National Institute For Health And Care Excellence Guidance Research Articles

Predicting the risk of pancreatic cancer in adults with new-onset diabetes: development and internal-external validation of a clinical risk prediction model.

The National Institute for Health and Care Excellence (NICE) recommends that people aged 60+ years with newly diagnosed diabetes and weight loss undergo abdominal imaging to assess for pancreatic cancer. More nuanced stratification could lead to enrichment of these referral pathways. Population-based cohort study of adults aged 30-85 years at type 2 diabetes diagnosis (2010-2021) using the QResearch primary care database in England linked to secondary care data, the national cancer registry and mortality registers. Clinical prediction models were developed to estimate risks of pancreatic cancer diagnosis within 2 years and evaluated using internal-external cross-validation. Seven hundred and sixty-seven of 253,766 individuals were diagnosed with pancreatic cancer within 2 years. Models included age, sex, BMI, prior venous thromboembolism, digoxin prescription, HbA1c, ALT, creatinine, haemoglobin, platelet count; and the presence of abdominal pain, weight loss, jaundice, heartburn, indigestion or nausea (previous 6 months). The Cox model had the highest discrimination (Harrell's C-index 0.802 (95% CI: 0.797-0.817)), the highest clinical utility, and was well calibrated. The model's highest 1% of predicted risks captured 12.51% of pancreatic cancer cases. NICE guidance had 3.95% sensitivity. A new prediction model could have clinical utility in identifying individuals with recent onset diabetes suitable for fast-track abdominal imaging.

A thematic analysis of National Institute for Health and Care Excellence responses to coroners’ concerns’

In England and Wales, law requires that coroners issue a Prevention of Future Death (PFD) report when they believe that action should be taken to prevent future deaths. Prevention of Future Death reports therefore provide an opportunity to learn and prevent harm. This study thematically analyses PFD reports received by the National Institute for Health and Care Excellence (NICE) along with the organisation's response. We undertook a framework analysis of PFD reports, the organisation's response, and supporting documents or correspondence. Our framework was developed with a deductive approach, with themes pre-selected using areas of interest to the inquiry, including NHS England's national standards for patient safety investigation. The review includes 39 reports dated from 2012 to 2020. Common health areas involved were intrapartum care and head injuries. Coroners frequently raised the issue of a lack of relevant NICE guidance, with NICE most often committing to reflecting on the issues raised through its established processes. Recent responses demonstrated greater consideration of implementation and engagement actions, along with a more collaborative approach and person-centred tone. This report provides insight into the PFD report practices of a national guidance producing and standard setting body in the UK. The report supports system-level understanding of current practices in relation to PFD reports. However, there are no means to assess if the Chief Coroner's Office and the wider safety system considered them an adequate response or whether the actions taken were effective. Recommendations are made to support transparency, learning and collaboration in an evolving patient safety landscape.

Machine Learning Applied to Cholesterol-Lowering Pharmacotherapy: Proof-of-Concept in High-Risk Patients Treated in Primary Care.

Objectives: Machine learning has potential to improve the management of lipid disorders. We explored the utility of machine learning in high-risk patients in primary care receiving cholesterol-lowering medications. Methods: Machine learning algorithms were created based on lipid management guidelines for England [National Institute for Health and Care Excellence (NICE) CG181] to reproduce the guidance with >95% accuracy. Natural language processing and therapy identification algorithms were applied to anonymized electronic records from six South London primary care general practices to extract medication information from free text fields. Results: Among a total of 48,226 adult patients, a subset of 5630 (mean ± standard deviation, age = 67 ± 13 years; male:female = 55:45) with a history of lipid-lowering therapy were identified. Additional major cardiometabolic comorbidities included type 2 diabetes in 13% (n = 724) and hypertension in 32% (n = 1791); all three risk factors were present in a further 28% (n = 1552). Of the 5630 patients, 4290 (76%) and 1349 (24%) were in primary and secondary cardiovascular disease prevention cohorts, respectively. Statin monotherapy was the most common current medication (82%, n = 4632). For patients receiving statin monotherapy, 71% (n = 3269) were on high-intensity therapy aligned with NICE guidance with rates being similar for the primary and secondary prevention cohorts. In the combined cohort, only 46% of patients who had been prescribed lipid-lowering therapy in the previous 12 months achieved the NICE treatment goal of >40% reduction in non-high-density lipoprotein cholesterol from baseline pretreatment levels. Based on the most recent data entry for patients not at goal the neural network recommended either increasing the dose of statin, adding complementary cholesterol-lowering medication, or obtaining an expert lipid opinion. Conclusions: Machine learning can be of value in (a) quantifying suboptimal lipid-lowering prescribing patterns, (b) identifying high-risk patients who could benefit from more intensive therapy, and (c) suggesting evidence-based therapeutic options.

