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Vitamin B12 (cobalamin; B12) is an essential micronutrient, but deficiency is common. The prompt diagnosis and treatment of B12 deficiency protects against megaloblastic anaemia, neuropathy and neuropsychiatric changes. Biomarkers of B12 status include the measurement of serum B12 (also known as total B12 or serum cobalamin), holotranscobalamin (holoTC or 'active B12'), methylmalonic acid (MMA) and total plasma homocysteine (Hcy). There is no 'gold standard' test for deficiency and the sensitivity and specificity of each biomarker for the evaluation of B12 status is affected by analytical and biological factors that may confer a high degree of diagnostic uncertainty. Limited access to technical and clinical expertise can lead to an over-reliance on the serum B12 test, which is readily available and highly automated. In some cases, the sequential use of different B12 status biomarkers or the calculation of a composite B12 status score, derived from a panel of B12 biomarkers and adjusted for folate status and age, can be used to detect deficient states that may otherwise be overlooked when using a single biomarker approach. This review summarizes the utility of B12-related biomarkers and describes approaches to their application and interpretation. [ABSTRACT FROM AUTHOR]

The UK National Institute for Health and Care Excellence (NICE) guidance for the treatment of depression is widely followed and has international influence. According to these guidelines, antidepressant medications are recommended for moderate to severe depression. Nonetheless, antidepressants are increasingly prescribed, including for cases of subthreshold and mild depression. This may indicate that a proportion of depressed patients uses pharmacological interventions with unclear evidence-base, though other factors such as physical and mental health comorbidities need to be accounted for. This study aims to investigate the prevalence and trends of antidepressant prescriptions among community-dwelling adults diagnosed with depression according to NICE recommendations. We conducted a systematic review of PsycInfo, PubMed/MEDLINE, and Scopus databases. Observational studies reporting on the prevalence of antidepressant treatments in UK adults diagnosed with depression were sought. Fifteen studies were included. The prevalence of antidepressants for depression treatment ranged from 30.8 to 95% and mainly concerned selective serotonin reuptake inhibitors (SSRIs) among classes of antidepressant drugs. Little information about depression severity as well as comorbid conditions was reported. High prevalence rates of antidepressant drug use highlight the widespread adoption of pharmacological interventions, while also raising concerns about compliance with NICE guidelines. Careful assessment of depressive illness severity and comorbidities is needed to ensure the delivery of adequate care to people with depression. Systematic Review Registration Number (PROSPERO) CRD42023448152. Highlights: This is a systematic review of the prevalence of antidepressant prescriptions for depression in the UK adult population. We found prevalence rates between 30.8% and 95% and a lack of reporting of reporting of depression severity, which questions the adherence to severity-based treatment strategy recommended by NICE. The focus of this study is limited to the adult population in the United Kingdom. The possible use of overlapping datasets for the included studies advises against data pooling. [ABSTRACT FROM AUTHOR]

Background: By 2030, projections indicate that nearly half of USS adults will be obese, with 29 states exceeding a 50% obesity rate. High Body Mass Index (BMI) presents particular challenges in treating diverticulitis, including worsened symptoms and increased risk of surgical complications. The Robotic Natural orifice Intracorporeal Anastomosis with Transrectal Extraction (NICE) procedure has been developed for colorectal surgeries to tackle these challenges. This study evaluates the efficacy of the Robotic NICE procedure in achieving comparable surgical outcomes in patients with both high and normal BMI. Methods: This retrospective cohort study assessed the outcomes of robotic-assisted colectomy utilizing the NICE technique in patients with diverticulitis, dividing them into two groups based on BMI: high BMI (≥ 30 kg/m^2) and non-high BMI (< 30 kg/m^2). Results: Among the 194 patients analyzed, the incidence of complicated diverticulitis was significantly higher in the high BMI group (60.5%) compared to the non-high BMI group (39%; p = 0.003).The high BMI group had higher ASA scores, indicating sicker patients. The high BMI group also had a significantly higher rate of unplanned operations within 30 days (7.9% vs. 1.7%, p = 0.034). However, no significant differences were observed in the length of hospital stay, time to first flatus, or ICU admission rates between the two groups. Binary logistic regression highlighted the length of stay as a significant predictor of postoperative complications (Odds Ratio: 1.9686, 95% CI: 1.372–2.825, p < 0.001). Other factors, including age, operative time, and gender, did not significantly predict complications. Conclusion: The findings suggest that the Robotic NICE procedure can mitigate some of the challenges typically associated with conventional minimally invasive surgery in which abdominal wall incision is made, providing consistent outcomes regardless of BMI. Further research is needed to explore long-term benefits, aiming to establish this approach as a standard for managing diverticulitis in our patient population. [ABSTRACT FROM AUTHOR]

Abstract Background and aims The NICE Highly Specialised Technology (HST) programme evaluates interventions for very rare conditions within the UK. This review aimed to analyse previous NICE HST appraisals and determine commonly used methods to overcome uncertainties relating to health-related quality of life (HRQoL) and disease burden for people with rare diseases and their caregivers. The review also aimed to identify areas where further methodological development is required. Approach and results A targeted review of all previous NICE HST appraisals published by the 28th February 2022, in which at least one committee meeting had taken place, was conducted. A total of 24 appraisals were included (17 fully completed and seven ongoing). Data were extracted by one reviewer. The evidence review group (ERG) and committee comments were compared against the NICE reference case and synthesised to identify the following methodological uncertainties that occurred most commonly: using alternatives to the EuroQol-5 Dimension (EQ-5D), sourcing HRQoL data from single-arm studies, measuring caregiver disutilities and estimating disease burden. Conclusions This review has highlighted the need for new methodology to reflect the impact of the diseases on people with rare diseases and their families. The review identified the following methodological requirements: alternative approaches that should be used when EQ-5D is not appropriate, methods to evaluate paediatric HRQoL and methods to quantify disease burden. This review also highlights the need to establish clear recommendations on the estimation of utilities across different rare diseases.

