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.

It is estimated that osteoporosis affects over 200 million people globally. Postmenopausal women (PMW) have an increased risk of developing osteoporosis due to low estrogen levels. This study assessed the safety and effectiveness of denosumab (Prolia®) relative to placebo, selective estrogen receptor modulators (SERMs) (bazedoxifene and raloxifene), and bisphosphonates (alendronate, ibandronate, risedronate, and zoledronate) for the treatment of osteoporosis in PMW.

Systematic searches were conducted in three biomedical databases (PubMed, the Cochrane Library, and Embase) to identify randomized controlled trials (RCTs) of PMW with osteoporosis allocated to denosumab, placebo, bisphosphonates, or SERMs. The Cochrane Risk of Bias 2.0 tool was used to critically appraise included RCTs. Pairwise and Bayesian network meta-analyses were performed on the following predetermined outcomes: fractures (vertebral and nonvertebral); adverse events (AEs); mortality; serious AEs (SAEs); withdrawals due to AEs; bone mineral density (BMD); and AEs caused by denosumab discontinuation.

The analyses included 12 RCTs (22 publications, 25,879 participants). Denosumab, ibandronate, alendronate, zoledronate, and risedronate produced a statistically significant improvement in total hip (TH) and lumbar-spine (LS) BMD, compared with placebo. Similarly, ibandronate, risedronate, and alendronate showed a statistically significant improvement in femoral neck (FN) BMD. Risedronate produced a statistically significant decrease in nonvertebral fractures (risk ratio 0.20, 95% confidence interval: 0.00, 0.97) relative to placebo. However, there were no significant differences between any of the interventions for rates of vertebral fractures, AEs, SAEs, withdrawals due to AEs, or mortality, compared with placebo.

None of the included trials reported evidence on AEs caused by denosumab discontinuation.

Denosumab was associated with significant improvements in both LS and TH BMD relative to placebo. Similarly, compared with placebo, denosumab was not associated with significant changes in nonvertebral or vertebral fractures. Denosumab was not associated with significant changes in safety outcomes relative to placebo. Given that some of the analyses suffered from statistical imprecision, these findings should be interpreted with caution. Regarding policy, continued funding of denosumab needs to be reviewed.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects quality of life and sometimes requires the use of multiple drugs. Therefore, it is relevant to address the experiences of patients, family members, and caregivers in relation to out-of-hospital SLE drug treatment. This paper presents the results of a pilot project of a Qualitative Evidence Synthesis (QES) conducted by the National Committee for Health Technology Incorporation (Conitec) in the Brazilian public health system.

For this thematic synthesis, a structured search was conducted in the MEDLINE, CINAHL, and LILACS databases. Seventeen articles were included, and their quality was evaluated using the Critical Appraisal Skills Program criteria. Article content, which was extracted into a spreadsheet adapted from JBI SUMARI, underwent thematic content analysis. Confidence in the findings was evaluated using the GRADE Confidence in the Evidence from Reviews of Qualitative Research tool.

Fifteen findings related to three central themes: self-image and appearance; SLE as a chronic disease (disease oscillation, recurrence of symptoms, fear of organ damage, expectation of cure or modification of the disease course, and frequency of medical appointments); and experience with drug therapy (belief in the need for drugs, skepticism, chronicity of treatment, financial difficulty, adverse effects as obstacles to adherence and a source of suffering, efficacy/effectiveness, large quantity and frequency of drugs, and multiple therapeutic attempts).

The findings suggest that patients, family members, and caregivers have an ambivalent relationship with drug treatment. Even though they believe in the effectiveness of the drugs, they also distrust the need to keep using them, especially when SLE is controlled. The improvement of cosmetic manifestations and adverse effects also seem to be important outcomes. Furthermore, the high occurrence of adverse effects and the daily use of many drugs can make treatment adherence harder. In any case, there is an expectation of cure or more significant impact on the course of the disease through pharmacotherapy.

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.

While the impact of health technology assessments (HTAs) is often not evaluated, some HTA bodies measure the impact of patient involvement in their processes. Evaluating how patient involvement is perceived by all stakeholders may help to improve practices and avoid activities that unduly burden patient and HTA communities. Frameworks and tools have been designed to analyze the impact of patient engagement along the healthcare development lifecycle. Reporting on the impact of patient involvement in HTA-specific activities, however, continues to be infrequent, unstandardized, and not comprehensive.

