Costs for pharmaceutical products are increasing. Pharmaceutical companies claim that high research and development (R&D) costs are the reason for the steep price increase of new products. However, there exists little data to support such claims; there is a lack of transparency in R&D cost reporting. This research intends to analyze and to disaggregate the costs of pharmaceutical R&D.

Studies on the costs of introducing new medications to the market can differ substantially in their methodology, their origin of data, and their results. A scoping review was conducted on costs of R&D for pharmaceutical products using Embase, PubMed, and EconLit, using a combination of the terms “drug research and development” and “costs” or “drug research and development” and “expenditure.” Additionally, semi structured interviews with 16 experts from non-governmental organizations (NGOs), pharmaceutical companies, academic researchers, and not-for-profit pharmaceutical companies were conducted to identify the main driving factors for rising costs of new drugs.

Out of 24 studies that analyzed mixed therapeutic fields, the five highest cost estimates had affiliations with industry or received funding from pharmaceutical companies. Non-affiliated researchers are unable to reproduce studies that use confidential data and therefore cannot check the validity of the results. Additionally, different definitions for R&D make analyzing costs challenging. The interviewees emphasized that driving factors influencing costs for pharmaceutical R&D are therapeutic indication, drug complexity, number of patients in clinical trials, length of the development process, and attrition rates.

Due to the diverse nature of drug development and the confidential information held by pharmaceutical companies, it is a challenge to provide an exact assessment of the average costs of pharmaceutical R&D. Transparency policies with well-defined definitions for R&D are necessary to level the information asymmetries between the private and the public at price negotiations.

The Regulation (EU) 2021/2282 on health technology assessment (HTAR) takes effect in January 2025 and aims to improve and accelerate patients’ access to new health technologies. We examine HTA timelines and outcomes for new active substances (NASs) commonly appraised in all of France, Germany, Poland, and Sweden from 2014 to 2022, providing insights into the European landscape before HTAR.

Public data was extracted from the HTA reports from the corresponding health authorities from France (HAS), Germany (IQWiG), Poland (AOTMiT), and Sweden (TLV) published between 1 January 2014 to 31 December 2022. NASs appraised by HTA in the four jurisdictions were referred to as common compounds. Time to recommendation was calculated as European Medicines Agency approval to HTA recommendation in the corresponding country. Differences in time parameters were assessed using the Kruskal–Wallis test. HTA recommendations were categorized as positive, positive with restrictions, and negative.

A total of 97 common compounds (75% chemical entities and 25% biotechnology products) were identified (388 HTA appraisals). Notably, 47/97 (48%) NASs were associated with anticancer drugs (ATC-code=L). The median (interquartile range) time to recommendation differed by jurisdiction: 128 (113, 169) days in Germany; 203 (151, 308) days in Sweden; France, 209 (162, 294) days; Poland, 479 (330, 738) days (p-value <2.2e-16). In addition, 62/97 (63.9%) products received their initial HTA recommendation in Germany, followed by 25/97 (25.8%) products in Sweden, and 10/97 (10.3%) in France. Only 7/97 (7%) of products exhibited unanimous HTA outcomes across jurisdictions.

Discrepancies in the time to HTA recommendation were identified across four prominent European jurisdictions, and consensus in HTA outcomes was notably limited across countries, underscoring the intricate landscape preceding the enforcement of the HTAR. The future implementation of HTAR holds the potential to address these disparities, fostering greater harmonization in HTA processes and outcomes across the European healthcare landscape.

Defining the population, intervention, comparator, outcomes (PICO) criteria is an essential step prior to performing a health technology assessment (HTA), but variations exist in how this step is performed.

A scoping review was performed to compare the processes and guidance provided for developing the PICO criteria for the assessment of new medicines across Australia, the UK, Canada, the US, European Union (as a single jurisdiction), Germany, France, the Netherlands, South Korea, and Taiwan. The websites of HTA agencies in these jurisdictions were searched for methodological guidance, and PubMed, Embase, and the HTA database were also searched for published literature on the topic of the process or methods for developing the PICO criteria.