Background and aims: The NICE Highly Specialised Technology (HST) programme evaluates interventions for very rare conditions within the UK. This review aimed to analyse previous NICE HST appraisals and determine commonly used methods to overcome uncertainties relating to health-related quality of life (HRQoL) and disease burden for people with rare diseases and their caregivers. The review also aimed to identify areas where further methodological development is required. Approach and results: A targeted review of all previous NICE HST appraisals published by the 28th February 2022, in which at least one committee meeting had taken place, was conducted. A total of 24 appraisals were included (17 fully completed and seven ongoing). Data were extracted by one reviewer. The evidence review group (ERG) and committee comments were compared against the NICE reference case and synthesised to identify the following methodological uncertainties that occurred most commonly: using alternatives to the EuroQol-5 Dimension (EQ-5D), sourcing HRQoL data from single-arm studies, measuring caregiver disutilities and estimating disease burden. Conclusions: This review has highlighted the need for new methodology to reflect the impact of the diseases on people with rare diseases and their families. The review identified the following methodological requirements: alternative approaches that should be used when EQ-5D is not appropriate, methods to evaluate paediatric HRQoL and methods to quantify disease burden. This review also highlights the need to establish clear recommendations on the estimation of utilities across different rare diseases. [ABSTRACT FROM AUTHOR]

In continuity with the research on social segregation and the phenomenon of urban gentrification, this article examines the cohabitation patterns of populations with diametrically opposed incomes within the same neighborhood, typically observed in the city center. This phenomenon is defined here as internal socio-economic polarization. It is measured through the combination of two original indexes (poverty and wealth indexes) constructed based on income deciles per consumption unit for the year of 2017. The analysis focuses on the municipality of Nice, characterized by a low demographic dynamic, a relative concentration of seniors, and a strong tourist attractiveness, particularly in the highly polarized neighborhoods that occupy almost the entire city center. This study is complemented by a principal component analysis summarizing the characteristics of the population and housing stock in the neighborhoods of Nice. The main objective of this research is to identify and locate polarized neighborhoods within the urban context of Nice, to analyze the distinctive traits of their population and housing stock, and, finally, to highlight potential trends in the population's socio-economic status. Moreover, the economic trajectories of polarized neighborhoods, in connection with their population and housing characteristics (such as the secondary use of a portion of the housing stock, often low-quality old buildings, social housing, and the overrepresentation of retirees), help explain the forms of socio-economic polarization observed in these neighborhoods (such as the indications of gentrification, unfinished gentrification, and sustainable cohabitation). [ABSTRACT FROM AUTHOR]

There are currently no guidelines in South Africa for effective decision making towards improving the health status of the population and ensuring fair and equitable resource allocation. This is because of the absence of a local health technology assessment (HTA) body and/or standardised framework for such assessments. Guidelines exist globally; however shortcomings include that they fail to make explicit allowance for rationing of care because of the affordability constraints. Contribution: This article highlights the dire need for effective implementation of health economics guidelines to ensure the best possible health outcomes within the affordability constraints present in the South African context.

Businesses that run in recycling industries are one of the trends that are now in demand by many parties and supported by both national and international governments, but in the practice of these business activities there are many components that must be considered, especially if an entity is in the business to business sector. PT Recycled Paper Hub came as an competitive alternative that offers products in the form of recycled paper materials with low impurity levels which will later be used by companies to be processed again into many forms including packaging. By analyzing and implementing a marketing mix approach in accordance with the vision and mission, analysis data obtained from research on internal and external strengths that are quantitative and qualitative, the data obtained reflects business activities in order to achieve business excellence. In this study, the marketing mix carried by PT Recycled Paper Hub is Direct Marketing NICE. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the impact of the National Institute for Health and Care Excellence's (NICE) new severity modifier, which has replaced the end-of-life (EoL) premium, on future NICE recommendations, considering past decision-making patterns. NICE technology appraisals (TAs) published between January 2020 and December 2022 were reviewed. Summary statistics were generated to assess how the new severity modifier might affect hypothetical decision making in historical TAs. A total of 138 data points were identified from 132 TAs. Although the EoL premium was applied in 46 appraisals (33%), 57 (39%) qualify for a severity-based quality-adjusted life-year (QALY) multiplier. Only 19 appraisals (14.6%) not receiving an EoL premium met the severity criteria, the majority (17) qualifying for a 1.2× multiplier. In appraisals predicted to meet the severity criteria, 45 (79%) were in oncology, making them 4.04 times (95% CI 1.91-9.02) more likely to qualify for a severity modifier than nononcology indications. Among historically EoL indications, 42 (91%) were predicted to meet the severity criteria, making them 14.8 times (95% CI 6.37-37.6) more likely to qualify for a severity modifier. The new severity modifier will predominantly benefit oncology indications, continuing their previous explicit prioritization under the EoL decision modifier. However, the new severity modifier is harder to achieve and less generous; only a fraction of appraisals qualify for the highest effective £51 000 per QALY threshold. The vast majority of indications previously approved at £50 000 per QALY would now need to meet a cost-effectiveness threshold of <£36 000. This may necessitate greater pricing flexibility from manufacturers and increase the likelihood of negative recommendations. • The National Institute for Health and Care Excellence has made major changes to the adjustment of their cost-effectiveness thresholds, replacing the "end-of-life" premium for life-extending treatments with a severity-based, tiered approach to valuing new technologies. • Based on historical decision making, very few technologies appraised by the National Institute for Health and Care Excellence are likely to be eligible for the highest cost-effectiveness threshold, with the new severity modifier continuing to predominantly benefit oncology technologies. • The vast majority of indications previously qualifying for the £50 000 per quality-adjusted life-year gained end-of-life premium would now need to meet a cost-effectiveness threshold of either £30 000 or £36 000. This more restrictive policy environment may present challenges to the introduction of new technologies into the United Kingdom, but may improve the allocation of resources to where they provide the greatest benefits. [ABSTRACT FROM AUTHOR]

In this update, we discuss a position statement from the National Institute of Health and Care Excellence (NICE) on the use of artificial intelligence for evidence generation and publications reviewing the use of real-world data as external control arms. Finally, we discuss a number of recent studies investigating the real-world effectiveness of glucagon-like peptide-1 receptor agonists and whether these studies are informative for reimbursement decision making.

