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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.)

Objectives: The availability of novel, more efficacious and expensive cancer therapies is increasing, resulting in significant treatment effect heterogeneity and complicated treatment and disease pathways. The aim of this study is to review the extent to which UK cancer technology appraisals (TAs) consider the impact of patient and treatment effect heterogeneity.Methods: A systematic search of National Institute for Health and Care Excellence TAs of colorectal, lung and ovarian cancer was undertaken for the period up to April 2020. For each TA, the pivotal clinical studies and economic evaluations were reviewed for considerations of patient and treatment effect heterogeneity. The study critically reviews the use of subgroup analysis and real-world translation in economic evaluations, alongside specific attributes of the economic modeling framework.Results: The search identified 49 TAs including 49 economic models. In total, 804 subgroup analyses were reported across 69 clinical studies. The most common stratification factors were age, gender, and Eastern Cooperative Oncology Group performance score, with 15% (119 of 804) of analyses demonstrating significantly different clinical outcomes to the main population; economic subgroup analyses were undertaken in only 17 TAs. All economic models were cohort-level with the majority described as partitioned survival models (39) or Markov/semi-Markov models. The impact of real-world heterogeneity on disease progression estimates was only explored in 2 models.Conclusion: The ability of current modeling approaches to capture patient and treatment effect heterogeneity is constrained by their limited flexibility and simplistic nature. This study highlights a need for the use of more sophisticated modeling methods that enable greater consideration of real-world heterogeneity. [ABSTRACT FROM AUTHOR]

To control costs and improve access, nations can adopt strategies employed in the United Kingdom to control pharmaceutical prices and spending. Current policy evolved from a system created in 1957 that allowed manufacturers to set launch prices, capped manufacturers' rates of return, and later cut list prices. These policies did not effectively control spending and had limited effects on purchase prices. The United Kingdom currently controls pharmaceutical spending in 4 ways. (a) Since 1999, it has typically paid no more than is cost-effective. (b) Since 2017, for medicines that will have a significant budget impact, National Health Service England seeks discounts from cost-effective prices or seeks to limit access for 2 years to patients with the greatest need. (c) Since 2014, statutes and a voluntary scheme have required branded manufacturers to pay the government rebates to recoup the difference between the global pharmaceutical budget and actual spending. (d) For hospitals, generics and some patented drugs are procured through competitive bidding; community pharmacies are reimbursed through a system that provides an incentive to beat average generic market prices. These policies controlled the growth of spending, with the largest effects following budget controls in 2014. Changes since 2008 have reduced savings, first by paying more than is cost-effective for cancer drugs and then by applying higher cost-effectiveness thresholds for some drugs used to treat cancer and certain other drugs. [ABSTRACT FROM AUTHOR]

Background: Proportional hazards (PH) is an assumption often made by researchers, despite evidence of nonproportionality in a significant proportion of clinical trials. In the presence of non-PH, the interpretation of hazard ratios, medians, and landmark survival as summary measures of treatment effect can become problematic. Several recent studies have recommended restricted mean survival time (RMST) as an alternative metric for survival analysis, particularly where non-PH may apply.Objectives: To determine the current approaches of health technology assessment (HTA) agencies to value assessment in the presence of non-PH, and the extent to which RMST is accepted as an alternative measure of treatment benefit.Methods: Methodological guidelines published by 10 HTA agencies were reviewed to establish recommended approaches for presenting survival benefit from clinical trials. Published HTA reports for 23 oncology agents approved by the US Food and Drug Administration and the European Medicines Agency since 2014 were reviewed to determine how guidelines are implemented in practice and identify instances where the PH assumption was tested and RMST analyses reported.Results: Testing for non-PH is not widely incorporated into HTA except by the UK National Institute for Health and Care Excellence. RMST is used infrequently but has been used in a number of countries, particularly by agencies that focus on cost effectiveness.Conclusions: HTA agencies vary in their approaches to non-PH. Most do not routinely check the PH assumption. RMST has played a role in assessing clinical benefit within HTA, although not consistently within countries (across drugs) or across countries (for the same drug). [ABSTRACT FROM AUTHOR]

