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  <front>
    <journal-meta>
      <journal-id journal-id-type="publisher-id">JPH</journal-id>
      <journal-id journal-id-type="nlm-ta">JMIR Public Health Surveill</journal-id>
      <journal-title>JMIR Public Health and Surveillance</journal-title>
      <issn pub-type="epub">2369-2960</issn>
      <publisher>
        <publisher-name>JMIR Publications</publisher-name>
        <publisher-loc>Toronto, Canada</publisher-loc>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id">v10i1e51323</article-id>
      <article-id pub-id-type="pmid">38838327</article-id>
      <article-id pub-id-type="doi">10.2196/51323</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Original Paper</subject>
        </subj-group>
        <subj-group subj-group-type="article-type">
          <subject>Original Paper</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Data-Driven Identification of Potentially Successful Intervention Implementations Using 5 Years of Opioid Prescribing Data: Retrospective Database Study</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="editor">
          <name>
            <surname>Mavragani</surname>
            <given-names>Amaryllis</given-names>
          </name>
        </contrib>
        <contrib contrib-type="editor">
          <name>
            <surname>Sanchez</surname>
            <given-names>Travis</given-names>
          </name>
        </contrib>
      </contrib-group>
      <contrib-group>
        <contrib contrib-type="reviewer">
          <name>
            <surname>Tolley</surname>
            <given-names>Clare</given-names>
          </name>
        </contrib>
        <contrib contrib-type="reviewer">
          <name>
            <surname>Leitch</surname>
            <given-names>Sharon</given-names>
          </name>
        </contrib>
      </contrib-group>
      <contrib-group>
        <contrib id="contrib1" contrib-type="author">
          <name name-style="western">
            <surname>Hopcroft</surname>
            <given-names>Lisa EM</given-names>
          </name>
          <degrees>PhD</degrees>
          <xref rid="aff1" ref-type="aff">1</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0002-7022-1322</ext-link>
        </contrib>
        <contrib id="contrib2" contrib-type="author">
          <name name-style="western">
            <surname>Curtis</surname>
            <given-names>Helen J</given-names>
          </name>
          <degrees>DPhil</degrees>
          <xref rid="aff1" ref-type="aff">1</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0003-3429-9576</ext-link>
        </contrib>
        <contrib id="contrib3" contrib-type="author">
          <name name-style="western">
            <surname>Croker</surname>
            <given-names>Richard</given-names>
          </name>
          <degrees>MSc</degrees>
          <xref rid="aff1" ref-type="aff">1</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0002-8114-9186</ext-link>
        </contrib>
        <contrib id="contrib4" contrib-type="author">
          <name name-style="western">
            <surname>Pretis</surname>
            <given-names>Felix</given-names>
          </name>
          <degrees>DPhil</degrees>
          <xref rid="aff2" ref-type="aff">2</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0003-1435-9295</ext-link>
        </contrib>
        <contrib id="contrib5" contrib-type="author">
          <name name-style="western">
            <surname>Inglesby</surname>
            <given-names>Peter</given-names>
          </name>
          <degrees>MPhil</degrees>
          <xref rid="aff1" ref-type="aff">1</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0002-7784-1719</ext-link>
        </contrib>
        <contrib id="contrib6" contrib-type="author">
          <name name-style="western">
            <surname>Evans</surname>
            <given-names>David</given-names>
          </name>
          <degrees>MPhil</degrees>
          <xref rid="aff1" ref-type="aff">1</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0002-1100-079X</ext-link>
        </contrib>
        <contrib id="contrib7" contrib-type="author">
          <name name-style="western">
            <surname>Bacon</surname>
            <given-names>Sebastian</given-names>
          </name>
          <degrees>BA</degrees>
          <xref rid="aff1" ref-type="aff">1</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0002-6354-3454</ext-link>
        </contrib>
        <contrib id="contrib8" contrib-type="author">
          <name name-style="western">
            <surname>Goldacre</surname>
            <given-names>Ben</given-names>
          </name>
          <degrees>MRCPsych</degrees>
          <xref rid="aff1" ref-type="aff">1</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0002-5127-4728</ext-link>
        </contrib>
        <contrib id="contrib9" contrib-type="author" corresp="yes">
          <name name-style="western">
            <surname>Walker</surname>
            <given-names>Alex J</given-names>
          </name>
          <degrees>PhD</degrees>
          <xref rid="aff1" ref-type="aff">1</xref>
          <address>
            <institution>Nuffield Department of Primary Care Health Sciences</institution>
            <institution>University of Oxford</institution>
            <addr-line>Radcliffe Primary Care Building</addr-line>
            <addr-line>Observatory Quarter</addr-line>
            <addr-line>Oxford, OX2 6GG</addr-line>
            <country>United Kingdom</country>
            <phone>44 01865289313</phone>
            <email>alex.walker@phc.ox.ac.uk</email>
          </address>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0003-4932-6135</ext-link>
        </contrib>
        <contrib id="contrib10" contrib-type="author">
          <name name-style="western">
            <surname>MacKenna</surname>
            <given-names>Brian</given-names>
          </name>
          <degrees>MPharm</degrees>
          <xref rid="aff1" ref-type="aff">1</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0002-3786-9063</ext-link>
        </contrib>
      </contrib-group>
      <aff id="aff1">
        <label>1</label>
        <institution>Nuffield Department of Primary Care Health Sciences</institution>
        <institution>University of Oxford</institution>
        <addr-line>Oxford</addr-line>
        <country>United Kingdom</country>
      </aff>
      <aff id="aff2">
        <label>2</label>
        <institution>Department of Economics</institution>
        <institution>University of Victoria</institution>
        <addr-line>Victoria, BC</addr-line>
        <country>Canada</country>
      </aff>
      <author-notes>
        <corresp>Corresponding Author: Alex J Walker <email>alex.walker@phc.ox.ac.uk</email></corresp>
      </author-notes>
      <pub-date pub-type="collection">
        <year>2024</year>
      </pub-date>
      <pub-date pub-type="epub">
        <day>5</day>
        <month>6</month>
        <year>2024</year>
      </pub-date>
      <volume>10</volume>
      <elocation-id>e51323</elocation-id>
      <history>
        <date date-type="received">
          <day>31</day>
          <month>7</month>
          <year>2023</year>
        </date>
        <date date-type="rev-request">
          <day>7</day>
          <month>11</month>
          <year>2023</year>
        </date>
        <date date-type="rev-recd">
          <day>23</day>
          <month>11</month>
          <year>2023</year>
        </date>
        <date date-type="accepted">
          <day>12</day>
          <month>2</month>
          <year>2024</year>
        </date>
      </history>
      <copyright-statement>©Lisa EM Hopcroft, Helen J Curtis, Richard Croker, Felix Pretis, Peter Inglesby, David Evans, Sebastian Bacon, Ben Goldacre, Alex J Walker, Brian MacKenna. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 05.06.2024.</copyright-statement>
      <copyright-year>2024</copyright-year>
      <license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/">
        <p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in JMIR Public Health and Surveillance, is properly cited. The complete bibliographic information, a link to the original publication on https://publichealth.jmir.org, as well as this copyright and license information must be included.</p>
      </license>
      <self-uri xlink:href="https://publichealth.jmir.org/2024/1/e51323" xlink:type="simple"/>
      <abstract>
        <sec sec-type="background">
          <title>Background</title>
          <p>We have previously demonstrated that opioid prescribing increased by 127% between 1998 and 2016. New policies aimed at tackling this increasing trend have been recommended by public health bodies, and there is some evidence that progress is being made.</p>
        </sec>
        <sec sec-type="objective">
          <title>Objective</title>
          <p>We sought to extend our previous work and develop a data-driven approach to identify general practices and clinical commissioning groups (CCGs) whose prescribing data suggest that interventions to reduce the prescribing of opioids may have been successfully implemented.</p>
        </sec>
        <sec sec-type="methods">
          <title>Methods</title>
          <p>We analyzed 5 years of prescribing data (December 2014 to November 2019) for 3 opioid prescribing measures—total opioid prescribing as oral morphine equivalent per 1000 registered population, the number of high-dose opioids prescribed per 1000 registered population, and the number of high-dose opioids as a percentage of total opioids prescribed. Using a data-driven approach, we applied a modified version of our change detection Python library to identify reductions in these measures over time, which may be consistent with the successful implementation of an intervention to reduce opioid prescribing. This analysis was carried out for general practices and CCGs, and organizations were ranked according to the change in prescribing rate.</p>
        </sec>
        <sec sec-type="results">
          <title>Results</title>
          <p>We identified a reduction in total opioid prescribing in 94 (49.2%) out of 191 CCGs, with a median reduction of 15.1 (IQR 11.8-18.7; range 9.0-32.8) in total oral morphine equivalence per 1000 patients. We present data for the 3 CCGs and practices demonstrating the biggest reduction in opioid prescribing for each of the 3 opioid prescribing measures. We observed a 40% proportional drop (8.9% absolute reduction) in the regular prescribing of high-dose opioids (measured as a percentage of regular opioids) in the highest-ranked CCG (North Tyneside); a 99% drop in this same measure was found in several practices (44%-95% absolute reduction). Decile plots demonstrate that CCGs exhibiting large reductions in opioid prescribing do so via slow and gradual reductions over a long period of time (typically over a period of 2 years); in contrast, practices exhibiting large reductions do so rapidly over a much shorter period of time.</p>
        </sec>
        <sec sec-type="conclusions">
          <title>Conclusions</title>
          <p>By applying 1 of our existing analysis tools to a national data set, we were able to identify rapid and maintained changes in opioid prescribing within practices and CCGs and rank organizations by the magnitude of reduction. Highly ranked organizations are candidates for further qualitative research into intervention design and implementation.</p>
        </sec>
      </abstract>
      <kwd-group>
