OBJECTIVE: To provide an overview of analytical methods in scientific literature for comparing uncontrolled medicine trials to external controls from individual patient-level real-world data (IPD-RWD). In addition, to compare these methods with recommendations made in guidelines from European regulatory and health technology assessment (HTA) organizations and with their evaluations described in assessment reports.
METHODS: A systematic literature review (until March 1st 2023) in PubMed and Connected Papers was performed to identify analytical methods for comparing uncontrolled trials with external controls from IPD-RWD. These methods were compared descriptively to methods recommended in method guidelines and encountered in assessment reports of the European Medicines Agency (2015-2020) and four European HTA organizations (2015-2023).
RESULTS: Thirty-four identified scientific articles described analytical methods for comparing uncontrolled trial data to IPD-RWD-based external controls. The various methods covered controlling for confounding and/or dependent censoring, correction for missing data; and analytical comparative modelling methods. Seven guidelines also focused on research design, RWD quality and transparency aspects, and four of those recommended analytical methods for comparisons with IPD-RWD. The methods discussed in regulatory (n=15) and HTA (n=35) assessment reports were often based on aggregate data and lacked transparency due to the few details provided.
CONCLUSIONS: Literature and guidelines suggest a methodological approach to comparing uncontrolled trials with external controls from IPD-RWD similar to target trial emulation, using state-of-the-art methods. External controls supporting regulatory and HTA decision-making were rarely in line with this approach. Twelve recommendations are proposed to improve the quality and acceptability of these methods.

Previous reviews on the cost of illness (COI) of Parkinson\'s disease (PD) have often focused on health-care costs due to PD, underestimating its effects on other sectors. This systematic review determines the COI of PD from a societal perspective. The protocol was registered in PROSPERO (ID: CRD42023428937). Embase, Medline, and EconLit were searched up to October 12, 2023, for studies determining the COI of PD from a societal perspective. From 2812 abstracts, 17 studies were included. The COI of PD averaged €20,911.37 per patient per year, increasing to almost €100,000 in the most severely affected patients. Health-care costs accounted for 46.1% of total costs, followed by productivity loss (37.4%) and costs to patient and family (16.4%). The COI of PD strongly varied between different geographical regions, with costs in North America 3.6 times higher compared to Asia. This study is the first to identify the relative importance of different cost items. Most important were reduced employment, government benefits, informal care, medication, nursing homes, and hospital admission. There was strong variety in the cost items that were included, with 55.2% of cost items measured in fewer than half of articles. Our review shows that PD-COI is high and appears in various cost sectors, with strong variety in the cost items included in different studies. Therefore, a guideline for the measurement of COI in PD should be developed to harmonize this. This article provides a first step toward the development of such a tool by identifying which cost items are most relevant. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Vaccine-preventable diseases continue to generate a substantial burden on health, healthcare systems, and societies, which is projected to increase with population ageing. There is a need to better understand the full value of adult immunisation programmes corresponding to the broader value of vaccine frameworks that are recommended for evidence-based decision-making. This review aims to summarise and map evidence for the value of selected adult immunisation programmes (seasonal influenza, pneumococcal disease, RSV, and HZ) in ten diverse countries. We conducted a structured literature review of evidence published from 2017 to 2023. An existing framework was used to structure the assessment, developing matrices demonstrating the elements of value evidenced for each vaccine and country of focus. Our analysis showed substantial evidence base on the value of adult immunisation programmes, but the availability of evidence varied by value element and by vaccine. The impact on the quality of life of the vaccinated individual was the most evidenced value element. Mortality benefits for vaccinated individuals and cost-offsets to healthcare systems were also well-evidenced. The availability of evidence for \'broader\' societal value elements (such as transmission value, carer productivity and impact on social equity, and antimicrobial resistance prevention) varied. No evidence was identified relating to the broader value elements of macroeconomic effects, value to other interventions, or effects on the quality of life of caregivers. Robust evidence exists to show that adult immunisation programmes generate substantial value for population health and health systems, yet some elements of broader value remain underrepresented in the academic literature. Without such evidence, the full value of immunisation programmes is underestimated, risking suboptimal policy decisions.