427 Systemic Imaging for Early Laryngeal Cancer; a Single Centre Review of Guideline Application in Contemporary Clinical Practice

Abstract Aim Early-stage laryngeal cancer (T1 and T2) has low rate of locoregional and distant metastasis. Therefore, National Institute for Health and Care Excellence (NICE) guidelines were updated in 2016 and recommended to no longer offer systemic staging for early laryngeal cancer because systemic imaging was not deemed to be cost effective. Our study aims to evaluate (1) if NICE guidance on the role of systemic imaging in the assessment and management of early laryngeal cancer is being followed in our centre (2) assess the impact of this practice on our patients (3) perform a cost analysis relevant to our institution. Method We retrospectively reviewed all laryngeal cases at a major H&N cancer centre between 01/01/2020 and 01/01/2022. The following information was collected for all the patients: neck/systemic imaging modalities performed on patients, demographics, site of original laryngeal tumour and any metastatic disease detected by systemic imaging. Next, we performed a cost analysis based on the cost analysis method undertaken by NICE. Results Our results showed n = 83 patients had laryngeal cancer between 01/01/2020 and 01/01/2022. Of which n = 30 had T1N0 and T2N0 disease. Systemic imaging found no metastatic disease, however n = 2 primary lung tumours and n = 1 lung infection was detected. The total cost for systemic imaging was £4,207.12 and total cost for neck imaging investigations it was £12,335.07. Conclusions Our study concludes NICE guidance is not being followed at our centre. Systemic imaging provides little benefit to patients and is an expensive practice.

Exploring the cost-effectiveness of case-finding for antenatal depression: an economic modelling study.

The NHS has limited human and financial resources, with particular pressures in primary care. The National Institute for Health and Care Excellence (NICE) makes decisions on which services can be commissioned within the NHS. Many women experiencing antenatal depression are not identified as such in routine care and so may not access support. Current NICE guidance does not recommend universal case-finding for antenatal depression; however, a programme targeted towards pregnant women with risk factors (for example, previous mental illness, traumatic life events) has not been considered. To explore the cost-effectiveness of case-finding for antenatal depression: targeted vs. universal vs. no case-finding. The following case-finding tools were evaluated: Edinburgh Postnatal Depression Scale, Whooley questions, PHQ-9. One- and two-stage strategies were considered (second tool administered following positive response to Whooley questions). A decision tree model of costs and health outcomes from 20-40 weeks' gestation was developed. Health was measured as quality-adjusted-life-years (QALYs). Costs included case-finding and treatment for depression. The two-stage Whooley/PHQ-9 option was the most cost-effective case-finding strategy. Implementing a universal case-finding strategy was associated with lower costs than no case-finding (£52 vs £61) and more QALYs (0.3458 vs 0.3455). Targeted case-finding has similar costs to no case-finding and more QALYs (0.3459), requiring a spend of £1775 to improve health by 1 QALY. Universal case-finding for antenatal depression is cost-saving and improves health compared with no case-finding. It should be considered by policymakers to improve the identification and support of women experiencing antenatal depression in primary and maternity care.

P59 Results of sentinel lymph node biopsies in thin melanomas (Breslow thickness 0.8–1.0 mm) and correlation with histopathological features

