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Objective: To develop a core outcome set (COS), an agreed minimum set of outcomes to measure and report in all studies evaluating the introduction and evaluation of novel surgical techniques.Summary Background Data: Agreement on the key outcomes to measure and report for safe and efficient surgical innovation is lacking, hindering transparency and risking patient harm.Methods: (I) Generation of a list of outcome domains from published innovation-specific literature, policy/regulatory body documents, and surgeon interviews; (II) Prioritization of identified outcome domains using an international, multi-stakeholder Delphi survey; (III) Consensus meeting to agree the final COS. Participants were international stakeholders, including patients/public, surgeons, device manufacturers, regulators, trialists, methodologists and journal editors.Results: 7,972 verbatim outcomes were identified, categorized into 32 domains, and formatted into survey items/questions. 410 international participants (220 professionals, 190 patients/public) completed at least one round 1 survey item, of which 153 (69.5%) professionals and 116 (61.1%) patients completed at least one round 2 item. 12 outcomes were scored ‘consensus in’ (‘very important’ by ≥70% of patients and professionals) and 20 ‘no consensus’. A consensus meeting, involving 19 professionals and 10 patient/public representatives, led to agreement on a final 8-domain COS. Six domains are specific to a surgical innovation context: modifications, unexpected disadvantages, device problems, technical procedure success, whether the overall desired effect was achieved, surgeons’/operators’ experience. Two domains relate to intended benefits and expected disadvantages.Conclusions: The COS is recommended for use in all studies prior to definitive RCT evaluation to promote safe, transparent, and efficient surgical innovation.

PURPOSE The European Organisation for Research and Treatment of Cancer (EORTC) Item Library is an interactive online platform currently composed of 950 unique items (questions) derived from 67 patient-reported outcome (PRO) questionnaires. PROs complement clinician adverse event (AE) reporting classifications like the Common Terminology Criteria for Adverse Events (CTCAE). This work aims to create a standardized framework using the CTCAE to systematically classify symptomatic AEs from the EORTC Item Library through linking individual items to corresponding AEs. METHODS The EORTC Item Library items were searched for within the CTCAE (v5.0) and linked to an AE if they were described within the AE's title, description, or grading. Symptoms described in EORTC items but not located in the CTCAE were coded as missing symptoms. Other nonsymptom EORTC items, not described within the CTCAE were assigned a non-CTCAE descriptive classification. Further descriptive codes (eg, multiple issues) were allocated to enable descriptive analysis. Two raters independently coded 26.2% (n = 249) of the items. The remaining 701 items were coded by one rater and verified by the second, followed by discussion with two additional raters to reach consensus. RESULTS Overall, 625 (65.8%) EORTC items were linked to 208 different AEs. Three hundred sixty-nine items provide information about non-CTCAE cancer–related issues and were categorized into seven descriptive classifications, including body image; emotional impact of a symptom, diagnosis, or treatment; global health and quality of life; and impact on life and daily activities. Inter-rater agreement for independent coding was 79.1%. Bowel urgency and tenesmus were identified as missing symptoms in CTCAEv5.0. CONCLUSION The EORTC Item Library provides considerable coverage of CTCAE toxicities, along with other complementary issues important to patients with cancer. Using the CTCAE clinical framework to classify symptomatic PRO items may facilitate PRO selection and use in clinical trials and routine care.

ObjectivesThe aim of this study is to explore the transparency of reporting primary outcome data within randomized controlled trials in the presence of missing data.Study design and settingA cohort examination of randomized controlled trials published in the four major medical journals (NEJM, JAMA, BMJ, Lancet) in 2013 and the first quarter of 2018. Data were extracted on reporting quality, the number of randomized participants, and the number of participants included within the primary outcome analysis with observed or imputed data.ResultsNinety-one of 159 (57%) studies analyzed from 2013 and 19 of 46 (41%) from 2018 included imputed data within the primary outcome analysis. Of these, only 13 of 91 (14%) studies from 2013 and 1 of 19 (5%) studies from 2018 explicitly reported the number of imputed values in the CONSORT diagram. Results' tables included levels of imputed data in 12 of 91 (13%) studies in 2013 and 4 of 19 (21%) in 2018. Consequently, identification of imputed data was a time-consuming task requiring extensive cross-referencing of all manuscript elements.ConclusionImputed primary outcome data are poorly reported. Participant flow diagrams frequently reported participant status which does not necessarily correlate to availability of data. We recommended that the number of imputed values are explicitly reported within CONSORT flow diagrams to increase transparency.

Background Surgeons routinely care for patients with life-limiting illness, requiring communication and symptom management skills supported by appropriate training. The objective of this study was to appraise and synthesize studies that assessed surgeon-directed training interventions that aimed to optimize communication and symptom management for patients with life-limiting illness. Methods A PRISMA-concordant systematic review was undertaken. MEDLINE, Embase, Allied and Complementary Medicine Database (AMED), and the Cochrane Central Register of Controlled Trials were searched from inception until October 2022 for studies reporting on the evaluation of surgeon-training interventions intending to improve surgeons’ communication or symptom management of patients with life-limiting disease. Data on the design, trainer and patient participants, and the intervention were extracted. Risk of bias was assessed. Results Of 7794 articles, 46 were included. Most studies employed a before–after approach (29 studies) and nine included control groups with five being randomized studies. General surgery was the most frequently included sub-specialty (22 studies). Trainers were described in 25 of 46 studies. Most training interventions aimed to improve communication skills (45 studies) and 13 different training interventions were described. Eight studies reported a measurable improvement in patient care, such as increased documentation of advance care discussions. Most study outcomes focused on surgeons’ knowledge (12 studies), skills (21 studies), and confidence/comfort (18 studies) in palliative communication skills. Studies had a high risk of bias. Conclusion Whilst interventions exist to improve the training of surgeons managing patients with life-threatening conditions, evidence is limited, and studies measure the direct impact on patient care insufficiently. Improved research is needed to lead to better methods for training surgeons to benefit patients.

Background Innovative surgical procedures and devices are often modified throughout their development and introduction into clinical practice. A systematic approach to reporting modifications may support shared learning and foster safe and transparent innovation. Definitions of ‘modifications’, and how they are conceptualized and classified so they can be reported and shared effectively, however, are lacking. This study aimed to explore and summarize existing definitions, perceptions, classifications and views on modification reporting to develop a conceptual framework for understanding and reporting modifications. Methods A scoping review was conducted in accordance with PRISMA Extension for Scoping Reviews (PRISMA-ScR) guidelines. Targeted searches and two database searches were performed to identify relevant opinion pieces and review articles. Included were articles relating to modifications to surgical procedures/devices. Data regarding definitions, perceptions and classifications of modifications, and views on modification reporting were extracted verbatim. Thematic analysis was undertaken to identify themes, which informed development of the conceptual framework. Results Forty-nine articles were included. Eight articles included systems for classifying modifications, but no articles reported an explicit definition of modifications. Some 13 themes relating to perception of modifications were identified. The derived conceptual framework comprises three overarching components: baseline data about modifications, details about modifications and impact/consequences of modifications. Conclusion A conceptual framework for understanding and reporting modifications that occur during surgical innovation has been developed. This is a first necessary step to support consistent and transparent reporting of modifications, to facilitate shared learning and incremental innovation of surgical procedures/devices. Testing and operationalization is now needed to realize the value of this framework.

ObjectiveTo review guidance, included in written local UK National Health Service (NHS) organisation policies, on information provision and consent for the introduction of new invasive procedures- including surgeries, and devices (IPs/Ds).DesignA qualitative documentary analysis of data on patient information provision and consent extracted from policies for the introduction of IP/Ds from NHS organisations in England and Wales.SettingNHS trusts in England and health boards in Wales, UK.ParticipantsBetween December 2017 and July 2018, 150 acute trusts in England and 7 health boards in Wales were approached for their policies for the introduction of new IP/Ds. In total, 123 policies were received, 11 did not fit the inclusion criteria and a further policy was included from a trust website resulting in 113 policies included for review.ResultsFrom the 113 policies, 22 did not include any statements on informed consent/information provision or lacked guidance on the information to be provided to patients and were hence excluded. Consequently, 91 written local NHS policies were included in the final dataset. Within the guidance obtained, variation existed on disclosure of the procedure’s novelty, potential risks, benefits, uncertainties, alternative treatments and surgeon’s experience. Few policies stated that clinicians should discuss the existing evidence associated with a procedure. Additionally, while the majority of policies referred to patients needing written information, this was often not mandated and few policies specified the information to be included.ConclusionsNearly a fifth of all the policies lacked guidance on information to be provided to patients. There was variability in the policy documents regarding what patients should be told about innovative procedures. Further research is needed to ascertain the information and level of detail appropriate for patients when considering innovative procedures. A core information set including patients’ and clinicians’ views is required to address variability around information provision/consent for innovative procedures.