Having a common framework to characterize and report on the impact of patient involvement may enable this practice to be optimized and harmonized across HTA contexts.

The Patient and Citizen Involvement Interest Group (PCIG) within Health Technology Assessment International set out to contextualize this impact and support reporting. A questionnaire was developed, piloted, and rolled out to collect multistakeholder personal perceptions of the impact of patient involvement in individual HTAs. Questions included: “What difference did you feel patient involvement made in the HTA activity?” and “What would have been missed without patient involvement?”. From January 2019 to September 2021, 24 responses (including one joint submission) were collected through the PCIG’s network from HTA bodies (11), patient representatives (12), and industry representatives (2) from North America (5), South America (3), Europe (13), and Australia (3).

Common themes were extracted from these experiences to characterize the impact of patient participation in HTA processes. Based on these commonalities, a harmonized framework consisting of three “domains” is proposed: impact on the decision-making process; impact on patient stakeholders; and impact on the HTA body. The framework includes a set of items under each domain to support reporting.

By having common language and measures, the HTA community can harmonize processes across jurisdictions to evaluate and communicate the value of patient involvement in HTA. Improving consistent reporting may facilitate more efficient process improvement for meaningful integration of patient stakeholders into HTA decision-making.

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.

Australian health technology assessment (HTA) committees and processes at the national level have needed to consider an increasing focus on patient involvement and interactions within their scope. As various approaches have been explored, the visibility and impacts of patient involvement and consumer representation has evolved markedly over the most recent five years.

Program activities were developed from review of contemporary HTA models of practice across various HTA sectors internationally alongside input from individual patients and patient groups. Practical application of program pilots was influenced by specific requirements of the Office of HTA, the coordination of HTA Committee procedures and timelines, and involvement of HTA Committee consumer members.

The development of capacity building programs for HTA consumer committee members, the growth of external activity and communications targeting patient groups and networks, and the establishment of an expert position to develop the HTA Consumer Evidence and Engagement Unit within the Department’s Office of HTA, are all examples of the work delivered in this period to better integrate patient evidence and inputs into HTA processes and decision-making. Activities over the next period will seek to establish formal frameworks for meaningful involvement that can demonstrate these contributions to evaluations and decision-making.

Various examples of patient involvement and participation in processes have evolved over time. The scope and impacts of these experiences have illustrated important participatory demands and resourcing needs, as well potential benefits for deliberations. The Australian Government and Departmental frameworks for HTA currently seek to enhance the development of patient evidence inputs and participation. These developments will be informed by the Australian context and comprehensive consultation with Australian patient groups and their networks. Strategies for improvements are anticipated to be relevant across all HTA processes and Committees within HTA areas.

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.

Fabry disease is a rare, inherited X-linked lysosomal storage disease characterized by a wide spectrum of heterogeneously progressive clinical phenotypes, and which results in progressive kidney disease, cardiomyopathy, cerebrovascular disease, and reduced life expectancy. Disease-specific therapy aims to improve symptoms, stabilize current disease and delay progression. In Australia treatment access requires that patients meet pre-specified criteria, which have been in place for more than 15 years. Patient questions prompted the patient organization, Fabry Australia, to investigate why these criteria had remained unchanged despite significant progress in the understanding and management of Fabry disease.

A panel comprising two members of Fabry Australia and its Medical Advisory Committee conducted a review of the literature. The aim of this was to inform the clinical quality of the Australian treatment access criteria with reference to international guidelines and contemporary data. The findings from the literature were applied to develop consensus recommendations for classification and Fabry-specific treatment initiation criteria in diagnosed patients.

Evidence supports earlier treatment with reduced barriers to access in some circumstances. Australian access criteria are misaligned with this. They do not distinguish between classical and non-classical Fabry phenotypes, neglect the impact of quality of life and gastrointestinal symptoms, and impose symptom-severity related criteria, which may lead to unnecessary treatment initiation delay. An updated framework is presented. It differentiates phenotypes, facilitates more timely access to Fabry-specific treatment for classical males, and supports relevant organ involvement criteria in classical females and patients with non-classical disease.

