Estimation of secondary endpoints in two-stage phase II oncology trials

In the development of a new treatment in oncology, phase II trials play a key role. On the basis of the data obtained during phase II, it is decided whether the treatment should be studied further. Therefore, the decision to be made on the basis of the data of a phase II trial must be as accurate as...
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Gespeichert in:

Autor*in:	Kunz, Cornelia Ursula - 1979- [verfasserIn] Kieser, Meinhard [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	30 December 2012

Schlagwörter:	clinical trial phase II secondary endpoint two-stage unbiased estimator

Anmerkung:	Gesehen am 06.11.2018 Special Issue: Papers from the 32nd Annual Conference of the International Society for Clinical Biostatistics
Umfang:	17

Übergeordnetes Werk:	Enthalten in: Statistics in medicine - Chichester [u.a.] : Wiley, 1982, 31(2012), 30, Seite 4352-4368
Übergeordnetes Werk:	volume:31 ; year:2012 ; number:30 ; pages:4352-4368 ; extent:17

Links:	Volltext Volltext

DOI / URN:	10.1002/sim.5585

Katalog-ID:	1582594996

Internformat


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245	1	0	\|a Estimation of secondary endpoints in two-stage phase II oncology trials \|c Cornelia Ursula Kunz and Meinhard Kieser
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520			\|a In the development of a new treatment in oncology, phase II trials play a key role. On the basis of the data obtained during phase II, it is decided whether the treatment should be studied further. Therefore, the decision to be made on the basis of the data of a phase II trial must be as accurate as possible. For ethical and economic reasons, phase II trials are usually performed with a planned interim analysis. Furthermore, the decision about stopping or continuing the study is usually based on a short-term outcome like tumor response, whereas secondary endpoints comprise stable disease, progressive disease, toxicity, and/or overall survival. The data obtained in a phase II trial are often analyzed and interpreted by applying the maximum likelihood estimator (MLE) without taking into account the sequential nature of the trial. However, this approach provides biased results and may therefore lead to wrong conclusions. Whereas unbiased estimators for two-stage designs have been derived for the primary endpoint, such estimators are currently not available for secondary endpoints. We present uniformly minimum variance unbiased estimators (UMVUE) for secondary endpoints in two-stage designs that allow stopping for futility (and efficacy). We compare the mean squared error of the UMVUE and the MLE and investigate the efficiency of the UMVUE. A clinical trial example illustrates the application.
650		4	\|a clinical trial
650		4	\|a phase II
650		4	\|a secondary endpoint
650		4	\|a two-stage
650		4	\|a unbiased estimator
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773	0	8	\|i Enthalten in \|t Statistics in medicine \|d Chichester [u.a.] : Wiley, 1982 \|g 31(2012), 30, Seite 4352-4368 \|h Online-Ressource \|w (DE-627)30246719X \|w (DE-600)1491221-1 \|w (DE-576)079719686 \|x 1097-0258 \|7 nnns
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912			\|a GBV_USEFLAG_U
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912			\|a GBV_ILN_20
912			\|a GBV_ILN_22
912			\|a GBV_ILN_23
912			\|a GBV_ILN_24
912			\|a GBV_ILN_31
912			\|a GBV_ILN_32
912			\|a GBV_ILN_39
912			\|a GBV_ILN_40
912			\|a GBV_ILN_60
912			\|a GBV_ILN_62
912			\|a GBV_ILN_63
912			\|a GBV_ILN_65
912			\|a GBV_ILN_69
912			\|a GBV_ILN_70
912			\|a GBV_ILN_73
912			\|a GBV_ILN_74
912			\|a GBV_ILN_90
912			\|a GBV_ILN_95
912			\|a GBV_ILN_100
912			\|a GBV_ILN_101
912			\|a GBV_ILN_105
912			\|a GBV_ILN_110
912			\|a GBV_ILN_120
912			\|a GBV_ILN_138
912			\|a GBV_ILN_150
912			\|a GBV_ILN_151
912			\|a GBV_ILN_161
912			\|a GBV_ILN_170
912			\|a GBV_ILN_171
912			\|a GBV_ILN_187
912			\|a GBV_ILN_213
912			\|a GBV_ILN_224
912			\|a GBV_ILN_230
912			\|a GBV_ILN_252
912			\|a GBV_ILN_266
912			\|a GBV_ILN_285
912			\|a GBV_ILN_293
912			\|a GBV_ILN_370
912			\|a GBV_ILN_602
912			\|a GBV_ILN_636
912			\|a GBV_ILN_647
912			\|a GBV_ILN_702
912			\|a GBV_ILN_2001
912			\|a GBV_ILN_2003
912			\|a GBV_ILN_2004
