To describe the type and level of ethical integration in published health technology assessment (HTA) reports and systematically identify the ethical approaches utilized.

A literature search was conducted with the Google™ search engine using the keyword “ethic” between 1 January 2015 and 20 August 2019. Only HTA assessment reports with a section on ethics were retained and classified according to their level of ethical integration: no ethical analysis, ethical issues highlighted, assessments according to legal or social norms, and assessments from a moral or axiological perspective—using a qualitative methodology to distinguish such integration.

This review yielded 188 reports with a section identified as being on ethics, produced by seventeen HTA agencies in eleven countries. One hundred and thirty-six reports did not develop an ethical analysis, thirty-one highlighted ethical issues, seventeen conducted a norm-based ethical assessment using a descriptive approach grounded in social norms, and four developed an assessment grounded in a moral or axiological perspective. The bioethical “four-principles” framework was used, but mainly for presenting ethical issues and not as a moral framework.

The majority of reports featuring a section on ethics mention ethical considerations without ethical analysis. Ethical issues are grouped with legal, social, and organizational issues and treated as contextual considerations that decision makers should be aware of. When reports present systematic norm-based ethical assessments from a descriptive perspective or ethical assessment based on a moral or axiological perspective, there is a tendency to ground these analyses in frameworks created for the purpose and reliant on a concept of ethics supporting them.

Hepatitis A (HA) is a liver disease with a low mortality rate, but it can cause debilitating symptoms and fulminant hepatitis in some cases. Its incidence is greater in geographical areas with poor sanitation and hygiene. Spain is considered a low-endemicity country, so universal childhood immunization against HA is currently not financed by the National Health System. The aim of this study was to synthesize the scientific evidence on the cost effectiveness of universal childhood vaccination against HA.

Full economic evaluations, published in the English or Spanish languages, were included if they reported outcome measures related to the prevention of HA, adverse effects, or incremental cost-effectiveness ratios (ICERs). The Medline, Embase and Cochrane Library databases were searched for articles published from the beginning of the databases to April 2018.

A total of 23 economic evaluations were included: one in a country of high endemicity, nine in countries of intermediate endemicity, and 13 in countries with low endemicity. Only one Spanish study, published in 1997, was found. Studies conducted in high- and intermediate- endemicity countries concluded that a universal childhood vaccination program against HA was a cost-effective option. However, in the case of countries with low endemicity the results were heterogeneous, although most agreed that a systematic vaccination strategy would not be a cost-effective option and that the adoption of such a strategy would not be justified given the limited benefits it would offer. The results of the economic evaluations depended on parameters such as the price and duration of the vaccine effect and the program coverage.

In countries with low endemicity the results were heterogeneous, although most studies concluded that the implementation of a universal vaccination strategy is not justified from the point of view of cost effectiveness.

The quality of life (QoL) of caregivers who look after individuals with drug-resistant focal-onset seizures (FOS) can be significantly affected by their caregiving responsibilities. This is widely recognized by various health technology assessment bodies, including the National Institute for Health and Care Excellence. The aim of this study was to assess the QoL and to generate health-related utility data for individuals caring for adults with drug-resistant FOS. This project will provide critical information on an often neglected and undervalued aspect of epilepsy.

An online survey including questions on sociodemographic characteristics, caregiver burden and productivity, the EQ-5D-5L, and the Care Related Quality of Life (CarerQol-7D) was administered to caregivers of individuals with drug-resistant FOS in the United Kingdom.

The analysis included 86 caregivers. The majority were men aged between 25 and 34 years whose caring responsibilities ranged from 25 to 34 hours per week. In the previous 28 days, most individuals they cared for experienced four FOS, with the longest seizure-free period ranging from 6 to 15 days. The patients had previously been prescribed at least four anti-seizure medications.

The caregivers’ mean EQ-5D-5L score was 0.66 (range -0.19 to 1), whilst the mean CarerQol-7D score was 71 (range 21 to 100). The most affected dimension of the EQ-5D-5L was self-care, while the most affected dimension of the CarerQol-7D was physical functioning.

Caring for people with drug-resistant FOS has a negative impact on the QoL of caregivers, particularly in the domains of self-care and physical functioning.