A well-performing health technology assessment system facilitates patient access to cost-effective treatments that improve health outcomes. Timely treatment initiation is important to avoid irreversible organ damage in Fabry patients. Patients’ questions about out-dated access criteria has prompted research and uncovered barriers that are no longer clinically valid. The perspectives of the patient as a stakeholder in their disease management should not be overlooked when assessing the value of health technologies in the rare disease setting.

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.

Umbrella digital health term (DHT) (digital health, eHealth, mHealth, telehealth, and telemedicine) definitions contain insufficient information about patient value for health economics and outcomes research and health technology assessment (HTA) purposes. Qualitative content analysis of secondary DHT (e.g., telesurgery and teleradiology) definitions was performed by the ISPOR Digital Health Special Interest Group to determine if they were more useful for health economics and outcomes research purposes.

Secondary DHT definitions were extracted from a previous scoping review and consolidated by reviewer pairs using uniform rules. Definitions were analyzed for explicit (directly stated) or implicit (inferred) information on 24 categories: Patient, Intervention, Comparator, Outcome, Timing, Setting (PICOTS); the Shannon-Weaver communication model (SWE) (sender, message, encoder, channel, decoder, and receiver, extended with mode of information exchange); the quality domains of Agency for Healthcare Research and Quality (AHRQ) (safe, effective, patient-centered, timely, efficient, and equitable); information related to applied technology or geographic scope; and the World Health Organization (WHO) classification of digital health interventions v1.0 (digital health interventions category, health system challenges, and system categories).

Across 107 unique definitions of 73 secondary DHTs, the number of explicitly or implicitly addressed categories across the frameworks ranged from zero to 15, with references to elements of PICOTS (79.4%), SWE (90.7%), AHRQ (30.8%), applied technology (52.3%), geographic scope (0%), and WHO frameworks (86.9%). PICOTS information was found for Patients in 35 percent of definitions, Intervention in 59 percent, Comparator in 20 percent, and Outcomes in 18 percent.

Secondary DHT definitions do not adequately specify PICOTS or other characteristics of interest for HTA. An online Delphi survey has been launched among a wider group of ISPOR members to identify the minimum information set to define patient facing DHTs for evidence summaries and value assessments. The results of this research should be shared for discussion with other digital health stakeholder groups.

Allocating government resources for drug treatments continues to be a challenge in health care, particularly given the increasing number of high-cost personalized drug treatments, finite resources, and aging population. Since taxpayers fund government health budgets, it is important to understand how they think funding should be distributed, considering attributes such as cost of drug treatments, risk of dying, commonality of medical conditions, and quality of life changes with drug treatments. The aim of this study was to understand what attributes of a medical condition and treatment determine a community’s willingness to fund new drug treatments. Two decision-making contexts were explored: the allocation of funds from a health budget and a willingness-to-pay (WTP) perspective.

A representative sample of 500 Australian adults completed an online survey. The survey comprised two discrete choice experiments (DCEs) with different framing: an allocation of government funds and a WTP for drug treatments. The government allocation DCE allowed a choice between two hypothetical alternatives, each describing the medical condition and the drug treatment, while the WTP for funding showed one hypothetical alternative with an option to not fund the drug treatment. Seven DCE attributes, informed by a literature review, were displayed in each choice set relating to the medical condition (risk of dying, prevalence, and ages affected) and to the drug treatment (change in quality of life, additional life-years, availability of other drug treatments, and cost to the government and the taxpayer).

The resulting DCE model will establish the funding prioritization choices made by the general community. We expect changes in quality of life and risk of dying to be very important attributes. Of key interest for this study is how the difference in the decision-making context impacts preferences. We expect taxpayers to employ a stricter rule set in funding decisions when paying out of pocket (WTP exercise).

The findings from this research have implications for decision makers when aligning funding decisions with community preferences and values.

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.

In recent years, most countries have struggled to meet the annual demand for increases in healthcare resources. This scenario poses a significant challenge for those who pay for or manage healthcare services, namely the clinicians and hospital managers Thus, value-based implementation for resource allocation may include disinvestment initiatives to maximize benefits to patients and the population. The purpose of this study was to explore the feasibility of incorporating a systematic and explicit value assessment in hospital-based decision-making for the prioritization of resource allocation.

