Patient information leaflets for placebo-controlled surgical trials: a review of current practice and recommendations for developers.

INTRODUCTION: Informed consent for participation in an RCT is an important ethical and legal requirement. In placebo surgical trials, further issues are raised, and to date, this has not been explored. Patient information leaflets (PILs) are a core component of the informed consent process. This study aimed to investigate the key content of PILs for recently completed placebo-controlled trials of invasive procedures, including surgery, to highlight areas of good practice, identify gaps in information provision for trials of this type and provide recommendations for practice. METHODS: PILs were sought from trials included in a recent systematic review of placebo-controlled trials of invasive procedures, including surgery. Trial characteristics and data on surgical and placebo interventions under evaluation were extracted. Directed content analysis was applied, informed by published regulatory and good practice guidance on PIL content and existing research on placebo-controlled surgical trials. Results were analysed using descriptive statistics and presented as a narrative summary. RESULTS: Of the 62 eligible RCTs, authors of 59 trials were contactable and 14 PILs were received for analysis. At least 50% of all PILs included content on general trial design. Explanations of how the placebo differs or is similar to the surgical intervention (i.e. fidelity) were reported in 6 (43%) of the included PILs. Over half (57%) of the PILs included information on the potential therapeutic benefits of the surgical intervention. One (7%) included information on potential indirect therapeutic benefits from invasive components of the placebo. Five (36%) presented the known risks of the placebo intervention, whilst 8 (57%) presented information on the known risks of the surgical intervention. A range of terms was used across the PILs to describe the placebo component, including 'control', 'mock' and 'sham'. CONCLUSION: Developers of PILs for placebo-controlled surgical trials should carefully consider the use of language (e.g. sham, mock), be explicit about how the placebo differs (or is similar) to the surgical intervention and provide balanced presentations of potential benefits and risks of the surgical intervention separately from the placebo. Further research is required to determine optimal approaches to design and deliver this information for these trials.

Opinion, uptake and current practice of robot-assisted upper gastrointestinal and oesophagogastric surgery in the UK: AUGIS national survey results.

INTRODUCTION: The uptake of upper gastrointestinal (GI) robotic surgery in the United Kingdom (UK), and Europe more widely, is expanding rapidly. This study aims to present a current snapshot of the practice and opinions of the upper GI community with reference to robotic surgery, with an emphasis on tertiary cancer (oesophagogastric) resection centres. METHODS: An electronic survey was circulated to the UK upper GI surgical community via national mailing lists, social media and at an open-invitation conference on robotic upper GI surgery in January 2023. The survey included questions on surgeons' current practice or planned adoption (if any) of robotics at individual and unit level, and their opinions on robotic upper GI surgery in general. Priority ranking and Likert-scale response options were used. RESULTS: In total, 81 respondents from 43 hospitals were included. Thirty-four resectional centres responded, including 30 of 31 (97%) recognised upper GI cancer centres in England. Respondents reported performing robotic surgery in 21 of 34 (61.8%) resectional centres, with a median of 65 procedures per centre performed at the time of the survey (range 0-500, interquartile range 93.75). Every centre without a robotic programme expressed a desire or had active plans to implement one. Respondents ranked surgeon ergonomics as the most important reason for pursuing robotics, followed by improvements in patient outcomes and oncological efficacy. CONCLUSIONS: Robotic upper GI practice is nascent but rapidly growing in the UK with plans for uptake in almost all tertiary centres. There is growing opinion that this is likely to become the predominant surgical approach in future with benefits to both patients and surgeons. This snapshot offers a point of reference to all stakeholders in upper GI surgery.

A systematic review of reporting quality for anaesthetic interventions in randomised controlled trials.

Interventions from randomised controlled trials can only be replicated if they are reported in sufficient detail. The results of trials can only be confidently interpreted if the delivery of the intervention was systematic and the protocol adhered to. We systematically reviewed trials of anaesthetic interventions published in 12 journals from January 2016 to September 2019. We assessed the detail with which interventions were reported, using the Consolidated Standards of Reporting Trials statement for non-pharmacological treatments. We analysed 162 interventions reported by 78 trials in 18,675 participants. Detail sufficiently precise to replicate the intervention was reported for 111 (69%) interventions. Intervention standardisation was reported for 135 (83%) out of the 162 interventions, and protocol adherence was reported for 20 (12%) interventions. Sixty (77%) out of the 78 trials reported the administrative context in which interventions were delivered and 36 (46%) trials detailed the expertise of the practitioners. We conclude that bespoke reporting tools should be developed for anaesthetic interventions and interventions in other areas such as critical care.

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.

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.

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.

Assessing the quality of written information provision for surgical procedures: a case study in oesophagectomy.