Summary: Background: The COVID-19 global pandemic placed unprecedented pressure on cancer services, requiring new interim Systemic Anti-Cancer Treatments (SACT) options to mitigate risks to patients and maintain cancer services. In this study we analyse interim COVID-19 SACT therapy options recommended in England, evaluating the evidence supporting inclusion and delineating how these have been integrated into routine cancer care. Methods: We performed a retrospective analysis of interim Systemic Anti-Cancer Treatments endorsed by NHS England during the COVID-19 pandemic. Interim therapy options were compared to baseline (replacement) therapies by comparing data from the key pivotal trial(s) in terms of clinical efficacy and potential benefits (e.g., reduced immunosuppression or improved adverse effect profile) within the context of the pandemic. Furthermore, we evaluated the evolution of these interim SACT options, exploring if these have been integrated into current treatment pathways or are no longer accessible at the pandemic end. Findings: 31 interim oncology treatment options, across 36 indications, for solid cancers were endorsed by NHS England between March 2020 and August 2021. Interim therapies focused on the metastatic setting (83%; 30/36), allowing greater utilisation of immune checkpoint inhibitors (45%; 14/31) and targeted therapies (26%; 8/31), in place of cytotoxic chemotherapy. Overall, 36% (13/36) of therapies could not have efficacy compared with baseline treatments due to a paucity of evidence. For those which could, 39% (9/23) had superior efficacy (e.g., overall survival), 26% (6/23) had equivocal efficacy and 35% (8/23) lower efficacy. 53% (19/36) of interim therapies had better or equivocal toxicity profiles (when assessable), and/or were associated with reduced immunosuppression. Almost half (47%; 17/36) of interim therapies did not have UK market authorisation, being classified as ‘off label’ use. Analysing access to interim options at the end of the pandemic (May 2023) identified 19 (53% 19/36) interim options were fully available, and a further four (11% 4/36) therapies were partially available. Interpretation: Interim SACT options, introduced in England, across a range of solid cancers supported delivery of cancer services during the pandemic. Most interim therapies did not demonstrate superior efficacy, but provided other important benefits (e.g., reduced immunosuppression) in the context of the pandemic. Funding: None.

Clinical guidelines for the assessment and management of atrial fibrillation emphasize the importance of taking the patient’s preferences into account. A detailed examination of those from the National Institute for Excellence in Health and Social Care (NICE) raise serious questions about whether the recommendations embed preferences about crucial trade-offs that pre-empt those of the patient; do not stress the need to provide them with the information on option consequences necessary for them to become an informed patient; and characterise them as ‘concordant’ or ‘discordant’ rather than independently valid. American and European guidelines do not differ significantly in these respects. [ABSTRACT FROM AUTHOR]

Summary: In 2023, the European Society of Cardiology (ESC) updated its infective endocarditis (IE) guidelines strongly endorsing antibiotic prophylaxis (AP) before invasive dental procedures (IDPs) for high-risk patients, elevating their recommendation to Class I. The American Heart Association (AHA) is aligned with this view and reaffirmed the need for AP to prevent IE in those at high-risk in its 2021 guidelines. In contrast, the UK's National Institute for Health and Care Excellence (NICE) recommends against routine AP use. Despite considerable new evidence, NICE has not reviewed this recommendation since 2015. In this Personal View, we review the new evidence that has arisen since 2015. Our analysis establishes the association between IDPs and IE and shows that AP is both safe and effective in reducing the IE-risk following IDPs in those at high-risk. Data also show that AP is cost-effective and would result in significant cost savings and health benefits if re-introduced into the UK's National Health Service for high-risk patients. Given these insights, we argue it is time NICE reviewed its guidance so that high-risk patients in the UK receive the same protection against IE that is afforded to patients in the rest of the world. Funding: The authors received no specific funding for this work.

This paper was written based on the “National Institute of Health and Clinical Excellence (NICE) Guideline on Treatment and Management of Psychosis and Schizophrenia in Adults” (2014 edition, updated until 2020 in the online format), of which it represents a faithful summary of the parts dedicated to the role of psychotherapy in the treatment of psychosis and schizophrenia, with particular reference to cognitive-behavioral psychotherapy. [ABSTRACT FROM AUTHOR]

