Patients’ EQ-5D health states are preferably valued using country-specific value sets. If value sets are not available, crosswalks may be used to estimate utility values. However, up until now the impact of using crosswalks instead of value sets on cost-utility outcomes remains unclear.

Trial-based cost-utility data were simulated for four conditions (depression, low back pain, osteoarthritis, and cancer), three levels of disease severity (mild, moderate, and severe), and three treatment effect sizes (small, medium, and large), resulting in 36 scenarios. For all scenarios, utility values were estimated using four scoring methods (EQ-5D-3L value set, EQ-5D-5L value set, 3L-to-5L crosswalk, and 5L-to-3L crosswalk) for three countries (the Netherlands, the United States, and Japan). Mean utility values, quality-adjusted life years (QALYs), incremental QALYs, and cost-utility outcomes (incremental cost-effectiveness ratios [ICER], probabilities of cost-effectiveness at willingness-to-pay [WTP] thresholds) were compared between value sets and crosswalks.

Differences between value sets and crosswalks ranged from -0.33 to 0.13 for mean utility values, from -0.18 to 0.13 for QALYs, and from -0.01 to 0.08 for incremental QALYs. Because of the small differences in incremental QALYs, ICERs between scoring methods were considerably different. For small effect sizes, at a WTP of EUR 20,000/QALY gained, the largest difference in the probability of cost-effectiveness was found for moderate cancer between the 5L value set and 3L-to-5L crosswalk (difference 0.63) using Japanese valuations. For medium effect sizes, the largest difference was found for mild cancer between the 3L value set and the 5L-to-3L crosswalk (difference 0.06) using Japanese valuations. For large effect sizes, the largest difference was found for mild osteoarthritis between the 3L value set and 5L-to-3L crosswalk (difference 0.08) using Japanese valuations.

Our findings indicate that reimbursement decisions may change depending on the use of crosswalks. Crosswalks are justifiable in absence of country-specific value sets but should not be considered a sustainable alternative for value sets.

This study reviewed all publicly available Japanese cost-effectiveness appraisals delivered by the Center for Outcomes Research and Economic Evaluation for Health (C2H) from the national institute of public health (NIPH) and analyzed the relationship between the outcomes of the health-economic assessments and the final price adjustment decisions made by the Ministry of Health, Labour and Welfare (MHLW).

Data were extracted from all official health-economic assessments published by C2H website for the analysis. The extractions were structured based on the following items: indication, assessment methodology, appropriate comparators, health-economic outcomes, and key uncertainties identified by C2H. The analysis was performed on 29th November 2021. A threshold of 5 million JPY per Quality Adjusted Life Year gained (JPY/QALY) was used for the incremental cost-effectiveness ratio (ICER) analysis cut-off.

Up to the time of this analysis, six health-economic assessments had been conducted for five products: three assessments performed cost-effectiveness analysis, one performed cost-minimization analysis and two performed cost-effectiveness and cost-minimization analysis for different comparators and different patient subgroups respectively. Among the five assessments’ reported ICER values, four of them are under the 5 million JPY/QALY threshold, ranging from 328,585 JPY/QALY to 483,056 JPY/QALY. However, price adjustments were still implemented on three out of the four products which were deemed to be cost-effective, ranging from -0.5 percent to -4.3 percent (mean: -3.0%). For the only product deemed to be not cost-effective, a price adjustment of -4.3 percent was implemented.

A price discount could be implemented regardless of whether the ICER value falls under the 5 million JPY/QALY threshold. However, a lower magnitude of price discount is likely to be applied by MHLW for more cost effective treatments. The outcome of this analysis may be limited by the small sample size and continuous monitoring of further HTA publications in Japan is needed.

The Brazilian HTA process includes calls for public consultations, in which society can give its opinion on reports emitted by the National Committee for Health Technology Incorporation (CONITEC). Open and closed queries for public consultation are performed by official formularies and are available online at CONITEC webpage. There are two categories of queries: clinical protocols and guidelines, and incorporation/exclusion demands. Incorporation/exclusion queries are subdivided in two additional categories: opinion and experience, or technical. In this study we analyze health professionals’ technical contributions and their opinion (pro or con) on the inclusion or exclusion of health technologies.

