The evolution of breast cancer (BC) treatments has resulted in tailored therapies for the different types and stages of BC. Each treatment has a profile of benefits and adverse effects which are taken into consideration when planning a treatment pathway. This study examines whether patients’ preferences are in line with what is considered important from decision makers viewpoint.

An online discrete choice experiment was conducted in six European countries (France, Germany, Ireland, Poland, Spain, UK) with BC patients. Six attributes were included: overall survival (OS), hyperglycemia, rash, pain, functional well-being (FWB), and out-of-pocket payment (OOP). Sixteen choice sets with two hypothetical treatments and a “No treatment” option were presented. Data were analyzed with the use of heteroscedastic conditional, mixed logistic, and latent class models. Marginal rate of substitution (MRS) were estimated for OOP versus the rest of attributes to establish the ranking of preferences for each attribute.

Two hundred and forty-seven patients with advanced or metastatic BC and 314 with early-stage BC responded. Forty-nine percent of patients were < 44 years old and 65 percent had completed university education. The MRS of the analysis demonstrated that “severe pain” is the highest dis-preferred attribute level, followed by “severe impairment in FWB” and OS. Four classes of patients as “decision makers” were identified.

This study suggests that there is heterogeneity in treatment preferences of BC patients depending on their sociodemographic and disease-related characteristics. In combination with clinical guidelines, patient preferences can support the selection and tailoring of treatment options.

Systematic reviews (SRs) are usually conducted by a highly specialized group of researchers. The routine involvement of methodological experts is a core methodological recommendation. The present commentary describes the qualifications required for information specialists and statisticians involved in SRs, as well as their tasks, the methodological challenges they face, and potential future areas of involvement.

Information specialists select the information sources, develop search strategies, conduct the searches, and report the results. Statisticians select the methods for evidence synthesis, assess the risk of bias, and interpret the results. The minimum requirements for their involvement in SRs are a suitable university degree (e.g., in statistics or librarian/information science or an equivalent degree), methodological and content expertise, and several years of experience.

The complexity of conducting SRs has greatly increased due to a massive rise in the amount of available evidence and the number and complexity of SR methods, largely statistical and information retrieval methods. Additional challenges exist in the actual conduct of an SR, such as judging how complex the research question could become and what hurdles could arise during the course of the project.

SRs are becoming more and more complex to conduct and information specialists and statisticians should routinely be involved right from the start of the SR. This increases the trustworthiness of SRs as the basis for reliable, unbiased and reproducible health policy, and clinical decision making.

To develop best-practice guidance for health technology assessment (HTA) agencies when appraising diagnostic tests for SARS-CoV-2 and treatments for COVID-19.

We used a policy sandbox approach to develop best-practice guidance for HTA agencies to approach known challenges associated with assessing tests and treatments for COVID-19. The guidance was developed by a multi-stakeholder workshop of twenty-one participants representing HTA agencies, clinical and patient experts, academia, industry, and a payer, from across Europe and North America. The workshop was supported by extensive background work to identify the key challenges, including: targeted reviews of existing COVID-related methods guidance for assessing interventions and clinical guidelines, engagement with clinical experts, a survey and workshop of HTA agencies, a systematic review of published economic evaluations, and a workshop of health economic modelers.

We suggest HTA agencies should consider using other types of evidence (e.g., real world) where high-quality randomized controlled trials may be lacking and healthcare systems would value timely HTA outputs. A “living” HTA approach may be useful, given the context of an evolving disease, scientific understanding and evidence base, allowing for decisions to be efficiently revisited in response to new information; particularly, if supported by a common “disease model” for COVID-19. Innovative ways of engaging with the public and clinicians, and early engagement with regulators and payers, are recommended.

HTA agencies should consider the elements of this guidance that are most suited to their existing processes to enable them to assess the effectiveness and value of interventions for COVID-19.

Remote patient monitoring (RPM) has emerged as a viable and valuable care delivery method to improve chronic disease management. In light of the high prevalence and substantial economic burden of cardiovascular disease (CVD), this systematic review examines the cost and cost-effectiveness of using RPM to manage CVD in the United States.

We systematically searched databases to identify potentially relevant research. Findings were synthesized for cost and cost-effectiveness by economic study type with consideration of study perspective, intervention, clinical outcome, and time horizon. The methodological quality was assessed using the Joanna Briggs Institute Checklist for Economic Evaluations.

