{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T03:05:24Z","timestamp":1789700724328,"version":"4.0.1"},"reference-count":16,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CPT Pharmacom &amp; Syst Pharma"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Exposure\u2010response (ER) analyses assessing the efficacy of large molecule therapeutics are often susceptible to confounding, where associations between drug exposure and patient disease severity can obscure true ER signals and complicate dose selection. To better understand the pharmaceutical industry perspectives on this challenge, the IQ consortium conducted a comprehensive survey targeting clinical pharmacologists, pharmacometricians, and statisticians. The survey, completed by 125 individuals from 23 pharmaceutical companies, aimed to assess awareness, perceived prevalence, mitigation strategies, and the overall role of ER analyses in the context of confounding. Results revealed strong industry awareness, with 88.0% of respondents acknowledging the relevance of ER confounding. However, uncertainty regarding its pervasiveness persists, particularly in non\u2010oncology settings (31.2% unsure). A consensus emerged on the value of dose\u2010ranging study designs as an effective mitigation strategy (81.6% agreement). In contrast, the use of advanced statistical methods for causal inference is inconsistent (45.6% usage), and confidence in their reliability is mixed, with 32.8% of respondents expressing uncertainty and most others rating them only moderate or somewhat reliable. While the majority agreed that confounded ER analyses should be interpreted with caution (79.2%), opinions diverged regarding their value in decision\u2010making when dose\u2010ranging data is insufficient. This uncertainty, coupled with a recognized need for additional alignment with health authorities, led to a call for best\u2010practice guidance (92.8% view as valuable). Overall, the survey findings highlight a need for an industry\u2010wide common approach and the development of clear frameworks to manage and interpret ER confounding for large molecule therapeutics.<\/jats:p>","DOI":"10.1002\/psp4.70318","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T05:37:28Z","timestamp":1788500248000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pharmaceutical Industry Perspectives on Exposure\u2010Response Confounding in Large Molecule Therapeutics: Results From an\n                    <scp>IQ<\/scp>\n                    Consortium Survey"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7009-3666","authenticated-orcid":false,"given":"Engie","family":"Salama","sequence":"first","affiliation":[{"name":"Clinical Pharmacology &amp; Pharmacometrics Xencor  Pasadena California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1480-0792","authenticated-orcid":false,"given":"Manisha","family":"Lamba","sequence":"additional","affiliation":[{"name":"Pharmacometrics &amp; Systems Pharmacology Pfizer  Pearl River New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9794-8601","authenticated-orcid":false,"given":"Sihem","family":"Ait\u2010Oudhia","sequence":"additional","affiliation":[{"name":"Quantitative Pharmacology and Pharmacometrics Merck &amp; Co, Inc.  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