On November 26th, 2021, formularies concerning concluded public consultations on health technology incorporation/exclusion reports were extracted from CONITEC website for the period, January 1, 2021 to November 26, 2021. Entries on the technical contributions formularies included a close-ended question about the opinion of participants on health technology incorporation/exclusion reports (“favorable”/“against”/“neither”).

A total of 63 health technology incorporation/exclusion queries were carried out during the study period, of which only 4 were exclusions. A total of 7783 contributions were registered. “Patients”, “Family or caregivers”, “Interest on the theme”, and “Health professionals”, accounted for 96.4% (10.9, 15.2, 17.1 and 53% respectively). Health professionals’ participation alone accounted for 4130 entries. Concerning the category “health professionals”, the total number of favorable opinions on the presented documents was 2740 (66.3%), 1306 (31.6%) disagreed, and 84 (2%) had no opinion.

Health professionals can be considered one of the main stakeholders considering HTA for technology incorporation in public health systems. Brazilian HTA reports are submitted to public consultation through queries, which are available open access at the Brazilian National Committee for Health Technology Incorporation website.

The European Network for Health Technology Assessment (EUnetHTA) was a voluntary cross-border initiative on HTA harmonization established by European Commission in 2005. Between 2016-2021, EUnetHTA completed 56 Joint Assessments (28 drugs; 28 other technologies) including 14 reviews of COVID treatments.

We conducted a review of the 14 EUnetHTA joint assessment reports of drugs in non-COVID 19 indications. We cross-referenced recommendations with national guidance in 30 member countries (including UK) and conducted an analysis of time to national assessment, choice of comparator, direct reference to EUnetHTA assessment, and time to reimbursement decision.

Six products in oncology, 2 in endocrine and metabolic diseases, 2 in infectious and parasitic diseases, and cardiovascular, digestive system, eye disorders and central nervous system (one each) were identified. On average, EUnetHTA published its recommendation 52 days after market authorization for oncology products and 33 days for non- oncology products. EUnetHTA recommendations considered on average 4 comparators (range 1-8) as part of the assessment. All of the 6 oncology products have been assessed by national HTA bodies, however uptake was low with an average of 5 reports referencing the EUnetHTA report. Similarly for the non-oncology products assessed only 3 of 30 HTA bodies cite the EUnetHTA report. Citing HTA bodies were: AETSA (Spain), HAS (France), INFARMED (Portugal), NoMA (Norway), and TLV (Sweden). There was no clear reduction in the time to reimbursement for these products in these markets.

According to EUnetHTA, there has been an increased use and dissemination of joint assessment reports since 2016. Our analysis shows that the level of implementation across countries is heterogeneous despite publication of the EUnetHTA reports shortly after market authorization. The future the EU HTA will depend on the timeliness, rigor and transparency of joint clinical assessment reports and improved uptake of these reports at a national level.

Health-related quality of life (HRQoL) data are necessary for conducting cost-utility analyses (CUAs) as part of health technology assessments (HTAs), but the lack of robust HRQoL data may delay or even prevent patient access to medicines when National Health Insurance is introduced in South Africa. This study aimed to make recommendations for evidence generation activities to support national HTA in the public health sector, with a focus on creating South African HRQoL data suitable for CUAs.

A systematic review of HRQoL research in South Africa formed the basis for three analyses. The first analysis quantified and evaluated the suitability of HRQoL studies for CUAs. The second analysis determined the performance indicators of the research output and identified collaborative networks through bibliometric analyses. The third analysis critiqued the translation methodology of the HRQoL instruments retrieved in the systematic review.

Based on the published literature, existing HRQoL data are unlikely to support CUAs because they were derived from observational or cross-sectional studies that lacked the methodological details necessary to determine their scientific merit according to HTA requirements. Overall, there was a lack of research continuity in this field, with numerous isolated research networks. Despite the strong contribution of South African based researchers and organizations in this area, their performance was below that of international counterparts. Since only a few HRQoL instruments suitable for CUAs would be valid in the South African context, HRQoL research output in South Africa could be optimized by using more rigorous study designs and by the expansion of researcher networks to include those working in HTA and related fields. The three-level EQ-5D is the tool best suited for use in South Africa, so its utilization should be encouraged and supported by establishing a South African value set.