912			\|a GBV_ILN_2005
912			\|a GBV_ILN_2006
912			\|a GBV_ILN_2007
912			\|a GBV_ILN_2008
912			\|a GBV_ILN_2009
912			\|a GBV_ILN_2010
912			\|a GBV_ILN_2011
912			\|a GBV_ILN_2014
912			\|a GBV_ILN_2015
912			\|a GBV_ILN_2018
912			\|a GBV_ILN_2020
912			\|a GBV_ILN_2021
912			\|a GBV_ILN_2025
912			\|a GBV_ILN_2026
912			\|a GBV_ILN_2027
912			\|a GBV_ILN_2031
912			\|a GBV_ILN_2034
912			\|a GBV_ILN_2037
912			\|a GBV_ILN_2038
912			\|a GBV_ILN_2039
912			\|a GBV_ILN_2044
912			\|a GBV_ILN_2048
912			\|a GBV_ILN_2049
912			\|a GBV_ILN_2050
912			\|a GBV_ILN_2055
912			\|a GBV_ILN_2056
912			\|a GBV_ILN_2057
912			\|a GBV_ILN_2059
912			\|a GBV_ILN_2061
912			\|a GBV_ILN_2064
912			\|a GBV_ILN_2068
912			\|a GBV_ILN_2088
912			\|a GBV_ILN_2093
912			\|a GBV_ILN_2106
912			\|a GBV_ILN_2108
912			\|a GBV_ILN_2110
912			\|a GBV_ILN_2111
912			\|a GBV_ILN_2112
912			\|a GBV_ILN_2113
912			\|a GBV_ILN_2118
912			\|a GBV_ILN_2119
912			\|a GBV_ILN_2122
912			\|a GBV_ILN_2129
912			\|a GBV_ILN_2143
912			\|a GBV_ILN_2144
912			\|a GBV_ILN_2147
912			\|a GBV_ILN_2148
912			\|a GBV_ILN_2152
912			\|a GBV_ILN_2153
912			\|a GBV_ILN_2188
912			\|a GBV_ILN_2190
912			\|a GBV_ILN_2232
912			\|a GBV_ILN_2336
912			\|a GBV_ILN_2470
912			\|a GBV_ILN_2472
912			\|a GBV_ILN_2507
912			\|a GBV_ILN_2522
912			\|a GBV_ILN_2548
912			\|a GBV_ILN_4012
912			\|a GBV_ILN_4035
912			\|a GBV_ILN_4037
912			\|a GBV_ILN_4046
912			\|a GBV_ILN_4112
912			\|a GBV_ILN_4125
912			\|a GBV_ILN_4126
912			\|a GBV_ILN_4242
912			\|a GBV_ILN_4246
912			\|a GBV_ILN_4249
912			\|a GBV_ILN_4251
912			\|a GBV_ILN_4305
912			\|a GBV_ILN_4306
912			\|a GBV_ILN_4307
912			\|a GBV_ILN_4313
912			\|a GBV_ILN_4322
912			\|a GBV_ILN_4323
912			\|a GBV_ILN_4324
912			\|a GBV_ILN_4325
912			\|a GBV_ILN_4326
912			\|a GBV_ILN_4333
912			\|a GBV_ILN_4334
912			\|a GBV_ILN_4335
912			\|a GBV_ILN_4336
912			\|a GBV_ILN_4338
912			\|a GBV_ILN_4393
912			\|a GBV_ILN_4700
951			\|a AR
952			\|d 31 \|j 2012 \|e 30 \|h 4352-4368 \|g 17
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982			\|2 2013 \|1 01 \|x DE-16-250 \|8 01 \|s s \|0 (DE-627)1410508463 \|a wissenschaftlicher Artikel (Zeitschrift)
982			\|2 2013 \|1 01 \|x DE-16-250 \|8 02 \|s s \|a per_2
982			\|2 2013 \|1 01 \|x DE-16-250 \|8 03 \|s s \|a s_17
982			\|2 2013 \|1 01 \|x DE-16-250 \|8 04 \|s p \|0 (DE-627)1473218446 \|a Kunz, Cornelia Ursula
982			\|2 2013 \|1 01 \|x DE-16-250 \|8 04 \|s k \|0 (DE-627)1416466967 \|a Medizinische Fakultät Heidelberg
982			\|2 2013 \|1 01 \|x DE-16-250 \|8 04 \|s s \|0 (DE-627)1410501914 \|a Verfasser
982			\|2 2013 \|1 01 \|x DE-16-250 \|8 04 \|s s \|a pos_1
982			\|2 2013 \|1 01 \|x DE-16-250 \|8 05 \|s p \|0 (DE-627)1450272401 \|a Kieser, Meinhard
982			\|2 2013 \|1 01 \|x DE-16-250 \|8 05 \|s k \|0 (DE-627)1416741593 \|a Institut für Medizinische Biometrie und Informatik
982			\|2 2013 \|1 01 \|x DE-16-250 \|8 05 \|s s \|0 (DE-627)1410501914 \|a Verfasser
982			\|2 2013 \|1 01 \|x DE-16-250 \|8 05 \|s s \|a pos_2

Indexfelder

author_variant	c u k cu cuk m k mk
matchkey_str	article:10970258:2012----::siainfeodredonsnwsaehs
oclc_num	1341022329
hierarchy_sort_str	30 December 2012
publishDate	2012
allfields	10.1002/sim.5585 doi (DE-627)1582594996 (DE-576)512594996 (DE-599)BSZ512594996 (OCoLC)1341022329 DE-627 ger DE-627 rda eng Kunz, Cornelia Ursula 1979- verfasserin (DE-588)1024218112 (DE-627)719391911 (DE-576)368162435 aut Estimation of secondary endpoints in two-stage phase II oncology trials Cornelia Ursula Kunz and Meinhard Kieser 30 December 2012 17 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Gesehen am 06.11.2018 Special Issue: Papers from the 32nd Annual Conference of the International Society for Clinical Biostatistics In the development of a new treatment in oncology, phase II trials play a key role. On the basis of the data obtained during phase II, it is decided whether the treatment should be studied further. Therefore, the decision to be made on the basis of the data of a phase II trial must be as accurate as possible. For ethical and economic reasons, phase II trials are usually performed with a planned interim analysis. Furthermore, the decision about stopping or continuing the study is usually based on a short-term outcome like tumor response, whereas