A health technology assessment of personalized nutrition interventions using the EUnetHTA HTA Core Model.

OBJECTIVES: Poor nutrition links to chronic diseases, emphasizing the need for optimized diets. The EU-funded project PREVENTOMICS, introduced personalized nutrition to address this. This study aims to perform a health technology assessment (HTA) comparing personalized nutrition interventions developed through this project, with non-personalized nutrition interventions (control) for people with normal weight, overweight, or obesity. The goal is to support decisions about further development and implementation of personalized nutrition. METHODS: The PREVENTOMICS interventions were evaluated using the European Network for HTA Core Model, which includes a methodological framework that encompasses different domains for value assessment. Information was gathered via [1] different statistical analyses and modeling studies, [2] questions asked of project partners and, [3] other (un)published materials. RESULTS: Clinical trials of PREVENTOMICS interventions demonstrated different body mass index changes compared to control; differences ranged from -0.80 to 0.20 kg/m2. Long-term outcome predictions showed generally improved health outcomes for the interventions; some appeared cost-effective (e.g., interventions in UK). Ethical concerns around health inequality and the lack of specific legal regulations for personalized nutrition interventions were identified. Choice modeling studies indicated openness to personalized nutrition interventions; decisions were primarily affected by intervention's price. CONCLUSIONS: PREVENTOMICS clinical trials have shown promising effectiveness with no major safety concerns, although uncertainties about effectiveness exist due to small samples (n=60-264) and short follow-ups (10-16 weeks). Larger, longer trials are needed for robust evidence before implementation could be considered. Among other considerations, developers should explore financing options and collaborate with policymakers to prevent exclusion of specific groups due to information shortages.

Real-world data: a comprehensive literature review on the barriers, challenges, and opportunities associated with their inclusion in the health technology assessment process.

Objective: This review aimed to assess the current use and acceptance of real-world data (RWD) and real-world evidence (RWE) in health technology assessment (HTA) process. It additionally aimed to discern stakeholders' viewpoints concerning RWD and RWE in HTA and illuminate the obstacles, difficulties, prospects, and consequences associated with the incorporation of RWD and RWE into the realm of HTA. Methods: A comprehensive PRISMA-based systematic review was performed in July 2022 in PubMed/Medline, Scopus, IDEAS-RePEc, International HTA database, and Centre for Reviews and Dissemination with ad hoc supplementary search in Google Scholar and international organization websites. The review included pre-determined inclusion criteria while the selection of eligible studies, the data extraction process and quality assessment were carried out using standardized and transparent methods. Results: Twenty-nine (n = 29) studies were included in the review out of 2,115 studies identified by the search strategy. In various global contexts, disparities in RWD utilization were evident, with randomized controlled trials (RCTs) serving as the primary evidence source. RWD and RWE played pivotal roles, surpassing relative effectiveness assessments (REAs) and significantly influencing decision-making and cost-effectiveness analyses. Identified challenges impeding RWD integration into HTA encompassed limited local data access, complexities in non-randomized trial design, data quality, privacy, and fragmentation. Addressing these is imperative for optimal RWD utilization. Incorporating RWD/RWE in HTA yields multifaceted advantages, enhancing understanding of treatment efficacy, resource utilization, and cost analysis, particularly via patient registries. RWE complements assessments of advanced therapy medicinal products (ATMPs) and rare diseases. Local data utilization strengthens HTA, bridging gaps when RCT data is lacking. RWD aids medical device decision-making, cancer drug reassessment, and indirect treatment comparisons. Challenges include data availability, stakeholder acceptance, expertise, and privacy. However, standardization, training, collaboration, and guidance can surmount these barriers, fostering enhanced RWD utilization in HTA. Conclusion: This study highlights the intricate global landscape of RWD and RWE acceptance in HTA. Recognizing regional nuances, addressing methodological challenges, and promoting collaboration are pivotal, among others, for leveraging RWD and RWE effectively in healthcare decision-making.

HTA community perspectives on the use of patient preference information: lessons learned from a survey with members of HTA bodies.

