Armando Vargas-Palacios

Background Anastomotic leakage (AL) following resection for rectal cancer has a significant negative impact on patients and represents a substantial economic burden. Intraoperative fluorescence angiography using indocyanine green (ICG+) is a potential strategy to reduce ALs. Findings from recent randomized controlled trials were positive; however, no full economic evaluations of ICG+ have been conducted to date. We conducted a cost-utility analysis of the ICG+ vs standard surgeon assessment (ICG-) using the IntAct trial data. Methods We took the perspective of the UK NHS over a 90-day post procedure horizon. EQ-5D-5L and resource use data were collected at baseline, 30 and 90 days in the UK trial sub-sample to enable estimation of quality-adjusted life years (QALYs) and costs. Incremental cost-effectiveness ratios (ICERs) were estimated using generalised linear regression models. Results We analysed data from n=345 UK patients finding negligible adjusted differences in QALYs (−0.001 in the primary multiply imputed analysis) at 90 days but modest cost savings (£73 [95% CI −£78, −£67] for the primary and £140 [95% CI −£150, −£129] for the secondary complete case analyses) per patient for ICG+. The ICER primary analysis indicated ICG+ was cost effective. Simulations indicated ICG+ had a 60% chance of being the optimal strategy in the primary analysis. Conclusions This research represents a novel contribution on the value of ICG+ for preventing ALs. Results indicate that ICG+ leads to modest cost savings. Together with the clinical effectiveness results, and the potential positive budget impact, the current results indicate ICG+ is likely to provide net health benefit.

Aim: Recovery after surgery for colorectal cancer is a complex process, involving numerous physiological, emotional, social and economic challenges. Good information is a key factor for enabling patients to recover well, but there is a paucity of evidence to guide how this should be done. A new information intervention (Recover Together) comprising a booklet, an online video and an inpatient goal board has been developed. This study explores its feasibility, as well as the feasibility of key study methods, during its first use in the United Kingdom National Health Service (NHS).Methods: This is a mixed methods, multi‐centre, feasibility study of a complex intervention. A total of 105 participants undergoing oncological colorectal surgery will be recruited across three to four study sites in the UK. Participants will receive each component of the Recover Together intervention at defined timepoints before and during hospital admission. A series of patient‐centred outcome instruments will be administered in hospital and during follow‐up at 30 days and 6 months. Outcomes of feasibility will comprise the time taken to establish the intervention at participating sites, assessments of intervention fidelity and acceptability, as well as return rates of key clinical outcome instruments. The mixed methods design will comprise interviews and focus groups with patients and health professionals, non‐participant observation in ward areas and clinics, user‐specific video analytics and daily photographs of the goal boards.Discussion: The findings of this study will provide a feasibility assessment of the Recover Together intervention when used for the first time in NHS practice. If shown to be feasible, this will guide the development of a future definitive study to explore the clinical and cost effectiveness of the Recover Together intervention to improve recovery after surgery.Clinical Trials Registration: ISRCTN62430915.