Two main approaches are used for developing the PICO criteria. In the UK, US, and European Union, a separate scoping process is used; in the remaining countries, the pharmaceutical manufacturer defines the PICO criteria as part of developing their dossier for submission. Guidance on PICO elements were similar in content but highly varied in the degree of guidance provided. The largest differences were in whether outcomes for people beyond the treated individual were recommended to be assessed.

A separate scoping phase allows stakeholder input into the criteria, which is important with the shift to incorporating more patient input into each phase of HTA. It can come at the cost of timeliness, so requires manufacturers to engage with the HTA systems earlier in the process.

Several countries established health technology assessment (HTA) processes to support decision-making. Considering the high volume of submissions processed by HTA agencies, approaches to determine factors associated with the approval would be beneficial. This study aimed to predict the final recommendation of the National Committee for Health Technology Incorporation (Conitec) using a natural language processing (NLP) algorithm for text extraction.

Conitec’s 2012 to 2022 reports (n=389) were split into 75 percent training and 25 percent testing data. Tokenization enabled NLP models: Least Absolute Shrinkage and Selection Operator (LASSO), logistic regression, support vector machine (SVM), random forest, neural network, and Extreme Gradient Boosting (XGBOOST). Evaluation criteria included accuracy, area under the receiver operating characteristic curve (ROC AUC) score, precision, and recall. Cluster analysis with k-modes identified two clusters (group 0 = approved, group 1 = rejected).

The neural network model demonstrated the best accuracy metrics with a precision of 0.815, accuracy of 0.769, ROC AUC of 0.871, and a recall of 0.746. Some tokenization identified that linguistic markers could contribute to the prediction of incorporation decision by the Brazilian HTA Committee, such as international HTA agencies’ experience and the government as the main requester. Cluster and XGBOOST analysis identified similar results with approved technologies with a predominance of drugs assessment, mainly requested by the government, and not approved mostly assessing drugs, the industry as the main requester.

The NLP model could identify predictors for the final decision process on the incorporation of health technologies in Brazil’s Unified Health System, opening paths for future work using HTA reports coming from other agencies. This model could potentially improve the throughput of HTA systems by supporting experts with prediction/factors/criteria for approval or nonapproval as an earlier step.

In recent years, large language models (LLMs) have emerged as powerful tools in natural language processing, presenting diverse opportunities across various sectors. In this context, the Agency for Health Quality and Assessment of Catalonia (AQuAS) is actively investigating how LLMs can enhance the development of health technology assessment (HTA) reports.

To assess the potential of LLMs in the development of HTA reports, our initial step involved a comprehensive review of technical literature to understand the functionalities of existing LLM tools. This effort was followed by a systematic identification of specific HTA report development tasks that these models could potentially facilitate. We then rigorously evaluated the performance of these tools in executing the delineated tasks, with a focus on meticulously recording the applied prompts and areas of high and low effectiveness, alongside any encountered errors and identified risks.

Among a range of commercial tools, ChatGPT and Microsoft Copilot were selected for exploration due to their accessibility, ease of use, and versatility. Both tools demonstrated acceptable performance in certain tasks (e.g., data extraction), while their efficacy was notably lower in others (e.g., information search). Additionally, a range of risks requiring mitigation were identified (e.g., hallucination or authority bias). Consequently, we drafted a proposal for an internal guide with directives for the technical staff of the HTA unit on utilizing these two tools. Additionally, we constituted a working group.

LLMs have emerged as promising tools in the field of HTA. Over the past months, AQuAS has been investigating the potential of these models to improve the HTA report development process, targeting enhanced efficiency and improved quality. This exploration has led to the identification of numerous opportunities and associated risks within this innovative application.

The European Digital Health Technology Assessment (EDiHTA), an EU-funded project, aims to deliver the first European digital HTA framework co-created by all relevant stakeholders, validated and ready to use. It responds to the need to harmonize tools, methods, guidelines, and frameworks that are already adopted or under development. All types of digital health technologies (DHTs) and Technology Readiness Levels (TRLs) are covered.

The EDiHTA project adopts a multistakeholder, multidomain, and modular approach to reach a consensus on a common HTA framework for DHTs (e.g., mApp, telemedicine, artificial intelligence). The currently available HTA frameworks refer to different DHTs (e.g., MAST, DiGA, MAS-AI), include different HTA domains, respond to the needs of different stakeholders, and are applicable in specific local and national contexts. In the majority of cases, they are applicable only in advance TRL. In a few cases, they are already adopted in regulatory/HTA processes. The lack of coordination and harmonization has significant implications for all stakeholders, manufacturers and patients included.