The use of placebo comparisons for randomised trials assessing the efficacy of surgical interventions is increasingly being considered. However, a placebo control is a complex type of comparison group in the surgical setting and, although powerful, presents many challenges.To provide a summary of knowledge on placebo controls in surgical trials and to summarise any recommendations for designers, evaluators and funders of placebo-controlled surgical trials.To carry out a state-of-the-art workshop and produce a corresponding report involving key stakeholders throughout.A workshop to discuss and summarise the existing knowledge and to develop the new guidelines.To assess what a placebo control entails and to assess the understanding of this tool in the context of surgery is considered, along with when placebo controls in surgery are acceptable (and when they are desirable). We have considered ethics arguments and regulatory requirements, how a placebo control should be designed, how to identify and mitigate risk for participants in these trials, and how such trials should be carried out and interpreted. The use of placebo controls is justified in randomised controlled trials of surgical interventions provided that there is a strong scientific and ethics rationale. Surgical placebos might be most appropriate when there is poor evidence for the efficacy of the procedure and a justified concern that results of a trial would be associated with a high risk of bias, particularly because of the placebo effect.The use of placebo controls is justified in randomised controlled trials of surgical interventions provided that there is a strong scientific and ethics rationale. Feasibility work is recommended to optimise the design and implementation of randomised controlled trials. An outline for best practice was produced in the form of the Applying Surgical Placebo in Randomised Evaluations (ASPIRE) guidelines for those considering the use of a placebo control in a surgical randomised controlled trial.Although the workshop participants involved international members, the majority of participants were from the UK. Therefore, although every attempt was made to make the recommendations applicable to all health systems, the guidelines may, unconsciously, be particularly applicable to clinical practice in the UK NHS.Future work should evaluate the use of the ASPIRE guidelines in making decisions about the use of a placebo-controlled surgical trial. In addition, further work is required on the appropriate nomenclature to adopt in this space.Funded by the Medical Research Council UK and the National Institute for Health Research as part of the Medical Research Council-National Institute for Health Research Methodology Research programme.One of the best ways to prove that a new medicine really works is to use a scientific test called a ‘placebo-controlled trial’. In this type of test, half of the participants are given a new pill and the other half are given a ‘placebo’, which is a dummy pill (usually a sugar pill) that is made to taste and look the same as the active pill, but has no active ingredients. The results are then compared. Just like medicines, new surgical procedures need to be tested to show that they are safe and benefit patients. Ideally, they would also be tested using the ‘placebo-controlled trial’ approach, but asking patients to have ‘dummy’ surgery is not the same as asking people to take a dummy pill. Placebo surgery raises lots of ethics questions and is controversial. As it is controversial, guidelines are needed to recommend when placebo surgery studies can be used (if at all) and what special considerations need to be taken into account. Our research team was commissioned to develop these guidelines.We summarised, to the best of our knowledge, all previous research that had used placebo surgery and reviewed all the ethics literature on this topic. We also looked at the latest scientific understanding of how placebos work. We then held a workshop to discuss and summarise the existing knowledge and to develop the new guidelines. This involved an international team of patients, surgeons, researchers, ethicists, psychologists, physiologists and funders. We published the guidelines [i.e. the ASPIRE (Applying Surgical Placebo in Randomised Evaluations) guidelines] in an influential medical journal and also wrote several other publications. This report provides a slightly more detailed version of our findings and recommendations.The guidelines will help researchers and doctors know when, and how, to best design placebo surgery studies in the future.

Advances in healthcare require safe and transparent innovation. Currently in surgery it can be difficult to identify when innovation is occurring because of inconsistent oversight and reporting. New ways of identifying, monitoring and reporting surgical innovation are called for in order to optimise the process.

ObjectiveTo establish the feasibility of a multicentre randomised controlled trial to assess the effectiveness and cost-effectiveness of a non-operative treatment pathway compared with appendicectomy in children with uncomplicated acute appendicitis.DesignFeasibility randomised controlled trial with embedded qualitative study to inform recruiter training to optimise recruitment and the design of a future definitive trial.SettingThree specialist paediatric surgery centres in the UK.PatientsChildren (aged 4–15 years) with a clinical diagnosis of uncomplicated acute appendicitis.InterventionsAppendicectomy or a non-operative treatment pathway (comprising broad-spectrum antibiotics and active observation).Main outcome measuresPrimary outcome measure was the proportion of eligible patients recruited. Secondary outcomes evaluated adherence to interventions, data collection during follow-up, safety of treatment pathways and clinical course.ResultsFifty per cent of eligible participants (95% CI 40 to 59) approached about the trial agreed to participate and were randomised. Repeated bespoke recruiter training was associated with an increase in recruitment rate over the course of the trial from 38% to 72%. There was high acceptance of randomisation, good patient and surgeon adherence to trial procedures and satisfactory completion of follow-up. Although more participants had perforated appendicitis than had been anticipated, treatment pathways were found to be safe and adverse event profiles acceptable.ConclusionRecruitment to a randomised controlled trial examining the effectiveness and cost-effectiveness of a non-operative treatment pathway compared with appendicectomy for the treatment of uncomplicated acute appendicitis in children is feasible.Trial registration numberNCT15830435.

ObjectiveOutcome selection and reporting in studies of novel surgical procedures and devices lacks standardisation, hindering safe and effective evaluation. A core outcome set (COS) to measure and report in all studies of surgical innovation is needed. We explored outcomes in a specific sample of innovative surgical device case studies to identify outcome domains specifically relevant to innovation to inform the development of a COS.DesignA targeted review of 11 purposive selected case studies of innovative surgical devices.MethodsElectronic database searches in PubMed (July 2018) identified publications reporting the introduction and evaluation of each device. Outcomes were extracted and categorised into domains until no new domains were conceptualised. Outcomes specifically relevant to evaluating innovation were further scrutinised.Results112 relevant publications were identified, and 5926 outcomes extracted. Heterogeneity in study type, outcome selection and reporting was observed across surgical devices. Categorisation of outcomes was performed for 2689 (45.4%) outcomes into five broad outcome domains. Outcomes considered key to the evaluation of innovation (n=66; 2.5%) were further categorised as surgeon/operator experience (n=40; 1.5%), unanticipated events (n=15, 0.6%) and modifications (n=11; 0.4%).ConclusionOutcome domains unique to evaluating innovative surgical devices have been identified. Findings have been combined with multiple other data sources relevant to the evaluation of surgical innovation to inform the development of a COS to measure and report in all studies evaluating novel surgical procedures/devices.

Background Many randomised controlled trials (RCTs) struggle to recruit, despite valiant efforts. The QRI (QuinteT Recruitment Intervention) uses innovative research methods to optimise recruitment by revealing previously hidden barriers related to the perceptions and experiences of recruiters and patients, and targeting remedial actions. It was designed to be integrated with RCTs anticipating difficulties at the outset. A new version of the intervention (QRI-Two) was developed for RCTs already underway with enrolment shortfalls. Methods QRIs in 12 RCTs with enrolment shortfalls during 2007–2017 were reviewed to document which of the research methods used could be rapidly applied to successfully identify recruitment barriers. These methods were then included in the new streamlined QRI-Two intervention which was applied in 20 RCTs in the USA and Europe during 2018–2019. The feasibility of the QRI-Two was investigated, recruitment barriers and proposed remedial actions were documented, and the QRI-Two protocol was finalised. Results The review of QRIs from 2007 to 2017 showed that previously unrecognised recruitment barriers could be identified but data collection for the full QRI required time and resources usually unavailable to ongoing RCTs. The streamlined QRI-Two focussed on analysis of screening/accrual data and RCT documents (protocol, patient-information), with discussion of newly diagnosed barriers and potential remedial actions in a workshop with the RCT team. Four RCTs confirmed the feasibility of the rapid application of the QRI-Two. When the QRI-Two was applied to 14 RCTs underway with enrolment shortfalls, an array of previously unknown/underestimated recruitment barriers related to issues such as equipoise, intervention preferences, or study presentation was identified, with new insights into losses of eligible patients along the recruitment pathway. The QRI-Two workshop enabled discussion of the newly diagnosed barriers and potential remedial actions to improve recruitment in collaboration with the RCT team. As expected, the QRI-Two performed less well in six RCTs at the start-up stage before commencing enrolment. Conclusions The QRI-Two can be applied rapidly, diagnose previously unrecognised recruitment barriers, and suggest remedial actions in RCTs underway with enrolment shortfalls, providing opportunities for RCT teams to develop targeted actions to improve recruitment. The effectiveness of the QRI-Two in improving recruitment requires further evaluation.

ObjectiveDuring development of complex surgical innovations, modifications occur to optimize safety and efficacy. Operators’ experiences (how professionals feel undertaking the innovation) drives this process but comprehensive overviews of measures of this concept are lacking. This study identified and appraised measures to assess operators’ experience of surgical innovation.Study design and settingThere were three phases: 1) Literature reviews identified measures of operators’ experience and concepts measured were extracted and grouped into domains. 2) Quality appraisal was conducted to assess content validity of identified instruments, and was supported by COSMIN methodology. Self-reported measurement instruments that had underdone formal development were eligible. Content validity was assessed using COSMIN criteria for good content validity (rated sufficient/insufficient/indeterminate/inconsistent), informed by standards for measurement development and domains identified in phase 1. 3) Instruments determined suitable and of sufficient quality underwent supplemental appraisal in interviews with international multi-disciplinary professionals and a focus group.ResultsLiterature reviews identified 16 measurement instruments from 243 studies. Most assessed ‘psychological’ experiences and ‘usability’. No instrument was specifically validated for innovative surgery. Three instruments were rated ‘sufficient’ (SURG-TLX) or ‘indeterminate’ (STAI,ISAT). Twenty professionals were interviewed (7 female; 15 specialties; 6 countries) and the focus group included 10 participants (4 professionals, 6 researchers). The SURG-TLX was considered the most relevant, comprehensive, and comprehensible instrument.ConclusionThe SURG-TLX is preliminarily recommended to measure operators’ experiences of innovation. Further work exploring its role and impact on surgical innovation is required.

