{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T10:46:16Z","timestamp":1783507576342,"version":"3.55.0"},"reference-count":26,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,2,11]],"date-time":"2023-02-11T00:00:00Z","timestamp":1676073600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012041","name":"Versus Arthritis","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012041","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacoepidemiology and Drug"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>Routinely collected prescription data provides drug exposure information for pharmacoepidemiology, informing start\/stop dates and dosage. Prescribing information includes structured data and unstructured free\u2010text instructions, which can include inherent variability, such as \u201cone to two tablets up to four times a day\u201d. Preparing drug exposure data from raw prescriptions to a research ready dataset is rarely fully reported, yet assumptions have considerable implications for pharmacoepidemiology. This may have bigger consequences for \u201cpro re nata\u201d (PRN) drugs. Our aim was, using a worked example of opioids and fracture risk, to examine the impact of incorporating narrative prescribing instructions and subsequent drug preparation assumptions on adverse event rates.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>R\u2010packages for extracting free\u2010text medication prescription instructions in a structured form (<jats:italic>doseminer<\/jats:italic>) and an algorithm for transparently processing drug exposure information (<jats:italic>drugprepr<\/jats:italic>) were developed. Clinical Practice Research Datalink GOLD was used to define a cohort of adult new opioid users without prior cancer. A retrospective cohort study was performed using data between January 1, 2017 and July 31, 2018. We tested the impact of varying drug preparation assumptions by estimating the risk of opioids on fracture risk using Cox proportional hazards models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>During the study window, 60\u2009394 patients were identified with 190\u2009754 opioid prescriptions. Free\u2010text prescribing instruction variability, where there was flexibility in the number of tablets to be administered, was present in 42% prescriptions. Variations in the decisions made during preparing raw data for analysis led to marked differences impacting the event number (<jats:italic>n<\/jats:italic>\u00a0=\u2009303\u2013415) and person years of drug exposure (5619\u20139832). The distribution of hazard ratios as a function of the decisions ranged from 2.71 (95% CI: 2.31, 3.18) to 3.24 (2.76, 3.82).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Assumptions made during the drug preparation process, especially for those with variability in prescription instructions, can impact results of subsequent risk estimates. The developed R packages can improve transparency related to drug preparation assumptions, in line with best practice advocated by international pharmacoepidemiology guidelines.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pds.5595","type":"journal-article","created":{"date-parts":[[2023,1,31]],"date-time":"2023-01-31T08:10:29Z","timestamp":1675152629000},"page":"651-660","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["\u201cTake up to eight tablets per day\u201d: Incorporating free\u2010text medication instructions into a transparent and reproducible process for preparing drug exposure data for pharmacoepidemiology"],"prefix":"10.1002","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1487-277X","authenticated-orcid":false,"given":"Meghna","family":"Jani","sequence":"first","affiliation":[{"name":"Centre for Epidemiology Versus Arthritis Centre for Musculoskeletal Research, The University of Manchester Manchester UK"},{"name":"NIHR Manchester Biomedical Research Centre Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre Manchester UK"},{"name":"Salford Royal Hospital Northern Care Alliance NHS Foundation Trust Salford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8621-6539","authenticated-orcid":false,"given":"Belay Birlie","family":"Yimer","sequence":"additional","affiliation":[{"name":"Centre for Epidemiology Versus Arthritis Centre for Musculoskeletal Research, The University of Manchester Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8026-5663","authenticated-orcid":false,"given":"David","family":"Selby","sequence":"additional","affiliation":[{"name":"Centre for Epidemiology Versus Arthritis Centre for Musculoskeletal Research, The University of Manchester Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2391-5575","authenticated-orcid":false,"given":"Mark","family":"Lunt","sequence":"additional","affiliation":[{"name":"Centre for Epidemiology Versus Arthritis Centre for Musculoskeletal Research, The University of Manchester Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0795-5363","authenticated-orcid":false,"given":"Goran","family":"Nenadic","sequence":"additional","affiliation":[{"name":"Department of Computer Science University of Manchester Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5881-4857","authenticated-orcid":false,"given":"William G.","family":"Dixon","sequence":"additional","affiliation":[{"name":"Centre for Epidemiology Versus Arthritis Centre for Musculoskeletal Research, The University of Manchester Manchester UK"},{"name":"NIHR Manchester Biomedical Research Centre Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre Manchester UK"},{"name":"Salford Royal Hospital Northern Care Alliance NHS Foundation Trust Salford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,2,11]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1001885"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12913\u2010016\u20101562\u20108"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.c5475"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.k3532"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen\u20102017\u2010017989"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/PDS.5346"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/S40264\u2010014\u20100214\u20103"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/pds.4440"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11606\u2010009\u20101218\u2010z"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgs.12148"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12911\u2010016\u20100255\u2010x"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/pds.5331"},{"key":"e_1_2_12_14_1","doi-asserted-by":"crossref","unstructured":"SelbyD YimerB MarwickB.Extract drug dosages from free\u2010text prescriptions. R Package Version 0.1.2. (2021).https:\/\/cran.r-project.org\/web\/packages\/doseminer\/index.html","DOI":"10.32614\/CRAN.package.doseminer"},{"key":"e_1_2_12_15_1","unstructured":"SelbyDA YimerBB.Pharmacoepidemiology with doseminer(2021).https:\/\/cran.r-project.org\/web\/packages\/doseminer\/vignettes\/case_study.html"},{"key":"e_1_2_12_16_1","doi-asserted-by":"crossref","unstructured":"YimerBB SelbyD JaniM NenadicG LuntM DixonW.drugprepr: Prepare Electronic Prescription Record Data to Estimate Drug Exposure. R package version 0.0.4. (2021).https:\/\/CRAN.R-project.org\/package=drugprepr","DOI":"10.32614\/CRAN.package.drugprepr"},{"key":"e_1_2_12_17_1","unstructured":"YimerBB SelbyD JaniM NenadicG LuntM DixonWG.Introduction to Drugprepr(2021).https:\/\/cran.r-project.org\/web\/packages\/drugprepr\/vignettes\/introduction.pdf"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1003270"},{"key":"e_1_2_12_19_1","first-page":"826","article-title":"Trends in high\u2010dose opioid prescribing in Canada","volume":"60","author":"Gomes T","year":"2014","journal-title":"Can Fam Physician"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1003829"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.39422"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1532\u20105415.2011.03318.x"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwt013"},{"key":"e_1_2_12_24_1","unstructured":"Github link for codelists and R scripts.2022.https:\/\/github.com\/belayb\/drug_prep_manuscript"},{"key":"e_1_2_12_25_1","unstructured":"European Medicines Agency.Assessment report for non\u2010steroidal anti\u2010inflammatory drugs (NSAIDs) and cardiovascular risk. Accessed May 15 2022.http:\/\/www.ema.europa.eu\/docs\/en_GB\/document_library\/Other\/2010\/01\/WC500054342.pdf"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/pds.5372"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/PDS.4372"}],"container-title":["Pharmacoepidemiology and Drug Safety"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pds.5595","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/pds.5595","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pds.5595","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,13]],"date-time":"2024-10-13T09:25:54Z","timestamp":1728811554000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pds.5595"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,11]]},"references-count":26,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2023,6]]}},"alternative-id":["10.1002\/pds.5595"],"URL":"https:\/\/doi.org\/10.1002\/pds.5595","archive":["Portico"],"relation":{},"ISSN":["1053-8569","1099-1557"],"issn-type":[{"value":"1053-8569","type":"print"},{"value":"1099-1557","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,11]]},"assertion":[{"value":"2022-07-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-01-25","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-02-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}