Randomized p$p$‐values for multiple testing and their application in replicability analysis

We are concerned with testing replicability hypotheses for many endpoints simultaneously. This constitutes a multiple test problem with composite null hypotheses. Traditional p$p$‐values, which are computed under least favorable parameter configurations (LFCs), are over‐conservative in the case of c...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Biometrical journal 2022-02, Vol.64 (2), p.384-409
Hauptverfasser: Hoang, Anh‐Tuan, Dickhaus, Thorsten
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 409
container_issue 2
container_start_page 384
container_title Biometrical journal
container_volume 64
creator Hoang, Anh‐Tuan
Dickhaus, Thorsten
description We are concerned with testing replicability hypotheses for many endpoints simultaneously. This constitutes a multiple test problem with composite null hypotheses. Traditional p$p$‐values, which are computed under least favorable parameter configurations (LFCs), are over‐conservative in the case of composite null hypotheses. As demonstrated in prior work, this poses severe challenges in the multiple testing context, especially when one goal of the statistical analysis is to estimate the proportion π0$\pi _0$ of true null hypotheses. Randomized p$p$‐values have been proposed to remedy this issue. In the present work, we discuss the application of randomized p$p$‐values in replicability analysis. In particular, we introduce a general class of statistical models for which valid, randomized p$p$‐values can be calculated easily. By means of computer simulations, we demonstrate that their usage typically leads to a much more accurate estimation of π0$\pi _0$ than the LFC‐based approach. Finally, we apply our proposed methodology to a real data example from genomics.
doi_str_mv 10.1002/bimj.202000155
format Article
fullrecord <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_proquest_miscellaneous_2479040084</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2628025699</sourcerecordid><originalsourceid>FETCH-LOGICAL-p1345-9515eb52f038ca24e4b34a05e1f59f10a93bf2dcabb5ec75330c8f7204f80c3d3</originalsourceid><addsrcrecordid>eNpd0clOwzAQBmALgWgpXDkiS_TAJWW8ZTlCxVJUhITgiCInccCVsxAnoHDiEXhGngSXlh44WSN_Gs3Mj9AhgQkBoKeJLhYTChQAiBBbaEgEJR4H5m-jITDKPBbyYID2rF04EwGnu2jAGPe5T8QQPd3LMqsK_aEyXI_r8ffn15s0nbI4rxpcdKbVtVG4VbbV5TN2GLcvSjdY1rXRqWx1VWJd4kb9lok2uu0dk6a32u6jnVwaqw7W7wg9Xl48TK-9-d3VbHo292rCuPAiQYRKBM2BhamkXPGEcQlCkVxEOQEZsSSnmWufCJUGgjFIwzygwPMQUpaxETpZ9a2b6tUN38aFtqkyRpaq6mxMeeA2Bwi5o8f_6KLqGjevUz4NgQo_ipw6WqsuKVQW140uZNPHf4dzIFqBd21Uv_knEC9jiZexxJtY4vPZ7c2mYj-wXoG3</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2628025699</pqid></control><display><type>article</type><title>Randomized p$p$‐values for multiple testing and their application in replicability analysis</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Hoang, Anh‐Tuan ; Dickhaus, Thorsten</creator><creatorcontrib>Hoang, Anh‐Tuan ; Dickhaus, Thorsten</creatorcontrib><description>We are concerned with testing replicability hypotheses for many endpoints simultaneously. This constitutes a multiple test problem with composite null hypotheses. Traditional p$p$‐values, which are computed under least favorable parameter configurations (LFCs), are over‐conservative in the case of composite null hypotheses. As demonstrated in prior work, this poses severe challenges in the multiple testing context, especially when one goal of the statistical analysis is to estimate the proportion π0$\pi _0$ of true null hypotheses. Randomized p$p$‐values have been proposed to remedy this issue. In the present work, we discuss the application of randomized p$p$‐values in replicability analysis. In particular, we introduce a general class of statistical models for which valid, randomized p$p$‐values can be calculated easily. By means of computer simulations, we demonstrate that their usage typically leads to a much more accurate estimation of π0$\pi _0$ than the LFC‐based approach. Finally, we apply our proposed methodology to a real data example from genomics.