The challenges faced in the design, conduct and analysis of surgical randomised controlled trials

Randomised evaluations of surgical interventions are rare; some interventions have been widely adopted without rigorous evaluation. Unlike other medical areas, the randomised controlled trial (RCT) design has not become the default study design for the evaluation of surgical interventions. Surgical trials are difficult to successfully undertake and pose particular practical and methodological challenges. However, RCTs have played a role in the assessment of surgical innovations and there is scope and need for greater use. This article will consider the design, conduct and analysis of an RCT of a surgical intervention. The issues will be reviewed under three headings: the timing of the evaluation, defining the research question and trial design issues. Recommendations on the conduct of future surgical RCTs are made. Collaboration between research and surgical communities is needed to address the distinct issues raised by the assessmentof surgical interventions and enable the conduct of appropriate and well-designed trials.The Health Services Research Unit is funded by the Scottish Government Health DirectoratesPeer reviewedPublisher PD

The challenges faced in the design, conduct and analysis of surgical randomised trials

Randomised evaluations of surgical interventions are rare; some interventions have been widely adopted without rigorous evaluation. Unlike other medical areas, the randomised controlled trial (RCT) design has not become the default study design for the evaluation of surgical interventions. Surgical trials are difficult to successfully undertake and pose particular practical and methodological challenges. However, RCTs have played a role in the assessment of surgical innovations and there is scope and need for greater use. This article will consider the design, conduct and analysis of an RCT of a surgical intervention. The issues will be reviewed under three headings: the timing of the evaluation, defining the research question and trial design issues. Recommendations on the conduct of future surgical RCTs are made. Collaboration between research and surgical communities is needed to address the distinct issues raised by the assessment of surgical interventions and enable the conduct of appropriate and well-designed trials

Relative effectiveness of robot-assisted and standard laparoscopic prostatectomy as alternatives to open radical prostatectomy for treatment of localised prostate cancer : a systematic review and mixed treatment comparison meta-analysis

© 2013 The Authors. BJU International © 2013 BJU International.Peer reviewedPublisher PD

Clinical and economic evaluation of laparoscopic surgery compared with medical management for gastro-oesophageal reflux disease : 5-year follow-up of multicentre randomised trial (the REFLUX trial)

Peer reviewedPublisher PD

Laparoscopic versus open colorectal surgery in the acute setting (LaCeS trial): a multicentre randomized feasibility trial

AbstractBackgroundApproximately 30,000 people per annum undergo major, emergency abdominal, gastrointestinal surgery, of which 36% (~10,800) are carried out for emergency colorectal pathology. Approximately 14% of all patients requiring emergency surgery undergo laparoscopic surgery. AimsThe aims of the LaCeS feasibility trial (Laparoscopic versus Open Colorectal Surgery in the Acute Setting) were to assess the feasibility, safety and acceptability of performing a large-scale definitive phase III randomised controlled trial with a comparison of emergency laparoscopic with open surgery for acute colorectal pathology. MethodsLaCeS was designed as a prospective, multicentre, single blind, parallel group, pragmatic, randomised controlled feasibility trial with an integrated qualitative study. Randomisation was performed centrally with patients being randomised on a 1:1 basis between laparoscopic or open surgery. ResultsA total of 64 patients were recruited across 5 centres. The overall average steady state recruitment rate was 1.2 patients/month. Baseline compliance for clinical and HrQoL data was 99.8% and 93.8% respectively. The conversion rate from laparoscopic to open surgery was 39.4% (95% CI 22.9% – 57.9%). The 30 day post-operative complication rate was 27.3% (95% CI 13.3- 45.5) in the laparoscopic arm and 41.9% (95% CI 24.6 – 60.9) in the open arm. DiscussionThe LaCeS feasibility trial has demonstrated that it is possible to evaluate laparoscopic surgery in the emergency colorectal setting within the context of a randomised controlled trial. LaCeS has demonstrated that it is possible to recruit to a surgical trial in the emergency setting, with good compliance to trial procedures and processes, and overall acceptability by patients and clinicians. The safety data obtained for laparoscopic emergency colorectal surgery indicate an acceptable safety profile, particularly when considering it to that observed in the open arm.Trial Registration ISRCTN15681041 https://doi.org/10.1186/ISRCTN15681041.Funding body: National Institute of Health Research – Research for Patient Benefi

