Patient-Reported Outcome Measures for Post-mastectomy Breast Reconstruction: A Systematic Review of Development and Measurement Properties.

BACKGROUND: Breast reconstruction (BR) is performed to improve outcomes for patients undergoing mastectomy. A recently developed core outcome set for BR includes six patient-reported outcomes that should be measured and reported in all future studies. It is vital that any instrument used to measure these outcomes as part of a core measurement set be robustly developed and validated so data are reliable and accurate. The aim of this systematic review is to evaluate the development and measurement properties of existing BR patient-reported outcome measures (PROMs) to inform instrument selection for future studies. METHODS: A PRISMA-compliant systematic review of development and validation studies of BR PROMs was conducted to assess their measurement properties. PROMs with adequate content validity were assessed using three steps: (1) the methodological quality of each identified study was assessed using the COSMIN Risk of Bias checklist; (2) criteria were applied for assessing good measurement properties; and (3) evidence was summarized and the quality of evidence assessed using a modified GRADE approach. RESULTS: Fourteen articles reported the development and measurement properties of six PROMs. Of these, only three (BREAST-Q, BRECON-31, and EORTC QLQ-BRECON-23) were considered to have adequate content validity and proceeded to full evaluation. This showed that all three PROMs had been robustly developed and validated and demonstrated adequate quality. CONCLUSIONS: BREAST-Q, BRECON-31, and EORTC QLQ-BRECON-23 have been well-developed and demonstrate adequate measurement properties. Work with key stakeholders is now needed to generate consensus regarding which PROM should be recommended for inclusion in a core measurement set.

Core outcome set for surgical trials in gastric cancer (GASTROS study): international patient and healthcare professional consensus.

BACKGROUND: Surgery is the primary treatment that can offer potential cure for gastric cancer, but is associated with significant risks. Identifying optimal surgical approaches should be based on comparing outcomes from well designed trials. Currently, trials report different outcomes, making synthesis of evidence difficult. To address this, the aim of this study was to develop a core outcome set (COS)-a standardized group of outcomes important to key international stakeholders-that should be reported by future trials in this field. METHODS: Stage 1 of the study involved identifying potentially important outcomes from previous trials and a series of patient interviews. Stage 2 involved patients and healthcare professionals prioritizing outcomes using a multilanguage international Delphi survey that informed an international consensus meeting at which the COS was finalized. RESULTS: Some 498 outcomes were identified from previously reported trials and patient interviews, and rationalized into 56 items presented in the Delphi survey. A total of 952 patients, surgeons, and nurses enrolled in round 1 of the survey, and 662 (70 per cent) completed round 2. Following the consensus meeting, eight outcomes were included in the COS: disease-free survival, disease-specific survival, surgery-related death, recurrence, completeness of tumour removal, overall quality of life, nutritional effects, and 'serious' adverse events. CONCLUSION: A COS for surgical trials in gastric cancer has been developed with international patients and healthcare professionals. This is a minimum set of outcomes that is recommended to be used in all future trials in this field to improve trial design and synthesis of evidence.

Patient experiences of an electronic PRO tailored feedback system for symptom management following upper gastrointestinal cancer surgery.

PURPOSE: Complications following upper gastrointestinal (UGI) surgery are common. Symptom-monitoring following discharge is not standardized. An electronic patient-reported outcome (ePRO) system providing feedback to patients and clinicians could support patients and improve outcomes. Little is known about patients' experiences of using such systems. This qualitative sub-study explored patients' perspectives of the benefits of using a novel ePRO system, developed as part of the mixed methods eRAPID pilot study, to support recovery following discharge after UGI surgery. METHODS: Patients completed the online ePRO symptom-report system post-discharge. Weekly interviews explored patients' experiences of using ePRO, the acceptability of feedback generated and its value for supporting their recovery. Interviews were audio-recorded and targeted transcriptions were thematically analysed. RESULTS: Thirty-five interviews with 16 participants (11 men, mean age 63 years) were analysed. Two main themes were identified: (1) reassurance and (2) empowerment. Feelings of isolation were common; many patients felt uninformed regarding their expectations of recovery and whether their symptoms warranted clinical investigation. Participants were reassured by tailored feedback advising them to contact their care team, alleviating their anxiety. Patients reported feeling empowered by the ePRO system and in control of their symptoms and recovery. CONCLUSION: Patients recovering at home following major cancer surgery regarded electronic symptom-monitoring and feedback as acceptable and beneficial. Patients perceived that the system enhanced information provision and provided a direct link to their care team. Patients felt that the system provided reassurance at a time of uncertainty and isolation, enabling them to feel in control of their symptoms and recovery.