        <kwd>electronic health records</kwd>
        <kwd>primary care</kwd>
        <kwd>general practice</kwd>
        <kwd>opioid analgesics</kwd>
        <kwd>data science</kwd>
        <kwd>implementation science</kwd>
        <kwd>data-driven</kwd>
        <kwd>identification</kwd>
        <kwd>intervention</kwd>
        <kwd>implementations</kwd>
        <kwd>proof of concept</kwd>
        <kwd>opioid</kwd>
        <kwd>unbiased</kwd>
        <kwd>prescribing data</kwd>
        <kwd>analysis tool</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec sec-type="introduction">
      <title>Introduction</title>
      <p>The prescription of opioids is common and appropriate in the management of acute pain, but their efficacy with regards to chronic pain is not supported by empirical evidence [<xref ref-type="bibr" rid="ref1">1</xref>], and there is a global problem with opioid overuse [<xref ref-type="bibr" rid="ref2">2</xref>]. Long-term use of opioids has been shown to be associated with the accumulating risk of dependence and overdose [<xref ref-type="bibr" rid="ref3">3</xref>]. The continually rising rates of opioid prescription, particularly in England and Wales [<xref ref-type="bibr" rid="ref4">4</xref>-<xref ref-type="bibr" rid="ref6">6</xref>], prompted the publication of new guidance in 2010 [<xref ref-type="bibr" rid="ref7">7</xref>] advocating for a cautious approach in the long-term prescribing of opioids [<xref ref-type="bibr" rid="ref8">8</xref>], and opioids have been a specific priority for governmental advisory groups [<xref ref-type="bibr" rid="ref9">9</xref>]. In 2019, Public Health England (PHE) published the <italic>Prescribed Medicines Review</italic>, which aimed to “identify the scale, distribution and causes of prescription drug dependence, and what might be done to address it” [<xref ref-type="bibr" rid="ref10">10</xref>]. This review included data from the National Health Service Business Services Authority (NHSBSA) primary care prescription data set, which suggested that some progress had been made in reducing opioid prescribing, with a small but consistent fall in rates between 2015 and 2018. However, there was also evidence that opioid prescribing remains a persistent public health problem in England, with higher rates of prescription in areas of higher deprivation and evidence that long-term prescribing was associated with opioid overdose and dependence. The first recommendation of this report was “increasing the availability and use of data on the prescribing of medicines that can cause dependence or withdrawal to support greater transparency and accountability and help ensure practice is consistent and in line with guidance” [<xref ref-type="bibr" rid="ref10">10</xref>].</p>
      <p>Our group produces OpenPrescribing [<xref ref-type="bibr" rid="ref11">11</xref>], which allows open access to the same NHSBSA primary care prescription data set used in the PHE review. It is a free and widely used tool with 20,000 unique users per month, where anyone can explore the prescriptions dispensed at any practice in England and monitor prescribing patterns down to the level of individual brands, formulations, and doses.</p>
      <p>In OpenPrescribing, we perform automated analyses to generate monthly reports covering 80 measures of prescribing safety, effectiveness, and cost. Our analyses included all general practices (GPs) and their regional organizations, which were known as clinical commissioning groups (CCGs) at the time of this study. Several measures have been developed to capture trends and variations in opioid prescribing [<xref ref-type="bibr" rid="ref12">12</xref>]. This window into national opioid prescribing data presents an opportunity to identify changes—both increases and decreases—in prescribing that could inform National Health Service (NHS) decision-making and policy.</p>
      <p>It is our experience that the best practice is typically defined by organizations identifying themselves as having improved, following the implementation and internal assessment of interventions. We are seeking to pursue an alternative, data-driven, and unbiased approach that instead exploits the national prescribing data set to identify prescribing patterns that may be representative of best practice (ie, where we can identify a significant reduction in opioid prescribing).</p>
      <p>We set out to apply our change detection algorithm [<xref ref-type="bibr" rid="ref13">13</xref>] to identify patterns indicative of maintained and significant reduction that may help identify best practices with regard to opioid prescribing policy.</p>
    </sec>
    <sec sec-type="methods">
      <title>Methods</title>
      <sec>
        <title>Study Design</title>
        <p>We conducted a retrospective database study using GP primary care electronic health record data from all GPs in England.</p>
      </sec>
      <sec>
        <title>Data Source</title>
        <p>We extracted data from the OpenPrescribing database. This imports openly accessible prescribing data from the large monthly files published by the NHSBSA, which contain data on cost and items prescribed for each month, for every typical GP and CCG in England since mid-2010 [<xref ref-type="bibr" rid="ref14">14</xref>]. We extracted data up to November 2019. We note that CCGs were replaced by integrated care boards as of July 1, 2022. We have retained results by CCGs as this was an active administrative unit of the NHS in England during the study period. The monthly prescribing data sets contain 1 row for each different medication and dose, in each prescribing organization in NHS primary care in England, describing the number of items (ie, prescriptions issued) and the total cost. These data are sourced from community pharmacy claims data and, therefore, contain all items that were dispensed. We extracted all available data for typical GPs, excluding other organizations such as prisons and hospitals, according to the NHS Digital data set of practice characteristics [<xref ref-type="bibr" rid="ref15">15</xref>]. The numbers of patients registered at each practice were obtained from NHS Digital [<xref ref-type="bibr" rid="ref15">15</xref>].</p>
      </sec>
      <sec>
        <title>Study Measures</title>
        <p>A total of 3 measures were used in this study to capture various aspects of opioid prescribing. The first (“total oral morphine equivalence per 1000 patients”) expresses the oral morphine equivalence (OME) of all opioid prescriptions per 1000 patients [<xref ref-type="bibr" rid="ref16">16</xref>]. The second and third look to capture information about regularly prescribed opioids— those used on a regular basis to control pain rather than preparations used for breakthrough pain or opioid injections. Of the regularly prescribed opioids, high-dose opioids were defined as those with ≥120 mg OME per day [<xref ref-type="bibr" rid="ref8">8</xref>]. The “high dose opioids as percentage regular opioids” measure captures the number of prescriptions of these high-dose, regularly prescribed opioids as a percentage of all long-acting opioids [<xref ref-type="bibr" rid="ref17">17</xref>]; the “high dose opioid items per 1000 patients” measure captures the same number of high-dose, long-acting opioids but expresses this per 1000 patients [<xref ref-type="bibr" rid="ref18">18</xref>]. For all measures, higher values represent higher rates of opioid prescription.</p>
        <p>In England, an individual will be registered at 1 GP or practice; and each practice belonged, at the time of analysis, to a regional CCG that can influence their prescribing. These organizations and their membership can change over time (eg, a practice may be reassigned to a different CCG, a CCG may be renamed or replaced, or a practice may close). In our results, we report results for any practice or CCG that existed during the study period, acknowledging that some of these no longer exist. CCGs have now also been replaced with subintegrated care board locations, but some still retain their previous CCG code.</p>
        <p>Practices may act independently to change prescribing or participate in an action coordinated by their CCG. We, therefore, conducted analysis at both organizational levels. Monthly values for each measure were calculated for every practice and CCG between December 2014 and November 2019 (this study period was chosen so as to assess prescribing rates over a reasonable period of time, without being affected by the COVID-19 pandemic). The monthly data were summarized as deciles and presented as decile charts across all practices or CCGs each month.</p>
      </sec>
      <sec>
        <title>Statistical Methods</title>
        <p>For this study, we used our innovative change detection Python library (available via the Python Package Index) [<xref ref-type="bibr" rid="ref19">19</xref>], which is an automated method of detecting change in time-series data. This algorithm was originally developed to determine how clinicians vary in their response to new guidance on existing or new interventions. By measuring the timing and magnitude of change in the relevant organizations, it is able to identify both steep, sudden changes and more gradual, smooth transitions over multiple months. The full methods are described elsewhere [<xref ref-type="bibr" rid="ref13">13</xref>] and the code is available for anyone to use as a single command with our open Python library [<xref ref-type="bibr" rid="ref19">19</xref>].</p>
        <p>Data for each of the 3 measures were analyzed for all 191 CCGs and 7458 practices. The time series for each organization was analyzed using our change detection algorithm (using the default parameters) to identify the location and magnitude of significant reductions in the measure (substantial increases were filtered out as they are not relevant to the research question). These results were then filtered to remove (1) a total of 678 closed or dormant practices and (2) a further 237 practices with a list size of less than 2000 (this latter group was excluded to avoid analyses of time series with a high level of noise due to low prescribing volume); this process left 6543 practices to be subject to further analysis. We filtered out practices where more than half of the monthly denominator values were 0 (either no registered population or no total opioid prescribing as per measure definitions) across the study period. Among the organizations where our code detected a substantial reduction, for each measure, we selected those whose starting level immediately before the reduction was in the top 20% of all practices (top 150) or CCGs (top 38); this was to remove any organizations with consistently low prescribing from our results. For each measure, we then ranked practices and CCGs by the total measured change (the percentage reduction between the predrop value and the end-drop value) to identify which organizations exhibited the most substantial reductions.</p>
        <p>The decile plots provided show an individual organization’s prescribing rates across the period (thick red line), in the context of all peer organizations (summarized using deciles, as blue lines).</p>
      </sec>
      <sec>
        <title>Software and Reproducibility</title>