This research sought to assess whether and how patient preference (PP) data are currently used within health technology assessment (HTA) bodies and affiliated organizations involved in technology/drug appraisals and assessments. An exploratory survey was developed by the PP Project Subcommittee of the HTA International Patient and Citizen Involvement Interest Group to gain insight into the use, impact, and role of PP data in HTA, as well as the perceived barriers to its incorporation. Forty members of HTA bodies and affiliated organizations from twelve countries completed the online survey. PP data were reported to be formally considered as part of the HTA evidence review process by 82.5 percent of the respondents, while 39.4 percent reported that most of the appraisals and assessments within their organization in the past year had submitted PP data. The leading reason for why PP data were not submitted in most assessments was time/resource constraints followed by lack of clarity on PP data impact. Participants reported that PP data had a moderate level of influence on the deliberative process and outcome of the decision, but a higher level of influence on the decision's quality. Most (81.8 percent) felt patient advocacy groups should be primarily responsible for generating and submitting this type of evidence. Insights from the survey confirm the use of PP data in HTA but reveal barriers to its broader and more meaningful integration. Encouragingly, participants believe obstacles can be overcome, paving the way for a second phase of research involving in-depth collaborative workshops with HTA representatives.

Cross-sectional analysis of use of real-world data in single technology appraisals of oncological medicine by the National Institute for Health and Care Excellence in 2011-2021.

OBJECTIVES: This study aims to identify how real-world data (RWD) have been used in single technology appraisals (STAs) of cancer drugs by the National Institute for Health and Care Excellence (NICE). DESIGN: Cross-sectional study of NICE technology appraisals of cancer drugs for which guidance was issued between January 2011 and December 2021 (n=229). The appraisals were reviewed following a published protocol to extract the data about the use of RWD. The use of RWD was analysed by reviewing the specific ways in which RWD were used and by identifying different patterns of use. PRIMARY OUTCOME MEASURE: The number of appraisals where RWD are used in the economic modelling. RESULTS: Most appraisals used RWD in their economic models. The parametric use of RWD was commonly made in the economic models (76% of the included appraisals), whereas non-parametric use was less common (41%). Despite widespread use of RWD, there was no dominant pattern of use. Three sources of RWD (registries, administrative data, chart reviews) were found across the three important parts of the economic model (choice of comparators, overall survival and volume of treatment). CONCLUSIONS: NICE has had a long-standing interest in the use of RWD in STAs. A systematic review of oncology appraisals suggests that RWD have been widely used in diverse parts of the economic models. Between 2011 and 2021, parametric use was more commonly found in economic models than non-parametric use. Nonetheless, there was no clear pattern in the way these data were used. As each appraisal involves a different decision problem and the ability of RWD to provide the information required for the economic modelling varies, appraisals will continue to differ with respect to their use of RWD.

Efficacy, safety, and cost-effectiveness analysis of Cerebrolysin in acute ischemic stroke: A rapid health technology assessment.

This study conducts a rapid health technology assessment to systematically evaluate the effectiveness, safety, and cost-effectiveness of Cerebrolysin as an adjunctive therapy for acute ischemic stroke to provide evidence-based medicine for clinical decisions of Cerebrolysin. All systematic reviews/meta-analyses, pharmacoeconomic studies, and health technology assessment reports of Cerebrolysin for the treatment of acute ischemic stroke before August 17, 2023, were retrieved from PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang, Weipu, Sinomed database and the official website of health technology assessment. According to the inclusion and exclusion criteria, 2 researchers independently carried out screening, data extraction, and quality evaluation and descriptively analyzed the results of the included studies. A total of 14 pieces of literature were incorporated, comprising 8 systematic reviews/meta-analyses and 6 pharmacoeconomic studies. In terms of effectiveness, compared to control groups, the use of Cerebrolysin as a treatment for acute ischemic stroke demonstrates certain advantages, including enhancement in total efficacy rate, neurological function, upper limb motor dysfunction, and facilitation of the recovery of activities of daily living. Especially in patients with moderate to severe acute ischemic stroke, Cerebrolysin has demonstrated the ability to enhance neurological function recovery and ameliorate disabilities. Regarding safety, adverse reactions were mild or comparable to those in the control group. The primary findings of economic studies reveal that advocating for the use of Cerebrolysin offers certain cost-effectiveness advantages. Cerebrolysin contributes to improved clinical efficacy and evaluation indexes while demonstrating favorable safety and economic benefits.