secondary endpoints comprise stable disease, progressive disease, toxicity, and/or overall survival. The data obtained in a phase II trial are often analyzed and interpreted by applying the maximum likelihood estimator (MLE) without taking into account the sequential nature of the trial. However, this approach provides biased results and may therefore lead to wrong conclusions. Whereas unbiased estimators for two-stage designs have been derived for the primary endpoint, such estimators are currently not available for secondary endpoints. We present uniformly minimum variance unbiased estimators (UMVUE) for secondary endpoints in two-stage designs that allow stopping for futility (and efficacy). We compare the mean squared error of the UMVUE and the MLE and investigate the efficiency of the UMVUE. A clinical trial example illustrates the application. clinical trial phase II secondary endpoint two-stage unbiased estimator Kieser, Meinhard verfasserin (DE-588)103276547X (DE-627)739277766 (DE-576)168963825 aut Enthalten in Statistics in medicine Chichester [u.a.] : Wiley, 1982 31(2012), 30, Seite 4352-4368 Online-Ressource (DE-627)30246719X (DE-600)1491221-1 (DE-576)079719686 1097-0258 nnns volume:31 year:2012 number:30 pages:4352-4368 extent:17 http://dx.doi.org/10.1002/sim.5585 Verlag Resolving-System Volltext https://onlinelibrary.wiley.com/doi/abs/10.1002/sim.5585 Verlag Volltext GBV_USEFLAG_U GBV_ILN_2013 ISIL_DE-16-250 SYSFLAG_1 GBV_KXP SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_647 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 31 2012 30 4352-4368 17 2013 01 DE-16-250 303046606X 00 --%%-- --%%-- --%%-- --%%-- l01 06-11-18 2013 01 DE-16-250 00 s hd2012 2013 01 DE-16-250 01 s (DE-627)1410508463 wissenschaftlicher Artikel (Zeitschrift) 2013 01 DE-16-250 02 s per_2 2013 01 DE-16-250 03 s s_17 2013 01 DE-16-250 04 p (DE-627)1473218446 Kunz, Cornelia Ursula 2013 01 DE-16-250 04 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 04 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 04 s pos_1 2013 01 DE-16-250 05 p (DE-627)1450272401 Kieser, Meinhard 2013 01 DE-16-250 05 k (DE-627)1416741593 Institut für Medizinische Biometrie und Informatik 2013 01 DE-16-250 05 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 05 s pos_2
spelling	10.1002/sim.5585 doi (DE-627)1582594996 (DE-576)512594996 (DE-599)BSZ512594996 (OCoLC)1341022329 DE-627 ger DE-627 rda eng Kunz, Cornelia Ursula 1979- verfasserin (DE-588)1024218112 (DE-627)719391911 (DE-576)368162435 aut Estimation of secondary endpoints in two-stage phase II oncology trials Cornelia Ursula Kunz and Meinhard Kieser 30 December 2012 17 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Gesehen am 06.11.2018 Special Issue: Papers from the 32nd Annual Conference of the International Society for Clinical Biostatistics In the development of a new treatment in oncology, phase II trials play a key role. On the basis of the data obtained during phase II, it is decided whether the treatment should be studied further. Therefore, the decision to be made on the basis of the data of a phase II trial must be as accurate as possible. For ethical and economic reasons, phase II trials are usually performed with a planned interim analysis. Furthermore, the decision about stopping or continuing the study is usually based on a short-term outcome like tumor response, whereas secondary endpoints comprise stable disease, progressive disease, toxicity, and/or overall survival. The data obtained in a phase II trial are often analyzed and interpreted by applying the maximum likelihood estimator (MLE) without taking into account the sequential nature of the trial. However, this approach provides biased results and may therefore lead to wrong conclusions. Whereas unbiased estimators for two-stage designs have been derived for the primary endpoint, such estimators are currently not available for secondary endpoints. We present uniformly minimum variance unbiased estimators (UMVUE) for secondary endpoints in two-stage designs that allow stopping for futility (and efficacy). We compare the mean squared error of the UMVUE and the MLE and investigate the efficiency of the UMVUE. A clinical trial example illustrates the application. clinical trial phase II secondary endpoint two-stage unbiased