To investigate the behavior of restricted mean survival time (RMST) and designs of a two-state Markov microsimulation model through a 2 × 4 × 2 full factorial experiment.

By projecting patient-wise 15-year-post-trial survival, we estimated life-year-gained between an intervention and a control group using data from the Cardiovascular Outcomes for People Using Anticoagulation Strategies Study (COMPASS). Projections considered either in-trial events or post-trial medications. They were compared based on three factors: (i) choice of probability of death, (ii) lengths of cycle, and (iii) usage of half-a-cycle age correction. Three-way analysis of variance and post-hoc Tukey's Honest Significant Difference test compared means among factors.

When both in-trial events and post-trial study medications were considered, monthly, quarterly, or semiannually were not different from one other in projected life-year-gained. However, the annual one was different from the others: mean and 95 percent confidence interval 252.2 (190.5–313.9) days monthly, 251.8 (192.0–311.6) quarterly, 249.1 (189.7–308.5) semiannually, and 240.8 (178.5–303.1) annually. The other two factors also impacted life-year-gained: background probability (269.1 [260.3–277.9] days projected with REACH-based-probabilities, 227.7 [212.6–242.8] with a USA life table); half-a-cycle age correction (245.5 [199.0–292] with correction and 251.4 [209.1–293.7] without correction). When not considering post-trial medications, only the choice of probability of death appeared to impact life-year-gained.

For a large trial or cohort, to optimally project life-year-gained, one should consider using (i) annual projections, (ii) life table probabilities, (iii) in-trial events, and (iv) post-trial medication use.

To assess the cost effectiveness from a Canadian perspective of index patient germline BRCA testing and then, if positive, family members with subsequent risk-reducing surgery (RRS) in as yet unaffected mutation carriers compared with no testing and treatment of cancer when it develops.

A patient level simulation was developed comparing outcomes between two groups using Canadian data. Group 1: no mutation testing with treatment if cancer developed. Group 2: cascade testing (index patient BRCA tested and first-/second-degree relatives tested if index patient/first-degree relative is positive) with RRS in carriers. End points were the incremental cost-effectiveness ratio (ICER) and budget impact.

There were 29,102 index patients: 2,786 ovarian cancer and 26,316 breast cancer (BC). Using the base-case assumption of 44 percent and 21 percent of women with a BRCA mutation receiving risk-reducing bilateral salpingo-oophorectomy and risk-reducing mastectomy, respectively, testing was cost effective versus no testing and treatment on cancer development, with an ICER of CAD 14,942 (USD 10,555) per quality-adjusted life-year (QALY), 127 and 104 fewer cases of ovarian and BC, respectively, and twenty-one fewer all-cause deaths. Testing remained cost effective versus no testing at the commonly accepted North American threshold of approximately CAD 100,000 (or USD 100,000) per QALY gained in all scenario analyses, and cost effectiveness improved as RRS uptake rates increased.

Prevention via testing and RRS is cost effective at current RRS uptake rates; however, optimization of uptake rates and RRS will increase cost effectiveness and can provide cost savings.

To provide insights into the attributes of health-related quality of life (HRQoL) research within the context of economic evaluations for a potential national health technology assessment process in South Africa, and make evidence generation recommendations.

A systematic review was conducted in January 2019 using Medline, the Web of Science (WoS) Core Collection and the South African SciELO collection via the WoS Platform, and in the Cochrane Library. No time restrictions were applied. Duplicate records were removed before first- and second-pass screening by two reviewers working independently.

The review identified 123 publications representing 104 studies since the first-published article appeared in 1996. Only eight studies were randomized controlled trials, most were cross-sectional (n = 54). The EQ-5D, SF-36, and WHOQOL-BREF were the most used HRQoL instruments (n = 35, n = 23, and n = 10, respectively). Instruments were frequently administered in multiple languages, reflecting the cultural groups in which the study was conducted, with the English version of instruments used most often. Studies were predominantly conducted within the public health sector (n = 67), in the Western Cape province (n = 46), in adults (n = 92) and people with HIV (n = 24).