Future data generation activities should incorporate the recommendations from this study because existing South African HRQoL data are likely to be inadequate for conducting CUAs in national HTA.

Damage to the central nervous system (CNS) in adulthood, may lead to cognitive impairments. In Germany, occupational therapy is most often prescribed for neurological diagnoses, including stroke and traumatic brain injury (351 and 343 cases per 100,000, respectively in 2018). For cognitive impairments, the primarily prescribed remedies are sensorimotor-perceptive, motor-functional and neuropsychologically oriented treatment or training of cognitive performance. Here we report the results of a health technology assessment (HTA) report on the clinical efficacy of occupational therapy for patients with cognitive impairments.

To assess clinical efficacy, a systematic overview was conducted based on published systematic reviews and HTA reports from the last ten years summarizing randomized controlled trials (RCTs) retrieved from four bibliographic databases. The target population included adult patients with cognitive impairments caused by diseases of the CNS, excluding moderate to severe dementia. The intervention studied is occupational therapy compared to no occupational therapy. Outcomes were cognitive abilities, independence, self-determination, health-related quality of life (QoL), and participation in activities of daily living (ADL).

Five systematic reviews comprising 1,316 patients were included. There is evidence for a small statistically significant positive effect on “general cognitive function” (10 RCTs, n=470) and on ADL (4 RCTs, n= 405). A non-quantified positive effect was reported on behavior control (1 RCT, n=96), and conflicting evidence on QoL (2 RCTs, n=214). No effect was found for individual components of cognition (5 RCTs, n=202), self-efficacy (1 RCT, n=98) and social participation (2 RCTs, n=194). The level of the evidence was low for all endpoints due to the high risk of bias and small sample sizes.

Based on this systematic overview, it cannot be demonstrated but also not ruled out that occupational therapy for cognitive impairment is an effective therapy for adults with cognitive impairments. The evidence is very uncertain due to small effects and high risk of bias, low statistical power, and heterogeneity of interventions and study populations.

The performance of diagnostic health technologies is usually assessed by comparing them with standard care using the kappa statistic. These comparisons are made based on comprehensive clinical information (e.g., anamnesis and complementary tests). However, not all digital applications (DAs) execute over complete information, which leads to work under non-uniform distribution of values. Using kappa statistic in this situation has serious methodological limitations. Kappa assumes that the marginal values are uniformly distributed and highly weights the discordant values when calculating concordance, which underestimates the real effectiveness of DAs (i.e., observed concordance). We aimed to present the application of the B statistic to WtsWrng, a symptom triage DA for individuals.

WtsWrng was used by 382 patients at the emergency department of a hospital. Diagnoses provided by WtsWrng, given 19 symptoms, were compared with those logged in the hospital’s electronic clinical records at discharge. Observed concordance was calculated using contingency tables. The concordance using the kappa and B statistics were compared for the 12 most frequent diagnoses at hospital discharge. Sensitivity and specificity were also calculated.

Real observed concordance fluctuated from 0.4 to 0.98 for the 12 most frequent diagnoses, eight of which had a concordance greater than 0.8. The results ranged from -0.005 to 0.37 when using the kappa statistic and from 0.36 to 0.99 when using the B statistic. The sensitivity and specificity of WtsWrng were greater than 0.8 for three and eight of the 12 diagnoses, respectively.

The results show that the B statistic is closer to the real observed concordance when kappa statistic assumptions are not fulfilled by a DA. Therefore, the B statistic is better suited for assessing the effectiveness of this type of technology. Analysis of WtsWrng using the B statistic showed that its diagnoses were close to those provided by clinicians, which were arrived at using complete clinical information. Moreover, the high specificity of the WtsWrng DA suggests that it is a good tool for determining the appropriate use of healthcare resources.

