improving Pain mAnagement for childreN and young people attendeD by Ambulance (PANDA): protocol for a realist review.

Acute Pain, Analgesia, Child, Emergency Medical Services, Paramedics, Paediatrics ALL Metrics - Views Downloads How to cite this article Nicholls G, Eaton G, Ortega M et al. improving Pain mAnagement for childreN and young people attendeD by Ambulance (PANDA): protocol for a realist review. [version 3; peer review: 3 approved]. NIHR Open Res 2025, 4:42 (https://doi.org/10.3310/nihropenres.13627.3) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente Select a format first ▬ ✚ Study Protocol Revised improving Pain mAnagement for childreN and young people attendeD by Ambulance (PANDA): protocol for a realist review. [version 3; peer review: 3 approved] Georgie Nicholls https://orcid.org/0000-0002-3936-2389 1, Georgette Eaton2,3, Marishona Ortega4, [...] Kacper Sumera https://orcid.org/0000-0002-1986-498X 5, Michael Baliousis https://orcid.org/0000-0002-8253-2208 6,7, Jessica Hodgson https://orcid.org/0000-0002-3198-890X 8, Despina Laparidou https://orcid.org/0000-0002-5427-7422 1, Aloysius Niroshan Siriwardena https://orcid.org/0000-0003-2484-8201 1, Paul Leighton9, Sarah Redsell10, Bill Lord https://orcid.org/0000-0001-8821-5353 11, Tatiana Bujor12, Gregory Adam Whitley https://orcid.org/0000-0003-2586-6815 1,13Georgie Nicholls https://orcid.org/0000-0002-3936-2389 1, Georgette Eaton2,3, [...] Marishona Ortega4, Kacper Sumera https://orcid.org/0000-0002-1986-498X 5, Michael Baliousis https://orcid.org/0000-0002-8253-2208 6,7, Jessica Hodgson https://orcid.org/0000-0002-3198-890X 8, Despina Laparidou https://orcid.org/0000-0002-5427-7422 1, Aloysius Niroshan Siriwardena https://orcid.org/0000-0003-2484-8201 1, Paul Leighton9, Sarah Redsell10, Bill Lord https://orcid.org/0000-0001-8821-5353 11, Tatiana Bujor12, Gregory Adam Whitley https://orcid.org/0000-0003-2586-6815 1,13 PUBLISHED 30 Jan 2025 Author details Author details 1 Community and Health Research Unit, University of Lincoln, Lincoln, England, LN6 7FS, UK 2 London Ambulance Service NHS Trust, London, England, SE1 8SD, UK 3 Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, England, OX2 6GG, UK 4 Libraries and Learning Skills, University of Lincoln, Lincoln, England, LN6 7TS, UK 5 East Midlands Ambulance Service NHS Trust, Nottingham, England, NG8 6PY, UK 6 School of Psychology, University of Lincoln, Lincoln, England, LN5 7TS, UK 7 Nottingham University Hospitals NHS Trust, Nottingham, England, NG5 1PB, UK 8 School of Medicine, University of Nottingham, Nottingham, England, NG7 2RD, UK 9 Applied Health Research Building (Building 42), University of Nottingham, Nottingham, England, NG7 2RD, UK 10 Faculty of Medicine & Health Sciences, University of Nottingham, Nottingham, England, NG7 2UH, UK 11 Monash University, Clayton, Victoria, Australia 12 The Medical School, Newcastle University, Newcastle upon Tyne, England, NE2 4HH, UK 13 Clinical Audit and Research Unit, East Midlands Ambulance Service NHS Trust, Lincoln, England, LN4 2HL, UK 2 London Ambulance Service NHS Trust, London, England, SE1 8SD, UK 3 Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, England, OX2 6GG, UK 4 Libraries and Learning Skills, University of Lincoln, Lincoln, England, LN6 7TS, UK 5 East Midlands Ambulance Service NHS Trust, Nottingham, England, NG8 6PY, UK 6 School of Psychology, University of Lincoln, Lincoln, England, LN5 7TS, UK 7 Nottingham University Hospitals NHS Trust, Nottingham, England, NG5 1PB, UK 8 School of Medicine, University of Nottingham, Nottingham, England, NG7 2RD, UK 9 Applied Health Research Building (Building 42), University of Nottingham, Nottingham, England, NG7 2RD, UK 10 Faculty of Medicine & Health Sciences, University of Nottingham, Nottingham, England, NG7 2UH, UK 11 Monash University, Clayton, Victoria, Australia 12 The Medical School, Newcastle University, Newcastle upon Tyne, England, NE2 4HH, UK 13 Clinical Audit and Research Unit, East Midlands Ambulance Service NHS Trust, Lincoln, England, LN4 2HL, UK Georgie Nicholls Roles: Data Curation, Formal Analysis, Methodology, Project Administration, Writing – Original Draft Preparation, Writing – Review & Editing Roles: Data Curation, Formal Analysis, Methodology, Project Administration, Writing – Original Draft Preparation, Writing – Review & Editing Georgette Eaton Roles: Methodology, Writing – Review & Editing Roles: Methodology, Writing – Review & Editing Marishona Ortega Roles: Methodology, Writing – Review & Editing Roles: Methodology, Writing – Review & Editing Kacper Sumera Roles: Methodology, Writing – Review & Editing Roles: Methodology, Writing – Review & Editing Michael Baliousis Roles: Methodology, Writing – Review & Editing Roles: Methodology, Writing – Review & Editing Jessica Hodgson Roles: Methodology, Writing – Review & Editing Roles: Methodology, Writing – Review & Editing Despina Laparidou Roles: Methodology, Writing – Review & Editing Roles: Methodology, Writing – Review & Editing Aloysius Niroshan Siriwardena Roles: Conceptualization, Funding Acquisition, Methodology, Writing – Review & Editing Roles: Conceptualization, Funding Acquisition, Methodology, Writing – Review & Editing Paul Leighton Roles: Conceptualization, Funding Acquisition, Methodology, Writing – Review & Editing Roles: Conceptualization, Funding Acquisition, Methodology, Writing – Review & Editing Sarah Redsell Roles: Conceptualization, Funding Acquisition, Methodology, Writing – Review & Editing Roles: Conceptualization, Funding Acquisition, Methodology, Writing – Review & Editing Bill Lord Roles: Conceptualization, Funding Acquisition, Methodology, Writing – Review & Editing Roles: Conceptualization, Funding Acquisition, Methodology, Writing – Review & Editing Tatiana Bujor Roles: Conceptualization, Methodology, Writing – Review & Editing Roles: Conceptualization, Methodology, Writing – Review & Editing Gregory Adam Whitley Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Methodology, Project Administration, Writing – Original Draft Preparation, Writing – Review & Editing Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Methodology, Project Administration, Writing – Original Draft Preparation, Writing – Review & Editing OPEN PEER REVIEW REVIEWER STATUS Each year in England, 450,000 children and young people (CYP) under 18 years of age are transported by ambulance to emergency departments. Approximately 20% of these suffer acute pain caused by illness or injury. Pain is a highly complex sensory and emotional experience. The intersection between acute pain, unwell CYP and the unpredictable pre-hospital environment is convoluted. Studies have shown that prehospital pain management in CYP is poor, with 61% of those suffering acute pain not achieving effective pain relief (abolition or reduction of pain score by 2 or more out of 10) when attended by ambulance. Consequences of poor acute pain management include altered pain perception, post-traumatic stress disorder and the development of chronic pain. This realist review will aim to understand how ambulance clinicians can provide improved prehospital acute pain management for CYP. A realist review will be conducted in accordance with the Realist And Meta-narrative Evidence Syntheses: Evolving Standards (RAMESES) guidance. A five-stage approach will be adopted; 1) Developing an Initial Programme Theory (IPT): develop an IPT with key stakeholder input and evidence from informal searching; 2) Searching and screening: conduct a thorough search of relevant research databases and other literature sources and perform screening in duplicate; 3) Relevance and rigour assessment: assess documents for relevance and rigour in duplicate; 4) Extracting and organising data: code relevant data into conceptual “buckets” using qualitative data analysis software; and 5) Synthesis and Programme Theory (PT) refinement: utilise a realist logic of analysis to generate context-mechanism-outcome configurations (CMOCs) within and across conceptual “buckets”, test and refine the IPT into a realist PT. The realist PT will enhance our understanding of what works best to improve acute prehospital pain management in CYP, which will then be tested and refined within a realist evaluation. PROSPERO Registration: CRD42024505978 Each year in England approximately 90,000 children and young people under 18 years of age suffer with acute pain and require transport by ambulance to emergency departments. The pain may have been caused by injuries such as wounds, burns or broken bones, or by illnesses such as tummy pain. Paramedics and other ambulance clinicians aim to reduce pain at the scene and during hospital transport. Whilst access to pain management is considered a fundamental human right, around 60% of children and young people who require an ambulance do not have their acute pain treated effectively. Without effective pain treatment, adverse consequences such as post-traumatic stress disorder may occur. We aim to understand how ambulance clinicians can provide improved prehospital acute pain management for children and young people. We will develop a theory about what is most important when considering the improvement of acute pain management for children and young people attended by ambulance. We will use published evidence, opinions from experts in the field, such as paramedics, paramedic educators and clinical leaders, and opinions from members of a Young Persons Advisory Group, to help us create this theory. We will then conduct a thorough search for any published documents that can help us test this theory. Such documents may include published journal articles, clinical practice guidelines, dissertations or newspaper articles for example. We will then use the information within all the relevant documents to test our theory and make refinements. This will allow us to produce a refined theory of what works best to improve acute pain suffered by children and young people who need an ambulance. We will then test and refine this theory in a future study by asking children, young people, parents, carers and ambulance clinicians about parts of the theory. Acute Pain, Analgesia, Child, Emergency Medical Services, Paramedics, Paediatrics Corresponding Author(s) Gregory Adam Whitley ([email protected]) Grant information: This project is funded by the National Institute for Health and Care Research (NIHR) under its [HEE/NIHR Integrated Clinical Academic Programme awarded to Gregory Adam Whitley (Grant Reference Number NIHR302875)]. The views expressed are those of the author(s) and not necessarily those of the NIHR, NHS or the Department of Health and Social Care. Georgie Nicholls was funded by the Advanced Clinical and Practitioner Academic Fellowship [NIHR302875]. Tatiana Bujor received reimbursement for involvement in line with NIHR INVOLVE rates, funded by the Advanced Clinical and Practitioner Academic Fellowship [NIHR302875]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Copyright: © 2025 Nicholls G et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite: Nicholls G, Eaton G, Ortega M et al. improving Pain mAnagement for childreN and young people attendeD by Ambulance (PANDA): protocol for a realist review. [version 3; peer review: 3 approved]. NIHR Open Res 2025, 4:42 (https://doi.org/10.3310/nihropenres.13627.3) First published: 23 Jul 2024, 4:42 (https://doi.org/10.3310/nihropenres.13627.1) Latest published: 30 Jan 2025, 4:42 (https://doi.org/10.3310/nihropenres.13627.3) Georgie Nicholls was funded by the Advanced Clinical and Practitioner Academic Fellowship [NIHR302875]. Tatiana Bujor received reimbursement for involvement in line with NIHR INVOLVE rates, funded by the Advanced Clinical and Practitioner Academic Fellowship [NIHR302875]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Minor amendments made in response to peer-review #3. We added references to support the definition of effective pain management, provided a justification for our search restrictions regarding date range and language, added some detail to the section “Step 5: Synthesis and programme theory refinement”, and added some detail to the section “Ambulance clinician involvement. Minor amendments made in response to peer-review #3. We added references to support the definition of effective pain management, provided a justification for our search restrictions regarding date range and language, added some detail to the section “Step 5: Synthesis and programme theory refinement”, and added some detail to the section “Ambulance clinician involvement. See the authors' detailed response to the review by Heli Salmi See the authors' detailed response to the review by Andrit Lourens See the authors' detailed response to the review by Simit Sapkota and Sunil Shrestha Ambulance services across England transport 4.7 million patients to emergency departments (ED) each year, of which 450,000 (9.5%) are children and young people (CYP) under 18 years of age1. Acute pain caused by injury or illness is a common symptom presented to ambulance clinicians, and is suffered by approximately 20% of transported CYP2. Paramedics and other ambulance clinicians aim to reduce pain at the scene and during hospital transport3, however this can be challenging in CYP due to a variety of barriers. These include fear and anxiety – which can distort pain assessment4, environmental factors, staff feeling ill prepared to manage pain due to limited education and training and low exposure rates to CYP, and difficulties in assessing and treating pain, particularly regarding limited analgesic options and difficulties of analgesic administration in CYP5. Access to pain management is considered a fundamental human right6 and effective pain relief has been identified as a key quality outcome measure for ambulance services7. Despite this, prehospital pain management in CYP is considered poor8,9. Ambulances, equipment and staff uniform, are often not tailored towards CYP, and as such, an ambulance call out can be a frightening experience5. A recent study found that only 39% of CYP who suffered acute pain in the prehospital setting achieved effective pain relief (defined as the abolition or reduction of pain >=2 points on a 10-point scale)2,10–12. The consequences of poor acute pain management may include the development of post-traumatic stress disorder13,14, altered pain perception15,16, and