Background: Hand eczema is common and a cause of morbidity and occupational disability. When education, irritant/contact allergen avoidance, moisturisation and topical corticosteroids are insufficient to control chronic hand eczema, ultraviolet therapy or systemic immune-modifying drugs are used. There is no treatment pathway generally accepted by UK dermatologists. Primary objective: Compare alitretinoin and ultraviolet therapy as first-line therapy in terms of disease activity at 12 weeks post planned start of treatment. Design: Prospective, multicentre, open-label, two-arm parallel group, adaptive randomised controlled trial with one planned interim analysis, and an economic evaluation. Setting: UK secondary care dermatology outpatient clinics. Participants: Patients with severe chronic hand eczema unresponsive to at least 4 weeks of treatment with potent topical corticosteroids. Primary end point: Natural logarithm of the Hand Eczema Severity Index + 1, 12 weeks post planned start of treatment. Randomisation: Participants randomised 1 : 1 by minimisation to alitretinoin or ultraviolet therapy for 12 to 24 weeks. Blinding: Blinded primary end-point assessor. Results: Intention-to-treat population: 441 (100.0%) participants; 220 (49.9%) alitretinoin and 221 (50.1%) ultraviolet therapy. At least one dose was received by 212 (96.4%) alitretinoin and 196 (88.7%) ultraviolet therapy participants. Primary outcome: The unadjusted median (interquartile range) relative change in hand eczema severity index at 12 weeks was 30% (10–70%) of that at baseline for alitretinoin compared with 50% (20–100%) for ultraviolet therapy. There was a statistically significant benefit of alitretinoin compared with ultraviolet therapy at 12 weeks, with an estimated fold change or relative difference (95% confidence interval) = 0.66 (0.52 to 0.82), p = 0.0003 at 12 weeks. There was no evidence of a difference at 24 or 52 weeks, with the estimated fold change (95% confidence interval) equal to 0.92 (0.798 to 1.08) and 1.27 (0.97 to 1.67), respectively. Primary analysis results were consistent for secondary end points: Fifty-nine per cent allocated to alitretinoin and 61% allocated to ultraviolet therapy achieved a clear/almost clear assessment during the trial period. Differential treatment compliance observed: 145 (65.9%) alitretinoin and 53 (24.0%) ultraviolet therapy participants confirmed compliance (≥ 80% received, no treatment breaks > 7 days during first 12 weeks). High levels of missing data were observed. Safety: One hundred and thirty-five reportable adverse events across 79 participants, 55 (25.0%) alitretinoin and 24 (10.9%) ultraviolet therapy. Four serious adverse events (two alitretinoin, two ultraviolet therapy). Four pregnancies reported (three alitretinoin, one ultraviolet therapy). No new safety signals were detected. Conclusion: As a first-line therapy, alitretinoin showed more rapid improvement and superiority to ultraviolet therapy at week 12. This difference was not observed at later time points. Alitretinoin is cost-effective at weeks 12 and 52. Ultraviolet therapy is cost-effective after 10 years, with a high degree of uncertainty. Hand eczema severity index may be a useful primary outcome measure for hand eczema trials; ALPHA results will inform future trials. Limitations: Treatment compliance was poor for ultraviolet therapy. Regular twice weekly treatment was not received by most patients. Assessment of long-term effects of randomised treatments was complicated by use of second-line treatments post treatment phase. Further work: Further analysis of substudies and pilot data will provide valuable information for future studies. A clear need for better therapeutic approaches for severe chronic hand eczema remains. Future studies will need to further address long-term benefits of treatments given. Trial registration: This trial is registered as ISRCTN80206075. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 12/186/01) and is published in full in Health Technology Assessment; Vol. 28, No. 59. See the NIHR Funding and Awards website for further award information.