Health technology assessment (HTA) has become a critical support to health policy decision-making. The HTA evaluation process requires transparency, formalized processes, clear timelines, and standardization according to international best practice. Tunisia is establishing an HTA-based decision-making system through the National Authority for Accreditation and Assessment in Healthcare (INEAS) to ensure impartiality and fairness in decision-making, which is important for an emerging democracy. INEAS opted for a participatory approach in developing the national health economic guidelines to better engage healthcare sector stakeholders in the HTA process. We aimed to present the main phases of the process used to develop the Tunisian health economic guidelines, the methodological choices for pharmacoeconomic evaluations, and the methodological choices for budget impact analyses.

The different phases of developing the guidelines were listed and reported.

The guidelines were developed under a technical cooperation program of the World Health Organization and involved collaboration between the Institut national d’excellence en santé et en services sociaux (INESSS in Quebec, Canada) and INEAS. The first version of the guidelines was drafted following a review of international HTA guidelines and best practice reference books, taking into account the Tunisian healthcare system context. This first draft was discussed in a workshop with the main health system stakeholders and then peer reviewed by international experts. Based on the feedback from experts, a second version was prepared and published on the INEAS website for public consultation. The Union of Innovative Pharmaceutical Research Companies (SEPHIRE), the National Health Insurance Fund (CNAM), and healthcare professionals provided the majority of feedback. The comments provided by SEPHIRE were discussed during a second workshop. The guidelines were revised and updated based on the comments provided and the final version was published in November 2021.

INEAS adopted a participatory approach for developing its economic guidelines, which enhanced engagement of the major health system stakeholders in the HTA implementation process in Tunisia.

Hansen’s disease, or leprosy, is a chronic bacterial infection that affects the nerves, skin, eyes, and nose lining. In 2019, there were 202,256 new cases reported globally, and nearly 28,000 new cases are diagnosed each year in Brazil. The best way to prevent the spread of Hansen’s disease is early diagnosis and treatment of infected individuals. Most diagnoses are done clinically, but only the microscopic analysis of slit-skin smears is funded in Brazil. Serologic and polymerase chain reaction (PCR) tests have also been developed to aid in the diagnosis. The goal of this study was to identify the most cost-effective strategy for increasing the diagnosis of Hansen’s disease in Brazil.

We examined the impact of the following four strategies using a decision tree model: (i) slit-skin smear only; (ii) PCR test only; (iii) serologic testing followed by slit-skin smear for positive samples; and (iv) serologic testing followed by slit-skin smear for positive samples and PCR test for negative serologic tests and negative slit-skin smears. The accuracy of the tests was determined using a systematic review and meta-analysis and validated by experts. The costs were calculated from the Brazilian health system perspective. Univariate and probabilistic analyses were also conducted.

Serologic testing or PCR followed by slit-skin smear was dominated in the economic model (more false-negative samples and more costly). The addition of serologic testing and PCR to the diagnostic sequence made the strategy more expensive than slit-skin smears alone, but it significantly reduced the percentage of false negative results (from 7.3 to 2.9%) at an estimated cost of USD 533.61 per incremental diagnosis. Disease prevalence was the most important variable in the sensitivity analysis.

This is the first cost-effectiveness model undertaken for Hansen’s disease. The results indicate that incorporating serology and PCR testing into the Brazilian health system could be an appealing option for reducing the spread of Hansen’s disease in Brazil.

The unemployment rates among people being treated for substance use disorder (SUD) are high, with Norwegian estimates ranging from 81 to 89 percent. A promising method for improving vocational outcome is Individual Placement and Support (IPS), where employment support is integrated into the treatment regimen. However, the expense and economic gain are covered by different societal sectors, which may be a disincentive for implementing this method. Thus, the aim of this study was to model the potential socioeconomic value of a new SUD treatment service.

For the simulation study, we made qualified assumptions about costs and socioeconomic gain based on data from scientific and administrative publications, expert opinion, and a randomized controlled trial of treatments for individuals with SUD that was set in a specialized Norwegian healthcare setting. We made assumptions about the proportion of patients likely to obtain employment after participating in the following three interventions: (i) treatment as usual; (ii) a self-help guide and additional workshop; and (iii) IPS.