        <p>Data management and analysis were carried out using Python (version 3.8; Python Software Foundation) and Google BigQuery. Our change detection library [<xref ref-type="bibr" rid="ref19">19</xref>] is a Python wrapper for the <italic>GETS</italic> R package [<xref ref-type="bibr" rid="ref20">20</xref>]. All our methods and underlying code are openly available on GitHub [<xref ref-type="bibr" rid="ref21">21</xref>]. The full results, summary statistics of changes detected, and top 10 CCGs and practices can be seen in the notebooks folder, in the files <italic>ccg-opioids-change-detection-analysis.ipynb</italic> and <italic>practice-opioids-change-detection-analysis.ipynb</italic>. All organizations that existed in the study period (including those that have since closed or been replaced) are included in these reports.</p>
      </sec>
      <sec>
        <title>Ethical Considerations</title>
        <p>This study uses open, publicly available, and anonymized data. This analysis did not need a review from an institutional review board because it used previously collected, fully anonymized data [<xref ref-type="bibr" rid="ref22">22</xref>]. Informed consent and compensation were similarly not required and would not be possible.</p>
      </sec>
    </sec>
    <sec sec-type="results">
      <title>Results</title>
      <sec>
        <title>Overview</title>
        <p>We identified substantial reductions in at least 49% of all CCGs (94/191, 49.2%) and practices (4100/7460, 55%) for all measures; summary statistics for these reductions are provided in <xref ref-type="table" rid="table1">Table 1</xref>. Note that these data describe all substantial reductions detected, that is, before filtering for a top 20% (top 38 CCGs or top 150 practices) starting value. For both CCGs and practices, reductions are on average greater for both high-dose opioid prescribing measures as compared to those observed for the total OME measure, although the IQR values demonstrate that there is also more variability in the high-dose opioid prescribing measures. Reductions appear more modest among CCGs than practices (with lower medians and lower maximum values), but these reductions may be more consistent (with lower variability and greater minimum values observed in CCGs as compared to practices). There is at least 1 practice in each measure where the reduction is almost 99% to 100% and at least 1 practice where the reduction detected is very close to 0.</p>
        <table-wrap position="float" id="table1">
          <label>Table 1</label>
          <caption>
            <p>Summary of all opioid reductions identified across clinical commissioning groups (n=191) and practices (n=7458) in England between December 2014 and November 2019 using the automated change detection algorithm<sup>a</sup>.</p>
          </caption>
          <table width="1000" cellpadding="5" cellspacing="0" border="1" rules="groups" frame="hsides">
            <col width="30"/>
            <col width="400"/>
            <col width="0"/>
            <col width="80"/>
            <col width="0"/>
            <col width="260"/>
            <col width="0"/>
            <col width="230"/>
            <thead>
              <tr valign="top">
                <td colspan="3">Organization and measure</td>
                <td colspan="2">Count, n</td>
                <td colspan="2">Reduction (%), median (IQR)</td>
                <td>Reduction (%), range</td>
              </tr>
            </thead>
            <tbody>
              <tr valign="top">
                <td colspan="8">
                  <bold>Clinical commissioning groups (n=191)</bold>
                </td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td>Total OME<sup>b</sup> per 1000 patients</td>
                <td colspan="2">94</td>
                <td colspan="2">15.1 (11.8-18.7)</td>
                <td colspan="2">9.0-32.8</td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td>High-dose opioids as percentage regular opioids</td>
                <td colspan="2">168</td>
                <td colspan="2">19.0 (13.7-25.8)</td>
                <td colspan="2">3.6-41.5</td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td>High-dose opioids per 1000 patients</td>
                <td colspan="2">115</td>
                <td colspan="2">22.2 (17.2-30.0)</td>
                <td colspan="2">1.0-45.4</td>
              </tr>
              <tr valign="top">
                <td colspan="8">
                  <bold>Practices (n=7460)</bold>
                </td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td>Total OME per 1000 patients</td>
                <td colspan="2">4100</td>
                <td colspan="2">28.2 (19.8-39.7)</td>
                <td colspan="2">0.1-99.1</td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td>High-dose opioids as percentage regular opioids (%)</td>
                <td colspan="2">4632</td>
                <td colspan="2">47.7 (33.0-65.9)</td>
                <td colspan="2">0.0-100.0</td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td>High-dose opioids per 1000 patients</td>
                <td colspan="2">4334</td>
                <td colspan="2">56.0 (37.7-73.4)</td>
                <td colspan="2">0.0-100.0</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="table1fn1">
              <p><sup>a</sup>Count indicates the number of organizations (clinical commissioning groups or practices) in which a reduction was identified. Median, IQR, and range summarize the size of the reductions identified in those organizations (expressed as % reduction from the predrop value to the end-drop value).</p>
            </fn>
            <fn id="table1fn2">
              <p><sup>b</sup>OME: oral morphine equivalence.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
      </sec>
      <sec>
        <title>Changes for CCGS</title>
        <p><xref ref-type="table" rid="table2">Table 2</xref> illustrates the CCGs that exhibited the biggest reduction in each of the 3 OpenPrescribing measures over the study period, detailing the proportion of change and the month in which the change started. Note that these CCGs meet the criteria for identification, that is, their prescribing rate immediately before the reduction was in the top 38 (20%) CCGs.</p>
        <p>The total OME measure shows a gradual reduction over time in all 3 CCGs, with the algorithm identifying a reduction of up to 31%. The results for the 2 regular high-dose opioid measures also exhibit a gradual reduction over time but capture greater reductions in regular high-dose opioid prescription, with 40% and 39% reductions identified as a proportion of all regular opioids and per 1000 patients respectively.</p>
        <table-wrap position="float" id="table2">
          <label>Table 2</label>
          <caption>
            <p>Automatically detected changes across 3 measures of opioid prescribing in a retrospective prescribing database study of CCGs<sup>a</sup> in England<sup>b</sup>.</p>
          </caption>
          <table width="1000" cellpadding="5" cellspacing="0" border="1" rules="groups" frame="hsides">
            <col width="30"/>
            <col width="110"/>
            <col width="220"/>
            <col width="190"/>
            <col width="140"/>
            <col width="160"/>
            <col width="150"/>
            <thead>
              <tr valign="top">
                <td colspan="2">Measure and rank</td>
                <td>CCG</td>
                <td>Absolute change detected (difference)<sup>c</sup></td>
                <td>Proportional change (%)<sup>d</sup></td>
                <td>Month when change was detected</td>
                <td>Decile chart</td>
              </tr>
            </thead>
            <tbody>
              <tr valign="top">
                <td colspan="7">
                  <bold>Total OME<sup>e</sup> per 1000 patients</bold>
                </td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td>1</td>
                <td>Vale Royal</td>
                <td>15,461</td>
                <td>31</td>
                <td>November 2015</td>
                <td>
                  <graphic xlink:href="publichealth_v10i1e51323_fig1.png" alt-version="no" mimetype="image" position="float" xlink:type="simple"/>
                </td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td>2</td>
                <td>Great Yarmouth and Waveney</td>
                <td>19,182</td>
                <td>26</td>
                <td>February 2017</td>
                <td>
                  <graphic xlink:href="publichealth_v10i1e51323_fig2.png" alt-version="no" mimetype="image" position="float" xlink:type="simple"/>
                </td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td>3</td>
                <td>Heywood, Middleton and Rochdale</td>
                <td>15,393</td>
                <td>26</td>
                <td>August 2017</td>
                <td>
                  <graphic xlink:href="publichealth_v10i1e51323_fig3.png" alt-version="no" mimetype="image" position="float" xlink:type="simple"/>
                </td>
              </tr>
              <tr valign="top">
                <td colspan="7">
                  <bold>High-dose opioids as percentage regular opioids<sup>f</sup></bold>
                </td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td>1</td>
                <td>North Tyneside</td>
                <td>8.9</td>
                <td>40</td>
                <td>September 2018</td>
                <td>
                  <graphic xlink:href="publichealth_v10i1e51323_fig4.png" alt-version="no" mimetype="image" position="float" xlink:type="simple"/>
                </td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td>2</td>
                <td>Great Yarmouth and Waveney</td>
                <td>8.7</td>
                <td>33</td>
                <td>May 2018</td>
                <td>
                  <graphic xlink:href="publichealth_v10i1e51323_fig5.png" alt-version="no" mimetype="image" position="float" xlink:type="simple"/>
                </td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td>3</td>
                <td>Heywood, Middleton and Rochdale</td>
                <td>8.9</td>
                <td>33</td>
                <td>September 2018</td>
                <td>
                  <graphic xlink:href="publichealth_v10i1e51323_fig6.png" alt-version="no" mimetype="image" position="float" xlink:type="simple"/>
                </td>
              </tr>
              <tr valign="top">
                <td colspan="7">
                  <bold>High-dose opioid items per 1000 patients</bold>
                </td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td>1</td>
                <td>Great Yarmouth and Waveney</td>
                <td>2.0</td>
                <td>39</td>
                <td>August 2017</td>
                <td>
                  <graphic xlink:href="publichealth_v10i1e51323_fig7.png" alt-version="no" mimetype="image" position="float" xlink:type="simple"/>
                </td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td>2</td>
                <td>Hastings and Rother</td>
                <td>1.3</td>
                <td>39</td>
                <td>February 2018</td>
                <td>
                  <graphic xlink:href="publichealth_v10i1e51323_fig8.png" alt-version="no" mimetype="image" position="float" xlink:type="simple"/>
                </td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td>3</td>
                <td>Heywood, Middleton and Rochdale</td>
                <td>1.6</td>
                <td>38</td>
                <td>August 2017</td>
                <td>
                  <graphic xlink:href="publichealth_v10i1e51323_fig9.png" alt-version="no" mimetype="image" position="float" xlink:type="simple"/>
