S.J. Chapman

Discontinuation and non-publication of surgical randomised controlled trials: observational study

Objective To determine the rate of early discontinuation and non-publication of randomised controlled trials involving patients undergoing surgery. Design Cross sectional observational study of registered and published trials. Setting Randomised controlled trials of interventions in patients undergoing a surgical procedure. Data sources The ClinicalTrials.gov database was searched for interventional trials registered between January 2008 and December 2009 using the keyword “surgery”. Recruitment status was extracted from the ClinicalTrials.gov database. A systematic search for studies published in peer reviewed journals was performed; if they were not found, results posted on the ClinicalTrials.gov results database were sought. Email queries were sent to trial investigators of discontinued and unpublished completed trials if no reason for the respective status was disclosed. Main outcome measures Trial discontinuation before completion and non-publication after completion. Logistic regression was used to determine the effect of funding source on publication status, with adjustment for intervention type and trial size. Results Of 818 registered trials found using the keyword “surgery”, 395 met the inclusion criteria. Of these, 21% (81/395) were discontinued early, most commonly owing to poor recruitment (44%, 36/81). The remaining 314 (79%) trials proceeded to completion, with a publication rate of 66% (208/314) at a median time of 4.9 (interquartile range 4.0-6.0) years from study completion to publication search. A further 6% (20/314) of studies presented results on ClinicalTrials.gov without a corresponding peer reviewed publication. Industry funding did not affect the rate of discontinuation (adjusted odds ratio 0.91, 95% confidence interval 0.54 to 1.55) but was associated with a lower odds of publication for completed trials (0.43, 0.26 to 0.72). Investigators’ email addresses for trials with an uncertain fate were identified for 71.4% (10/14) of discontinued trials and 83% (101/122) of unpublished studies. Only 43% (6/14) and 20% (25/122) replies were received. Email responses for completed trials indicated 11 trials in press, five published studies (four in non-indexed peer reviewed journals), and nine trials remaining unpublished. Conclusions One in five surgical randomised controlled trials are discontinued early, one in three completed trials remain unpublished, and investigators of unpublished studies are frequently not contactable. This represents a waste of research resources and raises ethical concerns regarding hidden clinical data and futile participation by patients with its attendant risks. To promote future efficiency and transparency, changes are proposed to research governance frameworks to overcome these concerns.

Social Media and Internet Driven Study Recruitment: Evaluating a New Model for Promoting Collaborator Engagement and Participation

Aims A substantial challenge facing multicentre audit and research projects is timely recruitment of collaborators and their study centres. Cost-effective strategies are required and fee-free social media has previously been identified as a potential conduit. We investigated and evaluated the effectiveness of a novel multi-format social media and Internet strategy for targeted recruitment to a national multicentre cohort study. Methods Interventions involved a new Twitter account, including weekly live question-and-answer sessions, a new Facebook group page, online YouTube presentations and an information page on a national association website. Link tracking analysis was undertaken using Google Analytics, which was then related to subsequent registration. Social influence was calculated using the proprietary Klout score. Results Internet traffic analysis identified a total of 1562 unique registration site views, of which 285 originated from social media (18.2%). Some 528 unique registrations were received, with 96 via social media platforms (18.2%). Traffic source analysis identified a separate national association webpage as resulting in the majority of registration page views (15.8%), followed by Facebook (11.9%), Twitter (4.8%) and YouTube (1.5%). A combination of publicity through Facebook, Twitter and the dedicated national association webpage contributed to the greatest rise in registration traffic and accounted for 312 (48%) of the total registrations within a 2-week period. A Twitter ‘social influence’ (Klout) score of 42/100 was obtained during this period. Conclusions Targeted social media substantially aided study dissemination and collaborator recruitment. It acted as an adjunct to traditional methods, accounting for 18.2% of collaborator registration in a short time period with no associated financial costs. We provide a practical model for designing future recruitment campaigns, and recommend Facebook, Twitter and targeted websites as the most effective adjuncts for maximising cost-effective study recruitment.

Promoting research and audit at medical school: evaluating the educational impact of participation in a student-led national collaborative study.

BackgroundMedical students often struggle to engage in extra-curricular research and audit. The Student Audit and Research in Surgery (STARSurg) network is a novel student-led, national research collaborative. Student collaborators contribute data to national, clinical studies while gaining an understanding of audit and research methodology and ethical principles. This study aimed to evaluate the educational impact of participation.MethodsParticipation in the national, clinical project was supported with training interventions, including an academic training day, an online e-learning module, weekly discussion forums and YouTube® educational videos. A non-mandatory, online questionnaire assessed collaborators’ self-reported confidence in performing key academic skills and their perceptions of audit and research prior to and following participation.ResultsThe group completed its first national clinical study (“STARSurgUK”) with 273 student collaborators across 109 hospital centres. Ninety-seven paired pre- and post-study participation responses (35.5%) were received (male = 51.5%; median age = 23). Participation led to increased confidence in key academic domains including: communication with local research governance bodies (p < 0.001), approaching clinical staff to initiate local collaboration (p < 0.001), data collection in a clinical setting (p < 0.001) and presentation of scientific results (p < 0.013). Collaborators also reported an increased appreciation of research, audit and study design (p < 0.001).ConclusionsEngagement with the STARSurg network empowered students to participate in a national clinical study, which increased their confidence and appreciation of academic principles and skills. Encouraging active participation in collaborative, student-led, national studies offers a novel approach for delivering essential academic training.

Does the extent of lymphadenectomy, number of lymph nodes, positive lymph node ratio and neutrophil-lymphocyte ratio impact surgical outcome of perihilar cholangiocarcinoma?