UKCTOCS provides an opportunity to explore symptoms in preclinical invasive epithelial ovarian cancer (iEOC). We report on symptoms in women with pre-clinical (screen-detected) cancers (PC) compared to clinically diagnosed (CD) cancers. In UKCTOCS, 202638 postmenopausal women, aged 50–74 were randomly allocated (April 17, 2001-September 29, 2005) 2:1:1 to no screening or annual screening till Dec 31,2011, using a multimodal or ultrasound strategy. Follow-up was through national registries. An outcomes committee adjudicated on OC diagnosis, histotype, stage. Eligible women were those diagnosed with iEOC at primary censorship (Dec 31, 2014). Symptom details were extracted from trial clinical-assessment forms and medical records. Descriptive statistics were used to compare symptoms in PC versus CD women with early (I/II) and advanced (III/IV/unable to stage) stage high-grade-serous (HGSC) cancer. ISRCTN-22488978; ClinicalTrials.gov -NCT00058032. 1133 (286PC; 847CD) women developed iEOC. Median age (years) at diagnosis was earlier in PC compared to CD (66.8PC, 68.7CD, p = 0.0001) group. In the PC group, 48% (112/234; 90%, 660/730CD) reported symptoms when questioned. Half PC (50%, 13/26PC; 36%, 29/80CD; p = 0.213) women with symptomatic HGSC had >1symptom, with abdominal symptoms most common, both in early (62%, 16/26, PC; 53% 42/80, CD; p = 0.421) and advanced (57%, 49/86, PC; 74%, 431/580, CD; p = 0.001) stages. In symptomatic early-stage HGSC, compared to CD, PC women reported more gastrointestinal (change in bowel habits and dyspepsia) (35%, 9/26PC; 9%, 7/80CD; p = 0.001) and systemic (mostly lethargy/tiredness) (27%, 7/26PC; 9%, 7/80CD; p = 0.017) symptoms. Our findings, add to the growing evidence, that we should reconsider what constitutes alert symptoms for early tubo-ovarian cancer. We need a more nuanced complex of key symptoms which is then evaluated and refined in a prospective trial. [Display omitted] • High alert ovarian cancer symptoms based on reports by clinically diagnosed women are associated with poorer outcomes. • In UKCTOCS, we explore prospectively preclinical symptoms in women detected by screening earlier in the natural history. • In high grade serous ovarian cancer, the symptom profile was different between women with preclinical and clinical disease. • Women with preclinical early stage high grade serous ovarian cancer reported more gastrointestinal and systemic symptoms. • Key symptoms were change in bowel habits, dyspepsia and tiredness. [ABSTRACT FROM AUTHOR]

Treatment guidelines are key drivers of prescribing practice in the management of Clostridioides difficile infection (CDI), but recommendations on best practice can vary. We conducted a cost-utility analysis to compare the treatment pathway recommended by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guideline with the pathway proposed by the National Institute for Health and Care Excellence (NICE) guideline, from the perspective of the UK National Health Service. A decision tree modelling approach was adopted to reflect the treatment pathway for CDI as outlined in ESCMID and NICE guidelines. Patients experiencing a CDI infection received up to three treatments per infection to achieve a response and could subsequently experience up to two recurrences. Data on patient demographics, treatment response, recurrence, utilities, CDI-related mortality, and costs were taken from published literature. The ESCMID treatment pathway was cost-effective versus the NICE treatment pathway at a threshold of £20 000 per quality-adjusted life year gained, with an incremental cost-effectiveness ratio of £4931. Cost-effectiveness was driven by differences in index infection recommendations (ESCMID recommends fidaxomicin as first-line treatment whereas NICE recommends vancomycin). The model results were robust to variations in inputs investigated in scenarios and sensitivity analyses, and probabilistic sensitivity analysis demonstrated that the ESCMID guideline treatment strategy had a 100% likelihood of being cost-effective versus the NICE treatment strategy. Compared with the NICE guideline, the ESCMID guideline recommendations for treating an index CDI represent the most cost-effective use of healthcare resources from the perspective of the UK National Health Service. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to compare reimbursement recommendations by the British National Institute for Health and Care Excellence (NICE) and the French National Authority for Health (Haute Autorité de Santé; HAS) for oncology new medicines indicated for the treatment of solid tumors. Methods: Public assessment reports published on NICE and HAS Web sites between January 1, 2015, and December 31, 2021, describing appraisals for public reimbursement for oncology new medicines indicated for the treatment of solid tumors were searched and systematically reviewed. Biosimilars and generic drugs were excluded from the analysis. Results: Overall, 119 public assessment reports published by NICE and 134 by HAS were identified, with 101 interventions assessed by both agencies. Of 101, 38 (38%) interventions received similar recommendations, 38 (38%) were recommended for different populations, and 25 (25%) were endorsed by one agency but rejected by the other. The main reason NICE would not recommend a drug was due to lack of cost-effectiveness, whereas HAS would primarily reject a drug on the grounds of insufficient clinical evidence. Conclusion: The major divergence between agencies is the key criterion used for reimbursement recommendations. NICE mainly considers cost-effectiveness, whereas HAS primarily focuses on the clinical value of interventions. This contributes to the variability in reimbursement recommendations and leads to differential access to oncology new medicines indicated for the treatment of solid tumors among patients in France, and England and Wales. Highlights: Both the National Institute for Health and Care Excellence (NICE) and the National Authority for Health (Haute Autorité de Santé; HAS) have established formal health technology assessment (HTA) processes and offer universal public health care coverage. However, both agencies diverge in the weight given to different elements of evidence during HTA evaluations. NICE uses cost-effectiveness as key criterion for recommendations on drug reimbursement, while HAS mostly limits its assessment to clinical value. For oncology new medicines indicated for treating solid tumors between 2015 and 2021, recommendations differed 62% of the time between NICE and HAS, primarily due to the distinct key decision-making criteria each HTA agency uses. For 4 interventions not endorsed by NICE, HAS saw these drugs as providing a substantial enhancement in clinical value over existing treatments, potentially providing an edge in price negotiations. Conversely, NICE deemed these drugs as not delivering adequate value for money in comparison with current therapies. A key difference between the 2 agencies is HAS's insistence on methodological rigor in efficacy results, compared with NICE's more flexible approach, considering descriptive efficacy results in cost-effectiveness modeling. [ABSTRACT FROM AUTHOR]