Systematic review of the introduction and evaluation of magnetic augmentation of the lower oesophageal sphincter for gastro-oesophageal reflux disease.

BACKGROUND: Magnetic sphincter augmentation (MSA) is reported to be an innovative alternative to antireflux surgery for patients with gastro-oesophageal reflux disease. Although used in practice, little is known about how it has been evaluated. This study aimed to systematically summarize and appraise the reporting of MSA and its introduction into clinical practice, in the context of guidelines (such as IDEAL) for evaluating innovative surgical devices. METHODS: Systematic searches were used to identify all published studies reporting MSA insertion. Data collected included patient selection, governance arrangements, surgeon expertise, technique description and outcome reporting. RESULTS: Searches identified 587 abstracts; 39 full-text papers were included (1 RCT 5 cohort, 3 case-control, 25 case series, 5 case reports). Twenty-one followed US Food and Drug Administration eligibility criteria for MSA insertion. Twenty-six documented that ethical approval was obtained. Two reported that participating surgeons received training in MSA; 18 provided information about how MSA insertion was performed, although techniques varied between studies. Follow-up ranged from 4 weeks to 5 years; in 14 studies, it was less than 1 year. CONCLUSION: Most studies on MSA lacked information about patient selection, governance, expertise, techniques and outcomes, or varied between studies. Currently, MSA is being used despite a lack of robust evidence for its effectiveness.

ANTECEDENTES: El aumento de esfínter con un dispositivo magnético (magnetic sphincter augmentation, MSA) se ha descrito como una alternativa innovadora a la cirugía antirreflujo para pacientes con enfermedad por reflujo gastroesofágico. Aunque este procedimiento se utiliza en la práctica, se sabe poco acerca de cómo ha sido evaluado. Este estudio se propuso resumir sistemáticamente y evaluar los trabajos sobre MSA y su introducción en la práctica clínica, en el contexto de las guías (como IDEAL) para la evaluación de dispositivos quirúrgicos innovadores. MÉTODOS: Se identificaron todos los estudios publicados que describían la colocación de MSA efectuando búsquedas sistemáticas. Los datos recogidos incluían la selección de los pacientes, disposiciones de gobernanza, experiencia del cirujano, descripción técnica, y descripción de resultados. RESULTADOS: Las búsquedas identificaron 587 resúmenes, incluyéndose 39 artículos completos (5 estudios de cohortes, 3 estudios de casos y controles, 26 series de casos, 5 casos clínicos). En 21 estudios se siguieron los criterios de elegibilidad de la FDA para la colocación de MSA. En 26 estudios se confirmaba que se había obtenido la aprobación ética. Dos estudios describieron que los cirujanos participantes habían recibido formación en MSA; 18 proporcionaron información sobre cómo se realizó la colocación de MSA, aunque las técnicas variaron entre los estudios. El seguimiento oscilaba entre 4 semanas y 5 años; en 14 estudios fue inferior a un año. CONCLUSIÓN: La mayoría de los estudios sobre MSA fueron casos aislados y series de casos, sin un incremento apreciable en la calidad de la evidencia sobre MSA. La información sobre la selección de los pacientes, gobernanza, experiencia, técnicas, y resultados estaba ausente o variaba entre los estudios, haciendo difíciles las comparaciones. En la actualidad, MSA se utiliza a pesar de la falta de evidencia robusta sobre su efectividad.

Optimizing the design of invasive placebo interventions in randomized controlled trials.

BACKGROUND: Placebo-controlled trials play an important role in the evaluation of healthcare interventions. However, they can be challenging to design and deliver for invasive interventions, including surgery. In-depth understanding of the component parts of the treatment intervention is needed to ascertain what should, and should not, be delivered as part of the placebo. Assessment of risk to patients and strategies to ensure that the placebo effectively mimics the treatment are also required. To date, no guidance exists for the design of invasive placebo interventions. This study aimed to develop a framework to optimize the design and delivery of invasive placebo interventions in RCTs. METHODS: A preliminary framework was developed using published literature to: expand the scope of an existing typology, which facilitates the deconstruction of invasive interventions; and identify placebo optimization strategies. The framework was refined after consultation with key stakeholders in surgical trials, consensus methodology and medical ethics. RESULTS: The resulting DITTO framework consists of five stages: deconstruct treatment intervention into constituent components and co-interventions; identify critical surgical element(s); take out the critical element(s); think risk, feasibility and role of placebo in the trial when considering remaining components; and optimize placebo to ensure effective blinding of patients and trial personnel. CONCLUSION: DITTO considers invasive placebo composition systematically, accounting for risk, feasibility and placebo optimization. Use of the framework can support the design of high-quality RCTs, which are needed to underpin delivery of healthcare interventions.