Abstract In July 2022, the National Institute for Health and Care Excellence (NICE) melanoma guidelines were updated to include recommendation for a sentinel lymph node (SLN) biopsy for those with a Breslow thickness of 0.8–1 mm and at least one of the following: ulceration, lymphovascular invasion and/or a mitotic index of ≥ 2 mm². SLN biopsy is a staging procedure and therefore has an impact on prognosis. However, SLN biopsy is an invasive procedure with associated morbidity. A 5-year retrospective review of melanoma data in the south east of Ireland was undertaken to establish the correlation between positive sentinel lymph node biopsies in 0.8–1.0-mm-thick melanomas and the risk factors outlined above. Melanoma outcomes, histopathology reports and outpatient clinic letters were assessed and data were extracted from 1 January 2018 to 31 December 2022 inclusive. A total of 52 patients were identified with a melanoma of Breslow thickness of 0.8–1 mm from the predetermined timeframe. Eight per cent (n = 4) of lesions were ulcerated. Thirteen per cent (n = 7) had a mitotic index of ≥ 2 mm². One lesion was both ulcerated and had a mitotic index of ≥ 2 mm². No lesions demonstrated lymphovascular invasion. Nineteen (36%) patients underwent SLN biopsy. All patients who underwent SLN biopsy were negative. One patient with an ulcerated melanoma did not undergo SLN biopsy and five with a mitotic index of ≥ 2 did not undergo SLN biopsy. There was no evidence of disease recurrence within the follow-up period (2 months–5 years). This population showed a 0% positivity rate on SLN biopsy. No correlation with mitotic index or ulceration and SLN biopsy was identified. No patients have developed local recurrence or metastatic disease within the follow-up period. This study supports the updated NICE guidance recommending SLN biopsies for thicker melanomas (i.e. Breslow thickness > 1.0 mm) and SLN biopsy in thinner melanomas (Breslow thickness 0.8–1 mm) only if concerning features are present on histology (i.e. ulceration, lymphovascular invasion and/or a mitotic index of ≥ 2).

Eye movement desensitisation and reprocessing as a treatment for PTSD, trauma, and trauma related symptoms in children with intellectual disabilities: a general review

PurposeThis paper aims to discuss the utility of eye movement desensitization and reprocessing (EMDR) therapy as a treatment for children with intellectual disabilities (ID) who have experienced trauma.Design/methodology/approachRelevant National Institute for Health and Care Excellence (NICE) guidance and literature were reviewed to provide support for the use of EMDR as a treatment for trauma in children with ID.FindingsThere is a growing body of evidence which demonstrates that EMDR therapy is successful for the treatment of trauma in adults and children. However, for children with ID, the research is limited despite those with ID being more likely than non-disabled peers to experience trauma such as abuse or neglect.Practical implicationsEMDR can only be facilitated by trained mental health nurses, psychiatrists, psychologists (clinical, forensic, counselling or educational) or occupational therapists or social workers with additional training. Finally, general practitioners who are experienced in psychotherapy or psychological trauma and have accreditation. Therefore, this highlights that there may be a lack of trained staff to facilitate this intervention and that those who are generally working with the client closely and long term such as learning disability nurses are not able to conduct this intervention.Originality/valueThis paper presents an account of NICE guidance and evidence of the efficacy of EMDR as a treatment for adults, children and those with ID.

CycLing and EducATion (CLEAT): protocol for a single centre randomised controlled trial of a cycling and education intervention versus standard physiotherapy care for the treatment of hip osteoarthritis

BackgroundOsteoarthritis (OA) is a chronic degenerative joint disorder for which there is no known cure. Non-surgical management for people with mild-to-moderate hip OA focuses mainly on alleviating pain and maximising function via the National Institute for Health and Care Excellence (NICE) recommended combination of education and advice, exercise, and, where appropriate, weight loss. The CHAIN (Cycling against Hip pAIN) intervention is a group cycling and education intervention conceived as a way of implementing the NICE guidance.MethodsCycLing and EducATion (CLEAT) is a pragmatic, two parallel arm, randomised controlled trial comparing CHAIN with standard physiotherapy care for the treatment of mild-to-moderate hip OA. We will recruit 256 participants referred to the local NHS physiotherapy department over a 24-month recruitment period. Participants diagnosed with hip OA according to NICE guidance and meeting the criteria for GP exercise referral will be eligible to participate. Primary outcome is the difference in Hip Disability and Osteoarthritis Outcome Score (HOOS) function, daily living subscale between those receiving CHAIN and standard physiotherapy care. Secondary outcomes include performance-based functional measures (40 m walking, 30s chair stand and stair climb tests), ability for patient to self-care (patient activation measure) and self-reported health-related resource use including primary and secondary care contacts. The primary economic endpoint is the number of quality adjusted life years (QALYs) at 24 weeks follow-up. The study is funded by the National Institute for Health Research, Research for Patient Benefit PB-PG-0816-20033.DiscussionThe literature identifies a lack of high-quality trials which inform on the content and design of education and exercise in the treatment of patients with hip OA and explore cost-effectiveness. CLEAT is a pragmatic trial which seeks to build further evidence of the clinical benefits of the CHAIN intervention compared to standard physiotherapy care within a randomised, controlled trial setting, and examine its cost-effectiveness.Trial registration numberISRCTN19778222. Protocol v4.1, 24th October 2022.

