Comprehensive genomic profiling (CGP) identifies many targets at once. However, it is challenging for reimbursement decision-makers to incorporate all potential effects in their assessment. The aim of this study is twofold: first, to identify which factors, besides effectiveness and costs, might influence the choice for CGP in advanced cancer patients, and second, to identify the available evidence for these factors.

We performed a systematic literature review in MEDLINE, Embase, and Scopus with a two-step design. First, a scoping search was performed to identify relevant factors. Extracted factors were grouped with domains of the EUnetHTA core model and ISPOR (Professional Society for Health Economics and Outcomes Research) “value flower.” Two expert sessions were held to validate factors and construct definitions. Second, a systematic search was conducted to identify the available empirical evidence for these factors. Eligibility criteria for the systematic search were the use of CGP (≥200 genes), advanced cancer patients, and the presentation of empirical evidence on one of the factors.

Five factors were identified in the scoping search: “feasibility” (adopting tests in the health care system), “test journey” (pathway from requesting tests until reporting of results), “wider implications of diagnostic results” (impact of test beyond identifying on-label treatments), “organization of laboratories” (organization of tests and access to tests), and “scientific spillover” (learnings of testing). Eighty-three articles were included following the systematic search, and empirical evidence was identified for the factors “test journey” and “wider implications of diagnostic results”. Few studies had adequate comparative study designs. Heterogeneity was observed among studies in the definitions of outcomes and the reported evidence.

Comprehensive reimbursement decision-making for CGP can be supported by including the five identified factors. However, quantifiable evidence was only identified for the “patient test journey” and “wider implications of diagnostic results”. Current literature provides limited high-quality evidence to establish the added benefit of CGP, as adequately designed comparisons are lacking. For evidence-based decision-making, uniform outcome measurements are recommended.

Patients with hematological malignancies are likely to develop hypogammaglobulinemia. Immunoglobulin (Ig) is commonly given to prevent infections, but its overall costs and cost-effectiveness are unknown.

A systematic review was conducted following the PRISMA guidelines to assess the evidence on the costs and cost-effectiveness of Ig, administered intravenously (IVIg) or subcutaneously (SCIg), in adults with hematological malignancies.

Six studies met the inclusion criteria, and only two economic evaluations were identified; one cost-utility analysis (CUA) of IVIg versus no Ig, and another comparing IVIg with SCIg. The quality of the evidence was low. Compared to no treatment, Ig reduced hospitalization rates. One study reported no significant change in hospitalizations following a program to reduce IVIg use, and an observational study comparing IVIg with SCIg suggested that there were more hospitalizations with SCIg but lower overall costs per patient. The CUA comparing IVIg versus no Ig suggested that IVIg treatment was not cost-effective, and the other CUA comparing IVIg to SCIg found that home-based SCIg was more cost-effective than IVIg, but both studies had serious limitations.

Our review highlighted key gaps in the literature: the cost-effectiveness of Ig in patients with hematological malignancies is very uncertain. Despite increasing Ig use worldwide, there are limited data regarding the total direct and indirect costs of treatment, and the optimal use of Ig and downstream implications for healthcare resource use and costs remain unclear. Given the paucity of evidence on the costs and cost-effectiveness of Ig treatment in this population, further health economic research is warranted.

Patient experience data (PED), encompassing patient preferences (PP), patient-reported outcomes (PROs), and patient input, play a pivotal role in understanding patient needs and informing healthcare decision-making, including reimbursement decisions. This study aimed to assess the current barriers hindering the integration of PED into practice and its particular challenges, opportunities, and concrete policy actions for the systematic implementation of PED.

Semistructured interviews (n=38) were conducted with industry (n=12), non-profit organizations and academia (n=4), regulatory authorities (n=6), health technology assessment (HTA) bodies and reimbursement agencies (n=6), and patient organizations (n=10) in Europe. A thematic analysis was conducted to explore stakeholders’ perspectives and to gain a comprehensive understanding of challenges and opportunities related to the systematic implementation of PED. Interview transcripts were analyzed using the thematic framework analysis to extract and elucidate the insights provided by the diverse stakeholders.