ANTECEDENTES: Los ensayos controlados con placebo juegan un papel importante en la evaluación de las intervenciones sanitarias. Sin embargo, pueden ser difíciles de diseñar e implementar en el caso de intervenciones invasivas, incluida la cirugía. Se necesita un conocimiento profundo de los componentes de la intervención terapéutica (para determinar qué se debe y qué no se debe administrar como parte del placebo). También se precisa de una evaluación del riesgo para los pacientes y de las estrategias para garantizar que el placebo imite el tratamiento de forma efectiva. Hasta la fecha no existen guías para el diseño de intervenciones invasivas con placebo. Este estudio tuvo como objetivo desarrollar un marco para optimizar el diseño y la práctica de intervenciones invasivas con placebo dentro en los ensayos clínicos aleatorizados (ECA). MÉTODOS: Utilizando la literatura publicada, se desarrolló un marco preliminar para i) ampliar el alcance de los modelos existentes para facilitar la deconstrucción de las actuaciones invasivas, y ii) identificar estrategias para optimizar el placebo. El marco se perfeccionó tras consultar con partes interesadas ​​en ensayos quirúrgicos, metodología de consenso y ética médica. RESULTADOS: El marco DITTO resultantes consiste en cinco etapas: Etapa 1: deconstrucción de la intervención de tratamiento en sus componentes esenciales y co-intervenciones; Etapa 2: identificar el(los) elemento(s) quirúrgico(s) básico(s); Etapa 3: eliminar el(los) elemento(s) básico(s); Etapa 4: considerar el riesgo, la viabilidad y el papel del placebo en el ensayo al tener en cuenta los demás componentes; y Etapa 5: optimizar el placebo para garantizar el cegamiento efectivo de los pacientes y del personal del ensayo. CONCLUSIÓN: DITTO considera de forma sistemática la naturaleza invasiva del placebo, teniendo en cuenta el riesgo, la viabilidad y la optimización del placebo. El uso de este marco de referencia puede ayudar al diseño de ECAs de alta calidad, necesarios para afianzar la implementación de intervenciones sanitarias.

A real-time electronic symptom monitoring system for patients after discharge following surgery: a pilot study in cancer-related surgery.

BACKGROUND: Advances in peri-operative care of surgical oncology patients result in shorter hospital stays. Earlier discharge may bring benefits, but complications can occur while patients are recovering at home. Electronic patient-reported outcome (ePRO) systems may enhance remote, real-time symptom monitoring and detection of complications after hospital discharge, thereby improving patient safety and outcomes. Evidence of the effectiveness of ePRO systems in surgical oncology is lacking. This pilot study evaluated the feasibility of a real-time electronic symptom monitoring system for patients after discharge following cancer-related upper gastrointestinal surgery. METHODS: A pilot study in two UK hospitals included patients who had undergone cancer-related upper gastrointestinal surgery. Participants completed the ePRO symptom-report at discharge, twice in the first week and weekly post-discharge. Symptom-report completeness, system actions, barriers to using the ePRO system and technical performance were examined. The ePRO surgery system is an online symptom-report that allows clinicians to view patient symptom-reports within hospital electronic health records and was developed as part of the eRAPID project. Clinically derived algorithms provide patients with tailored self-management advice, prompts to contact a clinician or automated clinician alerts depending on symptom severity. Interviews with participants and clinicians determined the acceptability of the ePRO system to support patients and their clinical management during recovery. RESULTS: Ninety-one patients were approached, of which 40 consented to participate (27 male, mean age 64 years). Symptom-report response rates were high (range 63-100%). Of 197 ePRO completions analysed, 76 (39%) triggered self-management advice, 72 (36%) trigged advice to contact a clinician, 9 (5%) triggered a clinician alert and 40 (20%) did not require advice. Participants found the ePRO system reassuring, providing timely information and advice relevant to supporting their recovery. Clinicians regarded the system as a useful adjunct to usual care, by signposting patients to seek appropriate help and enhancing their understanding of patients' experiences during recovery. CONCLUSION: Use of the ePRO system for the real-time, remote monitoring of symptoms in patients recovering from cancer-related upper gastrointestinal surgery is feasible and acceptable. A definitive randomised controlled trial is needed to evaluate the impact of the system on patients' wellbeing after hospital discharge.