                </td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="table2fn1">
              <p><sup>a</sup>CCG: clinical commissioning group.</p>
            </fn>
            <fn id="table2fn2">
              <p><sup>b</sup>Ranked top 3 CCGs exhibiting a reduction in each of the OpenPrescribing opioid measures (December 2014 to November 2019). The decile chart shows the prescription rate for the CCG as a thick red line; prescribing rates for all other CCGs are summarized using deciles (dotted blue lines) with the median highlighted (thick dashed blue line). Note, y-axis scales differ.</p>
            </fn>
            <fn id="table2fn3">
              <p><sup>c</sup>The absolute change is the difference between the starting value and final value during the detected change period.</p>
            </fn>
            <fn id="table2fn4">
              <p><sup>d</sup>The relative change gives the difference as a percentage of the starting value.</p>
            </fn>
            <fn id="table2fn5">
              <p><sup>e</sup>OME: oral morphine equivalence.</p>
            </fn>
            <fn id="table2fn6">
              <p><sup>f</sup>This measure is calculated as a percentage, so the absolute change represents the percentage points difference.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
      </sec>
      <sec>
        <title>Changes for Practices</title>
        <p><xref ref-type="table" rid="table3">Table 3</xref> illustrates the practices that exhibited the biggest change in each of the 3 OpenPrescribing measures over the study period, detailing the proportion of change and the month in which the change started. Note that these practices meet the criteria for identification as described in the “Statistical Methods” section, that is, their prescribing rate immediately before the reduction was in the top 150 (20%) practices.</p>
        <p>The practice time series (<xref ref-type="table" rid="table3">Table 3</xref>) are noticeably different from those of the CCGs (<xref ref-type="table" rid="table2">Table 2</xref>), the magnitude of the measured changes is larger, and the slope of the time series is much steeper for practices. In the case of the regular high-dose opioids as a percentage of all opioids, all 3 practices are seen to completely eliminate all regular high-dose opioids for several months; similarly, very low values are observed for the top 3 practices with regards to reductions in high-dose opioid items per 1000 patients.</p>
        <table-wrap position="float" id="table3">
          <label>Table 3</label>
          <caption>
            <p>Automatically detected changes across 3 measures of opioid prescribing in a retrospective prescribing database study of practices in England<sup>a</sup>.</p>
          </caption>
          <table width="1000" cellpadding="5" cellspacing="0" border="1" rules="groups" frame="hsides">
            <col width="30"/>
            <col width="110"/>
            <col width="220"/>
            <col width="190"/>
            <col width="140"/>
            <col width="160"/>
            <col width="150"/>
            <thead>
              <tr valign="top">
                <td colspan="2">Measure and rank</td>
                <td>Practice</td>
                <td>Absolute change detected (difference)<sup>b</sup></td>
                <td>Proportional change (%)<sup>c</sup></td>
                <td>Month when change was detected</td>
                <td>Chart</td>
              </tr>
            </thead>
            <tbody>
              <tr valign="top">
                <td colspan="7">
                  <bold>Total OME<sup>d</sup> per 1000 patients</bold>
                </td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td>1</td>
                <td>Practice A (Manchester CCG<sup>e</sup>)</td>
                <td>76,161</td>
                <td>74</td>
                <td>June 2018</td>
                <td>
                  <graphic xlink:href="publichealth_v10i1e51323_fig10.png" alt-version="no" mimetype="image" position="float" xlink:type="simple"/>
                </td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td>2</td>
                <td>Practice B (Manchester CCG)</td>
                <td>38,574</td>
                <td>62</td>
                <td>September 2018</td>
                <td>
                  <graphic xlink:href="publichealth_v10i1e51323_fig11.png" alt-version="no" mimetype="image" position="float" xlink:type="simple"/>
                </td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td>3</td>
                <td>Practice C (West Cheshire CCG)</td>
                <td>88,109</td>
                <td>61</td>
                <td>February 2017</td>
                <td>
                  <graphic xlink:href="publichealth_v10i1e51323_fig12.png" alt-version="no" mimetype="image" position="float" xlink:type="simple"/>
                </td>
              </tr>
              <tr valign="top">
                <td colspan="7">
                  <bold>High-dose opioids as percentage regular opioids<sup>f</sup></bold>
                </td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td>1</td>
                <td>Practice D (City and Hackney CCG)</td>
                <td>44</td>
                <td>99</td>
                <td>August 2018</td>
                <td>
                  <graphic xlink:href="publichealth_v10i1e51323_fig13.png" alt-version="no" mimetype="image" position="float" xlink:type="simple"/>
                </td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td>2</td>
                <td>Practice E (Harrow CCG)</td>
                <td>52</td>
                <td>99</td>
                <td>May 2017</td>
                <td>
                  <graphic xlink:href="publichealth_v10i1e51323_fig14.png" alt-version="no" mimetype="image" position="float" xlink:type="simple"/>
                </td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td>3</td>
                <td>Practice F (Ealing CCG)</td>
                <td>95</td>
                <td>99</td>
                <td>March 2016</td>
                <td>
                  <graphic xlink:href="publichealth_v10i1e51323_fig15.png" alt-version="no" mimetype="image" position="float" xlink:type="simple"/>
                </td>
              </tr>
              <tr valign="top">
                <td colspan="7">
                  <bold>High-dose opioid items per 1000 patients</bold>
                </td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td>1</td>
                <td>Practice G (Portsmouth CCG)</td>
                <td>3.6</td>
                <td>97</td>
                <td>August 2018</td>
                <td>
                  <graphic xlink:href="publichealth_v10i1e51323_fig16.png" alt-version="no" mimetype="image" position="float" xlink:type="simple"/>
                </td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td>2</td>
                <td>Practice H (Coventry and Rugby CCG)</td>
                <td>4.8</td>
                <td>97</td>
                <td>February 2018</td>
                <td>
                  <graphic xlink:href="publichealth_v10i1e51323_fig17.png" alt-version="no" mimetype="image" position="float" xlink:type="simple"/>
                </td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td>3</td>
                <td>Practice I (Salford CCG)</td>
                <td>4.8</td>
                <td>95</td>
                <td>February 2018</td>
                <td>
                  <graphic xlink:href="publichealth_v10i1e51323_fig18.png" alt-version="no" mimetype="image" position="float" xlink:type="simple"/>
                </td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="table3fn1">
              <p><sup>a</sup>Ranked top 3 practices exhibiting a reduction in each of the OpenPrescribing opioid measures (December 2014 to November 2019). The decile chart shows the prescription rate for the practice as a thick red line; prescribing rates for all other practices are summarized using deciles (dotted blue lines) with the median highlighted (thick dashed blue line). Note, y-axis scales differ<italic>.</italic></p>
            </fn>
            <fn id="table3fn2">
              <p><sup>b</sup>The absolute change is the difference between the starting value and final value during the detected change period.</p>
            </fn>
            <fn id="table3fn3">
              <p><sup>c</sup>The relative change gives the difference as a percentage of the starting value.</p>
            </fn>
            <fn id="table3fn4">
              <p><sup>d</sup>OME: oral morphine equivalence.</p>
            </fn>
            <fn id="table3fn5">
              <p><sup>e</sup>CCG: clinical commissioning group.</p>
            </fn>
            <fn id="table3fn6">
              <p><sup>f</sup>This measure is calculated as a percentage, so the absolute change represents the percentage points difference.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
      </sec>
    </sec>
    <sec sec-type="discussion">
      <title>Discussion</title>
      <sec>
        <title>Main Findings</title>
        <p>We have identified significant reductions in 3 measures of opioid prescribing using a data-driven approach in over 7000 practices across 191 CCGs in England (<xref ref-type="table" rid="table1">Table 1</xref>). These organizations have then been ranked by the magnitude of reduction to identify where the largest reductions have been realized. The top-ranked CCGs exhibit a slow and gradual reduction in opioid use (<xref ref-type="table" rid="table1">Tables 1</xref> and <xref ref-type="table" rid="table2">2</xref>); by contrast, the top-ranked practices exhibit rapid and sudden reductions over a few months (<xref ref-type="table" rid="table1">Tables 1</xref> and <xref ref-type="table" rid="table3">3</xref>). Opioid prescribing and treatment of pain more broadly can be complex, but our findings illustrate that some CCGs and practices appear to have significantly reduced their prescribing of opioids over the study period, more so than many of their peers.</p>
      </sec>
      <sec>
        <title>Findings in Context</title>
        <p>The PHE review identified evidence of tentative progress in reducing opioid prescribing between 2015 or 2016 and 2017 or 2018 [<xref ref-type="bibr" rid="ref10">10</xref>]. Our analysis includes and extends this time period and finds evidence that some organizations may be driving this tentative progress more than others (eg, the CCGs reported in <xref ref-type="table" rid="table2">Table 2</xref>).</p>
        <p>We do have evidence that 1 of the organizations that has emerged as a potential candidate by our methodology is a genuine example of improved performance. Between 2017 and 2019, Great Yarmouth and Waveney designed and implemented an extensive program of opioid reduction interventions, including target trajectories for improvement; incentive schemes for clinicians; dialogue with practice pharmacists, patient groups, and relevant clinical groups (eg, prescribing leads and pain management teams); new patient information materials; collecting case studies for discussion; and associated press and social media to raise awareness. While this CCG still exhibits high levels of opioid prescribing, rates have reduced significantly, with the organization being recognized for this progress nationally [<xref ref-type="bibr" rid="ref23">23</xref>]. Our methodology ranked Great Yarmouth and Waveney as first (reduction of 39% [absolute reduction 2.0] starting in August 2017) for high-dose opioid prescribing per 1000 patients and second (reduction of 33% [absolute reduction 8.7%] starting in May 2018) for high-dose opioid prescribing as a percentage of regular opioid prescribing, aligning with the period of intervention implementation.</p>