Background The complexities associated with delivering randomised surgical trials, such as clustering effects, by centre or surgeon, and surgical learning, are well known. Despite this, approaches used to manage these complexities, and opinions on these, vary. Guidance documents have been developed to support clinical trial design and reporting. This work aimed to identify and examine existing guidance and consider its relevance to clustering effects and learning curves within surgical trials. Methods A review of existing guidelines, developed to inform the design and analysis of randomised controlled trials, is undertaken. Guidelines were identified using an electronic search, within the Equator Network, and by a targeted search of those endorsed by leading UK funding bodies, regulators, and medical journals. Eligible documents were compared against pre-specified key criteria to identify gaps or inconsistencies in recommendations. Results Twenty-eight documents were eligible (12 Equator Network; 16 targeted search). Twice the number of guidance documents targeted design (n/N=20/28, 71%) than analysis (n/N=10/28, 36%). Managing clustering by centre through design was well documented. Clustering by surgeon had less coverage and contained some inconsistencies. Managing the surgical learning curve, or changes in delivery over time, through design was contained within several documents (n/N=8/28, 29%), of which one provided guidance on reporting this and restricted to early phase studies only. Methods to analyse clustering effects and learning were provided in five and four documents respectively (N=28). Conclusions To our knowledge, this is the first review as to the extent to which existing guidance for designing and analysing randomised surgical trials covers the management of clustering, by centre or surgeon, and the surgical learning curve. Twice the number of identified documents targeted design aspects than analysis. Most notably, no single document exists for use when designing these studies, which may lead to inconsistencies in practice. The development of a single document, with agreed principles to guide trial design and analysis across a range of realistic clinical scenarios, is needed.

BACKGROUND Surgical innovation can lead to important improvements in patient outcomes. Currently, information and knowledge about novel procedures and devices is disseminated informally and in an unstandardized way (e.g., through social media). This can lead to ineffective and inefficient sharing of learning amongst surgeons, which can result in harmful repetition of mistakes and delay in the uptake of promising innovation. Improvements are needed in the way that learning in surgical innovation is shared through development of novel, real-time, informed by contemporary and comprehensive investigation of existing methods. OBJECTIVE The aim of this scoping review is to explore the application of existing digital methods for training/education and feedback to surgeons in the context of performing invasive surgical procedures. This work will: (i) summarize existing methods for shared learning in surgery and how they are characterized and operationalized, (ii) examine the impact of their application, and (iii) explore their benefits and barriers to implementation. The findings of this scoping review will inform the development of novel, real-time methods to optimize shared learning in surgical innovation. METHODS This study will adhere to recommended guidance for conducting scoping reviews. A total of six different searches will be conducted within multiple sources (two electronic databases, journals, social media, grey literature, commercial websites, and snowball searches) to comprehensively identify relevant articles and data. Searches will be limited to articles published in English language within the last five years. Wherever possible, a two-stage study selection process will be followed whereby eligibility of articles will be assessed through title/abstract, and full-text screening independently by two reviewers. Inclusion criteria will be articles providing data on: (i) fully qualified theatre staff involved in performing invasive procedures, (ii) one or more methods for shared learning (i.e., digital means for training/education and feedback), and (iii) qualitative or quantitative evaluations of this method. Data will be extracted (10% double data extraction by an independent reviewer) into a piloted proforma and analyzed using descriptive statistics, narrative summaries and principles of thematic analysis. RESULTS The study commenced in October 2021 and is planned to be completed in 2022. To date, systematic searches were applied to two electronic databases (Medline, Web of Science) and returned a total of 6,994 records. The results of this scoping review will be published as open access in a peer-reviewed journal. CONCLUSIONS This scoping review of methods for shared learning in surgery is, to our knowledge, the most comprehensive and up-to-date investigation that maps the current information on this topic. Ultimately, efficient and effective sharing of information and knowledge of novel procedures and devices has the potential to optimize evaluation of early phase surgical research and reduce harmful innovation. CLINICALTRIAL n/a

Background Surgical innovation can lead to important improvements in patient outcomes. Currently, information and knowledge about novel procedures and devices are disseminated informally and in an unstandardized way (eg, through social media). This can lead to ineffective and inefficient knowledge sharing among surgeons, which can result in the harmful repetition of mistakes and delay in the uptake of promising innovation. Improvements are needed in the way that learning in surgical innovation is shared through the development of novel, real-time methods, informed by a contemporary and comprehensive investigation of existing methods. Objective The aim of this scoping review is to explore the application of existing digital methods for training/education and feedback to surgeons in the context of performing invasive surgical procedures. This work will (1) summarize existing methods for shared learning in surgery and how they are characterized and operationalized, (2) examine the impact of their application, and (3) explore their benefits and barriers to implementation. The findings of this scoping review will inform the development of novel, real-time methods to optimize shared learning in surgical innovation. Methods This study will adhere to the recommended guidelines for conducting scoping reviews. A total of 6 different searches will be conducted within multiple sources (2 electronic databases, journals, social media, gray literature, commercial websites, and snowball searches) to comprehensively identify relevant articles and data. Searches will be limited to articles published in the English language within the last 5 years. Wherever possible, a 2-stage study selection process will be followed whereby the eligibility of articles will be assessed through the title, abstract, and full-text screening independently by 2 reviewers. Inclusion criteria will be articles providing data on (1) fully qualified theater staff involved in performing invasive procedures, (2) one or more methods for shared learning (ie, digital means for training/education and feedback), and (3) qualitative or quantitative evaluations of this method. Data will be extracted (10% double data extraction by an independent reviewer) into a piloted proforma and analyzed using descriptive statistics, narrative summaries, and principles of thematic analysis. Results The study commenced in October 2021 and is planned to be completed in 2023. To date, systematic searches were applied to 2 electronic databases (MEDLINE and Web of Science) and returned a total of 10,093 records. The results of this scoping review will be published as open access in a peer-reviewed journal. Conclusions This scoping review of methods for shared learning in surgery is, to our knowledge, the most comprehensive and up-to-date investigation that maps current information on this topic. Ultimately, efficient and effective sharing of information and knowledge of novel procedures and devices has the potential to optimize the evaluation of early-phase surgical research and reduce harmful innovation. International Registered Report Identifier (IRRID) PRR1-10.2196/37544

Background There is limited randomized evidence on the comparative outcomes of early-stage lung cancer resection by video-assisted thoracoscopic surgery (VATS) versus open resection. Methods We conducted a parallel-group multicenter randomized trial that recruited participants with known or suspected early-stage lung cancer and randomly assigned them to open or VATS resection of their lesions. The primary outcome was physical function at 5 weeks as a measure of recovery using the European Organisation for Research and Treatment of Cancer core health-related quality of life questionnaire (QLQ-C30) (scores range from 0 to 100, with higher scores indicating better function; the clinical minimally important difference for improvement is 5 points). We followed the patients for an additional 47 weeks for other outcomes. Results A total of 503 participants were randomly assigned (247 to VATS and 256 to open lobectomy). At 5 weeks, median physical function was 73 in the VATS group and 67 in the open surgery group, with a mean difference of 4.65 points (95% confidence interval, 1.69 to 7.61). Of the participants allocated to VATS, 30.7% had serious adverse events after discharge compared with 37.8% of those allocated to open surgery (risk ratio, 0.81 [95% confidence interval, 0.66 to 1.00]). At 52 weeks, there were no differences in cancer progression-free survival (hazard ratio, 0.74 [0.43 to 1.27]) or overall survival (hazard ratio, 0.67 [0.32 to 1.40]). Comclusions VATS lobectomy for lung cancer is associated with a better recovery of physical function in the 5 weeks after random assignment compared with open surgery. Long-term oncologic outcomes will require continued follow-up to assess. (Funded by the National Institute for Health Research Health Technology Assessment programme [reference number 13/04/03]; ISRCTN number, ISRCTN13472721.)

Purpose of Review This review describes the latest evidence for the impact of bariatric surgery on health-related quality of life (HRQL). Recent Findings The impact of bariatric surgery on HRQL is less well-understood than its clinical effectiveness on weight and co-morbidities. Poor-quality study design and different HRQL measures challenge systematic reviews and meta-analyses. Available limited evidence suggests that physical aspects of HRQL may improve more than mental health aspects of HRQL after bariatric surgery, reaching maximal benefits 1–2 years post-surgery. Comparative HRQL analyses between bariatric procedures cannot be made due to a lack of randomised data. Qualitative research highlights the tensions patients experience after bariatric surgery, which provides insights to observed changes in HRQL. Summary Standardized HRQL measures are being developed and agreed to improve future evidence synthesis. Two multi-centre randomised trials of bariatric surgical procedures including detailed HRQL assessment are in progress. It is hoped that the combination of comparative high-quality HRQL data and information from qualitative studies will provide new insights into patient well-being and health after bariatric surgery.