Thirteen articles with fourteen studies published between 2011 and 2021 were included in the final review. Studies from the provider perspective with a narrow scope of cost components identified higher costs and similar effectiveness for the RPM group relative to the usual care group. However, studies from payer and healthcare sector perspectives indicate better clinical effectiveness of RPM relative to usual care, with two cost-utility analysis studies suggesting that RPM relative to usual care is a cost-effective tool for CVD management even at the conservative $50,000 per Quality-Adjusted Life-Year threshold. Additionally, all model-based studies revealed that RPM is cost-effective in the long run.

Full economic evaluations identified RPM as a potentially cost-effective tool, particularly for long-term CVD management. In addition to the current literature, rigorous economic analysis with a broader perspective is needed in evaluating the value and economic sustainability of RPM.

Despite increasing emphasis on the inclusion of patient input in health technology assessment (HTA) in Europe in particular, questions remain as to the integration of patient insight alongside other HTA inputs. This paper aims to explore how HTA processes, while ensuring the scientific quality of assessments, “make do” with patient knowledge elicited through patients’ involvement mechanisms.

The qualitative study analyzed institutional HTA and patient involvement in four European country contexts. We combined documentary analysis with interviews with HTA professionals, patient organizations, and health technology industry representatives, complemented with observational findings made during a research stay at an HTA agency.

We present three vignettes which showcase how different parameters of assessment become reframed upon the positioning of patient knowledge alongside other forms of evidence and expertise. Each vignette explores patients’ involvement during an assessment of a different type of technology and at a different stage of the HTA process. First, cost-effectiveness considerations were reframed during an appraisal of a rare disease medicine based on patient and clinician input regarding its treatment pathway; in the second vignette reframing amounted to what counts as a meaningful outcome measure for a glucose monitoring device; in the third, evaluating pediatric transplantation services involved reframing an option’s appropriateness from a question of moral to one of legal acceptability.

Making do with patient knowledge in HTA involves reframing of what is being assessed. Conceptualizing patients’ involvement in this way helps us to consider the inclusion of patient knowledge not as complementary to, but as something that can transform the assessment process.

This study aimed to assess whether there have been changes in the quality of clinical evidence submitted for government subsidy decisions on cancer medicines over the past 15 years.

We reviewed public summary documents (PSDs) reporting on subsidy decisions made by the Pharmaceutical Benefits Advisory Committee (PBAC) from July 2005 to July 2020. Information was extracted on the study design, directness of comparison, sample size, and risk of bias (RoB). Changes in the quality of evidence were assessed using regression analysis.

Overall, 214 PSDs were included in the analysis. Thirty-seven percent lacked direct comparative evidence. Thirteen percent presented observational or single-arm studies as the basis for decisions. Among PSDs presenting indirect comparisons, 78 percent reported transitivity issues. Nearly half (41 percent) of PSDs reporting on medicines supported by head-to-head studies noted there was a moderate/high/unclear RoB. PSDs reporting concerns with RoB increased by a third over the past 7 years, even after adjusting for disease rarity and trial data maturity (OR 1.30, 95% CI: 0.99, 1.70). No time trends were observed regarding the directness of clinical evidence, study design, transitivity issues, or sample size during any of the analyzed periods.

Our findings indicate that the clinical evidence supplied to inform funding decisions for cancer medicines is often of poor quality and has been deteriorating over time. This is concerning as it introduces greater uncertainty in decision making. This is particularly important as the evidence supplied to the PBAC is often the same as that supplied to other global decision-making bodies.

The aim of this study was to deliver insights from multiple stakeholders into actual and future collaboration for health technology assessment (HTA) in general and in oncology in particular.

Eighteen semi-structured interviews were conducted with experts from European HTA bodies (HTAbs), former board members of the European Network for Health Technology Assessment (EUnetHTA), and representatives from the pharmaceutical industry, a regulatory agency, academia, and patient organizations. The stakeholders were asked about their support of the EUnetHTA’s intent, about the general strengths and challenges of the EUnetHTA and its Joint Action 3 (JA 3), the strengths and challenges of the clinically oriented HTA collaboration in oncology during JA 3 across the technology life cycle, about future challenges to HTA in oncology with consequences for collaboration, and about collaboration in the economic domains of HTA. The transcribed interviews were analyzed qualitatively.