Oral Azacitidine for Maintenance Treatment of Acute Myeloid Leukaemia After Induction Therapy: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

The National Institute for Health and Care Excellence (NICE) invited the manufacturer (Celgene) of oral azacitidine (ONUREG), as part of the Single Technology Appraisal (STA) process, to submit evidence for the clinical effectiveness and cost-effectiveness of oral azacitidine for maintenance treatment of acute myeloid leukaemia (AML) after induction therapy compared with watch-and-wait plus best supportive care (BSC) and midostaurin. Kleijnen Systematic Reviews Ltd, in collaboration with Maastricht University Medical Centre+, was commissioned to act as the independent Evidence Review Group (ERG). This paper summarises the company submission (CS), presents the ERG's critical review on the clinical and cost-effectiveness evidence in the CS, highlights the key methodological considerations and describes the development of the NICE guidance by the Appraisal Committee. In the QUAZAR AML-001 trial, oral azacitidine significantly improved overall survival (OS) versus placebo: median OS gain of 9.9months (24.7months versus 14.8months; hazard ratio (HR) 0.69 (95% CI 0.55-0.86), p < 0.001). The median time to relapse was also better for oral azacitidine, and the incidences of TEAEs were similar for the two arms. The company excluded two of the comparators listed in the scope, low-dose cytarabine and subcutaneous azacitidine, informed only by clinical expert opinion, leaving only best supportive care (BSC) and midostaurin for the FLT3-ITD and/or FLT3-TKD (FLT3 mutation)-positive subgroup. An ITC comparing oral azacitidine to midostaurin as maintenance therapy in the appropriate subgroup demonstrated that the OS and relapse-free survival (RFS) HRs were favourable for oral azacitidine when compared with midostaurin. However, in the only available trial of midostaurin as maintenance treatment in AML that was used for this ITC, subjects were not randomised at the maintenance phase, but at induction, which posed a substantial risk of bias. The revised and final probabilistic incremental cost-effectiveness ratio (ICER) presented by the company, including a commercial arrangement, was £32,480 per quality-adjusted life year (QALY) gained for oral azacitidine versus watch-and-wait plus BSC. Oral azacitidine was dominant versus midostaurin in the FLT-3 subgroup. The ERG's concerns included the approach of modelling haematopoietic stem cell transplantation (HSCT), the generalisability of the population and the number of cycles of consolidation therapy pre-treatment in the QUAZAR AML-001 trial to UK clinical practice, and uncertainty in the relapse utility. The revised and final ERG base case resulted in a similar probabilistic ICER of £33,830 per QALY gained versus watch-and-wait plus BSC, but with remaining uncertainty. Oral azacitidine remained dominant versus midostaurin in the FLT-3 subgroup. After the second NICE appraisal committee meeting, the NICE Appraisal Committee recommended oral azacitidine (according to the commercial arrangement), within its marketing authorisation, as an option for maintenance treatment for AML in adults who are in complete remission, or complete remission with incomplete blood count recovery, after induction therapy with or without consolidation treatment, and cannot have or do not want HSCT.

A diagrammatic summary of updated NICE melanoma guidance: A simple way to mitigate human factors in MDTs and clinics

National Institute for Health and Care Excellence (NICE) has published an updated guideline on melanoma assessment and management in July 2022, which has included recommendation on BRAF analysis of primary melanoma tissue samples, staging with sentinel lymph node biopsy, guidance on patient follow-up as well as surveillance imaging requirement based on patients' melanoma stages. However, very often, assimilating this considerable amount of information in an efficient and accurate way can be challenging, especially in the setting of a busy multidisciplinary team (MDT) meeting. Human factors are well recognised as a key principle to mitigate against mistakes and human errors and thereby aiming to optimise patient care. To date, there is very limited literature available on the subject of the role of human factors in the context of MDT meetings. In recent years, the numbers and complexity of patients in cancer MDT meetings have grown significantly. Long MDT meetings could lead to distraction, loss of attention span, miscommunication, missed information, and hence increasing the risk of clinical error. We present a diagrammatic summary of the most recent NICE guidance for melanoma follow-up that is currently being used locally in our department. This aims to offer clarity and ease of use to help health care professionals to check patients' treatment pathways. It can also be included in patients' medical record for annotation or reference in future follow-up clinics, which is a simple measure to mitigate the risks of human factors, as well as ensuring consistency in continuity of patient care.