Based on early socioeconomic simulation modeling for the three interventions, IPS was found to be cost effective over a period of one to two years.

In this study we used early economic modeling to demonstrate the potential value of IPS for increasing employment rates among patients with SUD. Since it is important to secure evaluative support for an innovation at the earliest possible stage, early economic modeling may assist the innovator in implementing a health service that meets predefined user needs while also reducing associated risks. Although there is much uncertainty in such early stages due to a lack of valid data sources, early economic modeling may provide health authorities with much needed decision support when planning for future health services.

Fatigue in Parkinson’s Disease (PD) remains poorly understood. The comprovation derives from and is proven by psychometric scales. The objective is to prepare a Technical Scientific Report on the performance of scales in PD.

Based on the Methodological Guideline for the Preparation of Technical Scientific Report, Brazil 2014, we conducted a search on MEDLINE / PubMed, Virtual Health Library (BVS) and Cochrane, and then a review and critical evaluation of the studies and the quality of the evidence.

Nine studies were analyzed: three systematic reviews, one case-control and five cross-sectional studies. The following were evaluated: Fatigue Severity Scale (FSS), Fatigue Assessment of Chronic Illness Therapy (FACIT-F) and Parkinson’s Fatigue Scale (PFS-16). In Brazil, FSS and PFS-16 were validated. The studies have methodological weaknesses and moderate, low and very low evidence. However, FSS, FACIT-F and PFS-16 show potential for assessing fatigue in PD but further studies are needed.

Consensus on fatigue are recommended for Brazilian studies comparing FSS and FACIT-F with PFS-16 and longitudinal monitoring of patients.

Neurogenic bowel dysfunction occurs in people with central nervous system disease or injury and causes loss of bowel control and severe constipation. These problems involve a lot of anxiety and discomfort and can reduce the quality of life of those who suffer from them, therefore the management of symptoms is very important. Peristeen Plus is a transanal irrigation (TAI) system for bowel dysfunction management, used to empty the rectum and distal sigmoid colon, to prevent uncontrolled bowel movements or to relieve and prevent constipation.

A literature review was conducted. A total of 14 records were included to evaluate the benefits in terms of efficacy and safety associated with the adoption of the medical device. To assess the economic impact, two different budget impact models have been implemented. The first aimed at evaluating an incremental diffusion in a short-term time horizon (3 years) of the home distribution of the device compared to the direct and indirect distribution methods in the Italian context. The second model aimed at assessing the impact of the diffusion of the device in the clinical practice.

Overall, most studies demonstrate improved endpoints related to the severity of fecal incontinence, constipation and intestinal disorders in patients using the device. The economic assessments conducted estimate that the increase in the Italian care setting is associated with a saving of resources in each year under analysis. The diffusion of home distribution of the device would potentially be able to offer a lower absorption of resources compared to other distribution methods. In addition to this, there is an incremental saving correlated to the degree of diffusion of Peristeen Plus.

TAI is considered a safe and more effective method than conventional treatments for reducing fecal incontinence, constipation and improving quality of life. The results of our study confirm the benefits of TAI as a second-line treatment in case of failure of conventional medical therapy in the management of the neurogenic gut.

Parkinson’s disease (PD) is the second most common neurodegenerative disease in the world. High-intensity focused ultrasound (HIFU) is a new non-invasive therapeutic option for treating the motor symptoms of PD. HIFU is an imaging-guided procedure for therapeutic brain ablation that has been used for patients with essential tremor and neuropathic pain. It is indicated for patients older than 22 years of age who have PD that is refractory to drug treatment and are ineligible for surgery. The objective of this study was to conduct an early assessment of HIFU subthalamotomy for the treatment of motor symptoms in patients with PD.

HIFU was identified by the early awareness and alert system, SINTESIS- nuevas tecnologías, of the Agencia de Evaluación de Tecnologías Sanitarias at the Instituto de Salud Carlos III. Relevant literature published to October 2021 was identified by searching PubMed, EMBASE, ClinicalTrials.gov, and the Cochrane Library.