The participants perceived the intention and work quality of the EUnetHTA as positive. The experts described methodological, procedural, and capacity challenges in early dialogues (EDs) and rapid relative effectiveness assessments (REAs) meant to analyze clinical effectiveness in oncology. The majority attached increasing importance to collaboration in the future to cope with the uncertainty of HTA. Several stakeholders also proposed the incorporation of joint postlaunch evidence generation (PLEG) activities. Some gave sporadic suggestions for voluntary nonclinical collaboration as well.

Stakeholders’ continued readiness to discuss the remaining challenges to and sufficient resources for implementing HTA regulation, as well as further cooperative expansion along the technology life cycle, are necessary for improved HTA collaboration in Europe.

Value-based agreements (VBAs) link access, reimbursement, or price to the real-world usage and impact of a medicine, thereby enabling patient access while reducing clinical or financial uncertainty for the payer. VBAs have the potential to support improved patient outcomes, given the value-oriented approach to care, and lead to overall savings, while enabling payers to share risk and reduce uncertainty.

This commentary outlines the key challenges, enablers, and a framework for successful implementation by comparing the experience of two VBAs for AstraZeneca medicines, aiming to increase confidence in their future use.

Engagement by payers, manufacturers, physicians, and provider institutions, and robust data collection systems that are accessible, simple to use, and add little burden to physicians were key to successfully negotiating a VBA that worked for all stakeholders. In both country systems, a legal/policy framework enabled innovative contracting.

These examples demonstrate proof of concept for VBA implementation in different settings, and may inform future VBAs.

Health technology assessment (HTA) organizations vary in terms of how they conduct assessments. We assess whether and to what extent HTA bodies have adopted societal and novel elements of value in their economic evaluations.

After categorizing “societal” and “novel” elements of value, we reviewed fifty-three HTA guidelines. We collected data on whether each guideline mentioned each societal or novel element of value, and if so, whether the guideline recommended the element’s inclusion in the base case, sensitivity analysis, or qualitative discussion in the HTA.

The HTA guidelines mention on average 5.9 of the twenty-one societal and novel value elements we identified (range 0–16), including 2.3 of the ten societal elements and 3.3 of the eleven novel value elements. Only four value elements (productivity, family spillover, equity, and transportation) appear in over half of the HTA guidelines, whereas thirteen value elements are mentioned in fewer than one-sixth of the guidelines, and two elements receive no mention. Most guidelines do not recommend value element inclusion in the base case, sensitivity analysis, or qualitative discussion in the HTA.

Ideally, more HTA organizations will adopt guidelines for measuring societal and novel value elements, including analytic considerations. Importantly, simply recommending in guidelines that HTA bodies consider novel elements may not lead to their incorporation into assessments or ultimate decision making.

To assess the potential cost-effectiveness of neuromuscular electrical stimulation (NMES) for treatment of mild obstructive sleep apnea (OSA).

A decision-analytic Markov model was developed to estimate health state progression, incremental cost, and quality-adjusted life year (QALY) gain of NMES compared to no treatment, continuous airway pressure (CPAP), or oral appliance (OA) treatment. The base case assumed no cardiovascular (CV) benefit for any of the interventions, while potential CV benefit was considered in scenario analyses. Therapy effectiveness was based on a recent multi-center trial for NMES, and on the TOMADO and MERGE studies for OA and CPAP. Costs, considered from a United States payer perspective, were projected over lifetime for a 48-year-old cohort, 68% of whom were male. An incremental cost-effectiveness ratio (ICER) threshold of USD150,000 per QALY gained was applied.

From a baseline AHI of 10.2 events/hour, NMES, OA and CPAP reduced the AHI to 6.9, 7.0 and 1.4 events/hour respectively. Long-term therapy adherence was estimated at 65-75% for NMES and 55% for both OA and CPAP. Compared to no treatment, NMES added between 0.268 and 0.536 QALYs and between USD7,481 and USD17,445 in cost, resulting in ICERs between USD15,436 and USD57,844 per QALY gained. Depending on long-term adherence assumptions, either NMES or CPAP were found to be the preferred treatment option, with NMES becoming more attractive with younger age and assuming CPAP was not used for the full night in all patients.

NMES might be a cost-effective treatment option for patients with mild OSA.

This study explored experts’ views on the development of a proposed checklist for cost-of-illness (COI) studies. It also investigated experts’ perspectives on the use of COI studies and quality/critical appraisal tools used for COI studies as well as their experiences with the use of these tools.

Semi-structured, open-ended interviews were conducted with health economists and other experts working with COI studies and with experience of developing health economic guidelines or checklists. Participants were selected purposively using network and snowball sampling. A framework approach was applied for the thematic data analysis. Findings were reported narratively.