the subsequent development of chronic pain17,18. Typically, within the UK CYP who require an emergency ambulance for acute pain are attended by a registered paramedic or emergency medical technician (EMT). In more critical cases, they may also be attended by paramedics with enhanced skills or doctors via a specialist service. Pain is typically measured using the Face, Legs, Activity, Cry, Consolability (FLACC) scale for those unable to communicate their pain, the Wong and Baker FACES® scale for those aged 3 years and above, and the numeric pain rating scale for those aged around 8 years and above3. The scope of practice between these clinicians vary significantly, with EMTs able to administer only nitrous oxide and simple oral analgesics such as paracetamol and ibuprofen, to paramedics who can also administer paracetamol (intravenous) along with morphine sulfate (oral, subcutaneous, intramuscular, intravenous)19, to paramedics with enhanced skills who can also administer intravenous ketamine. Doctors have a much greater scope of analgesic options available, including fentanyl and diamorphine. The limited range of analgesic options available to UK ambulance clinicians are in part due to legal restrictions19,20 which preclude the use of key controlled drugs such as fentanyl by UK registered paramedics, which can be administered intranasally21 or via a lozenge22. Nitrous oxide is widely available to UK ambulance clinicians but is challenging to administer to CYP due to its cumbersome nature23. Methoxyflurane offers a promising alternative due to its light weight and ease of use, but is not currently licenced for children in the UK24, with results of a major clinical trial due soon25. These legal restrictions may change in the wake of the Manchester Arena Enquiry26 and the recent call to arms to “make children’s pain matter” by Eccleston et al.27, however reliance for improvement should not rest on single strategies. Whilst an increased range of analgesics would be welcome, it would unlikely resolve the complex challenge of providing effective prehospital pain management for CYP28, therefore other strategies should be explored. This realist review will aim to understand how ambulance clinicians can provide improved prehospital acute pain management for CYP. The review will focus on potential behaviour change intervention components that could be aimed at ambulance clinicians. A Young Persons Advisory Group (YPAG) has been set up to advise on the initial design of the PANDA Study29. The YPAG group will continue to provide input within this realist review. The group was recruited from a state funded secondary school and comprises 25 members in total. The age range of members spans from 12 to 18 years, 60% are female (n = 15), 64% White (n = 16), 24% Asian or Asian British (n = 6) and 13% Other or Mixed ethnicity (n = 3). Four of the YPAG members have experience of being in an ambulance with a painful condition, three have been in an ambulance for other reasons and four have witnessed friends or family members going into an ambulance. The YPAG group will meet to provide insights and suggestions to develop and refine the initial programme theory (IPT) and to assist in the interpretation of the synthesis and refinement of the realist programme theory. An established patient and public involvement group based at the University of Lincoln (the Healthier Ageing Patient and Public Involvement (HAPPI) group)), was involved during the initial design of the PANDA Study. The HAPPI group will continue to be involved at key stages throughout this realist review, particularly to assist with the interpretation of findings. The HAPPI Group members will provide input from a “public” perspective and will also bring external expertise to the project from their links to other patient and public involvement groups and from experience of advising several other prehospital ambulance-based research projects. The overall PANDA Study is a realist informed complex intervention development and feasibility study, consisting of a realist review, a realist evaluation, consensus workshops and a feasibility trial30. The aim of the PANDA Study is to develop and test an intervention to improve pre-hospital pain management for CYP by exploring what interventions work, for whom, in what context and how. This paper reports the protocol for the realist review component of the PANDA Study. The PANDA Study will be framed within a realist approach as described by Pawson31–33, which aligns to the Medical Research Council guidelines for complex intervention development34. A realist approach seeks to understand why, how, to what extent, for whom and in what circumstances a programme or intervention works35. It assumes that interventions or programmes themselves do not cause outcomes, rather, it is the resources offered by the intervention that trigger a response from the participant through underlying unseen mechanisms, that cause outcomes, within a specific context35. These context-mechanism-outcome configurations (CMOCs) are the foundation on which programme theory is built and may be informed by primary (realist evaluation) or secondary (realist review) data32,33. A realist review will be conducted, following the Realist And Meta-narrative Evidence Syntheses: Evolving Standards (RAMESES) guidance35. The realist review has been registered on PROSPERO, the international prospective register of systematic reviews (CRD42024505978)36. There are currently no equator network publication standards for realist review protocols, therefore we used the realist review publication standards as a framework to report this protocol37 The objectives for this realist review are: 1. To develop an IPT to map the key processes of prehospital acute pain management in CYP. 2. To focus on specific areas of the IPT to explore potential behaviour change intervention components aimed at ambulance clinicians and determine; for whom they work; in what circumstances; how; and to what extent they work. 3. To refine the IPT into a realist programme theory supported by context, mechanism, outcome configurations (CMOCs). We will adopt a five-stage approach to conduct this realist review, informed by the RAMSES guidance35, Pawson32 and a recent realist review38. These steps will include: The first stage of this realist review will involve locating existing theories about prehospital pain management in CYP. This will involve informal searches to identify key theories in the field, what the predictors, barriers and facilitators are for effective prehospital pain management in CYP, and which components of the process are considered most important. Whilst this process is subjective, we will offset this by involving multiple key stakeholder groups in the development of the IPT, namely an Ambulance Clinician Advisory Group (ACAG), a Young Persons Advisory Group (YPAG) and a PANDA Study Realist Review Working Group. The inclusion of these groups is important as realist reviews are driven by stakeholders, enabling the inclusion of multiple perspectives39,40. Informal searches will be conducted to ensure that relevant documents are identified, and key data are incorporated within the IPT development process. One member of the review team (GAW) has access to a large number of relevant documents (including journal articles, theses and book chapters), having recently completed a PhD on the topic of prehospital pain management in children. Combining these documents with stakeholder input and iterative discussion within the PANDA Study Realist Review Working Group will enable the development of our IPT. With the assistance of an academic librarian (MO), the IPT will be used as a framework to develop a comprehensive search strategy. Database Search: Relevant keywords, subject headings and Boolean operators will be used to search major bibliographic databases. The EBSCOHost platform will be used to search MEDLINE, Cumulative Index to Nursing & Allied Health (CINAHL) Complete, PsycINFO, Web of Science Core Collection, Education Source, Education Resources Information Centre (ERIC), and The Cochrane Library Searching Other Resources: The clinical trials registry ISRCTN will be searched, along with other literature sources such as ProQuest, including ProQuest Dissertations and Theses, and Google. Expert knowledge will also be used to identify relevant documents not found during these searches. Forward and backward citation tracking will be conducted for all included documents. Additional searches may be required during the realist review as programme theory testing and refinement progresses. Informed by a recent systematic mixed studies review on this topic that searched core databases from inception, and included papers from 2006 to 20205, we will restrict our search to documents published from January 2000 onwards, due to known limited evidence prior to 20005. In-line with a realist philosophy of science32, all sources of information may contribute to the development of realist programme theory, therefore we will include, where relevant, research articles, clinical practice guidelines, policy documents, websites of professional bodies or reputable organisations, conference abstracts, theses and dissertations, along with curricula. In addition to the wide range of documents eligible for inclusion, only documents reported in English (due to time and resource constraints) and involving or aimed at the following populations will be included: Documents will be excluded if they are: Based in the battlefield, in-hospital, primary care or helicopter emergency medical service (HEMS) setting. Documents from these settings would not be representative of standard ambulance service practice. Focussed on chronic pain. Documents reporting prehospital acute pain management data for children, young people and adults will be excluded if the data for CYP under 18 years of age cannot be isolated and extracted. Identified documents from the database search will be imported to Covidence (copyright licence obtained) software and screened independently in duplicate. Documents will be screened first by title and abstract, followed by full text review against the inclusion and exclusion criteria. Documents identified from other resources will be added to and managed within MS Excel software and screened independently in duplicate. These documents will be subject to an initial screen, similar in nature to the title and abstract screen, followed by a full-text screen, where the full document will be reviewed against the inclusion and exclusion criteria. Disagreements on inclusion will be resolved through discussion, or involvement of a third member of the review team. Documents deemed to meet the inclusion criteria will then be assessed for relevance and rigour, as per the RAMESES guidelines35. Relevance relates to the ability of data within a document to contribute to the testing and refinement of programme theory, and rigour relates to whether the methods used to generate the relevant data are credible and trustworthy35. Whilst there is relative consensus regarding the methods to assess the relevance of documents within a realist review, there is substantial uncertainty among academics regarding how best to assess rigour41. Given the adoption of a realist philosophy of science32, using a checklist approach to quality assessment, as standard within a systematic review42, is less helpful in a realist review due to the inclusive nature of data from a wide variety of sources. We will therefore not use critical appraisal/quality checklists as part of our rigour assessment. The assessment of relevance will be dichotomous (yes/no) and conducted within MS Excel software. Two reviewers will separately assess relevance of a small sample of documents and discuss with the PANDA Study Realist Review Working Group as a benchmarking exercise. If agreement is achieved, the remaining documents will be assessed for relevance, in duplicate. Disagreements will be resolved through discussion, or involvement of a third member of the review team. A third reviewer will assess 10% of reviewed documents to ensure consistency. Documents deemed not relevant will be excluded from the review. Rigour will be assessed in duplicate by two reviewers independently and based on reviewer judgement of document trustworthiness. A rating scale will be used to determine the rigour of each document (low, moderate or high rigour). Disagreements will be settled through discussion, or the involvement of a third reviewer. A third reviewer will assess 10% of reviewed documents to ensure consistency. Rigour will be assessed at the level of the data and at the level of the programme theory41. Documents deemed highly trustworthy and credible at the level of the data (for example where clear methods of data production are described and references for evidence sources are listed) and are coherent at the level of the programme theory and provide consilience and analogy (for example where the documents support the programme theory well), will be rated high. Rigour will not be used as a reason for exclusion43. Instead, CMOCs that are considered conceptually weak (i.e. the documents informing the CMOCs are mostly rated as low or moderate rigour) will be tested further through additional iterative searches, or within the realist evaluation. The number of included documents will be reported using a PRISMA flow diagram42. Data extraction will occur in two phases. 1. The characteristics of included documents will be manually extracted into a Microsoft Word document, including bibliographic information and details about document type and population. This will form the summary of included documents table. This will be performed by one reviewer and verified in full by a second. 