{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T10:27:38Z","timestamp":1783938458032,"version":"3.55.0"},"reference-count":34,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,5,21]],"date-time":"2021-05-21T00:00:00Z","timestamp":1621555200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmaceutical Statistics"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In the meta\u2010analytic surrogate evaluation framework, the trial\u2010level coefficient of determination  quantifies the strength of the association between the expected causal treatment effects on the surrogate (<jats:italic>S<\/jats:italic>) and the true (<jats:italic>T<\/jats:italic>) endpoints. Burzykowski and Buyse supplemented this metric of surrogacy with the surrogate threshold effect (STE), which is defined as the minimum value of the causal treatment effect on <jats:italic>S<\/jats:italic> for which the predicted causal treatment effect on <jats:italic>T<\/jats:italic> exceeds zero. The STE supplements  with a more direct clinically interpretable metric of surrogacy. Alonso et al. proposed to evaluate surrogacy based on the strength of the association between the individual (rather than expected) causal treatment effects on <jats:italic>S<\/jats:italic> and <jats:italic>T<\/jats:italic>. In the current paper, the individual\u2010level surrogate threshold effect (ISTE) is introduced in the setting where <jats:italic>S<\/jats:italic> and <jats:italic>T<\/jats:italic> are normally distributed variables. ISTE is defined as the minimum value of the individual causal treatment effect on <jats:italic>S<\/jats:italic> for which the lower limit of the prediction interval around the individual causal treatment effect on <jats:italic>T<\/jats:italic> exceeds zero. The newly proposed methodology is applied in a case study, and it is illustrated that ISTE has an appealing clinical interpretation. The R package surrogate implements the methodology and a web appendix (supporting information) that details how the analyses can be conducted in practice is provided.<\/jats:p>","DOI":"10.1002\/pst.2141","type":"journal-article","created":{"date-parts":[[2021,5,21]],"date-time":"2021-05-21T09:10:21Z","timestamp":1621588221000},"page":"1216-1231","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The individual\u2010level surrogate threshold effect in a causal\u2010inference setting with normally distributed endpoints"],"prefix":"10.1002","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4315-7406","authenticated-orcid":false,"given":"Wim","family":"Van der Elst","sequence":"first","affiliation":[{"name":"The Janssen Pharmaceutical companies of Johnson &amp; Johnson  Beerse Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariel Alonso","family":"Abad","sequence":"additional","affiliation":[{"name":"I\u2010BioStat, KU Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Coppenolle","sequence":"additional","affiliation":[{"name":"The Janssen Pharmaceutical companies of Johnson &amp; Johnson  Beerse Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7248-4273","authenticated-orcid":false,"given":"Paul","family":"Meyvisch","sequence":"additional","affiliation":[{"name":"Galapagos NV  Mechelen Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geert","family":"Molenberghs","sequence":"additional","affiliation":[{"name":"I\u2010BioStat, KU Leuven  Leuven Belgium"},{"name":"UHasselt  Hasselt Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,5,21]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/biom.12245"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/b138566"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/pst.207"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1201\/9781315372662"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.2307\/2533853"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/biostatistics\/1.1.49"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.4780110204"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.4780080407"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1177\/1740774513479522"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1080\/19466315.2019.1575276"},{"key":"e_1_2_10_12_1","first-page":"961","article-title":"Statistics and causal inference: comment: which ifs have causal answers","volume":"81","author":"Rubin DB","year":"1986","journal-title":"J Am Stat Assoc"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/biomet\/70.1.41"},{"key":"e_1_2_10_14_1","volume-title":"Longitudinal Data Analysis","author":"Fitzmaurice G","year":"2009"},{"key":"e_1_2_10_15_1","first-page":"1","article-title":"Surrogacy assessment using principal stratification when surrogate and outcome measures are multivariate normal","volume":"14","author":"Conlon ASC","year":"2013","journal-title":"Biostatistics"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.7939"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1080\/00224065.1998.11979816"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0006-341X.2002.00021.x"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1541-0420.2008.01014.x"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.7197"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.6807"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/pst.1924"},{"key":"e_1_2_10_23_1","volume-title":"Diagnostic and Statistical Manual of Mental Diseases","author":"American Psychiatric Association","year":"2000"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.2466\/pr0.1962.10.3.799"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00421012"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.191.50.s7"},{"key":"e_1_2_10_27_1","volume-title":"Handbook of Missing Data Methodology","author":"Molenberghs G","year":"2015"},{"key":"e_1_2_10_28_1","first-page":"953","article-title":"Ignorance and uncertainty regions as inferential tools in a sensitivity analysis","volume":"16","author":"Vansteelandt S","year":"2006","journal-title":"Stat Sin"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/0315-0860(87)90065-6"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1098\/rsta.1922.0009"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1515\/em-2012-0010"},{"key":"e_1_2_10_32_1","unstructured":"Van der ElstW.Statistical Evaluation Methodology for Surrogate Endpoints in Clinical Studies. [Unpublished PhD dissertation]. 2016."},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1177\/0962280211398037"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1080\/03610919908813578"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1177\/1740774514561046"}],"container-title":["Pharmaceutical Statistics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pst.2141","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/pst.2141","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pst.2141","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T05:37:00Z","timestamp":1693201020000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pst.2141"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,21]]},"references-count":34,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2021,11]]}},"alternative-id":["10.1002\/pst.2141"],"URL":"https:\/\/doi.org\/10.1002\/pst.2141","archive":["Portico"],"relation":{},"ISSN":["1539-1604","1539-1612"],"issn-type":[{"value":"1539-1604","type":"print"},{"value":"1539-1612","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,21]]},"assertion":[{"value":"2020-03-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-21","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}