Cost-effectiveness analyses (CEA) are important in healthcare decision-making and resource allocation; however, expanding the scope of CEAs beyond the traditional clinicoeconomic concepts to also include value elements such as health equity has attracted much interest in recent years. This umbrella review aimed to synthesize evidence on how equity concepts have been considered in modified types of CEAs. Publicly available articles in MEDLINE were searched on January 25, 2024, to identify systematic reviews (SLRs) published in English since 2013 that incorporate health equity considerations in CEAs. Title/abstract, full-text article screening and data extraction were conducted by a single reviewer and validated by a second reviewer. Results were qualitatively synthesized to identify common themes. Eight SLRs were included. Distributional CEAs (DCEA), equity-based weighting, extended CEA (ECEA), mathematical programming and multi-criteria decision analysis (MCDA) were the most discussed approaches. A lack of consensus on the best approach for incorporating health equity into CEAs was highlighted, as these approaches are not currently consistently used in decision-making. Important limitations included scarcity of robust data to inform health equity indices, bias associated with commonly used health outcome metrics and the challenge of accounting for additional contextual factors such as fairness and opportunity costs. Proposals to expand CEAs to address equity issues come with challenges due to data unavailability, methods complexity, and decision-makers unfamiliarity with these approaches. Our review indicates that extended and distributional CEAs can support decision-making by capturing the impact of inequity on the clinical and cost-effectiveness assessment of treatments, although future modeling should account for additional contextual factors such as fairness and opportunity costs. Recommendations for actions moving forward include standardization of data collection for outcomes related to equity and familiarity with methodologies to account for the complexities of integrating health equity considerations in CEAs.

There is global interest in institutionalizing Health Technology Assessment (HTA) to inform resource allocation decisions. However, institutionalization of HTA remains limited particularly in low- and lower-middle-income countries. We conducted this scoping review to synthesize evidence on factors that influence the institutionalization of HTA at the macro (national)-level across countries globally. We searched for relevant literature in six databases namely PubMed, Embase, CINAHL, Scopus, EconLit, and Google Scholar. We conducted the last search on December 31, 2021. We identified 77 articles that described factors that influence institutionalization of HTA across 135 high-, middle-, and low-income countries. We analyzed these articles thematically. We identified five sets of factors that influence the institutionalization of HTA across countries of different income levels. These factors include: (1) organizational resources such as organizational structures, and skilled human, financial, and information resources; (2) legal frameworks, policies, and guidelines for HTA; (3) learning and advocacy for HTA; (4) stakeholder-related factors such as stakeholders\' interests, awareness, and understanding; and (5) collaborative support for HTA through international networks and non-governmental and multi-lateral organizations. Countries seeking to institutionalize HTA should map the availability of the factors identified in this review. Developing these factors wherever necessary can influence a country\'s capacity to institutionalize the conduct and use of HTA.

OBJECTIVE: Estimates of minimally important differences (MID) can assist interpretation of data collected using patient-reported outcomes (PRO), but variability exists in the emphasis placed on MIDs in health technology assessment (HTA) guidelines. This study aimed to identify to what extent information on the MID of a commonly used PRO, the EQ-5D, is required and utilised by selected HTA agencies.
METHODS: Technology appraisal (TA) documents from HTA agencies in England, France, Germany, and the US between 2019 and 2021 were reviewed to identify documents which discussed MID of EQ-5D data as a clinical outcome assessment (COA) endpoint.
RESULTS: Of 151 TAs utilising EQ-5D as a COA endpoint, 58 (38%) discussed MID of EQ-5D data. Discussion of MID was most frequent in Germany, in 75% (n = 12/16) of Gemeinsamer Bundesausschuss (G-BA) and 44% (n = 34/78) of Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen, (IQWiG) TAs. MID was predominantly applied to the EQ-VAS (n = 50), most frequently using a threshold of > 7 or > 10 points (n = 13). G-BA and IQWiG frequently criticised MID analyses, particularly the sources of MID thresholds for the EQ-VAS, as they were perceived as being unsuitable for assessing the validity of MID.
CONCLUSIONS: MID of the EQ-5D was not frequently discussed outside of Germany, and this did not appear to negatively impact decision-making of these HTA agencies. While MID thresholds were often applied to EQ-VAS data in German TAs, analyses were frequently rejected in benefit assessments due to concerns with their validity. Companies should pre-specify analyses of continuous data in statistical analysis plans to be considered for treatment benefit assessment in Germany.