South African specific HRQoL studies have been conducted in a range of settings and populations using mostly generic HRQoL instruments in multiple languages. These studies may provide generalizable, real-world data due to their observational nature. However, more comparative and longitudinal studies should be conducted as this is preferred for economic evaluations and patient, disease, and treatment characteristics should be reported in full.

The Pharmaceutical Benefits Scheme (PBS) provides timely, reliable, and affordable access to necessary medicines for Australians. We reviewed the Pharmaceutical Benefits Advisory Committee (PBAC) submissions and their related outcomes and timelines since 2010.

We examined the PBS Website to identify submissions and their related PBAC outcomes for new medicines, new indications, and new combination products that had been considered by the PBAC since 2010.

Thirty-five PBAC meetings were held during the study period, at which the Committee considered 781 submissions (1,074 medicine/patient population pairings). We saw an increase in the annual number of submissions (medicine/patient population parings). The recommendation rate for the study period was higher than the rejection rate. The annual mean value for the period from the date of initial PBAC recommendation to the date of PBS listing ranged from 357 to 644 days; the annual mean value for the period of the date of PBAC recommendation to the date of PBS listing ranged from 187 to 245 days. It took, on average, 1.70 submissions that included an economic evaluation to obtain a PBAC recommendation. It took more submissions to obtain a PBAC recommendation for a cost-effectiveness analysis submission than it did for a CMA submission. The PBAC was willing to recommend medicines for most acceptable base-case incremental cost-effectiveness ratio (ICER) bands, and the majority of the PBAC did not recommended any medicine in the study period that had a base-case ICER >AUD75,000.

The results of our analyses reveal a minor reduction in the period from the date of PBAC recommendation to the date of PBS listing. Several analyses were hampered by a high proportion of missing data.

In the past decade, with the ever-increasing growth of information and communication technologies, telerehabilitation, especially home-based rehabilitation (HBR), has been widely considered by researchers. Many software systems are developed to address HBR programs, which includes various functionalities. The aim of this study is to review the functional features of these systems designed for remote supervising of HBR programs.

Scopus, PubMed, EMBASE, ISI Web of Science, Cochrane Library, IEEE Xplore Digital Library, and ProQuest databases were searched for English-language articles published between January 2008 and February 2018 to retrieve studies reported an home-based telerehabilitation software system aiming to remotely supervise HBR program.

A total of fifty studies that reported twenty-two unique systems met the inclusion criteria. Various functional features were identified including but not limited to exercise plan management, report/statistics generating, patient education, and task scheduling. Disorders or diseases addressed by these systems could mainly be grouped into five categories: musculoskeletal, neurological, respiratory, cardiovascular, and other health-related problems. Usability and acceptability, and clinical/patient outcomes were the most reported outcomes and data analysis was used by the majority of included studies to measure the outcomes.

Systems developed for supervising of HBR program are diverse. However, preliminary results of this review revealed that these systems share more or less common functionalities. However, further research is needed to determine the requirements, structure, and effectiveness of these systems in real-life settings.

Involving patients is a core principle which governs the work of the National Institute for Health and Care Excellence (NICE). To improve how patient evidence is identified and considered in health technology assessments (HTAs), NICE worked with patient organizations to review existing HTA methods and co-designed proposals for change.

A working group, including six patient organizations, oversaw the project, identifying and co-designing options for improvement. We held a stakeholder event with twenty-two patient organizations to identify themes for improving how we find and use patient evidence. We then ran an online quantitative and qualitative survey for targeted consultation with patient organizations to capture broader views.

The fifty-two people who responded to the consultation made the following suggestions:

1. (i) Provide information about uncertainties that patient evidence might help to address;

2. (ii) Explore the role of real-world evidence in patient involvement;

3. (iii) Provide training and support to patient organizations;

4. (iv) Create inclusive committee cultures; and

5. (v) Include additional touchpoints during HTAs to incorporate patient evidence.

This work identified improvements in seeking and incorporating patient evidence into HTA processes. Precise guidance for patient organizations will help them to submit evidence that will make the most impact. This is particularly important when assessing disruptive technologies where there are likely to be greater uncertainties and cost pressures. The results of this work will be developed into formal options for NICE to consider when updating its methods guides.