</description><identifier>ISSN: 0323-3847</identifier><identifier>EISSN: 1521-4036</identifier><identifier>DOI: 10.1002/bimj.202000155</identifier><identifier>PMID: 33464615</identifier><language>eng</language><publisher>Germany: Wiley - VCH Verlag GmbH &amp; Co. KGaA</publisher><subject>Computer Simulation ; Genomics ; hazard ratio order ; Hypotheses ; Mathematical models ; Meta-analysis ; Models, Statistical ; Null hypothesis ; proportion of true null hypotheses ; Schweder–Spjøtvoll estimator ; Statistical analysis ; Statistical models</subject><ispartof>Biometrical journal, 2022-02, Vol.64 (2), p.384-409</ispartof><rights>2021 The Authors. published by Wiley‐VCH GmbH</rights><rights>2021 The Authors. Biometrical Journal published by Wiley-VCH GmbH.</rights><rights>2021. This article is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><orcidid>0000-0002-0979-4914 ; 0000-0003-3084-3036</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fbimj.202000155$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fbimj.202000155$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,1411,27903,27904,45553,45554</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33464615$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hoang, Anh‐Tuan</creatorcontrib><creatorcontrib>Dickhaus, Thorsten</creatorcontrib><title>Randomized p$p$‐values for multiple testing and their application in replicability analysis</title><title>Biometrical journal</title><addtitle>Biom J</addtitle><description>We are concerned with testing replicability hypotheses for many endpoints simultaneously. This constitutes a multiple test problem with composite null hypotheses. Traditional p$p$‐values, which are computed under least favorable parameter configurations (LFCs), are over‐conservative in the case of composite null hypotheses. As demonstrated in prior work, this poses severe challenges in the multiple testing context, especially when one goal of the statistical analysis is to estimate the proportion π0$\pi _0$ of true null hypotheses. Randomized p$p$‐values have been proposed to remedy this issue. In the present work, we discuss the application of randomized p$p$‐values in replicability analysis. In particular, we introduce a general class of statistical models for which valid, randomized p$p$‐values can be calculated easily. By means of computer simulations, we demonstrate that their usage typically leads to a much more accurate estimation of π0$\pi _0$ than the LFC‐based approach. Finally, we apply our proposed methodology to a real data example from genomics.</description><subject>Computer Simulation</subject><subject>Genomics</subject><subject>hazard ratio order</subject><subject>Hypotheses</subject><subject>Mathematical models</subject><subject>Meta-analysis</subject><subject>Models, Statistical</subject><subject>Null hypothesis</subject><subject>proportion of true null hypotheses</subject><subject>Schweder–Spjøtvoll estimator</subject><subject>Statistical analysis</subject><subject>Statistical models</subject><issn>0323-3847</issn><issn>1521-4036</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><sourceid>EIF</sourceid><recordid>eNpd0clOwzAQBmALgWgpXDkiS_TAJWW8ZTlCxVJUhITgiCInccCVsxAnoHDiEXhGngSXlh44WSN_Gs3Mj9AhgQkBoKeJLhYTChQAiBBbaEgEJR4H5m-jITDKPBbyYID2rF04EwGnu2jAGPe5T8QQPd3LMqsK_aEyXI_r8ffn15s0nbI4rxpcdKbVtVG4VbbV5TN2GLcvSjdY1rXRqWx1VWJd4kb9lok2uu0dk6a32u6jnVwaqw7W7wg9Xl48TK-9-d3VbHo292rCuPAiQYRKBM2BhamkXPGEcQlCkVxEOQEZsSSnmWufCJUGgjFIwzygwPMQUpaxETpZ9a2b6tUN38aFtqkyRpaq6mxMeeA2Bwi5o8f_6KLqGjevUz4NgQo_ipw6WqsuKVQW140uZNPHf4dzIFqBd21Uv_knEC9jiZexxJtY4vPZ7c2mYj-wXoG3</recordid><startdate>202202</startdate><enddate>202202</enddate><creator>Hoang, Anh‐Tuan</creator><creator>Dickhaus, Thorsten</creator><general>Wiley - VCH Verlag GmbH &amp; Co. KGaA</general><scope>24P</scope><scope>WIN</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-0979-4914</orcidid><orcidid>https://orcid.org/0000-0003-3084-3036</orcidid></search><sort><creationdate>202202</creationdate><title>Randomized