2. Included documents will then be uploaded to NVivo version 14 (copyright licence obtained) software for data extraction (coding). Data will not be extracted per se, rather the full documents will be uploaded for coding. Qualitative and quantitative text that is relevant to the IPT will be coded; this may consist of descriptions, findings or explanations of programmes or interventions that aim to improve prehospital acute pain management for CYP37. Coding will be deductive (based on the IPT), inductive (where new conceptual buckets arise) and retroductive (when inferring causal mechanisms within CMOC development). Text will be coded as “parent nodes” or “child nodes” iteratively and combined/expanded during the organising phase of analysis. Coding will be conducted by one reviewer, with 10% of coded documents checked by a second reviewer. Codes assigned as “parent nodes” will be viewed as conceptual “buckets”44. Text may be coded into more than one conceptual “bucket”. As more sections of coded text are added to each conceptual “bucket”, two reviewers will periodically pause to determine, as far as possible, what is functioning as context, mechanism and outcome, thereby creating CMOCs. This process will use a realist logic of analysis32. This interpretation will be iterative in nature and reviewed extensively by the Working Group and key stakeholders to reduce researcher bias. Coded text from more than one conceptual “bucket” may be used to create CMOCs. For each developed CMOC, a new “parent node” will be created, with all the supporting data extracts for the CMOC added. This will ensure clean and clear traceability between source data, CMOC and programme theory. Each developed and substantiated CMOC will contribute to the development and refinement of the realist programme theory. CMOCs that are unsubstantiated, either due to low rigour or conflicting data, may be tested further through additional iterative searches or through the realist evaluation. Data to inform our interpretation of the relationships between contexts, mechanisms and outcomes will be sought across documents. There may be instances where data coded from documents contradict each other, or only supply part of the CMOC. We may juxtapose, reconcile, adjudicate, consolidate or situate (Pawson, 2006) findings throughout the analytic process, as necessary. We will test the IPT with data collected and synthesised from this review and refine it into realist programme theory supported by CMOCs. As this review is not assessing a specific intervention or programme, but rather the process of prehospital acute pain management in CYP, we anticipate the realist programme theory to be segregated into stages based on outcome, progressing from proximal outcomes (focussed on ambulance clinicians – such as confidence and knowledge) to more distal outcomes (focussed on CYP – such as pain severity). The programme theory developed from a recent realist review will be used as a framework to develop our realist programme theory45. The realist programme theory we develop will then be used to develop and test a complex intervention aimed at ambulance clinicians in a future stage of the PANDA Study. In addition to the patient and public involvement groups, we will involve other key stakeholders including ambulance clinicians, academics, clinical and non-clinical psychologists. An Ambulance Clinician Advisory Group (ACAG) has been established, with expertise from the fields of clinical practice, education, and senior leadership, ranging from the South to the North of England, and Scotland. The group will meet at several stages of the review to provide insights and their expert knowledge to help with the development and refinement of the IPT, provide advice and feedback on the PT as it develops, identify any relevant literature that will assist with the research and to facilitate the interpretation of the findings. A bespoke PANDA Study Realist Review Working Group has been created for the realist review component of the PANDA Study, which consists of academics with expertise on realist methods, the prehospital setting and the population of CYP, clinicians, ambulance service representatives, along with clinical and non-clinical psychologists. The group will meet monthly, or more if required, to discuss the progress of the realist review and provide expertise at all stages of the review. Not required. NVivo 14 is a proprietary software, free alternatives such as QualCoder (https://qualcoder.wordpress.com/) could be used. Covidence is a proprietary software, alternatives such as Rayyan (https://www.rayyan.ai/) have a free membership option. Georgie Nicholls: Data Curation, Formal Analysis, Methodology, Project Administration, Writing – Original Draft Preparation, Writing – Review & Editing Georgette Eaton: Methodology, Writing – Review & Editing Despina Laparidou: Methodology, Writing – Review & Editing Marishona Ortega: Methodology, Writing – Review & Editing Kacper Sumera: Methodology, Writing – Review & Editing Michael Baliousis: Methodology, Writing – Review & Editing Jessica Hodgson: Methodology, Writing – Review & Editing Aloysius Niroshan Siriwardena: Conceptualization, Funding Acquisition, Methodology, Writing – Review & Editing Paul Leighton: Conceptualization, Funding Acquisition, Methodology, Writing – Review & Editing Sarah Redsell: Conceptualization, Funding Acquisition, Methodology, Writing – Review & Editing Bill Lord: Conceptualization, Funding Acquisition, Methodology, Writing – Review & Editing Tatiana Bujor: Conceptualization, Methodology, Writing – Review & Editing Gregory Adam Whitley: Conceptualization, Funding Acquisition, Data Curation, Formal Analysis, Methodology, Project Administration, Writing – Original Draft Preparation, Writing – Review & Editing We acknowledge the following individuals and groups for their contribution to the PANDA Study: members of the Young Persons Advisory Group (YPAG), Queen Elizabeth’s High School (QEHS), Gainsborough, for their active participation in the design and delivery of the PANDA Study; Michael Betts (QEHS), Adrian O’Neill (QEHS) and Rick Eastham (QEHS) for setting up the YPAG group and for their ongoing support; members of the Healthier Ageing Patient and Public Involvement (HAPPI) group for their active participation in the design and delivery of the PANDA Study; Martin Esposito (Scottish Ambulance Service), Ashley Scaife (University of Huddersfield), Emily Hoyles (South East Coast Ambulance Service NHS Trust) and Sharon Young (East Midlands Ambulance Service NHS Trust) for their roles as members of the PANDA Study Ambulance Clinician Advisory Group; Tom Waterfield (Queen’s University Belfast), Samina Ali (University of Alberta), Michael Smyth (University of Warwick), Alison Porter (Swansea University) and Amanda Brewster (University of Lincoln HAPPI Group) for their roles as independent members of the PANDA Study steering committee; Gemma Squires (East Midlands Ambulance Service NHS Trust) and Robert Spaight (East Midlands Ambulance Service NHS Trust) for providing governance oversight as sponsor and expert advice. Faculty Opinions recommendedReferences - 1. NHS Digital: Hospital accident & emergency activity 2021–22. 2020; Accessed 19-Apr-2024. Reference Source - 2. Whitley GA, Hemingway P, Law GR, et al.: Predictors of effective management of acute pain in children within a UK ambulance service: a cross-sectional study. Am J Emerg Med. 2020; 38(7): 1424–1430. PubMed Abstract | Publisher Full Text - 3. Joint Royal Colleges Ambulance Liaison Committee and Association of Ambulance Chief Executives: JRCALC Clinical Guidelines 2022. Bridgwater: Class Professional Publishing; 2022. Reference Source - 4. Williams DM, Rindal KE, Cushman JT, et al.: Barriers to and enablers for prehospital analgesia for pediatric patients. Prehosp Emerg Care. 2012; 16(4): 519–526. PubMed Abstract | Publisher Full Text - 5. Whitley GA, Hemingway P, Law GR, et al.: The predictors, barriers and facilitators to effective management of acute pain in children by emergency medical services: a systematic mixed studies review. J Child Health Care. 2021; 25(3): 481–503. PubMed Abstract | Publisher Full Text | Free Full Text - 6. Brennan F, Lohman D, Gwyther L: Access to pain management as a human right. Am J Public Health. 2019; 109(1): 61–65. PubMed Abstract | Publisher Full Text | Free Full Text - 7. Turner J, Siriwardena AN, Coster J, et al.: Developing new ways of measuring the quality and impact of ambulance service care: the PhOEBE mixed-methods research programme. Programme Grants Appl Res. 2019; 7(3). PubMed Abstract | Publisher Full Text - 8. Samuel N, Steiner IP, Shavit I: Prehospital pain management of injured children: a systematic review of current evidence. Am J Emerg Med. 2015; 33(3): 451–454. PubMed Abstract | Publisher Full Text - 9. Lord B, Jennings PA, Smith K: The epidemiology of pain in children treated by paramedics. Emerg Med Australas. 2016; 28(3): 319–324. PubMed Abstract | Publisher Full Text - 10. Bulloch B, Tenenbein M: Assessment of clinically significant changes in acute pain in children. Acad Emerg Med. 2002; 9(3): 199–202. PubMed Abstract | Publisher Full Text - 11. Bailey B, Daoust R, Doyon-Trottier E, et al.: Validation and properties of the verbal numeric scale in children with acute pain. Pain. 2010; 149(2): 216–221. PubMed Abstract | Publisher Full Text - 12. Tsze DS, Hirschfeld G, von Baeyer CL, et al.: Clinically significant differences in acute pain measured on self-report pain scales in children. Acad Emerg Med. 2015; 22(4): 415–22. PubMed Abstract | Publisher Full Text | Free Full Text - 13. Sheridan RL, Stoddard FJ, Kazis LE, et al.: Long-term posttraumatic stress symptoms vary inversely with early opiate dosing in children recovering from serious burns: effects durable at 4 years. J Trauma Acute Care Surg. 2014; 76(3): 828–832. PubMed Abstract | Publisher Full Text - 14. Saxe G, Stoddard F, Courtney D, et al.: Relationship between acute morphine and the course of PTSD in children with burns. J Am Acad Child Adolesc Psychiatry. 2001; 40(8): 915–921. PubMed Abstract | Publisher Full Text - 15. Taddio A, Katz J, Ilersich AL, et al.: Effect of neonatal circumcision on pain response during subsequent routine vaccination. Lancet. 1997; 349(9052): 599–603. PubMed Abstract | Publisher Full Text - 16. Weisman SJ, Bernstein B, Schechter NL: Consequences of inadequate analgesia during painful procedures in children. Arch Pediatr Adolesc Med. 1998; 152(2): 147–149. PubMed Abstract | Publisher Full Text - 17. Daoust R, Paquet J, Cournoyer A, et al.: Relationship between acute pain trajectories after an emergency department visit and chronic pain: a Canadian prospective cohort study. BMJ Open. 2020; 10(12): e040390. PubMed Abstract | Publisher Full Text | Free Full Text - 18. McKillop HN, Banez GA: A broad consideration of risk factors in pediatric chronic pain: where to go from here? Children (Basel). 2016; 3(4): 38. PubMed Abstract | Publisher Full Text | Free Full Text - 19. The Human Medicines Regulations 2012. 2012. - 20. The Misuse of Drugs Regulations 2001. 2001. - 21. Lord B, Jennings PA, Smith K: Effects of the introduction of intranasal fentanyl on reduction of pain severity score in children: an interrupted time-series analysis. Pediatr Emerg Care. 2019; 35(11): 749–754. PubMed Abstract | Publisher Full Text - 22. Mahar PJ, Rana JA, Kennedy CS, et al.: A Randomized Clinical Trial of oral transmucosal fentanyl citrate versus intravenous morphine sulfate for initial control of pain in children with extremity injuries. Pediatr Emerg Care. 2007; 23(8): 544–548. PubMed Abstract | Publisher Full Text - 23. Whitley GA, Hemingway P, Law GR, et al.: Improving ambulance care for children suffering acute pain: a qualitative interview study. BMC Emerg Med. 2022; 22(1): 96. PubMed Abstract | Publisher Full Text | Free Full Text - 24. Electronic Medicines Compendium: PENTHROX 99.9%, 3 ml inhalation vapour, liquid. 2023; Accessed 19 Apr-2024. Reference Source - 25. Hartshorn S, Barrett MJ, Lyttle MD, et al.: Inhaled methoxyflurane (Penthrox®) versus placebo for injury-associated analgesia in children-the MAGPIE trial (MEOF-002): study protocol for a randomised controlled trial. Trials. 2019; 20(1): 393. PubMed Abstract | Publisher Full Text | Free Full Text - 26. Saunders J: Manchester Arena Inquiry Volume 2: emergency response. 2022; Accessed 06 Nov-2023. Reference Source - 27. Eccleston C, Fisher E, Howard RF, et al.: Delivering transformative action in paediatric pain: a Lancet Child & Adolescent Health Commission. Lancet Child Adolesc Health. 2021; 5(1): 47–87. PubMed Abstract | Publisher Full Text - 28. Lord B, Jennings PA, Smith K: Effects of the introduction of intranasal fentanyl on reduction of pain severity score in children: an interrupted time-series analysis. Pediatr Emerg Care. 2019; 35(11): 749–754. PubMed Abstract | Publisher Full Text - 29. Whitley GA, Siriwardena A, Redsell S, et al.: 236 developing a Young Persons Advisory Group (YPAG) to inform the design of a study to improve pre-hospital pain management for Children and Young People (CYP). BMJ Open. 2022; 12(Suppl 1): A2–A3. Publisher Full Text - 30. National Institute for Health and Care Research: Improving Pain mAnagement for childreN and young people attendeD by Ambulance (PANDA): a realist informed intervention development and feasibility study. 2023; Accessed 23 Apr-2024. Reference Source - 31. Pawson R: The science of evaluation: a realist manifesto. SAGE Publications; 2013. Publisher Full Text - 32. Pawson R: Evidence-based policy: a realist perspective. SAGE Publications; 2006. Reference Source - 33. Pawson R, Tilley N: Realistic evaluation. SAGE Publications; 1997. Reference Source - 34. Skivington K, Matthews L, Simpson SA, et al.: A new framework for developing and evaluating complex interventions: update of Medical Research Council guidance. BMJ. 2021; 374: n2061. PubMed Abstract | Publisher Full Text | Free Full Text - 35. Wong G, Greenhalgh T, Westhorp G, et al.: Development of methodological guidance, publication standards and training materials for realist and meta-narrative reviews: the RAMESES (Realist And Meta-narrative Evidence Syntheses - Evolving Standards) project. Health Serv Deliv Res. 2014; 2(30). PubMed Abstract | Publisher Full Text - 36. Horner G, Siriwardena A, Hodgson J, et al.: How can ambulance clinicians provide improved acute pain management for children and young people (PANDA Study)? A realist review. 