Background Video-assisted thoracoscopic surgery (VATS) approaches are increasingly used in lung cancer surgery, but little is known about their impact on patients’ health-related quality of life (HRQL). This prospective study measured recovery and HRQL in the year after VATS for non-small cell lung cancer (NSCLC) and explored the feasibility of HRQL data collection in patients undergoing VATS or open lung resection. Patients and Methods Consecutive patients referred for surgical assessment (VATS or open surgery) for proven/suspected NSCLC completed HRQL and fatigue assessments before and 1, 3, 6 and 12 months post-surgery. Mean HRQL scores were calculated for patients who underwent VATS (segmental, wedge or lobectomy resection). Paired t-tests compared mean HRQL between baseline and expected worst (1 month), early (3 months) and longer-term (12 months) recovery time points. Results A total of 92 patients received VATS, and 18 open surgery. Questionnaire response rates were high (pre-surgery 96–100%; follow-up 67–85%). Pre-surgery, VATS patients reported mostly high (good) functional health scores [(European Organisation for Research and Treatment of Cancer) EORTC function scores > 80] and low (mild) symptom scores (EORTC symptom scores Conclusions Lung resection has a considerable detrimental impact on patients’ HRQL that is not fully resolved 12 months post-surgery, despite a VATS approach. Graphic Abstract

Objective\ud \ud To investigate the functional and quality of life (QoL) outcomes of treatments for localised prostate cancer and inform treatment decision-making.\ud \ud \ud \ud Patients and Methods\ud \ud Men aged 50–69 years diagnosed with localised prostate cancer by prostate-specific antigen testing and biopsies at nine UK centres in the Prostate Testing for Cancer and Treatment (ProtecT) trial were randomised to, or chose one of, three treatments. Of 2565 participants, 1135 men received active monitoring (AM), 750 a radical prostatectomy (RP), 603 external-beam radiotherapy (EBRT) with concurrent androgen-deprivation therapy (ADT) and 77 low-dose-rate brachytherapy (BT, not a randomised treatment). Patient-reported outcome measures (PROMs) completed annually for 6 years were analysed by initial treatment and censored for subsequent treatments. Mixed effects models were adjusted for baseline characteristics using propensity scores.\ud \ud \ud \ud Results\ud \ud Treatment-received analyses revealed different impacts of treatments over 6 years. Men remaining on AM experienced gradual declines in sexual and urinary function with age (e.g., increases in erectile dysfunction from 35% of men at baseline to 53% at 6 years and nocturia similarly from 20% to 38%). Radical treatment impacts were immediate and continued over 6 years. After RP, 95% of men reported erectile dysfunction persisting for 85% at 6 years, and after EBRT this was reported by 69% and 74%, respectively (P

IntroductionThe development of innovative invasive procedures and devices are essential to improving outcomes in healthcare. However, how these are introduced into practice has not been studied in detail. The Lotus study will follow a wide range of ‘case studies’ of new procedures and/or devices being introduced into NHS trusts to explore what information is communicated to patients, how procedures are modified over time and how outcomes are selected and reported.Methods and analysisThis qualitative study will use ethnographic approaches to investigate how new invasive procedures and/or devices are introduced. Consultations in which the innovation is discussed will be audio-recorded to understand information provision practice. To understand if and how procedures evolve, they will be video recorded and non-participant observations will be conducted. Post-operative interviews will be conducted with the innovating team and patients who are eligible for the intervention. Audio-recordings will be audio-recorded, transcribed verbatim and analysed thematically using constant comparison techniques. Video-recordings will be reviewed to deconstruct procedures into key components and document how the procedure evolves. Comparisons will be made between the different data sources.Ethics and disseminationThe study protocol has Health Research Authority (HRA) and Health and Care Research Wales approval (Ref 18/SW/0277). Results will be disseminated at appropriate conferences and will be published in peer-reviewed journals. The findings of this study will provide a better understanding of how innovative invasive procedures and/or devices are introduced into practice.

Complex interventions are commonly used in the health and social care services, public health practice, and other areas of social and economic policy that have consequences for health. Such interventions are delivered and evaluated at different levels, from individual to societal. Examples include a new surgical procedure, the redesign of a health care programme, and a change in welfare policy. The UK Medical Research Council (MRC) published a framework for researchers and research funders on developing and evaluating complex interventions in 2000 and revised guidance in 2006.[1] Although these documents continue to be widely used and are now accompanied by a range of more detailed guidance on specific aspects of the research process,[2–5] there have been important conceptual, methodological and theoretical developments since 2006. These developments have been addressed in a new framework commissioned by the National Institute of Health Research (NIHR) and the MRC.[6] The framework aims to help researchers work with other stakeholders to identify the key questions about complex interventions, and to design and conduct research with a diversity of perspectives and appropriate choice of methods., The work was funded by the NIHR (Department of Health and Social Care 73514) and Medical Research Council (MRC). Additional time on the study was funded by grants from the MRC for Kathryn Skivington (MC_UU_12017/11, MC_UU_00022/3), Lynsay Matthews, Sharon Anne Simpson, Laurence Moore (MC_UU_12017/14, MC_UU_00022/1), Peter Craig (MC_UU_12017/15, MC_UU_00022/2), Martin White (MC_UU_12015/6 and MC_UU_00006/7). Additional time on the study was also funded by grants from the Chief Scientist Office of the Scottish Government Health Directorates for Kathryn Skivington (SPHSU11 and SPHSU18), Lynsay Matthews, Sharon Anne Simpson and Laurence Moore (SPHSU14 and SPHSU16), and Peter Craig (SPHSU13 and SPHSU15). Kathryn Skivington and Sharon Anne Simpson were also supported by an MRC Strategic Award (MC_PC_13027). JBl received funding from NIHR Biomedical Research Centre at University Hospitals Bristol NHS Foundation Trust and the University of Bristol and by the MRC ConDuCT-II Hub (Collaboration and innovation for Difficult and Complex randomised controlled Trials In Invasive procedures - MR/K025643/1). MP is funded in part as director of the NIHR’s Public Health Policy Research Unit.

Patient-reported outcomes (PROs) are used in clinical trials to provide valuable evidence on the impact of disease and treatment on patients' symptoms, function and quality of life. High-quality PRO data from trials can inform shared decision-making, regulatory and economic analyses and health policy. Recent evidence suggests the PRO content of past trial protocols was often incomplete or unclear, leading to research waste. To address this issue, international, consensus-based, PRO-specific guidelines were developed: the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT)-PRO Extension. The SPIRIT-PRO Extension is a 16-item checklist which aims to improve the content and quality of aspects of clinical trial protocols relating to PRO data collection to minimise research waste, and ultimately better inform patient-centred care. This SPIRIT-PRO explanation and elaboration (E&E) paper provides information to promote understanding and facilitate uptake of the recommended checklist items, including a comprehensive protocol template. For each SPIRIT-PRO item, we provide a detailed description, one or more examples from existing trial protocols and supporting empirical evidence of the item's importance. We recommend this paper and protocol template be used alongside the SPIRIT 2013 and SPIRIT-PRO Extension paper to optimise the transparent development and review of trial protocols with PROs. ispartof: BMJ OPEN vol:11 issue:6 ispartof: location:England status: published

BackgroundMany completed trials of interventions for uncomplicated gallstone disease are not as helpful as they could be due to lack of standardisation across studies, outcome definition, collection and reporting. This heterogeneity of outcomes across studies hampers useful synthesis of primary studies and ultimately negatively impacts on decision making by all stakeholders. Core outcome sets offer a potential solution to this problem of heterogeneity and concerns over whether the ‘right’ outcomes are being measured. One of the first steps in core outcome set generation is to identify the range of outcomes reported (in the literature or by patients directly) that are considered important.ObjectivesTo develop a systematic map that examines the variation in outcome reporting of interventions for uncomplicated symptomatic gallstone disease, and to identify other outcomes of importance to patients with gallstones not previously measured or reported in interventional studies.ResultsThe literature search identified 794 potentially relevant titles and abstracts of which 137 were deemed eligible for inclusion. A total of 129 randomised controlled trials, 4 gallstone disease specific patient-reported outcome measures (PROMs) and 8 qualitative studies were included. This was supplemented with data from 6 individual interviews, 1 focus group (n=5 participants) and analysis of 20 consultations. A total of 386 individual recorded outcomes were identified across the combined evidence: 330 outcomes (which were reported 1147 times) from trials evaluating interventions, 22 outcomes from PROMs, 17 outcomes from existing qualitative studies and 17 outcomes from primary qualitative research. Areas of overlap between the evidence sources existed but also the primary research contributed new, unreported in this context, outcomes.ConclusionsThis study took a rigorous approach to catalogue and map the outcomes of importance in gallstone disease to enhance the development of the COS ‘long’ list. A COS for uncomplicated gallstone disease that considers the views of all relevant stakeholders is needed.

