{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T17:55:17Z","timestamp":1767203717538,"version":"build-2238731810"},"update-to":[{"DOI":"10.3310\/nihropenres.13716.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T00:00:00Z","timestamp":1744243200000}},{"DOI":"10.3310\/nihropenres.13716.2","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T00:00:00Z","timestamp":1744243200000}}],"reference-count":51,"publisher":"National Institute for Health and Care Research","license":[{"start":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T00:00:00Z","timestamp":1744243200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.nationalarchives.gov.uk\/doc\/open-government-licence\/version\/3\/"}],"funder":[{"name":"National Institute for Health Research (NIHR), Applied Research Collaboration Kent, Surrey, and Sussex","award":["ARC KSS PCC50"],"award-info":[{"award-number":["ARC KSS PCC50"]}]}],"content-domain":{"domain":["openresearch.nihr.ac.uk"],"crossmark-restriction":false},"short-container-title":["NIHR Open Res"],"abstract":"<ns3:p>Background Opioids are frequently prescribed for short-term acute pain following surgery. Used appropriately, opioids deliver extremely favourable pain relief. Used longer than 90-days, however, can result in health complications, including unintentional overdose and addiction. Globally, &gt;40 million people are dependent on opioids and annually &gt;100,000 die from opioid misuse. With &gt;4.7 million surgical procedures occurring annually in the United Kingdom it is imperative that opioid-use is managed upon discharge. A declining General Practitioner (GP) workforce and increased patient numbers, however, means gaps in healthcare during transfer of care. Here we report a mixed-methods protocol to understand the feasibility, and acceptability of a clinical pharmacist (CP)-led early opioid deprescribing intervention for discharged surgical patients. Methods DESCALE is a multicentre, non-randomised, pragmatic feasibility study. Participants aged \u226518 years who have undergone a surgical procedure at a single NHS trust in Southeast England and discharged with opioids and without a history of long-term opioid use, cancer diagnosis or study contraindications will be offered a Medicines Use Review (MUR) within 7\u201310 days of discharge. The MUR will be delivered by CPs at participating GP practices. Feasibility outcomes will focus on recruitment, fidelity of CPs to deliver the MUR, and barriers within primary care that affect delivery of the intervention, with a maximum sample size of 100. Clinical outcomes will focus on the number of participants that reduce or stop opioid use within 91 days. Prescribing, medical, surgical, and demographic data for individual participants will be collected and analysed to inform future trial design. Qualitative interviews with participants and associated healthcare professionals will explore acceptability and implementation of the intervention. Conclusion Data collected with respect to opioid use post-surgery, feasibility and acceptability of the intervention, patient experience and outcome data will inform the design of future research and larger clinical trials.<\/ns3:p>","DOI":"10.3310\/nihropenres.13716.3","type":"journal-article","created":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T09:24:35Z","timestamp":1744277075000},"page":"48","update-policy":"https:\/\/doi.org\/10.3310\/nihropenres.crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacist-led DE-eSCALation of opioids post-surgical dischargE (DESCALE) \u2013 A multi-centre, non-randomised, feasibility study protocol"],"prefix":"10.3310","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6778-9929","authenticated-orcid":false,"given":"Emma L","family":"Veale","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5417-545X","authenticated-orcid":false,"given":"Johanna","family":"Theron","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7121-0414","authenticated-orcid":false,"given":"Melanie","family":"Rees-Roberts","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9805-7421","authenticated-orcid":false,"given":"Julie H","family":"Hedayioglu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5437-0045","authenticated-orcid":false,"given":"Ellie","family":"Santer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabina","family":"Hulbert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6231-0707","authenticated-orcid":false,"given":"Vanessa J","family":"Short","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"6221","published-online":{"date-parts":[[2025,4,10]]},"reference":[{"key":"ref-1","doi-asserted-by":"publisher","first-page":"6-12","DOI":"10.4103\/0970-9185.105784","article-title":"Opioid and chronic non-cancer pain.","volume":"29","author":"S Gupta","year":"2013","journal-title":"J Anaesthesiol Clin Pharmacol."