One prospective study and one randomized controlled trial (RCT) were found that assessed the efficacy and safety of HIFU subthalamotomy for treating the motor symptoms of PD. The Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale Part III (MDS-UPDRS III) was used to measure changes in symptoms (>30% change from baseline was considered clinically relevant). Both studies reported a reduction of symptoms in the intervention group. The MDS-UPDRS III score changed from 16.6 to 7.5 six months after treatment in the prospective study and from 19.9 to 9.9 four months after treatment in the RCT (a decrease of 11.6 points was observed after 12 months). The main adverse events reported were dyskinesia, speech and gait disturbances, and weakness, all of which resolved without treatment.

The results regarding the efficacy and safety of HIFU for treating the motor symptoms of PD are promising. HIFU is a non-invasive procedure that eliminates the risks associated with surgery. Although rapid diffusion of this technology is expected, further studies and economic evaluation are needed.

Migraine is a multifactorial pathology that affects 12 percent of the world’s population. Relivion® MG (Neurolief Inc., USA) is a non-invasive self-administered device for external combined occipital and trigeminal nerve stimulation that has been recently approved for marketing in Europe and the USA. The objective of this study was to conduct an early assessment of the efficacy and safety of Relivion for the treatment of migraine episodes.

Relivion was identified by the early awareness and alert system, SINTESIS- nuevas tecnologías, of the Agencia de Evaluación de Tecnologías Sanitarias at the Instituto de Salud Carlos III. An early assessment of the technology was conducted by reviewing relevant clinical studies published to 29 September 2021. The literature was identified by searching PubMed, Embase, the International Clinical Trials Registry Platform, ClinicalTrials.gov, and the Cochrane Library.

Two randomized, sham-controlled double-blind trials were found. They assessed side effects and pain relief, response rate, and pain freedom two hours after treatment. One study included 55 patients and the other (the RIME study) included 131 patients. The rate of pain relief two hours after treatment ranged from 60 to 76 percent in the treatment group and from 31 to 37 percent in the control group (p<0.01). The response rate, defined as at least 50 percent pain reduction two hours after treatment, was significantly higher in the treatment group (67 to 70% versus 32 to 42%). The percentage of patients free of pain two hours after treatment ranged from 42 to 46 percent in the treatment group, compared with 11 to 12 percent in the control group (p<0.0001). No notable adverse events were recorded.

Preliminary results indicated that Relivion effectively and safely relieves or eliminates acute migraine pain. However, more comparative studies are needed. The use of Relivion could improve the control of symptoms and improve quality of life in patients with migraine.

The constant evolution of high-priced hospital drugs with large uncertainties are increasingly challenging the sustainability of many healthcare reimbursement systems. Consequently, more attention is paid to exploring innovative payment and reimbursement models that may contribute to sustainable healthcare funding mechanisms yet still ensure timely patient access to health intervention. However, more insight is needed into the experiences of stakeholders involved in making payment and reimbursement arrangements as they may play an essential part in successfully implementing innovative reimbursement and payment models in the future.

Between May and July 2021, a survey was sent out to Dutch stakeholders directly or indirectly involved in payment and reimbursement agreements. The survey questioned the current use of and future preferences for reimbursement and payment models for high priced hospital drugs using Likert scales. Results were analyzed using descriptive statistics.

Our inquiry shows that currently financial-based reimbursement models are applied most often, especially discounts due to their simplicity. In the future, outcome-based reimbursement models are preferred more, particularly pay-for-outcome. The main challenge for implementation is generating evidence in practice.

Upfront payment is currently the most frequently applied payment model, according to the respondents, whereas delayed payment models are preferred to be applied more often. Particularly payment at outcome-achieved models are preferred but they can be administratively difficult to arrange.

The respondents are moderately satisfied with the payment and reimbursing system in the Netherlands, arguing that especially transparency about the final agreement and mutual trust could be improved.