ObjectivesCOVID-19 presents a risk of infection and transmission for operating theatre teams. Guidelines to protect patients and staff emerged and changed rapidly based on expert opinion and limited evidence. This paper presents the experiences and innovations developed by international surgical teams during the early stages of the pandemic to attempt to mitigate risk.DesignIn-depth, semistructured interviews were audio recorded, transcribed and analysed thematically using methods of constant comparison.Participants43 participants, including surgeons from a range of specialties (primarily general surgery, otolaryngology, neurosurgery, cardiothoracic and ophthalmology), anaesthetists and those in nursing roles.SettingThe UK, Italy, Spain, the USA, China and New Zealand between March and May 2020.ResultsSurgical teams sought to mitigate COVID-19 risks by modifying their current practice with an abundance of strategies and innovations. Communication and teamwork played an integral role in how teams adapted, although participants reflected on the challenges of having to improvise in real time. Uncertainties remained about optimal surgical practice and there were significant tensions where teams were forced to balance what was best for patients while contemplating their own safety.ConclusionsThe perceptions of risks during a pandemic such as COVID-19 can be complex and context dependent. Management of these risks in surgery must be driven by evidence‐based practice resulting from a pragmatic and novel approach to collation of global evidence. The context of surgery has changed dramatically, and surgical teams have developed a plethora of innovations. There is an urgent need for high-quality evidence to inform surgical practice that optimises the safety of both patients and healthcare professionals as the COVID-19 pandemic unfolds.

OBJECTIVE: The Core Outcome Set-STAndards for Development (COS-STAD) contains 11 standards (12 criteria) that are deemed to be the minimum design recommendations for all core outcome set (COS) development projects. Cancer is currently the disease area with the highest number of published COSs and is a major cause of worldwide morbidity and mortality. The aim of this study was to provide a baseline of cancer COS standards.STUDY DESIGN AND SETTING: Systematic reviews of COSs have identified 307 published COS studies. Cancer COSs were eligible for inclusion. Two reviewers independently assessed each of the COSs against the 12 criteria.RESULTS: Forty-nine cancer COSs were included; none met all 12 criteria representing the 11 minimum standards assessed in this study (range = 4-11 criteria, median = 6 criteria). All studies met the four scope standards, eight (16%) met all three standards for stakeholders involved, and two (4%) met all four standards for consensus process standards.CONCLUSION: With the exception of "scope" specification, there is much need for improvement. Poor reporting often made it challenging to assess whether minimum standards were met. The consensus process criteria were most difficult to assess, particularly those that required an assessment of being a priori. This is the first application of COS-STAD criteria to studies that have developed COSs and provides a baseline of cancer COS standards of development.

Background RCTs in surgery are challenging owing to well established methodological issues. Well designed pilot and feasibility studies (PFS) may help overcome such issues to inform successful main trial design and conduct. This study aimed to analyse protocols of UK-funded studies to explore current use of PFS in surgery and identify areas for practice improvement. Methods PFS of surgical interventions funded by UK National Institute for Health Research programmes from 2005 to 2015 were identified, and original study protocols and associated publications sourced. Data extracted included study design characteristics, reasons for performing the work including perceived uncertainties around conducting a definitive main trial, and whether the studies had been published. Results Thirty-five surgical studies were identified, of which 29 were randomized, and over half (15 of 29) included additional methodological components (such as qualitative work examining recruitment, and participant surveys studying current interventions). Most studies focused on uncertainties around recruitment (32 of 35), with far fewer tackling uncertainties specific to surgery, such as intervention stability, implementation or delivery (10 of 35). Only half (19 of 35) had made their results available publicly, to date. Conclusion The full potential of pretrial work to inform and optimize definitive surgical studies is not being realized.

Objective To establish current practice of the management of learning and clustering effects, by treating center and surgeon, in the design and analysis of randomized surgical trials. Study design and setting The need for more surgical randomized trials is well recognized, and in recent years conduct has grown. Rigorous design, conduct, and analyses of such studies is important. Two methodological challenges are clustering effects, by center or surgeon, and surgical learning on trial outcomes. Sixteen leading journals were searched for randomized trials published within a two-year period. Data were extracted on considerations for learning and clustering effects. Results A total of 247 eligible studies were identified. Trials accounted for learning with 2% using an expertise-based design and 39% accounting for expertise by predefining surgeon credentials. One study analyzed learning. Clustering, by site and surgeon, was commonly managed by stratifying randomization, although one-third of center and 40% of surgeon stratified trials did not also adjust analysis. Conclusion Considerations for surgical learning and clustering effects are often unclear. Methods are varied and demonstrate poor adherence to established reporting guidelines. It is recommended that researchers consider these issues on a trial-by-trial basis, and report methods or justify where not needed to inform interpretation of results.

BackgroundInternational stakeholder participation is important in the development of core outcome sets (COS). Stakeholders, however, may value health outcomes differently when regional differences are considered. Here, we explore how region, health income and participant characteristics influence prioritisation of outcomes during development of a COS for gastric cancer surgery trials (the GASTROS study).Methods952 participants from 55 countries participating in a Delphi survey during COS development were eligible for inclusion. Recruits were grouped according to region (East or West), country income classification (high and low-to-middle income) and other characteristics (e.g. patients; age, sex, time since surgery, mode of treatment, surgical approach and healthcare professionals; clinical experience). Groups were compared with respect to how they categorised outcomes (‘consensus in’, ‘consensus out’, ‘no consensus’). Outcomes categorised as ‘consensus in’ or ‘consensus out’ by all 3 stakeholder groups would be automatically included in or excluded from the COS respectively.ResultsIn total, 13 outcomes were categorised ‘consensus in’, 13 ‘consensus out’ and 31 ‘no consensus’. There was little variation in prioritisation of outcomes by stakeholders from Eastern or Western countries and high or low-to-middle income countries. There was little variation in outcome prioritisation within either health professional or patient groups.ConclusionOur study suggests that there is little variation in opinion within stakeholder groups when participant region and other characteristics are considered. This finding may help COS developers when designing their Delphi surveys and recruitment strategies. Further work across other clinical fields is needed before broad recommendations can be made.

Background Typically, subgroup analyses in clinical trials are conducted by comparing the intervention effect in each subgroup by means of an interaction test. However, trials are rarely, if ever, adequately powered for interaction tests, so clinically important interactions may go undetected. We discuss the application of Bayesian methods by using expert opinions alongside the trial data. We applied this methodology to the VeRDiCT trial investigating the effect of preoperative volume replacement therapy (VRT) versus no VRT (usual care) in diabetic patients undergoing cardiac surgery. Two subgroup effects were of clinical interest, a) preoperative renal failure and b) preoperative type of antidiabetic medication. Methods Clinical experts were identified within the VeRDiCT trial centre in the UK. A questionnaire was designed to elicit opinions on the impact of VRT on the primary outcome of time from surgery until medically fit for hospital discharge, in the different subgroups. Prior beliefs of the subgroup effect of VRT were elicited face-to-face using two unconditional and one conditional questions per subgroup analysis. The robustness of results to the ‘community of priors’ was assessed. The community of priors was built using the expert priors for the mean average treatment effect, the interaction effect or both in a Bayesian Cox proportional hazards model implemented in the STAN software in R. Results Expert opinions were obtained from 7 clinicians (6 cardiac surgeons and 1 cardiac anaesthetist). Participating experts believed VRT could reduce the length of recovery compared to usual care and the greatest benefit was expected in the subgroups with the more severe comorbidity. The Bayesian posterior estimates were more precise compared to the frequentist maximum likelihood estimate and were shifted toward the overall mean treatment effect. Conclusions In the VeRDiCT trial, the Bayesian analysis did not provide evidence of a difference in treatment effect across subgroups. However, this approach increased the precision of the estimated subgroup effects and produced more stable treatment effect point estimates than the frequentist approach. Trial methodologists are encouraged to prospectively consider Bayesian subgroup analyses when low-powered interaction tests are planned. Trial registration ISRCTN, ISRCTN02159606. Registered 29th October 2008.

Background Little is known about the electronic collection and clinical feedback of patient-reported outcomes (ePROs) following surgical discharge. This systematic review summarized the evidence on the collection and uses of electronic systems to collect PROs after discharge from hospital after surgery. Method Systematic searches of MEDLINE, Embase, PsycINFO, CINAHL and Cochrane Central were undertaken from database inception to July 2019 using terms for ‘patient reported outcomes’, ‘electronic’, ‘surgery’ and ‘at home’. Primary research of all study designs was included if they used electronic systems to collect PRO data in adults after hospital discharge following surgery. Data were collected on the settings, patient groups and specialties, ePRO systems (including features and functions), PRO data collected, and integration with health records. Results Fourteen studies were included from 9474 records, including two RCTs and six orthopaedic surgery studies. Most studies (9 of 14) used commercial ePRO systems. Six reported types of electronic device were used: tablets or other portable devices (3 studies), smartphones (2), combination of smartphones, tablets, portable devices and computers (1). Systems had limited features and functions such as real-time clinical feedback (6 studies) and messaging service for patients with care teams (3). No study described ePRO system integration with electronic health records to support clinical feedback. Conclusion There is limited reporting of ePRO systems in the surgical literature, and ePRO systems lack integration with hospital clinical systems. Future research should describe the ePRO system and ePRO questionnaires used, and challenges encountered during the study, to support efficient upscaling of ePRO systems using tried and tested approaches., This systematic review examined the use of electronic systems to collect patient-reported outcomes (ePROs) post-discharge after surgery. Fourteen studies were included - most used commercial ePRO systems, few reported the types of electronic devices used, systems had limited features and functions and none described integration of the system with electronic health records. There is limited reporting of ePRO systems in surgical literature.