Twenty-one experts from eleven different countries were interviewed. COI studies were found to be relevant to estimate the overall burden of a disease, to draw attention to disease areas, to understand different cost components, to explain cost variability, to inform decision making, and to provide input for full economic evaluations. Experts reported a lack of a standardized critical appraisal tool for COI studies. Their experience related predominantly to guidelines and checklists designed for full economic evaluations to review and assess COI studies. The following themes emerged when discussing the checklist: (i) the need for a critical appraisal tool, (ii) format and practicality, (iii) assessing the questions, (iv) addressing subjectivity, and (v) guidance requirements.

The interviews provided relevant input for the development of a checklist for COI studies that could be used as a minimum standard and for international application. The interviews confirmed the important need for a checklist for the critical appraisal of COI studies.

To develop a consensus-based checklist that can be used as a minimum standard to appraise the comprehensiveness, transparency and consistency of cost-of-illness (COI) studies. This is important when, for instance, reviewing and assessing COI studies as part of a systematic review or when building an economic model.

The development process of the consensus-based checklist involved six steps: (i) a scoping review, (ii) an assessment and comparison of the different checklists and their questions, (iii) the development of a (preliminary) checklist, (iv) expert interviews, (v) the finalization of the checklist, and (vi) the development of guidance statements explaining each question.

The result was a consensus-based checklist for the critical appraisal of COI studies, comprising seventeen main questions (and some additional subquestions) across three domains: (i) study characteristics; (ii) methodology and cost analysis; and (iii) results and reporting. Guidance statements were developed describing the purpose and meaning behind each question and listing examples of best practice. The following answer categories were suggested to be applied when answering the questions in the checklist: Yes, Partially, No, Not Applicable, or Unclear.

The consensus-based checklist for COI studies is a first step toward standardizing the critical appraisal of COI studies and is one that could be considered a minimum standard. The checklist can help to improve comprehensiveness, transparency and consistency in COI studies, to address heterogeneity, and to enable better comparability of methodological approaches across international studies.

To assess the clinical effectiveness of fluticasone furoate nasal spray (FFNS) versus placebo on nasal symptoms and safety in children with perennial allergic rhinitis (AR).

A comprehensive review was conducted with data obtained from Medline and Embase databases up to April 2023. The population of interest was patients aged 2–12 years with perennial AR. The selection was limited to randomized controlled trials (RCTs), comparing FFNS with placebo. Outcomes of interest included the reflective total nasal symptoms scores (rTNSS) and safety. To assess the minimal clinically important difference for rTNSS, the Cohen’s guideline was used. If the pooled standardized mean difference (SMD) and the lower limit of the 95 percent confidence interval (CI) exceeded the threshold of −0.20, effects were considered clinically significant.

Three RCTs (959 pediatric patients) were selected. One study evaluated the short-term use of FFNS, another evaluated the long-term use of FFNS, and another evaluated both the short-term and long-term use of FFNS. FFNS produced a statistically significant reduction over placebo in rTNSS (SMD −0.18; 95 percent CI −0.35 to −0.01, p = 0.03) in long-term treatment studies, but not in short-term treatment studies. However, since the mean reduction did not reach the minimum clinically important difference (SMD −0.20), these results were considered clinically not relevant. Safety outcomes with FFNS were similar to placebo.

The currently available evidence suggests that FFNS, 110 μg once daily, compared to placebo, does not produce a meaningful clinical effect on nasal symptom in children with perennial AR.

Integrating social values into health technology assessment processes is an important component of proper healthcare priority setting. This study aims to identify social values related to healthcare priority setting in Iran.

A scoping review was conducted on original studies that investigating social values in the healthcare system in Iran. The databases of PubMed, EMBASE, and EBSCO were searched with no restrictions on time and language. The reported criteria were clustered using Sham’s framework of social value analysis in health policy.

Twenty-one studies published between 2008 and 2022 met the inclusion criteria. Fourteen of the included studies followed a quantitative approach with different methods to identify criteria, and the remaining seven studies used a qualitative approach. A total of fifty-five criteria were extracted and clustered into necessity, quality, sustainability, and process categories. Only six studies found criteria that were related to processes. Only three studies used public opinions as a source of value identification and eleven studies investigated the weight of criteria. None of the included studies explored the interdependency of the criteria.