Abemaciclib in Combination with Endocrine Therapy for Adjuvant Treatment of Hormone Receptor-Positive, HER2-Negative, Node-Positive Early Breast Cancer: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

The National Institute for Health and Care Excellence (NICE) invited the manufacturer (Eli Lilly) of abemaciclib (Verzenios) to submit evidence for the clinical and cost effectiveness of this drug in combination with endocrine therapy (ET) for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-positive early breast cancer at high risk of recurrence, as part of the Institute's Single Technology Appraisal (STA) process. Kleijnen Systematic Reviews Ltd, in combination with Newcastle University, was commissioned to act as the independent Evidence Review Group (ERG). This paper summarised the Company Submission (CS), presents the ERG's critical review of the clinical and cost-effectiveness evidence in the CS, highlights the key methodological considerations, and describes the development of the NICE guidance by the Appraisal Committee. The ERG produced a critical review of the evidence for the clinical and cost-effectiveness evidence in the CS and also independently searched for relevant evidence and modified the manufacturer decision analytic model to examine the impact of altering some of the key assumptions. A systematic literature review identified the MonarchE trial, an ongoing, open-label, randomised, double blind trial involving 5637 people comparing abemaciclib in combination with ET versus ET alone. The trial included two cohorts that used different inclusion criteria to define high risk of recurrence. The ERG considered Cohort 1 as an adequate representation of this population and the AC concluded that Cohort 1 was generalisable to National Health Service clinical practice. Trial results showed improvements in invasive disease-free survival for the abemaciclib arm, which was considered an appropriate surrogate outcome. The ERG believed that the modelling structure presented in the de novo economic model by the company was appropriate but highlighted several areas of uncertainty that had the potential to have a significant impact on the resulting incremental cost-effectiveness ratio (ICER). Areas of uncertainty included the extrapolation of long-term survival curves, the duration of treatment effect and treatment waning, and the proportion of patients who receive other CDK4/6 treatments for metastatic disease after receiving abemaciclib. ICER estimates were £9164 per quality-adjusted life-year gained for the company's base-case and £17,810 for the ERG's base-case. NICE recommended abemaciclib with ET as an option for the adjuvant treatment of HR-positive, HER2-negative, node-positive early breast cancer at high risk of recurrence.

Pralsetinib for RET Fusion-Positive Advanced Non-small-Cell Lung Cancer: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

The National Institute for Health and Care Excellence (NICE) invited the manufacturer (Roche) of pralsetinib (Gavreto®), as part of the single technology appraisal (STA) process, to submit evidence for the clinical effectiveness and cost effectiveness of pralsetinib for the treatment of adult patients with rearranged during transfection (RET) fusion-positive advanced non-small-cell lung cancer (NSCLC) not previously treated with a RET inhibitor. Kleijnen Systematic Reviews Ltd, in collaboration with University Medical Center Groningen, was commissioned to act as the independent Evidence Review Group (ERG). This paper summarizes the company submission (CS), presents the ERG's critical review of the clinical and cost-effectiveness evidence in the CS, highlights the key methodological considerations, and describes the development of the NICE guidance by the Appraisal Committee. The CS reported data from the ARROW trial. ARROW is a single-arm, multicenter, non-randomized, open-label, multi-cohort study in patients with RET fusion-positive NSCLC and other advanced solid tumors. The CS included both untreated and pre-treated RET fusion-positive NSCLC patients, among other disease types. The comparators in the untreated population were pembrolizumab + pemetrexed + chemotherapy and pembrolizumab monotherapy. The comparators for the pre-treated population were docetaxel monotherapy, docetaxel + nintedanib, and platinum-based chemotherapy ± pemetrexed. As no comparators were included in ARROW, an indirect treatment comparison was conducted to estimate relative effectiveness. The ERG's concerns included the immaturity of data, small sample size, and lack of comparative safety evidence. The ERG considers the clinical evidence presented to be insufficiently robust to inform the economic model. Even when all the ERG preferred assumptions were implemented in the model, uncertainty remained on a number of issues, such as the appropriateness of the hazard ratios and the methods and data used to derive them, long-term efficacy of pralsetinib, and direct evidence for health-related quality of life (HRQoL). NICE did not recommend pralsetinib within its marketing authorization for treating RET fusion-positive advanced non-small-cell lung cancer (NSCLC) in adults who have not had a RET inhibitor before. The uncertainty of the clinical evidence and the estimates of cost effectiveness were too high to be considered a cost-effective use of NHS resources. Therefore, pralsetinib was not recommended for routine use.