Challenges in evaluating surgical innovation

Research on surgical interventions is associated with several methodological and practical challenges of which few, if any, apply only to surgery. However, surgical evaluation is especially demanding because many of these challenges coincide. In this report, the second of three on surgical innovation and evaluation, we discuss obstacles related to the study design of randomised controlled trials and non-randomised studies assessing surgical interventions. We also describe the issues related to the nature of surgical procedures—for example, their complexity, surgeon-related factors, and the range of outcomes. Although difficult, surgical evaluation is achievable and necessary. Solutions tailored to surgical research and a framework for generating evidence on which to base surgical practice are essential.The Balliol Colloquium has been supported by Ethicon UK with unrestricted educational grants and by the National Institute of Health Research Health Technology Assessment Programme. The Balliol Colloquium was administratively and financially supported by the Nuffield Department of Surgery at the University of Oxford and the Department of Surgery at McGill University. JAC holds a Medical Research Council UK special training fellowship. The University of Aberdeen’s Health Services Research Unit is core funded by the Chief Scientist Offi ce of the Scottish Government Health Directorates. IB is supported by a grant from the Société Française de Rhumatologie and Lavoisier Program (Ministère des Aff aires Etrangères et Européennes). PLE is a DPhil Candidate in Evidence-Based Health Care at Oxford University

Enhanced recovery after surgery (ERAS) interventions and outcome from colorectal surgery