Background: Surgical site infections (SSIs) are costly and associated with poorer patient outcomes. Intraoperative surgical site irrigation and intra-cavity lavage may reduce the risk of SSIs through removal of dead or damaged tissue, metabolic waste, and site exudate. Irrigation with antibiotic or antiseptic solutions may further reduce the risk of SSI because of bacteriocidal properties. Randomized controlled trials (RCTs) have been conducted comparing irrigation solutions, but important comparisons (e.g., antibiotic vs. antiseptic irrigation) are absent. We use systematic review-based network meta-analysis (NMA) of RCTs to compare irrigation solutions for prevention of SSI. Methods: We used Cochrane methodology and included all RCTs of participants undergoing a surgical procedure with primary site closure, in which method of irrigation was the only systematic difference between groups. We used a random effects Bayesian NMA to create a connected network of comparisons. Results are presented as odds ratios (OR) of SSI, where OR Results: We identified 42 eligible RCTs with 11,726 participants. Most were at unclear or high risk of bias. The RCTs included groups given no irrigation or non-antibacterial, antiseptic, or antibiotic irrigation. There was substantial heterogeneity, and a random effects model was selected. Relative to non-antibacterial irrigation, mean OR of SSI was 0.439 (95% credible interval: 0.282, 0.667) for antibiotic irrigation and 0.573 (0.321, 0.953) for antiseptic agents. No irrigation was similar to non-antibacterial irrigation (OR 0.959 [0.555, 1.660]). Antibiotic and antiseptic irrigation were ranked as most effective for preventing SSIs; this conclusion was robust to potential bias. Conclusions: Our NMA found that antibiotic and antiseptic irrigation had the lowest odds of SSI. There was high heterogeneity, however, and studies were at high risk of bias. A large RCT directly comparing antibiotic irrigation with both antiseptic and non-antibacterial irrigation is needed to define the standard of care for SSI prevention by site irrigation.

Background Core outcome sets (COS) should be relevant to key stakeholders and widely applicable so that researchers are willing to use them when designing trials. Many COS developers have utilised online Delphi surveys which enable wider international stakeholder participation. Despite broader participation, most international COS projects have restricted Delphi surveys to a single language potentially excluding important opinion from those who are not fluent in the survey language.Methods A structured review of current approaches to translating Delphi surveys for COS development was undertaken. We present a proposed methodology adapted from international guidance. Results Four studies were identified from our structured review. Wide variation exists in the methodological approaches to translating Delphi surveys for the developing of COS. Issues which arise when developing multi-language Delphi surveys include establishing translation groups, timelines, financial implications, strategies to maximise recruitment and regulatory approvals.Conclusion Consideration of the issues described will improve planning by other COS developers and can be used to widen international participation from both patients and healthcare professionals.

IntroductionSurgery (oesophagectomy), with neoadjuvant chemo(radio)therapy, is the main curative treatment for patients with oesophageal cancer. Several surgical approaches can be used to remove an oesophageal tumour. The Ivor Lewis (two-phase procedure) is usually used in the UK. This can be performed as an open oesophagectomy (OO), a laparoscopically assisted oesophagectomy (LAO) or a totally minimally invasive oesophagectomy (TMIO). All three are performed in the National Health Service, with LAO and OO the most common. However, there is limited evidence about which surgical approach is best for patients in terms of survival and postoperative health-related quality of life.Methods and analysisWe will undertake a UK multicentre randomised controlled trial to compare LAO with OO in adult patients with oesophageal cancer. The primary outcome is patient-reported physical function at 3 and 6 weeks postoperatively and 3 months after randomisation. Secondary outcomes include: postoperative complications, survival, disease recurrence, other measures of quality of life, spirometry, success of patient blinding and quality assurance measures. A cost-effectiveness analysis will be performed comparing LAO with OO. We will embed a randomised substudy to evaluate the safety and evolution of the TMIO procedure and a qualitative recruitment intervention to optimise patient recruitment. We will analyse the primary outcome using a multi-level regression model. Patients will be monitored for up to 3 years after their surgery.Ethics and disseminationThis study received ethical approval from the South-West Franchay Research Ethics Committee. We will submit the results for publication in a peer-reviewed journal.Trial registration numberNCT10386621.

ObjectivesPatient-reported outcome (PRO) measurements used in cancer research can assess a number of health domains. Our primary objective was to investigate which broad types of PRO domains (namely, functional health, symptoms, and global quality of life [QoL]) most frequently yielded significant differences between treatments in randomized controlled trials (RCTs).MethodsA total of 229 RCTs published between January 2004 and February 2019, conducted on patients diagnosed with the most common solid malignancies and assessed using the European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30, were considered. Studies were identified systematically using literature searches in key electronic databases. Unlike other PRO measurements typically used in RCTs, the scoring algorithm of the multidimensional EORTC QLQ-C30 allowed us to clearly distinguish the 3 broad types of PRO domains.ResultsIn total, 134 RCTs (58.5%) reported statistically significant differences between treatment arms for at least 1 of the QLQ-C30 domains. Most frequently, differences were reported for 2 or all 3 broad types of PRO domains (78 of 134 trials; 58.2%). In particular, 35 trials (26.1%) found significant differences for symptoms, functional health, and global QoL, 24 trials (17.9%) for symptoms and functional health, 11 trials (8.2%) for functional health and global QoL, and 8 trials (6.0%) for symptoms and global QoL. The likelihood of finding a statistically significant difference between treatment arms was not associated with key study characteristics, such as study design (ie, open-label vs blinded trials) and industry support.ConclusionsOur findings emphasize the importance of a multidimensional PRO assessment to most comprehensively capture the overall burden of therapy from the patients’ standpoint.

As pathological confirmation of lung cancer influences treatment selection for suspected early stage lung cancer, high pre-treatment tissue confirmation rates (90%) have been recommended by the National Lung Cancer Audit 2018. However, this practice prior to radical management of patients with early stage lung cancer has never been studied. Using prospective collection of pre-defined biopsy data within multi-disciplinary teams in UK centres, we sought to define the management and outcomes of incomplete pre-treatment tissue confirmation of primary lung cancer in patients undergoing surgery in a multi-centre clinical trial. Methods VIOLET is an UK National Institute of Healthcare Research (NIHR) Health Technology Assessment (HTA) funded clinical trial (Ref: 13/04/03) comparing video-assisted thoracic surgery (VATS) versus open surgery for known or suspected lung cancer. Diagnostic patient pathways were identified and documented for participants with and without pre-surgical tissue confirmation of primary lung cancer. Methods of tissue confirmation (where undertaken) were documented, with resected pathology report as reference compared against the outcome of inappropriate lobectomy (benign disease or secondary lung cancer). Results From July 2015 to February 2019 a total of 2,109 patients were screened, of whom 503 patients were eligible and consented to participate in VIOLET. In total 263 (52%) of patients had a pre-operative pathologic confirmed diagnosis of primary lung cancer. Of the remaining 240 (48%) patients, the majority 205 (85%) did not have a pre-operative biopsy attempted and 35 patients (15%) received a pre-operative non-diagnostic biopsy. Of the 240 patients who entered the operating theatre without pathological confirmation of primary lung cancer, biopsy and frozen section analysis was undertaken in 144 (60%) patients. In the remaining 96 (40%) a lobectomy was undertaken without tissue confirmation (19% of the cohort of 503 trial participants). The overall lobectomy rate for benign disease was 6/503 (1.2%). Conclusions Our results suggest low levels of inappropriate resection can be achieved with a pre-surgical tissue confirmation rates of approximately 50% through a combination of intra-operative confirmatory biopsy and correct risk estimation of lung cancer. The practice would need to be monitored to ensure acceptable levels are consistently achieved across multi-disciplinary teams caring for patients with suspected primary lung cancer.

AimsTo determine the prevalence of anxiety and depression amongst participants with severe or complex obesity randomised and selected for bariatric surgery in a large multi-centre trial.To describe the change in prevalence of anxiety and depression amongst participants who had undergone bariatric surgery, within 6 months of randomisation and at 12 months post-randomisation.MethodThe By-Band-Sleeve (BBS) study is a multi-site randomised controlled trial evaluating the surgical management of severe or complex obesity and is the largest trial of its kind. Participants completed the Hospital Anxiety and Depression Scale (HADS) on study enrolment (pre-randomisation) and at 12 months post-randomisation. In this sub-study, we describe provisional data concerning the baseline prevalence of anxiety and depression along with change in median HADS symptom score amongst those who actually underwent bariatric surgery.Result758 participants met the criteria for study inclusion with 716 (94.46%) and 712 (93.93%) individuals fully completing questionnaires for HADS-A and HADS-D. At pre-randomisation, the prevalence of possible (HADS A/D = 8-10) and probable (HADS A/D >11) anxiety or depression was 46.19% (n 330/716) and 48.17% (n 48.17%) respectively. Paired and complete HADS-A and HADS-D questionnaires were available for 70.25% (n 503/716) and 69.94% (n 498/712) participants. There was a highly statistically significant decrease in median HADS-A and HADS-D scores at 12 months post-randomisation (Wilcoxon signed-rank test p < 0.001). This was coupled with a statistically significant reduction in the proportion of cases with possible and probable anxiety (–9.54%, p < 0.001) and also depression (–22.21%, p < 0.001) at 12 months post-randomisation.ConclusionOur results characterise the high rate of psychological comorbidity amongst patients with severe or complex obesity selected for bariatric surgery. Whilst bariatric surgery remains the most clinically effective treatment for severe obesity, its effects on long-term post-operative mental health outcomes are less clear. These findings contribute to the growing body of evidence calling for increased pre/post-operative mental health surveillance and integrated care for this cohort of patients.