Subarachnoid haemorrhage caused by a ruptured aneurysm: diagnosis and management. NG 228. Commentary on the role of CT in diagnosis of subarachnoid haemorrhage for patients presenting within 6 h of thunderclap headache

The National Institute for Health and Care Excellence (NICE) have recently (23/11/22) published guidance that covers the diagnosis and management of patients that present with subarachnoid haemorrhage (SAH) due to rupture of a brain aneurysm. 1 NICE Subarachnoid haemorrhage caused by a ruptured aneurysm: diagnosis and management. NICE guideline [NG228]. Published: 23 November. 2022; (https://www.nice.org.uk/guidance/ng228 (accessed 30/12/2022)) Google Scholar NICE guidance provides critically reviewed evidence-based information for commissioners, for all healthcare professionals involved in the care of patients with aneurysmal SAH, for patients, their families, and carers.

Step-Wise Management of Anemia in Patients With Chronic Kidney Disease in Primary Care: Qualitative Study.

Anemia is common in chronic kidney disease (CKD) and is associated with increased cardiovascular risk and reduced quality of life, but is often sub-optimally managed. Most patients are managed in primary care alongside other comorbidities. Interventions to improve the management of anemia in CKD in this setting are needed. We conducted a qualitative study to evaluate how an audit-based education (ABE) intervention might improve the management of anemia in CKD. We explored outcomes that would be relevant to practitioners and patients, that exposed variation of practice from National Institute for Health and Care Excellence (NICE) guidelines, and whether the intervention was feasible and acceptable. Practitioners (n = 5 groups) and patients (n = 7) from 4 London general practices participated in discussions. Practitioners welcomed the evidence-based step-wise intervention. However, prescribing erythropoiesis-stimulating agents (ESAs) was felt to be outside of their scope of practice. There was a gap between NICE guidance and clinical practice in primary care. Iron studies were not well understood and anemia management was often conservative or delayed. Patients were often unaware of having CKD, and were more concerned about their other comorbidities, but largely trusted their GPs to manage them appropriately. The first steps of the intervention were welcomed by practitioners, but they expressed concerns about independently prescribing ESAs. Renal physicians and GPs could develop shared care protocols for ESA use in primary care. There is scope to improve awareness of renal anemia, and enhance knowledge of guideline recommendations; and our intervention should be modified accordingly.

Draft NICE guidance says statins can now be considered for people at lower risk of cardiovascular disease

More patients could be considered for statin therapy to prevent cardiovascular disease (CVD) under updated draft guidelines from the National Institute for Health and Care Excellence (NICE). The draft guidance, which is an update to existing guidance on risk assessment and reduction in cardiovascular disease, includes a new recommendation that statins can now […]

PD17 Automating The Impact Reporting Of NICE Guidance

IntroductionThe National Institute for Health and Care Excellence (NICE) intends to automate the way it monitors the uptake, impact, and value of its guidance. Traditionally this has been done by developing impact reports, long documents that, while well received, are time consuming to develop and can quickly become outdated.MethodsWe focused on a novel topic that would benefit from new data sources to examine its impact: a rapid guideline for managing the long-term effects of coronavirus disease 2019 (COVID-19). We shortlisted “measurable” recommendations within the guideline that were likely to be captured in data collections. We then reviewed available data sources that included relevant up-to-date data. Finally, we explored what existing methods were available to NICE for automating impact reporting.ResultsFor long COVID-19 we accessed OpenSAFELY, a secure, transparent software platform for primary care COVID-19 data that was developed in response to the pandemic. This captured data on the management of long COVID-19 in primary care as well as onward referral to specialist clinics. In addition, we accessed data from the CVD-COVID-UK/COVID-IMPACT Consortium, which links general practice records with primary care dispensing data. This enabled us to analyze the impact of the pandemic on the prescribing and dispensing of cardiovascular disease medications. Working with our digital team we developed an automated impact reporting dashboard using Google’s data studio. This enabled different views of the data, for example by region or socioeconomic status, to be presented in an automated way.ConclusionsAutomating the impact reporting of NICE guidance provides up-to-date information on its value to the health system. While we were able to collect new sources of data and automate some aspects of how these were viewed, full automation requires several enablers. These include an application programming interface between the data sources and NICE, and ensuring that NICE guidance is computer readable so that its measurement is practical in healthcare systems.