},{"key":"ref-2","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD012509.pub2","article-title":"Adverse events associated with medium- and long-term use of opioids for chronic non-cancer pain: an overview of cochrane reviews.","volume":"10","author":"C Els","year":"2017","journal-title":"Cochrane Database Syst Rev."},{"key":"ref-3","doi-asserted-by":"publisher","first-page":"943-945","DOI":"10.1002\/cpt.1050","article-title":"The president\u2019s commission on combating drug addiction and the opioid crisis: origins and recommendations.","volume":"103","author":"B Madras","year":"2018","journal-title":"Clin Pharmacol Ther."},{"key":"ref-4","doi-asserted-by":"publisher","first-page":"44-49","DOI":"10.1016\/j.drugpo.2018.06.015","article-title":"Stigma and the public health agenda for the opioid crisis in America.","volume":"59","author":"P Corrigan","year":"2018","journal-title":"Int J Drug Policy."},{"key":"ref-5","article-title":"Deaths related to drug poisoning in England and Wales: 2020 registrations. 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Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/4-48\/v3\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/4-48\/v3\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/4-48\/v3\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T06:40:07Z","timestamp":1753339207000},"score":1,"resource":{"primary":{"URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/4-48\/v3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,10]]},"references-count":51,"URL":"https:\/\/doi.org\/10.3310\/nihropenres.13716.3","relation":{"has-version":[{"id-type":"doi","id":"10.3310\/nihropenres.13716.2","asserted-by":"subject"},{"id-type":"doi","id":"10.3310\/nihropenres.13716.1","asserted-by":"subject"}]},"ISSN":["2633-4402"],"issn-type":[{"value":"2633-4402","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,10]]},"assertion":[{"value":"Indexed","URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/4-48\/v3#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.3310\/nihropenres.15070.r34399, Judy Mullan, University of Wollongong, Wollongong, New South Wales, 28 Jan 2025, version 2, indexed","URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/4-48\/v2#referee-response-34399","order":0,"name":"referee-response-34399","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.3310\/nihropenres.14892.r33044, Neetu Bansal, The University of Manchester, Manchester, England, 25 Oct 2024, version 1, 3 approved with reservations","URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/4-48\/v1#referee-response-33044","order":1,"name":"referee-response-33044","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Emma Veale<\/b>; \n<i>Posted: 07 Jan 2025<\/i>; Thank you for the opportunity to review this submission, which addresses the important issue of problematic long-term opioid use in post-surgical patients. The mixed-methods approach employed in this feasibility study is well thought out and pragmatic, making it suitable for exploring the practicalities of early opioid de-escalation in primary care settings.  \n<b><i>Dear Dr Bansal, thank you for reviewing the manuscript, for your positive comments and recommendations to improve it. We realise that in an attempt to be concise we have missed some important details. We have responded to your queries below in bold and in the edited manuscript. <\/i><\/b>  There are several strengths in the study's aims and objectives, particularly in addressing a key public health issue. However, there are also a few areas that would benefit from further clarification and refinement to enhance the study\u2019s overall impact and feasibility. Below are some points for consideration: &nbsp;  Some objectives, such as &quot;ascertain stakeholder acceptability of the intervention&quot; and &quot;ascertain participant acceptability of the intervention,&quot; are somewhat broad and vague. These could be more clearly defined by specifying the exact dimensions of acceptability that will be measured, such as willingness to participate, perceived effectiveness, or identification of barriers to implementation.   While stakeholder interviews are mentioned, there is no clear identification of who the stakeholders are (e.g., GPs, surgeons, pharmacists, patients). Clarifying the stakeholder groups and how their perspectives will be incorporated into the analysis would strengthen the study. It would also be helpful to describe how the results from these interviews will influence the development or adaptation of the intervention  \n<i><b>We agree, these objectives are vague and concede that we have inadvertently oversimplified Table1 in an attempt to be concise. We have clarified the stakeholder groups that will be approached and added more detail around what information will be collected to inform the design of a future intervention in Table 1 and in the manuscript.