Evidence Synthesis and Linkage for Modelling the Cost-Effectiveness of Diagnostic Tests: Preliminary Good Practice Recommendations.

OBJECTIVES: To develop preliminary good practice recommendations for synthesising and linking evidence of treatment effectiveness when modelling the cost-effectiveness of diagnostic tests. METHODS: We conducted a targeted review of guidance from key Health Technology Assessment (HTA) bodies to summarise current recommendations on synthesis and linkage of treatment effectiveness evidence within economic evaluations of diagnostic tests. We then focused on a specific case study, the cost-effectiveness of troponin for the diagnosis of myocardial infarction, and reviewed the approach taken to synthesise and link treatment effectiveness evidence in different modelling studies. RESULTS: The Australian and UK HTA bodies provided advice for synthesising and linking treatment effectiveness in diagnostic models, acknowledging that linking test results to treatment options and their outcomes is common. Across all reviewed models for the case study, uniform test-directed treatment decision making was assumed, i.e., all those who tested positive were treated. Treatment outcome data from a variety of sources, including expert opinion, were utilised for linked clinical outcomes. Preliminary good practice recommendations for data identification, integration and description are proposed. CONCLUSION: Modelling the cost-effectiveness of diagnostic tests poses unique challenges in linking evidence on test accuracy to treatment effectiveness data to understand how a test impacts patient outcomes and costs. Upfront consideration of how a test and its results will likely be incorporated into patient diagnostic pathways is key to exploring the optimal design of such models. We propose some preliminary good practice recommendations to improve the quality of cost-effectiveness evaluations of diagnostics tests going forward.

Real-world evidence for coverage determination of treatments for rare diseases.

Health technology assessment (HTA) decisions for pharmaceuticals are complex and evolving. New rare disease treatments are often approved more quickly through accelerated approval schemes, creating more uncertainties about clinical evidence and budget impact at the time of market entry. The use of real-world evidence (RWE), including early coverage with evidence development, has been suggested as a means to support HTA decisions for rare disease treatments. However, the collection and use of RWE poses substantial challenges. These challenges are compounded when considered in the context of treatments for rare diseases. In this paper, we describe the methodological challenges to developing and using prospective and retrospective RWE for HTA decisions, for rare diseases in particular. We focus attention on key elements of study design and analyses, including patient selection and recruitment, appropriate adjustment for confounding and other sources of bias, outcome selection, and data quality monitoring. We conclude by offering suggestions to help address some of the most vexing challenges. The role of RWE in coverage and pricing determination will grow. It is, therefore, necessary for researchers, manufacturers, HTA agencies, and payers to ensure that rigorous and appropriate scientific principles are followed when using RWE as part of decision-making.

Preparing future doctors for evidence-based practice: a study on health technology assessment awareness and its predictors in Malaysia.

OBJECTIVES: To determine the level of awareness of health technology assessment (HTA) and its predictors among clinical year medical students in public universities in Klang Valley, Malaysia. METHODS: A cross-sectional study using the stratified random sampling method was conducted among clinical year medical students in four public universities in Klang Valley, Malaysia. Data on the level of awareness of HTA and its associated factors were collected using a self-administered online questionnaire. Descriptive, bivariate, and multivariate analyses were performed using IBM SPSS version 27 to determine the level of awareness of HTA and its predictors. RESULTS: Majority (69 percent) of participants had a low level of awareness of HTA. The predictors of high-level awareness of HTA were attitude toward HTA (adjusted odds ratio (AOR) = 7.417, 95 percent confidence interval (CI): 3.491, 15.758), peer interaction on HTA (AOR = 0.320, 95 percent CI: 0.115, 0.888), and previous training on HTA (AOR = 4.849, 95 percent CI: 1.096, 21.444). CONCLUSIONS: Most future doctors in public universities exhibit a low awareness of HTA. This study highlights the interplay between attitudes toward HTA, peer interaction, and previous training as influential predictors of HTA awareness. An integrated and comprehensive educational approach is recommended to cultivate a positive attitude and harness the positive aspects of peer interaction while mitigating the potential negative impact of misconceptions. Emphasizing early exposure to HTA concepts through structured programs is crucial for empowering the upcoming generation of healthcare professionals, enabling them to navigate HTA complexities and contribute to evidence-based healthcare practices in Malaysia and beyond.