Cleft lip and/or palate (CL/P) is one of the most common congenital conditions worldwide. Individuals born with CL/P will embark on a long-term treatment pathway throughout childhood and often into adulthood. As they grow older, young people become more involved in medical decisions. The National Institute for Clinical Excellence (NICE) has published guidance for health professionals on how transitions of responsibility should be managed in health services. The aim of the current study was to examine the extent to which the NICE recommendations are currently being implemented in UK CL/P services according to young adults' first-hand accounts. Semi-structured interviews were carried out with 15 young adults with CL/P aged 16-25 years. Interview questions were designed to map onto the NICE guidance. Data were analysed to assess whether each guideline was met, partially met, or not met for each individual participant. Overall, findings suggest that further consideration is needed as to how best to implement the recommendations effectively. The introduction of assigned transition workers in CL/P services to co-ordinate transition to adult care offers one possible solution. Focusing on the provision of holistic, patient-centred care, this aspect of the CL/P service could include giving patients access to medical history documentation, liaison with key health professionals including GPs and dental practitioners, and the development of age-appropriate resources to facilitate the transition process. [ABSTRACT FROM AUTHOR]

A different laundry business service exists in Indonesia, especially in Jakarta and its surroundings. This business plan offers a special premium laundry service for 4 and 5-star hotels. PT. Luxury Indah Jaya (Luxury Laundry) as a provider of premium laundry services for 4 and 5-star hotels focuses on B2B but still pays attention to the needs of the end user. This marketing plan will be formulated and explained regarding marketing goals and objectives, STP marketing strategy, marketing mix with the NICE approach, sales activities, and calculation of income streams and Investment Feasibility Analysis. This research was conducted using qualitative methods aimed at determining the feasibility of a premium-class laundry business marketing plan specifically for 4 & 5-star hotels. With good marketing planning, companies can conduct in-depth analysis and evaluation of new business opportunities or investment projects. This is certainly very helpful in assessing investment feasibility, market growth potential, income potential, and associated risks. [ABSTRACT FROM AUTHOR]

This article provides a brief overview of the key aspects of planning, conducting, and reporting NICE clinical practice data collection and analysis studies, as well as general information about the sources of real-world data (RWD) and their use in NICE management decision-making algorithms. The difficulties of finding and using RWD are described, as well as methods for overcoming them, brief NICE recommendations for assessing the suitability of data and an algorithm for conducting quantitative studies to collect evidence from RWD are given.

The real-world data are used in drug authorization procedures, comparative efficacy and safety research, to make changes in the Summary of Product Characteristics, clinical recommendations. One more aspect where RWD/RWE can be used is the health technology assessment. Although there is a clear need for high-quality recommendations regarding RWE studies, published today documents do not contain clear instructions.

Abstract Objectives Dealing with uncertainty is one of the critical topics in health technology assessment. The greater decision uncertainty in appraisals, the less clear the clinical- and cost-effectiveness of the health technology. Although the development of targeted cancer therapies (TCTs) has improved patient health care, additional complexity has been introduced in drug appraisals due to targeting more specific populations. Real-world data (RWD) are expected to provide helpful information to fill the evidence gaps in appraisals. This study compared appraisals of TCTs with those of non-targeted cancer therapies (non-TCTs) regarding sources of uncertainty and reviewed how RWD have been used to supplement the information in these appraisals. Methods This study reviews single technology appraisals (STAs) of oncology medicines performed by the National Institute for Health and Care Excellence (NICE) over 11 years up to December 2021. Three key sources of uncertainty were identified for comparison (generalisability of clinical trials, availability of direct treatment comparison, maturity of survival data in clinical trials). To measure the intensity of use of RWD in appraisals, three components were identified (overall survival, volume of treatment, and choice of comparators). Results TCTs received more recommendations for provision through the Cancer Drugs Fund (27.7, 23.6% for non-TCT), whereas similar proportions were recommended for routine commissioning. With respect to sources of uncertainty, the external validity of clinical trials was greater in TCT appraisals (p = 0.026), whereas mature survival data were available in fewer TCT appraisals (p = 0.027). Both groups showed similar patterns of use of RWD. There was no clear evidence that RWD have been used more intensively in appraisals of TCT. Conclusions Some differences in uncertainty were found between TCT and non-TCT appraisals. The appraisal of TCT is generally challenging, but these challenges are neither new nor distinctive. The same sources of uncertainty were often found in the non-TCT appraisals. The uncertainty when appraising TCT stems from insufficient data rather than the characteristics of the drugs. Although RWD might be expected to play a more active role in appraisals of TCT, the use of RWD has generally been limited.

The article focuses on Stephen's infancy and its implications in James Joyce "A Portrait of the Artist as a Young Man," exploring themes of rebellion, obedience, and artistic development. Topics include the symbolic significance of Stephen's babble reflecting infancy, his struggle between pleasing authorities and pursuing personal desires, and the transformative journey towards artistic independence and self-discovery.

Aim: NICE’s highly specialized technology (HST) evaluations are highly restrictive in terms of entry criteria and as a consequence, the vast majority of rare disease medicines are assessed through NICE’s standard, single technology appraisal (STA) route. We explored whether NICE shows flexibility and pragmatism when evaluating treatments for rare diseases through its STA process. Materials & methods: We matched a sample of recent, randomly selected STAs for rare diseases to STAs for non-rare diseases and conducted a thematic analysis to identify patterns in NICE’s decision-making, with a specific focus on the application of NICE’s published methods and the handling of uncertainty. Results: Three themes emerged where some flexibility was shown: ‘handling of uncertainty and discretion’, ‘application of NICE methods’ and ‘commercial arrangements’. Rare disease technologies were generally subject to longer appraisal times than those for non-rare diseases. Conclusion: Although NICE shows a degree of flexibility and pragmatism toward uncertainties in the evidence base for rare disease medicines, this is often off-set by a lengthy appraisal process, which can lead to delays in patients receiving vital treatment.

