{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T11:46:57Z","timestamp":1785930417154,"version":"3.56.0"},"reference-count":21,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Therapeutic Advances in Drug Safety"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>The FDA\u2019s Guidance for an industry evaluating drug effects on the ability to operate a motor vehicle describes the need to evaluate drug-induced neurobehavioral impairment. However, the guidance does not provide instruction or the means to implement the analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>The proposed Construct provides a means to operationalize the evaluation of adverse event datasets for this disorder.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design:<\/jats:title>\n                    <jats:p>A noninterventional pharmacoepidemiologic methods development study using routinely collected health data.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Preferred terms for the Construct were derived by mapping the domains of concern cited by the Guidance to the corresponding MedDRA terms. Additional terms were derived from the MedDRA preferred terms cited in the warning section of labels from drugs with a warning about driving or operating machinery. The performance of the Construct was evaluated by comparing adverse events for the FDA Adverse Event Reporting System (FAERS) database for drugs considered to be of high risk versus low risk for this condition using descriptive statistics and a nonparametric test.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      A Construct of PTs (neurobehavioral impairment term list; NITL) was obtained after identification of 55 drugs with the Warning in their FDA-approved label for driving or operating machinery based on drug-induced neurobehavioral impairment. Additional terms not covered in the labels were derived from the five domains of interest cited in the Guidance for a total of 52 PTs. Comparison of the difference in the proportion of FAERS reports with the NITL terms in drugs with and without the relevant labeling was nominally significant (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009&lt;\u20090.0001; Kruskal\u2013Wallis ChiSquare approximation).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>A MedDRA-based Construct was generated for the selection of adverse events related to drug-induced neurobehavioral impairment. The Construct discriminated high- from low-risk drugs based on publicly available adverse event profiles. Further evaluation with clinical trial data will be needed to facilitate its use for signal detection in safety analysis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/20420986261472321","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T08:56:48Z","timestamp":1785747408000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Development and validation of a MedDRA-based signal detection construct for drug-induced neurobehavioral impairment"],"prefix":"10.1177","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8874-3401","authenticated-orcid":false,"given":"Christopher D.","family":"Breder","sequence":"first","affiliation":[{"name":"CIRCA-PHD LLC, Bethesda, MD 20817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,8,3]]},"reference":[{"key":"e_1_3_4_2_2","unstructured":"National Library of Medicine. ClinicalTrials.Gov. https:\/\/clinicaltrials.gov\/ (2025 accessed 1 October 2025)."},{"key":"e_1_3_4_3_2","unstructured":"United States Food and Drug Administration. Evaluating drug effects on the ability to operate a motor vehicle guidance for industry. Silver Spring https:\/\/www.fda.gov\/Drugs\/GuidanceComplianceRegulatoryInformation\/Guidances\/default.htm (November 2017)."},{"key":"e_1_3_4_4_2","unstructured":"United States Food and Drug Administration. Consult Memorandum. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2015\/022526Orig1s000OtherR.pdf."},{"key":"e_1_3_4_5_2","unstructured":"Introductory Guide for Standardised MedDRA Queries (SMQs) Version 28.0 Introductory Guide for Standardised MedDRA Queries (SMQs). 2025."},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.k3532"},{"key":"e_1_3_4_7_2","unstructured":"MedDRA Maintenance and Support Services Organization. MedDRA Browsers. MedDRA Medical Dictionary for Regulatory Activities https:\/\/www.meddra.org\/browsers (2025 accessed 29 November 2025)."},{"key":"e_1_3_4_8_2","unstructured":"MedDRA Maintenance and Support Services Organization. MedDRA Hierarchy. Medical Dictionary for Regulatory Activities https:\/\/www.meddra.org\/how-to-use\/basics\/hierarchy (2025 accessed 29 November 2025)."},{"key":"e_1_3_4_9_2","unstructured":"NCTR Bioinformatics. FDALabel Version 2.9 https:\/\/nctr-crs.fda.gov\/fdalabel\/ui\/search (2025 accessed 29 November 2025)."},{"key":"e_1_3_4_10_2","unstructured":"United States Food and Drug Administration. Drugs@FDA https:\/\/www.accessdata.fda.gov\/scripts\/cder\/daf\/ (2025 accessed 11 May 2025)."},{"key":"e_1_3_4_11_2","unstructured":"United States Food and Drug Administration. FDA Adverse Event Reporting System Database. https:\/\/fis.fda.gov\/sense\/app\/95239e26-e0be-42d9-a960-9a5f7f1c25ee\/sheet\/7a47a261-d58b-4203-a8aa-6d3021737452\/state\/analysis."},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40290-016-0136-8"},{"key":"e_1_3_4_13_2","unstructured":"SAS. JMP https:\/\/www.jmp.com\/en\/home (2025 accessed 30 September 2025)."},{"key":"e_1_3_4_14_2","unstructured":"Altasciences. Studying the effects of drugs on driving. Clinical Leader https:\/\/www.clinicalleader.com\/doc\/studying-the-effects-of-drugs-on-driving-0001 (2025 Accessed 11 May 2025)."},{"key":"e_1_3_4_15_2","article-title":"To judge sleep aids, U.S. looks at drowsy driving in the morning","author":"Thomas K.","year":"2013","unstructured":"Thomas K. To judge sleep aids, U.S. looks at drowsy driving in the morning. New York Times, 13 August 2013.","journal-title":"New York Times"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2013.02.004"},{"key":"e_1_3_4_17_2","unstructured":"CIOMS-MedDRA RedBook_ republished https:\/\/cioms.ch\/publications\/product\/council-for-international-organizations-of-medical-sciences-cioms\/ (2025 accessed 2 August 2025)."},{"key":"e_1_3_4_18_2","first-page":"882","article-title":"Evaluation of automated term groupings for detecting anaphylactic shock signals for drugs","volume":"2012","author":"Souvignet J","year":"2012","unstructured":"Souvignet J, Declerck G, Trombert B, et al. Evaluation of automated term groupings for detecting anaphylactic shock signals for drugs. AMIA Annu Symp Proc 2012; 2012: 882\u2013890.","journal-title":"AMIA Annu Symp Proc"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.2165\/00002018-200326030-00002"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.2165\/00002018-200528110-00002"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/sdata.2014.43"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2012.50"}],"container-title":["Therapeutic Advances in Drug Safety"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/20420986261472321","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/20420986261472321","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/20420986261472321","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T11:18:54Z","timestamp":1785928734000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/20420986261472321"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8]]},"references-count":21,"alternative-id":["10.1177\/20420986261472321"],"URL":"https:\/\/doi.org\/10.1177\/20420986261472321","relation":{},"ISSN":["2042-0986","2042-0994"],"issn-type":[{"value":"2042-0986","type":"print"},{"value":"2042-0994","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8]]},"article-number":"20420986261472321"}}