OP64 NICE Listens: Engaging The Public On How To Address Health Inequalities In Health Technology Assessment And Guideline Development

IntroductionInvolving and engaging the public is an essential step to engender trust and confidence in HTA organizations. In 2021 the National Institute for Health and Care Excellence (NICE) launched NICE Listens, a new programme of deliberative public engagement seeking to address topics that have complex social, moral, or ethical dimensions. Health inequalities (HI), defined as unfair and avoidable differences in health across populations, was the first topic. The aim was to understand how the public would like NICE to act in regard to HI. Despite repeated attempts to tackle HI in England, the gaps in life expectancy between the most and least deprived continue to widen. NICE has committed to addressing HI in its five-year strategy and NICE Listens forms part of a comprehensive engagement strategy to understand how best to do this.MethodsTwenty-eight (28) members of the public from across England took part in four iterative two-hour online workshops, held fortnightly in late 2021. They consisted of both plenary and breakout sessions and incorporated a range of stimuli including trade-off exercises and interview clips with HI experts.ResultsThe findings show clear public support for HI being a high priority for NICE, albeit with limits on how and when HI should be addressed. Actions towards reducing HI should focus on supporting a preventative and systemic response. Importantly, there is a need for a transparent process for incorporating HI within NICE guidance as well as rigorous staff training in understanding and addressing HI. Recommending technologies that benefit the majority even when not accessible for all is acceptable if there are clear plans to manage access gaps.ConclusionsReducing health inequalities should be a high priority for NICE and other HTA organizations. Organizations should seek to have clear processes for embedding HI in decision-making. Priority should be given to actions that focus on prevention of ill health and those that have wider system impacts.

OP92 Impact Of Real-World Evidence On Health Technology Assessment And National Guidance For Interventional Procedures: A UK Perspective

IntroductionThe National Institute for Health and Care Excellence (NICE) interventional procedures programme (IPP) issues guidance on the safety and efficacy of new interventional procedures (IPS). The IPP considers a range of evidence from randomized controlled trials (RCTs) to case series to make final recommendations. Real-world evidence (RWE) can provide additional information on long-term outcomes and patient population characteristics that are not easily captured by RCTs. This study explores the impact of RWE in complementing RCTs on long-term safety and efficacy for national guidance development.MethodsWe review the impact of RWE in IPS guidance (IPG) updates and change in guidance recommendations in the last 5 years. This is done by analyzing NICE guidance updates and supporting evidence. A range of RWE was considered in the supporting evidence, for example, registries and clinical audits.ResultsThe addition of RWE evidence to IPP guidance update has led to significant changes in the recommendations. For example, in one recent IPG, standard arrangements recommendation based on short-term RCT evidence was changed to a research recommendation when RWE showed an increase in long-term adverse effects. In another recent IPG update, special arrangements recommendation based on short-term RCT evidence was changed to a research recommendation when RWE reported long-term inferior efficacy and safety for the new intervention compared to current standard of care. A complete overview of results of the last 5 years will also be presented at the meeting.ConclusionsThese findings indicate that increased availability of RWE in HTA has the potential to impact national guidance recommendations. In addition, it shows how RWE can fill the evidence base gaps created by RCTs. Such data can confirm or contradict the findings of RCTs, or generate questions needing further research, or support disinvestment in non-effective technologies.