Technological and computational advancements offer new tools for the collection and analysis of real-world data (RWD). Considering the substantial effort and resources devoted to collecting RWD, a greater return would be achieved if real-world evidence (RWE) was effectively used to support Health Technology Assessment (HTA) and decision making on medical technologies. A useful question is: To what extent are RWD suitable for generating RWE?

We mapped existing RWD sources in Europe for three case studies: hip and knee arthroplasty, transcatheter aortic valve implantation (TAVI) and mitral valve repair (TMVR), and robotic surgery procedures. We provided a comprehensive assessment of their content and appropriateness for conducting the HTA of medical devices. The identification of RWD sources was performed combining a systematic search on PubMed with gray literature scoping, covering fifteen European countries.

We identified seventy-one RWD sources on arthroplasties; ninety-five on TAVI and TMVR; and seventy-seven on robotic procedures. The number, content, and integrity of the sources varied dramatically across countries. Most sources included at least one health outcome (97.5%), with mortality and rehospitalization/reoperation the most common; 80% of sources included resource outcomes, with length of stay the most common, and comparators were available in almost 70% of sources.

RWD sources bear the potential for the HTA of medical devices. The main challenges are data accessibility, a lack of standardization of health and economic outcomes, and inadequate comparators. These findings are crucial to enabling the incorporation of RWD into decision making and represent a readily available tool for getting acquainted with existing information sources.

Several targeted immune modulators (TIMs) have demonstrated effectiveness in moderate-to-severe ulcerative colitis, including adalimumab, golimumab, infliximab, infliximab biosimilars, tofacitinib, ustekinumab, and vedolizumab. In addition to assessing individual TIMs, evaluating TIM sequences can inform clinical care as well as coverage and reimbursement policies. Our objective was to identify optimal treatment sequences based on maximum net health benefit (NHB), lowest total cost (cost minimizing), quality-adjusted life-year (QALY) maximization, or convenience (avoidance of intravenous treatments), and to evaluate their cost effectiveness compared with conventional treatment from the health sector perspective.

We developed a Markov model with eight-week cycles and a lifetime time horizon. The health states were active, clinical response without remission, remission, and death. TIM efficacy was informed by a network meta-analysis conducted by the Institute for Clinical and Economic Review. Sequences were generated by ranking TIMs and then conventional treatment according to NHB, cost minimization, QALY maximization, or convenience and combining top ranked TIMs in the biologic naïve and biologic experienced populations. NHB was calculated at USD 150,000 per QALY. Probabilistic sensitivity analysis (PSA) was undertaken to estimate the probability of each sequence having the highest NHB rank, QALY maximizing rank, and cost-minimizing rank.

Twenty-one sequences were evaluated. The sequence with the highest NHB was infliximab followed by tofacitinib (-0.12 QALYs), which also had the lowest incremental costs (USD37,266). For orally and subcutaneously administered TIMs, the sequence of golimumab-tofacitinib had the highest NHB (-0.34 QALYs). Ustekinumab-vedolizumab was not only the top ranked sequence as measured by QALY maximization (0.172 incremental QALYs), but it also had the highest total incremental cost (USD166,094). Results of the PSA were consistent with deterministic rankings for the top-ranking sequences and showed that the top two or three regimens were close in magnitude.

The optimal sequence with regard to NHB and cost minimization was infliximab or biosimilars, followed by tofacitinib, adalimumab, or vedolizumab. Sequences that generated the most QALYs began with ustekinumab, followed by vedolizumab, tofacitinib, and adalimumab.

Da Vinci robotic-assisted surgery (RAS) has been evaluated by health technology assessment (HTA) organizations across the world. This study aimed to analyze the existing HTA reports over years, countries, and procedures.

Publicly available health technology appraisal reports on RAS published from January 2000 to November 2020 were identified via a targeted literature search. The literature search was conducted in PubMed, the Centre for Reviews and Dissemination database, the International Network of Agencies for Health Technology Assessment database, and Google scholar. Reports related to the da Vinci RAS were included. Full texts of reports were used for the analysis.

For the HTAs that recommended RAS, the directional conclusion was considered as positive. For HTA reports that discouraged the use of RAS, the directional conclusion was considered as negative. The rest were considered as neutral. The reports were analyzed by year, country, and procedure.

