Statistical Considerations for Cardiovascular Outcome Trials in Patients with Type 2 Diabetes Mellitus

Statistics in Biopharmaceutical Research

Volumn 9, Issue 4, 2017, Pages 347-360

  Marchenko, Olga ^a   Jiang, Qi ^b   Chuang Stein, Christy ^c   Mehta, Cyrus ^d   Levenson, Mark ^e   Russek Cohen, Estelle ^e   Liu, Lingyun ^d   Sanchez Kam, Matilde ^f   Zink, Richard ^g   Ke, Chunlei ^b   Ma, Haijun ^b   Maca, Jeff ^a   Park, Soomin ^h  

^a IQVIA   (United States)

^b AMGEN INC   (United States)

^c Chuang Stein Consulting   (United States)

^d Cytel Corporation   (United States)

^e CENTER FOR DRUG EVALUATION AND RESEARCH   (United States)

^f Arena Pharmaceuticals GmbH   (Switzerland)

^g University of North Carolina at Chapel Hill   (United States)

^h ELI LILLY AND COMPANY   (United States)

Author keywords

Cardiovascular risk; CVOT; Diabetes mellitus; Event window; Missing data; Multiplicity; Subgroup analysis

Indexed keywords

ALOGLIPTIN; CANAGLIFLOZIN; SAXAGLIPTIN;

ALL CAUSE MORTALITY; ARTICLE; CARDIOVASCULAR RISK; COMORBIDITY; DIABETES CONTROL; GEOGRAPHIC DISTRIBUTION; HEART FAILURE; HEART MUSCLE REVASCULARIZATION; HOSPITALIZATION; HUMAN; KIDNEY DISEASE; MAJOR ADVERSE CARDIAC EVENT; NON INSULIN DEPENDENT DIABETES MELLITUS; REASSURANCE; RISK ASSESSMENT; SIMULATION; SMOKING; UNSTABLE ANGINA PECTORIS;

EID: 85041281594     PISSN: None     EISSN: 19466315     Source Type: Journal    
DOI: 10.1080/19466315.2017.1280411     Document Type: Article

References (35)

