Medical research relies on clinical trials to assess therapeuticbenefits. Because of the effort and cost involved in these studies,investigators frequently use analyses of subgroups of studyparticipants to extract as much information as possible. Suchanalyses, which assess the heterogeneity of treatment effectsin subgroups of patients, may provide useful information forthe care of patients and for future research. However, subgroupanalyses also introduce analytic challenges and can lead tooverstated and misleading results.1,2,3,4,5,6,7 This reportoutlines the challenges associated with conducting and reportingsubgroup analyses, and it sets forth guidelines for their usein the Journal. . . [Full Text of this Article]
Subgroup Analyses and Related Concepts
Subgroup Analysis
Heterogeneity and Statistical Interactions
Multiplicity
Prespecified Analysis versus Post Hoc Analysis
Subgroup Analyses in the Journal — Assessment of Reporting Practices
Analysis of Our Findings and Guidelines for Reporting Subgroups
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(2008). Toll-like Receptor 4 Polymorphisms and Aspergillosis in Stem-Cell Transplantation. NEJM
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359: 1735-1736
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Fatkenheuer, G., Nelson, M., Lazzarin, A., Konourina, I., Hoepelman, A. I.M., Lampiris, H., Hirschel, B., Tebas, P., Raffi, F., Trottier, B., Bellos, N., Saag, M., Cooper, D. A., Westby, M., Tawadrous, M., Sullivan, J. F., Ridgway, C., Dunne, M. W., Felstead, S., Mayer, H., van der Ryst, E., the MOTIVATE 1 and MOTIVATE 2 Study Teams,
(2008). Subgroup Analyses of Maraviroc in Previously Treated R5 HIV-1 Infection. NEJM
359: 1442-1455
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26: 4385-4393
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Vermorken, J. B., Mesia, R., Rivera, F., Remenar, E., Kawecki, A., Rottey, S., Erfan, J., Zabolotnyy, D., Kienzer, H.-R., Cupissol, D., Peyrade, F., Benasso, M., Vynnychenko, I., De Raucourt, D., Bokemeyer, C., Schueler, A., Amellal, N., Hitt, R.
(2008). Platinum-Based Chemotherapy plus Cetuximab in Head and Neck Cancer. NEJM
359: 1116-1127
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(2008). Flaws in the U.S. Food and Drug Administration's Rationale for Supporting the Development and Approval of BiDil as a Treatment for Heart Failure Only in Black Patients.. J Law Med Ethics
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Kastrati, A., Neumann, F.-J., Mehilli, J., Byrne, R. A., Iijima, R., Buttner, H. J., Khattab, A. A., Schulz, S., Blankenship, J. C., Pache, J., Minners, J., Seyfarth, M., Graf, I., Skelding, K. A., Dirschinger, J., Richardt, G., Berger, P. B., Schomig, A., the ISAR-REACT 3 Trial Investigators,
(2008). Bivalirudin versus Unfractionated Heparin during Percutaneous Coronary Intervention. NEJM
359: 688-696
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Cooper, D. A., Steigbigel, R. T., Gatell, J. M., Rockstroh, J. K., Katlama, C., Yeni, P., Lazzarin, A., Clotet, B., Kumar, P. N., Eron, J. E., Schechter, M., Markowitz, M., Loutfy, M. R., Lennox, J. L., Zhao, J., Chen, J., Ryan, D. M., Rhodes, R. R., Killar, J. A., Gilde, L. R., Strohmaier, K. M., Meibohm, A. R., Miller, M. D., Hazuda, D. J., Nessly, M. L., DiNubile, M. J., Isaacs, R. D., Teppler, H., Nguyen, B.-Y., the BENCHMRK Study Teams,
(2008). Subgroup and Resistance Analyses of Raltegravir for Resistant HIV-1 Infection. NEJM
359: 355-365
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Gueugniaud, P.-Y., David, J.-S., Chanzy, E., Hubert, H., Dubien, P.-Y., Mauriaucourt, P., Braganca, C., Billeres, X., Clotteau-Lambert, M.-P., Fuster, P., Thiercelin, D., Debaty, G., Ricard-Hibon, A., Roux, P., Espesson, C., Querellou, E., Ducros, L., Ecollan, P., Halbout, L., Savary, D., Guillaumee, F., Maupoint, R., Capelle, P., Bracq, C., Dreyfus, P., Nouguier, P., Gache, A., Meurisse, C., Boulanger, B., Lae, C., Metzger, J., Raphael, V., Beruben, A., Wenzel, V., Guinhouya, C., Vilhelm, C., Marret, E.
(2008). Vasopressin and Epinephrine vs. Epinephrine Alone in Cardiopulmonary Resuscitation. NEJM
359: 21-30
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WALKER, E., HERNANDEZ, A. V., KATTAN, M. W.
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Pocock, S. J, Travison, T. G, Wruck, L. M
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336: 1166-1169
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Pocock, S. J., Lubsen, J., Wang, R., Lagakos, S. W.
(2008). More on Subgroup Analyses in Clinical Trials. NEJM
358: 2076-2077
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Brasher, P. M.A., Brant, R. F.
(2008). Problems of multiplicity/Problemes de multiplicite. Canadian J. Anesthesia
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Ramalingam, S. S., Dahlberg, S. E., Gray, R., Langer, C. J., Belani, C. P., Brahmer, J. R., Sandler, A. B., Schiller, J. H., Johnson, D. H.
(2008). Meaningful Subset Analyses Contribute to Optimal Patient Care. JCO
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Proestel, S., Kent, D., Hayward, R., Wang, R., Lagakos, S. W., Drazen, J. M.
(2008). Subgroup analyses in clinical trials.. NEJM
358: 1199-1199
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