Evidence suggests that several criteria other than cost per health unit also need to be considered in healthcare priority setting. Previous studies have paid little attention to the social values that underlie priority setting and policy-making processes. To reach consensus on social values related to healthcare priority setting, future researches need to involve broader stakeholders’ perspectives as a valuable source of social values in a fair process.

To summarize the key methodological challenges identified by health technology assessment (HTA) agencies assessing gene therapy (GT) and consideration of broad elements of value.

Economic evaluations (EEs) of voretigene neparvovec (VN) in RPE65-mediated inherited retinal disease (IRD) published in English were selected. HTA evaluations from Australia, Canada, Ireland, Scotland, England, and the United States were reviewed. An existing methodological framework was used to identify the challenges and considerations.

Eight unique EEs were identified of which six were evaluated by HTA agencies. Incremental cost-effectiveness ratios ranged from $68,951 to $643,813 per quality-adjusted life-years (QALY) gained (healthcare perspective) and dominant to $480,130 per QALY gained (societal perspective). The key challenges were the lack of validated surrogate outcome, utility values and indirect costs from IRD patients, and limited evidence of the long-term treatment effect. Two HTA agencies reviewed a range of novel broader elements of value and whether they were associated with VN while other agencies discussed some elements of broader value. Caregiver disutility was included in some, but not all, evaluations.

The methodological challenges were consistent with innovative interventions for rare diseases and managed using standard methods. Broader value was important to decision-makers but inconsistently applied across agencies. Possible reasons are limitations in the evidence available of the broader benefits that VN offers and how to incorporate these within an EE. A need exists for greater guidance and consistency across jurisdictions regarding the consideration of broader value that considers latest best practice.

Health technology assessments (HTAs) of robotic assisted surgery (RAS) face several challenges in assessing the value of robotic surgical platforms. As a result of using different assessment methods, previous HTAs have reached different conclusions when evaluating RAS. While the number of available systems and surgical procedures is rapidly growing, existing frameworks for assessing MedTech provide a starting point, but specific considerations are needed for HTAs of RAS to ensure consistent results. This work aimed to discuss different approaches and produce guidance on evaluating RAS.

A consensus conference research methodology was adopted. A panel of 14 experts was assembled with international experience and representing relevant stakeholders: clinicians, health economists, HTA practitioners, policy makers, and industry. A review of previous HTAs was performed and seven key themes were extracted from the literature for consideration. Over five meetings, the panel discussed the key themes and formulated consensus statements.

A total of ninety-eight previous HTAs were identified from twenty-five total countries. The seven key themes were evidence inclusion and exclusion, patient- and clinician-reported outcomes, the learning curve, allocation of costs, appropriate time horizons, economic analysis methods, and robotic ecosystem/wider benefits.

Robotic surgical platforms are tools, not therapies. Their value varies according to context and should be considered across therapeutic areas and stakeholders. The principles set out in this paper should help HTA bodies at all levels to evaluate RAS. This work may serve as a case study for rapidly developing areas in MedTech that require particular consideration for HTAs.

Uncertainty is a fundamental component of decision making regarding access to and pricing and reimbursement of drugs. The context-specific interpretation and mitigation of uncertainty remain major challenges for decision makers. Following the 2021 HTAi Global Policy Forum, a cross-sectoral, interdisciplinary HTAi-DIA Working Group (WG) was initiated to develop guidance to support stakeholder deliberation on the systematic identification and mitigation of uncertainties in the regulatory-HTA interface.

Six online discussions among WG members (Dec 2021–Sep 2022) who examined the output of a scoping review, two literature-based case studies and a survey; application of the initial guidance to a real-world case study; and two international conference panel discussions.

The WG identified key concepts, clustered into twelve building blocks that were collectively perceived to define uncertainty: “unavailable,” “inaccurate,” “conflicting,” “not understandable,” “random variation,” “information,” “prediction,” “impact,” “risk,” “relevance,” “context,” and “judgment.” These were converted into a checklist to explain and define whether any issue constitutes a decision-relevant uncertainty. A taxonomy of domains in which uncertainty may exist within the regulatory-HTA interface was developed to facilitate categorization. The real-world case study was used to demonstrate how the guidance may facilitate deliberation between stakeholders and where additional guidance development may be needed.

The systematic approach taken for the identification of uncertainties in this guidance has the potential to facilitate understanding of uncertainty and its management across different stakeholders involved in drug development and evaluation. This can improve consistency and transparency throughout decision processes. To further support uncertainty management, linkage to suitable mitigation strategies is necessary.