The EDiHTA project adopts a holistic approach involving all relevant stakeholders for consensus building at national and European levels. Cross-border collaboration among stakeholders will be reinforced by the definition of a common taxonomy based on consensus building, and the development and validation of common methods and the HTA framework. Evidence requirements will be defined and made more transparent to increase support for health technology manufacturers. In addition, the harmonization effort, together with the development of a digital platform for the HTA framework, will allow faster and safer access to DHTs by patients/citizens.

The goal of the EDiHTA project is to provide the first European digital HTA framework for DHTs that will be adopted by all relevant stakeholders along the lifecycle of digital technologies to promote sustainable health systems. A consortium comprising 15 partners from eight countries, including all relevant stakeholders, works to reach these goals within the next four years.

Use of multiparametric magnetic resonance imaging (mpMRI) in the prostate cancer (PCa) diagnostic pathway could reduce prostate biopsy (Bx) in Bx-naive patients. The objective was to assess the feasibility of implementing a new PCa diagnostic pathway with the addition of mpMRI in a real care environment.

Following an HTA report published in 2019 by our team, a committee involving stakeholders (e.g., urologists, radiologists, hospital managers) was created to review the PCa diagnostic pathway including mpMRI in Bx-naive patients and both systematic and targeted 3DTRUS-MRI fusion Bx when Bx was recommended. Data in the new PCa diagnostic pathway were collected between September 2021 and June 2022. The comparison group is a cohort of 629 men who underwent an initial systematic transrectal ultrasound Bx in 2017 when prostate mpMRI was not available. Clinically significant PCa (csPCa) was defined as Grade Group ≥2.

In 2021 and 2022, 1,336 Bx-naive patients were referred to a urologist. Recommendations were: 703 (53%) for follow-up in six to 12 months, 254 (19%) directly to systematic Bx, and 379 (28%) to mpMRI. Overall, csPCa was diagnosed in 246/427 (58%) patients referred to mpMRI or Bx in the 2021 to 2022 cohort compared to 274/629 (44%) patients in the 2017 cohort (p<0.05). The new diagnostic pathway prevented 33 percent of patients from having Bx. Shorter delays between initial consultation with urologists and transmission of Bx results were observed for patients referred directly for prostate Bx compared to mpMRI before Bx (mean: 2.8 vs 9.1 months).

Experimentation in a real care setting has highlighted the added value of the early involvement of urologists in the diagnostic pathway of prostate cancer for the triage of patients. Integration of mpMRI was associated with a lower number of patients referred for prostate Bx and a higher csPCa detection rate.

Technical aids (TAs) are health devices (e.g., hearing aids, prostheses, wheelchairs) used to restore a body function or compensate for disability. In France, TAs are assessed based on clinical data, as are any medical devices (MDs). Considering that TAs are special MDs (no curative action), specific assessment methods might be proposed. The methods used in Europe were explored.

To learn about TA evaluation practices in Europe, the French National Authority for Health (HAS) sent a survey to nine identified European health technology assessment (HTA) agencies. The questionnaire was specific to TAs, and the questions asked were about: (i) the reimbursement of TAs (reimbursed or not, at national or local level), (ii) the HTA process (HTA process or not, HTA process description), and (iii) the methods used (any specific methods for assessing TAs other than HTA methods to assess “classic” MDs).

All the European HTA agencies contacted provided a response. All these countries have a healthcare system that allows TAs to be reimbursed. In Austria, Ireland, Italy, the Netherlands, Norway, Portugal, Spain, and the United Kingdom, TAs must be CE-marked and comply with technical standards to be reimbursed; no clinical data are required. However, the National Institute for Health and Care Excellence provides recommendations for certain TA categories. In Germany, the CE-marking and the respect of technical standards are mandatory, and certain TAs need to show a medical benefit (e.g., orthoses); nevertheless, there are no specific methods to assess TAs.

Overall, the feedback obtained does not reveal any specific evaluation method applied to TA assessment in the various European countries analyzed. France stands out from these European countries regarding the assessment of TAs because of its one-stop-shop system for health technology developers and the HAS requirements for technical and clinical data.