2024; Accessed 23 Apr-2024. Reference Source - 37. Wong G, Greenhalgh T, Westhorp G, et al.: RAMESES publication standards: realist syntheses. BMC Med. 2013; 11(1): 21. PubMed Abstract | Publisher Full Text | Free Full Text - 38. Wong G, Brennan N, Mattick K, et al.: Interventions to improve antimicrobial prescribing of doctors in training: the IMPACT (IMProving Antimicrobial presCribing of doctors in Training) realist review. BMJ Open. 2015; 5(10): e009059. PubMed Abstract | Publisher Full Text | Free Full Text - 39. Rycroft-Malone J, McCormack B, Hutchinson AM, et al.: Realist synthesis: illustrating the method for implementation research. Implement Sci. 2012; 7(1): 33. PubMed Abstract | Publisher Full Text | Free Full Text - 40. Kantilal K, Hardeman W, Whiteside H, et al.: Realist review protocol for understanding the real-world barriers and enablers to practitioners implementing self-management support to people living with and beyond cancer. BMJ Open. 2020; 10(9): e037636. PubMed Abstract | Publisher Full Text | Free Full Text - 41. Dada S, Dalkin S, Gilmore B, et al.: Applying and reporting relevance, richness and rigour in realist evidence appraisals: advancing key concepts in realist reviews. Res Synth Methods. 2023; 14(3): 504–514. PubMed Abstract | Publisher Full Text - 42. Page MJ, McKenzie JE, Bossuyt PM, et al.: The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021; 372: n71. PubMed Abstract | Publisher Full Text | Free Full Text - 43. Weetman K, Wong G, Scott E, et al.: Improving best practice for patients receiving hospital discharge letters: a realist review. BMJ Open. 2019; 9(6): e027588. PubMed Abstract | Publisher Full Text | Free Full Text - 44. Howe J, MacPhee M, Duddy C, et al.: A realist review of medication optimisation of community dwelling service users with serious mental illness. BMJ Qual Saf. 2025; 34(1): 40–52. PubMed Abstract | Publisher Full Text | Free Full Text - 45. Price T, Brennan N, Wong G, et al.: Remediation programmes for practising doctors to restore patient safety: the RESTORE realist review. Health Serv Deliv Res. 2021; 9(11): 1–116. PubMed Abstract | Publisher Full Text Author details Author details 1 Community and Health Research Unit, University of Lincoln, Lincoln, England, LN6 7FS, UK 2 London Ambulance Service NHS Trust, London, England, SE1 8SD, UK 3 Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, England, OX2 6GG, UK 4 Libraries and Learning Skills, University of Lincoln, Lincoln, England, LN6 7TS, UK 5 East Midlands Ambulance Service NHS Trust, Nottingham, England, NG8 6PY, UK 6 School of Psychology, University of Lincoln, Lincoln, England, LN5 7TS, UK 7 Nottingham University Hospitals NHS Trust, Nottingham, England, NG5 1PB, UK 8 School of Medicine, University of Nottingham, Nottingham, England, NG7 2RD, UK 9 Applied Health Research Building (Building 42), University of Nottingham, Nottingham, England, NG7 2RD, UK 10 Faculty of Medicine & Health Sciences, University of Nottingham, Nottingham, England, NG7 2UH, UK 11 Monash University, Clayton, Victoria, Australia 12 The Medical School, Newcastle University, Newcastle upon Tyne, England, NE2 4HH, UK 13 Clinical Audit and Research Unit, East Midlands Ambulance Service NHS Trust, Lincoln, England, LN4 2HL, UK 2 London Ambulance Service NHS Trust, London, England, SE1 8SD, UK 3 Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, England, OX2 6GG, UK 4 Libraries and Learning Skills, University of Lincoln, Lincoln, England, LN6 7TS, UK 5 East Midlands Ambulance Service NHS Trust, Nottingham, England, NG8 6PY, UK 6 School of Psychology, University of Lincoln, Lincoln, England, LN5 7TS, UK 7 Nottingham University Hospitals NHS Trust, Nottingham, England, NG5 1PB, UK 8 School of Medicine, University of Nottingham, Nottingham, England, NG7 2RD, UK 9 Applied Health Research Building (Building 42), University of Nottingham, Nottingham, England, NG7 2RD, UK 10 Faculty of Medicine & Health Sciences, University of Nottingham, Nottingham, England, NG7 2UH, UK 11 Monash University, Clayton, Victoria, Australia 12 The Medical School, Newcastle University, Newcastle upon Tyne, England, NE2 4HH, UK 13 Clinical Audit and Research Unit, East Midlands Ambulance Service NHS Trust, Lincoln, England, LN4 2HL, UK Georgie Nicholls Roles: Data Curation, Formal Analysis, Methodology, Project Administration, Writing – Original Draft Preparation, Writing – Review & Editing Roles: Data Curation, Formal Analysis, Methodology, Project Administration, Writing – Original Draft Preparation, Writing – Review & Editing Georgette Eaton Roles: Methodology, Writing – Review & Editing Roles: Methodology, Writing – Review & Editing Marishona Ortega Roles: Methodology, Writing – Review & Editing Roles: Methodology, Writing – Review & Editing Kacper Sumera Roles: Methodology, Writing – Review & Editing Roles: Methodology, Writing – Review & Editing Michael Baliousis Roles: Methodology, Writing – Review & Editing Roles: Methodology, Writing – Review & Editing Jessica Hodgson Roles: Methodology, Writing – Review & Editing Roles: Methodology, Writing – Review & Editing Despina Laparidou Roles: Methodology, Writing – Review & Editing Roles: Methodology, Writing – Review & Editing Aloysius Niroshan Siriwardena Roles: Conceptualization, Funding Acquisition, Methodology, Writing – Review & Editing Roles: Conceptualization, Funding Acquisition, Methodology, Writing – Review & Editing Paul Leighton Roles: Conceptualization, Funding Acquisition, Methodology, Writing – Review & Editing Roles: Conceptualization, Funding Acquisition, Methodology, Writing – Review & Editing Sarah Redsell Roles: Conceptualization, Funding Acquisition, Methodology, Writing – Review & Editing Roles: Conceptualization, Funding Acquisition, Methodology, Writing – Review & Editing Bill Lord Roles: Conceptualization, Funding Acquisition, Methodology, Writing – Review & Editing Roles: Conceptualization, Funding Acquisition, Methodology, Writing – Review & Editing Tatiana Bujor Roles: Conceptualization, Methodology, Writing – Review & Editing Roles: Conceptualization, Methodology, Writing – Review & Editing Gregory Adam Whitley Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Methodology, Project Administration, Writing – Original Draft Preparation, Writing – Review & Editing Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Methodology, Project Administration, Writing – Original Draft Preparation, Writing – Review & Editing Competing interests No competing interests were disclosed. Grant information This project is funded by the National Institute for Health and Care Research (NIHR) under its [HEE/NIHR Integrated Clinical Academic Programme awarded to Gregory Adam Whitley (Grant Reference Number NIHR302875)]. The views expressed are those of the author(s) and not necessarily those of the NIHR, NHS or the Department of Health and Social Care. Georgie Nicholls was funded by the Advanced Clinical and Practitioner Academic Fellowship [NIHR302875]. Tatiana Bujor received reimbursement for involvement in line with NIHR INVOLVE rates, funded by the Advanced Clinical and Practitioner Academic Fellowship [NIHR302875]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Georgie Nicholls was funded by the Advanced Clinical and Practitioner Academic Fellowship [NIHR302875]. Tatiana Bujor received reimbursement for involvement in line with NIHR INVOLVE rates, funded by the Advanced Clinical and Practitioner Academic Fellowship [NIHR302875]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Article Versions (3) Copyright © 2025 Nicholls G et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. metrics VIEWS $counts.viewCount downloads Citations CITE how to cite this article Nicholls G, Eaton G, Ortega M et al. improving Pain mAnagement for childreN and young people attendeD by Ambulance (PANDA): protocol for a realist review. [version 3; peer review: 3 approved]. NIHR Open Res 2025, 4:42 (https://doi.org/10.3310/nihropenres.13627.3) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. track receive updates on this article Track an article to receive email alerts on any updates to this article. Current Reviewer Status: ? Key to Reviewer Statuses VIEW HIDE ApprovedThe paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approvedFundamental flaws in the paper seriously undermine the findings and conclusions Version 3 VERSION 3 PUBLISHED 30 Jan 2025 Revised Views 0 How to cite this report: Sapkota S and Shrestha S. Reviewer Report For: improving Pain mAnagement for childreN and young people attendeD by Ambulance (PANDA): protocol for a realist review. [version 3; peer review: 3 approved]. NIHR Open Res 2025, 4:42 (https://doi.org/10.3310/nihropenres.15093.r34668) The direct URL for this report is: https://openresearch.nihr.ac.uk/articles/4-42/v3#referee-response-34668 https://openresearch.nihr.ac.uk/articles/4-42/v3#referee-response-34668 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Reviewer Report 06 Feb 2025 Approved VIEWS 0 The authors have answer all our ... Continue reading We confirm that we have read this submission and believe that we have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Close The authors have answer all our queries. The article is approved without reservation. Competing Interests: No competing interests were disclosed. Reviewer Expertise: I am a clinical oncologist working in Nepal, with a special interest in pain management and palliative care. I have been trying to formulate a rational use of opioids within the country. CITE HOW TO CITE THIS REPORT Sapkota S and Shrestha S. Reviewer Report For: improving Pain mAnagement for childreN and young people attendeD by Ambulance (PANDA): protocol for a realist review. [version 3; peer review: 3 approved]. NIHR Open Res 2025, 4:42 (https://doi.org/10.3310/nihropenres.15093.r34668) The direct URL for this report is: https://openresearch.nihr.ac.uk/articles/4-42/v3#referee-response-34668 https://openresearch.nihr.ac.uk/articles/4-42/v3#referee-response-34668 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. Views 0 How to cite this report: Lourens A. Reviewer Report For: improving Pain mAnagement for childreN and young people attendeD by Ambulance (PANDA): protocol for a realist review. [version 3; peer review: 3 approved]. NIHR Open Res 2025, 4:42 (https://doi.org/10.3310/nihropenres.15093.r34669) The direct URL for this report is: https://openresearch.nihr.ac.uk/articles/4-42/v3#referee-response-34669 https://openresearch.nihr.ac.uk/articles/4-42/v3#referee-response-34669 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Reviewer Report 31 Jan 2025 Approved VIEWS 0 No ... Continue reading I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Close No additional comments Competing Interests: No competing interests were disclosed. Reviewer Expertise: Published several articles related to acute pain management in the prehospital setting as well as published evidence synthesis articles. CITE HOW TO CITE THIS REPORT Lourens A. Reviewer Report For: improving Pain mAnagement for childreN and young people attendeD by Ambulance (PANDA): protocol for a realist review. [version 3; peer review: 3 approved]. NIHR Open Res 2025, 4:42 (https://doi.org/10.3310/nihropenres.15093.r34669) The direct URL for this report is: https://openresearch.nihr.ac.uk/articles/4-42/v3#referee-response-34669 https://openresearch.nihr.ac.uk/articles/4-42/v3#referee-response-34669 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. Version 2 VERSION 2 PUBLISHED 05 Sep 2024 Revised Views 0 How to cite this report: Sapkota S and Shrestha S. Reviewer Report For: improving Pain mAnagement for childreN and young people attendeD by Ambulance (PANDA): protocol for a realist review. [version 3; peer review: 3 approved]. NIHR Open Res 2025, 4:42 (https://doi.org/10.3310/nihropenres.14914.r32872) The direct URL for this report is: https://openresearch.nihr.ac.uk/articles/4-42/v2#referee-response-32872 https://openresearch.nihr.ac.uk/articles/4-42/v2#referee-response-32872 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Reviewer Report 08 Oct 2024 Approved with Reservations VIEWS 0 The PANDA study protocol addresses an important issue in pediatric prehospital pain management but could benefit from refinements to enhance clarity and impact. We confirm that we have read this submission and believe that we have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however we have significant reservations, as outlined above. Close - A realist approach is appropriate but insufficient detail on how stakeholder input will The PANDA study protocol addresses an important issue in pediatric prehospital pain management but could benefit from refinements to enhance clarity and impact. - A realist approach is appropriate but insufficient detail on how stakeholder input will systematically shape the Initial Programme Theory (IPT). Greater clarity on the theoretical model for pain management would strengthen the conceptual foundation. - Including a wide range of sources is good, but more detail is needed on how relevance and rigor will be assessed, particularly for non-research documents. Justification for restricting to English-language and post-2000 documents should be included. - The tools for assessing pain in children are mentioned, but the limitations of these tools and how they may affect the synthesis need more discussion. The chosen threshold for pain relief (a reduction of 2 points on a 10-point scale) should also be better justified. - While the CMOC process is well-planned, the manuscript should specify how reviewer bias will be minimized during coding and synthesis. Handling contradictions in the literature also requires more explanation. - The protocol should extend its focus beyond developing a programme theory to outline potential interventions, ensuring practical relevance. - More clarity is needed on how input from PPI groups will be integrated into the review process and how differing views between stakeholders will be managed. - The process for assessing study rigor should be clarified with specific criteria, even if formal checklists aren't used. Additionally, themes like trauma-informed care that may emerge during synthesis should be given attention. - While including PPI groups is commendable, the protocol could benefit from ensuring that stakeholders, especially ambulance clinicians, represent diverse geographic areas and levels of experience. Variations in regional policies, resource availability, and clinician experience can significantly impact pain management practices. - To maximize the utility of the findings, it would be beneficial to outline how the programme theory might be adapted or applied to international settings where ambulance systems and regulations differ from the UK. This would broaden the impact of the review and make it