A systematic review and in-depth analysis of outcome reporting in early phase studies of colorectal cancer surgical innovation.

AIM: Early phase studies are essential to evaluate new technologies prior to randomized evaluation. Evaluation is limited, however, by inconsistent measurement and reporting of outcomes. This study examines outcome reporting in studies of innovative colorectal cancer surgery. METHODS: Systematic searches identified studies of invasive procedures treating primary colorectal adenocarcinoma. Included were a random sample of studies which authors reported as 'new' or 'modified'. Outcomes were extracted verbatim and categorized using an existing framework of 32 domains relevant to early phase studies. Outcomes were classified as 'measured' (where there was an explicit statement to that effect or evidence that data collection had occurred) or 'mentioned but not measured' (where outcomes were discussed but data collection was not evident). Patterns of identified outcomes are described. RESULTS: Of 8373 records, 816 were potentially eligible. Full-text review of a random sample of 218 studies identified 51 for inclusion of which 34 (66%) were 'new' and 17 (33%) were 'modified'. Some 2073 outcomes were identified, and all mapped to domains. 'Anticipated disadvantages' were most frequently identified [660 (32%) outcomes identified across 50 (98%) studies]. No domain was represented in all studies. Under half (944, 46%) of outcomes were 'measured'. 'Surgeon's/operator's experience of the innovation' was more frequently 'mentioned but not measured' [207 (18%) outcomes across 46 (90%) studies] than 'measured' [17 (2%) outcomes, 11 (22%) studies]. CONCLUSION: There is outcome reporting heterogeneity in studies of early phase colorectal cancer surgery. The adoption of core outcome sets may help to resolve these inconsistencies and enable efficient evaluation of surgical innovations.

Patient-Reported Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate Cancer.

BACKGROUND: Robust data on patient-reported outcome measures comparing treatments for clinically localized prostate cancer are lacking. We investigated the effects of active monitoring, radical prostatectomy, and radical radiotherapy with hormones on patient-reported outcomes. METHODS: We compared patient-reported outcomes among 1643 men in the Prostate Testing for Cancer and Treatment (ProtecT) trial who completed questionnaires before diagnosis, at 6 and 12 months after randomization, and annually thereafter. Patients completed validated measures that assessed urinary, bowel, and sexual function and specific effects on quality of life, anxiety and depression, and general health. Cancer-related quality of life was assessed at 5 years. Complete 6-year data were analyzed according to the intention-to-treat principle. RESULTS: The rate of questionnaire completion during follow-up was higher than 85% for most measures. Of the three treatments, prostatectomy had the greatest negative effect on sexual function and urinary continence, and although there was some recovery, these outcomes remained worse in the prostatectomy group than in the other groups throughout the trial. The negative effect of radiotherapy on sexual function was greatest at 6 months, but sexual function then recovered somewhat and was stable thereafter; radiotherapy had little effect on urinary continence. Sexual and urinary function declined gradually in the active-monitoring group. Bowel function was worse in the radiotherapy group at 6 months than in the other groups but then recovered somewhat, except for the increasing frequency of bloody stools; bowel function was unchanged in the other groups. Urinary voiding and nocturia were worse in the radiotherapy group at 6 months but then mostly recovered and were similar to the other groups after 12 months. Effects on quality of life mirrored the reported changes in function. No significant differences were observed among the groups in measures of anxiety, depression, or general health-related or cancer-related quality of life. CONCLUSIONS: In this analysis of patient-reported outcomes after treatment for localized prostate cancer, patterns of severity, recovery, and decline in urinary, bowel, and sexual function and associated quality of life differed among the three groups. (Funded by the U.K. National Institute for Health Research Health Technology Assessment Program; ProtecT Current Controlled Trials number, ISRCTN20141297 ; ClinicalTrials.gov number, NCT02044172 .).

Value of surgical pilot and feasibility study protocols.

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.