This article provides an overview of approaches to the use of real-world data (RWD) and real-world evidence (RWE) in the processes of registration and health technology assessment in Canada and the UK, as well as a brief description of tools for health management decision-making, the Canadian Real-world Evidence for Value in Cancer Collaboration and electronic databases and registries. Information is provided on when RWE submission is possible and recommended, and what requirements the regulatory agencies have for RWD and RWE.

Publicly funded healthcare systems, including those in Canada, the United Kingdom (UK), and Australia, often use health technology assessment (HTA) to inform drug reimbursement decision-making, based on dossiers submitted by manufacturers, and HTA agencies issue publicly available reports to support funding recommendations. However, the level of information reported by HTA agencies in these reports may vary. To provide insights on this issue, we describe and assess the reporting of economic methods in recent oncology HTA recommendations from the Canadian Agency for Drugs and Technologies in Health (CADTH), National Institute for Health and Care Excellence (NICE), and Pharmaceutical Benefits Advisory Committee (PBAC). Publicly available HTA recommendations and reports for oncology drugs issued by CADTH over a 2-year period, 2019–2020, were identified and compared with the corresponding HTA documents from NICE and the PBAC. Reporting of key model characteristics and attributes, survival analysis methods, methodological criticisms, and re-assessment of the economic results were characterized using descriptive statistics. Dichotomous differences in the methodological criticisms observed between the three agencies were assessed using Cochran’s Q tests and substantiated using pairwise McNemar tests. Chi-squared tests were used to assess the dichotomous differences in the reporting of methods and explore the potential relationships between categorical variables, where appropriate. HTAs published by CADTH, NICE, and the PBAC consistently reported a broad spectrum of descriptive information on the economic models submitted by manufacturers. While common economic evaluation attributes were well-reported across the three HTA agencies, significant differences in the reporting of survival analysis methods and methodological criticisms were observed. NICE consistently reported more comprehensive information, compared to either CADTH or PBAC. Despite these differences, broadly similar recommendation rates were observed between CADTH and NICE. The PBAC was found to be more restrictive. Based on our 2-year sample of oncology, the HTAs published by CADTH matched with the corresponding HTAs from NICE and PBAC; we observed important variations in the reporting of economic evidence, especially technical aspects, such as survival analysis, across the three agencies. In addition to guidelines for HTA submissions by manufacturers, the community of HTA agencies should also have common standards for reporting the results of their assessments, though the information and opinions reported may differ.

Dynamic Cone Penetration Test (CPTu) profile offshore sediments by impact penetration. To exploit their results in full, the measured data are converted to obtain a quasi-static equivalent profile. Dynamic CPTu conversion requires calibrated correction models. Calibration is currently done by using paired (i.e., very close) quasi-static and dynamic tests. It is shown here that paired test data, which may be inconvenient to acquire offshore, are not strictly necessary to convert dynamic CPTu data. A new probabilistic methodology is proposed to call upon quasi-static results from a much wider area in the conversion procedure. Those results feed the prior distribution of a converted profile, within a Bayesian updating scheme where strain-rate coefficient and correction model error are also described by updated stochastic variables. The updating scheme is solved numerically using the Transitional Markov Chain Monte Carlo sampling algorithm. To avoid undue influence of local profile heterogeneity, the statistic treatment of the quasi-static CPTu data takes place in the frequency domain, using a discrete cosine transform. The new procedure is applied to a CPTu campaign offshore Nice (France): dynamic tests are converted with equal precision using quasi-static data acquired at distances orders of magnitude larger than what was previously employed. [ABSTRACT FROM AUTHOR]

Current topographic survey technology provides high-resolution (HR) datasets for urban environments. Incorporating this HR information in models aiming to provide flood risk assessment is desirable because the flood wave propagation is depending on the urban topographic features, i.e. buildings, bridges and street networks. Conceptual, numerical and practical challenges arise from the application of shallow water models to HR urban flood modeling. For instance, numerical challenges are occurrence of wet-dry fronts, geometric discontinuities in the urban environment and discontinuous solutions, i.e. shock waves. These challenges can be overcome by using a Godunov-type scheme. However, the computational cost of this type of schemes is high, such that HR two-dimensional shallow water simulations with practical relevance have to be run on supercomputers. The porous shallow water model is an alternative approach that aims to reduce computational cost by using a coarse resolution and accounting for unresolved processes by means of the porosity terms. Usually, a speedup between two and three orders of magnitude in comparison to HR simulations can be obtained. This study reports preliminary results of a practical test case concerning pluvial flooding in a district of the city of Nice, France, caused by the intense rainfall event on October 3rd, 2015. HR topography data set on a 1 m resolution is available for the district, whereby street features of infra-metric dimensions have been included. A reference solution is calculated by a HR shallow water model on a 1 m by 1 m structured computational grid. The porous shallow water model is run on a 10 m by 10 m grid and the influence of the drag source term is studied. The model results show a large deviation, which is caused by the poor meshing strategy of the porous shallow water (AP) model. The study also summarizes practical challenges that arise during the application of the AP and HR models to a large urban catchment. The main difficulty is to obtain a good mesh. In smaller scale investigations, the mesh is currently constructed by hand such that the cell edges align with buildings. This approach is not feasible for large scale urban catchments with a large number of buildings. Future steps that have to be taken, such as a strategy for automatic mesh generation, are reported on.

