000144995 001__ 144995 000144995 005__ 20240321221018.0 000144995 0247_ $$2doi$$a10.1002/pst.1992 000144995 0247_ $$2pmid$$apmid:31899854 000144995 0247_ $$2ISSN$$a1539-1604 000144995 0247_ $$2ISSN$$a1539-1612 000144995 0247_ $$2altmetric$$aaltmetric:73601015 000144995 037__ $$aDZNE-2020-00359 000144995 041__ $$aEnglish 000144995 082__ $$a610 000144995 1001_ $$0P:(DE-HGF)0$$aBenda, Norbert$$b0$$eCorresponding author 000144995 245__ $$aEnrichment designs using placebo nonresponders. 000144995 260__ $$aNew York, NY$$bWiley$$c2020 000144995 264_1 $$2Crossref$$3online$$bWiley$$c2020-01-03 000144995 264_1 $$2Crossref$$3print$$bWiley$$c2020-05-01 000144995 3367_ $$2DRIVER$$aarticle 000144995 3367_ $$2DataCite$$aOutput Types/Journal article 000144995 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1685015343_32156 000144995 3367_ $$2BibTeX$$aARTICLE 000144995 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000144995 3367_ $$00$$2EndNote$$aJournal Article 000144995 520__ $$aEnrichment designs that select placebo nonresponders have gained much attention during the last years in areas with high placebo response rates, eg, in depression. Proposals were made that re-randomize patients who did not respond to placebo during a first study phase as the sequential parallel design (SPD). This design uses in a second phase an enriched patient population where the treatment effect is expected to be more pronounced. This may be problematic if an effect in the overall population is claimed. Proposals were made to combine the treatment effects in the overall population from study phase 1 and the enriched population from study phase 2, alleviating but not solving the issue of a potential selection bias. This paper shows how this bias corresponding to the effect difference between the overall population and the enriched population depends on the variability of a potential subject-by-treatment interaction. Sample sizes are given, which lead to a significant result in the combining test with a given probability if actually the average effect in the overall population is zero. If, on the other hand, no subject-by-treatment interaction is given, the enrichment is shown to be inefficient. We conclude that enrichment designs using placebo nonresponders are not able to claim a positive average effect in the overall population if a subject-by-treatment interaction cannot be excluded. It cannot be used to demonstrate positive efficacy in the overall population in a pivotal phase III trial but may be used in early phases to demonstrate varying treatment effects between patients. 000144995 536__ $$0G:(DE-HGF)POF3-345$$a345 - Population Studies and Genetics (POF3-345)$$cPOF3-345$$fPOF III$$x0 000144995 542__ $$2Crossref$$i2020-01-03$$uhttp://creativecommons.org/licenses/by-nc-nd/4.0/ 000144995 542__ $$2Crossref$$i2020-01-03$$uhttp://doi.wiley.com/10.1002/tdm_license_1.1 000144995 588__ $$aDataset connected to CrossRef, PubMed, 000144995 650_2 $$2MeSH$$aData Interpretation, Statistical 000144995 650_2 $$2MeSH$$aDouble-Blind Method 000144995 650_2 $$2MeSH$$aHumans 000144995 650_2 $$2MeSH$$aModels, Statistical 000144995 650_2 $$2MeSH$$aPlacebo Effect 000144995 650_2 $$2MeSH$$aRandomized Controlled Trials as Topic: statistics & numerical data 000144995 650_2 $$2MeSH$$aResearch Design: statistics & numerical data 000144995 650_2 $$2MeSH$$aTreatment Outcome 000144995 7001_ $$0P:(DE-2719)2810511$$aHänisch, Britta$$b1$$eLast author$$udzne 000144995 77318 $$2Crossref$$3journal-article$$a10.1002/pst.1992$$b : Wiley, 2020-01-03$$n3$$p303-314$$tPharmaceutical Statistics$$v19$$x1539-1604$$y2020 000144995 773__ $$0PERI:(DE-600)2083706-9$$a10.1002/pst.1992$$gVol. 19, no. 3, p. 303 - 314$$n3$$p303-314$$tPharmaceutical statistics$$v19$$x1539-1604$$y2020 000144995 8564_ $$uhttps://pub.dzne.de/record/144995/files/DZNE-2020-00359.pdf$$yOpenAccess 000144995 8564_ $$uhttps://pub.dzne.de/record/144995/files/DZNE-2020-00359.pdf?subformat=pdfa$$xpdfa$$yOpenAccess 000144995 909CO $$ooai:pub.dzne.de:144995$$pdnbdelivery$$pdriver$$pVDB$$popen_access$$popenaire 000144995 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2810511$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b1$$kDZNE 000144995 9131_ $$0G:(DE-HGF)POF3-345$$1G:(DE-HGF)POF3-340$$2G:(DE-HGF)POF3-300$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lErkrankungen des Nervensystems$$vPopulation Studies and Genetics$$x0 000144995 9141_ $$y2020 000144995 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2020-02-26 000144995 915__ $$0LIC:(DE-HGF)CCBYNCND4$$2HGFVOC$$aCreative Commons Attribution-NonCommercial-NoDerivs CC BY-NC-ND 4.0 000144995 915__ $$0StatID:(DE-HGF)3001$$2StatID$$aDEAL Wiley$$d2020-02-26$$wger 000144995 915__ $$0StatID:(DE-HGF)0510$$2StatID$$aOpenAccess 000144995 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bPHARM STAT : 2021$$d2022-11-17 000144995 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2022-11-17 000144995 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2022-11-17 000144995 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search$$d2022-11-17 000144995 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC$$d2022-11-17 000144995 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2022-11-17 000144995 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2022-11-17 000144995 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences$$d2022-11-17 000144995 915__ $$0StatID:(DE-HGF)9900$$2StatID$$aIF < 5$$d2022-11-17 000144995 9201_ $$0I:(DE-2719)1013010$$kAG Hänisch ; 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