We identified 65 HTA reports comprising 128 procedure-level assessments of RAS by 42 HTA organizations in 21 countries over 20 years. The annual number of assessments increased over time. The countries that completed the most assessments were Sweden (14 reports, including 15 procedure-level assessments: 13% positive and 80% neutral) and Canada (11 reports, including 20 procedure-level assessments: 65% positive).

The topics of the assessments covered 27 surgical indications in urology, gynecology, thoracic, general, and ear, nose, and throat. The conclusions of the HTAs varied by surgical indication. Prostatectomy (33 reports: 85% neutral or positive) was the most widely assessed surgical indication, followed by hysterectomy (16 reports: 81% neutral or positive), nephrectomy (15 reports: 73% neutral or positive), and rectal resection (10 reports: 100% neutral or positive).

The number and breadth of HTAs on RAS have grown at an increasing rate over the last 20 years. The directional conclusion of assessments varied by procedure and country. Further analysis is warranted to understand the factors contributing to HTA conclusions on RAS.

Peer review of searches is a process whereby both the search strategies and the search process description are reviewed, ideally using an evidence-based checklist.

As the search strategy underpins any well-conducted evidence synthesis, its quality could affect the final result. Evidence shows, however, that search strategies are prone to error.

There is increasing awareness and use of the PRESS Evidence-Based Checklist and peer review of search strategies, at the outset of evidence syntheses, prior to the searches being run, and this is now recommended by a number of evidence synthesis organizations.

Searches for evidence syntheses should be peer reviewed by a suitably qualified and experienced librarian or information specialist after being designed, ideally, by another suitably qualified and experienced librarian or information specialist. Peer review of searches should take place at two important stages in the evidence synthesis process; at the outset of the project prior to the searches being run and at the prepublication stage. There is little empirical evidence, however, to support the effectiveness of peer review of searches. Further research is required to assess this. Those wishing to stay up to date with the latest developments in information retrieval, including peer review of searches, should consult the SuRe Info resource (http://www.sure-info.org), which seeks to help information specialists and others by providing easy access to the findings from current information retrieval methods research and thus support more research-based information retrieval practice.

Transcatheter aortic valve implantation (TAVI) represents a new treatment option for aortic stenosis. This study aimed to evaluate the cost utility of TAVI, compared with clinical treatment, in patients with inoperable severe aortic stenosis from the perspective of the Brazilian public health system.

A Markov model with monthly cycles and a five percent annual discount rate was constructed. A five-year time horizon was chosen, to minimize the uncertainties inherent with data extrapolations, based on the only randomized head-to-head trial, Placement of AoRTic TraNscathetER Valve Trial (PARTNER B). All costs were obtained from Brazil's official healthcare data. Utilities for clinical treatment 0.6 (range 0.56–0.63) and TAVI 0.71 (range 0.69–0.72) were based on studies that used the EuroQol-5D instrument. TAVI's utility measures were penalized by 25 percent in the first month, based on the estimate of the procedure's impact on quality of life provided by the National Institute of Health and Care Excellence in the United Kingdom. Lastly, deterministic and probabilistic sensitivity analyses were used to evaluate the robustness of the results.

The incremental cost-effectiveness ratio was USD35,880 per quality-adjusted life-year (QALY), a result that was mainly sensitive to TAVI's cost in the univariate analysis. In the probabilistic analysis, all values were above the reference willingness-to-pay threshold of three times the Brazilian per capita gross domestic product (USD18,042 per QALY).

In conclusion, even though there is no established willingness-to-pay threshold in Brazil, the cost of TAVI may represent an obstacle for its incorporation into the Brazilian public health system.

Conventional appraisal and reimbursement processes are being challenged by the increasing number of rare disease treatments (RDTs) with a small evidence base and often a high price. Processes to appraise RDTs vary across countries; some use standard processes, others have separate processes or adapted processes that explicitly deal with rare disease specificities. The objective of this study was to examine the impacts of different appraisal processes for two RDTs.

A case study analysis was conducted using countries with different forms of appraisal processes for RDTs for which public health technology assessment (HTA) reports were available. Two contrasting RDTs were chosen according to the criteria: rare versus ultra-rare treatment, affecting child versus adult, life-threatening versus disabling. Information from public HTA reports for each country's RDT appraisal was extracted into templates, allowing a systematic comparison of the appraisals across countries and identification of the impact of the different processes in practice.