e16057 Background: Patients with localised oesophageal adenocarcinoma or squamous cell cancer are frequently offered surgery, usually with neoadjuvant treatment. Whether minimally invasive surgical approaches are superior to standard open procedures in terms of patient recovery and survival benefit is unclear. Well-designed and well-conducted pragmatic trials are limited. The ROMIO study compared laparoscopic abdominal surgery and thoracotomy (LAO) with open oesophagectomy (OO), to test the hypothesis that LAO allows faster recovery than OO whilst maintaining the survival benefit of surgery. Methods: A pragmatic multi-centre randomised controlled trial (1:1 LAO vs. OO) was conducted in 9 major cancer centres in the UK. Included were patients with localised adenocarcinoma or squamous cell cancer selected by a multi-disciplinary team for oesophagectomy with or without neoadjuvant treatment. Surgery was quality assured by provision of a protocol, pre-operative video assessment of the 40 participating surgeons and intra-operative photographs of key agreed surgical components. The primary outcome was the physical function scale of the EORTC QLQ-C30 assessed during the first 3 months. Results: At enrolment to ROMIO 447 (85%) of 526 participants were male, mean age was 67 years (SD 9), 469 (89%) had an adenocarcinoma, 368 (70%) had a clinically staged T3 or T4a tumour, 295 (56%) had clinically positive nodes, and 438 (83%) underwent neoadjuvant treatment. 263 were randomly allocated to each of the two procedures, with 241 (92%) undergoing their allocated open surgery and 237 (91%) undergoing their allocated LAO (hybrid) surgery. Analyses are underway and this presentation will include the primary outcome measure and other short-term clinical outcomes including key complications and survival during the first 90 days (clinical data >95% complete). Conclusions: ROMIO is the largest multi-centre randomised controlled surgical trial of minimal access versus open surgical approaches for oesophageal cancer. The provision of a surgical quality assessment tool will supplement trial data to provide for the first-time evidence of surgical standards of both approaches. Clinical trial information: ISRCTN10386621.

8504 Background: Video assisted thoracoscopic surgery (VATS) is a popular access for lung cancer resection. However, there is limited information from RCTs from in-hospital to one-year clinical efficacy, safety and oncologic outcomes of a minimal access approach. Methods: VIOLET is a parallel group multi-center RCT conducted in 9 centers in the United Kingdom that recruited participants with known or suspected (cT1-3, N0-1 and M0) lung cancer (ISRCTN13472721). Trial protocol: https://bmjopen.bmj.com/content/9/10/e029507.info. Results: From July 2015 to February 2019, 503 participants were randomized to VATS (n=247) or open (n=256) lobectomy. Patients allocated to VATS had less pain with a mean difference (MD) in visual analogue score of -0.54 (95%CI -0.99 to -0.10) despite less analgesic consumption (mean ratio 0.90, 95%CI 0.80 to 1.01). After discharge pain was consistent on multiple sub-scales including overall pain (MD -7.19, -10.59 to -3.80), chest pain (MD -4.66, -7.96 to -1.36) and an 18% relative risk (RR) reduction in incision pain (RR 0.82; 0.72 to 0.94) up to one-year. Better functional recovery continued in VATS arm after discharge with better physical function (primary outcome) with MD of 4.65 (1.69 to 7.61; P=0.002) at 5 weeks and overall improvement in global health status with a MD of 4.21 (1.62 to 6.79; P=0.001). In hospital, VATS arm had fewer complications (RR 0.74, 0.66 to 0.84; P

e13598 Background: The impact on cancer outcomes from the Covid-19 pandemic has yet to be determined. Concerns persist on screening, delays in diagnosis, treatment interruptions and outcomes of infection in the immunosuppressed. The need for agile working has been exemplified by establishment of Nightingale Hospitals, staff redeployment and sudden integration of virtual consultations into clinical working. With most cancer clinical trials halted, recruitment into COVID-19 research became essential and embedded into the everyday. Here we present how rapid implementation of COVID-19 randomised clinical trials within an NHS organisation during the pandemic was achieved. Methods: A COVID-19 senior facilitation committee was set up to provide oversight, maximise staff capacity and resource and prioritise studies. Specific strategies to maximise access and clinical trials recruitment for patients including children and those with solid tumours were designed. These included presence of a research nurse at clinical ward rounds and team meetings, the promotion of protocol and informed consent training to all including doctors in the acute settings and weekly research meetings to share-best practice. Reflecting on learnings from this time provide an opportunity to consider how we adjust working for our patients in the future. Results: The integration of research into the everyday working of clinical teams looking after patients with COVID-19 has become the norm. The provision of protocol and informed consent training for all levels of staff and the consideration of all patients for trials during clinical ward rounds and multi-disciplinary meetings, have ensured access to trials has become embedded. The integration of research nurses working, upskilling and prompting clinical colleagues has ensured equity of access and provided a research presence and focus during the busy clinical day. The adoption of cross-disciplinary working, sharing best practice and a culture of commitment and support to the trials ensures no patient is denied the opportunity to participate. Three RTCs opened over 7 weeks. At one site 1904 patients were screened for one of the randomised-controlled trials and over 18% of these patients (351) were recruited and 175 patients declined. Conclusions: The pandemic has had a devastating impact across the UK. However, a coordinated and collaborative multi-disciplinary approach has supported high recruitment and equity of access for patients into COVID-19 trials. Learnings from this work may lead to embedding clinical trials and access to translational research for cancer patients in the future as we recover from the full impact of the pandemic. COVID-19 research has demonstrated how increased recruitment accelerates access and implementation of new innovations and novel drug combinations.The full impact of improved access to cancer research in the future during COVID recovery is worthy of more research.

e24117 Background: The EORTC Item Library is an online, interactive platform comprised of 950 distinct questions (items) from 67 different EORTC patient-reported outcome (PRO) questionnaires, covering a range of symptomatic toxicities, types of functioning, and impact on quality of life. These PROs provide a patient-centred perspective, complementing clinician adverse event (AE) reporting using classifications like the CTCAE. In order to summarize the coverage of symptomatic toxicities and facilitate the identification of items through use of a standardized framework, a mapping study was carried out, aimed at creating a coding system to classify EORTC items according to the CTCAE and link them to corresponding AEs. Methods: All items were searched for within the CTCAE (v5.0) using a deductive approach. Items were coded as linked if they were described within an AE’s title, description, or grading. Items not suitable for CTCAE coding were inductively assigned a descriptive classification. Descriptive classifications were also applied along with CTCAE codes when they provided additional information. Symptoms described in EORTC items but not located in the CTCAE were coded as missing and additional codes were assigned to highlight EORTC items capturing multiple underlying issues and diagnosis only CTCAE codes. Two raters independently coded 249 items and agreement was calculated. The remaining 701 items were coded by one rater and verified by the second, with a third introduced to discuss any discrepancies until a consensus was reached. Results: Agreement for raters following independent coding was 77.9% for at least one AE per item. In total, 625 (65.8%) items were linked to 208 different AEs. Fatigue was the most commonly linked AE, representing 4.9% of linked AEs. The majority of linked items were associated with one (65.6%) or two (23.5%) AEs, with some linked to three or more (10.9%). Multiple linkage resulted from different symptoms relating to the same issue/diagnosis or one symptom relating to multiple diagnoses. Two symptoms captured by six EORTC items but not found in the CTCAE were identified: bowel urgency and tenesmus. Seven descriptive non-CTCAE classifications emerged, with most of these covering the emotional impact of symptom, diagnosis, or treatment (33.6%) and information/satisfaction with care (31.7%). Nineteen items (2%) were linked to multiple underlying issues, and 43 (4.5%) to diagnosis only CTCAE codes. Conclusions: The EORTC Item Library provides extensive coverage of CTCAE symptomatic toxicities, along with other issues that are important to cancer patients, including emotional well-being and satisfaction with care services. Classifying symptomatic PRO items following the CTCAE clinical framework may facilitate future PRO selection and use in clinical trials and routine care.

Introduction The introduction of biological and synthetic meshes has revolutionised the practice of implant-based breast reconstruction (IBBR) but evidence for effectiveness is lacking. The iBRA (implant Breast Reconstruction evAluation) study is a national trainee-led project that aims to explore the practice and outcomes of IBBR to inform the design of a future trial. We report the results of the iBRA National Practice Questionnaire (NPQ) which aimed to comprehensively describe the provision and practice of IBBR across the UK. Methods A questionnaire investigating local practice and service provision of IBBR developed by the iBRA Steering Group was completed by trainee and consultant leads at breast and plastic surgical units across the UK. Summary data for each survey item were calculated and variation between centres and overall provision of care examined. Results 81 units within 79 NHS-hospitals completed the questionnaire. Units offered a range of reconstructive techniques, with IBBR accounting for 70% (IQR:50–80%) of participating units' immediate procedures. Units on average were staffed by 2.5 breast surgeons (IQR:2.0–3.0) and 2.0 plastic surgeons (IQR:1.0–3.0) performing 35 IBBR cases per year (IQR:20-50). Variation was demonstrated in the provision of novel different techniques for IBBR especially the use of biological (n = 62) and synthetic (n = 25) meshes and in patient selection for these procedures. Conclusions The iBRA-NPQ has demonstrated marked variation in the provision and practice of IBBR in the UK. The prospective audit phase of the iBRA study will determine the safety and effectiveness of different approaches to IBBR and allow evidence-based best practice to be explored., Highlights • Implant breast reconstruction (IBBR) and the range of techniques is poorly evidence based. • We aimed to explore the current practice of IBBR in the UK to inform the design of a future definitive study. • Significant variation was demonstrated in the availability of techniques and patient selection for IBBR. • There is a need for well-designed studies to establish best practice and improve outcomes for patients considering IBBR.

