{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T18:23:25Z","timestamp":1780338205338,"version":"3.54.1"},"reference-count":35,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2023,2,24]],"date-time":"2023-02-24T00:00:00Z","timestamp":1677196800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006209","name":"Radboud Universitair Medisch Centrum","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006209","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Prescription opioid use has increased steadily in many Western countries over the past two decades, most notably in the US, Canada, and most European countries, including the Netherlands. Especially the increasing use of prescription opioids for chronic non-cancer pain has raised concerns. Most opioids in the Netherlands are prescribed in general practices. However, little is known about variation in opioid prescribing between general practices. To better understand this, we investigated practice variation in opioid prescribing for non-cancer pain between Dutch general practices.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>Data from 2017\u20132019 of approximately 10% of all Dutch general practices was used. Each year included approximately 1000000 patients distributed over approximately 380 practices. The primary outcome was the proportion of patients with chronic (&gt;90 days) <jats:underline>high-dose<\/jats:underline> (\u226590 oral morphine equivalents) opioid prescriptions. The secondary outcome was the proportion of patients with chronic (&lt;90 oral morphine equivalents) opioid prescriptions. Practice variation was expressed as the ratio of the 95th\/5th percentiles and the ratio of mean top 10\/bottom 10. Funnel plots were used to identify outliers. Potential factors associated with unwarranted variation were investigated by comparing outliers on practice size, patient neighbourhood socioeconomic status, and urbanicity.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Results were similar across all years. The magnitude of variation for chronic <jats:underline>high-dose<\/jats:underline> opioid prescriptions in 2019 was 7.51-fold (95%\/5% ratio), and 15.1-fold (top 10\/bottom 10 ratio). The percentage of outliers in the funnel plots varied between 13.8% and 21.7%. Practices with high <jats:italic>chronic<\/jats:italic> <jats:underline><jats:italic>high-dose<\/jats:italic><\/jats:underline> <jats:italic>opioid prescription proportions<\/jats:italic> were larger, and had more patients from lower income and densely populated areas.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>There might be unwarranted practice variation in chronic <jats:underline>high-dose<\/jats:underline> opioid prescriptions in primary care, pointing at possible inappropriate use of opioids. This appears to be related to socioeconomic status, urbanicity, and practice size. Further investigation of the factors driving practice variation can provide target points for quality improvement and reduce inappropriate care and unwarranted variation.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0282222","type":"journal-article","created":{"date-parts":[[2023,2,24]],"date-time":"2023-02-24T18:47:51Z","timestamp":1677264471000},"page":"e0282222","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":9,"title":["Practice variation in opioid prescribing for non-cancer pain in Dutch primary care: A retrospective database study"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7858-7153","authenticated-orcid":true,"given":"G. A.","family":"Kalkman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Kramers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. T.","family":"van Dongen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. J.","family":"Schers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0962-2944","authenticated-orcid":true,"given":"R. L. M.","family":"van Boekel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. M.","family":"Bos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9551-1564","authenticated-orcid":true,"given":"K.","family":"Hek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. F. A.","family":"Schellekens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Atsma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,2,24]]},"reference":[{"issue":"1","key":"pone.0282222.ref001","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1097\/FTD.0000000000000789","article-title":"Is Europe Facing an Emerging Opioid Crisis Comparable to the U.S.?","volume":"43","author":"J van Amsterdam","year":"2021","journal-title":"Therapeutic Drug Monitoring."