Although immense progress has been made in the fields of chemo- and radiotherapy during the last decades, surgery is still the ultimate cure for the majority of patients with colorectal cancer. Since colorectal cancer most often presents at a high age and in patients often suffering from a large burden of comorbidity, it is important to develop strategies to improve postoperative recovery and outcome, not only for the patient, but also from a health economic perspective. ERAS (Enhanced Recovery After Surgery) is an evidence-based concept aiming to reduce surgical stress, shown to reduce perioperative morbidity, improve postoperative recovery and shorten length of stay (LOS). Today, the international ERAS® Society Interactive Audit System (EIAS) includes a database containing more than 80 000 patients, each patient with more than 300 perioperative variables recorded. The database is a valuable source for research and a guide for surgical centres to sustain and improve principles of perioperative care. Within the research field of ERAS, our research group identified two major questions that need further investigation. First, single interventions included in the ERAS protocol require further evaluation regarding the impact on the protocol as a whole. Second, most studies have so far been focusing on short-term outcomes after surgery. The effect of an ERAS-program on long- term outcome is however, largely unknown. The overall aim of this thesis was to investigate these topics and hopefully fill some of the knowledge gaps concerning these questions. In paper I we evaluated the effect of perioperative fluid management on short-term postoperative outcomes and 5-year survival after surgery. This single-center cohort study included patients with colorectal cancer operated between 2002 to 2007. In all, 911 patients were enrolled. Patients receiving 3000 mL. A restrictive fluid management was associated with shorter LOS (mean 5.6 vs 9.0 days, p < 0.001), lower risk of complications (odds ratio (OR) 0.44, 95 % confidence interval (CI) (0.28 – 0.71)) and symptoms delaying discharge (OR 0.47, 95 % CI (0.32 - 0.70)). The risk of cancer specific death was significantly reduced (hazard ratio (HR) 0.45, 95 % CI (0.25 – 0.81)). The study concluded a possible association between a restrictive fluid regimen and improved short- and long-term outcomes. In paper II the aim was to compare robotic and laparoscopic rectal tumor surgery within an ERAS setting regarding short-term outcomes and compliance to the ERAS protocol. This single-center cohort study included 47 patients operated with laparoscopic technique between January 2011 to April 2014 and 72 patients operated with robotic technique between April 2014 to January 2017. Robotic surgery was associated with shorter LOS (median 3 vs 7 days, p < 0.001), lower rate of complications (25 % vs 49 %, p < 0.01) and a lower conversion rate to open surgery (11 % vs 34 %, p = 0.002). Results endured in multivariate analysis. Compliance to the ERAS protocol showed no difference between groups. The conclusion, in this single-center cohort study, was that robotic rectal tumor surgery demonstrated superior short-term outcomes compared to laparoscopic rectal tumor surgery. In paper III the Swedish part of the international ERAS database was used to compare short- term outcome in patients operated on with robotic, laparoscopic and open rectal tumor surgery. Compliance to the ERAS® Society Guidelines was compared between groups. This multi- center retrospective cohort study included 3125 patients between January 2010 to February 2020. Robotic surgery showed similar complication rates compared to open surgery (35.9 % vs 40.9 %, OR 1.15, 95% CI (0.93, 1.41)) and laparoscopic surgery (35.9 % vs 31.2 %, OR 0.88, 95% CI (0.71, 1.08)). LOS was shorter in the robotic group, median 6 days vs 9 days in the open group (incidence rate ratio (IRR) 1.35, 95% CI (1.27, 1.44)) and 7 days in the laparoscopic group (IRR 1.14, 95% CI (1.07, 1.21)). Robotic surgery had a lower conversion rate compared to laparoscopic surgery (8.3 % vs 18.0 %, OR 2.58, 95 % CI (1.85, 3.60)). Pre- and intraoperative compliance to the ERAS protocol were similar between groups. In conclusion, this multi-center cohort study demonstrated shorter LOS in robotic surgery vs open and laparoscopic surgery and lower conversion rate to open surgery in the robotic group vs the laparoscopic group. In paper IV the aim was to identify predictors for anastomotic leakage (AL) in patients operated with anterior resection (AR) included in the Swedish part of the international ERAS database. Altogether 1900 patients were investigated between January 2010 to February 2020, 155 patients with AL and 1745 patients without AL. Obesity (OR 1.71, 95 % CI (1.04, 2.80)), male gender (OR 1.88, 95 % CI (1.28, 2.75)), duration of primary surgery (OR 1.13, 95 % CI (1.02, 1.24)), peritoneal contamination (OR 1.78, 95 % CI (1.01, 3.16)) and surgery late in the study period (OR 1.89, 95 % CI (1.18, 3.01)) were all independent predictors for AL. Patients suffering from AL had longer LOS (median 7 vs 15 days, p < 0.001) and higher rate of reoperations (69.7 % vs 6.6 %, p <0.001) compared to patients without AL. No difference in pre- and intraoperative compliance was seen between groups. In conclusion, this multi-center cohort study showed that male gender, obesity, duration of surgery, surgery late in the study period and peritoneal soiling were independent predictors for AL

Structural and Care Process Improvement of Ward-based Postoperative Care to Optimise Surgical Outcomes