Reports from Belgium, England, France, Germany, Italy, Netherlands, Norway, Scotland, Sweden, and the USA were selected for nusinersen (for spinal muscular atrophy) and voretigene neparvovec (for inherited retinal disorders). Countries with separate or adapted processes had more consistent approaches for managing RDT-related issues during appraisal, such as stakeholder involvement and criteria to address the specificities of RDTs, creating more transparency in decision-making.

Findings suggest that separate or adapted approaches for RDT appraisal may facilitate more structured, consistent decision-making and better management of RDT specificities.

A growing number of evaluation frameworks have emerged over recent years addressing the unique benefits and risk profiles of new classes of digital health technologies (DHTs). This systematic review aims to identify relevant frameworks and synthesize their recommendations into DHT-specific content to be considered when performing Health Technology Assessments (HTAs) for DHTs that manage chronic noncommunicable disease at home.

Searches were undertaken of Medline, Embase, Econlit, CINAHL, and The Cochrane Library (January 2015 to March 2020), and relevant gray literature (January 2015 to August 2020) using keywords related to HTA, evaluation frameworks, and DHTs. Included framework reference lists were searched from 2010 until 2015. The EUNetHTA HTA Core Model version 3.0 was selected as a scaffold for content evaluation.

Forty-four frameworks were identified, mainly covering clinical effectiveness (n = 30) and safety (n = 23) issues. DHT-specific content recommended by framework authors fell within 28 of the 145 HTA Core Model issues. A further twenty-two DHT-specific issues not currently in the HTA Core Model were recommended.

Current HTA frameworks are unlikely to be sufficient for assessing DHTs. The development of DHT-specific content for HTA frameworks is hampered by DHTs having varied benefit and risk profiles. By focusing on DHTs that actively monitor/treat chronic noncommunicable diseases at home, we have extended DHT-specific content to all nine HTA Core Model domains. We plan to develop a supplementary evaluation framework for designing research studies, undertaking HTAs, and appraising the completeness of HTAs for DHTs.

Although randomized controlled trials (RCTs) are recognized as providing the highest level of clinical evidence, few medical device RCTs are available due to underfunding or inherent challenges associated with trial design. This study examines the extent to which real-world evidence (RWE) supports the recommendations made by the National Institute for Health and Care Excellence Medical Technologies Evaluation Programme (MTEP).

All MTEP guidance documents published online prior to October 2020 were reviewed. The “case for adoption” recommendation, type of clinical data, and clinical critiques for each MTEP submission were extracted and categorized. RWE was defined as studies with neither blinding nor prospective selection or control of patient characteristics.

Of the MTEP submissions reviewed, 34 of 45 (76%) received a positive recommendation. Independent of outcome, all submissions included RWE, but only 19 (42%) utilized RCT evidence (15 were recommended and four were not). Meta-analyses of RWE were used whenever possible. The most common clinical critiques in unsuccessful submissions were the following: (i) not generalizable to the United Kingdom National Health Service (NHS); (ii) low quality; (iii) likelihood of bias; (iv) trial design faults; (v) uncertain benefit; and (vi) evidence unrelated to scope.

This study suggests that while the use of RCTs has not always led to a positive recommendation, RWE can be valuable in decision-making. Evidence that is generalizable to the NHS, is related to the scope, and shows clear indication of benefit is more likely to positively influence MTEP decision-making.

Established and emerging technologies—such as wearable sensors, smartphones, mobile apps, and artificial intelligence—are shaping positive healthcare models and patient outcomes. These technologies have the potential to become precision health (PH) innovations. However, not all innovations meet regulatory standards or have the required scientific evidence to be used for health applications. In response, an assessment framework was developed to facilitate and standardize the assessment of innovations deemed suitable for PH.

A scoping literature review undertaken through PubMed and Google Scholar identified approximately 100 relevant articles. These were then shortlisted (n = 12) to those that included specific metrics, criteria, or frameworks for assessing technologies that could be applied to the PH context.

The proposed framework identified nine core criteria with subcriteria and grouped them into four categories for assessment: technical, clinical, human factors, and implementation. Guiding statements with response options and recommendations were used as metrics against each criterion.