BACKGROUND:Randomized controlled trials (RCTs) involving surgical procedures are challenging for recruitment and infrequent in the specialty of bariatrics. The pilot phase of the By-Band-Sleeve study (gastric bypass versus gastric band versus sleeve gastrectomy) provided the opportunity for an investigation of recruitment using a QuinteT Recruitment Intervention (QRI).PATIENTS/METHODS:The QRI investigated recruitment in two centers in the pilot phase comparing bypass and banding, through the analysis of 12 in-depth staff interviews, 84 audio-recordings of patient consultations, 19 non-participant observations of consultations and patient screening data. QRI findings were developed into a plan of action and fed back to centers to improve information provision and recruitment organization.RESULTS:Recruitment proved to be extremely difficult with only two patients recruited during the first two months. The pivotal issue in Center A was that an effective and established clinical service could not easily adapt to the needs of the RCT. There was little scope to present RCT details or ensure efficient eligibility assessment, and recruiters struggled to convey equipoise. Following presentation of QRI findings, recruitment in Center A increased from 9% in the first two months (2/22) to 40% (26/65) in the four months thereafter. Center B, commencing recruitment three months after Center A, learnt from the emerging issues in Center A and set up a special clinic for trial recruitment. The trial successfully completed pilot recruitment and progressed to the main phase across 11 centers.CONCLUSIONS:The QRI identified key issues that enabled the integration of the trial into the clinical setting. This contributed to successful recruitment in the By-Band-Sleeve trial-currently the largest in bariatric practice-and offers opportunities to optimize recruitment in other trials in bariatrics.International Journal of Obesity accepted article preview online, 03 July 2017. doi:10.1038/ijo.2017.153.

Background: Malnutrition is common in patients undergoing gastric cancer resection, leading to weight loss, although little is known about how this impacts on health related quality of life (HRQL) This study aimed to explore the association between HRQL and weight loss in patients 2 years after curative gastric cancer resection. Methods: Consecutive patients undergoing curative gastric cancer resection and surviving at least 2 years without disease recurrence were recruited. Patients completed the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the specific module for gastric cancer (STO22) before and 2 years postoperatively and associations between HRQL scores and patients with and without ≥ 10% body weight loss (BWL) were examined. Results: A total of 76 patients were included, of whom 51 (67%) had BWL ≥ 10%. At 2 years postoperatively, BWL ≥ 10% was associated with deterioration of all functional aspects of quality of life, with persistent pain (21.6%), diarrhoea (13.7%) and nausea/vomiting (13.7%). By contrast, none of the patients with BWL < 10% experienced severe nausea/vomiting, pain or diarrhoea. Conclusions: Disabling symptoms occurred more frequently in patients with ≥ 10% BWL than in those with < 10% BWL, with a relevant negative impact on HRQL. A cause-effect relationship between weight loss and postoperative outcome remains unsolved.

OBJECTIVE: The aim of this study was to assess long-term health-related quality of life (HRQL) in patients after thoracoscopic and open esophagectomy. SUMMARY OF BACKGROUND DATA: Trials comparing minimally invasive with open transthoracic esophagectomy have shown improved short-term outcomes; however, long-term HRQL data are lacking. This prospective nonrandomized study compared HRQL and survival after thoracoscopically assisted McKeown esophagectomy (TAMK) and open transthoracic Ivor Lewis esophagectomy (TTIL) for esophageal or gastroesophageal junction (GEJ) cancer. METHODS: Patients with esophageal or GEJ cancer selected for TAMK or TTIL completed baseline and follow-up HRQL assessments for up to 24 months using the EORTC generic and disease-specific measures, QLQ-C30 and QLQ-OES18. Baseline clinical variables were examined between the treatment groups and changes in mean HRQL scores over time estimated and tested using generalised estimating equations with propensity score (generated by boosted regression) adjustment. RESULTS: Of the 487 patients, 377 underwent TAMK and 110 underwent TTIL. Most clinical variables were similar in the 2 groups; however, there were significantly more patients with AJCC stage 3 disease who underwent TTIL than TAMK (54% vs 32%, P < 0.01) and this was reflected in the survival data.Mean symptom scores for pain were significantly higher in the TTIL group than in TAMK for 2 years postoperatively (P = 0.036). In addition, mean constipation scores were significantly higher for the TTIL group, with a 15-point difference in mean score at 3 months postoperatively (P = 0.037). CONCLUSIONS: This large comprehensive nonrandomized analysis of longitudinal HRQL shows that TTIL is associated with more pain and constipation than TAMK.

Although bariatric surgery is the most effective treatment for severe and complex obesity, less is known about its psychosocial impact. This systematic review synthesizes qualitative studies investigating the patient perspective of living with the outcomes of surgery. A total of 2,604 records were screened, and 33 studies were included. Data extraction and thematic synthesis yielded three overarching themes: control, normality and ambivalence. These were evident across eight organizing sub-themes describing areas of life impacted by surgery: weight, activities of daily living, physical health, psychological health, social relations, sexual life, body image and eating behaviour and relationship with food. Throughout all these areas, patients were striving for control and normality. Many of the changes experienced were positive and led to feeling more in control and 'normal'. Negative changes were also experienced, as well as changes that were neither positive nor negative but were nonetheless challenging and required adaptation. Thus, participants continued to strive for control and normality in some aspects of their lives for a considerable time, contributing to a sense of ambivalence in accounts of life after surgery. These findings demonstrate the importance of long-term support, particularly psychological and dietary, to help people negotiate these challenges and maintain positive changes achieved after bariatric surgery.

Background Recruitment to randomised controlled trials (RCTs) can be challenging, with most trials not reaching recruitment targets. Randomised feasibility studies can be set up prior to a main trial to identify and overcome recruitment obstacles. This paper reports on an intervention—the QuinteT Recruitment Intervention (QRI)—to optimise recruitment within a randomised feasibility study of surgical treatments for patients with Dupuytren’s contracture (the HAND-1 study). Methods The QRI was introduced in 2-phases: phase 1 sought to understand the recruitment challenges by interviewing trial staff, scrutinising screening logs and analysing audio-recorded patient consultations; in phase 2 a tailored plan of action consisting of recruiter feedback and training was delivered to address the identified challenges. Results Two key recruitment obstacles emerged: (1) issues with the recruitment pathway, in particular methods to identify potentially eligible patients and (2) equipoise of recruiters and patients. These were addressed by liaising with centres to share good practice and refine their pathway and by providing bespoke feedback and training on consent discussions to individual recruiters and centres whilst recruitment was ongoing. The HAND-1 study subsequently achieved its recruitment target. Conclusions Transferable lessons learnt from the QRI in the feasibility study will be implemented in the definitive RCT, enabling a “head start” in the tackling of wider issues around screening methods and consent discussions in the set up/early recruitment study phases, with ongoing QRI addressing specific issues with new centres and recruiters. Findings from this study are likely to be relevant to other surgical and similar trials that are anticipated to encounter issues around patient and recruiter equipoise of treatments and variation in recruitment pathways across centres. The study also highlights the value of feasibility studies in fine-tuning design and conduct issues for definitive RCTs. Embedding a QRI in an RCT, at feasibility or main stage, offers an opportunity for a detailed and nuanced understanding of key recruitment challenges and the chance to address them in “real-time” as recruitment proceeds.

Worldwide, there are at least 230 million invasive procedures performed annually and most of us will undergo several in our lifetime. There is therefore a need for high-quality evidence to underpin this clinical area. Currently, however, there is no widely accepted definition of an invasive procedure and the terms ‘surgery’ and ‘interventional procedure’ are characterised inconsistently. We propose a definition for invasive procedures which addresses the limitations of those currently available. Our definition was developed from an analysis of the 3946 papers from the last decade. A preliminary definition was created based on existing definitions and applied to a variety of papers reporting all types of procedures. This definition was continuously updated and applied iteratively to all articles. The definition has three key components: (1) method of access to the body, (2) instrumentation and (3) requirement for operator skill. It therefore encapsulates all types of invasive procedure regardless of the method of access to the body (incision, natural orifice or percutaneous access), and is relevant whatever the clinical discipline (eg, obstetric, cardiac, dental, interventional cardiology or radiology). Crucially, the definition excludes medicinal products, except where their administration occurs within an invasive procedure (and thereby involves operator skill). The application of a universal definition of an invasive procedure will (1) inform the selection of relevant methods for study design, (2) streamline evidence synthesis and (3) improve research tracking, helping to identify evidence gaps and direct research funds.