Background Lymph node (LN) status is an important predictor of survival following resection of perihilar cholangiocarcinoma (PHCCA). Controversies still exist with regard to the prognostic value of optimum extent of lymphadenectomy, total number of nodes removed, LN ratio (LNR) and neutrophil–lymphocyte ratio (NLR) on overall survival (OS) and disease-free survival (DFS) following PHCCA resection. Methods From 1994 to 2010, 84 PHCCAs were resected; 78 are included in this analysis. Kaplan–Meier survival curves were studied using log-rank statistics to assess which variables affected OS and DFS. The variables that showed statistical significance (P<0.05) on Kaplan–Meier univariate analysis were subjected to multivariate analysis using Cox proportional hazards model. Results Five-year OS for node-positive status (n=45) was 10%, whereas node-negative (n=33) OS was 41% (P<0.001). Similarly, 5-year DFS was worse in the node-positive group (8%) than in the node-negative group (36%, P=0.001). There was no difference in 5-year OS (31 vs. 12%, P=0.135) and DFS (22 vs. 16%, P=0.518) between those with regional lymphadenectomy and those who underwent regional plus para-aortic lymphadenectomy, respectively. On univariate analysis, patients with 20 or more LNs removed had worse 5-year OS (0%) when compared with those with less than 20 LNs removed (29%, P=0.047). Moderate/poor tumour differentiation, distant metastasis and LN involvement were independent predictors of OS. Positive LNR had no effect on OS. Vascular invasion and an LNR of at least 0.37 were independent predictors of DFS. NLR had no effect on OS and DFS. Conclusion Extended lymphadenectomy patients (≥20 LNs) had worse OS when compared with those with more limited (<20 LNs) resection. An LNR of at least 0.37 is an independent predictor of DFS.

Longitudinal analysis of reporting and quality of systematic reviews in high-impact surgical journals.

The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta‐Analyses) Statement aims to optimize the reporting of systematic reviews. The performance of the PRISMA Statement in improving the reporting and quality of surgical systematic reviews remains unclear.

Multicentre observational cohort study of NSAIDs as risk factors for postoperative adverse events in gastrointestinal surgery

Introduction Non-steroidal anti-inflammatory drugs (NSAIDs) are recommended as postoperative analgesia by the Enhanced Recovery After Surgery Society. Recent studies have raised concerns that NSAID administration following colorectal anastomosis may be associated with increased risk of anastomotic leak. This multicentre study aims to determine NSAIDs’ safety profile following gastrointestinal resection. Methods and analysis This prospective, multicentre cohort study will be performed over a 2-week period utilising a collaborative methodology. Consecutive adults undergoing open or laparoscopic, elective or emergency gastrointestinal resection will be included. The primary end point will be the 30-day morbidity, assessed using the Clavien-Dindo classification. This study will be disseminated through medical student networks, with an anticipated recruitment of at least 900 patients. The study will be powered to detect a 10% increase in complication rates with NSAID use. Ethics and dissemination Following the Research Ethics Committee Chairpersons review, a formal waiver was received. This study will be registered as a clinical audit or service evaluation at each participating hospital. Dissemination will take place through previously described novel research collaborative networks.

Postoperative ileus following major colorectal surgery.

Postoperative ileus (POI) is characterized by delayed gastrointestinal recovery following surgery. Current knowledge of pathophysiology, clinical interventions and methodological challenges was reviewed to inform modern practice and future research.

Underreporting of Secondary Endpoints in Randomized Trials: Cross-sectional, Observational Study.

Objective: To determine if underreporting of secondary endpoints in randomized controlled trials occurs, using surgical site infection (SSI) as an example. Background: SSI is a commonly measured endpoint in surgical trials and can act as a proxy marker for primary and secondary endpoint assessments across trials in a range of medical specialties. Methods: Cross-sectional observational study of randomized trials including patients undergoing gastrointestinal surgery published in a representative selection of general medical and general surgical journals. Studies were included if SSI assessment was a prespecified endpoint. Adjusted binary logistic regression was used to identify factors associated with a high rate of SSI detection (≥10%). Results: From 216 trials including 45,633 patients, the pooled SSI rate was 7.7% (3519/45,633), which was significantly higher when assessed as a primary endpoint (12.6%, 1993/15,861, 49 studies) vs as a secondary endpoint (5.1%, 1526/29,772, 167 studies, P < 0.001). When assessed as a secondary outcome, standardized definitions and formal clinical reviews were used significantly less often. When adjusted for surgical contamination and methodological confounders, secondary assessment was associated with reduced SSI detection compared with primary assessment (adjusted odds ratio 0.24, 95% confidence interval 0.08–0.69, P = 0.008). Conclusions: Secondary endpoint assessment of SSI in randomized trials was associated with significantly reduced rigor and subsequent detection rates compared with assessment as a primary endpoint. Trial investigators should ensure that primary and secondary endpoint assessments are equally robust. PRISMA guidelines should be updated to promote the conduct of meta-analysis based only on primary outcomes from randomized controlled trials.

Surgical training and clinical trial involvement—the trainees’ view

As surgical trainees across multiple disciplines, it is our collective aim for all surgical patients to have the opportunity to participate in at least one clinical trial during their hospital episode.1 We recognise that most patients wish to have this option,2 and we want our training to facilitate this. Because patients have the right to be involved in improving surgical …

Ban on publishing industry funded research could harm surgical innovation.

A blanket ban on publishing drug industry funded research has implications for surgical research.1 Industry collaborations in surgery involve drugs and devices, with the latter driving technological advancement. Recent efforts—encouraged by the Royal College of Surgeons of England (RCSEng)—have focused on strengthening these collaborations to promote and …