Impact of the National Institute for Health and Care Excellence (NICE) guidance on medical technology uptake: analysis of the uptake of spinal cord stimulation in England 2008–2012

Background: The National Institute for Health and Care Excellence (NICE) Technology Appraisal Guidance on spinal cord stimulation (SCS) was published in 2008 and updated in 2012 with no change. This guidance recommends SCS as a cost-effective treatment for patients with neuropathic pain. Objective: To assess the impact of NICE guidance by comparing SCS uptake in England pre-NICE (2008–2009) and post-NICE (2009–2012) guidance. We also compared the English SCS uptake rate with that of Belgium, the Netherlands, France and Germany. Design: SCS implant data for England was obtained from the Hospital Episode Statistics (HES) database and compared with other European countries where comparable data were available. Results: The HES data showed small increases in SCS implantation and replacement/revision procedures, and a large increase in SCS trials between 2008 and 2012. The increase in the total number of SCS procedures per million of population in England is driven primarily by revision/replacements and increased trial activity. Marked variability in SCS uptake at both health regions and primary care trust level was observed. Conclusions: Despite the positive NICE recommendation for the routine use of SCS, we found no evidence of a significant impact on SCS uptake in England. Rates of SCS implantation in England are lower than many other European countries

The Effectiveness and Cost-Effectiveness of Spinal Cord Stimulation for Refractory Angina (RASCAL Study): A Pilot Randomized Controlled Trial

Background: Patients with “refractory angina” (RA) unsuitable for coronary revascularization experience high levels of hospitalization and poor health‐related quality of life. Randomized trials have shown spinal cord stimulation (SCS) to be a promising treatment for chronic stable angina and RA; however, none has compared SCS with usual care (UC). The aim of this pilot study was to address the key uncertainties of conducting a definitive multicenter trial to assess the clinical and cost‐effectiveness of SCS in RA patients, i.e., recruitment and retention of patients, burden of outcome measures, our ability to standardize UC in a UK NHS setting. Methods: RA patients deemed suitable were randomized in a 1:1 ratio to SCS plus UC (SCS group) or UC alone (UC group). We sought to assess: recruitment, uptake, and retention of patients; feasibility and acceptability of SCS treatment; the feasibility and acceptability of standardizing UC; and the feasibility and acceptability of the proposed trial outcome measures. Patient outcomes were assessed at baseline (prerandomization) and three and six months postrandomization. Results: We failed to meet our planned recruitment target (45 patients) and randomized 29 patients (15 SCS group, 14 UC group) over a 42‐month period across four sites. None of the study participants chose to withdraw following consent and randomization. With exception of two deaths, all completed evaluation at baseline and follow‐up. Although the study was not formally powered to compare outcomes between groups, we saw a trend toward larger improvements in both primary and secondary outcomes in the SCS group. Conclusions: While patient recruitment was found to be challenging, levels of participant retention, outcome completion, and acceptability of SCS therapy were high. A number of lessons are presented in order to take forward a future definitive pragmatic randomized trial

The effectiveness and cost-effectiveness of spinal cord stimulation for refractory angina (RASCAL study): study protocol for a pilot randomized controlled trial