estimator Kieser, Meinhard verfasserin (DE-588)103276547X (DE-627)739277766 (DE-576)168963825 aut Enthalten in Statistics in medicine Chichester [u.a.] : Wiley, 1982 31(2012), 30, Seite 4352-4368 Online-Ressource (DE-627)30246719X (DE-600)1491221-1 (DE-576)079719686 1097-0258 nnns volume:31 year:2012 number:30 pages:4352-4368 extent:17 http://dx.doi.org/10.1002/sim.5585 Verlag Resolving-System Volltext https://onlinelibrary.wiley.com/doi/abs/10.1002/sim.5585 Verlag Volltext GBV_USEFLAG_U GBV_ILN_2013 ISIL_DE-16-250 SYSFLAG_1 GBV_KXP SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_647 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 31 2012 30 4352-4368 17 2013 01 DE-16-250 303046606X 00 --%%-- --%%-- --%%-- --%%-- l01 06-11-18 2013 01 DE-16-250 00 s hd2012 2013 01 DE-16-250 01 s (DE-627)1410508463 wissenschaftlicher Artikel (Zeitschrift) 2013 01 DE-16-250 02 s per_2 2013 01 DE-16-250 03 s s_17 2013 01 DE-16-250 04 p (DE-627)1473218446 Kunz, Cornelia Ursula 2013 01 DE-16-250 04 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 04 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 04 s pos_1 2013 01 DE-16-250 05 p (DE-627)1450272401 Kieser, Meinhard 2013 01 DE-16-250 05 k (DE-627)1416741593 Institut für Medizinische Biometrie und Informatik 2013 01 DE-16-250 05 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 05 s pos_2
allfields_unstemmed	10.1002/sim.5585 doi (DE-627)1582594996 (DE-576)512594996 (DE-599)BSZ512594996 (OCoLC)1341022329 DE-627 ger DE-627 rda eng Kunz, Cornelia Ursula 1979- verfasserin (DE-588)1024218112 (DE-627)719391911 (DE-576)368162435 aut Estimation of secondary endpoints in two-stage phase II oncology trials Cornelia Ursula Kunz and Meinhard Kieser 30 December 2012 17 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Gesehen am 06.11.2018 Special Issue: Papers from the 32nd Annual Conference of the International Society for Clinical Biostatistics In the development of a new treatment in oncology, phase II trials play a key role. On the basis of the data obtained during phase II, it is decided whether the treatment should be studied further. Therefore, the decision to be made on the basis of the data of a phase II trial must be as accurate as possible. For ethical and economic reasons, phase II trials are usually performed with a planned interim analysis. Furthermore, the decision about stopping or continuing the study is usually based on a short-term outcome like tumor response, whereas secondary endpoints comprise stable disease, progressive disease, toxicity, and/or overall survival. The data obtained in a phase II trial are often analyzed and interpreted by applying the maximum likelihood estimator (MLE) without taking into account the sequential nature of the trial. However, this approach provides biased results and may therefore lead to wrong conclusions. Whereas unbiased estimators for two-stage designs have been derived for the primary endpoint, such estimators are currently not available for secondary endpoints. We present uniformly minimum variance unbiased estimators (UMVUE) for secondary endpoints in two-stage designs that allow stopping for futility (and efficacy). We compare the mean squared error of the UMVUE and the MLE and investigate the efficiency of the UMVUE. A clinical trial example illustrates the application. clinical trial phase II secondary endpoint two-stage unbiased estimator Kieser, Meinhard verfasserin (DE-588)103276547X (DE-627)739277766 (DE-576)168963825 aut Enthalten in Statistics in medicine Chichester [u.a.] : Wiley, 1982 31(2012), 30, Seite 4352-4368 Online-Ressource (DE-627)30246719X (DE-600)1491221-1 (DE-576)079719686 1097-0258 nnns volume:31 year:2012 number:30 pages:4352-4368 extent:17 http://dx.doi.org/10.1002/sim.5585 Verlag Resolving-System Volltext https://onlinelibrary.wiley.com/doi/abs/10.1002/sim.5585 Verlag Volltext GBV_USEFLAG_U GBV_ILN_2013 ISIL_DE-16-250 SYSFLAG_1 GBV_KXP SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_647 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 31 2012 30 4352-4368 17 2013 01 DE-16-250 303046606X 00 --%%-- --%%-- --%%-- --%%-- l01 06-11-18 2013 01 DE-16-250 00 s hd2012 2013 01 DE-16-250 01 s (DE-627)1410508463 wissenschaftlicher Artikel (Zeitschrift) 2013 01 DE-16-250 02 s per_2 2013 01 DE-16-250 03 s s_17 2013 01 DE-16-250 04 p (DE-627)1473218446 Kunz, Cornelia Ursula 2013 01 DE-16-250 04 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 04 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 04 s pos_1 2013 01 DE-16-250 05 p (DE-627)1450272401 Kieser, Meinhard 2013 01 DE-16-250 05 k (DE-627)1416741593 Institut für Medizinische Biometrie und Informatik 2013 01 DE-16-250 05 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 05 s pos_2