OBJECTIVE: To examine the content and quality of written information provided by surgical centres for patients undergoing oesophagectomy for cancer. DESIGN: Cross-sectional study of the content of National Health Service (NHS) patient information leaflets (PILs) about oesophageal cancer surgery, using a modified framework approach. DATA SOURCES: Written information leaflets from 41 of 43 cancer centres undertaking surgery for oesophageal cancer in England and Wales (response rate 95.3%). ELIGIBILITY CRITERIA: All English language versions of PILs about oesophagectomy. RESULTS: 32 different PILs were identified, of which 2 were generic tools (Macmillan 'understanding cancer of the gullet' and EIDO 'oesophagectomy'). Although most PILs focused on describing in-hospital adverse events, information varied widely and was often misleading. Just 1 leaflet described survival benefits of surgery and 2 mentioned the possibility of disease recurrence. CONCLUSIONS: Written information provided for patients by NHS cancer centres undertaking oesophagectomy is inconsistent and incomplete. It is recommended that surgeons work together with patients to agree on standards of information provision of relevance to all stakeholders' needs.

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.

Core information set for oesophageal cancer surgery.

BACKGROUND: Surgeons provide patients with information before surgery, although standards of information are lacking and practice varies. The development and use of a 'core information set' as baseline information before surgery may improve understanding. A core set is a minimum set of information to use in all consultations before a specific procedure. This study developed a core information set for oesophageal cancer surgery. METHODS: Information was identified from the literature, observations of clinical consultations and patient interviews. This was integrated to create a questionnaire survey. Stakeholders (patients and professionals) were surveyed twice to assess views on importance of information from 'not essential' to 'absolutely essential' using Delphi methods. Items not meeting predefined criteria were discarded after each survey and the final retained items were voted on, in separate patient and professional stakeholder meetings, to agree the core set. RESULTS: Some 67 information items were identified initially from multiple sources. Survey response rates were 76·5 per cent (185 of 242) and 54·8 per cent (126 of 230) for patients and professionals respectively (first round), and over 83 per cent in both groups thereafter. Health professionals rated short-term clinical outcomes most highly (technical complications), whereas patients prioritized information related to long-term benefits. The consensus meetings agreed the final set, which consisted of: in-hospital milestones to recovery, rates of open-and-close surgery, in-hospital mortality, major complications (reoperation), milestones in recovery after discharge, longer-term eating and drinking and overall quality of life, and chances of survival. CONCLUSION: This study has established a core information set for surgery for oesophageal cancer.

Systematic review of surgical innovation reporting in laparoendoscopic colonic polyp resection.

BACKGROUND: The IDEAL framework (Idea, Development, Exploration, Assessment, Long-term study) proposes a staged assessment of surgical innovation, but whether it can be used in practice is uncertain. This study aimed to review the reporting of a surgical innovation according to the IDEAL framework. METHODS: Systematic literature searches identified articles reporting laparoendoscopic excision for benign colonic polyps. Using the IDEAL stage recommendations, data were collected on: patient selection, surgeon and unit expertise, description of the intervention and modifications, outcome reporting, and research governance. Studies were categorized by IDEAL stages: 0/1, simple technical preclinical/clinical reports; 2a, technique modifications with rationale and safety data; 2b, expanded patient selection and reporting of both innovation and standard care outcomes; 3, formal randomized controlled trials; and 4, long-term audit and registry studies. Each stage has specific requirements for reporting of surgeon expertise, governance details and outcome reporting. RESULTS: Of 615 abstracts screened, 16 papers reporting outcomes of 550 patients were included. Only two studies could be put into IDEAL categories. One animal study was classified as stage 0 and one clinical study as stage 2a through prospective ethical approval, protocol registration and data collection. Studies could not be classified according to IDEAL for insufficient reporting details of patient selection, relevant surgeon expertise, and how and why the technique was modified or adapted. CONCLUSION: The reporting of innovation in the context of laparoendoscopic colonic polyp excision would benefit from standardized methods.

Delphi survey to identify topics to be addressed at the initial follow-up consultation after oesophageal cancer surgery.

BACKGROUND: There is no consensus among patients and healthcare professionals (HCPs) on the topics that need to be addressed after oesophageal cancer surgery. The aim of this study was to identify these topics, using a two-round Delphi survey. METHODS: In round 1, patients and HCPs (surgeons, dieticians, nurses) were invited to rate the importance of 49 topics. The proportion of panellists that considered a topic to be of low, moderate or high importance was then calculated for each of these two groups. Based on these proportions and the i.q.r., topics were categorized as: 'consensus to be included', 'consensus to be excluded' and 'no consensus'. Only topics in the first category were included in the second round. In round 2, panellists were provided with individual and group feedback. To be included in the final list, topics had to meet criteria for consensus and stability. RESULTS: There were 108 patients and 77 HCPs in the round 2 analyses. In general, patients and HCPs considered the same topics important. The final list included 23 topics and revealed that it was most important to address: cancer removed/lymph nodes, the new oesophagus, eating and drinking, surgery, alarming new complaints and the recovery period. CONCLUSION: The study provides surgeons with a list of topics selected by patients and HCPs that may be addressed systematically at the initial follow-up consultation after oesophageal cancer surgery.

Outcome reporting in neoadjuvant surgical trials: a systematic review of the literature and proposals for new standards.