Background Posterior cervical foraminotomy and anterior cervical discectomy are routinely used operations to treat cervical brachialgia, although definitive evidence supporting superiority of either is lacking. Objective The primary objective was to investigate whether or not posterior cervical foraminotomy is superior to anterior cervical discectomy in improving clinical outcome. Design This was a Phase III, unblinded, prospective, United Kingdom multicentre, parallel-group, individually randomised controlled superiority trial comparing posterior cervical foraminotomy with anterior cervical discectomy. A rapid qualitative study was conducted during the close-down phase, involving remote semistructured interviews with trial participants and health-care professionals. Setting National Health Service trusts. Participants Patients with symptomatic unilateral cervical brachialgia for at least 6 weeks. Interventions Participants were randomised to receive posterior cervical foraminotomy or anterior cervical discectomy. Allocation was not blinded to participants, medical staff or trial staff. Health-care use from providing the initial surgical intervention to hospital discharge was measured and valued using national cost data. Main outcome measures The primary outcome measure was clinical outcome, as measured by patient-reported Neck Disability Index score 52 weeks post operation. Secondary outcome measures included complications, reoperations and restricted American Spinal Injury Association score over 6 weeks post operation, and patient-reported Eating Assessment Tool-10 items, Glasgow–Edinburgh Throat Scale, Voice Handicap Index-10 items, PainDETECT and Numerical Rating Scales for neck and upper-limb pain over 52 weeks post operation. Results The target recruitment was 252 participants. Owing to slow accrual, the trial closed after randomising 23 participants from 11 hospitals. The qualitative substudy found that there was support and enthusiasm for the posterior cervical FORaminotomy Versus Anterior cervical Discectomy in the treatment of cervical brachialgia trial and randomised clinical trials in this area. However, clinical equipoise appears to have been an issue for sites and individual surgeons. Randomisation on the day of surgery and processes for screening and approaching participants were also crucial factors in some centres. The median Neck Disability Index scores at baseline (pre surgery) and at 52 weeks was 44.0 (interquartile range 36.0–62.0 weeks) and 25.3 weeks (interquartile range 20.0–42.0 weeks), respectively, in the posterior cervical foraminotomy group (n = 14), and 35.6 weeks (interquartile range 34.0–44.0 weeks) and 45.0 weeks (interquartile range 20.0–57.0 weeks), respectively, in the anterior cervical discectomy group (n = 9). Scores appeared to reduce (i.e. improve) in the posterior cervical foraminotomy group, but not in the anterior cervical discectomy group. The median Eating Assessment Tool-10 items score for swallowing was higher (worse) after anterior cervical discectomy (13.5) than after posterior cervical foraminotomy (0) on day 1, but not at other time points, whereas the median Glasgow–Edinburgh Throat Scale score for globus was higher (worse) after anterior cervical discectomy (15, 7, 6, 6, 2, 2.5) than after posterior cervical foraminotomy (3, 0, 0, 0.5, 0, 0) at all postoperative time points. Five postoperative complications occurred within 6 weeks of surgery, all after anterior cervical discectomy. Neck pain was more severe on day 1 following posterior cervical foraminotomy (Numerical Rating Scale – Neck Pain score 8.5) than at the same time point after anterior cervical discectomy (Numerical Rating Scale – Neck Pain score 7.0). The median health-care costs of providing initial surgical intervention were £2610 for posterior cervical foraminotomy and £4411 for anterior cervical discectomy. Conclusions The data suggest that posterior cervical foraminotomy is associated with better outcomes, fewer complications and lower costs, but the trial recruited slowly and closed early. Consequently, the trial is underpowered and definitive conclusions cannot be drawn. Recruitment was impaired by lack of individual equipoise and by concern about randomising on the day of surgery. A large prospective multicentre trial comparing anterior cervical discectomy and posterior cervical foraminotomy in the treatment of cervical brachialgia is still required. Trial registration This trial is registered as ISRCTN10133661. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 27, No. 21. See the NIHR Journals Library website for further project information.

The UK NHS Women’s National Breast Screening programme aims to detect breast cancer early. The reference standard approach requires mammograms to be independently double-read by qualified radiology staff. If two readers disagree, arbitration by an independent reader is undertaken. Whilst this process maximises accuracy and minimises recall rates, the procedure is labour-intensive, adding pressure to a system currently facing a workforce crisis. Artificial intelligence technology offers an alternative to human readers. While artificial intelligence has been shown to be non-inferior versus human second readers, the minimum requirements needed (effectiveness, set-up costs, maintenance, etc) for such technology to be cost-effective in the NHS have not been evaluated. We developed a simulation model replicating NHS screening services to evaluate the potential value of the technology. Our results indicate that if non-inferiority is maintained, the use of artificial intelligence technology as a second reader is a viable and potentially cost-effective use of NHS resources.