HTA and reimbursement interviewees agreed on the value of including quality-of-life data, particularly when assessed using validated PRO measures. Despite acknowledging the potential of PP, there remained reluctance to integrate PP into reimbursement decision-making. Participants expressed divergent opinions regarding who should collect PED, with some regulators favoring industry, while HTA and reimbursement agencies emphasized transparency and independent PED collection. Limited experience in assessing PED also contributed to hesitancy, underscoring the need for more guidelines, especially at the national reimbursement level. Stakeholders endorsed collaboration through joint scientific consultations, expressing optimism about the impact of the Regulation (EU) 2021/2282 on health technology assessment (HTAR).

This study emphasizes the high potential of PED in informing reimbursement decision-making, fostering a more patient-centered approach. Stakeholder disparities highlight the complexity, necessitating more guidance, scientific robustness, transparency, and collaboration. In light of these stakeholder considerations, the upcoming HTAR holds promise to enhance the systematic implementation of PED, aligning healthcare decision-making with patients’ needs and preferences.

Time to reimbursement has been described as a hurdle to availability of new medicines to European patients, with assessment and decision-making processes frequently quoted as taking the majority of time. In light of the upcoming Regulation (EU) 2021/2282 on health technology assessment (HTAR), the aim was to examine timelines and health technology assessment (HTA) recommendations for orphan drugs in Ireland.

The study reviewed all orphan drug submissions to the National Centre for Pharmacoeconomics (NCPE) from January 2020 to December 2023 inclusive. The number of days from marketing authorization to rapid review (RR) commissioning was calculated. The RR and HTA recommendations were identified for all medicines. The timelines for the RR and HTA process were evaluated.

Of the 66 submissions identified, 38 percent were made prior to marketing authorization (MA), eight percent were made within 30 days of MA, and 79 percent were made 30 days post MA. RRs were completed within 32 days (mean). Full HTA was recommended in 62 percent (n=41). Price negotiations were recommended in 38 percent (50% of which have been reimbursed to date). Where a full HTA was recommended (n=41), 20 have been completed to date (price negotiations were recommended in 90%). For those 20 HTAs completed, 11 have been reimbursed to date; a decision is pending for the remainder. HTAs were completed within 200 days (mean).

Data shows that the majority of submissions were made 30 days post MA. A pragmatic approach may have to be taken nationally to accommodate the HTAR post 2024 and those submissions that are made prior to publication of a joint clinical assessment. The majority of orphan drug HTA recommendations lead to reimbursement recommendations.

In France, decisions for pricing and reimbursement for medicinal products are based on appraisals performed by the National authority for health (Haute Autorité de Santé (HAS)). During the appraisal process, additional real-world evidence can be requested as “Post-Registration Studies” (PRS) when there are uncertainties in evidence that could be resolved by additional data collection. To facilitate PRS planning, a retrospective exploratory analysis was conducted to identify the characteristics of medicinal products associated with a PRS request.

This analysis encompassed all appraisals finalized between January 1, 2016 and December 31, 2021 and compared products for which the appraisal led to a PRS request with those that did not.

Six hundred positive opinions for reimbursement were identified, with a PRS request present in 17 percent (n = 103) of cases. The independent characteristics associated with a PRS request were a mild or moderate clinical benefit score, a major to moderate or minor clinical added value score, previous availability under an early access program, and certain therapeutic areas (neurology, pulmonology, and endocrinology). These findings suggest two different profiles of PRS requests: (i) products for which there is uncertainty in the size of the clinical benefit and (ii) innovative products for which a substantial benefit is expected but uncertainties persist.

These results will assist health technology developers to better anticipate data generation to promptly address uncertainties identified by HAS. It may also help HAS and other assessment agencies to work together to improve postlaunch evidence generation according to the characteristics of the medicinal products.

Introduced in July 2021, early access to pharmaceuticals allows French patients to have rapid and reimbursed access to presumed innovative medicines prior to marketing authorization or regular reimbursement registration. The French National Authority for Health (Haute Autorité de Santé [HAS]) is responsible for granting early access authorizations and for health technology assessment upstream of regular reimbursement. This analysis evaluates the outcomes of the 2021 reform.