A literature review of quality assessment and applicability to HTA of risk prediction models of coronary heart disease in patients with diabetes.

This literature review had two objectives: to identify models for predicting the risk of coronary heart diseases in patients with diabetes (DM); and to assess model quality in terms of risk of bias (RoB) and applicability for the purpose of health technology assessment (HTA). We undertook a targeted review of journal articles published in English, Dutch, Chinese, or Spanish in 5 databases from 1st January 2016 to 18th December 2022, and searched three systematic reviews for the models published after 2012. We used PROBAST (Prediction model Risk Of Bias Assessment Tool) to assess RoB, and used findings from Betts et al. 2019, which summarized recommendations and criticisms of HTA agencies on cardiovascular risk prediction models, to assess model applicability for the purpose of HTA. As a result, 71 % and 67 % models reporting C-index showed good discrimination abilities (C-index >= 0.7). Of the 26 model studies and 30 models identified, only one model study showed low RoB in all domains, and no model was fully applicable for HTA. Since the major cause of high RoB is inappropriate use of analysis method, we advise clinicians to carefully examine the model performance declared by model developers, and to trust a model if all PROBAST domains except analysis show low RoB and at least one validation study conducted in the same setting (e.g. country) is available. Moreover, since general model applicability is not informative for HTA, novel adapted tools may need to be developed.

Conducting a health technology assessment in the West Bank, occupied Palestinian territory: lessons from a feasibility project.

OBJECTIVES: To achieve universal health coverage (UHC), countries must make difficult choices to optimize the use of scarce resources. There is a growing interest in using evidence-based priority setting processes, such as Health Technology Assessment (HTA), to inform these decisions. In 2020, the Palestinian Institute of Public Health (PNIPH) and the Norwegian Institute of Public Health (NIPH) initiated a pilot to test the feasibility of coproducing an HTA on breast cancer screening in the West Bank, occupied Palestinian Territory. Additionally, a secondary aim was to test whether using an adaptive HTA (aHTA) approach that searched and transferred published evidence syntheses could increase the speed of HTA production. METHODS: The applied stepwise approach to the HTA is described in detail and can be summarized as defining a core team, topic selection, and prioritization; undertaking the HTA including adaptation using tools from the European Network for HTA (EUnetHTA) and stakeholder engagement; and concluding with dissemination. RESULTS: The aHTA approach was faster but not as quick as anticipated, which is attributed to (i) the lack of availability of local evidence for contextualizing findings and (ii) the necessity to build trust between the team and stakeholders. Some delays followed from the COVID-19 pandemic, which showed the importance of good risk anticipation and mitigation. Lastly, other important lessons included the ability of virtual collaborations, the value of capacity strengthening initiatives within low- and middle-income countries (LMICs), and the need for early stakeholder engagement. Overall, the pilot was successfully completed. CONCLUSION: This was the first HTA of its kind produced in Palestine, and despite the challenges, it shows that HTA analysis is feasible in this setting.

A blueprint for health technology assessment capacity building: lessons learned from Malta.