The Belgian Health Care Knowledge Centre (KCE) formally involves stakeholders in HTA since 2012. Patients are treated as one stakeholder amongst others, but it is recognized that patient involvement (PI) requires a different approach. The success of implementing PI depends, however, on the organizational culture toward PI.

The objective of this study was to map the PI culture at KCE in the context of the development of organization-wide supported position statements about PI.

A nominal group technique was used to measure the PI culture at KCE. Arguments for and against PI and conditions for PI in different phases of the HTA process were collected. A literature review and interviews fed the draft position statements, for which support was assessed by means of a two-round Delphi process.

Arguments in favor of PI in HTA related to the relevance of the scope, expertise with data collection, bringing in fresh ideas for study design, access to survey participants, validation of data analyses, adherence to recommendations. Disadvantages and risks included the lack of scientific knowledge of involved patients, resources requirements, conflicts of interest, and heterogeneity within patient populations. Conditions for meaningful PI referred to measures mitigating the identified disadvantages. Eighteen position statements supported by KCE could be formulated.

The KCE culture seems predominantly positive toward PI, although attitudes vary between HTA researchers. KCE recognizes the potential value of PI in HTA, but considers the level of involvement to be contingent on the topic and phase in the HTA process.

Mental health problems can lead to costs and benefits in other sectors (e.g. in the education sector) in addition to the healthcare sector. These related costs and benefits are known as intersectoral costs and benefits (ICBs). Although some ICBs within the education sector have been identified previously, little is known about their extensiveness and transferability, which is crucial for their inclusion in health economics research.

The aim of this study was to identify ICBs in the education sector, to validate the list of ICBs in a broader European context, and to categorize the ICBs using mental health as a case study.

Previously identified ICBs in the education sector were used as a basis for this study. Additional ICBs were extracted from peer-reviewed literature in PubMed and grey literature from six European countries. A comprehensive list of unique items was developed based on the identified ICBs. The list was validated by surveying an international group of educational experts. The survey results were used to finalize the list, which was categorized according to the care atom.

Additional ICBs in the education sector were retrieved from ninety-six sources. Fourteen experts from six European countries assessed the list for completeness, clarity, and relevance. The final list contained twenty-four ICBs categorized into input, throughput, and output.

By providing a comprehensive list of ICBs in the education sector, this study laid further foundations for the inclusion of important societal costs in health economics research in the broader European context.

Despite the efforts of the European Union (EU) to promote voluntary cooperation among Health Technology Assessment (HTA) agencies, different reimbursement decisions for the same drug are made across European countries. The aim of this paper is to compare the agreement of cancer drug reimbursement decisions using inter-rater reliability measures.

This study is based on primary data on 161 cancer drug reimbursement decisions from nine European countries from 2002 to 2014. To achieve our goal, we use two measures to analyze agreement, in other words, congruency: (i) percentage of agreement and (ii) the κ score.

One main conclusion can be drawn from the analysis. There is a weak to medium agreement among cancer drug decisions in the European countries analyzed (based on the percentage of agreement and the κ score). England and Scotland show the highest consistency between the two measures, showing a medium agreement. These results are in line with previous literature on the congruency of HTA decisions.

This paper contributes to the HTA literature, by highlighting the extent of weak to medium agreement among cancer decisions in Europe.

To examine the association between physician–patient treatments shared decision making (SDM), patient satisfaction, and adoption of a new health technology.

A cross-sectional study was conducted from July 2016 to October 2016 in Fujian Province and Shanghai, in Eastern China. A total of 542 physicians and 619 patients in eleven hospitals were surveyed. Patients and their treating physicians completed self-reported questionnaires on patient–physician SDM, satisfaction with treatment decision making and adoption of a new health technology. Correlation analysis, multivariate logistic regression and multivariate linear regression were performed.

The majority (68.20 percent) of patients preferred SDM. Involvement of patients in SDM was positively associated with their satisfaction with treatment decision making (p < .001) and adoption of a new health technology (p < .05). Better concordance between their preference and actual SDM was positively associated with patients' adoption behavior (p < .05), but no statistically significant association was found between concordance and satisfaction.