Background: The RASCAL (R efractory A ngina S pinal C ord stimulation and usuAL care) pilot study seeks to assess the feasibility of a definitive trial to assess if addition of spinal cord stimulation (SCS) to usual care is clinically superior and more cost-effective than usual care alone in patients with refractory angina. Methods/design: This is an external pilot, patient-randomized controlled trial. The study will take place at three centers in the United Kingdom - South Tees Hospitals NHS Foundation Trust (The James Cook University Hospital), Dudley Group of Hospitals NHS Foundation Trust, and Basildon and Thurrock University Hospitals NHS Foundation Trust. The subjects will be 45 adults with refractory angina, that is, limiting angina despite optimal anti-angina therapy, Canadian Cardiovascular Society Functional Classification Class III and IV, angiographically documented coronary artery disease not suitable for revascularization, satisfactory multidisciplinary assessment and demonstrable ischemia on functional testing. The study will be stratified by center, age and Canadian Cardiovascular Society Functional Classification. Interventions will involve spinal cord stimulation plus usual care (‘SCS group’) or usual care alone (‘UC group’). Usual care received by both groups will include consideration of an education session with a pain consultant, trial of a transcutaneous electrical neurostimulation, serial thoracic sympathectomy and oral/systemic analgesics. Expected outcomes will be recruitment and retention rates; reasons for agreeing/declining participation; variability in primary and secondary outcomes (to inform power calculations for a definitive trial); and completion rates of outcome measures. Trial patient-related outcomes include disease-specific and generic health-related quality of life, angina exercise capacity, intake of angina medications, frequency of angina attacks, complications and adverse events, and satisfaction. Discussion: The RASCAL pilot trial seeks to determine the feasibility and design of a definitive randomized controlled trial comparing the addition of spinal cord stimulation to usual care versus usual care alone for patients with refractory angina. Fifteen patients have been recruited since recruitment opened in October 2011. The trial was originally scheduled to end in April 2013 but due to slow recruitment may have to be extended to late 2013

Spinal Cord Stimulation for Neuropathic Pain in England From 2010 to 2020: A Hospital Episode Statistics Analysis.

Spinal cord stimulation (SCS) is a recognized intervention for the management of chronic neuropathic pain. The United Kingdom National Institute of Health and Care Excellence has recommended SCS as a management option for chronic neuropathic pain since 2008. The aim of this study is to undertake an assessment of SCS uptake across the National Health Service in England up to 2020. Hospital Episode Statistics were obtained for patients with neuropathic pain potentially eligible for SCS and patients receiving an SCS-related procedure. Data were retrieved nationally and per region from the years 2010-2011 to 2019-2020. There were 50,288 adults in England attending secondary care with neuropathic pain in 2010-2011, increasing to 66,376 in 2019-2020. The number of patients with neuropathic pain with an SCS procedure increased on a year-to-year basis until 2018-2019. However, less than 1% of people with neuropathic pain received an SCS device with no evidence of an increase over time when considering the background increase in neuropathic pain prevalence. Only a small proportion of patients in England with neuropathic pain potentially eligible for SCS receives this intervention. The recommendation for routine use of SCS for management of neuropathic pain has not resulted in an uptake of SCS over the last decade

Older people presenting to the emergency department after a fall: a population with substantial recurrent healthcare use

ABSTRACT Objectives To document patient characteristics, care pathways, healthcare use and costs of fall-related emergency department (ED) presentations by older adults. Participants and methods All fallers aged $70 years, presenting to the ED of a 450-bed metropolitan university hospital in Sydney, Australia (1 April 2007 through 31 March 2009) were studied. Data were collected from the ED electronic information system, ED clinical records and the hospital electronic information system database. Population estimates for 2008 for the local areas served by the hospital were used to estimate ED presentation rates. Results Of 18 902 all-cause ED presentations, 3220 (17.0%) were due to a fall. Among fallers, 35.4% had one or more ED presentations and 20.3% had had one or more hospital admissions in the preceding 12 months. Fall-related ED presentation led directly to hospital admission in 42.7% of the cases, the majority of which (78.0%) received acute care only (length of stayd14.4 days for men and 13.7 days for women) and the remaining cases underwent further inpatient rehabilitation (length of stay 35.6 days for men and 3

A randomised trial of the effect of omega-3 polyunsaturated fatty acid supplements on the human intestinal microbiota