The proposed framework supports health services, health technology innovators, and researchers in leveraging current and emerging technologies for PH innovations. It covers a comprehensive set of criteria as part of the assessment process of these technologies.

The United Kingdom spends approximately GBP4.2 billion (USD5.6 billion; EUR4.7 billion) each year on medical devices, but healthcare providers receive little health technology assessment (HTA) guidance on cost-effective device procurement. Our objective was to assess the availability of HTA guidance for medical technologies and to identify key challenges related to the economic assessment of these technologies.

National Institute for Health and Care Excellence technology appraisal (TA) and Medical Technologies Evaluation Programme (MTEP) appraisals published online between November 2009 and October 2020 were identified. The “case for adoption” recommendation, type of devices, and critiques of economic analyses for each MTEP appraisal were extracted and categorized.

In comparison to 415 publicly available TAs for pharmaceuticals, only 45 medical technologies have been appraised through the MTEP. MTEP-submitted technologies can be categorized into diagnostic (7), monitoring (3), prophylaxis (5), therapeutic (28), and other (2). Furthermore, 11 were implants, seven were used by patients, and 27 had provider interaction. Major points of MTEP criticism were a failure to model cost consequences, training costs, and organizational impact. There was also the barrier of transferring costs across budgeting divisions.

In comparison to HTA guidance for pharmaceuticals, there is a dearth of medical device guidance. Therapeutic and implantable devices appear to be disproportionately overrepresented in the MTEP process. This may be because their appraisal is most akin to pharmaceuticals, for which HTA processes are well established. To encourage more HTAs of medical devices, HTA guidance should elaborate on issues specifically related to medical devices.

Robotic surgery (RS) can offer benefits compared to freehand surgery (FS) in the treatment of patients with spinal diseases. The aim of this study was to assess efficacy and safety of RS versus FS in spinal fusion. The outcomes considered were accuracy in the placement of pedicle screws, surgical times, hospital stay, exposure to radiation, and complications.

A systematic review and meta-analysis were performed by researchers at the Instituto de Salud Carlos III (ISCIII). Studies published until June 2019 in the English, Spanish, or French languages were retrieved. The data analyses and risk of bias assessments were undertaken using RevMan 5.3.

Eight randomized controlled trials including 610 patients (RS: 308, FS: 302) were found. The mean age of the patients ranged from 56 to 68 years in the FS group and from 55 to 68 years in the RS group. The percentage of women included ranged from 46 to 73 percent undergoing FS and from 33 to 70 percent undergoing RS. The main diagnosis was degenerative spine disease. The number of screws implanted ranged from 22 to 584 for FS and 23 to 532 for RS. The robots used were the SpineAssist and Renaissance Guidance System (Mazor Robotics, Ltd) and the TiRobot® Orthopaedic Robotic System (Beijing Tinavi Medical Technologies Co., Ltd). Pedicle screw placement within the safety zone (Grades A and B on the Gertzbein and Robbins scale) ranged from 93 to 100 percent in FS and from 85 to 100 percent in RS (relative risk 1.0, 95% confidence interval [CI] 0.99–1.03; p = 0.36) (I2=75%; p = 0.0005). Regarding intervention time, the meta-analysis showed a mean difference (MD) of 15.2 minutes (95% CI 5.35–25.05; p = 0.002) (I2 = 0%; p = 0.39) in favor of FS. The MD in hospital stay was 0.36 days (95% CI -1.03–0.31; p = 0.30) (I2 = 62%; p = 0.07), which was not statistically significant. Contradictory results were found for fluoroscopy time, although RS was associated with a lower radiation dose than FS (p < 0.05). In relation to safety, studies only reported on rates of surgical revision, which ranged from 0 to 2 after FS and from 0 to 10 after RS. The risk or bias was unclear in most studies.

We found no conclusive results suggesting benefits for spinal fusion using RS compared with FS. Further research with adequate selection of patients, type of robot, and comparator is needed.

The Scottish Medicines Consortium (SMC) conducts early health technology assessment (HTA) of new medicines. The advice is implemented at the local level by 14 Health Board Area Drug and Therapeutics Committees (ADTCs). The primary output is a published document, the Detailed Advice Document (DAD), which aims to describe the strengths and weaknesses of the evidence considered and the rationale for the decision. We examined how the DAD is being used to determine areas for improvement.