OBJECTIVES: The development and strengthening of health technology assessment (HTA) capacity on the individual and organizational level and the wider environment is relevant for cooperation on HTAs. Based on the Maltese case, we provide a blueprint for building HTA capacity. METHODS: A set of activities were developed based on Pichler et al.'s framework and the starting HTA capacity in Malta. Individual level activities focused on strengthening epidemiological and health economic skills through online and in-person training. On the organizational level, a new HTA framework was developed which was subsequently utilized in a shadow assessment. Awareness campaign activities raised awareness and support in the wider environment where HTAs are conducted and utilized. RESULTS: The time needed to build HTA capacity exceeded the planned two years accommodating the learning progress of the assessors. In addition to the planned trainings, webinars supplemented the online courses, allowing for more knowledge exchange. The advanced online course was extended over time to facilitate learning next to the assessors' daily tasks. Training sessions were added to implement the new economic evaluation framework, which was utilized in a second shadow assessment. Awareness by decision-makers was achieved with reports, posters, and an article on the current and developing HTA capacity. CONCLUSIONS: It takes time and much (hands-on) training to build skills for conducting complex assessment such as HTAs. Facilitating exchange with knowledgeable parties is crucial for succeeding as well as the buy-in of local managers motivating staff. Decision-makers need to be on-boarded for the continued success of HTA capacity building.

Assessment of quality of data submitted for NICE technology appraisals over two decades.

BACKGROUND: The National Institute for Health and Care Excellence (NICE) pioneered the Health Technology Assessment (HTA) processes and methodologies. Technology appraisals (TAs) focus on pharmaceutical products and clinical and economic data, which are presented by the product manufacturers to the NICE appraisal committee for decision-making. Uncertainty in data reduces the chance of a positive outcome from the HTA process or requires a higher discount. OBJECTIVE: To investigate the quality of clinical data (comparator, quality of life (QoL), randomised controlled trials (RCTs) and overall quality of evidence) submitted by the manufacturers to NICE. DESIGN: This retrospective evaluation analysed active TAs published between 2000 and 2019 (up to TA600). METHODS: For all TAs, we extracted data from the Assessment Group and Evidence Review Group reports and Final Appraisal Determinations on (1) the quality of submitted RCTs and (2) the overall quality of evidence submitted for decision-making. For single TAs, we also extracted data and its critique on QoL and comparators. Each category was scored for quality and analysed using descriptive statistics. RESULTS: 409 TAs were analysed (multiple technology appraisals (MTA)=104, single technology appraisal (STA)=305). In two-thirds of TAs, the overall quality of evidence was either poor (n=224, 55%) or unacceptable (n=41, 10%). In 39% (n=119) of the STAs, the quality of comparative evidence was considered poor, and in 17% (n=51) unacceptable. In 44% (n=135) of STAs, the quality of QoL data was considered poor, 15% (n=47) unacceptable, 33% (n=102) acceptable and 7% (n=21) as good. Over 20 years of longitudinal analysis did not show improvements in the quality of evidence submitted to NICE. CONCLUSION: We found that the primary components of clinical evidence influencing NICE's decision-making framework were of poor quality. It is essential to continue to generate robust clinical data for premarket and postmarket introduction of medicines into clinical practice to ensure they deliver benefits to patients.

Minimally Invasive Bleb Surgery for Glaucoma: A Health Technology Assessment.