p$p$‐values for multiple testing and their application in replicability analysis</title><author>Hoang, Anh‐Tuan ; Dickhaus, Thorsten</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p1345-9515eb52f038ca24e4b34a05e1f59f10a93bf2dcabb5ec75330c8f7204f80c3d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Computer Simulation</topic><topic>Genomics</topic><topic>hazard ratio order</topic><topic>Hypotheses</topic><topic>Mathematical models</topic><topic>Meta-analysis</topic><topic>Models, Statistical</topic><topic>Null hypothesis</topic><topic>proportion of true null hypotheses</topic><topic>Schweder–Spjøtvoll estimator</topic><topic>Statistical analysis</topic><topic>Statistical models</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hoang, Anh‐Tuan</creatorcontrib><creatorcontrib>Dickhaus, Thorsten</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Wiley Free Content</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Biometrical journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hoang, Anh‐Tuan</au><au>Dickhaus, Thorsten</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Randomized p$p$‐values for multiple testing and their application in replicability analysis</atitle><jtitle>Biometrical journal</jtitle><addtitle>Biom J</addtitle><date>2022-02</date><risdate>2022</risdate><volume>64</volume><issue>2</issue><spage>384</spage><epage>409</epage><pages>384-409</pages><issn>0323-3847</issn><eissn>1521-4036</eissn><abstract>We are concerned with testing replicability hypotheses for many endpoints simultaneously. This constitutes a multiple test problem with composite null hypotheses. Traditional p$p$‐values, which are computed under least favorable parameter configurations (LFCs), are over‐conservative in the case of composite null hypotheses. As demonstrated in prior work, this poses severe challenges in the multiple testing context, especially when one goal of the statistical analysis is to estimate the proportion π0$\pi _0$ of true null hypotheses. Randomized p$p$‐values have been proposed to remedy this issue. In the present work, we discuss the application of randomized p$p$‐values in replicability analysis. In particular, we introduce a general class of statistical models for which valid, randomized p$p$‐values can be calculated easily. By means of computer simulations, we demonstrate that their usage typically leads to a much more accurate estimation of π0$\pi _0$ than the LFC‐based approach. Finally, we apply our proposed methodology to a real data example from genomics.</abstract><cop>Germany</cop><pub>Wiley - VCH Verlag GmbH &amp; Co. KGaA</pub><pmid>33464615</pmid><doi>10.1002/bimj.202000155</doi><tpages>26</tpages><orcidid>https://orcid.org/0000-0002-0979-4914</orcidid><orcidid>https://orcid.org/0000-0003-3084-3036</orcidid><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 0323-3847
ispartof Biometrical journal, 2022-02, Vol.64 (2), p.384-409
issn 0323-3847
1521-4036
language eng
recordid cdi_proquest_miscellaneous_2479040084
source MEDLINE; Wiley Online Library Journals Frontfile Complete
subjects Computer Simulation
Genomics
hazard ratio order
Hypotheses
Mathematical models
Meta-analysis
Models, Statistical
Null hypothesis
proportion of true null hypotheses
Schweder–Spjøtvoll estimator
Statistical analysis
Statistical models
title Randomized p$p$‐values for multiple testing and their application in replicability analysis
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-21T14%3A39%3A50IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Randomized%20p$p$%E2%80%90values%20for%20multiple%20testing%20and%20their%20application%20in%20replicability%20analysis&rft.jtitle=Biometrical%20journal&rft.au=Hoang,%20Anh%E2%80%90Tuan&rft.date=2022-02&rft.volume=64&rft.issue=2&rft.spage=384&rft.epage=409&rft.pages=384-409&rft.issn=0323-3847&rft.eissn=1521-4036&rft_id=info:doi/10.1002/bimj.202000155&rft_dat=%3Cproquest_pubme%3E2628025699%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2628025699&rft_id=info:pmid/33464615&rfr_iscdi=true