<\/b><\/i> &nbsp;  The objective to &quot;Measure the capabilities of trained clinical pharmacists&quot; references &quot;observational competency checks by the Clinical Lead,&quot; but there is no information on how these checks will be standardised across different pharmacists or validated. Providing more detail on how competency will be measured (e.g., using competency frameworks or objective performance metrics) would enhance the robustness of this objective. Additional information on the training modules used to assess pharmacist capabilities would also be useful.  \n<b><i>Response: We determined that this type of MUR being delivered was standard procedure for the pharmacists participating in the study (most had been involved in a high-use opioid study previously with the clinical lead), and patients recruited deemed low-risk compared to long-term users of opioids. Therefore, the competency would be as expected in undertaking a standard MUR. However, all pharmacists received additional training by the Clinical Lead to conduct the MUR for the purpose of the study. For this they received an hour-long opioid lecture at the start, with signposting to multiple learning resources and regular individual contact with Dr Theron on each patient\u2019s reduction programme. For this feasibility study, we designed broad reduction pathways options (A, B, C,) for the pharmacists to follow and weekly drop-in sessions with the Clinical Lead for pharmacists to discuss any clinical queries that may have arisen. Each pharmacist also has a responsible GP to check their prescriptions as part of the partaking surgeries\u2019 agreement. Fidelity checks of the filled CRFs are performed by the research team and during the Clinical Lead\u2019s drop-in sessions for the pharmacists. We have replaced the word measure with assess. It is possible that more in-depth training in the form of modules may be a finding of our qualitative interviews with participating pharmacists.<\/i><\/b> &nbsp;  The use of EQ-5D-5L for measuring quality of life and pain scores is appropriate, but there is no mention of how changes in these metrics will be analysed in relation to opioid de-escalation. Outlining a plan for analysing pain and quality of life data in relation to opioid use (e.g., through subgroup analyses) would strengthen the interpretation of outcomes  \n<b><i>Thank you for pointing this out. We have added a bit more information as to how we will use this data in the analysis section.<\/i><\/b>  There is no clear plan for managing participants who do not respond to the intervention or who drop out before completion. Including an objective or process for handling non-responders would provide valuable insights into barriers to intervention effectiveness and inform the design of future studies.  \n<i><b>The practices collect baseline data (age, gender and surgical procedure) of all participants eligible for the intervention on the recruitment log. This data will be used to determine whether these factors influence non\/participation in the study. We have tried to make this clearer in the objectives and participant recruitment section. Unfortunately, due to the short time frame between identifying participants and inviting them to the study, we can only approach eligible participants once.<\/b><\/i>  \n<b>Additional Considerations:<\/b>  \n<b>Introduction<\/b>: The statement that opioids cause &quot;more pain&quot; needs clarification. It would be helpful to explicitly reference opioid-induced hyperalgesia to clarify that you are referring to increased sensitivity to pain as a potential side effect of long-term opioid use.  \n<b><i>Thank you for pointing this out. It had slipped in from previous lay summaries of the research. We have amended this<\/i><\/b>.  \n<b>Methods<\/b>:  It is unclear how often the discharge list will be generated and what the process will be for identifying patients. Providing more detail on how discharge lists will be compiled and reviewed would improve the transparency of participant identification.    \n<b><i>We had written under recruitment, that searches would be undertaken on a weekly basis, however this would be at the discretion and capacity of the practice and pharmacists to do this. I have adjusted to say weekly\/bi-monthly as this is more realistic of what we are experiencing. I agree that the method used to search for eligible patients is lacking. This is because individual GP practices have had to develop searches based on the systems that they use and the way in which they handle the discharge lists. No practice has been the same and will be reported as one of the barriers! <\/i><\/b> &nbsp;    What is the level of buy-in from clinical pharmacists? Will the same pharmacist consistently see each patient during follow-up? Consistency in pharmacist-patient interaction could influence outcomes, so it would be helpful to clarify this aspect.    \n<b><i>We will capture the level of buy-in from pharmacists through the interview process. We intend to interview pharmacists that engaged and those that didn\u2019t engage at practices which had undergone site-initiation. Time permitting, we will also approach pharmacists from other practices that had initially expressed an interest but did not participate. I have added this to the objectives.  