Summary: In this editorial we, as members of the 2022 NICE Guideline Committee, highlight and discuss what, in our view, are the key guideline recommendations (generated through evidence synthesis and consensus) for mental health professionals when caring for people after self-harm, and we consider some of the implementation challenges. [ABSTRACT FROM AUTHOR]

Objectives: Dealing with uncertainty is one of the critical topics in health technology assessment. The greater decision uncertainty in appraisals, the less clear the clinical- and cost-effectiveness of the health technology. Although the development of targeted cancer therapies (TCTs) has improved patient health care, additional complexity has been introduced in drug appraisals due to targeting more specific populations. Real-world data (RWD) are expected to provide helpful information to fill the evidence gaps in appraisals. This study compared appraisals of TCTs with those of non-targeted cancer therapies (non-TCTs) regarding sources of uncertainty and reviewed how RWD have been used to supplement the information in these appraisals.Methods: This study reviews single technology appraisals (STAs) of oncology medicines performed by the National Institute for Health and Care Excellence (NICE) over 11 years up to December 2021. Three key sources of uncertainty were identified for comparison (generalisability of clinical trials, availability of direct treatment comparison, maturity of survival data in clinical trials). To measure the intensity of use of RWD in appraisals, three components were identified (overall survival, volume of treatment, and choice of comparators).Results: TCTs received more recommendations for provision through the Cancer Drugs Fund (27.7, 23.6% for non-TCT), whereas similar proportions were recommended for routine commissioning. With respect to sources of uncertainty, the external validity of clinical trials was greater in TCT appraisals (p = 0.026), whereas mature survival data were available in fewer TCT appraisals (p = 0.027). Both groups showed similar patterns of use of RWD. There was no clear evidence that RWD have been used more intensively in appraisals of TCT.Conclusions: Some differences in uncertainty were found between TCT and non-TCT appraisals. The appraisal of TCT is generally challenging, but these challenges are neither new nor distinctive. The same sources of uncertainty were often found in the non-TCT appraisals. The uncertainty when appraising TCT stems from insufficient data rather than the characteristics of the drugs. Although RWD might be expected to play a more active role in appraisals of TCT, the use of RWD has generally been limited. [ABSTRACT FROM AUTHOR]

Background: National Institute for Health and Care Excellence (NICE, 2013) Guidance on Self-Harm states that professionals supporting people who self-harm should demonstrate compassion, respect and dignity. This literature review examines the evidence for professionals' attitudes towards people with intellectual disabilities who self-harm.Method: Four databases (PsychInfo, IBSS, CINAHL and Medline) were systematically searched to find relevant research since 2000.Results: Four studies met the criteria. Attitudes of professionals supporting people with intellectual disabilities are contrasted with those of professionals in settings focused on supporting people without intellectual disabilities. Professionals supporting people with intellectual disabilities tended to display attitudes and attributions reflective of biobehavioural and psychosocial theories of self-harm, with a greater emphasis on relationships.Conclusion: Much more research is needed which examines the attitudes of professionals supporting people with intellectual disabilities who self-harm. [ABSTRACT FROM AUTHOR]

In this update, we discuss recent publications examining the use of real-world data as a measure of treatment effectiveness in submissions to the National Institute of Health and Care Excellence, the results of a pilot study from the Coalition to Advance Real-World Evidence initiative and a validation study of synthetic data.

In this update, we discuss an article covering the implementation challenges of the upcoming European Union Health Technology Assessment regulation, particularly focusing on the complexity of population, intervention, comparator and outcomes requirements across member states; a user guide to applying generalized cost-effectiveness analysis for broader value assessment and finally highlight an ongoing debate surrounding National Institute for Health and Care Excellence's severity modifier implementation.

Objectives: This study investigates factors associated with use of real-world data (RWD) in economic modelling for single technology appraisals (STAs) of cancer drugs by the National Institute for Health and Care Excellence (NICE) to improve systematic understanding of the use of RWD., Methods: The data were extracted from STAs of cancer drugs, for which NICE issued guidance between January 2011 and December 2022 (n=267). Binary regression was used to test hypotheses concerning the greater or lesser use of RWD. Bonferroni-Holm correction was used to control error rates in multiple hypotheses tests. Several explanatory variables were considered in this analysis, including time (Time), incidence rate of disease (IR), availability of direct treatment comparison (AD), generalisability of trial data (GE), maturity of survival data in trial (MS) and previous technology recommendations by NICE (PR). The primary outcome variable was any use of RWD. Secondary outcome variables were specific uses of RWD in economic models., Results: AD had a statistical negative association with any use of RWD whereas no associations with non-parametric and parametric use of RWD were found. Time had several statistical associations with use of RWD (validating survival distributions for the intervention, estimating progression-free survival for the intervention, estimating overall survival for comparators and transition probabilities)., Conclusions: RWD were more likely to be used in economic modelling of cancer drugs when randomised controlled trials failed to provide relevant clinical information of the drug for appraisals, particularly in the absence of direct treatment comparisons. These results, based on analysis of data systematically collected from previous appraisals, suggest that uses of RWD were associated with data gaps in the economic modelling. While this result may support some of the claimed advantages of using RWD when evidence is absent, the question, the extent to which use of RWD in indirect treatment comparisons reduces uncertainty is still to be determined., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jiyeon Kang is supported by the Centre for Cancer Biomarkers, University of Bergen, funded by the Research Council of Norway grant number (223250). She also holds a ESRC (Economic and Social Research Council) postdoctoral fellowship. The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Also, any fellowship or external contribution had no impacts on this paper. John Cairns is a diagnostic advisory committee member of the National Institute for Health and Care Excellence., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Abstract Aims Evaluate whether UK National Institute for Health & Care Excellence (NICE) chronic heart failure (HF) guidelines can be safely and effectively refined through specialist referral management. Methods and results All referrals to a UK centre 1/3/2019–30/5/2019 and 1/6/2020–31/7/2020 were reviewed by HF specialists. Patients were triaged to specialist assessment in HF clinic, according to the NICE HF diagnostic pathway [urgency based on N‐terminal pro brain natriuretic peptide (NTproBNP) levels], or the referrer given remote Advice & Guidance (A&G), to aid primary care management. Standardized triage criteria for recommending primary care management were (i) presentation inconsistent with HF, (ii) competing comorbidity/frailty meant specialist assessment in clinic not in patient's best interests, (iii) recent assessment for same condition, or (iv) patient had known HF. Following triage patients managed in the primary care were categorized as low or high risk of adverse outcomes. Outcome measures were 90 day all‐cause and HF hospital admission and mortality rates. Four hundred and eighty‐six patients had the median age of 80 (74–86) years, and 253 (52%) were male. Two hundred and six (42%) had NTproBNP > 2000 pg/mL. Primary care management was recommended for 128 patients (26%): 105 (22%) A&G alone and 23 input from community HF nurse specialists. Primary care management was recommended due to the following: presentation inconsistent with HF 53 (42%), more important competing comorbidity/frailty 35 (27%), recent assessment 17 (13%), and known HF 23 (18%). Patients managed in primary care had higher rates of all‐cause hospitalization (30% vs. 19%; P = 0.018) and death (7% vs. 2%; P = 0.0054) than those seen in HF clinic. Of those managed in primary care, 50 (39%) were determined to be at low risk and 78 (61%) at high risk. High‐risk patients were older (87 vs. 80 years; P = 0.0026), had much higher NTproBNP (2666 vs. 697 pg/mL; P