        <p>The new national policy for the optimization and personalization of various addiction-forming medications, including opioids, lacks practical detail on implementation for GPs to reduce opioid prescribing [<xref ref-type="bibr" rid="ref24">24</xref>,<xref ref-type="bibr" rid="ref25">25</xref>]. Different innovations are being implemented in the United Kingdom [<xref ref-type="bibr" rid="ref26">26</xref>-<xref ref-type="bibr" rid="ref28">28</xref>], and these strategies are associated with observable changes in prescribing practices. However, some may succeed in 1 area but not another. GPs undertake complex decision-making on opioid prescribing, balancing benefits and harms [<xref ref-type="bibr" rid="ref29">29</xref>], but struggle with limited time and alternatives for chronic pain [<xref ref-type="bibr" rid="ref30">30</xref>,<xref ref-type="bibr" rid="ref31">31</xref>]. Further practical guidelines for GPs on appropriate prescribing could help with tapering and effective communication strategies [<xref ref-type="bibr" rid="ref26">26</xref>,<xref ref-type="bibr" rid="ref30">30</xref>]. Tools such as that demonstrated in this paper, highlighting positive changes, could help to inspire and motivate practices or regions to make changes, while also giving them other organizations to contact about how changes have been achieved.</p>
      </sec>
      <sec>
        <title>Implications for Research and Policy</title>
        <p>We are seeking to implement this methodology as a new “Improvement Radar” tool on OpenPrescribing, with the intention of systematically identifying candidates for further qualitative research across multiple important public health prescribing measures to better understand the patterns shown, for example, to uncover and learn from effective practice or refine our measures to exclude artifacts. It is our experience that best practice is typically defined by organizations identifying themselves as having improved, following implementation and internal assessment of interventions. Using the Improvement Radar, policy makers interested in spreading the best practice can systematically identify organizations that may have already implemented effective interventions. However, it is critical that policy makers undertake further investigations for reasons outlined in the limitations. This tool offers an opportunity to reduce the resources needed to identify best practices. Similarly, local medicines optimization teams may wish to use data and tools like this to identify peers across the country who have already delivered successful interventions to inform local initiatives. Further quantitative research is also possible from the data set, for example, drilling down by opioid type and monitoring the impact of any local or national interventions or policies.</p>
      </sec>
      <sec>
        <title>Strengths and Limitations</title>
        <p>The national prescribing data used for this analysis, being collected for reimbursement purposes, are highly complete and accurate. We have taken into account most (6543/7458, 87.7%) typical primary care practices in England, thereby minimizing the risk of biased sampling. Executing this analysis in an existing, open platform such as OpenPrescribing ensures accountability and transparency—both identified as priorities in the PHE report [<xref ref-type="bibr" rid="ref10">10</xref>]; by default, all code in this study, from data curation to completed output, is shared openly on GitHub and the Python Package Index. Furthermore, there exists a robust and tested framework with which relevant new measures can be introduced or existing measures can be amended as required in order to respond to any evolving change in tackling opioid dependency and abuse. Our use of OME conversion permits the reporting of trends for opioid medicines overall while accounting for variation in strength.</p>
        <p>We also note some limitations. First, the prescribing data set does not include secondary care prescriptions as this was unavailable at the time of the study [<xref ref-type="bibr" rid="ref32">32</xref>], and as such, the opioid measures implemented here may underestimate the extent of opioid prescribing nationally, although financial data would indicate that the vast majority of analgesics (British National Formulary (BNF) section 4.7, which includes the BNF subsection 4.7.2 opioid analgesics) are prescribed in primary care [<xref ref-type="bibr" rid="ref33">33</xref>]. Second, we acknowledge that practice-level time-series data, in particular, could be significantly impacted by local circumstances, including low patient numbers, a change in patient population, a change to prescription frequency (eg, from weekly to monthly scripts), or a shift in responsibility of opioid prescribing (eg, from primary to secondary care) and, therefore, that an apparent reduction in any opioid measure may not be due to a successful intervention. For example, practice G (<xref ref-type="table" rid="table3">Table 3</xref>) rapidly increased their high-dose opioid items per 1000 patients in 2016 followed by a similar rapid reduction 2 years later; this could be due to a change to daily prescribing as can be clinically justified for some patients. While we acknowledge these limitations, it is important to note that the intention of this methodology was always to rank or prioritize organizations for further investigation, rather than definitively ascribe reductions in opioid prescribing to successful interventions.</p>
      </sec>
      <sec>
        <title>Conclusions</title>
        <p>We have demonstrated that data-driven approaches to detect substantial changes in time-series data have potential value in the context of opioid prescribing. We have been able to rank organizations with regards to the extent of opioid prescribing reduction; organizations occupying the top of that list show large drops that warrant further qualitative investigation and could be indicative of success in tackling an important public health concern.</p>
        <p>Should this further qualitative research reveal that reductions have been driven by well-designed and well-implemented interventions, methods of best practice will have been identified using an unbiased, evidence-based approach. The organizations found to be implementing this best practice may have valuable insights, approaches, and policies to share regarding how positive change can be achieved elsewhere. It also demonstrates, particularly in the most robust and gradual change observed among CCGs, that positive change is possible and, therefore, that continued and wider success in reducing opioid prescribing is dependent, at least in part, on closing the implementation gap.</p>
      </sec>
    </sec>
  </body>
  <back>
    <app-group/>
    <glossary>
      <title>Abbreviations</title>
      <def-list>
        <def-item>
          <term id="abb1">BNF</term>
          <def>
            <p>British National Formulary</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb2">CCG</term>
          <def>
            <p>clinical commissioning group</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb3">GP</term>
          <def>
            <p>general practice</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb4">NHS</term>
          <def>
            <p>National Health Service</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb5">NHSBSA</term>
          <def>
            <p>National Health Service Business Services Authority</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb6">OME</term>
          <def>
            <p>oral morphine equivalence</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb7">PHE</term>
          <def>
            <p>Public Health England</p>
          </def>
        </def-item>
      </def-list>
    </glossary>
    <ack>
      <p>We are grateful to wider National Health Service (NHS) colleagues for discussions that have informed our work on this topic. This project is funded by the National Institute for Health Research (NIHR) under its Research for Patient Benefit (RfPB) Programme (PB-PG-0418-20036). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. Funders had no role in the study design, collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.</p>
    </ack>
    <notes>
      <sec>
        <title>Data Availability</title>
        <p>The data sets generated and analyzed during this study are available in the “opioids-change-detection-notebook” repository [<xref ref-type="bibr" rid="ref21">21</xref>]. All our methods and code can also be found in this repository [<xref ref-type="bibr" rid="ref21">21</xref>]. The underlying data are available via the National Health Service Business Services Authority (NHSBSA) [<xref ref-type="bibr" rid="ref14">14</xref>].</p>
      </sec>
    </notes>
    <fn-group>
      <fn fn-type="con">
        <p>AJW, HJC, BG, and BM contributed to the conceptualization. PI, DE, and SB contributed to the data curation. LEMH, AJW, and BM performed the formal analysis. AJW, HJC, and BG contributed to the funding acquisition. LEMH, AJW, HJC, RC, and BM performed the investigation. LEMH, AJW, HJC, RC, and BM contributed to the methodology. PI, DE, and SB contributed to the resources. FP, PI, DE, and SB contributed to the software. BG performed the supervision. LEMH, AJW, HJC, and BM did the visualization. LEMH, AJW, HJC, and BM contributed to writing—original draft. All authors contributed to writing—review and editing.</p>
      </fn>
      <fn fn-type="conflict">
        <p>All authors have completed the International Committee of Medical Journal Editors (ICMJE) uniform disclosure form and declare the following: BG has received research funding from the Bennett Foundation, the Laura and John Arnold Foundation, the National Health Service (NHS) National Institute for Health Research (NIHR), the NIHR School of Primary Care Research, NHS England, the NIHR Oxford Biomedical Research Centre, the Mohn-Westlake Foundation, NIHR Applied Research Collaboration Oxford and Thames Valley, the Wellcome Trust, the Good Thinking Foundation, Health Data Research UK, the Health Foundation, the World Health Organization, UK Research and Innovation Medical Research Council (UKRI MRC), Asthma UK, the British Lung Foundation, and the Longitudinal Health and Wellbeing strand of the National Core Studies programme; he has previously been a nonexecutive director at NHS Digital; he also receives personal income from speaking and writing for lay audiences on the misuse of science. BMK is also employed by NHS England working on medicines policy and clinical lead for primary care medicines data.</p>
      </fn>
    </fn-group>
    <ref-list>
      <ref id="ref1">
        <label>1</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Ballantyne</surname>
              <given-names>JC</given-names>
            </name>
            <name name-style="western">
              <surname>Kalso</surname>
              <given-names>E</given-names>
            </name>
            <name name-style="western">
              <surname>Stannard</surname>
              <given-names>C</given-names>
            </name>
          </person-group>
          <article-title>WHO analgesic ladder: a good concept gone astray</article-title>