We conducted semi-structured interviews with a purposive sample of SMC and ADTC members and formulary pharmacists, who are one of the key audiences. Interviews were recorded and transcribed using Microsoft Teams and coded in NVivo. The results were assessed via thematic analysis, which included major themes such as the structure and content of the DAD and its usefulness in supporting implementation of the advice from an ADTC perspective.

Following initial interviews (n = 7), some early themes have emerged. The DAD is a valued tool describing the assessment of a medicine's clinical and cost effectiveness. The current length of the DADs and the technical language used can limit the accessibility of information, and there have been suggestions on how to improve the structure and content. Additional interviews are still being completed and full interview results (available early 2021) will be analyzed to identify key themes.

The DAD is the primary output of SMC's HTA process, which includes decisions on whether a medicine can be routinely prescribed in the National Health Service Scotland. DADs have increased in length over the years, reflecting the increasing complexity of new medicines and a corresponding increase in the size of pharmaceutical company submissions. The interviews conducted to date suggest that the DADs are highly regarded and support implementation of new medicines advice by the ADTC. The findings of this evaluation will lead to an action plan for improvement.

The objective of this exploratory analysis is to reflect and discuss which criteria of multiple criteria decision analysis (MCDA) would be relevant as part of value determination when appraising healthcare interventions in the Lebanese context.

A workshop was conducted as part of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Lebanon Chapter and included the two frameworks: Evidence and Value: Impact on Decision Making (EVIDEM) and Advance Value Framework. Thirty-seven participants expressed their individual preferences through a qualitative and a quantitative exercise.

In the qualitative analysis of both frameworks, participants unanimously agreed on the relevance of comparative efficacy, safety, and impact of medical costs. In EVIDEM, disease severity and unmet needs were also considered to be important criteria by more than 90 percent of the participants. In the quantitative analysis of both frameworks, disease severity ranked first (a mean normalized weight of .1 in EVIDEM and .27 in Advance Value Framework), followed by the size of the population (.09), the type of therapeutic benefit at the patient level (.09) and population level (.08), and the efficacy (.07) in EVIDEM. In the Advance Value Framework, the combined unmet need/disease severity criteria were followed by direct and meaningful end points (.15), safety (.12), contraindications (.08), and indirect surrogate end points (.07).

The results were concordant with those reported in countries that have conducted similar surveys such as France, Italy, and Spain. The MCDA methodology could be used as a cornerstone to enhance evidence-based discussions among Lebanese stakeholders involved in evaluation and decision-making purposes.

The Scottish Medicines Consortium (SMC) conducts early health technology assessment (HTA) of new medicines on behalf of the National Health Service Scotland based on pharmaceutical company submissions. As the appraisals are conducted close to the point of marketing authorization, there is often a lack of direct head-to-head data. In 2019, assessment of relevant comparative efficacy was informed via indirect treatment comparisons (ITC) in 55 percent (36/66) of submissions. While the ITCs are essential to the decision-making process, they are frequently incomplete.

A focus group was conducted with the clinical assessment team (n = 11) to explore problems in the submission process and to identify areas for improvement. It was agreed that providing improved guidance to companies prior to submission may prevent future inconsistencies. A working group (n = 5) was tasked with identifying and implementing potential solutions. The group reviewed the focus group findings, relevant literature, and guidance from other organizations. Draft guidance was developed that was reviewed by two pharmaceutical industry representatives (SMC subcommittee members).

Findings from the focus group highlighted issues broadly related to the incomplete presentation and reporting of ITCs. The improved guidance document outlined specific requirements in a checklist format for reporting and presenting the results of different ITC data. This guidance was published in February 2020. To evaluate the impact of the updated guidance and to identify any further changes required, a follow-up focus group and survey of industry representatives is planned for March 2021.

The aim of the ITC guidance is to provide pharmaceutical companies with direction to improve the quality and transparency of reporting, which will in turn improve the quality of HTAs and thus strengthen the recommendations provided by the SMC. The follow-up focus groups and survey will assess the impact of the guidance. It is acknowledged that the results of this process may be limited by the small sample size and short duration of the assessment.