allfieldsGer	10.1002/sim.5585 doi (DE-627)1582594996 (DE-576)512594996 (DE-599)BSZ512594996 (OCoLC)1341022329 DE-627 ger DE-627 rda eng Kunz, Cornelia Ursula 1979- verfasserin (DE-588)1024218112 (DE-627)719391911 (DE-576)368162435 aut Estimation of secondary endpoints in two-stage phase II oncology trials Cornelia Ursula Kunz and Meinhard Kieser 30 December 2012 17 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Gesehen am 06.11.2018 Special Issue: Papers from the 32nd Annual Conference of the International Society for Clinical Biostatistics In the development of a new treatment in oncology, phase II trials play a key role. On the basis of the data obtained during phase II, it is decided whether the treatment should be studied further. Therefore, the decision to be made on the basis of the data of a phase II trial must be as accurate as possible. For ethical and economic reasons, phase II trials are usually performed with a planned interim analysis. Furthermore, the decision about stopping or continuing the study is usually based on a short-term outcome like tumor response, whereas secondary endpoints comprise stable disease, progressive disease, toxicity, and/or overall survival. The data obtained in a phase II trial are often analyzed and interpreted by applying the maximum likelihood estimator (MLE) without taking into account the sequential nature of the trial. However, this approach provides biased results and may therefore lead to wrong conclusions. Whereas unbiased estimators for two-stage designs have been derived for the primary endpoint, such estimators are currently not available for secondary endpoints. We present uniformly minimum variance unbiased estimators (UMVUE) for secondary endpoints in two-stage designs that allow stopping for futility (and efficacy). We compare the mean squared error of the UMVUE and the MLE and investigate the efficiency of the UMVUE. A clinical trial example illustrates the application. clinical trial phase II secondary endpoint two-stage unbiased estimator Kieser, Meinhard verfasserin (DE-588)103276547X (DE-627)739277766 (DE-576)168963825 aut Enthalten in Statistics in medicine Chichester [u.a.] : Wiley, 1982 31(2012), 30, Seite 4352-4368 Online-Ressource (DE-627)30246719X (DE-600)1491221-1 (DE-576)079719686 1097-0258 nnns volume:31 year:2012 number:30 pages:4352-4368 extent:17 http://dx.doi.org/10.1002/sim.5585 Verlag Resolving-System Volltext https://onlinelibrary.wiley.com/doi/abs/10.1002/sim.5585 Verlag Volltext GBV_USEFLAG_U GBV_ILN_2013 ISIL_DE-16-250 SYSFLAG_1 GBV_KXP SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_647 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 31 2012 30 4352-4368 17 2013 01 DE-16-250 303046606X 00 --%%-- --%%-- --%%-- --%%-- l01 06-11-18 2013 01 DE-16-250 00 s hd2012 2013 01 DE-16-250 01 s (DE-627)1410508463 wissenschaftlicher Artikel (Zeitschrift) 2013 01 DE-16-250 02 s per_2 2013 01 DE-16-250 03 s s_17 2013 01 DE-16-250 04 p (DE-627)1473218446 Kunz, Cornelia Ursula 2013 01 DE-16-250 04 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 04 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 04 s pos_1 2013 01 DE-16-250 05 p (DE-627)1450272401 Kieser, Meinhard 2013 01 DE-16-250 05 k (DE-627)1416741593 Institut für Medizinische Biometrie und Informatik 2013 01 DE-16-250 05 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 05 s pos_2