We did not stipulate that the same pharmacist must complete follow-up reviews with the same participate. We have left this decision to the discretion of the practice. However, as the pharmacist books the next appointment with the patient at the MUR and most practices only have one pharmacist participating this has occurred spontaneously.<\/i><\/b> &nbsp;    Clarification is needed regarding the types of surgical procedures included in the study. Will both minor and major surgeries be included, and will day-case procedures also be part of the intervention?    \n<b><i>We include all types of surgical procedure (inpatient and outpatient), with the exclusion of caesarean sections and cancer patients. We have amended the inclusion criteria to be clearer.<\/i><\/b>    Exclusion criteria - how will you decide on 'severe' co-existing medical condition&nbsp;(using standardised co-morbidity scoring systems for example)    \n<b><i>No scoring is done, the rationale used will be the same as in any other clinic situation. Where there is uncertainty about a participant\u2019s suitability, this is discussed directly with the Clinical Lead who is the lead Clinician of a Chronic Pain service. If during the time of the project that assessing the severity of a medical condition is proving difficult for pharmacists, then we would report this as a barrier and use this information to adapt the intervention going forward. We have amended the exclusion criteria to reflect this.<\/i><\/b>    Pathway C - refer to non-pharmacological options as an option?    \n<b><i>This is not an option of this pathway or the project and would relate more to patients that are suffering from chronic pain (&gt;91 days) conditions or those that continue with opioids past 90 days and who are transferred back into the system for support.<\/i><\/b>    Pathway C - Continuation of opioids, &nbsp;benefits of taking opioids outweigh the risk of discontinuing opioid therapy - can you give examples of such situations as this appears vague    \n<b><i>This relates to the pain scores, where the patient is still suffering from severe pain at the time of the MUR which would warrant a continuation of opioids and in some circumstances potentially an increase in dose or a change in medication. We have amended the text to reflect this.<\/i><\/b>    Recruitment period Jan to September 2014. States 17 participants recruited. Does this refer to the patients? As per protocol sample size to aim for is around 100 participants.    \n<b><i>Yes, this related to the number of patients recruited at the time of submission of the manuscript. However, it should read 2024, not 2014!<\/i><\/b>  In summary, this is a well-constructed study that addresses an important topic. Strengthening the clarity and detail in the areas highlighted above would enhance the study\u2019s feasibility and robustness, ensuring it provides actionable insights into the effectiveness of early opioid de-escalation.  \n<b><i>Thank you!<\/i><\/b>","URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/4-48\/v3#referee-comment-3403","order":2,"name":"referee-comment-3403","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.3310\/nihropenres.15070.r34398, Liz Shaw, University of Exeter, Exeter, England, 23 Jan 2025, version 2, indexed","URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/4-48\/v2#referee-response-34398","order":3,"name":"referee-response-34398","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.3310\/nihropenres.15070.r34493, Deepika Rao, Dartmouth College, Hanover, NH, 04 Mar 2025, version 2, indexed","URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/4-48\/v2#referee-response-34493","order":4,"name":"referee-response-34493","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Emma Veale<\/b>; \n<i>Posted: 18 Mar 2025<\/i>; Thank you for reading the manuscript and your helpful comments. In response to your question; we did not offer any payment to participate in the study, as is standard in these types of trials. However after low response rate we amended our protocol to offer a &pound;25 shopping for any participants taking part in a post-intervention interview. We have amended the protocol to reflect this.","URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/4-48\/v3#referee-comment-3421","order":5,"name":"referee-comment-3421","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This project is funded by the National Institute for Health and Care Research (NIHR) under its Applied Research Collaboration Kent, Surrey, and Sussex (Grant Reference Number ARC KSS PCC50).  The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":6,"name":"grant-information","label":"Grant Information"},{"value":"This open access work is licensed under the Open Government Licence v3.0.","order":0,"name":"copyright-info","label":"Copyright"}]}}