SDM was the most important predictor of patients' satisfaction with decision making and adoption of a new health technology. Therefore, better communication between physicians and patients is recommended to improve their SDM, increase patient satisfaction and to assist with the adoption of new technologies. Training healthcare provider and teaching communication skills in working with patients in the initial stage of technology diffusion is required.

Telestroke is an effective way to improve care and health outcomes for stroke patients. This study evaluates the cost-effectiveness of a French telestroke network.

A decision analysis model was built using population-based data. We compared short-term clinical outcomes and costs for the management of acute ischemic stroke patients before and after the implementation of a telestroke network from the point of view of the national health insurance system. Three effectiveness endpoints were used: hospital death, death at 3 months, and severe disability 3 months after stroke (assessed with the modified Rankin scale). Most clinical and economic parameters were estimated from the medical files of 742 retrospectively included patients. Sensitivity analyses were performed.

The analyses revealed that the telestroke strategy was more effective and slightly more costly than the reference strategy (25 disability cases avoided per 1,000 at 3 months, 6.7 avoided hospital deaths, and 13 avoided deaths at 3 months for an extra cost of EUR 97, EUR 138, and EUR 154, respectively). The results remained robust in the sensitivity analyses.

In France, telestroke is an effective strategy for improving patient outcomes and, despite the extra cost, it has a legitimate place in the national health care system.

The objectives of the study were to establish a benchmarking tool to collect metrics to enable increased clarity regarding the differences and similarities across health technology assessment (HTA) agencies, to assess performance within and across HTA agencies, identify areas in the HTA processes in which time is spent and to enable ongoing performance improvement.

Common steps and milestones in the HTA process were identified for meaningful benchmarking among agencies. A benchmarking tool consisting of eighty-six questions providing information on HTA agency organizational aspects and information on individual new medicine review timelines and outcomes was developed with the input of HTA agencies and validated in a pilot study. Data on 109 HTA reviews from five HTA agencies were analyzed to demonstrate the utility of this tool.

This study developed an HTA benchmarking methodology, comparative metrics showed considerable differences among the median timelines from assessment and appraisal to final HTA recommendation for the five agencies included in this analysis; these results were interpreted in conjunction with agency characteristics.

It is feasible to find consensus among HTA agencies regarding the common milestones of the review process to map jurisdiction-specific processes against agreed metrics. Data on characteristics of agencies such as their scope and remit enabled results to be interpreted in the appropriate local context. This benchmarking tool has promising potential utility to improve the transparency of the review process and to facilitate both quality assurance and performance improvement in HTA agencies.

Consideration of ethical, legal, and social issues plus patient values (ELSI+) in health technology assessment (HTA) is challenging because of a lack of conceptual clarity and the multi-disciplinary nature of ELSI+. We used concept mapping to identify key concepts and inter-relationships in the ELSI+ domain and provide a conceptual framework for consideration of ELSI+ in HTA.

We conducted a scoping review (Medline and EMBASE, 2000–2016) to identify ELSI+ issues in the HTA literature. Items from the scoping review and an expert brainstorming session were consolidated into eighty ELSI+-related statements, which were entered into Concept Systems® Global MAX™ software. Participants (N = 38; 36 percent worked as researchers, 21 percent as academics; 42 percent self-identified as HTA experts) sorted the statements into thematic groups, and rated them on importance in making decisions about adopting technologies in Canada, from 1 (not at all important) to 5 (extremely important). We used Concept Systems® Global MAX™ software to create and analyze concept maps with four to sixteen clusters.

Our final ELSI+ map consisted of five clusters, with each cluster representing a different concept and the statements within each cluster representing the same concept. Based on the concepts, we named these clusters: patient preferences/experiences, patient quality of life/function, patient burden/harm, fairness, and organizational. The highest mean importance ratings were for the statements in the patient burden/harm (3.82) and organizational (3.92) clusters.

This study suggests an alternative approach to ELSI+, based on conceptual coherence rather than academic disciplines. This will provide a foundation for incorporating ELSI+ into HTA.

Health Canada is committed to the modernization of the use of real-world data (RWD) and evidence (RWE) to support regulatory decisions. As such, telephone interviews with stakeholders, including government decision makers, health technology assessment (HTA) producers, industry, and patients, to understand their experiences with and perspectives on how to enhance RWE use for medical devices were performed.