more globally relevant. - Given the complexity of pediatric pain management, including input from other medical disciplines (e.g., pediatricians, pain specialists) in addition to ambulance clinicians may provide a more holistic perspective, particularly on pharmacological and non-pharmacological interventions. - The focus of the review is primarily on acute pain management, but considering the long-term outcomes of prehospital pain experiences, such as the risk of developing chronic pain or PTSD, could add valuable insight into how early interventions may prevent later complications. - Is the rationale for, and objectives of, the study clearly described? Yes - Is the study design appropriate for the research question? Yes - Are sufficient details of the methods provided to allow replication by others? Partly - Are the datasets clearly presented in a useable and accessible format? Not applicable Competing Interests: No competing interests were disclosed. Reviewer Expertise: I am a clinical oncologist working in Nepal, with a special interest in pain management and palliative care. I have been trying to formulate a rational use of opioids within the country. CITE HOW TO CITE THIS REPORT Sapkota S and Shrestha S. Reviewer Report For: improving Pain mAnagement for childreN and young people attendeD by Ambulance (PANDA): protocol for a realist review. [version 3; peer review: 3 approved]. NIHR Open Res 2025, 4:42 (https://doi.org/10.3310/nihropenres.14914.r32872) The direct URL for this report is: https://openresearch.nihr.ac.uk/articles/4-42/v2#referee-response-32872 https://openresearch.nihr.ac.uk/articles/4-42/v2#referee-response-32872 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. - Author Response 30 Jan 2025Gregory Whitley, Community and Health Research Unit, University of Lincoln, Lincoln, LN6 7FS, UK30 Jan 2025Author ResponseThank you for your time taken to review our manuscript. Your comments are very much appreciated. We have provided responses below: - Greater detail on how the involved stakeholders - Greater detail on how the involved stakeholders shaped the initial programme theory will be detailed in the final review paper. - We feel that the description of our assessment of relevance and rigour is adequate. These steps will be described further in the final review paper. - We have amended some text to justify the language restriction placed on the review: “only documents reported in English (due to time and resource constraints)” - We have amended some text to justify the date restriction placed on the review: “we will restrict our search to documents published from January 2000 onwards, due to known limited evidence prior to 20005” - We have added references to support the claim that a 2-point reduction in pain is clinically meaningful. In realist reviews, qualitative data plays a much greater role in synthesis than quantitative data, due to its explanatory value. We will acknowledge the limitations of pain assessment tools and their impact on the synthesis within the final review paper. - We have explained that 10% of coding will be checked by a second reviewer, and we have added some text to explain how bias was reduced during synthesis. We have also explained in the protocol that we may juxtapose, reconcile, adjudicate, consolidate or situate findings – this will help to address contradictions in the literature. - We certainly will not stop at the development of a realist programme theory. Under the Methods - Study Design section we explain that this review forms the first part of a sequence of studies that we hope will lead to the development and testing of a complex intervention. We have already added a sentence to the Programme theory refinement section to reiterate this and provide a sense of forward momentum at the end of the paper. This was to address comment #5 from peer-reviewer 2. - The manuscript explains how patient and public involvement will be achieved within the review at the start of the methods section. We have explained that both groups will be involved at the start and end of the review. We will elaborate on the exact nature of their involvement in the final review paper. - We understand the request for more detail regarding the rigour assessment, however we feel we have provided enough detail. We specified the criteria in the Rigour section, which involved assessing the description of methods to generate data and the listing of references for evidence sources. We are unable to speculate on potential themes that may or may not arise from the synthesis process. - We have commented on the diversity of the YPAG group. The ambulance clinician group was small on purpose to maximise participation during discussions. We ensured the selection of ambulance clinicians from difference areas of practice, including clinical practice, education and leadership. We have added a comment regarding the geography of the ACAG group. - We will be including documents from the international landscape and in the final review paper we will comment on the scope of generalisability of the review findings. It would be beyond the scope of the protocol to comment on the scope of generalisability. - We agree with your comments about including an interdisciplinary team in this review. The Working Group contained members with experience from the fields of General Practice, Nursing, Paramedicine and Psychology. A study Steering Committee, containing consultant pediatric emergency medicine physicians, also had oversight and input into this review – these members have been acknowledged. - Thank you for the comment about long-term outcomes of prehospital pain experiences. We are anticipating this will come out in the review findings. Thank you for your time taken to review our manuscript. Your comments are very much appreciated. We have provided responses below:Competing Interests: None. Close- Greater detail on how the involved stakeholders shaped the initial programme theory will be detailed in the final review paper. - We feel that the description of our assessment of relevance and rigour is adequate. These steps will be described further in the final review paper. - We have amended some text to justify the language restriction placed on the review: “only documents reported in English (due to time and resource constraints)” - We have amended some text to justify the date restriction placed on the review: “we will restrict our search to documents published from January 2000 onwards, due to known limited evidence prior to 20005” - We have added references to support the claim that a 2-point reduction in pain is clinically meaningful. In realist reviews, qualitative data plays a much greater role in synthesis than quantitative data, due to its explanatory value. We will acknowledge the limitations of pain assessment tools and their impact on the synthesis within the final review paper. - We have explained that 10% of coding will be checked by a second reviewer, and we have added some text to explain how bias was reduced during synthesis. We have also explained in the protocol that we may juxtapose, reconcile, adjudicate, consolidate or situate findings – this will help to address contradictions in the literature. - We certainly will not stop at the development of a realist programme theory. Under the Methods - Study Design section we explain that this review forms the first part of a sequence of studies that we hope will lead to the development and testing of a complex intervention. We have already added a sentence to the Programme theory refinement section to reiterate this and provide a sense of forward momentum at the end of the paper. This was to address comment #5 from peer-reviewer 2. - The manuscript explains how patient and public involvement will be achieved within the review at the start of the methods section. We have explained that both groups will be involved at the start and end of the review. We will elaborate on the exact nature of their involvement in the final review paper. - We understand the request for more detail regarding the rigour assessment, however we feel we have provided enough detail. We specified the criteria in the Rigour section, which involved assessing the description of methods to generate data and the listing of references for evidence sources. We are unable to speculate on potential themes that may or may not arise from the synthesis process. - We have commented on the diversity of the YPAG group. The ambulance clinician group was small on purpose to maximise participation during discussions. We ensured the selection of ambulance clinicians from difference areas of practice, including clinical practice, education and leadership. We have added a comment regarding the geography of the ACAG group. - We will be including documents from the international landscape and in the final review paper we will comment on the scope of generalisability of the review findings. It would be beyond the scope of the protocol to comment on the scope of generalisability. - We agree with your comments about including an interdisciplinary team in this review. The Working Group contained members with experience from the fields of General Practice, Nursing, Paramedicine and Psychology. A study Steering Committee, containing consultant pediatric emergency medicine physicians, also had oversight and input into this review – these members have been acknowledged. - Thank you for the comment about long-term outcomes of prehospital pain experiences. We are anticipating this will come out in the review findings. COMMENTS ON THIS REPORT - Author Response 30 Jan 2025Gregory Whitley, Community and Health Research Unit, University of Lincoln, Lincoln, LN6 7FS, UK30 Jan 2025Author ResponseThank you for your time taken to review our manuscript. Your comments are very much appreciated. We have provided responses below: - Greater detail on how the involved stakeholders - Greater detail on how the involved stakeholders shaped the initial programme theory will be detailed in the final review paper. - We feel that the description of our assessment of relevance and rigour is adequate. These steps will be described further in the final review paper. - We have amended some text to justify the language restriction placed on the review: “only documents reported in English (due to time and resource constraints)” - We have amended some text to justify the date restriction placed on the review: “we will restrict our search to documents published from January 2000 onwards, due to known limited evidence prior to 20005” - We have added references to support the claim that a 2-point reduction in pain is clinically meaningful. In realist reviews, qualitative data plays a much greater role in synthesis than quantitative data, due to its explanatory value. We will acknowledge the limitations of pain assessment tools and their impact on the synthesis within the final review paper. - We have explained that 10% of coding will be checked by a second reviewer, and we have added some text to explain how bias was reduced during synthesis. We have also explained in the protocol that we may juxtapose, reconcile, adjudicate, consolidate or situate findings – this will help to address contradictions in the literature. - We certainly will not stop at the development of a realist programme theory. Under the Methods - Study Design section we explain that this review forms the first part of a sequence of studies that we hope will lead to the development and testing of a complex intervention. We have already added a sentence to the Programme theory refinement section to reiterate this and provide a sense of forward momentum at the end of the paper. This was to address comment #5 from peer-reviewer 2. - The manuscript explains how patient and public involvement will be achieved within the review at the start of the methods section. We have explained that both groups will be involved at the start and end of the review. We will elaborate on the exact nature of their involvement in the final review paper. - We understand the request for more detail regarding the rigour assessment, however we feel we have provided enough detail. We specified the criteria in the Rigour section, which involved assessing the description of methods to generate data and the listing of references for evidence sources. We are unable to speculate on potential themes that may or may not arise from the synthesis process. - We have commented on the diversity of the YPAG group. The ambulance clinician group was small on purpose to maximise participation during discussions. We ensured the selection of ambulance clinicians from difference areas of practice, including clinical practice, education and leadership. We have added a comment regarding the geography of the ACAG group. - We will be including documents from the international landscape and in the final review paper we will comment on the scope of generalisability of the review findings. It would be beyond the scope of the protocol to comment on the scope of generalisability. - We agree with your comments about including an interdisciplinary team in this review. The Working Group contained members with experience from the fields of General Practice, Nursing, Paramedicine and Psychology. A study Steering Committee, containing consultant pediatric emergency medicine physicians, also had oversight and input into this review – these members have been acknowledged. - Thank you for the comment about long-term outcomes of prehospital pain experiences. We are anticipating this will come out in the review findings. Thank you for your time taken to review our manuscript. Your comments are very much appreciated. We have provided responses below:Competing Interests: None. Close- Greater detail on how the involved stakeholders shaped the initial programme theory will be detailed in the final review paper. - We feel that the description of our assessment of relevance and rigour is adequate. These steps will be described further in the final review paper. - We have amended some text to justify the language restriction placed on the review: “only documents reported in English (due to time and resource constraints)” - We have amended some text to justify the date restriction placed on the review: “we will restrict our search to documents published from January 2000 onwards, due to known limited evidence