          <source>BMJ</source>
          <year>2016</year>
          <volume>352</volume>
          <fpage>i20</fpage>
          <pub-id pub-id-type="doi">10.1136/bmj.i20</pub-id>
          <pub-id pub-id-type="medline">26739664</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref2">
        <label>2</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <collab>The Lancet Regional Health—Americas</collab>
          </person-group>
          <article-title>Opioid crisis: addiction, overprescription, and insufficient primary prevention</article-title>
          <source>Lancet Reg Health Am</source>
          <year>2023</year>
          <volume>23</volume>
          <fpage>100557</fpage>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://linkinghub.elsevier.com/retrieve/pii/S2667-193X(23)00131-X"/>
          </comment>
          <pub-id pub-id-type="doi">10.1016/j.lana.2023.100557</pub-id>
          <pub-id pub-id-type="medline">37497399</pub-id>
          <pub-id pub-id-type="pii">S2667-193X(23)00131-X</pub-id>
          <pub-id pub-id-type="pmcid">PMC10366477</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref3">
        <label>3</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Els</surname>
              <given-names>C</given-names>
            </name>
            <name name-style="western">
              <surname>Jackson</surname>
              <given-names>TD</given-names>
            </name>
            <name name-style="western">
              <surname>Hagtvedt</surname>
              <given-names>R</given-names>
            </name>
            <name name-style="western">
              <surname>Kunyk</surname>
              <given-names>D</given-names>
            </name>
            <name name-style="western">
              <surname>Sonnenberg</surname>
              <given-names>B</given-names>
            </name>
            <name name-style="western">
              <surname>Lappi</surname>
              <given-names>VG</given-names>
            </name>
            <name name-style="western">
              <surname>Straube</surname>
              <given-names>S</given-names>
            </name>
          </person-group>
          <article-title>High-dose opioids for chronic non-cancer pain: an overview of Cochrane reviews</article-title>
          <source>Cochrane Database Syst Rev</source>
          <year>2017</year>
          <volume>10</volume>
          <issue>10</issue>
          <fpage>CD012299</fpage>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://europepmc.org/abstract/MED/29084358"/>
          </comment>
          <pub-id pub-id-type="doi">10.1002/14651858.CD012299.pub2</pub-id>
          <pub-id pub-id-type="medline">29084358</pub-id>
          <pub-id pub-id-type="pmcid">PMC6485814</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref4">
        <label>4</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Mordecai</surname>
              <given-names>L</given-names>
            </name>
            <name name-style="western">
              <surname>Reynolds</surname>
              <given-names>C</given-names>
            </name>
            <name name-style="western">
              <surname>Donaldson</surname>
              <given-names>LJ</given-names>
            </name>
            <name name-style="western">
              <surname>de C Williams</surname>
              <given-names>AC</given-names>
            </name>
          </person-group>
          <article-title>Patterns of regional variation of opioid prescribing in primary care in England: a retrospective observational study</article-title>
          <source>Br J Gen Pract</source>
          <year>2018</year>
          <volume>68</volume>
          <issue>668</issue>
          <fpage>e225</fpage>
          <lpage>e233</lpage>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://bjgp.org/lookup/pmidlookup?view=long&#38;pmid=29440012"/>
          </comment>
          <pub-id pub-id-type="doi">10.3399/bjgp18X695057</pub-id>
          <pub-id pub-id-type="medline">29440012</pub-id>
          <pub-id pub-id-type="pii">bjgp18X695057</pub-id>
          <pub-id pub-id-type="pmcid">PMC5819988</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref5">
        <label>5</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Curtis</surname>
              <given-names>HJ</given-names>
            </name>
            <name name-style="western">
              <surname>Croker</surname>
              <given-names>R</given-names>
            </name>
            <name name-style="western">
              <surname>Walker</surname>
              <given-names>AJ</given-names>
            </name>
            <name name-style="western">
              <surname>Richards</surname>
              <given-names>GC</given-names>
            </name>
            <name name-style="western">
              <surname>Quinlan</surname>
              <given-names>J</given-names>
            </name>
            <name name-style="western">
              <surname>Goldacre</surname>
              <given-names>B</given-names>
            </name>
          </person-group>
          <article-title>Opioid prescribing trends and geographical variation in England, 1998-2018: a retrospective database study</article-title>
          <source>Lancet Psychiatry</source>
          <year>2019</year>
          <volume>6</volume>
          <issue>2</issue>
          <fpage>140</fpage>
          <lpage>150</lpage>
          <pub-id pub-id-type="doi">10.1016/S2215-0366(18)30471-1</pub-id>
          <pub-id pub-id-type="medline">30580987</pub-id>
          <pub-id pub-id-type="pii">S2215-0366(18)30471-1</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref6">
        <label>6</label>
        <nlm-citation citation-type="book">
          <person-group person-group-type="author">
            <collab>OECD</collab>
          </person-group>
          <source>Addressing Problematic Opioid Use in OECD Countries</source>
          <year>2019</year>
          <publisher-loc>Paris</publisher-loc>
          <publisher-name>OECD Publishing</publisher-name>
        </nlm-citation>
      </ref>
      <ref id="ref7">
        <label>7</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <collab>The British Pain Society</collab>
          </person-group>
          <article-title>Opioids for persistent pain: summary of guidance on good practice from the British Pain Society</article-title>
          <source>Br J Pain</source>
          <year>2012</year>
          <volume>6</volume>
          <issue>1</issue>
          <fpage>9</fpage>
          <lpage>10</lpage>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://europepmc.org/abstract/MED/26516460"/>
          </comment>
          <pub-id pub-id-type="doi">10.1177/2049463712436536</pub-id>
          <pub-id pub-id-type="medline">26516460</pub-id>
          <pub-id pub-id-type="pii">10.1177_2049463712436536</pub-id>
          <pub-id pub-id-type="pmcid">PMC4590092</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref8">
        <label>8</label>
        <nlm-citation citation-type="web">
          <article-title>Opioids aware</article-title>
          <source>Faculty of Pain Medicine of the Royal College of Anaesthetists</source>
          <access-date>2022-02-18</access-date>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://fpm.ac.uk/opioids-aware">https://fpm.ac.uk/opioids-aware</ext-link>
          </comment>
        </nlm-citation>
      </ref>
      <ref id="ref9">
        <label>9</label>
        <nlm-citation citation-type="web">
          <article-title>Reducing opioid-related deaths in the UK</article-title>
          <source>Advisory Council on the Misuse of Drugs</source>
          <year>2016</year>
          <access-date>2024-03-12</access-date>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/576560/ACMD-Drug-Related-Deaths-Report-161212.pdf">https://assets.publishing. service.gov.uk/government/uploads/system/uploads/attachment_data/file/576560/ACMD-Drug-Related-Deaths-Report-161 212.pdf</ext-link>
          </comment>
        </nlm-citation>
      </ref>
      <ref id="ref10">
        <label>10</label>
        <nlm-citation citation-type="web">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Taylor</surname>
              <given-names>S</given-names>
            </name>
            <name name-style="western">
              <surname>Annand</surname>
              <given-names>F</given-names>
            </name>
            <name name-style="western">
              <surname>Burkinshaw</surname>
              <given-names>P</given-names>
            </name>
            <name name-style="western">
              <surname>Greaves</surname>
              <given-names>F</given-names>
            </name>
            <name name-style="western">
              <surname>Kelleher</surname>
              <given-names>M</given-names>
            </name>
            <name name-style="western">
              <surname>Knight</surname>
              <given-names>J</given-names>
            </name>
            <name name-style="western">
              <surname>Perkins</surname>
              <given-names>C</given-names>
            </name>
            <name name-style="western">
              <surname>Tran</surname>
              <given-names>A</given-names>
            </name>
            <name name-style="western">
              <surname>White</surname>
              <given-names>M</given-names>
            </name>
            <name name-style="western">
              <surname>Marsden</surname>
              <given-names>J</given-names>
            </name>
          </person-group>
          <article-title>Dependence and withdrawal associated with some prescribed medicines: an evidence review</article-title>
          <source>Public Health England</source>
          <access-date>2024-03-12</access-date>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/940255/PHE_PMR_report_Dec2020.pdf">https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/940255/PHE_PMR_report_Dec2020.pdf</ext-link>
          </comment>
        </nlm-citation>
      </ref>
      <ref id="ref11">
        <label>11</label>
        <nlm-citation citation-type="web">
          <article-title>Explore England's prescribing data</article-title>
          <source>OpenPrescribing</source>
          <year>2023</year>
          <access-date>2023-07-27</access-date>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://openprescribing.net/">https://openprescribing.net/</ext-link>
          </comment>
        </nlm-citation>
      </ref>
      <ref id="ref12">
        <label>12</label>
        <nlm-citation citation-type="web">
          <article-title>Opioid prescribing measures</article-title>
          <source>OpenPrescribing</source>
          <access-date>2022-02-10</access-date>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://openprescribing.net/measure/?tags=opioids">https://openprescribing.net/measure/?tags=opioids</ext-link>
          </comment>
        </nlm-citation>
      </ref>
      <ref id="ref13">
        <label>13</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Walker</surname>
              <given-names>AJ</given-names>
            </name>
            <name name-style="western">
              <surname>Pretis</surname>
              <given-names>F</given-names>
            </name>
            <name name-style="western">
              <surname>Powell-Smith</surname>
              <given-names>A</given-names>
            </name>