Thirty-four semi-structured telephone interviews with forty key informants were conducted. Transcripts were reviewed independently by one individual to identify, define, and categorize key concepts and were verified by a second reviewer.

There are expectations for Health Canada to provide a framework and guidance on RWE use, identify relevant outcomes for data collection and criteria for data quality, conduct post-market surveillance more systematically, and partner with HTA organizations to develop methods for RWE generation. Stakeholders interviewed support the RWE use for regulatory decisions and HTA recommendations. Moreover, robust scientific methods for RWE generation will be critical to ensure that relevant questions are asked and rigorous statistical analyses are done to answer them. Patients are likely to consent to share their anonymized or de-identified medical information for nonprofit purposes.

Key concepts from the interviews centered on the current and future RWE use for medical devices, considerations for the organizational, medical, scientific, and legal aspects and privacy issues of RWD collection or RWE generation, and options to implement the use of RWD and RWE. Our study findings will help inform the development of an RWE framework for regulatory decisions and HTA recommendations.

In 2018, the National Centre for Pharmacoeconomics (NCPE) was commissioned to conduct a health technology assessment (HTA) of one of the first commercially available chimeric antigen receptor (CAR) T-cell therapies, tisagenlecleucel. CAR T-cells are a major advance in personalized cancer treatment, demonstrating promising outcomes in relapsed/refractory pediatric acute lymphoblastic leukemia (pALL). However, the results are based on short-term follow up, limiting their value in predicting long-term survival and leading to uncertainty about the most appropriate survival modeling method to employ. This study aimed to address these limitations by means of expert elicitation.

An expert elicitation method, the histogram technique, was employed. A predefined discrete numerical scale was presented in Microsoft Excel® and the expert was asked to place twenty crosses on a frequency chart. These crosses represented the expert's beliefs about the distribution of particular quantities. Each cross represented five percent of the probabilistic distribution. Individual distributions were then aggregated across experts using linear pooling.

A total of seventeen experts were invited to take part; eight agreed to participate and five completed the exercise. Three experts did not consider tisagenlecleucel to be a “curative” therapy because patients had a higher risk of death, compared with the age- and sex-matched general population. The aggregated distributions indicated the five-year overall survival rate to be thirty-three percent (95% CI 8.65–56.88) in patients who do not receive a subsequent stem cell transplant and twenty percent (95% CI 2.38 -52.04) in those who do.

The results of this study will be used to calibrate CD19 CAR T-cell therapy survival estimates presented in HTA submissions to the NCPE to ensure more robust assessments. They will also be used to inform the construction of a de novo cost-utility model for examining the cost effectiveness of CD19 CAR T-cell therapies for relapsed/refractory pALL in the Irish healthcare setting.

Physicians' attitudes and adoption behavior toward the delivery of prenatal tests take vital significance for its influence on their professional practice and patient acceptance. This study aimed to identify how physicians have perceived the diffusion of non-invasive prenatal testing (NIPT) in China.

A cross-sectional study was conducted from July 2016 to October 2016 in Shanghai, and Fujian and Sichuan Provinces in China. Physicians working on prenatal screening completed a self-report questionnaire. Following Roger's diffusion of innovation model, multivariable logistic regressions were performed separately for the following key elements of the theory which influence diffusion: physician-perceived attributes of NIPT, communication channels, the nature of the social system, the extent of change agent (who introduces innovations into a society), promotion efforts, and physicians' benefits from adopting NIPT.

Most specialists had a positive attitude (53.2 percent) toward NIPT, whereas 58.9 percent of physicians had already adopted NIPT in their clinical practice. Physician adoption of NIPT was positively associated with the strength of HTA evidence (p = .03), perceived communication frequency with colleagues (p = .04), adoption by other physicians (p = .07), hospital competition (p = .06), hospital teaching status (p = .02), perceived for-profit genetic testing company's promotion (p < .001), and perceived clinical practice skill improvement (p = .02). However, the adoption behavior toward NIPT may be negatively associated with physician-perceived ethical concerns of NIPT (p = .06).