Quality assurance of surgery in the randomized ST03 trial of perioperative chemotherapy in carcinoma of the stomach and gastro-oesophageal junction.

BACKGROUND: The UK Medical Research Council ST03 trial compared perioperative epirubicin, cisplatin and capecitabine (ECX) chemotherapy with or without bevacizumab (B) in gastric and oesophagogastric junctional cancer. No difference in survival was noted between the arms of the trial. The present study reviewed the standards and performance of surgery in the context of the protocol-specified surgical criteria. METHODS: Surgical and pathological clinical report forms were reviewed to determine adherence to the surgical protocols, perioperative morbidity and mortality, and final histopathological stage for all patients treated in the study. RESULTS: Of 1063 patients randomized, 895 (84·2 per cent) underwent resection; surgical details were available for 880 (98·3 per cent). Postoperative assessment data were available for 873 patients; complications occurred in 458 (52·5 per cent) overall, of whom 71 (8·1 per cent) developed complications deemed to be life-threatening by the responsible clinician. The most common complications were respiratory (211 patients, 24·2 per cent). The anastomotic leak rate was 118 of 873 (13·5 per cent) overall; among those who underwent oesophagogastrectomy, the rate was higher in the group receiving ECX-B (23·6 per cent versus 9·9 per cent in the ECX group). Pathological assessment data were available for 845 patients. At least 15 nodes were removed in 82·5 per cent of resections and the median lymph node harvest was 24 (i.q.r. 17-34). Twenty-five or more nodes were removed in 49·0 per cent of patients. Histopathologically, the R1 rate was 24·9 per cent (208 of 834 patients). An R1 resection was more common for proximal tumours. CONCLUSION: In the ST03 trial, the performance of surgery met the protocol-stipulated criteria. Registration number: NCT00450203 ( http://www.clinicaltrials.gov).

Evaluation of an early-stage innovation for full-thickness excision of benign colonic polyps using the IDEAL framework.

AIMS: Colectomy is the current approach for patients with endoscopically unresectable benign polyps but risks considerable morbidity. Full-thickness laparoendoscopic excision (FLEX) is a novel procedure, specifically developed to treat endoscopically unresectable benign colonic polyps, which could reduce the treatment burden of the current approach and improve outcomes. However, traditional evaluations of surgical innovations lack methodological rigour. This study reports the development and feasibility of the FLEX procedure in selected patients. METHOD: A prospective development study using the Idea, Development, Evaluation, Assessment, Long-term study (IDEAL) framework was undertaken, by one surgeon, of the FLEX procedure in selected patients with endoscopically unresectable benign colonic polyps. Three-dimensional (3D)-CT colonography reconstructions were used preoperatively to rehearse patient-specific, critical manoeuvres. Targetted, full-thickness excision was performed: after marking the margin of the caecal polyp using circumferential endoscopic argon plasma coagulation, transmural endoscopic sutures were used to evert the bowel and resection was undertaken by laparoscopic linear stapling. Feasibility outcomes (establishing 'local success') included evidence of complete polyp resection without adverse events (especially safe closure of the excision site). RESULTS: Ten patients [median (interquartile range) age: 74 (59-78) years] with polyp median diameters of 35 (30-41) mm, were referred for and consented to receive the FLEX procedure. During the same time frame, no patient underwent colectomy for benign polyps. One further patient received FLEX for local excision of a presumed malignant polyp because severe comorbidity prohibited standard procedures. The FLEX procedure was successfully performed locally, with complete resection of the polyp and safe closure of the excision site, in eight patients. Three noncompleted procedures were converted to laparoscopic segmental colectomy under the same anaesthetic because of endoscopic inaccessibility (two patients) and transcolonic suture failure (one patient). CONCLUSIONS: The FLEX procedure is still under development. Early data demonstrate that it is safe for excision of selected benign polyps. Modifications to transcolonic suture delivery are now required and there is a need for wider adoption before more definitive evaluation can be performed.

Core information set for informed consent to surgery for oral or oropharyngeal cancer: A mixed-methods study.