Background: Glaucoma is the term for a group of eye disorders that causes progressive damage to the optic nerve, which can lead to visual impairment and, potentially, irreversible blindness. Minimally invasive bleb surgery (MIBS) reduces eye pressure through the implantation of a device that creates a new subconjunctival outflow pathway for eye fluid drainage. MIBS is a less invasive alternative to conventional/incisional glaucoma surgery (e.g., trabeculectomy). We conducted a health technology assessment of MIBS for people with glaucoma, which included an evaluation of effectiveness, safety, the budget impact of publicly funding MIBS, and patient preferences and values. Methods: We performed a systematic literature search of the clinical evidence. We assessed the risk of bias of each included study using the Cochrane Risk of Bias 1.0 tool for randomized controlled trials (RCTs) and the Risk of Bias Assessment tool for Nonrandomized Studies (RoBANS) for comparative observational studies, and the quality of the body of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. We conducted an economic literature search and we estimated the budget impact of publicly funding MIBS in Ontario. We did not conduct a primary economic evaluation due to the limited long-term effectiveness data. We summarized the preferences and values evidence from previous health technology assessments to understand the perspectives and experiences of patients with glaucoma. Results: We included 41 studies (2 RCTs and 39 comparative observational studies) in the clinical evidence review. MIBS may reduce intraocular pressure and the number of medications used, but we are uncertain if MIBS results in outcomes similar to trabeculectomy (GRADE: Moderate to Very low). Compared with trabeculectomy, MIBS may result in fewer follow-up visits and interventions, and adverse events (GRADE: Moderate to Very Low). MIBS may also reduce intraocular pressure and the number of antiglaucoma medications used, compared with other glaucoma treatments, but the evidence is uncertain (GRADE: Very low). Our economic evidence review identified two directly applicable studies. The results of these studies indicate that the cost-effectiveness of MIBS is highly uncertain, and the cost of glaucoma interventions are likely to vary across provinces. The annual budget impact of publicly funding MIBS in Ontario ranged from $0.11 million in year 1 to $0.67 million in year 5, for a total 5-year budget impact estimate of $1.93 million. Preferences and values evidence suggests that fear of ultimate blindness and difficulty managing medication for glaucoma led patients to explore other treatment options such as MIBS. Glaucoma patients found minimally invasive glaucoma surgery (MIGS) procedure beneficial, with minimal side effects and recovery time. Conclusions: Minimally invasive bleb surgery reduces intraocular eye pressure and the number of antiglaucoma medications needed, but we are uncertain if the outcomes are similar to trabeculectomy (GRADE: Moderate to Very low). However, MIBS may be safer than trabeculectomy (GRADE: Moderate to Very low) and result in fewer follow-ups (GRADE: Moderate to Very low). MIBS may also improve glaucoma symptoms compared with other glaucoma treatments, but the evidence is very uncertain (GRADE: Very low).We estimate that publicly funding MIBS would result in an additional cost of $1.93 million over 5 years. Patients who underwent MIGS procedures found them to be generally successful and beneficial, with minimal side effects and recovery time. We could not draw conclusions about specific MIBS procedures or long-term outcomes.

Intrathecal Drug Delivery Systems for Cancer Pain: A Health Technology Assessment.

Background: Pain is a common and very distressing symptom for adults and children with cancer. Compared with other routes of delivery, infusing pain medication directly into the intrathecal space around the spinal cord may reduce the incidence of systemic side effects and allow for more rapid and effective pain relief. We conducted a health technology assessment of intrathecal drug delivery systems (IDDSs) for adults and children with cancer pain, which included an evaluation of effectiveness, safety, cost-effectiveness, the budget impact of publicly funding IDDSs, patient preferences and values, and ethical considerations. Methods: We performed a systematic literature search of the clinical evidence to retrieve systematic reviews, and we selected and reported results from 2 recent reviews that were relevant to our research questions. We complemented the chosen systematic reviews with a literature search to identify primary studies published after December 2020. We used the Risk of Bias in Systematic Reviews (ROBIS) tool to assess the risk of bias of each included systematic review. We assessed the quality of the body of evidence according to the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) Working Group criteria. We performed a systematic economic literature search and conducted a cost-effectiveness analysis comparing IDDSs with standard care (i.e., non-IDDS methods of pain management) from a public payer perspective. We also analyzed the budget impact of publicly funding IDDSs in Ontario. To contextualize the potential value of IDDSs, we spoke with patients with cancer pain and with caregivers of patients with cancer pain. We explored ethical considerations from a review of published literature on the use of IDDSs for the management of cancer pain in adults and children as well as a review of the other components of this health technology assessment to identify ethical considerations relevant to the Ontario context. Results: We included 2 systematic reviews (1 on adults and 1 on children) in the clinical evidence review. In adults with cancer pain who have a life expectancy greater than 6 months, intrathecal drug delivery was associated with a significant reduction in pain intensity compared with before implantation up to a 1-year follow-up (GRADE: Moderate to Low). Improved pain management appeared to be maintained beyond a 4-week follow-up. IDDSs likely decrease the use of systemic opioids (GRADE: Moderate to Low). They may also improve health-related quality of life (GRADE: Low), functional outcomes (GRADE: Low), and survival (GRADE: Low to Very low). In children with cancer pain, IDDSs may reduce pain intensity, improve functional outcomes, and improve survival, but the evidence is very uncertain (all GRADEs: Very low). IDDS implantation carries certain rare risks related to mechanical errors, drug-related side effects, and surgical complications. There are inherent limitations in conducting research in patients with refractory cancer pain; therefore, it is unlikely that higher-quality evidence will emerge in the next few years. Our primary economic evaluation found that IDDSs are more effective and more costly than standard care. The incremental cost-effectiveness ratio of IDDSs compared with standard care is $57,314 per quality-adjusted life-year (QALY) gained. The probability of IDDSs being cost-effective versus standard care is 43.46% at a willingness-to-pay of $50,000 per QALY gained and 72.54% at a willingness-to-pay of $100,000 per QALY gained. Publicly funding IDDSs in Ontario would cost an additional $0.27 million per year, for a total of $1.34 million over the next 5 years. The patients with cancer pain and caregivers with whom we spoke described the debilitating nature of cancer pain and the difficulty of finding effective pain management options. Patients with experience of an IDDS spoke of its effectiveness and its positive impact on their quality of life and mental health. Implementing IDDSs for patients with cancer pain raises several ethical and equity considerations related to the experiences and management of cancer pain, how limitations in evidence may entail uncertainties in clinical and health system decision-making, as well as clinical, geographic, and health system access barriers. Conclusions: Intrathecal drug delivery likely reduces pain intensity and decreases the use of systemic opioids in adults with cancer pain who have a life expectancy greater than 6 months. It may also improve health-related quality of life, functional outcomes, and survival, although the evidence for survival is very uncertain. The clinical evidence in children with cancer pain is very uncertain. IDDS implantation is reasonably safe. Intrathecal drug delivery is more effective and more costly than standard care. We estimate that funding IDDSs in Ontario will result in additional costs of $0.27 million per year, for a total of $1.34 million over the next 5 years. Considerations related to funding and implementing IDDSs for patients with cancer pain in Ontario will require explicit and focused attention to considerations of equity and access in the diagnosis and management of cancer pain and in the use, clinical uptake, and delivery of IDDS pain management.