prior to 20005” - We have added references to support the claim that a 2-point reduction in pain is clinically meaningful. In realist reviews, qualitative data plays a much greater role in synthesis than quantitative data, due to its explanatory value. We will acknowledge the limitations of pain assessment tools and their impact on the synthesis within the final review paper. - We have explained that 10% of coding will be checked by a second reviewer, and we have added some text to explain how bias was reduced during synthesis. We have also explained in the protocol that we may juxtapose, reconcile, adjudicate, consolidate or situate findings – this will help to address contradictions in the literature. - We certainly will not stop at the development of a realist programme theory. Under the Methods - Study Design section we explain that this review forms the first part of a sequence of studies that we hope will lead to the development and testing of a complex intervention. We have already added a sentence to the Programme theory refinement section to reiterate this and provide a sense of forward momentum at the end of the paper. This was to address comment #5 from peer-reviewer 2. - The manuscript explains how patient and public involvement will be achieved within the review at the start of the methods section. We have explained that both groups will be involved at the start and end of the review. We will elaborate on the exact nature of their involvement in the final review paper. - We understand the request for more detail regarding the rigour assessment, however we feel we have provided enough detail. We specified the criteria in the Rigour section, which involved assessing the description of methods to generate data and the listing of references for evidence sources. We are unable to speculate on potential themes that may or may not arise from the synthesis process. - We have commented on the diversity of the YPAG group. The ambulance clinician group was small on purpose to maximise participation during discussions. We ensured the selection of ambulance clinicians from difference areas of practice, including clinical practice, education and leadership. We have added a comment regarding the geography of the ACAG group. - We will be including documents from the international landscape and in the final review paper we will comment on the scope of generalisability of the review findings. It would be beyond the scope of the protocol to comment on the scope of generalisability. - We agree with your comments about including an interdisciplinary team in this review. The Working Group contained members with experience from the fields of General Practice, Nursing, Paramedicine and Psychology. A study Steering Committee, containing consultant pediatric emergency medicine physicians, also had oversight and input into this review – these members have been acknowledged. - Thank you for the comment about long-term outcomes of prehospital pain experiences. We are anticipating this will come out in the review findings. Views 0 How to cite this report: Lourens A. Reviewer Report For: improving Pain mAnagement for childreN and young people attendeD by Ambulance (PANDA): protocol for a realist review. [version 3; peer review: 3 approved]. NIHR Open Res 2025, 4:42 (https://doi.org/10.3310/nihropenres.14914.r32837) The direct URL for this report is: https://openresearch.nihr.ac.uk/articles/4-42/v2#referee-response-32837 https://openresearch.nihr.ac.uk/articles/4-42/v2#referee-response-32837 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Reviewer Report 30 Sep 2024 Approved VIEWS 0 Thank you for considering my comments/suggestions and revising ... Continue reading I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Close Thank you for considering my comments/suggestions and revising the protocol. I have no further additions to make. Competing Interests: No competing interests were disclosed. Reviewer Expertise: Published several articles related to acute pain management in the prehospital setting as well as published evidence synthesis articles. CITE HOW TO CITE THIS REPORT Lourens A. Reviewer Report For: improving Pain mAnagement for childreN and young people attendeD by Ambulance (PANDA): protocol for a realist review. [version 3; peer review: 3 approved]. NIHR Open Res 2025, 4:42 (https://doi.org/10.3310/nihropenres.14914.r32837) The direct URL for this report is: https://openresearch.nihr.ac.uk/articles/4-42/v2#referee-response-32837 https://openresearch.nihr.ac.uk/articles/4-42/v2#referee-response-32837 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. Views 0 How to cite this report: Salmi H. Reviewer Report For: improving Pain mAnagement for childreN and young people attendeD by Ambulance (PANDA): protocol for a realist review. [version 3; peer review: 3 approved]. NIHR Open Res 2025, 4:42 (https://doi.org/10.3310/nihropenres.14914.r32836) The direct URL for this report is: https://openresearch.nihr.ac.uk/articles/4-42/v2#referee-response-32836 https://openresearch.nihr.ac.uk/articles/4-42/v2#referee-response-32836 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Reviewer Report 10 Sep 2024 Approved VIEWS 0 Thank you for the revised ... Continue reading I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Close Thank you for the revised article! I have no further suggestions. Competing Interests: No competing interests were disclosed. Reviewer Expertise: paediatric critical care CITE HOW TO CITE THIS REPORT Salmi H. Reviewer Report For: improving Pain mAnagement for childreN and young people attendeD by Ambulance (PANDA): protocol for a realist review. [version 3; peer review: 3 approved]. NIHR Open Res 2025, 4:42 (https://doi.org/10.3310/nihropenres.14914.r32836) The direct URL for this report is: https://openresearch.nihr.ac.uk/articles/4-42/v2#referee-response-32836 https://openresearch.nihr.ac.uk/articles/4-42/v2#referee-response-32836 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. Version 1 VERSION 1 PUBLISHED 23 Jul 2024 Views 0 How to cite this report: Salmi H. Reviewer Report For: improving Pain mAnagement for childreN and young people attendeD by Ambulance (PANDA): protocol for a realist review. [version 3; peer review: 3 approved]. NIHR Open Res 2025, 4:42 (https://doi.org/10.3310/nihropenres.14796.r32432) The direct URL for this report is: https://openresearch.nihr.ac.uk/articles/4-42/v1#referee-response-32432 https://openresearch.nihr.ac.uk/articles/4-42/v1#referee-response-32432 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Reviewer Report 14 Aug 2024 Approved with Reservations VIEWS 0 The authors have decided to conduct a study on how children in pain are currently managed by their prehospital emergency care providers. Then, according to literature and the current practices and circumstances, they will identify ideas for improvement, ands ... Continue reading I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close The authors have decided to conduct a study on how children in pain are currently managed by their prehospital emergency care providers. Then, according to literature and the current practices and circumstances, they will identify ideas for improvement, ands strategies for improvement. Ultimately, they will provide a framework about a programme. I am happy that the authors have decided to address such an important topic in paediatric critical care. I am not familiar with the research tools the authors describe, but they seem solid and relevant. I have a few suggestions for amendments to the protocol and to the article. I think this study protocol presentation would benefit from a “clinical touch”, both in order to make it more feasible and easier to understand for other clinicians. To meet this end, I am happy that the authors have decided to address such an important topic in paediatric critical care. I am not familiar with the research tools the authors describe, but they seem solid and relevant. I have a few suggestions for amendments to the protocol and to the article. I think this study protocol presentation would benefit from a “clinical touch”, both in order to make it more feasible and easier to understand for other clinicians. To meet this end, - please explain the EMS system/ prehospital care in your context for a reader coming outside of the UK. Who attends to severely injured children in the prehospital setting? A nurse, a paramedic, a non-specialist doctor, an emergency physician, an anaesthesiologist, a paediatric anaesthesiologist? Or does it depend on the region or the case or other facts? Does this influence the choice of medications available? How are the care providers educated for paediatric pain and do all of them attend to children? - Please discuss all relevant analgesic measures. If fentanyl is not available, what about other opioids? intravenously administered opioids? (es-)ketamine? what about adjuvant sedation and airway management to enable sufficient pain relief? - please explain how pain is rated in your system. If the targeted pain relief outcome is at least -2 p on the scale, what scale (I presume it to be NRS or VAS or similar – but how is it assessed in infants and toddlers?) - Perhaps the analysis should include a measure aiming at understanding how pain in children is evaluated in prehospital care. This may be the reason why children are undermedicated (if the personnel is only trained for pain score ratings, by definition all children under school age will not be able to provide a scale and are therefore at risk of not being medicated; also, the treatment response (-2 on the scale) will be impossible to achieve. Based on the results you will have, should your project also include a training tool for evaluating pain in children of different age? - Your project is very important and ambitious. I congratulate you on that. When you’ll go as far, why leave it to a “framework for a programme” phase and not develop a full, even preliminary, programme for better pain relief for children in the prehospital care instead? I am afraid there is a risk that without this aim, the study will miss a final clinical aspect and remain too abstract to be easily used for education in the prehospital services. If, on the other hand, you wrote this with a final clinical programme in mind, your conclusions and suggestions for future would be more easily read and adopted to practice by the busy clinicians in the field. To my understanding, the study setting would enable this kind of development. - Is the rationale for, and objectives of, the study clearly described? Yes - Is the study design appropriate for the research question? Yes - Are sufficient details of the methods provided to allow replication by others? Yes - Are the datasets clearly presented in a useable and accessible format? Yes Competing Interests: No competing interests were disclosed. Reviewer Expertise: paediatric critical care CITE HOW TO CITE THIS REPORT Salmi H. Reviewer Report For: improving Pain mAnagement for childreN and young people attendeD by Ambulance (PANDA): protocol for a realist review. [version 3; peer review: 3 approved]. NIHR Open Res 2025, 4:42 (https://doi.org/10.3310/nihropenres.14796.r32432) The direct URL for this report is: https://openresearch.nihr.ac.uk/articles/4-42/v1#referee-response-32432 https://openresearch.nihr.ac.uk/articles/4-42/v1#referee-response-32432 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. - Author Response 05 Sep 2024Gregory Whitley, Community and Health Research Unit, University of Lincoln, Lincoln, LN6 7FS, UK05 Sep 2024Author ResponseThank you for your thorough review of our manuscript. We appreciate your comments about needing a more clinical focus and have responded accordingly. We now feel that the manuscript is ... Continue reading Thank you for your thorough review of our manuscript. We appreciate your comments about needing a more clinical focus and have responded accordingly. We now feel that the manuscript is much improved. We have addressed the following points: - We have added a section to the introduction to give local context to the EMS system in the UK. We have described the scope of analgesic availability across the different clinician levels and described typical pain assessment processes. We have already alluded to the limited education and training around pain management for CYP in the first paragraph and so did not wish to labour this point any further. - We agree that pain assessment should form a core component of the synthesis. We will perform synthesis on all included documents and where able, we will develop CMOCs related to pain assessment. It is likely that the programme theory resulting from this review will allude to the pain assessment process, however we are unable to speculate at this stage. We also agree that a training tool to facilitate the pain assessment process in CYP would be helpful. Again, we anticipate this coming out in the synthesis of this review somewhat, and in the subsequent stages of the PANDA Study, and it is likely to form a component of the future complex intervention, however we are unable to speculate on this and wish to be led by the data. - We appreciate your kind comments and agree this is important and ambitious work. We certainly will not stop at the development of a realist programme theory. Under the Methods - Study Design section we explain that this review forms the first part of a sequence of studies that we hope will lead to the development and testing of a complex intervention. We have added a sentence to the Programme theory refinement section to reiterate this and provide a sense of forward momentum at the end of the paper. Thank you for your thorough review of our manuscript. We appreciate your comments about needing a more clinical focus and have responded accordingly. We now feel that the manuscript is much improved. We have addressed the following points:Competing Interests: None. Close- We have added a section to the introduction to give local context to the EMS system in the UK. We have described the scope of analgesic availability across the different clinician levels and described typical pain assessment processes. We have already alluded to the limited education and training around pain management for CYP in the first paragraph and so did not wish to labour this point any further. - We agree that pain assessment should