OBJECTIVES: To develop a core information set for informed consent to surgery for oral/oropharyngeal surgery. A core information set is baseline information rated important by patients and surgeons and is intended to improve patients' understanding of the intended procedure. DESIGN: A mixed-methods study. Systematic reviews of scientific and written healthcare literature, qualitative interviews and observations, Delphi surveys, and group consensus meetings identified information domains of importance for consent. SETTING: A regional head and neck clinic in the United Kingdom. Questionnaire participants were recruited from around the UK. PARTICIPANTS: Patients about to undergo, or who had previously undergone, surgery for oral/oropharyngeal cancer. Healthcare professionals involved in the management of head and neck cancer. MAIN OUTCOME MEASURES: The main outcome was a core information set. RESULTS: Systematic reviews, interviews and consultation observations yielded 887 pieces of information that were categorised into 87 information domains. Survey response rates were 67% (n = 50) and 71% (n = 52) for patient and healthcare professional groups in round one. More than 90% responded in each group in the second round. Healthcare professionals were more likely to rate information about short-term or peri-operative events as important while patients rated longer term issues about survival and quality of life. The consensus-building process resulted in an agreed core information set of 13 domains plus two procedure-specific domains about tracheostomy and free-flap surgery. CONCLUSION: This study produced a core information set for surgeons and patients to discuss before surgery for oral/oropharyngeal cancer. Future work will optimise ways to integrate core information into routine consultations.

Enabling recruitment success in bariatric surgical trials: pilot phase of the By-Band-Sleeve study.

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 qualitative research integrated in trials (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 2 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 2 months (2/22) to 40% (26/65) in the 4 months thereafter. Center B, commencing recruitment 3 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.

Adaptation of the By-Band randomized clinical trial to By-Band-Sleeve to include a new intervention and maintain relevance of the study to practice.

BACKGROUND: Recruitment into surgical RCTs can be threatened if new interventions available outside the trial compete with those being evaluated. Adapting the trial to include the new intervention may overcome this issue, yet this is not often done in surgery. This paper describes the challenges, rationale and methods for adapting an RCT to include a new intervention. METHODS: The By-Band study was designed in the UK in 2009-2010 to compare the effectiveness of laparoscopic adjustable gastric band and Roux-en-Y gastric bypass for severe obesity. It contained a pilot phase to establish whether recruitment was possible, and the grant proposal specified that an adaptation to include sleeve gastrectomy would be considered if practice changed and recruitment was successful. Information on changing obesity surgery practice, updated evidence and expert opinion about trial design were used to inform the adaptation. RESULTS: The pilot phase recruited over 13 months in 2013-2014 and randomized 80 patients (79 anticipated). During this time, major changes in obesity practice in the UK were observed, with gastric band reducing from 32·6 to 15·8 per cent and sleeve gastrectomy increasing from 9·0 to 28·1 per cent. The evidence base had not changed markedly. The British Obesity and Metabolic Surgery Society and study oversight committees supported an adaptation to include sleeve gastrectomy, and a proposal to do so was approved by the funder. CONCLUSION: Adaptation of a two-group surgical RCT can allow evaluation of a third procedure and maintain relevance of the RCT to practice. It also optimizes the use of existing trial infrastructure to answer an additional important research question. Registration number: ISRCTN00786323 (http://www.isrctn.com/).

Standardizing and monitoring the delivery of surgical interventions in randomized clinical trials.

BACKGROUND: The complexity of surgical interventions has major implications for the design of RCTs. Trials need to consider how and whether to standardize interventions so that, if successful, they can be implemented in practice. Although guidance exists for standardizing non-pharmaceutical interventions in RCTs, their application to surgery is unclear. This study reports new methods for standardizing the delivery of surgical interventions in RCTs. METHODS: Descriptions of 160 surgical interventions in existing trial reports and protocols were identified. Initially, ten reports were scrutinized in detail using a modified framework approach for the analysis of qualitative data, which informed the development of a preliminary typology. The typology was amended with iterative sequential application to all interventions. Further testing was undertaken within ongoing multicentre RCTs. RESULTS: The typology has three parts. Initially, the overall technical purpose of the intervention is described (exploration, resection and/or reconstruction) in order to establish its constituent components and steps. This detailed description of the intervention is then used to establish whether and how each component and step should be standardized, and the standards documented within the trial protocol. Finally, the typology provides a framework for monitoring the agreed intervention standards during the RCT. Pilot testing within ongoing RCTs enabled standardization of the interventions to be agreed, and case report forms developed to capture deviations from these standards. CONCLUSION: The typology provides a framework for use during trial design to standardize the delivery of surgical interventions and document these details within protocols. Application of this typology to future RCTs may clarify details of the interventions under evaluation and help successful interventions to be implemented.

What surgeons tell patients and what patients want to know before major cancer surgery: a qualitative study.