},{"issue":"8","key":"pone.0282222.ref002","doi-asserted-by":"crossref","first-page":"e1910223","DOI":"10.1001\/jamanetworkopen.2019.10223","article-title":"Opioid Prescription Patterns and Risk Factors Associated With Opioid Use in the Netherlands","volume":"2","author":"A Bedene","year":"2019","journal-title":"JAMA Netw Open"},{"issue":"10","key":"pone.0282222.ref003","doi-asserted-by":"crossref","first-page":"e498","DOI":"10.1016\/S2468-2667(19)30128-8","article-title":"Trends in use and misuse of opioids in the Netherlands: a retrospective, multi-source database study","volume":"4","author":"GA Kalkman","year":"2019","journal-title":"The Lancet Public Health"},{"issue":"26","key":"pone.0282222.ref004","doi-asserted-by":"crossref","first-page":"697","DOI":"10.15585\/mmwr.mm6626a4","article-title":"Vital Signs: Changes in Opioid Prescribing in the United States, 2006\u20132015.","volume":"66","author":"GP Guy","year":"2017","journal-title":"MMWR Morb Mortal Wkly Rep."},{"key":"pone.0282222.ref005","unstructured":"Zorginstituut Nederland. GIP databank [updated 19-04-2022; cited 2022 15 July]. Available from: https:\/\/www.gipdatabank.nl\/databank."},{"key":"pone.0282222.ref006","first-page":"D3854","article-title":"Toename in extramuraal opio\u00efdgebruik in Nederland.","volume":"163","author":"MHJ Schepens","year":"2019","journal-title":"Ned Tijdschr Geneeskd"},{"key":"pone.0282222.ref007","volume-title":"Voorschrijven van opio\u00efden in de huisartsenpraktijk","author":"Y Weesie","year":"2016"},{"issue":"23","key":"pone.0282222.ref008","doi-asserted-by":"crossref","first-page":"2448","DOI":"10.1001\/jama.2018.18472","article-title":"Opioids for chronic noncancer pain: A systematic review and meta-analysis","volume":"320","author":"JW Busse","year":"2018","journal-title":"JAMA"},{"issue":"15","key":"pone.0282222.ref009","doi-asserted-by":"crossref","first-page":"1624","DOI":"10.1001\/jama.2016.1464","article-title":"CDC Guideline for Prescribing Opioids for Chronic Pain\u2014United States, 2016","volume":"315","author":"D Dowell","year":"2016","journal-title":"JAMA"},{"issue":"3","key":"pone.0282222.ref010","doi-asserted-by":"crossref","first-page":"e190665","DOI":"10.1001\/jamanetworkopen.2019.0665","article-title":"Trends and Patterns of Geographic Variation in Opioid Prescribing Practices by State, United States, 2006\u20132017","volume":"2","author":"LZ Schieber","year":"2019","journal-title":"JAMA Netw Open"},{"issue":"2","key":"pone.0282222.ref011","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/S2215-0366(18)30471-1","article-title":"Opioid prescribing trends and geographical variation in England, 1998\u20132018: a retrospective database study","volume":"6","author":"HJ Curtis","year":"2019","journal-title":"Lancet Psychiatry"},{"issue":"7","key":"pone.0282222.ref012","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1001\/jamainternmed.2016.2737","article-title":"Hospital Prescribing of Opioids to Medicare Beneficiaries.","volume":"176","author":"AB Jena","year":"2016","journal-title":"JAMA Intern Med"},{"issue":"7","key":"pone.0282222.ref013","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1056\/NEJMsa1610524","article-title":"Opioid-Prescribing Patterns of Emergency Physicians and Risk of Long-Term Use","volume":"376","author":"ML Barnett","year":"2017","journal-title":"N Engl J Med"},{"issue":"4","key":"pone.0282222.ref014","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1093\/intqhc\/mzaa023","article-title":"Understanding unwarranted variation in clinical practice: a focus on network effects, reflective medicine and learning health systems.","volume":"32","author":"F Atsma","year":"2020","journal-title":"Int J Qual Health Care"},{"key":"pone.0282222.ref015","doi-asserted-by":"crossref","first-page":"d1513","DOI":"10.1136\/bmj.d1513","article-title":"Time to tackle unwarranted variations in practice","volume":"342","author":"JE Wennberg","year":"2011","journal-title":"BMJ"},{"issue":"12","key":"pone.0282222.ref016","doi-asserted-by":"crossref","first-page":"2205","DOI":"10.1377\/hlthaff.2013.0879","article-title":"Access, affordability, and insurance complexity are often worse in the United States compared to ten other countries.","volume":"32","author":"C Schoen","year":"2013","journal-title":"Health Aff (Millwood)."},{"issue":"5","key":"pone.0282222.ref017","doi-asserted-by":"crossref","first-page":"e153","DOI":"10.1016\/j.amepre.2018.06.008","article-title":"Opioid Prescribing by Specialty and Volume in the U.S.","volume":"55","author":"GP Guy","year":"2018","journal-title":"Am J Prev Med"},{"issue":"10","key":"pone.0282222.ref018","doi-asserted-by":"crossref","first-page":"e1003270","DOI":"10.1371\/journal.pmed.1003270","article-title":"Time trends and prescribing patterns of opioid drugs in UK primary care patients with non-cancer pain: A retrospective cohort study","volume":"17","author":"M Jani","year":"2020","journal-title":"PLOS Medicine"},{"key":"pone.0282222.ref019","first-page":"1","article-title":"Monitoring Opioids in Europe: The Need for Shared Definitions and Measuring Drivers of Opioid Use and Related Harms.","author":"GA Kalkman","year":"2022","journal-title":"Eur Addict Res."