            <name name-style="western">
              <surname>Goldacre</surname>
              <given-names>B</given-names>
            </name>
          </person-group>
          <article-title>Variation in responsiveness to warranted behaviour change among NHS clinicians: novel implementation of change detection methods in longitudinal prescribing data</article-title>
          <source>BMJ</source>
          <year>2019</year>
          <volume>367</volume>
          <fpage>l5205</fpage>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="http://www.bmj.com/lookup/pmidlookup?view=long&#38;pmid=31578187"/>
          </comment>
          <pub-id pub-id-type="doi">10.1136/bmj.l5205</pub-id>
          <pub-id pub-id-type="medline">31578187</pub-id>
          <pub-id pub-id-type="pmcid">PMC6771379</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref14">
        <label>14</label>
        <nlm-citation citation-type="web">
          <article-title>English Prescribing Data (EPD)</article-title>
          <source>NHS Business Services Authority</source>
          <access-date>2022-02-24</access-date>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://www.nhsbsa.nhs.uk/prescription-data/prescribing-data/english-prescribing-data-epd">https://www.nhsbsa.nhs.uk/prescription-data/prescribing-data/english-prescribing-data-epd</ext-link>
          </comment>
        </nlm-citation>
      </ref>
      <ref id="ref15">
        <label>15</label>
        <nlm-citation citation-type="web">
          <article-title>Number of patients registered at a GP practice</article-title>
          <source>NHS Digital</source>
          <year>2018</year>
          <access-date>2018-11-20</access-date>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://digital.nhs.uk/data-and-information/publications/statistical/patients-registered-at-a-gp-practice">https://digital.nhs.uk/data-and-information/publi cations/statistical/patients-registered-at-a-gp-practice</ext-link>
          </comment>
        </nlm-citation>
      </ref>
      <ref id="ref16">
        <label>16</label>
        <nlm-citation citation-type="web">
          <article-title>Prescribing of opioids (total oral morphine equivalence) by all Sub-ICB locations</article-title>
          <source>OpenPrescribing</source>
          <access-date>2023-02-06</access-date>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://openprescribing.net/measure/opioidome/">https://open prescribing.net/measure/opioidome/</ext-link>
          </comment>
        </nlm-citation>
      </ref>
      <ref id="ref17">
        <label>17</label>
        <nlm-citation citation-type="web">
          <article-title>High dose opioid items as percentage regular opioids by all sub-ICB locations</article-title>
          <source>OpenPrescribing</source>
          <year>2023</year>
          <access-date>2022-02-17</access-date>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://openprescribing.net/measure/opioidspercent/">https://open prescribing.net/measure/opioidspercent/</ext-link>
          </comment>
        </nlm-citation>
      </ref>
      <ref id="ref18">
        <label>18</label>
        <nlm-citation citation-type="web">
          <article-title>High dose opioids per 1000 patients by all sub-ICB locations</article-title>
          <source>OpenPrescribing</source>
          <year>2023</year>
          <access-date>2022-02-17</access-date>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://openprescribing.net/measure/opioidper1000/">https://openprescribing.net/measure/opioidper1000/</ext-link>
          </comment>
        </nlm-citation>
      </ref>
      <ref id="ref19">
        <label>19</label>
        <nlm-citation citation-type="web">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Walker</surname>
              <given-names>A</given-names>
            </name>
          </person-group>
          <article-title>Change detection in prescribing data</article-title>
          <source>change_detection 0.3.5</source>
          <year>2020</year>
          <access-date>2020-01-31</access-date>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://pypi.org/project/change_detection/">https://pypi.org/project/change_detec tion/</ext-link>
          </comment>
        </nlm-citation>
      </ref>
      <ref id="ref20">
        <label>20</label>
        <nlm-citation citation-type="web">
          <article-title>gets: General-to-Specific (GETS) modelling and indicator saturation methods</article-title>
          <source>Comprehensive R Archive Network (CRAN)</source>
          <year>2022</year>
          <access-date>2023-07-26</access-date>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://cran.r-project.org/web/packages/gets/index.html">https://cran.r-project.org/web/packages/gets/index.html</ext-link>
          </comment>
        </nlm-citation>
      </ref>
      <ref id="ref21">
        <label>21</label>
        <nlm-citation citation-type="web">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Walker</surname>
              <given-names>A</given-names>
            </name>
            <name name-style="western">
              <surname>Hopcroft</surname>
              <given-names>L</given-names>
            </name>
            <name name-style="western">
              <surname>MacKenna</surname>
              <given-names>B</given-names>
            </name>
            <name name-style="western">
              <surname>Bacon</surname>
              <given-names>S</given-names>
            </name>
          </person-group>
          <article-title>Opioids-change-detection-notebook</article-title>
          <source>GitHub</source>
          <access-date>2023-07-26</access-date>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://github.com/ebmdatalab/opioids-change-detection-notebook">https://github.com/ebm datalab/opioids-change-detection-notebook</ext-link>
          </comment>
        </nlm-citation>
      </ref>
      <ref id="ref22">
        <label>22</label>
        <nlm-citation citation-type="web">
          <article-title>Oxford University research support—research ethics FAQ</article-title>
          <source>University of Oxford</source>
          <access-date>2024-01-05</access-date>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://researchsupport.admin.ox.ac.uk/governance/ethics/faqs-glossary/faqs#collapse410581">https://researchsupport.admin.ox.ac.uk /governance/ethics/faqs-glossary/faqs#collapse410581</ext-link>
          </comment>
        </nlm-citation>
      </ref>
      <ref id="ref23">
        <label>23</label>
        <nlm-citation citation-type="web">
          <article-title>Winner—high dose opiate reduction in Great Yarmouth and Waveney (2019)</article-title>
          <source>PrescQIPP</source>
          <access-date>2022-02-23</access-date>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://www.prescqipp.info/community-resources/innovation-and-best-practice/winner-high-dose-opiate-reduction-in-great-yarmouth-and-waveney-2019/">https://www.prescqipp.info/community-resources/innovation-and-best-practice/winner-high-dose-opiate-reduction-in-great-yarmouth-and-waveney-2019/</ext-link>
          </comment>
        </nlm-citation>
      </ref>
      <ref id="ref24">
        <label>24</label>
        <nlm-citation citation-type="web">
          <article-title>Chronic pain (primary and secondary) in over 16s: assessment of all chronic pain and management of chronic primary pain</article-title>
          <source>National Institute for Health and Care Excellence</source>
          <access-date>2023-09-12</access-date>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://www.nice.org.uk/guidance/NG193">https://www.nice.org.uk/guidance/NG193</ext-link>
          </comment>
        </nlm-citation>
      </ref>
      <ref id="ref25">
        <label>25</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Richards</surname>
              <given-names>GC</given-names>
            </name>
            <name name-style="western">
              <surname>Anwar</surname>
              <given-names>S</given-names>
            </name>
            <name name-style="western">
              <surname>Quinlan</surname>
              <given-names>J</given-names>
            </name>
          </person-group>
          <article-title>Averting a UK opioid crisis: getting the public health messages 'right'</article-title>
          <source>J R Soc Med</source>
          <year>2022</year>
          <volume>115</volume>
          <issue>5</issue>
          <fpage>161</fpage>
          <lpage>164</lpage>
          <pub-id pub-id-type="doi">10.1177/01410768221089015</pub-id>
          <pub-id pub-id-type="medline">35352589</pub-id>
          <pub-id pub-id-type="pmcid">PMC9069619</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref26">
        <label>26</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>van Rysewyk</surname>
              <given-names>S</given-names>
            </name>
            <name name-style="western">
              <surname>Blomkvist</surname>
              <given-names>R</given-names>
            </name>
            <name name-style="western">
              <surname>Chuter</surname>
              <given-names>A</given-names>
            </name>
            <name name-style="western">
              <surname>Crighton</surname>
              <given-names>R</given-names>
            </name>
            <name name-style="western">
              <surname>Hodson</surname>
              <given-names>F</given-names>
            </name>
            <name name-style="western">
              <surname>Roomes</surname>
              <given-names>D</given-names>
            </name>
            <name name-style="western">
              <surname>Smith</surname>
              <given-names>BH</given-names>
            </name>
            <name name-style="western">
              <surname>Toye</surname>
              <given-names>F</given-names>
            </name>
          </person-group>
          <article-title>Understanding the lived experience of chronic pain: a systematic review and synthesis of qualitative evidence syntheses</article-title>
          <source>Br J Pain</source>
          <year>2023</year>
          <volume>17</volume>
          <issue>6</issue>
          <fpage>592</fpage>
          <lpage>605</lpage>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://europepmc.org/abstract/MED/37969135"/>
          </comment>
          <pub-id pub-id-type="doi">10.1177/20494637231196426</pub-id>
          <pub-id pub-id-type="medline">37969135</pub-id>
          <pub-id pub-id-type="pii">10.1177_20494637231196426</pub-id>
          <pub-id pub-id-type="pmcid">PMC10642495</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref27">
        <label>27</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Sandhu</surname>
              <given-names>HK</given-names>
            </name>
            <name name-style="western">
              <surname>Booth</surname>
              <given-names>K</given-names>
            </name>
            <name name-style="western">
              <surname>Furlan</surname>
              <given-names>AD</given-names>
            </name>
            <name name-style="western">
              <surname>Shaw</surname>
              <given-names>J</given-names>
            </name>
            <name name-style="western">
              <surname>Carnes</surname>
              <given-names>D</given-names>
            </name>
            <name name-style="western">
              <surname>Taylor</surname>