Background: Several Central and Eastern European (CEE) countries require cost-utility analyses (CUAs) to support reimbursement formulary listing. However, CUAs informed by local evidence are often unavailable, and the cost-effectiveness of the several currently reimbursed biologicals is unclear. Aim: To estimate the cost-effectiveness as multiples of per capita GDP/quality adjusted life years (QALY) of four biologicals (infliximab, etanercept, adalimumab, golimumab) currently reimbursed in six CEE countries in six inflammatory rheumatoid and bowel disease conditions. Methods: Systematic literature review of published cost-utility analyses in the selected conditions, using the United Kingdom (UK) as reference country and with study selection criteria set to optimize the transfer of results to the CEEs. Prices in each CEE country were pro-rated against UK prices using purchasing power parity (PPP)-adjusted per capita GDP, and local GDP per capita/QALY ratios estimated. Results: Central and Eastern European countries list prices were 144-333 % higher than pro rata prices. Out of 85 CUAs identified by previous systematic literature reviews, 15 were selected as a convenience sample for estimating the cost-effectiveness of biologicals in the CEE countries in terms of per capita GDP/QALY. Per capita GDP/QALY values varied from 0.42 to 6.4 across countries and conditions (Bulgaria: 0.97-6.38; Czech Republic: 0.42-2.76; Hungary: 0.54-3.54; Poland: 0.59-3.90; Romania: 0.77-5.07; Slovakia: 0.55-3.61). Conclusion: While results must be interpreted with caution, calculating pro rata (cost-effective) prices and per capita GDP/QALY ratios based on CUAs can aid reimbursement decision-making in the absence of analyses using local data. [ABSTRACT FROM AUTHOR]

Summary: The purpose of the study was to estimate the cost-effectiveness of balloon kyphoplasty compared to nonsurgical management and vertebroplasty for the treatment of hospitalised osteoporotic vertebral compression fractures in the UK. A cost-effectiveness model was constructed and used for analysis. Balloon kyphoplasty may be cost-effective compared to relevant alternatives. Introduction: The objective of this study was to estimate the cost-effectiveness of balloon kyphoplasty (BKP) for the treatment of patients hospitalised with acute osteoporotic vertebral compression fracture (OVCF) compared to percutaneous vertebroplasty (PVP) and nonsurgical management (NSM) in the UK. Methods: A Markov simulation model was developed to evaluate treatment with BKP, NSM and PVP in patients with symptomatic OVCF. Data on health-related quality of life (HRQoL) with acute OVCF were derived from the FREE and VERTOS II randomised clinical trials (RCTs) and normalised to the NSM arm in the FREE trial. Estimated differences in mortality among the treatments and costs for NSM were obtained from the literature whereas procedure costs for BKP and PVP were obtained from three National Health Service hospitals. It was assumed that BKP and PVP reduced hospital length of stay by 6 days compared to NSM. Results: The incremental cost-effectiveness ratio was estimated at Great Britain Pound Sterling (GBP) 2,706 per quality-adjusted life year (QALY) and GBP 15,982 per QALY compared to NSM and PVP, respectively. Sensitivity analysis showed that the cost-effectiveness of BKP vs. NSM was robust when mortality and HRQoL benefits with BKP were varied. The cost-effectiveness of BKP compared to PVP was particularly sensitive to changes in the mortality benefit. Conclusion: BKP may be a cost-effective strategy for the treatment of patients hospitalised with acute OVCF in the UK compared to NSM and PVP. Additional RCT data on the benefits of BKP and PVP compared to simulated sham surgery and further data on the mortality benefits with BKP compared to NSM and PVP would reduce uncertainty. [ABSTRACT FROM AUTHOR]

Balloon kyphoplasty (BKP) is a procedure used to treat vertebral compression fractures (VCFs). We developed a cost-effectiveness model to evaluate BKP in United Kingsdom patients with hospitalised VCFs and estimated the cost-effectiveness of BKP compared to non-surgical management. The results indicate that BKP provides a cost-effective alternative for treating these patients. VCFs of osteoporotic patients are associated with chronic pain, a reduction in health-related quality of life (QoL) and high healthcare costs. BKP is a minimally invasive procedure that has resulted in pain relief, vertebral body height-restoration, decreased kyphosis and improved physical functioning in patients with symptomatic VCFs. BKP was shown to improve health-related QoL in a 12-month interim analysis of a randomised phase-III trial. The objectives of this study were to develop a Markov cost-effectiveness model to evaluate BKP in patients with painful hospitalised VCFs and to estimate the cost-effectiveness of BKP compared with non-surgical management in a UK setting. It was assumed that QoL-benefits found at 12 months linearly approached zero during another 2 years, and that patients receiving BKP warranted six fewer hospital bed days compared with patients given non-surgical management. The procedure was associated with quality-adjusted life-years (QALY)-gains of 0.17 and cost/QALY-gains at £8,800. The results were sensitive to assumptions about avoided length of hospital-stay and persistence of kyphoplasty-related QoL-benefits. In conclusion, the results indicate that BKP provides a cost-effective alternative for treating patients with hospitalised VCFs in a UK-setting. [ABSTRACT FROM AUTHOR]

The input of pathologists is essential for the conduct of many forms of research, including clinical trials. As the custodians of patient samples, pathology departments have a duty to ensure compliance with the relevant regulations, standards and guidelines to ensure the ethical and effective use for their intended investigational analysis, including when patients are participating in a research study. The results of research studies have impacts beyond the research study itself as they may inform changes in policy and practice or support the licensing of medicines and devices. Compliance with regulations and standards provides public assurance that the rights, safety and wellbeing of research participants are protected, that the data have been collected and processed to ensure their integrity and that the research will achieve its purpose. The requirements of the regulatory environment should not be seen as a barrier to research and should not significantly impact on the work of the laboratory once established and integrated into practice. This paper highlights important regulations, policy, standards and available guidance documents that apply to research involving NHS pathology departments and academic laboratories that are contributing to research involving human subjects., Competing Interests: No competing interests were disclosed., (Copyright: © 2019 Driskell OJ et al.)