BACKGROUND: The information surgeons impart to patients and information patients want about surgery for cancer is important but rarely examined. This study explored information provided by surgeons and patient preferences for information in consultations in which surgery for oesophageal cancer surgery was discussed. METHODS: Pre-operation consultations in which oesophagectomy was discussed were studied in three United Kingdom hospitals and patients were subsequently interviewed. Consultations and interviews were audio-recorded, transcribed in full and anonymized. Interviews elicited views about the information provided by surgeons and patients' preferences for information. Thematic analysis of consultation-interview pairs was used to investigate similarities and differences in the information provided by surgeons and desired by patients. RESULTS: Fifty two audio-recordings from 31 patients and 7 surgeons were obtained (25 consultations and 27 patient interviews). Six consultations were not recorded because of equipment failure and four patients declined an interview. Surgeons all provided consistent, extensive information on technical operative details and in-hospital surgical risks. Consultations rarely included discussion of the longer-term outcomes of surgery. Whilst patients accepted that information about surgery and risks was necessary, they really wanted details about long-term issues including recovery, impact on quality of life and survival. CONCLUSIONS: This study demonstrated a need for surgeons to provide information of importance to patients concerning the longer term outcomes of surgery. It is proposed that "core information sets" are developed, based on surgeons' and patients' views, to use as a minimum in consultations to initiate discussion and meet information needs prior to cancer surgery.

Patient-reported outcomes during and after definitive chemoradiotherapy for oesophageal cancer.

BACKGROUND: Limited data describe patient-reported outcomes (PROs) of localised oesophageal cancer treated with definitive chemoradiotherapy(CRT). The phase 2/3 SCOPE-1 trial assessed the effectiveness of CRT±cetuximab. The trial for the first time provided an opportunity to describe PROs from a multi-centre group of patients treated with CRT that are presented here. METHODS: Patients undergoing CRT±cetuximab within the SCOPE-1 trial (258 patients from 36 UK centres) completed generic-, disease- and treatment-specific health-related quality of life (HRQL) questionnaires (EORTC QLQ-C30, QLQ-OES18, Dermatology Life-Quality Index (DLQI)) at baseline and at 7, 13, 24, 52 and 104 weeks. Mean EORTC functional scale scores (>15 point change significant), DLQI scores (>4 point change significant) and proportions of patients (>15% significant) with 'minimal' or 'severe' symptoms are presented. RESULTS: Questionnaire response rates were good. At baseline, EORTC functional scores were high (>75%) and few symptoms were reported except for severe problems with fatigue, insomnia and eating-related symptoms (e.g., appetite loss, dysphagia, dry mouth) in both groups(>15%). Functional aspects of health deteriorated and symptoms increased with treatment and by week 13 global quality of life, physical, role and social function significantly deteriorated and more problems with fatigue, dyspnoea, appetite loss and trouble with taste were reported. Recovery occurred by 6 months (except severe fatigue and insomnia in >15% of patients) and maintained at follow-up with no differences between groups. CONCLUSIONS: CRT for localised oesophageal cancer has a significant detrimental impact on many aspects of HRQL; however, recovery is achieved by 6 months and maintained with the exception of persisting problems with severe fatigue and insomnia. The data suggest that the HRQL recovery after definitive CRT is quicker, and there is little lasting deficit compared with treatment including surgery. These data need to be compared with HRQL data from studies evaluating treatments including surgery for oesophageal cancer.

Development of a core outcome set for research and audit studies in reconstructive breast surgery.

