Development of gatekeeping strategies in confirmatory clinical trials
This paper discusses multiplicity issues arising in confirmatory clinical trials with hierarchically ordered multiple objectives. In order to protect the overall type I error rate, multiple objectives are analyzed using multiple testing procedures. When the objectives are ordered and grouped in mult...
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| Published in: | Biometrical journal Vol. 53; no. 6; pp. 875 - 893 |
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| Main Authors: | , , , |
| Format: | Journal Article |
| Language: | English |
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Weinheim
WILEY-VCH Verlag
01-11-2011
WILEY‐VCH Verlag Wiley - VCH Verlag GmbH & Co. KGaA |
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| Abstract | This paper discusses multiplicity issues arising in confirmatory clinical trials with hierarchically ordered multiple objectives. In order to protect the overall type I error rate, multiple objectives are analyzed using multiple testing procedures. When the objectives are ordered and grouped in multiple families (e.g. families of primary and secondary endpoints), gatekeeping procedures are employed to account for this hierarchical structure. We discuss considerations arising in the process of building gatekeeping procedures, including proper use of relevant trial‐specific information and criteria for selecting gatekeeping procedures. The methods and principles discussed in this paper are illustrated using a clinical trial in patients with type II diabetes mellitus. |
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| AbstractList | This paper discusses multiplicity issues arising in confirmatory clinical trials with hierarchically ordered multiple objectives. In order to protect the overall type I error rate, multiple objectives are analyzed using multiple testing procedures. When the objectives are ordered and grouped in multiple families (e.g. families of primary and secondary endpoints), gatekeeping procedures are employed to account for this hierarchical structure. We discuss considerations arising in the process of building gatekeeping procedures, including proper use of relevant trial‐specific information and criteria for selecting gatekeeping procedures. The methods and principles discussed in this paper are illustrated using a clinical trial in patients with type II diabetes mellitus. |
| Author | Millen, Brian A. Paux, Gautier Brechenmacher, Thomas Dmitrienko, Alex |
| Author_xml | – sequence: 1 givenname: Alex surname: Dmitrienko fullname: Dmitrienko, Alex email: alexei@lilly.com organization: Eli Lilly and Company, Indianapolis, IN 46285, USA – sequence: 2 givenname: Brian A. surname: Millen fullname: Millen, Brian A. organization: Eli Lilly and Company, Indianapolis, IN 46285, USA – sequence: 3 givenname: Thomas surname: Brechenmacher fullname: Brechenmacher, Thomas organization: Dainippon Sumitomo Pharma Co., Ltd., 33-94 Enoki-Cho, Suita, Osaka 564-0053, Japan – sequence: 4 givenname: Gautier surname: Paux fullname: Paux, Gautier organization: Sanofi pasteur, 1541, Avenue Marcel Mérieux, 69280 Marcy-l'Étoile, France |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/22069199$$D View this record in MEDLINE/PubMed |
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| CitedBy_id | crossref_primary_10_1038_tp_2016_152 crossref_primary_10_1080_10543406_2013_834920 crossref_primary_10_1177_1740774520944377 crossref_primary_10_1080_19466315_2013_807749 crossref_primary_10_5183_jjscs_1411001_213 crossref_primary_10_1002_sim_7506 crossref_primary_10_2217_cer_14_24 crossref_primary_10_1002_bimj_201200047 crossref_primary_10_1111_wrr_12630 crossref_primary_10_1002_sim_5642 crossref_primary_10_1002_bimj_201100258 crossref_primary_10_1016_S0140_6736_23_00061_2 crossref_primary_10_1080_10543406_2015_1074917 crossref_primary_10_1111_acel_12400 crossref_primary_10_1016_j_appet_2019_104397 crossref_primary_10_5691_jjb_36_S165 crossref_primary_10_1186_1471_244X_12_232 crossref_primary_10_1002_sim_6425 crossref_primary_10_1016_j_eclinm_2021_101261 crossref_primary_10_1097_MD_0000000000020085 crossref_primary_10_1002_sim_5537 crossref_primary_10_1089_cap_2016_0189 crossref_primary_10_1080_10543406_2015_1092032 crossref_primary_10_1002_sim_5990 crossref_primary_10_1002_sim_6985 crossref_primary_10_1016_S2213_8587_19_30151_2 crossref_primary_10_2139_ssrn_3924150 crossref_primary_10_1080_10543406_2017_1399900 crossref_primary_10_1177_026119291704500608 crossref_primary_10_1093_gerona_glv057 |
| Cites_doi | 10.1002/pst.301 10.1016/S0197-2456(97)00075-5 10.1080/10543406.2011.551333 10.1002/sim.3307 10.1201/9781584889854 10.1002/sim.4008 10.1080/10543406.2011.551334 10.1080/10543400802541693 10.1002/bimj.200610361 10.1002/9780470316672 10.1002/sim.3513 10.1002/sim.3495 10.1093/biomet/63.3.655 10.1080/01621459.1997.10473682 10.1198/jasa.2009.tm08538 10.1214/aos/1028144846 10.1016/S0378-3758(01)00077-5 10.1002/(SICI)1097-0258(19980930)17:18<2133::AID-SIM901>3.0.CO;2-2 10.1198/sbr.2010.09014 10.1002/pst.190 |
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| SubjectTerms | Biometry Clinical trials Clinical Trials as Topic - methods Diabetes mellitus Diabetes Mellitus, Type 2 - drug therapy Error analysis Familywise error rate Goals Humans Hypoglycemic Agents - adverse effects Hypoglycemic Agents - therapeutic use Multiple tests Power Structural hierarchy Testing procedures |
| Title | Development of gatekeeping strategies in confirmatory clinical trials |
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