In collaboration with the national regulatory body (ANSM) and the Ministry of Health, a descriptive and retrospective analysis has been conducted to assess the impact of this reform. The data were extracted from published HAS decisions and from the HAS internal information system (EVAMED). The period considered is the first two years of the reform, from 1 July 2021 to 30 June 2023. Different information has been analyzed, such as conclusions of decisions returned, therapeutic areas concerned, and decision processing time. An additional analysis focused on HAS opinions on regular reimbursement for the medicines for which early access was granted.

In two years, over 250 applications (including first applications, modifications, and renewals) have been submitted, increasing over time, and 180 decisions were issued by HAS within this period. Eighty percent of HAS decisions were positive for early access. Among the medicines for which early access was granted, 86 were also assessed for regular reimbursement, of which 78 percent obtained a positive clinical added value score (at least ASMR IV). Overall, the early access program is estimated to have facilitated coverage approximately nine months before regular reimbursement and benefited over 100,000 patients.

Manufacturers make extensive use of early access applications. A positive assessment of the reform outcomes emerges from this analysis, emphasizing the role of HAS in accelerating patient access to presumed innovative treatments. In light of US experience and of the uncertainties surrounding fast-track authorization procedures, monitoring of the French early access system will continue.

The management of rare diseases is rarely addressed among policymakers and public communities. It is hindered by the lack of information on its epidemiology and burden, especially from the perspective of patients and families with rare diseases. This study aims to understand the perceptions of rare disease patients and their families in the management of rare diseases in Malaysia.

A qualitative interview was used to explore the perceptions of patients and families regarding the management of rare diseases in Malaysia. In-depth interviews were conducted with the rare disease patients or their parents/guardians provided by three major rare disease advocacy groups, between 1 July and 15 September 2016. The interviews focused on two key areas: the challenges associated with rare disease and the issues related to accessing medication.

Out of the nineteen recruited participants, seventeen (89.5 percent) completed the interview sessions. The significance of awareness, knowledge, and support from others emerged as crucial for families and patients living with rare diseases. Despite facing delayed diagnosis and treatment, a majority of patients and parents expressed satisfaction with the advancements in rare disease management. Nevertheless, a prominent challenge revolves around access to enzyme replacement therapy for eligible patients.

This study emphasizes the importance of healthcare professionals understanding patient with rare diseases perceptions to tailor communication strategies, provide accurate information, and address concerns effectively. The message underscores the significance of collaboration between healthcare providers and patient support groups to deliver adequate health information, potentially enhancing patients’ understanding and their illness perceptions.

Rare diseases (RD)-related policies have received significant attention due to the pressing medical requirements associated with these medical conditions and the substantial impact and treatments they may have on healthcare budgets. Nevertheless, policymakers frequently encounter difficulties in managing issues concerning resource allocation and prioritization within this population. Realizing the need to address such problems, this study was conducted to develop a framework based on the multicriteria decision analysis to improve RD reimbursement prioritization in Malaysia.

Primarily, a scoping review was performed to identify the methods and criteria used for the reimbursement of RD treatment, followed by strategic stakeholder engagement and a deliberative process on determining the best approach for the framework, including criteria identification, elicitation of weights, and a pilot assessment using the framework.

The findings reflected the priorities and perspectives of the stakeholders, which identified eight key criteria and their associated weights, namely effectiveness (19.6 percent), disease severity (15.6 percent), safety (14.2 percent), access to treatment (12.6 percent), economic consideration (12.2 percent), type of therapeutic treatment (11.5 percent), availability of alternatives (8.3 percent), and population group (6 percent).

In summary, the developed framework was well-accepted by the Rare Disease Committee, which will be applied as part of the committee deliberation for transparent and equitable decision making on fund allocation and reimbursement of orphan and RD treatment in Malaysia.

The 2021 reform of early access (EA) for medicinal products in France includes a mandatory data collection for each patient. The objective of this work was to perform a two-year review of the protocols for therapeutic use and data collection (PUT-RD) validated by the health technology assessment body (Haute Autorité de Santé [HAS]) in collaboration with the national regulatory body where applicable.