Justifying the source of external comparators in single-arm oncology health technology submissions: a review of NICE and PBAC assessments.

Background: The drive to expedite patient access for diseases with high unmet treatment needs has come with an increasing use of single-arm trials (SATs), especially in oncology. However, the lack of control arms in such trials creates challenges to assess and demonstrate comparative efficacy. External control (EC) arms can be used to bridge this gap, with various types of sources available to obtain relevant data. Objective: To examine the source of ECs in single-arm oncology health technology assessment (HTA) submissions to the National Institute for Health and Care Excellence (NICE) and the Pharmaceutical Benefits Advisory Committee (PBAC) and how this selection was justified by manufacturers and assessed by the respective HTA body. Methods: Single-arm oncology HTA submission reports published by NICE (England) and PBAC (Australia) from January 2011 to August 2021 were reviewed, with data qualitatively synthesized to identify themes. Results: Forty-eight oncology submissions using EC arms between 2011 and 2021 were identified, with most submissions encompassing blood and bone marrow cancers (52%). In HTA submissions to NICE and PBAC, the EC arm was typically constructed from a combination of data sources, with the company's justification in data source selection infrequently provided (PBAC [2 out of 19]; NICE [6 out of 29]), although this lack of justification was not heavily criticized by either HTA body. Conclusion: Although HTA bodies such as NICE and PBAC encourage that EC source justification should be provided in submissions, this review found that this is not typically implemented in practice. Guidance is needed to establish best practices as to how EC selection should be documented in HTA submissions.

R WE ready for reimbursement? A round up of developments in real-world evidence relating to health technology assessment: part 14.

In this latest update we highlight: a publication from the US FDA regarding the definitions of real-world data (RWD) and real-world evidence (RWE); a publication from academic researchers on a demonstration project for target trial emulation; a publication from the National Institute of Health and Care Excellence (NICE) on the 1 year anniversary of their RWE framework; and a publication from NICE and Flatiron Health on the utility of US RWD for initial UK health technology assessment decision making.

