isrctn.org Identifier: ISRCTN80500123.

ObjectiveIn 2001, the National Institute for Health Research Cancer Research Network (NCRN) was established, leading to a rapid increase in clinical research activity across the English NHS. Using colorectal cancer (CRC) as an example, we test the hypothesis that high, sustained hospital-level participation in interventional clinical trials improves outcomes for all patients with CRC managed in those research-intensive hospitals.DesignData for patients diagnosed with CRC in England in 2001–2008 (n=209 968) were linked with data on accrual to NCRN CRC studies (n=30 998). Hospital Trusts were categorised by the proportion of patients accrued to interventional studies annually. Multivariable models investigated the relationship between 30-day postoperative mortality and 5-year survival and the level and duration of study participation.ResultsMost of the Trusts achieving high participation were district general hospitals and the effects were not limited to cancer ‘centres of excellence’, although such centres do make substantial contributions. Patients treated in Trusts with high research participation (≥16%) in their year of diagnosis had lower postoperative mortality (p<0.001) and improved survival (p<0.001) after adjustment for casemix and hospital-level variables. The effects increased with sustained research participation, with a reduction in postoperative mortality of 1.5% (6.5%–5%, p<2.2×10−6) and an improvement in survival (p<10−19; 5-year difference: 3.8% (41.0%–44.8%)) comparing high participation for ≥4 years with 0 years.ConclusionsThere is a strong independent association between survival and participation in interventional clinical studies for all patients with CRC treated in the hospital study participants. Improvement precedes and increases with the level and years of sustained participation.

BackgroundCommonly in surgical randomised controlled trials (RCT) the experimental treatment is a relatively new technique which the surgeons may still be learning, while the control is a well-established standard. This can lead to biased comparisons between treatments. In this paper we discuss the implementation of approaches for addressing this issue in the ROLARR trial, and points of consideration for future surgical trials.MethodsROLARR was an international, randomised, parallel-group trial comparing robotic vs. laparoscopic surgery for the curative treatment of rectal cancer. The primary endpoint was conversion to open surgery (binary). A surgeon inclusion criterion mandating a minimum level of experience in each technique was incorporated. Additionally, surgeon self-reported data were collected periodically throughout the trial to capture the level of experience of every participating surgeon.Multi-level logistic regression adjusting for operating surgeon as a random effect is used to estimate the odds ratio for conversion to open surgery between the treatment groups. We present and contrast the results from the primary analysis, which did not account for learning effects, and a sensitivity analysis which did.ResultsThe primary analysis yields an estimated odds ratio (robotic/laparoscopic) of 0.614 (95% CI 0.311, 1.211; p = 0.16), providing insufficient evidence to conclude superiority of robotic surgery compared to laparoscopic in terms of the risk of conversion to open.The sensitivity analysis reveals that while participating surgeons in ROLARR were expert at laparoscopic surgery, some, if not all, were still learning robotic surgery. The treatment-effect odds ratio decreases by a factor of 0.341 (95% CI 0.121, 0.960; p = 0.042) per unit increase in log-number of previous robotic operations performed by the operating surgeon. The odds ratio for a patient whose operating surgeon has the mean experience level in ROLARR – 152.46 previous laparoscopic, 67.93 previous robotic operations – is 0.40 (95% CI 0.168, 0.953; p = 0.039).ConclusionsIn this paper we have demonstrated the implementation of approaches for accounting for learning in a practical example of a surgery RCT analysis. The results demonstrate the value of implementing such approaches, since we have shown that without them the ROLARR analysis would indeed have been confounded by the learning effects.Trial registrationInternational Standard Randomised Controlled Trial Number (ISRCTN) registry, ID: ISRCTN80500123. Registered on 27 May 2010.

AimAnastomotic leak (AL) is a major complication of rectal cancer surgery. Despite advances in surgical practice, the rates of AL have remained static, at around 10–15%. The aetiology of AL is multifactorial, but one of the most crucial risk factors, which is mostly under the control of the surgeon, is blood supply to the anastomosis. The MRC/NIHR IntAct study will determine whether assessment of anastomotic perfusion using a fluorescent dye (indocyanine green) and near‐infrared laparoscopy can minimize the rate of AL leak compared with conventional white‐light laparoscopy. Two mechanistic sub‐studies will explore the role of the rectal microbiome in AL and the predictive value of CT angiography/perfusion studies.MethodIntAct is a prospective, unblinded, parallel‐group, multicentre, European, randomized controlled trial comparing surgery with intra‐operative fluorescence angiography (IFA) against standard care (surgery with no IFA). The primary end‐point is rate of clinical AL at 90 days following surgery. Secondary end‐points include all AL (clinical and radiological), change in planned anastomosis, complications and re‐interventions, use of stoma, cost‐effectiveness of the intervention and quality of life. Patients should have a diagnosis of adenocarcinoma of the rectum suitable for potentially curative surgery by anterior resection. Over 3 years, 880 patients from 25 European centres will be recruited and followed up for 90 days.DiscussionIntAct will rigorously evaluate the use of IFA in rectal cancer surgery and explore the role of the microbiome in AL and the predictive value of preoperative CT angiography/perfusion scanning.

Objective-To determine whether accurate remote echocardiographic diagnosis of congenital heart disease could be achieved using a low cost telemedicine system. Design-Echocardiographic images obtained by a paediatrician from neonates suspected of having congenital heart disease were transmitted by a telemedicine link across two integrated service digital network (ISDN) lines to a regional paediatric cardiology unit for interpretation by a consultant paediatric cardiologist. The "tele-echo" diagnosis was verified by the paediatric cardiologist on direct consultation and echocardiography. Setting-Neonatal unit of Altnagelvin Hospital, Londonderry (a district general hospital) and the regional paediatric cardiology department, Royal Belfast Hospital for Sick Children. Main outcome measures-Accuracy of the diagnosis made using the telemedicine link; impact on patient management. Results-Between September 1995 and September 1997 echocardiographic images were transmitted on 63 patients. A diagnosis was made in 61 (97%) (transmitted images were unsatisfactory in two). Congenital heart disease was diagnosed in 42 patients. Fourteen patients with major congenital heart disease were accurately diagnosed within 24 hours of admission using the telemedicine link and were transferred to the regional paediatric cardiology unit. A further 28 with less serious congenital heart disease continued to be managed at the district general hospital. Congenital heart disease was excluded in 19. Follow up consultation confirmed accurate diagnosis or exclusion of congenital heart disease in 57 (93%). There were four inaccurate diagnoses (6.3%; three undetected small ventricular septal defects and one pulmonary stenosis). Conclusions-Transmitted images were of suYcient quality to allow confirmation or exclusion of major congenital heart disease. The telemedicine link facilitated early diagnosis and initiation of appropriate management in patients with complex congenital heart disease and avoided the need for transfer in those where significant congenital heart disease was excluded. (Heart 1999;82:217-221)