The minimum dataset defined in the PUT-RD varies depending on the regulatory status of the product and may include patients’ characteristics, conditions of use, efficacy, and safety data. A descriptive review of the PUT-RDs approved between 1 July 2021 and 30 June 2023 was carried out by HAS. The following information was retrieved in each published PUT-RD: type of EA (pre- or post-marketing authorization); collection of efficacy data (yes or no) (if yes, inclusion of a patient-reported outcome measure [PROM] or no); type of data source (registry or electronic platform provided by a contract research organization [CRO]).

During the review period, a total of 98 PUT-RDs were validated, corresponding to 98 EA favorable decisions. EAs were authorized prior to marketing authorization in 40 percent of the cases. A collection of follow-up efficacy data was planned in 52 PUT-RDs, including integration of patients’ perspectives through a PROM in 32 PUT-RDs. Data collection through a registry was planned in six PUT-RDs (using the DESCAR-T registry), otherwise data collection was mainly planned through private electronic platforms operated by CROs (80% of the PUT-RDs).

To optimize the generation of relevant clinical data to be used in the regular HTA process, EAs should be requested early, prior to marketing authorization. Additionally, the use of existing data sources, in particular disease registries, is to be developed to avoid duplicate data collection and alleviate the burden for healthcare professionals.

Total hip arthroplasty (THA) is an orthopedic intervention that generates substantial costs to national healthcare systems due to the number of interventions and the cost per intervention. We performed a cost comparison analysis in Austria and Switzerland.

Data from the national joint arthroplasty register in Switzerland and internal information from the national healthcare services in Austria and Switzerland were compared for patient demographics, interventional characteristics, and costs adjusted for inflation and purchasing power from 2015 to 2021.

The average age for primary THA in Austria was from 67.4 to 67.8 years with 55.9–57.2 percent female patients and from 68.5 to 69.3 years with 52.4–53.8 percent female patients in Switzerland. The annual incidence rate for primary THA rose from 210.28/100k to 216.6/100k in Austria and from 212/100k to 250/100k in Switzerland. After correction for inflation, costs were −1.91 percent lower in Austria in 2021 than in 2015 and −2.57 percent lower in Switzerland. After correction for purchasing power, costs were higher in Austria. The average hospital stay after THA in Austria was reduced by 20 percent (11.7 days/2015 vs. 9.4 days/2021) and 25 percent in Switzerland (8.4 days/2015 vs. 6.4 days/2021). Revision rate was 2.5–3.2 percent in Austria and 2.8–3.2 percent in Switzerland.

The patient population was comparable while patients undergoing primary THA in Austria stay longer in hospital and have relatively higher costs when adjusted for currency, purchasing power, and inflation. The use of standardized registers would be helpful to compare outcomes and costs.

Preadoption assessments are the most frequent type of evaluation conducted by the Spanish Network of Agencies for Health Technology Assessment and Services of the National Health System (RedETS). RedETS aimed to develop a framework to utilize real-world data (RWD) to better adjust its assessments to the Spanish population’s context and provide live assessments throughout the lifecycle of health technologies.

A working group within RedETS was set up, which held several meetings to define the primary uses of RWD in the short term. Next, a manual review was conducted on national and international initiatives that provided guidance on the use of RWD in HTA. Common pathways for utilizing RWD in HTA were identified. The working group agreed to outline and explain the key overarching steps and provide general guidelines for working with RWD, developing as illustration a use case for an interventional technology. The Big Data project of Aragon (BIGAN) was chosen as the data source for the use case.

We formulated a case for leveraging RWD in the assessment of implantable cardiac defibrillators (ICDs) for the prevention of sudden cardiac death (SCD). Based on this scenario, we developed a methodological framework outlining a workflow consistent with RedETS practices. RWD complemented the usual process of systematic review of a technology. Crucial steps comprised the definition of data requirements through a data model specification, an exploratory data analysis, and the construction of a decision model. We presented solutions for dealing with unavailable data on essential variables and unstructured records. We discussed the main limitations to account for when working with RWD.

The task ahead holds great hope but requires overcoming some challenges to fully deploy RWD-driven methods. This entails fostering collaboration with health authorities and designated data holders to address data access challenges. In the short term, it is essential to include data scientists in assessment teams and provide appropriate capacity-building to encompass RWD tools and modeling techniques.