BACKGROUND: The use of neoadjuvant therapy before surgery for gastrointestinal cancer is increasing; however, patients may not complete both treatment components. Understanding completion rates of each treatment stage is necessary for treatment evaluation and to inform decision-making. This study evaluates reporting for recent neoadjuvant surgical trials, focusing on treatment progression and other key outcomes. METHODS: Systematic literature searches identified randomized and nonrandomized phase II and III studies evaluating neoadjuvant treatment and surgery for esophageal, stomach, and colorectal cancer, and colorectal liver metastases. Rates of reporting of failure to complete neoadjuvant treatment, nonprogression to surgery after neoadjuvant treatment, and nonresection at planned surgery were assessed. For each measure, reporting was categorized as "full," "partial," and "absent" according to predefined criteria, and reasons for nonprogression at each stage of treatment were examined to inform proposed standards. RESULTS: Of 9854 abstracts, 123 papers were reviewed and 62 articles were included, reporting outcomes for 9126 patients. Details of noncompletion of neoadjuvant treatment and nonprogression to surgery were completely absent in 21 (33.9%) and 19 (30.6%) studies, respectively. Reporting of nonresection at planned surgery was also deficient, with 21 (33.9%) studies providing no information about this outcome. Reasons for noncompletion and nonprogression were similar and included disease progression, treatment toxicity, and patient choice. Common reasons for nonresection were locally advanced disease and the discovery of unsuspected metastases. CONCLUSIONS: Reports of recent neoadjuvant surgical trials often fail to include treatment progression and other key outcomes. These findings support the need for minimum reporting standards.

Evaluating the role of fluorodeoxyglucose positron emission tomography-computed tomography in multi-disciplinary team recommendations for oesophago-gastric cancer.

BACKGROUND: National guidelines recommend that fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) is performed in all patients being considered for radical treatment of oesophageal or oesophago-gastric cancer without computerised tomography scan (CTS) evidence of metastasis. Guidance also mandates that all patients with cancer have treatment decisions made within the context of a multi-disciplinary team (MDT) meeting. Little is known, however, about the influence of PET-CT on decision making within MDTs. The aim of this study was to assess the role of PET-CT in oesophago-gastric cancer on MDT decision making. METHODS: A retrospective analysis of a prospectively held database of all patients with biopsy-proven oesophageal or oesophago-gastric cancer discussed by a specialist MDT was interrogated. Patients selected for radical treatment without CTS evidence of M1 disease were identified. The influence of PET-CT on MDT decision making was examined by establishing whether the PET-CT confirmed CTS findings of M0 disease (and did not change the patient staging pathway) or whether the PET-CT changed the pathway by showing unsuspected M1 disease, refuting CTS suspicious metastases, or identifying another lesion (needing further investigation). RESULTS: In 102 MDT meetings, 418 patients were discussed, of whom 240 were initially considered for radical treatment and 238 undergoing PET-CT. The PET-CT confirmed CTS findings for 147 (61.8%) and changed MDT recommendations in 91 patients (38.2%) by (i) identifying M1 disease (n=43), (ii) refuting CTS suspicions of M1 disease (n=25), and (iii) identifying new lesions required for investigations (n=23). CONCLUSION: The addition of PET-CT to standard staging for oesophageal cancer led to changes in MDT recommendations in 93 (38.2%) patients, improving patient selection for radical treatment. The validity of the proposed methods for evaluating PET-CT on MDT decision making requires more work in other centres and teams.

A prospective study of patient reported outcomes in pancreatic and peri-ampullary malignancy.

BACKGROUND: The purpose of the present study was to describe the impact of treatment of pancreatic and peri-ampullary malignancy on patient reported outcomes (PRO). However, limited data are available describing the impact of curative or palliative therapy on pancreatic/peri-ampullary malignancy and quality of life. METHODS: Patients selected for pancreaticoduodenectomy (PD) completed the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire pre-surgery and 6 weeks, 3, 6, 12, 18, and 24 months postoperatively. Patients selected for palliative treatments completed the same questionnaire before treatment and monthly thereafter. Mean scores and 95 % confidence intervals (CI) were calculated for functional scales. Symptom scales and single items were categorized as either minimal or severe, and they were reported as proportions of patients experiencing severe symptoms with 95 % CI. RESULTS: A total of 100 patients (53 planned PD, 47 palliative) were enrolled. Of the 53 patients planned for surgery, 12 had tumors that were unresectable and 41 underwent pancreatoduodenectomy (PD). Seven patients were excluded because of benign histology or concurrent malignancy. Baseline questionnaire compliance was 70 %. For those undergoing PD, there were 53 complications, 7 deaths at 1 year, and 14 deaths at 2 years. Post-surgery most functions and symptoms deteriorated. Recovery in global health and most symptoms occurred by 3 months, and functional scales recovered by 6 months. Recovery of PRO was maintained in the survivors at 2 years. Palliative patients had poorer function and more symptoms at baseline; however, poor follow-up questionnaire compliance prevented further analysis of this group. CONCLUSIONS: Pancreaticoduodenectomy has a short-term negative impact on PRO that recovers within 6 months and is maintained at 2 years in survivors. Further work evaluating palliative and curative treatment in larger patient groups with disease-specific questionnaires is necessary.