Objectives: The primary objective of this study was to compare the availability and access of orphan medicinal products (OMPs) in the devolved nations in the United Kingdom (UK), France, Germany, Italy and Spain. Availability is defined as the possibility to prescribe OMPs. Access refers to their full or partial reimbursement by the public health service., Methods: Data were collated on: marketing authorisations, Health Technology Assessment (HTA) decisions, commissioning, and reimbursement decisions, and respective dates of these events for all the OMPs centrally authorised. Indicators of availability of and access to OMPs were calculated in each country and compared., Results: We found that since the implementation of the OMPs Regulation in 2000 to end of May 2016, 143 OMPs obtained a marketing authorisation in the European Union. These OMPs are most widely accessible in Germany and France. In the other countries between 30 and 60% of OMPs are reimbursed. In particular in England, less than 50% of centrally authorised OMPs are routinely funded by the NHS, with one-third of these recommended by NICE. In Germany reimbursement is automatically granted to all medicines which receive a marketing authorisation, immediately after authorisation - but since 2011, there is an evaluation and potentially a pricing negotiation between companies and sickness funds (third party payers). In the other countries, the shortest time from authorisation to a reimbursement decision is observed in Italy and France where it takes 18.6 and 19.5 months respectively on average., Conclusions: Marketing authorisation granted to OMPs is only the first step, as medicines reach patients when reimbursement decisions are implemented by national health systems (this applies to non-OMPs too). We found that more than a half of centrally authorised OMPs were available in the five selected countries, but that access to patients was further restricted by different national reimbursement policies, especially in the UK, Italy and Spain.

Background: A recent study by Page et al. (PLoS Med. 2016;13(5):e1002028) claimed that increasing numbers of reviews are being published and many are poorly-conducted and reported. The aim of the present study was to assess how well reporting standards of systematic reviews produced in a Health Technology Assessment (HTA) context compare with reporting in Cochrane and other 'non-Cochrane' systematic reviews from the same years (2004 and 2014), as reported by Page et al. (PLoS Med. 2016;13(5):e1002028)., Methods: All relevant UK HTA programme systematic reviews published in 2004 and 2014 were identified. After piloting of the form, two reviewers each extracted relevant data on conduct and reporting from these reviews. These data were compared with data for Cochrane and "non-Cochrane" systematic reviews, as published by Page et al. (PLoS Med. 2016;13(5):e1002028). All data were tabulated and summarized., Results: There were 30 UK HTA programme systematic reviews and 300 other systematic reviews, including Cochrane reviews (n = 45). The percentage of HTA reviews with required elements of conduct and reporting was frequently very similar to Cochrane and much higher than all other systematic reviews, e.g. availability of protocols (90, 98 and 16% respectively); the specification of study design criteria (100, 100, 79%); the reporting of outcomes (100, 100, 78%), quality assessment (100, 100, 70%); the searching of trial registries for unpublished data (70, 62, 19%); reporting of reasons for excluding studies (91, 91 and 70%) and reporting of authors' conflicts of interests (100, 100, 87%). HTA reviews only compared less favourably with Cochrane and other reviews in assessments of publication bias., Conclusions: UK HTA systematic reviews are often produced within a specific policy-making context. This context has implications for timelines, tools and resources. However, UK HTA systematic reviews still tend to present standards of conduct and reporting equivalent to "gold standard" Cochrane reviews and superior to systematic reviews more generally.

The article presents information on the history of health technology assessment (HTA). HTA started in the U.S. with the establishment of the U.S. Office of Technology Assessment (OTA) in 1972, which was disbanded in 1995. In 1999, Great Britain established the National Institute for Clinical Excellence (NICE), which reportedly contributed to the globalization of HTA. The article also presents a comparison between HTA and evidence-based medicine (EBM).

The article presents information on the history of health technology assessment (HTA) in Great Britain. Health technology assessment reportedly expanded at a fast pace in the 1990s, after the British National Health Service (NHS) decided to spend up to 1.5% of its budget on research and development (R&D). It is stated that the international image of HTA in Great Britain was strengthened after the establishment of the National Institute for Clinical Excellence (NICE) in 1999.