Mental illnesses during pregnancy and after birth (perinatal period) affect one in five mothers and one in ten fathers. They can have adverse implications for child health and development and come with substantial economic costs. Many countries have developed integrated care models. We aim to summarize the international care model recommendations and contrast them with the current situation in Austria.

We conducted a scoping review of guidelines and recommendations for perinatal and infant mental health care (PIMHC) models and synthesized them into a best-practice model. The model overview targets prevention, early identification, and care of perinatal mental illness (PMI), as well as professional groups involved. We identified available Austrian PIMHC services via online search and expert consultation, clustered them according to our international model structure, and visualized availability on a geographical map. Additionally, we analyzed the use of five core mental health benefits from health insurance data. We narratively contrasted international recommendations with the Austrian availability and use of services.

International recommendations suggest integrating primary prevention, systematic screening, and stepped care. After identifying a PMI, a care pathway needs to be defined, including diagnostic and coordinated needs-based care. For severe PMI, specialized services should be available and provided by trained psychiatrists and specialists, such as perinatal mental health midwives. In Austria, various services for different severity levels of PMI are available. However, large geographical variations and gaps exist regarding specialist services, such as mother–baby units. Specially trained health professionals are lacking. Still, almost one in five mothers claimed one of the defined mental health benefits during the perinatal period.

PIMHC in Austria currently does not follow best-practice recommendations. The main gaps are in providing guideline-based specialized care by trained professionals. Insurance-funded mental health service use during the perinatal period corresponds with international prevalence figures, although only a part of available services is included in the analysis. To ensure women receive high-quality care, PIMHC needs to be more prioritized.

Several drugs are licensed for the treatment of relapsing-remitting multiple sclerosis (RRMS) in Brazil. The technological horizon of the disease introduces some additional therapies not yet approved in the country. The objective of this study was to establish an efficiency frontier for medicines used for RRMS, to guide the entry of new therapies into the market.

Primary data on the annualized relapse rate (ARR) and sustained disability progression for six months (CDP6), from 15 different therapies approved in Brazil, were obtained from the literature. Two network meta-analyses (NMA) were conducted comparing multiple treatments based on ARR and CDP6. A Markov model with transition states based on the Expanded Disability Status Scale (EDSS), with an annual cycle and a lifetime time horizon, was built to carry out the cost–utility assessment with an efficiency frontier.

NMA results for ARR and CDP6 were used as inputs for the economic model. In the cost–utility analysis, all strategies were dominated by the lowest-cost medication (teriflunomide) and the most effective one (alemtuzumab). In the deterministic sensitivity analysis, alemtuzumab was the dominant drug in 78 percent of simulations. In probabilistic analysis, most medications had an incremental cost-effectiveness ratio (ICER) below the Brazilian cost-effectiveness threshold in over 90 percent of simulations (approximately USD8,000/quality-adjusted life years [QALY]). An efficiency frontier was established between teriflunomide and alemtuzumab, with an ICER of USD11,141/QALY.

RRMS presents a scenario where several therapies compete for the Brazilian market, but only two of these drugs remained within the established efficiency frontier: alemtuzumab and teriflunomide. For the sustainability of public and private health systems, the efficiency frontier could serve as a cost-effectiveness benchmark, requiring new therapies considering entering the market to adapt to the set parameters.

Innovative designs have been used to enhance trial efficiency and enable access to novel treatments when traditional randomized controlled trials (RCTs) were considered operationally challenging to implement. Besides demonstrating scientific and regulatory rigor, innovative approaches also need to be perceived favorably by payers. This work delves into payer perspectives on innovative designs, identifying circumstances that contribute to higher payer acceptability.

Using targeted searches, we mapped clinical trials since 2010 with novel design elements, including adaptive, master protocol, hybrid, enrichment, and innovative endpoints. Sixty-two asset-indication examples using these designs were identified across different therapeutic areas. Based on the availability of health technology assessment (HTA) reports and the innovative element’s impact on final HTA outcome, 17 of these identified examples were developed as case studies to highlight the designs’ implications for access. Interviews with eight payer-experts across US, France, Germany, and Japan were conducted to further validate the research, explore scenario analyses, and clarify how circumstances impacted payer acceptability of the studied innovative trial designs.