In the UK, the NHS National Breast Screening programme, which aims to detect breast cancer at earlier stages, has been shown to be cost-effective. ^1,2 The reference standard within the service is for mammograms to be independently double-read³. The double reading is performed by consultant radiologists, consultant radiographers, advanced practitioners, and breast clinicians. If the readers disagree, then arbitration by a single or several readers will take place. This process has reduced false positives and recall rates whilst producing a high level of accuracy, ⁴ but the process is labour-intensive. In the UK, this has put the service under pressure due to a radiology work force crisis. Artificial intelligence (AI) technology has been suggested as a substitute for a human reader as a solution.⁵ While such technology has shown to be non-inferior in performance as a second reader⁶, the minimum requirements needed (effectiveness, set-up costs, maintenance, etc) for such technology to be a cost-effective alternative for use in the NHS, have not been evaluated. To assess the later, we developed a simulation model replicating the UK NHS screening services. Our results indicate that if non-inferiority is maintained, the use of an AI technology as a second reader is a viable and potentially cost-effective alternative for use in a service such as the NHS.

Background: Preliminary studies using the FENIX™ (Torax Medical, Minneapolis, MN, USA) magnetic sphincter augmentation device suggest that it is safe to use for the treatment of adult faecal incontinence, but efficacy data are limited. Objective: To compare FENIX with sacral nerve stimulation for the treatment of adult faecal incontinence in terms of safety, efficacy, quality of life and cost-effectiveness. Design, setting and participants: Multicentre, parallel-group, unblinded, randomised trial comparing FENIX with sacral nerve stimulation in participants suffering moderate to severe faecal incontinence. Interventions: Participants were randomised on an equal basis to either sacral nerve stimulation or FENIX. Follow-up occurred 2 weeks postoperatively and at 6, 12 and 18 months post randomisation. Main outcome and measure: The primary outcome was success, defined as device in use and ≥ 50% improvement in Cleveland Clinic Incontinence Score at 18 months post randomisation. Secondary outcomes included complication rates, quality of life and cost-effectiveness. Between 30 October 2014 and 23 March 2017, 99 participants were randomised across 18 NHS sites (50 participants to FENIX vs. 49 participants to sacral nerve stimulation). The median time from randomisation to FENIX implantation was 57.0 days (range 4.0–416.0 days), and the median time from randomisation to permanent sacral nerve stimulation was 371.0 days (range 86.0–918.0 days). A total of 45 out of 50 participants underwent FENIX implantation and 29 out of 49 participants continued to permanent sacral nerve stimulation. The following results are reported, excluding participants for whom the corresponding outcome was not evaluable. Overall, there was success for 10 out of 80 (12.5%) participants, with no statistically significant difference between the two groups [FENIX 6/41 (14.6%) participants vs. sacral nerve stimulation 4/39 (10.3%) participants]. At least one postoperative complication was experienced by 33 out of 45 (73.3%) participants in the FENIX group and 9 out of 40 (22.5%) participants in the sacral nerve stimulation group. A total of 15 out of 50 (30%) participants in the FENIX group ultimately had to have their device explanted. Slightly higher costs and quality-adjusted life-years (incremental = £305.50 and 0.005, respectively) were observed in the FENIX group than in the sacral nerve stimulation group. This was reversed over the lifetime horizon (incremental = –£1306 and –0.23 for costs and quality-adjusted life-years, respectively), when sacral nerve stimulation was the optimal option (net monetary benefit = –£3283), with only a 45% chance of FENIX being cost-effective. Limitations: The SaFaRI study was terminated in 2017, having recruited 99 participants of the target sample size of 350 participants. The study is, therefore, substantially underpowered to detect differences between the treatment groups, with significant uncertainty in the cost-effectiveness analysis. Conclusions: The SaFaRI study revealed inefficiencies in the treatment pathways for faecal incontinence, particularly for sacral nerve stimulation. The success of both FENIX and sacral nerve stimulation was much lower than previously reported, with high postoperative morbidity in the FENIX group. Future work: Further research is needed to clarify the treatment pathways for sacral nerve stimulation and to determine its true clinical and cost-effectiveness. Trial registration: Current Controlled Trials ISRCTN16077538. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 18. See the NIHR Journals Library website for further project information.