              <given-names>SJC</given-names>
            </name>
            <name name-style="western">
              <surname>Abraham</surname>
              <given-names>C</given-names>
            </name>
            <name name-style="western">
              <surname>Alleyne</surname>
              <given-names>S</given-names>
            </name>
            <name name-style="western">
              <surname>Balasubramanian</surname>
              <given-names>S</given-names>
            </name>
            <name name-style="western">
              <surname>Betteley</surname>
              <given-names>L</given-names>
            </name>
            <name name-style="western">
              <surname>Haywood</surname>
              <given-names>KL</given-names>
            </name>
            <name name-style="western">
              <surname>Iglesias-Urrutia</surname>
              <given-names>CP</given-names>
            </name>
            <name name-style="western">
              <surname>Krishnan</surname>
              <given-names>S</given-names>
            </name>
            <name name-style="western">
              <surname>Lall</surname>
              <given-names>R</given-names>
            </name>
            <name name-style="western">
              <surname>Manca</surname>
              <given-names>A</given-names>
            </name>
            <name name-style="western">
              <surname>Mistry</surname>
              <given-names>D</given-names>
            </name>
            <name name-style="western">
              <surname>Newton</surname>
              <given-names>S</given-names>
            </name>
            <name name-style="western">
              <surname>Noyes</surname>
              <given-names>J</given-names>
            </name>
            <name name-style="western">
              <surname>Nichols</surname>
              <given-names>V</given-names>
            </name>
            <name name-style="western">
              <surname>Padfield</surname>
              <given-names>E</given-names>
            </name>
            <name name-style="western">
              <surname>Rahman</surname>
              <given-names>A</given-names>
            </name>
            <name name-style="western">
              <surname>Seers</surname>
              <given-names>K</given-names>
            </name>
            <name name-style="western">
              <surname>Tang</surname>
              <given-names>NKY</given-names>
            </name>
            <name name-style="western">
              <surname>Tysall</surname>
              <given-names>C</given-names>
            </name>
            <name name-style="western">
              <surname>Eldabe</surname>
              <given-names>S</given-names>
            </name>
            <name name-style="western">
              <surname>Underwood</surname>
              <given-names>M</given-names>
            </name>
          </person-group>
          <article-title>Reducing opioid use for chronic pain with a group-based intervention: a randomized clinical trial</article-title>
          <source>JAMA</source>
          <year>2023</year>
          <volume>329</volume>
          <issue>20</issue>
          <fpage>1745</fpage>
          <lpage>1756</lpage>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://europepmc.org/abstract/MED/37219554"/>
          </comment>
          <pub-id pub-id-type="doi">10.1001/jama.2023.6454</pub-id>
          <pub-id pub-id-type="medline">37219554</pub-id>
          <pub-id pub-id-type="pii">2805141</pub-id>
          <pub-id pub-id-type="pmcid">PMC10208139</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref28">
        <label>28</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Wood</surname>
              <given-names>S</given-names>
            </name>
            <name name-style="western">
              <surname>Foy</surname>
              <given-names>R</given-names>
            </name>
            <name name-style="western">
              <surname>Willis</surname>
              <given-names>TA</given-names>
            </name>
            <name name-style="western">
              <surname>Carder</surname>
              <given-names>P</given-names>
            </name>
            <name name-style="western">
              <surname>Johnson</surname>
              <given-names>S</given-names>
            </name>
            <name name-style="western">
              <surname>Alderson</surname>
              <given-names>S</given-names>
            </name>
          </person-group>
          <article-title>General practice responses to opioid prescribing feedback: a qualitative process evaluation</article-title>
          <source>Br J Gen Pract</source>
          <year>2021</year>
          <volume>71</volume>
          <issue>711</issue>
          <fpage>e788</fpage>
          <lpage>e796</lpage>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://bjgp.org/lookup/pmidlookup?view=long&#38;pmid=33979300"/>
          </comment>
          <pub-id pub-id-type="doi">10.3399/BJGP.2020.1117</pub-id>
          <pub-id pub-id-type="medline">33979300</pub-id>
          <pub-id pub-id-type="pii">BJGP.2020.1117</pub-id>
          <pub-id pub-id-type="pmcid">PMC8407857</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref29">
        <label>29</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Toye</surname>
              <given-names>F</given-names>
            </name>
            <name name-style="western">
              <surname>Seers</surname>
              <given-names>K</given-names>
            </name>
            <name name-style="western">
              <surname>Tierney</surname>
              <given-names>S</given-names>
            </name>
            <name name-style="western">
              <surname>Barker</surname>
              <given-names>KL</given-names>
            </name>
          </person-group>
          <article-title>A qualitative evidence synthesis to explore healthcare professionals' experience of prescribing opioids to adults with chronic non-malignant pain</article-title>
          <source>BMC Fam Pract</source>
          <year>2017</year>
          <volume>18</volume>
          <issue>1</issue>
          <fpage>94</fpage>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://bmcfampract.biomedcentral.com/articles/10.1186/s12875-017-0663-8"/>
          </comment>
          <pub-id pub-id-type="doi">10.1186/s12875-017-0663-8</pub-id>
          <pub-id pub-id-type="medline">29178843</pub-id>
          <pub-id pub-id-type="pii">10.1186/s12875-017-0663-8</pub-id>
          <pub-id pub-id-type="pmcid">PMC5702226</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref30">
        <label>30</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Punwasi</surname>
              <given-names>R</given-names>
            </name>
            <name name-style="western">
              <surname>de Kleijn</surname>
              <given-names>L</given-names>
            </name>
            <name name-style="western">
              <surname>Rijkels-Otters</surname>
              <given-names>JBM</given-names>
            </name>
            <name name-style="western">
              <surname>Veen</surname>
              <given-names>M</given-names>
            </name>
            <name name-style="western">
              <surname>Chiarotto</surname>
              <given-names>A</given-names>
            </name>
            <name name-style="western">
              <surname>Koes</surname>
              <given-names>B</given-names>
            </name>
          </person-group>
          <article-title>General practitioners' attitudes towards opioids for non-cancer pain: a qualitative systematic review</article-title>
          <source>BMJ Open</source>
          <year>2022</year>
          <volume>12</volume>
          <issue>2</issue>
          <fpage>e054945</fpage>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://bmjopen.bmj.com/lookup/pmidlookup?view=long&#38;pmid=35105588"/>
          </comment>
          <pub-id pub-id-type="doi">10.1136/bmjopen-2021-054945</pub-id>
          <pub-id pub-id-type="medline">35105588</pub-id>
          <pub-id pub-id-type="pii">bmjopen-2021-054945</pub-id>
          <pub-id pub-id-type="pmcid">PMC8808445</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref31">
        <label>31</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Cross</surname>
              <given-names>AJ</given-names>
            </name>
            <name name-style="western">
              <surname>Buchbinder</surname>
              <given-names>R</given-names>
            </name>
            <name name-style="western">
              <surname>Mathieson</surname>
              <given-names>S</given-names>
            </name>
            <name name-style="western">
              <surname>Bourne</surname>
              <given-names>A</given-names>
            </name>
            <name name-style="western">
              <surname>Maher</surname>
              <given-names>CG</given-names>
            </name>
            <name name-style="western">
              <surname>Lin</surname>
              <given-names>CWC</given-names>
            </name>
            <name name-style="western">
              <surname>O'Connor</surname>
              <given-names>DA</given-names>
            </name>
          </person-group>
          <article-title>Barriers and enablers to monitoring and deprescribing opioid analgesics for chronic non-cancer pain: a systematic review with qualitative evidence synthesis using the theoretical domains framework</article-title>
          <source>BMJ Qual Saf</source>
          <year>2022</year>
          <volume>31</volume>
          <issue>5</issue>
          <fpage>387</fpage>
          <lpage>400</lpage>
          <pub-id pub-id-type="doi">10.1136/bmjqs-2021-014186</pub-id>
          <pub-id pub-id-type="medline">35064054</pub-id>
          <pub-id pub-id-type="pii">bmjqs-2021-014186</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref32">
        <label>32</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Goldacre</surname>
              <given-names>B</given-names>
            </name>
            <name name-style="western">
              <surname>MacKenna</surname>
              <given-names>B</given-names>
            </name>
          </person-group>
          <article-title>The NHS deserves better use of hospital medicines data</article-title>
          <source>BMJ</source>
          <year>2020</year>
          <volume>370</volume>
          <fpage>m2607</fpage>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://www.bmj.com/content/370/bmj.m2607"/>
          </comment>
          <pub-id pub-id-type="doi">10.1136/bmj.m2607</pub-id>
          <pub-id pub-id-type="medline">32680848</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref33">
        <label>33</label>
        <nlm-citation citation-type="web">
          <article-title>Prescribing costs in hospitals and the community: England April 2016 to March 2021</article-title>
          <source>NHS Business Services Authority</source>
          <year>2021</year>
          <access-date>2022-02-24</access-date>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://nhsbsa-opendata.s3.eu-west-2.amazonaws.com/pchc/pchc-2020-2021-narrative-v001.html">https://nhsbsa-opendata.s3.eu-west-2.amazonaws.com/pchc/pchc-2020-2021-narrative-v001.html</ext-link>
          </comment>
        </nlm-citation>
      </ref>
    </ref-list>
  </back>
</article>