While oncology has historically spearheaded innovative trial designs, other therapeutic areas are now incorporating innovative elements. Nonetheless, published payer guidance on innovative designs remains limited. We identified seven circumstances impacting payer acceptance of innovative designs: disease prognosis, eligible patient population size, type of treatment, mode of action, availability of treatment alternatives, comparative benefit versus standard of care, and launch sequence. Patient population size had the greatest impact on payer decisions, followed by comparative benefit and type of treatment; this suggests that payers may be inclined to accept innovative trial designs for small populations with high unmet need or therapies with transformative clinical benefits.

Innovative trials trade some scientific validity for increased practicality compared to traditional RCTs. Stakeholders need to align on appropriateness and scientific validity of innovative designs for access decisions, while implementing measures to minimize uncertainties. Collaboration across stakeholders including regulators, payers, and manufacturers is needed to refine innovative methodologies and guide policies to improve the relevance of innovative trials for decision-making.

There are concerns with the National Institute for Health and Care Excellence (NICE) conditional approval process with respect to the quality and reliability of the methods of evidence generation, analysis, and reporting; and on the increasing focus on OwR (only with research) in preference to OiR (only in research). Our study critically appraises the methods, quality, and risk of bias of the evidence generated in response to NICE conditionally approved technologies.

Our study reviewed pharmaceutical technologies appraised by NICE: technology appraisals approved between March 2000 and September 2022 and highly specialized technologies approved up to October 2023. From those, we identified appraisals with OiR and OwR conditional recommendations, and summarized the evidence requested by NICE as part of conditional approval. Then, evidence resubmitted to NICE for reappraisal was analyzed for its compliance with NICE’s initial recommendations for further research and assessed using the Cochrane Collaboration’s tools for risk of bias in randomized trials and the ROBINS-I tool for the non-randomized evidence.

NICE made 54 conditional recommendations relating to technology appraisals (TAs) (13 OiR and 41 OwR) and five highly specialized technologies (HSTs). From those, 16 TAs presented additional evidence for reappraisal [nine OiR and seven OwR] and three HSTs [three OwR]. Two of the nine reappraised TAs with OiR recommendation and four of the seven OwR fully complied with NICE’s request for further evidence. All three HSTs complied in full. However, the majority of reappraised TAs and HSTs included evidence that was deemed to be at serious, high, moderate, or unclear risk of bias.

The quality of evidence presented to NICE following conditional approval varies considerably. There is often widespread noncompliance with requests for further research when conditionally approving a pharmaceutical technology. Complying with NICE’s requests, however, does not necessarily guarantee high-quality evidence when the technology is reappraised. Evidence generated in response to NICE conditional approval recommendations should be subject to quality standards.

To assess the health technology assessment (HTA) process in Greece from its establishment in 2018 until 2023 in terms of timeliness and productivity.

Data were collected from the HTA Committee’s database and other publicly available sources. The overall study timeframe was divided into three periods: (i) July 2018–January 2020, (ii) January 2020–July 2021, and (iii) July 2021–February 2023.

During the study period, a total of 1,157 applications for medicinal products (MPs) (including 219 new active substances (NAS) and orphans) were submitted to the HTA Committee. The number of HTA recommendations increased from 60 (first period) to 641 (third period), while the backlog of MPs pending HTA and price negotiations decreased from 89 and 106 (January 2020) to 8 and 44 (February 2023), respectively. The median time intervals for all application types decreased significantly over time. In February 2023, the median time for clinical data assessment of NAS (excluding orphans) almost halved from 207 days in the first period to 114 days; median times for NAS and orphans from regulatory approval to HTA application were 420 and 457 days, and from HTA application to reimbursement 228 and 417 days, respectively.

The performance of the HTA process in Greece improved significantly over time, with increased MP appraisals, backlog reduction, and decreased timelines. Delays in reimbursement of NAS were mainly caused by the long gap between regulatory approval and HTA application. Overall, HTA review times in Greece are now on par with that of well-established European HTA systems.