},{"key":"pone.0282222.ref020","volume-title":"NHG-Richtlijn pijn","author":"L De Jong","year":"2018"},{"key":"pone.0282222.ref021","unstructured":"Hasselaar J. Nivel Primary Care Database [updated 31-8-20221-11-2022]. Available from: https:\/\/www.nivel.nl\/en\/nivel-zorgregistraties-eerste-lijn\/nivel-primary-care-database."},{"issue":"6","key":"pone.0282222.ref022","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1007\/s10389-016-0753-4","article-title":"The historical development of the Dutch Sentinel General Practice Network from a paper-based into a digital primary care monitoring system","volume":"24","author":"C Schweikardt","year":"2016","journal-title":"Journal of Public Health"},{"key":"pone.0282222.ref023","unstructured":"World Health Organisation. Definition and general considerations 2018 [1-11-2022]. Available from: https:\/\/www.whocc.no\/ddd\/definition_and_general_considera\/."},{"key":"pone.0282222.ref024","volume-title":"ICPC, international classification of primary care","author":"H Lamberts","year":"1987"},{"issue":"6","key":"pone.0282222.ref025","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1002\/pds.3945","article-title":"A synthesis of oral morphine equivalents (OME) for opioid utilisation studies.","volume":"25","author":"S Nielsen","year":"2016","journal-title":"Pharmacoepidemiol Drug Saf"},{"issue":"3","key":"pone.0282222.ref026","doi-asserted-by":"crossref","first-page":"e11929","DOI":"10.2196\/11929","article-title":"Estimating Morbidity Rates Based on Routine Electronic Health Records in Primary Care: Observational Study.","volume":"7","author":"MMJ Nielen","year":"2019","journal-title":"JMIR Medical Informatics."},{"issue":"8","key":"pone.0282222.ref027","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1002\/sim.1970","article-title":"Funnel plots for comparing institutional performance.","volume":"24","author":"DJ Spiegelhalter","year":"2005","journal-title":"Stat Med"},{"issue":"5","key":"pone.0282222.ref028","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1136\/qshc.2005.013755","article-title":"Handling over-dispersion of performance indicators.","volume":"14","author":"DJ Spiegelhalter","year":"2005","journal-title":"Quality and Safety in Health Care"},{"key":"pone.0282222.ref029","volume-title":"R: A Language and Environment for Statistical Computing","author":"R Core Team","year":"2020"},{"key":"pone.0282222.ref030","author":"C. Mainey","year":"2020","journal-title":"FunnelPlotR: Funnel Plots for Comparing Institutional Performance"},{"issue":"3","key":"pone.0282222.ref031","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1111\/jep.13181","article-title":"Unwarranted clinical variation in health care: Definitions and proposal of an analytic framework.","volume":"26","author":"K Sutherland","year":"2020","journal-title":"J Eval Clin Pract"},{"issue":"8","key":"pone.0282222.ref032","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1002\/ejp.1409","article-title":"The European epidemic: Pain prevalence and socioeconomic inequalities in pain across 19 European countries.","volume":"23","author":"A Todd","year":"2019","journal-title":"Eur J Pain."},{"issue":"3","key":"pone.0282222.ref033","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.pain.2008.04.003","article-title":"Socioeconomic disadvantage and pain","volume":"136","author":"EL Poleshuck","year":"2008","journal-title":"Pain"},{"issue":"11","key":"pone.0282222.ref034","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1016\/j.jamda.2018.07.009","article-title":"Opioid Prescribing Behavior in Long-Term Geriatric Care in the Netherlands.","volume":"19","author":"MJM Martens","year":"2018","journal-title":"J Am Med Dir Assoc."},{"issue":"9","key":"pone.0282222.ref035","doi-asserted-by":"crossref","first-page":"e012669","DOI":"10.1136\/bmjopen-2016-012669","article-title":"Do GPs know their patients with cancer? Assessing the quality of cancer registration in Dutch primary care: a cross-sectional validation study.","volume":"6","author":"A Sollie","year":"2016","journal-title":"BMJ Open."}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0282222","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,24]],"date-time":"2023-02-24T18:48:13Z","timestamp":1677264493000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0282222"}},"subtitle":[],"editor":[{"given":"Tim","family":"Luckett","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2023,2,24]]},"references-count":35,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,2,24]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0282222","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,24]]}}}