{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T16:26:51Z","timestamp":1791563211966,"version":"4.3.4"},"reference-count":34,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T00:00:00Z","timestamp":1736812800000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacoepidemiology and Drug"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Masking is a reporting bias where drug safety signals are muffled by elevated reporting of other medications in spontaneous reporting databases. While the impact of masking is often limited, its effect when using restricted designs, such as active comparators, can be consequential.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We used data from the US Food and Drugs Administration Adverse Event Reporting System (1999Q3\u20102013Q3) to study masking in a real\u2010world example. Rosiglitazone, a thiazolidinedione with elevated reporting after safety concerns over cardiovascular risks, was the masking candidate. We hypothesized that stimulated reporting masked signals for another thiazolidinedione, pioglitazone. We computed estimates of proportional reporting ratios and information components, using the Bayesian confidence propagation neural network, for pioglitazone\u2010myocardial infarction and pioglitazone\u2010cardiac failure under unrestricted and active comparator designs, with and without the mask, before (1999Q3\u20102007Q1) and after (2007Q2\u20102013Q3) safety concerns. Relative change\u2010in\u2010estimates were computed to compare results with and without rosiglitazone.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>From 1999Q3\u20102007Q1, relative change\u2010in\u2010estimates of proportional reporting ratio for pioglitazone\u2010myocardial infarction was 0.00 in unrestricted design and 0.10 in active comparator, and for pioglitazone\u2010cardiac failure, the change was 0.01 and 0.62, respectively. From 2007Q2\u20102013Q3, relative change\u2010in\u2010estimates for pioglitazone\u2010myocardial infarction was 0.41 in unrestricted design and 18.00 in active comparator; the change for pioglitazone\u2010cardiac failure was 0.04 and 1.03, respectively. Relative changes in estimates of information component mirrored these trends.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Masking can influence signal detection in active comparator designs where external events impact reporting rates in reference sets. Evaluating masking in related contexts is essential for drug safety monitoring and resource allocation for follow\u2010up studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pds.70102","type":"journal-article","created":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T01:59:57Z","timestamp":1736906397000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Masking in Active Comparator Designs in Pharmacovigilance: A Retrospective Bias Analysis on the Spontaneous Reporting of Thiazolidinediones and Cardiovascular Events"],"prefix":"10.1002","volume":"34","author":[{"given":"William","family":"Bai","sequence":"first","affiliation":[{"name":"School of Epidemiology and Public Health University of Ottawa  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6005-4006","authenticated-orcid":false,"given":"Antonios","family":"Douros","sequence":"additional","affiliation":[{"name":"School of Epidemiology and Public Health University of Ottawa  Ottawa Ontario Canada"},{"name":"Department of Epidemiology, Biostatistics and Occupational Health McGill University  Montreal Quebec Canada"},{"name":"Institute of Clinical Pharmacology and Toxicology Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher A.","family":"Gravel","sequence":"additional","affiliation":[{"name":"School of Epidemiology and Public Health University of Ottawa  Ottawa Ontario Canada"},{"name":"Department of Epidemiology, Biostatistics and Occupational Health McGill University  Montreal Quebec Canada"},{"name":"Department of Mathematics and Statistics University of Ottawa  Ottawa Ontario 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Working Group \u201cPractical Aspects of Signal Detection in Pharmacovigilance \u201dCIOMS (2010) https:\/\/cioms.ch\/publications\/product\/practical\u2010aspects\u2010of\u2010signal\u2010detection\u2010in\u2010pharmacovigilance\u2010report\u2010of\u2010cioms\u2010working\u2010group\u2010viii\/."},{"key":"e_1_2_11_18_1","unstructured":"Food and Drugs Administration \u201cDrug Approval Package: Avandia (Rosiglitazone Maleate) Tablets \u201daccessed July 29 2024 https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/99\/21071_avandia.cfm."},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.3233\/JRS\u20102012\u20100559"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa072761"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1080\/10408444.2017.1351420"},{"key":"e_1_2_11_22_1","unstructured":"Center for Drug Evaluation \u201cFDA Adverse Event Reporting System (FAERS) Public Dashboard.\u201dFDA. accessed July 20 2024 https:\/\/www.fda.gov\/drugs\/questions\u2010and\u2010answers\u2010fdas\u2010adverse\u2010event\u2010reporting\u2010system\u2010faers\/fda\u2010adverse\u2010event\u2010reporting\u2010system\u2010faers\u2010public\u2010dashboard."},{"key":"e_1_2_11_23_1","unstructured":"International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) \u201cMedical Dictionary for Regulatory Activities \u201daccessed July 29 2024 https:\/\/www.meddra.org\/."},{"key":"e_1_2_11_24_1","unstructured":"Food and Drugs Administration \u201cFDA Drug Safety Communication: FDA Requires Removal of Some Prescribing and Dispensing Restrictions for Rosiglitazone\u2010Containing Diabetes Medicines.\u201d"},{"key":"e_1_2_11_25_1","unstructured":"Food and Drugs Administration \u201cFDA Drug Safety Communication: Update to Ongoing Safety Review of Actos (Pioglitazone) and Increased Risk of Bladder Cancer \u201daccessed July 29 2024 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