Navigating the unknown: how to best 'reflect' standard of care in indications without a dedicated treatment pathway in health technology assessment submissions.

There is an urgent need for expedited approval and access for new health technologies targeting rare and very rare diseases, some of which are associated with high unmet treatment needs. Once a new technology achieves regulatory approval, the technology needs to be assessed by health technology assessment (HTA) bodies to inform coverage and reimbursement decisions. This assessment quantitatively examines the clinical effectiveness, safety and/or economic impact of the new technology relative to standard of care (SoC) in a specific market. However, in rare and very rare diseases, the patient populations are small and there is often no established treatment pathway available to define 'SoC'. In these situations, several challenges arise to assess the added benefit of a new technology - both clinically and economically - due to lack of established SoC to guide an appropriate comparator selection. These challenges include: How should 'SoC' be defined and characterized in HTA submissions for new technologies aiming to establish new treatment standards? What is usual care without an established clinical pathway? How should the evidence for the comparator 'SoC' (i.e., usual care) arm be collected in situations with low patient representation and, sometimes, limited disease-specific clinical knowledge in certain geographies? This commentary outlines the evidence generation challenges in designing clinical comparative effectiveness for a new technology when there is a lack of established SoC. The commentary also proposes considerations to facilitate the reliable integration of real-world evidence into HTA and decision-making based on the collective experience of the authors.

A Review of Current Approaches to Evaluating and Reimbursing New Medicines in a Subset of OECD Countries.

OBJECTIVES: The aim of this study was to review the current evaluation and funding processes for new drugs in different developed countries, to provide a comparative framework with detailed, homogeneous, and up-to-date information. METHODS: Scientific publications, reports and websites were reviewed between July and December 2021 using PubMed, Google Scholar, and grey literature sources. The main items searched were actors and processes, including timelines, characteristics of clinical and economic evaluations, participation of stakeholders, elements of price and reimbursement decisions, cost-effectiveness thresholds and specific funds. The analysed 13 countries were Australia, Canada, England, France, Germany, Italy, Japan, the Netherlands, Portugal, Scotland, South Korea, Spain and Sweden. RESULTS: Eight countries perform the assessment process separated from the pricing decision. Countries measure each drug's added therapeutic value through multi-attribute value scales, algorithms, non-prescriptive lists of criteria, or quality-adjusted life years (QALYs). Health technology assessment (HTA) methodologies differ in their outcome measures, elicitation techniques, comparators, and perspectives. The criteria used for pricing and reimbursement include humanistic, clinical, and economic aspects. Only Scotland, England, the Netherlands, Canada and Portugal use explicit efficiency thresholds. Health care professionals participate in all assessment committees, and patients are becoming increasingly involved in most countries. The official time from marketing authorisation to the completion of the evaluation and pricing processes varied from 126 to 540 days. CONCLUSIONS: Most analysed countries show a trend towards value-based approaches that consider value for money to society, but also other economic, clinical, and humanistic criteria. Good practices included robustness, transparency, independence, and participation.

Social care data in the UK; current landscape, challenges, and future recommendations.

OBJECTIVES: Social care in the United Kingdom (UK) refers to care provided due to age, illness, disability, or other circumstances. Social care provision offers an intermediary step between hospital discharge and sufficient health for independent living, which subsequently helps with National Health Service (NHS) bed capacity issues. UK Health Technology Assessments (HTAs) do not typically include social care data, possibly due to a lack of high-quality, accessible social care data to generate evidence suitable for submissions. METHODS: We identified and characterized secondary sources of UK social care data suitable for research (as of 2021). Sources were identified and profiled by desk research, supplemented by information from custodians and data experts. RESULTS: We identified twenty-one sources; six high potential (three national, three regional data sources), five future potential, seven limited potential, and three not considered further (outdated or lacking social care data). CONCLUSION: Despite identifying numerous sources of social care data across the UK, opportunities and access for researchers appeared limited and could be improved. This would facilitate a deeper understanding of the clinical and economic burden of disease, the impact of medicines and vaccines on social care, enable better-informed HTA submissions and more efficient allocation of NHS and local council social care resources.