Fenfluramine for Treating Dravet Syndrome: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

Fenfluramine, tradename Fintepla®, was appraised within the National Institute for Health and Care Excellence (NICE) single technology appraisal (STA) process as Technology Appraisal 808. Within the STA process, the company (Zogenix International) provided NICE with a written submission and a mathematical health economic model, summarising the company's estimates of the clinical effectiveness and cost-effectiveness of fenfluramine for patients with Dravet syndrome (DS). This company submission (CS) was reviewed by an evidence review group (ERG) independent of NICE. The ERG, Kleijnen Systematic Reviews in collaboration with Maastricht University Medical Centre, produced an ERG report. This paper presents a summary of the ERG report and the development of the NICE guidance. The CS included a systematic review of the evidence for fenfluramine. From this review the company identified and presented evidence from two randomised trials (Study 1 and Study 1504), an open-label extension study (Study 1503) and 'real world evidence' from a prospective and retrospective study. Both randomised trials were conducted in patients up to 18 years of age with DS, whose seizures were incompletely controlled with previous anti-epileptic drugs. A Bayesian network meta-analysis was performed to compare fenfluramine with cannabidiol plus clobazam. There was no evidence of a difference between any doses of fenfluramine and cannabidiol in the mean convulsive seizure frequency (CSF) rate during treatment. However, fenfluramine increased the number of patients achieving ≥50% reduction in CSF frequency from baseline compared to cannabidiol. The company used an individual-patient state-transition model (R version 3.5.2) to model cost-effectiveness of fenfluramine. The CSF and convulsive seizure-free days were estimated using patient-level data from the placebo arm of the fenfluramine registration studies. Subsequently, a treatment effect of either fenfluramine or cannabidiol was applied. Utility values for the economic model were obtained by mapping Pediatric Quality of Life Inventory data from the registration studies to EuroQol-5D-3L Youth (EQ-5D-Y-3L). The company included caregiver utilities in their base-case, as the severe needs of patients with DS have a major impact on parents and caregivers. There were several key issues. First, the company included caregiver utilities in the model in a way that when patients in the economic model died, the corresponding caregiver utility was also set to zero. Second, the model was built in R statistical software, resulting in transparency issues. Third, the company assumed the same percentage reduction for convulsive seizure days as was estimated for CSF. Fourth, during the final appraisal committee meeting, influential changes were made to the model that were not in line with the ERG's preferences (but were accepted by the appraisal committee). The company's revised and final incremental cost effectiveness ratio(ICER) in line with committee preferences resulted in fenfluramine dominating cannabidiol. Fenfluramine was recommended as an add-on to other antiepileptic medicines for treating seizures associated with DS in people aged 2 years and older in the National Health Service(NHS).

Using 5 consecutive years of NICE guidance to describe the characteristics and influencing factors on the economic evaluation of orphan oncology drugs.

ObjectiveOrphan oncology drugs used in this article were defined by the type of disease treated by drugs, as drugs used to treat rare diseases with a prevalence of ≤ 500 per million people per year. In this article, our concern was to explore focus on the economic evaluation of the National Institute for Health and Care Excellence (NICE), when orphan oncology drugs were appraised for reimbursement, and provide advice and suggestions to decision-makers.MethodsA retrospective study was used in this study. Thirty guidance were gathered as our subject by NICE from 2016 to 2020, excluded drugs were not identified as orphan by European Medicines Agency (EMA) and orphan drugs were not used for cancer, and orphan oncology drugs were terminated at the time of data collection at NICE. Qualitative analysis, descriptive statistics, and Fisher's exact test were conducted.ResultsOf all guidance, the partitioned survival model was used most to appraise orphan oncology drugs, and every drug had a kind of commercial arrangement such as patient access scheme (PAS), managed access arrangements (MAAs), and commercial access agreement (CAAs). End of life is an important indicator that had been defined by NICE in the methods of technology appraisal in 2013, and drugs that met the criterion would be given a higher threshold of ICER. In addition, we found that potential health benefits were increasingly concerned such as drug delivery.ConclusionIn the setting of uncertain clinical and cost efficacy, orphan oncology drugs are comprehensively evaluated in multiple additional dimensions, which include life-extending benefits, and innovation. NICE uses a combination of special considerations for incomplete data, appropriate economic models, and appropriate health technology assessment (HTA) methods during the assessment process, besides, orphan oncology drugs with insufficiency evidence were recommended Cancer Drugs fund (CDF) to afford for patients, which would obtain more availability and accessibility, based on which, high-quality drugs for treating rare cancers can fall within the scope of affordable healthcare provided by the English medical insurance fund.