Diabetes is a key risk factor for cardiovascular disease (CVD), with a two-to-four-times higher risk than that in non-diabetes. The health burden associated with CVD imposes a major economic concern on healthcare systems and on society. We sought to estimate the future burden of CVD in terms of health and economic outcomes in type 2 diabetes (T2D) from 2022 to 2031.

From Australian public healthcare and societal perspectives over the next decade, two dynamic models with annual cycles were designed to predict myocardial infarction (MI) and stroke in patients aged 40 to 90 years. First events at risk of CVD people were estimated using the 2013 pooled cohort equation, while recurrent events in existing CVD were acquired from the global Reduction of Atherothrombosis for Continued Health registry. Costs and utilities were obtained using public sources. Outcomes were fatal and non-fatal MI and stroke, years of life lived, quality-adjusted life years (QALYs), total direct and indirect costs. An annual discount rate of 5 percent was used.

Over the next 10 years, the model projected a total of 83,618 non-fatal MIs (95% confidence interval [CI]: 83,170, 84,053) and 58,774 non-fatal strokes (95% CI: 58,458, 59,013). In terms of health outcomes, total years of life lived and QALYs were 9,549,487 (95% CI: 9,416,423, 9,654,043) and 6,632,897 (95% CI: 5,065,606, 7,591,679), respectively. In terms of economic outcomes, total direct and indirect were AUD9.59 billion (USD6.38 billion) (95% CI: AUD1.90 billion [USD1.26 billion], AUD30.45 billion [USD20.26 billion]) and AUD9.07 billion (USD6.03 billion) (95% CI: AUD663.53 million [USD441.61 million], AUD33.19 billion [USD21.96 billion]), respectively. The chronic costs of CVD contributed most of the total direct cost, while morbidity contributed most of the total indirect costs.

Our study shows that from 2022 to 2031, CVD as a complication from T2D will cause a significant impact on the Australian healthcare system and society. These estimates can be used to explore different strategies to optimize the control of risk factors for the prevention and management of CVD in T2D in Australia.

Surrogate endpoints are increasingly being used in the pivotal trials of cancer drugs to underpin (conditional) regulatory approval. We examined the relationship between the use of surrogate measures in pivotal trials underpinning cancer drug approvals by the European Medicines Agency (EMA) between 2017 and 2022 and health technology assessment (HTA) recommendations made by the National Centre for Pharmacoeconomics in Ireland (NCPE).

A previously published methodology was used to identify cancer drug indications that received (conditional) marketing authorization between 2017 and 2022, inclusive. EMA-approved cancer drugs were categorized using the following benefit categories, based on pivotal trial endpoints: overall survival (OS), progression-free survival (PFS), disease response (DR), and single-arm trials (SATs). The NCPE website was searched to identify indications that had undergone, at least, a rapid review (RR) assessment. The NCPE recommendation for each assessment was recorded. Additional data including the incremental quality-adjusted life years (QALY) gain reported in cost-effectiveness analyses were extracted for indications that had undergone a full HTA.

One hundred and eight cancer drug indications were identified, comprising 68 cancer drugs. In 2017, OS, PFS, and SAT benefit underpinned equal proportions of approvals (28.6% each). In 2022, SAT underpinned the largest proportion of approvals (53.6%). As of June 2023, 77 indications (71.3%) had undergone at least a RR assessment; 31 indications had completed a full HTA appraisal. All of the indications underpinned by SAT evidence (n=7) received a conditional negative recommendation. Indications with SAT evidence had a mean incremental QALY gain of 1.88 (standard deviation [SD] 1.20), whereas indications with an OS benefit had a mean incremental QALY gain of 0.81 (SD 0.36).

The proportion of cancer drug indications receiving regulatory approval on the basis of SAT evidence, where no direct comparative evidence is available, is increasing. This results in additional uncertainty in the comparative benefit of cancer drugs supported by SAT evidence. The study is limited by the sample size of HTA appraisals included. Further in-depth analysis of factors influencing NCPE recommendations is needed.