allfieldsSound	10.1002/sim.5585 doi (DE-627)1582594996 (DE-576)512594996 (DE-599)BSZ512594996 (OCoLC)1341022329 DE-627 ger DE-627 rda eng Kunz, Cornelia Ursula 1979- verfasserin (DE-588)1024218112 (DE-627)719391911 (DE-576)368162435 aut Estimation of secondary endpoints in two-stage phase II oncology trials Cornelia Ursula Kunz and Meinhard Kieser 30 December 2012 17 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Gesehen am 06.11.2018 Special Issue: Papers from the 32nd Annual Conference of the International Society for Clinical Biostatistics In the development of a new treatment in oncology, phase II trials play a key role. On the basis of the data obtained during phase II, it is decided whether the treatment should be studied further. Therefore, the decision to be made on the basis of the data of a phase II trial must be as accurate as possible. For ethical and economic reasons, phase II trials are usually performed with a planned interim analysis. Furthermore, the decision about stopping or continuing the study is usually based on a short-term outcome like tumor response, whereas secondary endpoints comprise stable disease, progressive disease, toxicity, and/or overall survival. The data obtained in a phase II trial are often analyzed and interpreted by applying the maximum likelihood estimator (MLE) without taking into account the sequential nature of the trial. However, this approach provides biased results and may therefore lead to wrong conclusions. Whereas unbiased estimators for two-stage designs have been derived for the primary endpoint, such estimators are currently not available for secondary endpoints. We present uniformly minimum variance unbiased estimators (UMVUE) for secondary endpoints in two-stage designs that allow stopping for futility (and efficacy). We compare the mean squared error of the UMVUE and the MLE and investigate the efficiency of the UMVUE. A clinical trial example illustrates the application. clinical trial phase II secondary endpoint two-stage unbiased estimator Kieser, Meinhard verfasserin (DE-588)103276547X (DE-627)739277766 (DE-576)168963825 aut Enthalten in Statistics in medicine Chichester [u.a.] : Wiley, 1982 31(2012), 30, Seite 4352-4368 Online-Ressource (DE-627)30246719X (DE-600)1491221-1 (DE-576)079719686 1097-0258 nnns volume:31 year:2012 number:30 pages:4352-4368 extent:17 http://dx.doi.org/10.1002/sim.5585 Verlag Resolving-System Volltext https://onlinelibrary.wiley.com/doi/abs/10.1002/sim.5585 Verlag Volltext GBV_USEFLAG_U GBV_ILN_2013 ISIL_DE-16-250 SYSFLAG_1 GBV_KXP SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_647 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 31 2012 30 4352-4368 17 2013 01 DE-16-250 303046606X 00 --%%-- --%%-- --%%-- --%%-- l01 06-11-18 2013 01 DE-16-250 00 s hd2012 2013 01 DE-16-250 01 s (DE-627)1410508463 wissenschaftlicher Artikel (Zeitschrift) 2013 01 DE-16-250 02 s per_2 2013 01 DE-16-250 03 s s_17 2013 01 DE-16-250 04 p (DE-627)1473218446 Kunz, Cornelia Ursula 2013 01 DE-16-250 04 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 04 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 04 s pos_1 2013 01 DE-16-250 05 p (DE-627)1450272401 Kieser, Meinhard 2013 01 DE-16-250 05 k (DE-627)1416741593 Institut für Medizinische Biometrie und Informatik 2013 01 DE-16-250 05 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 05 s pos_2
language	English
source	Enthalten in Statistics in medicine 31(2012), 30, Seite 4352-4368 volume:31 year:2012 number:30 pages:4352-4368 extent:17
sourceStr	Enthalten in Statistics in medicine 31(2012), 30, Seite 4352-4368 volume:31 year:2012 number:30 pages:4352-4368 extent:17
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institution	findex.gbv.de
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topic_facet	clinical trial phase II secondary endpoint two-stage unbiased estimator
sw_local_iln_str_mv	2013:hd2012 DE-16-250:hd2012 2013:wissenschaftlicher Artikel (Zeitschrift) DE-16-250:wissenschaftlicher Artikel (Zeitschrift) 2013:per_2 DE-16-250:per_2 2013:s_17 DE-16-250:s_17 2013:Kunz, Cornelia Ursula DE-16-250:Kunz, Cornelia Ursula 2013:Medizinische Fakultät Heidelberg DE-16-250:Medizinische Fakultät Heidelberg 2013:Verfasser DE-16-250:Verfasser 2013:pos_1 DE-16-250:pos_1 2013:Kieser, Meinhard DE-16-250:Kieser, Meinhard 2013:Institut für Medizinische Biometrie und Informatik DE-16-250:Institut für Medizinische Biometrie und Informatik 2013:pos_2 DE-16-250:pos_2
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container_title	Statistics in medicine
authorswithroles_txt_mv	Kunz, Cornelia Ursula @@aut@@ Kieser, Meinhard @@aut@@
publishDateDaySort_date	2012-01-01T00:00:00Z