BACKGROUND: Appropriate outcome selection is essential if research is to guide decision-making and inform policy. Systematic reviews of the clinical, cosmetic and patient-reported outcomes of reconstructive breast surgery, however, have demonstrated marked heterogeneity, and results from individual studies cannot be compared or combined. Use of a core outcome set may improve the situation. The BRAVO study developed a core outcome set for reconstructive breast surgery. METHODS: A long list of outcomes identified from systematic reviews and stakeholder interviews was used to inform a questionnaire survey. Key stakeholders defined as individuals involved in decision-making for reconstructive breast surgery, including patients, breast and plastic surgeons, specialist nurses and psychologists, were sampled purposively and sent the questionnaire (round 1). This asked them to rate the importance of each outcome on a 9-point Likert scale from 1 (not important) to 9 (extremely important). The proportion of respondents rating each item as very important (score 7-9) was calculated. This was fed back to participants in a second questionnaire (round 2). Respondents were asked to reprioritize outcomes based on the feedback received. Items considered very important after round 2 were discussed at consensus meetings, where the core outcome set was agreed. RESULTS: A total of 148 items were combined into 34 domains within six categories. Some 303 participants (51·4 per cent) (215 (49·5 per cent) of 434 patients; 88 (56·4 per cent) of 156 professionals) completed and returned the round 1 questionnaire, and 259 (85·5 per cent) reprioritized outcomes in round 2. Fifteen items were excluded based on questionnaire scores and 19 were carried forward to the consensus meetings, where a core outcome set containing 11 key outcomes was agreed. CONCLUSION: The BRAVO study has used robust consensus methodology to develop a core outcome set for reconstructive breast surgery. Widespread adoption by the reconstructive community will improve the quality of outcome assessment in effectiveness studies. Future work will evaluate how these key outcomes should best be measured.

Systematic review and critical appraisal of the impact of acellular dermal matrix use on the outcomes of implant-based breast reconstruction.

BACKGROUND: Acellular dermal matrix (ADM) may improve outcomes in implant-based breast reconstruction (IBBR). The aim of this study was critically to appraise and evaluate the current evidence for ADM-assisted IBBR. METHODS: Comprehensive electronic searches identified complete papers published in English between January 2000 and August 2013, reporting any outcome of ADM-assisted IBBR. All systematic reviews, randomized clinical trials (RCTs) and non-randomized studies (NRSs) with more than 20 ADM recipients were included. Studies were critically appraised using AMSTAR for systematic reviews, the Cochrane risk-of-bias tool for RCTs and its adaptation for NRSs. Characteristics and results of identified studies were summarized. RESULTS: A total of 69 papers (8 systematic reviews, 1 RCT, 40 comparative studies and 20 case series) were identified, all of which were considered at high risk of bias, mostly due to patient selection and selective outcome reporting. The median ADM group sample size was 51.0 (i.q.r. 33.0-127.0). Most studies were single-centre (54), and they were often single-surgeon (16). ADM was most commonly used for immediate (40) two-stage IBBR (36) using human ADM (47), with few studies evaluating ADM-assisted single-stage procedures (10). All reported clinical outcomes (for example implant loss) and more than half of the papers (33) assessed process outcomes, but few evaluated cosmesis (16) or patient-reported outcomes (10). Heterogeneity between study design and, especially, outcome measurement precluded meaningful data synthesis. CONCLUSION: Current evidence for the value of ADMs in IBBR is limited. Use in practice should therefore be considered experimental, and evaluation within registries or well designed and conducted studies, ideally RCTs, is recommended to prevent widespread adoption of a potentially inferior intervention.

Systematic review of intervention design and delivery in pragmatic and explanatory surgical randomized clinical trials.

BACKGROUND: Surgical interventions are complex, with multiple components that require consideration in trial reporting. This review examines the reporting of details of surgical interventions in randomized clinical trials (RCTs) within the context of explanatory and pragmatic study designs. METHODS: Systematic searches identified RCTs of surgical interventions published in 2010 and 2011. Included studies were categorized as predominantly explanatory or pragmatic. The extent of intervention details in the reports were compared with the CONSORT statement for reporting trials of non-pharmacological treatments (CONSORT-NPT). CONSORT-NPT recommends reporting the descriptions of surgical interventions, whether they were standardized and adhered to (items 4a, 4b and 4c). Reporting of the context of intervention delivery (items 3 and 15) and operator expertise (item 15) were assessed. RESULTS: Of 4541 abstracts and 131 full-text articles, 80 were included (of which 39 were classified as predominantly pragmatic), reporting 160 interventions. Descriptions of 129 interventions (80.6 per cent) were provided. Standardization was mentioned for 47 (29.4 per cent) of the 160 interventions, and 22 articles (28 per cent) reported measurement of adherence to at least one aspect of the intervention. Seventy-one papers (89 per cent) provided some information about context. For one-third of interventions (55, 34.4 per cent), some data were provided regarding the expertise of personnel involved. Reporting standards were similar in trials classified as pragmatic or explanatory. CONCLUSION: The lack of detail in trial reports about surgical interventions creates difficulties in understanding which operations were actually evaluated. Methods for designing and reporting surgical interventions in RCTs, contributing to the quality of the overall study design, are required. This should allow better implementation of trial results into practice.