Despite the preference healthcare payers have for using outcome-based reimbursement models and delayed payment models, currently they are rarely applied. The insights from our survey can provide Dutch stakeholders with future direction when implementing innovative reimbursement and payment models. Attention should be paid to which barriers are currently perceived and how policy structures can facilitate implementation. Further research should focus on exploring which combinations of reimbursement and payment models are most likely to be successful in the Netherlands.

This study aims to (i) describe the (evidence-based) reimbursement process of hospital individual services, (ii) evaluate the accordance between evidence-based recommendations and reimbursement decision of individual services and (iii) elaborate potential aspects that play a role in the decision-making process in Austria.

The reimbursement process is described based on selected relevant sources such as official documents. Evidence-based recommendations and subsequent reimbursement decisions for the annual maintenance of the hospital individual service catalogue in Austria between 2008 and 2020 were analyzed using a mixed methods approach, encompassing descriptive statistics and a focus group with Austrian decisionmakers.

One hundred and eighteen evidence-based recommendations were analyzed. There were 93 (78.8%) negative and 25 (21.2%) positive evidence-based recommendations. In total, 107 out of 118 evidence-based recommendations (90.1%) did not lead to a deviating reimbursement decision. We identified six aspects that may have played a role in the decision-making process for the annual maintenance of the hospital individual service catalogue, with clinical evidence being the most notable. Further aspects included quality assurance/organizational aspects (i.e., structural quality assurance), costs (if comparable to already existing medical services, not: cost-effectiveness), procedural aspects (e.g., if certain criteria for adoption have not been met formally through the proposals), “other countries” (i.e., taking into account how other countries decided) and situational aspects (such as the COVID-19 pandemic).

There is good accordance between evidence-based recommendations and reimbursement decisions regarding hospital individual services in Austria. Beyond clinical evidence, organizational aspects seem to be considered often with regard to quality assurance but costs do not appear to play a major role. The Austrian system has mechanisms in place that can restrict widespread adoption of novel hospital individual services with uncertain clinical benefits. Future studies could investigate how well these mechanisms work and how they compare to other health systems in Europe.

The number of novel therapies that achieve registration in oncology based on limited clinical evidence like non-randomized studies (NRS) is increasing. Dutch health authorities determine the therapeutic value of medicines evaluated in randomized controlled trials based on formal criteria for minimal relative efficacy or clinical treatment guidelines. However, there are no criteria to determine the therapeutic benefit of treatments assessed in NRS, which impacts reimbursement and patient access. Additionally, clinicians in the Netherlands see potential clinical benefit in off-label use but are currently unable to prescribe these because of absent clinical evidence.

This review aims to identify and summarize initiatives to improve patient access to oncology therapies with limited or no clinical evidence in the Netherlands.

Relevant public reimbursement documents for the Netherlands were identified through a pragmatic literature review.

The main initiatives to improve access for therapies with limited clinical evidence are outside regular reimbursement pathways.

The Drug Rediscovery Protocol (DRUP, initiated 2016) and drug access protocol (DAP, initiated 2021) are two initiatives to improve access in solid tumor oncology. DRUP collects real-world data and provides access for targeted therapies in patients with targetable mutations in off-label indications. At least 25 therapies have been included to date.

DAP uses the same data framework to reimburse on-label solid tumor therapies through a managed entry agreement based on response. The first participating therapies are cemiplimab (NRS, failed ZiN reimbursement), entrectinib and larotrectinib (both NRS, tumor-agnostic).

Finally, Dutch clinical experts proposed criteria for therapeutic value of therapies studied NRS in oncology.

Patient access to both off-label and on-label oncology therapies is addressed in DRUP and DAP. New criteria for the therapeutic value of therapies studied in NRS may decrease the relevance of DAP, although these criteria would not address the need for comparative evidence for cost-effectiveness analysis.

Implicit factors can be defined as any criteria that play a role in the health technology assessment (HTA) deliberative process but are not part of the HTA framework. To date, very few studies have explored the influence of implicit factors on this process. This survey of HTA experts in five European countries aimed to analyze the influence of implicit factors on the HTA deliberative process.