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Whereas unbiased estimators for two-stage designs have been derived for the primary endpoint, such estimators are currently not available for secondary endpoints. We present uniformly minimum variance unbiased estimators (UMVUE) for secondary endpoints in two-stage designs that allow stopping for futility (and efficacy). We compare the mean squared error of the UMVUE and the MLE and investigate the efficiency of the UMVUE. 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author	Kunz, Cornelia Ursula 1979-
spellingShingle	Kunz, Cornelia Ursula 1979- misc clinical trial misc phase II misc secondary endpoint misc two-stage misc unbiased estimator 2013 hd2012 2013 wissenschaftlicher Artikel (Zeitschrift) 2013 per_2 2013 s_17 2013 Kunz, Cornelia Ursula 2013 Medizinische Fakultät Heidelberg 2013 Verfasser 2013 pos_1 2013 Kieser, Meinhard 2013 Institut für Medizinische Biometrie und Informatik 2013 pos_2 Estimation of secondary endpoints in two-stage phase II oncology trials
authorStr	Kunz, Cornelia Ursula 1979-
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illustrated	Not Illustrated
issn	1097-0258
topic_title	2013 01 DE-16-250 00 s hd2012 2013 01 DE-16-250 01 s (DE-627)1410508463 wissenschaftlicher Artikel (Zeitschrift) 2013 01 DE-16-250 02 s per_2 2013 01 DE-16-250 03 s s_17 2013 01 DE-16-250 04 p (DE-627)1473218446 Kunz, Cornelia Ursula 2013 01 DE-16-250 04 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 04 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 04 s pos_1 2013 01 DE-16-250 05 p (DE-627)1450272401 Kieser, Meinhard 2013 01 DE-16-250 05 k (DE-627)1416741593 Institut für Medizinische Biometrie und Informatik 2013 01 DE-16-250 05 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 05 s pos_2 Estimation of secondary endpoints in two-stage phase II oncology trials Cornelia Ursula Kunz and Meinhard Kieser clinical trial phase II secondary endpoint two-stage unbiased estimator
topic	misc clinical trial misc phase II misc secondary endpoint misc two-stage misc unbiased estimator 2013 hd2012 2013 wissenschaftlicher Artikel (Zeitschrift) 2013 per_2 2013 s_17 2013 Kunz, Cornelia Ursula 2013 Medizinische Fakultät Heidelberg 2013 Verfasser 2013 pos_1 2013 Kieser, Meinhard 2013 Institut für Medizinische Biometrie und Informatik 2013 pos_2
topic_unstemmed	misc clinical trial misc phase II misc secondary endpoint misc two-stage misc unbiased estimator 2013 hd2012 2013 wissenschaftlicher Artikel (Zeitschrift) 2013 per_2 2013 s_17 2013 Kunz, Cornelia Ursula 2013 Medizinische Fakultät Heidelberg 2013 Verfasser 2013 pos_1 2013 Kieser, Meinhard 2013 Institut für Medizinische Biometrie und Informatik 2013 pos_2
topic_browse	misc clinical trial misc phase II misc secondary endpoint misc two-stage misc unbiased estimator 2013 hd2012 2013 wissenschaftlicher Artikel (Zeitschrift) 2013 per_2 2013 s_17 2013 Kunz, Cornelia Ursula 2013 Medizinische Fakultät Heidelberg 2013 Verfasser 2013 pos_1 2013 Kieser, Meinhard 2013 Institut für Medizinische Biometrie und Informatik 2013 pos_2
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title	Estimation of secondary endpoints in two-stage phase II oncology trials
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title_full	Estimation of secondary endpoints in two-stage phase II oncology trials Cornelia Ursula Kunz and Meinhard Kieser
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title_sort	estimation of secondary endpoints in two-stage phase ii oncology trials
title_auth	Estimation of secondary endpoints in two-stage phase II oncology trials
abstract	In the development of a new treatment in oncology, phase II trials play a key role. On the basis of the data obtained during phase II, it is decided whether the treatment should be studied further. Therefore, the decision to be made on the basis of the data of a phase II trial must be as accurate as possible. For ethical and economic reasons, phase II trials are usually performed with a planned interim analysis. Furthermore, the decision about stopping or continuing the study is usually based on a short-term outcome like tumor response, whereas secondary endpoints comprise stable disease, progressive disease, toxicity, and/or overall survival. The data obtained in a phase II trial are often analyzed and interpreted by applying the maximum likelihood estimator (MLE) without taking into account the sequential nature of the trial. However, this approach provides biased results and may therefore lead to wrong conclusions. Whereas unbiased estimators for two-stage designs have been derived for the primary endpoint, such estimators are currently not available for secondary endpoints. We present uniformly minimum variance unbiased estimators (UMVUE) for secondary endpoints in two-stage designs that allow stopping for futility (and efficacy). We compare the mean squared error of the UMVUE and the MLE and investigate the efficiency of the UMVUE. A clinical trial example illustrates the application. Gesehen am 06.11.2018 Special Issue: Papers from the 32nd Annual Conference of the International Society for Clinical Biostatistics
abstractGer	In the development of a new treatment in oncology, phase II trials play a key role. On the basis of the data obtained during phase II, it is decided whether the treatment should be studied further. Therefore, the decision to be made on the basis of the data of a phase II trial must be as accurate as possible. For ethical and economic reasons, phase II trials are usually performed with a planned interim analysis. Furthermore, the decision about stopping or continuing the study is usually based on a short-term outcome like tumor response, whereas secondary endpoints comprise stable disease, progressive disease, toxicity, and/or overall survival. The data obtained in a phase II trial are often analyzed and interpreted by applying the maximum likelihood estimator (MLE) without taking into account the sequential nature of the trial. However, this approach provides biased results and may therefore lead to wrong conclusions. Whereas unbiased estimators for two-stage designs have been derived for the primary endpoint, such estimators are currently not available for secondary endpoints. We present uniformly minimum variance unbiased estimators (UMVUE) for secondary endpoints in two-stage designs that allow stopping for futility (and efficacy). We compare the mean squared error of the UMVUE and the MLE and investigate the efficiency of the UMVUE. A clinical trial example illustrates the application. Gesehen am 06.11.2018 Special Issue: Papers from the 32nd Annual Conference of the International Society for Clinical Biostatistics
abstract_unstemmed	In the development of a new treatment in oncology, phase II trials play a key role. On the basis of the data obtained during phase II, it is decided whether the treatment should be studied further. Therefore, the decision to be made on the basis of the data of a phase II trial must be as accurate as possible. For ethical and economic reasons, phase II trials are usually performed with a planned interim analysis. Furthermore, the decision about stopping or continuing the study is usually based on a short-term outcome like tumor response, whereas secondary endpoints comprise stable disease, progressive disease, toxicity, and/or overall survival. The data obtained in a phase II trial are often analyzed and interpreted by applying the maximum likelihood estimator (MLE) without taking into account the sequential nature of the trial. However, this approach provides biased results and may therefore lead to wrong conclusions. Whereas unbiased estimators for two-stage designs have been derived for the primary endpoint, such estimators are currently not available for secondary endpoints. We present uniformly minimum variance unbiased estimators (UMVUE) for secondary endpoints in two-stage designs that allow stopping for futility (and efficacy). We compare the mean squared error of the UMVUE and the MLE and investigate the efficiency of the UMVUE. A clinical trial example illustrates the application. Gesehen am 06.11.2018 Special Issue: Papers from the 32nd Annual Conference of the International Society for Clinical Biostatistics
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title_short	Estimation of secondary endpoints in two-stage phase II oncology trials
url	http://dx.doi.org/10.1002/sim.5585 https://onlinelibrary.wiley.com/doi/abs/10.1002/sim.5585
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Estimation of secondary endpoints in two-stage phase II oncology trials

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