Background: Cognitive Behavioural Analysis System of Psychotherapy (CBASP) is an evidenced based treatment model for chronically depressed patients. Aims: The main aim of this service evaluation was to assess the acceptability and clinical impact of CBASP for chronic depression within an Improving Access to Psychological Therapies (IAPT) service. Method: Routinely collected data were analysed for all patients that received CBASP treatment focussing on the recovery rates of these patients in terms of depression, anxiety and social functioning. Interviews were conducted with patients who had recently been discharged from CBASP therapist within one month of the follow-up date, explore their experiences of therapy. Results: Outcome data for 27 patients suggested substantial reduction in scoring on measures of depression and anxiety following CBASP treatment. Across all interviews it was clear that patients developed an insight and understanding of how their behaviours affect the outcome of interpersonal situations. Conclusions: Results from this service evaluation suggest that CBASP is acceptable to service users and has a positive clinical impact in terms of IAPT recovery targets for anxiety, depression and social functioning. [ABSTRACT FROM AUTHOR]

Publicly funded healthcare systems, including those in Canada, the United Kingdom (UK), and Australia, often use health technology assessment (HTA) to inform drug reimbursement decision-making, based on dossiers submitted by manufacturers, and HTA agencies issue publicly available reports to support funding recommendations. However, the level of information reported by HTA agencies in these reports may vary. To provide insights on this issue, we describe and assess the reporting of economic methods in recent oncology HTA recommendations from the Canadian Agency for Drugs and Technologies in Health (CADTH), National Institute for Health and Care Excellence (NICE), and Pharmaceutical Benefits Advisory Committee (PBAC). Publicly available HTA recommendations and reports for oncology drugs issued by CADTH over a 2-year period, 2019–2020, were identified and compared with the corresponding HTA documents from NICE and the PBAC. Reporting of key model characteristics and attributes, survival analysis methods, methodological criticisms, and re-assessment of the economic results were characterized using descriptive statistics. Dichotomous differences in the methodological criticisms observed between the three agencies were assessed using Cochran's Q tests and substantiated using pairwise McNemar tests. Chi-squared tests were used to assess the dichotomous differences in the reporting of methods and explore the potential relationships between categorical variables, where appropriate. HTAs published by CADTH, NICE, and the PBAC consistently reported a broad spectrum of descriptive information on the economic models submitted by manufacturers. While common economic evaluation attributes were well-reported across the three HTA agencies, significant differences in the reporting of survival analysis methods and methodological criticisms were observed. NICE consistently reported more comprehensive information, compared to either CADTH or PBAC. Despite these differences, broadly similar recommendation rates were observed between CADTH and NICE. The PBAC was found to be more restrictive. Based on our 2-year sample of oncology, the HTAs published by CADTH matched with the corresponding HTAs from NICE and PBAC; we observed important variations in the reporting of economic evidence, especially technical aspects, such as survival analysis, across the three agencies. In addition to guidelines for HTA submissions by manufacturers, the community of HTA agencies should also have common standards for reporting the results of their assessments, though the information and opinions reported may differ. [ABSTRACT FROM AUTHOR]

Patient-reported outcome (PRO) data are increasingly being included in Health Technology Assessment (HTA) submissions for oncology drugs. This study aims to provide differences in PRO evidence requirements in oncology across key HTA bodies and calls for its harmonization. Method guidance provided by HTA bodies in Germany, France and the UK, and analysis of HTA reports of 20 oncology case studies were evaluated in this review. Differences exist between HTA bodies regarding guidance on how PRO data should be collected, reported and analyzed as well as how the data are reviewed and considered in oncology HTAs. HTA bodies can play a key role to harmonize PRO method guidance in collaboration with regulators and sponsors. [ABSTRACT FROM AUTHOR]

Assisted reproductive technologies (ARTs) promise childbirth to those who are involuntarily childless. Despite an increase in their availability, they remain inaccessible because they are expensive. Some jurisdictions fund or subsidise ARTs. Central to ART funding decisions is the question of whether they are medically needed. This arises first at the stage of whether ARTs are funded at all, and second, in determining who, among those that are involuntarily childless, should access funded ARTs. I compare four representative models to demonstrate that centring medical need at these two stages raises problems of (a) undermining the welfare of ART seekers; (b) discrimination against same-sex couples and single women; (c) prioritising the medical needs of some groups over others; (d) budgetary competition with other medical services; and (e) inconsistent practices across jurisdictions. This has the effect of intensifying the stratified pressure to have children faced by women across the world. Drawing on this, I argue that centring medical need in ART funding is inconsistent with the international human right to health. I further claim that an alternative reproductive health approach to funding has the potential to undo the exclusionary nature of the social pressure to have children. [ABSTRACT FROM AUTHOR]