Semi-structured interviews with 20 HTA experts from five European countries (France, Germany, Italy, Spain, and the United Kingdom) were conducted from February to May 2021. The main topics of the interviews were: the HTA deliberative process; the degree of influence on the HTA deliberative process of a set of factors previously identified in a systematic literature review performed by the authors; and recommendations for improving the deliberative process.

All but two of the experts concurred that implicit factors played a role in the deliberative process. German experts considered that the factors explored had a low influence on the process. Burden of disease and unmet need scored highest, followed by the professional experience of the people involved in the HTA deliberative process. To improve the deliberative process, experts suggested expanding the external stakeholder perspective (i.e., including patients, the pharmaceutical industry, and the public), increasing transparency when revealing implicit factors, and implementing a methodology to mitigate the influence of implicit factors.

Our survey indicates a need to increase external involvement in the process and to develop a methodology for unmasking the implicit factors in the deliberative process. This may be achieved by either updating the current frameworks to include these implicit factors or by developing new methods to address them. Further research may explore approaches to acknowledge the implicit factors in the HTA deliberative process in a systematic manner.

The European Network for Health Technology Assessment (EUnetHTA) has led together, with member states, several joint actions, including Joint Clinical Assessments (JCA), under the form of project-based voluntary cooperation, which outputs and transferability of those projects in other European countries remains somehow limited. In June 2021, the European Council has reached an agreement on the European Health Technology Assessment (HTA) regulation, which is entering into force gradually. Initially limited to oncology products, then extended to orphan/advanced therapy, and after a five to eight-year additional period, it will apply to all centrally approved products. The JCA will consist of a focused scientific analysis on relative effectiveness assessment, including the health condition, technology description, clinical effectiveness, and safety. These analyses will also include information relating to the degree of certainty. We consider that the evidence appraisal might have limitations, and transferability would not be generalizable. We aim to determine the potential drivers and barriers for HTA transferability in EU4, employing the analysis of a case example where JCA was conducted.

Employing an oncology JCA, we will compare an HTA analysis conducted in EU4 countries (Germany, France, Italy, and Spain). Overview and background information on countries involved in the JCA, and EU4 HTA system will be provided, followed by HTA outcome and main evidence requirements, reimbursement outcome, and pricing agreements.

Study results supporting HTA outcomes may focus on the population assessed, the comparator considered, and uncertainty management. A conceptual adaptation about the scope of the EU JCA regulation will be discussed, to understand its potential advantages to individual HTAs in Europe and remaining gaps to effectively inform HTA or decision-making process.

The analysis of pricing and reimbursement outcomes can further help understand potential barriers and drivers for JCA transferability and potential areas of evidence generation requirements.

Appropriate care programs differ in the way and the extent to which they involve or collaborate with stakeholders. Here we describe the collaboration of two national appropriate care programs with gynecologists to improve the curative care of women with cervical intraepithelial neoplasia (CIN), a cervical pre-malignancy.

The present case report describes the collaboration based on project documentation.

The Appropriate Care program from the Dutch National Health Care Institute performs a systematic cyclic health technology assessment to examine the degree to which care in the insured package is provided to patients. The full cycle consists of four phases: screening, in-depth analysis, implementation, and evaluation. The results of the in-depth analysis are discussed with the stakeholders. This is followed by written agreements on multiple actions to improve healthcare from the patient perspective. For CIN these actions encompass improvements in a top-down fashion; for example, by updating guidelines to eliminate unwanted practice variation and creating tools for shared decision-making. These actions were supplemented by the development of audit and feedback information on a national and local level. The development was supported by a second national appropriate care program, Healthcare Evaluation and Appropriate Use. The results of the first production run of the audit and feedback information were disseminated by the Dutch Society of Obstetrics and Gynaecology and more than 50 healthcare institutions. This information was used to prioritize modular guideline updates and helped pinpoint the main areas of improvement of individual healthcare institutions. A future production run of audit and feedback information will facilitate the Plan-Do-Check-Act cycle on a local and national level.

In the case we present, the collaboration between appropriate care programs and healthcare professionals led to a synergy between top-down (updating and disseminating guidelines and tools for shared decision-making) and bottom-up (learning from audit and feedback information) activities to improve curative care for women with CIN.