Objective; Omega-3 polyunsaturated fatty acids (PUFAs) have anticolorectal cancer (CRC) activity. The intestinal microbiota has been implicated in colorectal carcinogenesis. Dietary omega-3 PUFAs alter the mouse intestinal microbiome compatible with antineoplastic activity. Therefore, we investigated the effect of omega-3 PUFA supplements on the faecal microbiome in middle-aged, healthy volunteers (n=22). Design A randomised, open-label, cross-over trial of 8 weeks’ treatment with 4 g mixed eicosapentaenoic acid/docosahexaenoic acid in two formulations (soft-gel capsules and Smartfish drinks), separated by a 12-week ‘washout’ period. Faecal samples were collected at five time-points for microbiome analysis by 16S ribosomal RNA PCR and Illumina MiSeq sequencing. Red blood cell (RBC) fatty acid analysis was performed by liquid chromatography tandem mass spectrometry. Results; Both omega-3 PUFA formulations induced similar changes in RBC fatty acid content, except that drinks were associated with a larger, and more prolonged, decrease in omega-6 PUFA arachidonic acid than the capsule intervention (p=0.02). There were no significant changes in α or β diversity, or phyla composition, associated with omega-3 PUFA supplementation. However, a reversible increased abundance of several genera, including Bifidobacterium, Roseburia and Lactobacillus was observed with one or both omega-3 PUFA interventions. Microbiome changes did not correlate with RBC omega-3 PUFA incorporation or development of omega-3 PUFA-induced diarrhoea. There were no treatment order effects. Conclusion; Omega-3 PUFA supplementation induces a reversible increase in several short-chain fatty acid-producing bacteria, independently of the method of administration. There is no simple relationship between the intestinal microbiome and systemic omega-3 PUFA exposure. Trial registration number; ISRCTN18662143

Comparing mutation calls in fixed tumour samples between the Affymetrix OncoScan® Array and PCR based next-generation sequencing

Background: The importance of accurate and affordable mutation calling in fixed pathology samples is becoming increasingly important as we move into the era of personalised medicine. The Affymetrix OncoScan® Array platform is designed to produce actionable mutation calls in archival material. Methods: We compared calls made using the OncoScan platform with calls made using a custom designed PCR panel followed by next-generation sequencing (NGS), in order to benchmark the sensitivity and specificity of the OncoScan calls in a large cohort of fixed tumour samples. 392 fixed, clinical samples were sequenced, encompassing 641 PCR regions, 403 putative positive calls and 1528 putative negative calls. Results: A small number of mutations could not be validated, either due to large indels or pseudogenes impairing parts of the NGS pipeline. For the remainder, if calls were filtered according to simple quality metrics, both sensitivity and specificity for the OncoScan platform were over 98%. This applied even to samples with poorer sample quality and lower variant allele frequency (5–10%) than product claims indicated. Conclusions: This benchmarking study will be useful to users and potential users of this platform, who wish to compare technologies or interpret their own results

Screening trials of spinal cord stimulation for neuropathic pain in England—a budget impact analysis

Screening trials of spinal cord stimulation (SCS) prior to full implantation of a device are recommended by expert guidelines and international regulators. The current study sought to estimate the budget impact of a screening trial of SCS and the costs or savings of discontinuing the use of a screening trial. A budget impact analysis was performed considering a study population that reflects the size and characteristics of a patient population with neuropathic pain in England eligible for SCS. The perspective adopted was that of the NHS with a 5-year time horizon. The base case analysis indicate that a no screening trial strategy would result in cost-savings to the NHS England of £400,000–£500,000 per year. Sensitivity analyses were conducted to evaluate different scenarios. If ≥5% of the eligible neuropathic pain population received a SCS device, cost-savings would be >£2.5 million/year. In contrast, at the lowest assumed cost of a screening trial (£1,950/patient), a screening trial prior to SCS implantation would be cost-saving. The proportion of patients having an unsuccessful screening trial would have to be ≥14.4% for current practice of a screening trial to be cost-saving. The findings from this budget impact analysis support the results of a recent UK multicenter randomized controlled trial (TRIAL-STIM) of a policy for the discontinuation of compulsory SCS screening trials, namely that such a policy would result in considerable cost-savings to healthcare systems