1. Alosh, M., Fritsch, H., and Mahjoob, M., Pennello, K., Rothmann, M., Russek-Cohen, E., Smith, F., Wilson, S., and Yue, L., (2015), “Statistical Considerations on Subgroup Analysis in Clinical Trials,” Statistics in Biopharmaceutical Research, 7, 286–304.
2. Amit, O., Heiberger, R. M., and Lane, P. W., (2008), “Graphical Approaches to the Analysis of Safety Data from Clinical Trials,” Pharmaceutical Statistics, 7, 20–35.
3. Benjamini, Y., and Hochberg, Y., (1995), “Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing,” Journal of the Royal Statistical Society, Series B, 57, 289–300.
4. Berry, S. M., and Berry, D. A., (2004), “Accounting for Multiplicities in Assessing Drug Safety: A Three-Level Hierarchical Mixture Model,” Biometrics, 60, 418–426.
5. Bhatt, D. L., Lincoff, A. M., Gibson, C. M., et al. (2009), “Intravenous Platelet Blockade with Cangrelor during PCI,” The New England Journal of Medicine, 361, 2330–2341.
6. Chen, J., Quan, H., Gallo, P., Menjoge, S., Luo, X., Tanaka, Y., Li, G., Ouyang, S. P., Binkowitz, B., Ibia, E., Talerico, S., and Ikeda, K., (2011a), “Consistency of Treatment Effect Across Regions in Multiregional Clinical Trials, Part 1: Design Considerations,” Drug Information Journal, 45, 595–602.
7. ——— (2011b), “Consistency of Treatment Effect across Regions in Multiregional Clinical Trials, Part 2: Monitoring, Reporting, and Interpretation,” Drug Information Journal, 45, 603–608.
8. Chuang-Stein, C., Li, Y., Kawai, N., Komiyama, O., and Kuribayashi, K., (2015), “Detecting Safety Signals in Subgroups,” in Quantitative Evaluation of Safety in Drug Development: Design, Analysis and Reporting, eds. Q., Jiang, and H. A., Xia, Boca Raton, FL: Chapman & Hall, pp. 289–319.
9. Committee for Medicinal Products for Human Use (CHMP) (2014). “Guideline on the Investigation of Subgroups in Confirmatory Clinical Trials (draft),” London: European Medicines Agency. Available at http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2014/02/WC500160523.pdf.
10. Crowe, B. J., Xia, H. A., Berlin, J. A., Watson, D. J., Shi, H., Lin, S. L., Kuebler, J., Schriver, R. C., Santanello, N. C., Rochester, G., Porter, J. B., Oster, M., Mehrotra, D. V., Li, Z., King, E. C., Harpur, E. S., and Hall, D. B., (2009), “Recommendations for Safety Planning, Data Collection, Evaluation and Reporting During Drug, Biologic and Vaccine Development: A Report of the Safety Planning, Evaluation, and Reporting Team,” Clinical Trials, 6, 430–440.
11. Cui, L., Hung, H. M., Wang, S. J., and Tsong, Y., (2002), “Issues Related to Subgroup Analysis in Clinical Trials,” Journal of Biopharmaceutical Statistics, 12, 347–358.
12. DuMouchel, W., (2012), “Multivariate Bayesian Logistic Regression for Analysis of Clinical Study Safety Issues,” Statistical Science, 27, 319–339.
13. Dunnett, C. W., (1955), “A Multiple Comparison Procedure for Comparing Several Treatments with a Control,” Journal of the American Statistical Association, 50, 1096–1121.
14. FDA Guidance to Industry (2008), “Diabetes Mellitus — Evaluating Cardiovascular Risk in New Antidiabetic Therapies to Treat Type 2 Diabetes,” available at http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm071627.pdf
15. Gao, P., Liu, L., and Mehta, C. R., (2014), “Adaptive Sequential Testing for Multiple Comparisons,” Journal of Biopharmaceutical Statistics, 24, 1–24.
16. Geiger, M. J., Mehta, C., Turner, J. R., Arbet-Engels, C., Hantel, S., Hirshberg, B., Koglin, J., Mendzelevski, B., Sager, P. T., Shapiro, D., Stewart, M., Todaro, T. G., and Gaydos, B., (2015), “Clinical Development Approaches and Statistical Methodologies to Prospectively Assess the Cardiovascular Risk of New Antidiabetic Therapies for Type 2 Diabetes,” Therapeutic Innovation and Regulatory Science, 49, 50–64.
17. Ghosh, D., and Lin, D. Y., (2000), “Nonparametric Analysis of Recurrent Events and Death,” Biometrics, 56, 554–561.
18. Hirshberg, B., and Katz, A., (2013), “Cardiovascular Outcome Studies With Novel Antidiabetes Agents: Scientific and Operational Considerations,” Diabetes Care, 36, S253–S258.
19. Hughes, S., (2014), “The Prevention of Missing Data,” in Clinical Trials with Missing Data. A Guide for Practitioners, eds. M., O'kelly, and B., Ratitch, New York: Wiley, pp. 36–52.
20. Huque, M. F., Dmitrienko, A., and D'Agostino, R., (2013), “Multiplicity Issues in Clinical Trials with Multiple Objectives,” Statistics in Biopharmaceutical Research, 5, 321–337.
21. Kordzakhia, G., and Dmitrienko, A., (2012), “Superchain Procedures in Clinical Trials with Multiple Objectives,” Statistics in Medicine, 32, 486–508.
22. Li, Q., and Lagakos, S., (1997), “Use of the Wei-Lin-Weissfeld Method for the Analysis of a Recurring and a Terminating Event,” Statistics in Medicine, 16, 925–940.
23. Li, Z., Chuang-Stein, C., and Hoseyni, C., (2007), “The Probability of Observing Negative Subgroup Results when the Treatment Effect Is Positive and Homogeneous Across all Subgroups,” Drug Information Journal, 41, 47–56.
24. Little, R. J., D'Agostino, R., and Cohen, M. L., (2012), “The Prevention and Treatment of Missing Data in Clinical Trials,” The New England Journal of Medicine, 367, 1355–1360.
25. Magirr, D., Jaki, T., and Whitehead, J., (2012), “A Generalized Dunnett Test for Multi-Arm Multi-Stage Clinical Studies with Treatment Selection,” Biometrika, 99, 494–501.
26. Marchenko, O., Jiang, Q., Chakravarty, A., Ke, C., Ma, H., Maca, J., Russek-Cohen, E., Sanchez-Kam, M., Zink, R., and Chuang-Stein, C., (2015), “Evaluation and Review of Strategies to Assess Cardiovascular Risk in Clinical Trials in Patients with Type 2 Diabetes Mellitus,” Statistics in Biopharmaceutical Research, 7, 253–266.
27. Mehta, C., (2015), “Adaptive Designs to Demonstrate Risk Reduction in CV Outcome Trials: A Case Study of the EXAMINE Trial,” in Presentation at 2015 DIA, 51st Annual Meeting.
28. Mehta, C., Gao, P., Bhatt, D. L., Harrington, R. A., Skerjanec, S., and Ware, J. H., (2009), “Optimizing Trial Design: Sequential, Adaptive, and Enrichment Strategies,” Circulation, 119, 597–605.
29. Pocock, S. J., Assmann, S. E., Enos, L. E., and Kasten, L. E., (2002), “Subgroup Analysis, Covariate Adjustment and Baseline Comparisons in Clinical Trial Reporting: Current Practice and Problems,” Statistics in Medicine, 21, 2917–2930.
30. Quan, H., Mingyu, L., Chen, J., Gallo, P., Binkowitz, B., Ibia, E., Tanaka, Y., Ouyang, S. P., Luo, X., Li, G., Menjoge, S., Talerico, S., and Ikeda, K., (2010), “Assessment of Consistency of Treatment Effects in Multiregional Clinical Trials,” Drug Information Journal, 44, 617– 632.
31. Ruberg, S. J., Chen, L., and Wang, Y., (2010), “The Mean Does not Mean as Much Anymore: Finding Subgroups for Tailored Therapeutics,” Clinical Trials, 7, 574–583.
32. Ussher, J. R., and Drucker, D. J., (2014), “Cardiovascular Actions of Incretin-based Therapies,” Circulation Research, American Heart Association, 114, 1788–1803.
33. Whitehead, A., (2002), Meta-Analysis of Controlled Clinical Trials, New York: John Wiley and Sons.
34. Xia, H. A., Ma, H., and Carlin, B. P., (2011), “Bayesian Hierarchical Modeling for Detecting Safety Signals in Clinical Trials,” Journal of Biopharmaceutical Statistics, 21, 1006–1029.
35. Zinman, B., Wanner, C., Lachin, J. M., Fitchett, D., Hantel, S., Mattheus, M., Devins, T., Johansen, O. E., Woerle, H. J., Broedl, U. C., and Inzucchi, S. E., (2015), “Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes,” The New England Journal of Medicine, 373, 2117–2128.