Obstetricians and gynecologists’ positive perceptions facilitate the adoption of NIPT. Combined with cost-effectiveness analysis of prenatal screening methods, health policy makers can promote the adoption of appropriate, cost-effective prenatal screening in pregnant women.

To synthetize the state of the art of methods for identifying candidate technologies for disinvestment and propose an evidence-based framework for executing this task.

An interpretative review was conducted. A systematic literature search was performed to identify secondary or tertiary research related to disinvestment initiatives and/or any type of research that specifically described one or more methods for identifying potential candidates technologies, services, or practices for disinvestment. An iterative and critical analysis of the methods described alongside the disinvestment initiatives was performed.

Seventeen systematic reviews on disinvestment or related terms (health technology reassessment or medical reversal) were retrieved and methods of 45 disinvestment initiatives were compared. On the basis of this evidence, we proposed a new framework for identifying these technologies based on the wide definition of evidence provided by Lomas et al. The framework comprises seven basic approaches, eleven triggers and thirteen methods for applying these triggers, which were grouped in embedded and ad hoc methods.

Although identification methods have been described in the literature and tested in different contexts, the proliferation of terms and concepts used to describe this process creates considerable confusion. The proposed framework is a rigorous and flexible tool that could guide the implementation of strategies for identifying potential candidates for disinvestment.

This study estimates the maximum price at which mesenchymal stem cell (MSC) therapy is deemed cost-effective for septic shock patients and identifies parameters that are most important in making treatment decisions.

We developed a probabilistic Markov model according to the sepsis care trajectory to simulate costs and quality-adjusted life years (QALYs) of septic shock patients receiving either MSC therapy or usual care over their lifetime. We calculated the therapeutic headroom by multiplying the gains attributable to MSCs with willingness-to-pay (WTP) threshold and derived the maximum reimbursable price (MRP) from the expected net monetary benefit and savings attributable to MSCs. We performed scenario analyses to assess the impact of changes to assumptions on the study findings. A value of information analysis is performed to identify parameters with greatest impact on the uncertainty around the cost-effectiveness of MSC therapy.

At a WTP threshold of $50,000 per QALY, the therapeutic headroom and MRP of MSC therapy were $20,941 and $16,748, respectively; these estimates increased with the larger WTP values and the greater impact of MSCs on in-hospital mortality and hospital discharge rates. The parameters with greatest information value were MSC's impact on in-hospital mortality and the baseline septic shock in-hospital mortality.

At a common WTP of $50,000/QALY, MSC therapy is deemed to be economically attractive if its unit cost does not exceed $16,748. This ceiling price can be increased to $101,450 if the therapy significantly reduces both in-hospital mortality and increases hospital discharge rates.

Turkey's health reforms started in 2003 with providing changes in regulatory, financing, and healthcare services. Access to health care and pharmaceuticals increased rapidly, and this resulted with an increase in public pharmaceutical expenditures. Our study aims to quantify and to evaluate the impact of a specific process within the Turkish system called “Medicines Brought From Abroad" (MBFA).

We reviewed the general reimbursement legislations of Social Security Institution (SSI), the guideline on MBFA, the SSI reimbursement list, the list of MBFA published by the Ministry of Health to describe the current supply mechanism of medicines and, in particular, the role of MBFA.

Total costs of the of MBFA medicines over the period 2011–17 went up to more than $520 million, which takes 7.5 percent of total public pharmaceutical expenditure for 2017. Our results showed that MBFA provides access to many orphan drugs and in total, forty-two orphan drugs listed in MBFA accounted for 83 percent of all MBFA budget in the year 2017. Nine of the top ten MBFA medicines were orphan drugs and total costs were $408 million. The highest budget impact was for eculizumab for “paroxysmal nocturnal hemoglobinuria” (PNH), covering 31 percent of total MBFA costs and 2.3 percent of overall drug costs in 2017.

Turkey faced significant challenges for creating an access pathway for innovative medicines while continuing the sustainability of the public pharmaceutical budget like many other countries. Therefore, it may be argued that Turkey needs to create an independent health technology assessment organization to provide sustainable access to medicines in the future.