form a core component of the synthesis. We will perform synthesis on all included documents and where able, we will develop CMOCs related to pain assessment. It is likely that the programme theory resulting from this review will allude to the pain assessment process, however we are unable to speculate at this stage. We also agree that a training tool to facilitate the pain assessment process in CYP would be helpful. Again, we anticipate this coming out in the synthesis of this review somewhat, and in the subsequent stages of the PANDA Study, and it is likely to form a component of the future complex intervention, however we are unable to speculate on this and wish to be led by the data. - We appreciate your kind comments and agree this is important and ambitious work. We certainly will not stop at the development of a realist programme theory. Under the Methods - Study Design section we explain that this review forms the first part of a sequence of studies that we hope will lead to the development and testing of a complex intervention. We have added a sentence to the Programme theory refinement section to reiterate this and provide a sense of forward momentum at the end of the paper. COMMENTS ON THIS REPORT - Author Response 05 Sep 2024Gregory Whitley, Community and Health Research Unit, University of Lincoln, Lincoln, LN6 7FS, UK05 Sep 2024Author ResponseThank you for your thorough review of our manuscript. We appreciate your comments about needing a more clinical focus and have responded accordingly. We now feel that the manuscript is ... Continue reading Thank you for your thorough review of our manuscript. We appreciate your comments about needing a more clinical focus and have responded accordingly. We now feel that the manuscript is much improved. We have addressed the following points: - We have added a section to the introduction to give local context to the EMS system in the UK. We have described the scope of analgesic availability across the different clinician levels and described typical pain assessment processes. We have already alluded to the limited education and training around pain management for CYP in the first paragraph and so did not wish to labour this point any further. - We agree that pain assessment should form a core component of the synthesis. We will perform synthesis on all included documents and where able, we will develop CMOCs related to pain assessment. It is likely that the programme theory resulting from this review will allude to the pain assessment process, however we are unable to speculate at this stage. We also agree that a training tool to facilitate the pain assessment process in CYP would be helpful. Again, we anticipate this coming out in the synthesis of this review somewhat, and in the subsequent stages of the PANDA Study, and it is likely to form a component of the future complex intervention, however we are unable to speculate on this and wish to be led by the data. - We appreciate your kind comments and agree this is important and ambitious work. We certainly will not stop at the development of a realist programme theory. Under the Methods - Study Design section we explain that this review forms the first part of a sequence of studies that we hope will lead to the development and testing of a complex intervention. We have added a sentence to the Programme theory refinement section to reiterate this and provide a sense of forward momentum at the end of the paper. Thank you for your thorough review of our manuscript. We appreciate your comments about needing a more clinical focus and have responded accordingly. We now feel that the manuscript is much improved. We have addressed the following points:Competing Interests: None. Close- We have added a section to the introduction to give local context to the EMS system in the UK. We have described the scope of analgesic availability across the different clinician levels and described typical pain assessment processes. We have already alluded to the limited education and training around pain management for CYP in the first paragraph and so did not wish to labour this point any further. - We agree that pain assessment should form a core component of the synthesis. We will perform synthesis on all included documents and where able, we will develop CMOCs related to pain assessment. It is likely that the programme theory resulting from this review will allude to the pain assessment process, however we are unable to speculate at this stage. We also agree that a training tool to facilitate the pain assessment process in CYP would be helpful. Again, we anticipate this coming out in the synthesis of this review somewhat, and in the subsequent stages of the PANDA Study, and it is likely to form a component of the future complex intervention, however we are unable to speculate on this and wish to be led by the data. - We appreciate your kind comments and agree this is important and ambitious work. We certainly will not stop at the development of a realist programme theory. Under the Methods - Study Design section we explain that this review forms the first part of a sequence of studies that we hope will lead to the development and testing of a complex intervention. We have added a sentence to the Programme theory refinement section to reiterate this and provide a sense of forward momentum at the end of the paper. Views 0 How to cite this report: Lourens A. Reviewer Report For: improving Pain mAnagement for childreN and young people attendeD by Ambulance (PANDA): protocol for a realist review. [version 3; peer review: 3 approved]. NIHR Open Res 2025, 4:42 (https://doi.org/10.3310/nihropenres.14796.r32435) The direct URL for this report is: https://openresearch.nihr.ac.uk/articles/4-42/v1#referee-response-32435 https://openresearch.nihr.ac.uk/articles/4-42/v1#referee-response-32435 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Reviewer Report 13 Aug 2024 Approved with Reservations VIEWS 0 Peer-review Report: Thank you for the opportunity to peer-review the realist review protocol titled ‘improving Pain mAnagement for childreN and young people attendeD by Ambulance (PANDA): protocol for a realist review.’ aiming to understand how ambulance clinicians can provide ... Continue reading I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close Thank you for the opportunity to peer-review the realist review protocol titled ‘improving Pain mAnagement for childreN and young people attendeD by Ambulance (PANDA): protocol for a realist review.’ aiming to understand how ambulance clinicians can provide ... Continue reading Peer-review Report: Thank you for the opportunity to peer-review the realist review protocol titled ‘improving Pain mAnagement for childreN and young people attendeD by Ambulance (PANDA): protocol for a realist review.’ aiming to understand how ambulance clinicians can provide improved prehospital acute pain management for Children and Young People. The protocol proposes a five-step approach for conducting the review following the RAMESES guidance to create context-mechanism-outcome configurations and test and refine the Initial Programme Theory into a realist Programme Theory. Overall, the protocol is well-written and structured with the methods describing the core steps required to ensure scientific soundness and reproducibility. I am confident that this review will contribute positively to the field of study, and I wish all involved the best with the overall research project. I do, however, have some comments and suggestions detailed below. Comments:

Methods: As per my comment below ‘perform screening in duplicate’ is captured under step 2 of the methods of the study, however, screening is part of the selection of the sources to be included which is step 3. I would suggest that the authors move it to step 3.

Overall, the introduction is well-written and concise providing general background information, what is known and not known about the topic in the specific population and articulating the rationale for conducting the realist review. Two minor comments for the authors to consider. Please consider reviewing the last sentence of the first paragraph of the introduction. The sentence is quite long, and it is challenging to read and understand the first time. I would suggest ending the sentence after ‘… variety of barriers’ followed by discussing the barriers in a subsequent sentence or two. My comment relates more to readability and understanding of the contents of the sentence, the information provided is valid and relevant. After abbreviating the term ‘children and young people (CYP)’, I would suggest that the abbreviation is used consistently throughout the introduction and the rest of the manuscript. I would also suggest that the authors ensure that all abbreviations are used consistently throughout the protocol manuscript once abbreviated. There are some inconsistencies in the manuscript.

Patient and Public Involvement In the first paragraph of the section, the abbreviation ‘IPT’ is used, however, the term is only abbreviated later in the methods section. In addition, the term is abbreviated a few subsequent times. Please consider correcting this. In the first sentence of the second paragraph of the section, the word ‘group’ appears twice ‘(the Healthier Ageing Patient and Public Involvement group (HAPPI) Group)). Perhaps the first ‘group’ is unnecessary. Step 2: Searching and Screening I would suggest that ‘The Cochrane Library’ be moved to the list of bibliographic databases searched instead of grey literature. Although ‘The Cochrane Library’ can provide access to a broad array of source documents including protocols of ongoing trials/systematic reviews, it is predominantly a source of completed systematic reviews and RCTs. The sub-heading ‘Grey Literature Search’ could be changed to ‘Searching Other Resources’ as a more commonly used sub-heading allowing for broader inclusion. Inclusion Criteria For the population inclusion criteria please change the bullet point “Ambulance clinicians (including but not limited to paramedics, emergency medical technicians, prehospital emergency nurses) who attend to CYP suffering acute pain.” Documents published from January 2000 onwards should rather be a search restriction and documents reported in English, an inclusion criterion. For both, the authors should consider provide a justification for the decision to exclude publications before 2000 and non-English documents. Exclusion Criteria I would argue that the last paragraph under this section discussing the screening of the search results against the eligibility (inclusion and exclusion) criteria is part of ‘Step 3: Document Selection’ as it is part of the stages of selecting sources for the review. Please move to Step 3. In line with this, the headings for Step 2 should be revised. Suggested options for heading ‘Step 2: Evidence Search’ Step 3: Document Selection In evidence synthesis, the results of searches and the screening process are commonly reported using a PRISMA flow diagram. Please consider adding that the selection of included sources will be reported using a PRISMA flow diagram. The reference for a PRISMA flow diagram is already in the reference list (reference 39). For the screening of sources and the assessment of relevance and rigour, please indicate whether the duplicate screening/assessment will be conducted independently. Rigour Please check the spelling of rigour in the second sentence under the sub-heading ‘Rigour’. Step 4: Extracting and organising data Although the authors describe that coding will be done by one reviewer and 10% checked by a second reviewer, this detail is not described for the data extraction process. Please describe this (how many reviewers will be involved, how will the reviewer(s) extract the data, and how will the data be checked) for the data extraction process as well. Programme theory refinement Please review the sentence to read ‘The programme theory developed from a recent realist review will be used as a framework to develop our realist programme theory. Thank you for the opportunity to peer-review the realist review protocol titled ‘improving Pain mAnagement for childreN and young people attendeD by Ambulance (PANDA): protocol for a realist review.’ aiming to understand how ambulance clinicians can provide improved prehospital acute pain management for Children and Young People. The protocol proposes a five-step approach for conducting the review following the RAMESES guidance to create context-mechanism-outcome configurations and test and refine the Initial Programme Theory into a realist Programme Theory. Overall, the protocol is well-written and structured with the methods describing the core steps required to ensure scientific soundness and reproducibility. I am confident that this review will contribute positively to the field of study, and I wish all involved the best with the overall research project. I do, however, have some comments and suggestions detailed below. Comments:

Methods: As per my comment below ‘perform screening in duplicate’ is captured under step 2 of the methods of the study, however, screening is part of the selection of the sources to be included which is step 3. I would suggest that the authors move it to step 3.

Overall, the introduction is well-written and concise providing general background information, what is known and not known about the topic in the specific population and articulating the rationale for conducting the realist review. Two minor comments for the authors to consider. Please consider reviewing the last sentence of the first paragraph of the introduction. The sentence is quite long, and it is challenging to read and understand the first time. I would suggest ending the sentence after ‘… variety of barriers’ followed by discussing the barriers in a subsequent sentence or two. My comment relates more to readability and understanding of the contents of the sentence, the information provided is valid and relevant. After abbreviating the term ‘children and young people (CYP)’, I would suggest that the abbreviation is used consistently throughout the introduction and the rest of the manuscript. I would also suggest that the authors ensure that all abbreviations are used consistently throughout the protocol manuscript once abbreviated. There are some inconsistencies in the manuscript.