Much of the variation seen in surgical outcomes can be explained by differences in the quality of management of post-operative complications and ward-based care. The surgical ward round (WR) is critical to determining post-operative care and serves as the primary point of interaction between clinician and patient. Despite this, it is an area not subject to training or assessment at present. This thesis demonstrates the high degree of variability which exists in the conduct of WRs. It establishes the link between suboptimal patient assessment and increased risk of preventable post-operative complications. These place patients not only at risk of short-term deterioration, but result in reduced long-term survival as well. In order to quantify WR quality, a novel assessment tool has been developed and validated within a simulated environment. Ward simulation is a nascent branch of simulation which has been only preliminarily explored to date. A simulation environment was developed to take advantage of the known benefits of simulation such as controllability, reproducibility, and recordability, whilst maintaining a high level of fidelity and realism. An evidence-based curriculum for surgical WR training was designed and implemented in a simulation-based course. By focusing on structured generic processes of patient assessment and management, this resulted in significant improvement of trainee performance in routine WRs. To ensure standardised and optimum management of specific conditions, checklists have proven themselves to be of great value in a number of surgical and medical disciplines. Surgical complications are common, yet their management often suboptimal. As part of this thesis, evidence-based protocols for the management of the six most common complications were designed and validated. The implementation of these in a simulation-based randomised, controlled trial has resulted in greatly increased adherence to evidence-based standards of care, as well as improved communication and clinician performance. This thesis explores the variance currently present in surgical ward rounds, and the potentially grave consequences of this for patient outcomes. To date, WRs have been one of the last areas of surgical care still dependent on the Halstedian principle of experiential learning alone. The tools have now been developed with which to assess, improve, and standardise critical structures and care processes in the assessment and management of the post-operative surgical patient. Future implementation of these and integration into surgical curricula will benefit clinician training, patient care, and surgical outcomes alike.Open Acces

Laparoscopic cholecystectomy versus conservative management for adults with uncomplicated symptomatic gallstones : the C-GALL RCT

Acknowledgements The authors wish to thank the men and women who participated in C-GALL. We also thank the CHaRT data coordinators and trials managers who helped support the study: Zoe Batham, Louise Campbell, Janice Cruden, Dianne Dejean, Jackie Ellington, Andrea Fraser and Bev Smith (data coordinators), Tracey Davidson and Alison McDonald (Trial managers). We are grateful to Kirsty McCormack and John Norrie for their help and advice in developing the grant proposal, to the Programming Team in CHaRT for developing and maintaining the study website. We thank Juliette Snow and Rachael West for their help with contracting, and Louise Cotterell, Kerry Duffus and Anne Buckle for their assistance in managing the budget. Our thanks go also to the Research Governance team (Louise King, Stacey Dawson, Lynn McKay) at the University of Aberdeen for their advice and support during the study. Thanks to Jamie McAllister (NHS Grampian) for providing unit cost data for the within trial economic analysis. Thanks to the Chen et al. for allowing the C-GALL group the use of the Otago ConditionSpecific Questionnaire (OCSQ) for gallstone disease, developed by Chen et al. in the University of Otago, New Zealand.1,2 1. Chen TY, Landmann MG, Potter JC, van Rij AM. Questionnaire to aid priority and outcomes assessment in gallstone disease. ANZ J Surg. 2006;76(7):569-74. 2. Chen TY. A novel set of condition-specific quality of life questionnaires in elective general surgical patient prioritization and outcome assessment [dissertation]. Dunedin (NZ): University of Otago; 2012. Retrieved from http://hdl.handle.net/10523/2588 Members of the PMG for their ongoing support and advice. The independent members of the TSC and DMC, and the staff at the recruiting sites (listed below) who facilitated recruitment, treatment and follow up of trial participants. Trial funding This project was funded by the National Institute for Health Research (NIHR) XXX programme and will be published in full in HTA journal; Vol. XX, No. XXPeer reviewe

Feasibility of Post-Operative Mobile Health Monitoring Among Colorectal Surgery Patients

Post-operative readmission following colorectal surgery is a common and costly occurrence. Remote health monitoring via mobile applications has the potential to reduce post-operative readmissions by early identification of complications. This intervention depends on patient acceptance and compliance with available technology. The feasibility of home monitoring using automated daily surveys and wound photo uploads, delivered via a mobile health application, was tested in the immediate post-operative period after colorectal surgery. Patient compliance, the association between generated alerts and readmissions, and patient satisfaction were measured. Patient satisfaction was high; 80.5% of patients reported that they felt safer going home knowing that they were monitored and 76.2% of patients reported that they would use the current app for post-operative monitoring again. However, only 37.0% of patients answered the survey at least 80% of the time in the first 2 weeks following discharge. Patient compliance significantly limited the feasibility of post-operative monitoring using our mobile health application