UNASSIGNED: Identify, through a systematic review, the main domains and methods to support health technology assessment of Medical Devices (MD) from the perspective of technological incorporation into healthcare systems.
UNASSIGNED: Performed structured searches in MEDLINE, Embase, BVS, Cochrane Library, and Web of Science for full studies published between 2017 and May 2023. Selection, extraction, and quality assessment were performed by two blinded reviewers, and discrepancies were resolved by a third reviewer.
UNASSIGNED: A total of 5,790 studies were retrieved, of which 41 were included. We grouped the identified criteria into eight domains for the evaluations.
UNASSIGNED: Overall, studies discuss the need to establish specific methods for conducting HTA in MD. Due to the wide diversity of MD types, a single methodological guideline may not encompass all the specificities and intrinsic characteristics of the plurality of MD. Studies suggest using clustering criteria through technological characterization as a strategy to make the process as standardized as possible.

OBJECTIVE: This systematic literature review aimed to explore experiences worldwide of societal preferences integration into health technology assessments (HTAs) for rare diseases (RDs) and orphan drugs (ODs) through the implementation of multicriteria decision analysis (MCDA), discrete choice experiments (DCEs), and person trade-off (PTO) methods, among others.
METHODS: A systematic search of the literature was conducted in April 2021 using PubMed, Cochrane, Embase, and Scopus databases. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses approach was used for the review phases. Finally, the Promoting Action on Research Implementation in Health Services framework was used to discuss the implementation of these instruments in the RD context.
RESULTS: A total of 33 articles met the inclusion criteria. The studies measured societal preferences for RD and OD as part of HTA using MCDA (n = 17), DCE (n = 8), and PTO (n = 4), among other methods (n = 4). These found that patients and clinicians do not prioritize funding based on rarity. The public is willing to allocate funds only if the OD demonstrates effectiveness and improves the quality of life, considering as relevant factors disease severity, unmet health needs, and quality of life. Conversely, HTA agency experts preferred their current approach, placing more weight on cost-effectiveness and evidence quality, even though they expressed concern about the fairness of the drug review process.
CONCLUSIONS: MCDA, PTO, and DCE are helpful and transparent methods for assessing societal preferences in HTA for RD and OD. However, their methodological limitations, such as arbitrary criteria selection, subjective scoring methods, framing effects, weighting adaptation, and value measurement models, could make implementation challenging.

UNASSIGNED: A robust Health Technology Assessment (HTA) framework is crucial to address the rising burden of healthcare costs and to inform decision-making to promote high-quality health systems. This research aims to describe the HTA methods and mechanisms for the successful implementation of HTA in the WHO South-East Asia region, and contextualize the synthesized evidence relevant to Indian settings.
UNASSIGNED: Realist review involves developing a program theory by conducting a systematic search strategy, screening, study selection, data extraction, and data synthesis. A systematic search for literature will be conducted on PubMed (NCBI), EMBASE (Elsevier), Scopus (Elsevier), Web of Science (Clarivate), and ProQuest Central for identifying the methods used for HTA of health technology interventions. Stakeholder consultations will be conducted to develop a program theory following the Context-Mechanism-Outcome configurations (CMOcs) framework. Searches for primary evidence will be conducted iteratively. Data will be extracted and tested against the programme theory. The proposed realist review will be reported as per the Realist and MEta-narrative Evidence Syntheses: Evolving Standards [RAMESES II] guidelines.
UNASSIGNED: To our knowledge, there has been no comprehensive review conducted to understand the mechanisms of HTA methods in the WHO South-East Asia region. The findings from the realist review will help us understand the mechanisms through which the HTA could work in WHO South-East Asian countries. We will then contextualize the findings obtained from evidence to Indian settings, based on program theory development through stakeholder consultation. A framework will be developed that can be used by policymakers/HTA experts in India for effective implementation of the same.

Comprehensive Genomic Profiling (CGP) allows for the identification of many targets. Reimbursement decision-making is, however, challenging because besides the health benefits of on-label treatments and costs, other factors related to diagnostic and treatment pathways may also play a role. The aim of this study was to identify which other factors are relevant for the technology assessment of CGP and to summarize the available evidence for these factors. After a scoping search and two expert sessions, five factors were identified: feasibility, test journey, wider implications of diagnostic results, organisation of laboratories, and \"scientific spillover\". Subsequently, a systematic search identified 83 studies collecting mainly evidence for the factors \"test journey\" and \"wider implications of diagnostic results\". Its nature was, however, of limited value for decision-making. We recommend the use of comparative strategies, uniformity in outcome definitions, and the inclusion of a comprehensive set of factors in future evidence generation.