Patient and Public Involvement In the first paragraph of the section, the abbreviation ‘IPT’ is used, however, the term is only abbreviated later in the methods section. In addition, the term is abbreviated a few subsequent times. Please consider correcting this. In the first sentence of the second paragraph of the section, the word ‘group’ appears twice ‘(the Healthier Ageing Patient and Public Involvement group (HAPPI) Group)). Perhaps the first ‘group’ is unnecessary. Step 2: Searching and Screening I would suggest that ‘The Cochrane Library’ be moved to the list of bibliographic databases searched instead of grey literature. Although ‘The Cochrane Library’ can provide access to a broad array of source documents including protocols of ongoing trials/systematic reviews, it is predominantly a source of completed systematic reviews and RCTs. The sub-heading ‘Grey Literature Search’ could be changed to ‘Searching Other Resources’ as a more commonly used sub-heading allowing for broader inclusion. Inclusion Criteria For the population inclusion criteria please change the bullet point “Ambulance clinicians (including but not limited to paramedics, emergency medical technicians, prehospital emergency nurses) who attend to CYP suffering acute pain.” Documents published from January 2000 onwards should rather be a search restriction and documents reported in English, an inclusion criterion. For both, the authors should consider provide a justification for the decision to exclude publications before 2000 and non-English documents. Exclusion Criteria I would argue that the last paragraph under this section discussing the screening of the search results against the eligibility (inclusion and exclusion) criteria is part of ‘Step 3: Document Selection’ as it is part of the stages of selecting sources for the review. Please move to Step 3. In line with this, the headings for Step 2 should be revised. Suggested options for heading ‘Step 2: Evidence Search’ Step 3: Document Selection In evidence synthesis, the results of searches and the screening process are commonly reported using a PRISMA flow diagram. Please consider adding that the selection of included sources will be reported using a PRISMA flow diagram. The reference for a PRISMA flow diagram is already in the reference list (reference 39). For the screening of sources and the assessment of relevance and rigour, please indicate whether the duplicate screening/assessment will be conducted independently. Rigour Please check the spelling of rigour in the second sentence under the sub-heading ‘Rigour’. Step 4: Extracting and organising data Although the authors describe that coding will be done by one reviewer and 10% checked by a second reviewer, this detail is not described for the data extraction process. Please describe this (how many reviewers will be involved, how will the reviewer(s) extract the data, and how will the data be checked) for the data extraction process as well. Programme theory refinement Please review the sentence to read ‘The programme theory developed from a recent realist review will be used as a framework to develop our realist programme theory. - Is the rationale for, and objectives of, the study clearly described? Yes - Is the study design appropriate for the research question? Yes - Are sufficient details of the methods provided to allow replication by others? Yes - Are the datasets clearly presented in a useable and accessible format? Not applicable Competing Interests: No competing interests were disclosed. Reviewer Expertise: Published several articles related to acute pain management in the prehospital setting as well as published evidence synthesis articles. CITE HOW TO CITE THIS REPORT Lourens A. Reviewer Report For: improving Pain mAnagement for childreN and young people attendeD by Ambulance (PANDA): protocol for a realist review. [version 3; peer review: 3 approved]. NIHR Open Res 2025, 4:42 (https://doi.org/10.3310/nihropenres.14796.r32435) The direct URL for this report is: https://openresearch.nihr.ac.uk/articles/4-42/v1#referee-response-32435 https://openresearch.nihr.ac.uk/articles/4-42/v1#referee-response-32435 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. - Author Response 05 Sep 2024Gregory Whitley, Community and Health Research Unit, University of Lincoln, Lincoln, LN6 7FS, UK05 Sep 2024Author ResponseThank you for your thorough review of our manuscript. We appreciate your comments and have responded accordingly. We now feel that the manuscript is much improved. We have addressed the ... Continue reading Thank you for your thorough review of our manuscript. We appreciate your comments and have responded accordingly. We now feel that the manuscript is much improved. We have addressed the following points: - We are unable to move the statement re. screening in duplicate to Step 3 because Step 2 and 3 are distinct. We screened documents in duplicate for Step 2, and then assessed relevance and rigour in duplicate for Step 3. The assessment of relevance did inform inclusion, whereas the assessment of rigour did not. We feel it is important to make the statements re. duplicate screening and duplicate assessment for Step 2 and Step 3 separately. We have also relabelled Step 3 for further clarity. - We have edited the sentence in the Introduction to improve readability. - We have replaced all references to “children and young people” with the abbreviation “CYP” after its first definition. - We have addressed the error re. the definition of “IPT”. - We have addressed the error re. the definition of “HAPPI” group. - We have moved The Cochrane Library to the Database Search and rephrased “grey literature search” to “searching other resources”. - We have edited the inclusion criteria as suggested and provided a justification for searching from January 2000 onwards. - We understand the confusion and similarity between Step 2 Searching and screening, and Step 3 Document selection. According to realist methodology these are distinct steps. We have renamed Step 3 to “Relevance and rigour assessment” for clarity. - We have stated that number of included documents will be reported using a PRISMA flow diagram and clarified that all duplicate screening and assessment will be conducted separately. - We have amended the spelling of “rigor”. - We have clarified that data extract of document characteristics will be performed by one reviewer and verified by a second. We will not extract data for the purpose of analysis per se, but rather we will upload the full documents for initial coding – we have clarified this. - We have edited the sentence regarding programme theory refinement. Thank you for your thorough review of our manuscript. We appreciate your comments and have responded accordingly. We now feel that the manuscript is much improved. We have addressed the following points:Competing Interests: None. Close- We are unable to move the statement re. screening in duplicate to Step 3 because Step 2 and 3 are distinct. We screened documents in duplicate for Step 2, and then assessed relevance and rigour in duplicate for Step 3. The assessment of relevance did inform inclusion, whereas the assessment of rigour did not. We feel it is important to make the statements re. duplicate screening and duplicate assessment for Step 2 and Step 3 separately. We have also relabelled Step 3 for further clarity. - We have edited the sentence in the Introduction to improve readability. - We have replaced all references to “children and young people” with the abbreviation “CYP” after its first definition. - We have addressed the error re. the definition of “IPT”. - We have addressed the error re. the definition of “HAPPI” group. - We have moved The Cochrane Library to the Database Search and rephrased “grey literature search” to “searching other resources”. - We have edited the inclusion criteria as suggested and provided a justification for searching from January 2000 onwards. - We understand the confusion and similarity between Step 2 Searching and screening, and Step 3 Document selection. According to realist methodology these are distinct steps. We have renamed Step 3 to “Relevance and rigour assessment” for clarity. - We have stated that number of included documents will be reported using a PRISMA flow diagram and clarified that all duplicate screening and assessment will be conducted separately. - We have amended the spelling of “rigor”. - We have clarified that data extract of document characteristics will be performed by one reviewer and verified by a second. We will not extract data for the purpose of analysis per se, but rather we will upload the full documents for initial coding – we have clarified this. - We have edited the sentence regarding programme theory refinement. COMMENTS ON THIS REPORT - Author Response 05 Sep 2024Gregory Whitley, Community and Health Research Unit, University of Lincoln, Lincoln, LN6 7FS, UK05 Sep 2024Author ResponseThank you for your thorough review of our manuscript. We appreciate your comments and have responded accordingly. We now feel that the manuscript is much improved. We have addressed the ... Continue reading Thank you for your thorough review of our manuscript. We appreciate your comments and have responded accordingly. We now feel that the manuscript is much improved. We have addressed the following points: - We are unable to move the statement re. screening in duplicate to Step 3 because Step 2 and 3 are distinct. We screened documents in duplicate for Step 2, and then assessed relevance and rigour in duplicate for Step 3. The assessment of relevance did inform inclusion, whereas the assessment of rigour did not. We feel it is important to make the statements re. duplicate screening and duplicate assessment for Step 2 and Step 3 separately. We have also relabelled Step 3 for further clarity. - We have edited the sentence in the Introduction to improve readability. - We have replaced all references to “children and young people” with the abbreviation “CYP” after its first definition. - We have addressed the error re. the definition of “IPT”. - We have addressed the error re. the definition of “HAPPI” group. - We have moved The Cochrane Library to the Database Search and rephrased “grey literature search” to “searching other resources”. - We have edited the inclusion criteria as suggested and provided a justification for searching from January 2000 onwards. - We understand the confusion and similarity between Step 2 Searching and screening, and Step 3 Document selection. According to realist methodology these are distinct steps. We have renamed Step 3 to “Relevance and rigour assessment” for clarity. - We have stated that number of included documents will be reported using a PRISMA flow diagram and clarified that all duplicate screening and assessment will be conducted separately. - We have amended the spelling of “rigor”. - We have clarified that data extract of document characteristics will be performed by one reviewer and verified by a second. We will not extract data for the purpose of analysis per se, but rather we will upload the full documents for initial coding – we have clarified this. - We have edited the sentence regarding programme theory refinement. Thank you for your thorough review of our manuscript. We appreciate your comments and have responded accordingly. We now feel that the manuscript is much improved. We have addressed the following points:Competing Interests: None. Close- We are unable to move the statement re. screening in duplicate to Step 3 because Step 2 and 3 are distinct. We screened documents in duplicate for Step 2, and then assessed relevance and rigour in duplicate for Step 3. The assessment of relevance did inform inclusion, whereas the assessment of rigour did not. We feel it is important to make the statements re. duplicate screening and duplicate assessment for Step 2 and Step 3 separately. We have also relabelled Step 3 for further clarity. - We have edited the sentence in the Introduction to improve readability. - We have replaced all references to “children and young people” with the abbreviation “CYP” after its first definition. - We have addressed the error re. the definition of “IPT”. - We have addressed the error re. the definition of “HAPPI” group. - We have moved The Cochrane Library to the Database Search and rephrased “grey literature search” to “searching other resources”. - We have edited the inclusion criteria as suggested and provided a justification for searching from January 2000 onwards. - We understand the confusion and similarity between Step 2 Searching and screening, and Step 3 Document selection. According to realist methodology these are distinct steps. We have renamed Step 3 to “Relevance and rigour assessment” for clarity. - We have stated that number of included documents will be reported using a PRISMA flow diagram and clarified that all duplicate screening and assessment will be conducted separately. - We have amended the spelling of “rigor”. - We have clarified that data extract of document characteristics will be performed by one reviewer and verified by a second. We will not extract data for the purpose of analysis per se, but rather we will upload the full documents for initial coding – we have clarified this. - We have edited the sentence regarding programme theory refinement. Alongside their report, reviewers assign a status to the article: - Approved - Approved with reservations - Not approved | Invited Reviewers | ||| |---|---|---|---| | 1 | 2 | 3 | | | Version 3 (revision) 30 Jan 25 | read | read | | | Version 2 (revision) 05 Sep 24 | read | read | read | | Version 1 23 Jul 24 | read | read | Sign up for content alerts You are now signed up to receive this alert Alongside their report, reviewers assign a status to the article: Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved - fundamental flaws in the paper seriously undermine the findings and conclusions Provide sufficient details of any financial or non-financial competing interests to enable users to assess whether your comments might lead a reasonable person to question your impartiality. Consider the following examples, but note that this is not an exhaustive list: Examples of 'Non-Financial Competing Interests' - Within the past 4 years, you have held joint grants, published or collaborated with any of the authors of the selected paper. - You have a close personal relationship (e.g. parent, spouse, sibling, or domestic partner) with any of the authors. - You are a close professional associate of any of the authors (e.g. scientific mentor, recent student). - You work at the same institute as any of the authors. - You hope/expect to benefit (e.g. favour or employment) as a result of your submission. - You are an Editor for the journal in which the article is published. Examples of 'Financial Competing Interests' - You expect to receive, or in the past 4 years have received, any of the following from any commercial organisation that may gain financially from your submission: a salary, fees, funding, reimbursements. - You expect to receive, or in the past 4 years have received, shared grant support or other funding with any of the authors. - You hold, or are currently applying for, any patents or significant stocks/shares relating to the subject matter of the paper you are commenting on. Sign up for content alerts and receive a weekly or monthly email with all newly published articles Register with NIHR Open Research Already registered? Sign in close Error If you are a previous or current NIHR award holder, sign up for information about developments, publishing and publications from NIHR Open Research. We'll keep you updated on any major new updates to NIHR Open Research Sign In If you've forgotten your password, please enter your email address below and we'll send you instructions on how to reset your password. Email us for further assistance. The email address should be the one you originally registered with F1000. Email address not valid, please try again You registered with F1000 via Google, so we cannot reset your password. To sign in, please click here. If you still need help with your Google account password, please click here. You registered with F1000 via Facebook, so we cannot reset your password. To sign in, please click here. If you still need help with your Facebook account password, please click here. Code not correct, please try again Server error, please try again. If your email address is registered with us, we will email you instructions to reset your password. If you think you should have received this email but it has not arrived, please check your spam filters and/or contact for further assistance. Please wait...