The Middle East and North Africa region accounts for the largest prevalence of type 2 diabetes (T2D). Qatar ranks top 10 for global T2D prevalence, with 17 percent in 2022. Also, 50 to 70 percent of the cardiovascular events occurred in T2D. We sought to estimate the future health and economic burden of cardiovascular disease (CVD) in T2D from 2023 to 2032.

A dynamic multistate model in people with T2D was constructed. The demographic profile of the population was based on Qatari citizens and residents with T2D aged 40 to 90 years in 2022. First CVD events (i.e., myocardial infarction [MI] and stroke) were calculated via the 2013 Pooled Cohort Equation using data from Primary Health Care Corporation. Recurrent CVD events were sourced from the global Reduction of Atherothrombosis for Continued Health (REACH) registry. Outcomes were MI and stroke, years of life lived, quality-adjusted life years (QALYs), total direct and productivity loss costs. Utility and cost model inputs were drawn from published sources. The model adopted a Qatari societal perspective.

The model estimates 123,524 non-fatal MIs (95% uncertainty interval [UI]: 116,923, 130,065), 70,466 non-fatal strokes (95% UI: 67,945, 73,476) and 15,410 CVD deaths (95% UI: 15,217, 15,794), respectively. T2D population accrued 4,834,146 (95% UI: 4,781,235, 4,881,695) total years of life lived and 3,817,246 (95% UI: 3,756,963, 3,870,616) total QALYs. Direct costs accounted for 59.52 percent of the total costs, with a projection of QAR43.59 billion (USD11.98 billion) (95% UI: QAR9.14 billion [USD2.5 billion], QAR134.20 billion [USD36.87 billion]), while the total indirect costs were expected to exceed QAR29.65 billion (USD8.14 billion) (95% UI: QAR2.40 billion [USD659.34 million], QAR113 billion [USD31.04 billion]).

This study highlights that the considerable rising burden of CVD in T2D in Qatar will impact not only the healthcare system but also the society overall. The findings may be used to prioritize strategies targeting T2D to prevent CVD burden.

The National Institute for Health and Care Excellence (NICE) heard from small organizations how resource intensive and difficult it is for them participate in medicines health technology assessments (HTA) since the COVID-19 pandemic. To provide additional support for these organizations or to provide alternative patient input, NICE explored implementing surveys directly with patients to share with patient stakeholder organizations and NICE’s HTA medicines committees.

Patient organizations and colleagues at NICE were included in the background investigation. Informal interviews were conducted with the HTA bodies in Wales and health technology colleagues in NICE about their experience of this method of patient input.

Two approaches were piloted:

(i) Developing the online questionnaire using the Summary of Information for Patients.

(ii) Developing a jointly branded questionnaire collaboratively with the patient organization and implementing a data-sharing agreement to share the raw data.

The survey was distributed by the patient organization, analyzed by NICE, and shared with the patient organization to inform their submission to NICE.

The results of the background investigation showed that the option to include this additional method of input could provide valuable support for patient organizations and has the potential to increase the amount and quality of patient input to an HTA committee.

Both pilots were successful in:

• • Supporting patient organizations’ input into a medicines HTA

• • Reducing the resources required from patient organizations.

• The second pilot added more value due to:

• • Collaboration, relationship, and building trust

• • Joint development of the survey

• • Data sharing and potential to add to patient evidence about a disease and treatments.

Surveys conducted directly with patients can help patient organizations participate in medicines HTAs, but they are only one element of developing more innovative and sustainable patient involvement in the process. HTA bodies need to innovate and work collaboratively with patient stakeholders to produce a menu of options for involvement so that it can be tailored to stakeholders’ resources.

In 2021, approximately 15,000 men in Germany died from prostate cancer (PCa). The national health policy is considering shifting from annual digital rectal examination (DRE)-based screening to an age-related prostate-specific antigen (PSA)-based risk-adapted and organized screening strategy. Our research investigated the cost–utility of the current DRE-based strategy versus organized age-related PSA-based risk-adaptive PCa screening strategies in Germany.

We adapted the Swedish Prostata model to the German context, recalibrating it with PCa clinical and epidemiological data from the national and state registries. The model includes preclinical and clinical disease health states defined by tumor, nodal, and metastatic stages and Gleason scores, and assumes that the benefits of screening arise from stage shift. We assessed the cost–utility of 14 strategies, ranging from no screening to DRE, and age-related, PSA-based, risk-adapted screening. Health state utility values and test characteristics were sourced from the literature. Inpatient and outpatient care costs were derived from the German diagnostic-related groups and uniform-based valuation systems.