An evidence-informed stakeholder engagement workshop was held with approximately 50 hospital directors and utilized a scenario analysis of making decisions for hospital procurement. The key question discussed was what should be considered when making decisions about resource allocation and disinvestment in health services at the hospital level. The participants were divided into five groups with a mix of multilevel institutional categories. Each group was given a similar resource allocation scenario, a wish list, and a shift list. The participants were involved in a facilitated discussion on the process, criteria for prioritization, and the justification of their final selections. Subsequently, a deliberative discussion was held at the end of the workshop to explore the feasibility of this prioritization method.

Prioritization criteria that were identified and unanimously agreed upon included effectiveness, safety, burden of disease, suitability of services, human resources and facilities, and economic considerations. The deliberative discussion also highlighted the impact of the disinvestment of services, managing the expectation of patients and clinicians, and monitoring and audit mechanisms.

The value of disinvestment should not compromise access to services and quality of care. There is a huge potential for implementing a systematic and explicit value assessment in hospital-based decision-making for prioritization of resource allocation. Further refinement of the process and mitigation of challenges will enable its use.

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.

National health insurance (NHI) Taiwan has provided additional markups on dental service fees for people with specific disabilities, and the expenditure has increased significantly from TWD473 million (USD15 million) in 2016 to TWD722 million (USD24 million) in 2022. The purpose of this study was to determine oral health risk and to develop a risk assessment model for capitation outpatient dental payments in children with Autism.

Based on the literature and expert opinion, we developed a level of oral health risk model from the claim records of 2019. The model uses oral outpatient claim data to analyze: (i) the degree of caries disease; (ii) the level of dental fear or cooperation; and (iii) the level of tooth structure. Each factor was given a score from zero to four and a total score was calculated. Low-, medium-, and high-risk groups were formed based on the total points. The oral health risk capitation models are estimated by ordinary least squares using an individual’s annual outpatient dental expenditure in 2019 as the dependent variable. For subgroups based on age group and level of disability, expenditures predicted by the models are compared with actual outpatient dental expenditures. Predictive R-squared and predictive ratios were used to evaluate the model’s predictability.

The demographic variables, level of oral health risk, preventive dental care, and the type of dental health care predicted 30 percent of subsequent outpatient dental expenditure in children with autism. For subgroups (age group and disability level) of high-risk patients, the model substantially overpredicted the expenditure, whereas underprediction occurred in the low-risk group.

The risk-adjusted model based on principal oral health was more accurate in predicting an individual’s future expenditure than the relevant study in Taiwan. The finding provides insight into the important risk factor in the outpatient dental expenditure of children with autism and the fund planning of dental services for people with specific disabilities.

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.

New methodologies such as machine learning are becoming widely available and are increasingly used. However, more guidance on their role in the context of economic evaluations would be beneficial.

We developed a machine learning model to predict recurrent depressive episodes and incorporated the model outcomes in a health economic model to assess the cost effectiveness of offering targeted prevention of recurrent depression. We considered the impact on cost effectiveness (defined as cost per quality-adjusted life-year) for machine learning models with different thresholds for classifying a patient as being at risk, resulting in different precision-recall pairs.

Targeted prevention of recurrent depression could enhance the cost effectiveness of depression treatment by preventing a small number of recurrent depressive episodes in patients where the estimated risk of recurrence is relatively high. More depressive episodes could be prevented with the trade-off of less cost effectiveness for the healthcare system.

Health economic modeling approaches can be augmented with machine learning methods, which broadens the areas in which evidence can be generated for policy makers to base their budget allocation. The precision of such predictive machine learning models must be high enough to be able to improve a care-as-usual healthcare system. Machine learning models generally let you set the level of precision acquired, at the cost of a possibly low recall, thereby limiting the impact on the healthcare system as a whole. More and better data for training these machine learning models will allow developed models to better distinguish patients who will and won’t develop a recurrent depressive episode, and for higher recall given a desired precision threshold. This will translate into a more substantial improvement in the treatment of depressive disorders in the healthcare system.