Biostatistics and Clinical Research, Côte de Nacre University Hospital
[4] Department of Infectious Diseases, Côte de Nacre University Hospital
来源：
BMC Medical Research Methodology | / 6卷 / 1期
关键词：
Human Immunodeficiency Virus; Abacavir; Virologic Failure; Consort Statement; Equivalence Trial;
D O I：
10.1186/1471-2288-6-46
中图分类号：
学科分类号：
摘要：
Background: The interpretation of the results of active-control trials regarding the efficacy and safety of a new drug is important for drug registration and following clinical use. It has been suggested that non-inferiority and equivalence studies are not reported with the same quantitative rigor as superiority studies. Methods: Standard methodological criteria for non-inferiority and equivalence trials including design, analysis and interpretation issues were applied to 18 recently conducted large non-inferiority (15) and equivalence (3) randomized trials in the field of AIDS antiretroviral therapy. We used the continuity-corrected non-inferiority chi-square to test 95% confidence interval treatment difference against the predefined non-inferiority margin. Results: The pre-specified non-inferiority margin ranged from 10% to 15%. Only 4 studies provided justification for their choice. 39% of the studies (7/18) reported only intent-to-treat (ITT) analysis for the primary endpoint. When on-treatment (OT) and ITT statistical analyses were provided, ITT was favoured over OT for results interpretation for all but one study, inappropriately in this statistical context. All but two of the studies concluded there was "similar" efficacy of the experimental group. However, 9/18 had inconclusive results for non-inferiority. Conclusion: Conclusions about non-inferiority should be drawn on the basis of the confidence interval analysis of an appropriate primary endpoint, using the predefined criteria for non-inferiority, in both OT and ITT, in compliance with the non-inferiority and equivalence CONSORT statement. We suggest that the use of the non-inferiority chi-square test may provide additional useful information. © 2006 Parienti et al; licensee BioMed Central Ltd.
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共 32 条
[1]  
Piaggio G., Elbourne D.R., Altman D.G., Pocock S.J., Evans S.J., Reporting of noninferiority and equivalence randomized trials: An extension of the CONSORT statement, Jama, 295, pp. 1152-1160, (2006)
[2]  
Temple R., Ellenberg S.S., Placebo-controlled trials and active-control trials in the evaluation of new treatments. Part 1: Ethical and scientific issues, Ann Intern Med, 133, pp. 455-463, (2000)
[3]  
Djulbegovic B., Clarke M., Scientific and ethical issues in equivalence trials, Jama, 285, pp. 1206-1208, (2001)
[4]  
Staszewski S., Morales-Ramirez J., Tashima K.T., Rachlis A., Skiest D., Stanford J., Stryker R., Johnson P., Labriola D.F., Farina D., Manion D.J., Ruiz N.M., Efavirenz plus zidovudine and lamivudine, efavirenz plus indinavir, and indinavir plus zidovudine and lamivudine in the treatment of HIV-1 infection in adults. Study 006 Team, N Engl J Med, 341, pp. 1865-1873, (1999)
[5]  
Walmsley S., Bernstein B., King M., Arribas J., Beall G., Ruane P., Johnson M., Johnson D., Lalonde R., Japour A., Brun S., Sun E., Lopinavir-ritonavir versus nelfinavir for the initial treatment of HIV infection, N Engl J Med, 346, pp. 2039-2046, (2002)
[6]  
Parienti J.J., Tenofovir, equivalence, and noninferiority, Jama, 292, (2004)
[7]  
Kirshner B., Methodological standards for assessing therapeutic equivalence, J Clin Epidemiol, 44, pp. 839-849, (1991)
[8]  
Jones B., Jarvis P., Lewis J.A., Ebbutt A.F., Trials to assess equivalence: The importance of rigorous methods, Bmj, 313, pp. 36-39, (1996)
[9]  
McAlister F.A., Sackett D.L., Active-control equivalence trials and antihypertensive agents, Am J Med, 111, pp. 553-558, (2001)
[10]  
Staszewski S., Keiser P., Montaner J., Raffi F., Gathe J., Brotas V., Hicks C., Hammer S.M., Cooper D., Johnson M., Tortell S., Cutrell A., Thorborn D., Isaacs R., Hetherington S., Steel H., Spreen W., Abacavir-lamivudine-zidovudine vs indinavir-lamivudine-zidovudine in antiretroviral-naive HIV-infected adults: A randomized equivalence trial, Jama, 285, pp. 1155-1163, (2001)
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