Among all strategies evaluated and compared with no screening, the “DRE only” strategy led to substantial overdiagnosis, the highest incremental cost, and minimal quality-adjusted life years (QALY) gains. PSA testing starting at 50 to 60 years with reflex MRI for PSA greater than 3 ng/mL cases followed by combined systemic and targeted biopsy reduced the number of biopsies and overdiagnosis by 75 percent and 26 percent, albeit for fewer QALYs and higher costs (dominated) than the same strategy without reflex MRI. The PSA-based risk-adaptive strategy, starting at 50 to 60 years without reflex MRI, demonstrated an 85 percent probability of being cost effective within the EUR30,000 (USD32,211) to EUR100,000 (USD107,369)/QALY willingness-to-pay range.

While Germany’s HTA emphasizes clinically added benefits and health-related quality of life, cost-effectiveness analysis substantiates this evidence. As a standalone early detection tool, DRE leads to substantial overdiagnosis, unnecessary biopsies, and increased healthcare costs. Overall, this study demonstrated the importance of age-related PSA risk-adaptive PCa screening. The value of MRI deserves further investigation, considering MRI’s positive effect on screening acceptability.

Multimodal prehabilitation, including interventions like physiotherapy, combined with frailty screening and a shared decision-making conference for frail elderly patients before elective surgery is an innovative approach currently under investigation (PRAEP-GO RCT, NCT04418271). The PRAEP-GO intervention aims to enhance postoperative outcomes and prevent care dependency. Our aim is to systematically assess the scale-up potential of PRAEP-GO within the German healthcare system.

We are conducting a scalability analysis using the Intervention Scalability Assessment Tool (ISAT). The ISAT questionnaire comprises two parts: (A) “Setting the scene,” describing the current health service situation (e.g., intervention characteristics, political context), and (B) “Intervention implementation planning,” outlining future requirements (e.g., workforce, infrastructure), with open-ended questions and a scalability readiness assessment using a scale. Our analysis involves three stages: (i) health economists from the PRAEP-GO research team individually answering ISAT questions, (ii) trialists from the PRAEP-GO research team interviewed in a group, and (iii) external experts representing relevant stakeholders for future implementation interviewed in an advisory board meeting.

Data collection for stage (i) and (ii) has been completed, while data collection for stage (iii) is expected to be completed in February 2024. The preliminary findings for part (A) highlight the need for a sustainable approach to manage an aging and increasingly frail patient population requiring surgery. There is no clinical guideline available for the management of this population group. Regarding part (B), the current infrastructure (e.g., therapy facilities) and personnel structures might need to be adapted and should be expanded for large-scale application. Employing professionals to coordinate the patient pathway was recommended, along with adjustments to reimbursement structures.

In PRAEP-GO, we are pursuing a multidisciplinary process with the aim of supporting health decisions that promote an equitable, efficient, and high-quality healthcare system meeting the challenges of an aging population due to demographic change. The PRAEP-GO trial is currently exploring this approach on a small scale. Existing infrastructure and personnel structures would need to be adapted and expanded for scale-up.

Detail on a technology’s projected therapeutic use is required for horizon scanning. The International Horizon Scanning Initiative (IHSI) database will utilize natural language processing (NLP) augmented by human curation to generate an estimated indication for technologies in development. We compared the estimated indication, generated as a test-set for NLP, with health technology developers’ (HTDs) proposed indications identified from Ireland’s horizon scanning system (HSS).

Eight oncology technologies common to both Ireland’s HSS and the IHSI database were analyzed. The analysis included unlicensed technologies in late-stage development that have not submitted a European marketing authorization application. Ireland’s HSS receives data on proposed indications for technologies from HTDs. IHSI database curators extract and convert terms from clinical trials into structured inputs (condition, combination therapy, stage of disease, place in treatment, patient/disease-specific subgroups) to produce an estimated indication for a technology. We sought to identify, by structured input, the degree of alignment between HTDs’ proposed indications with the IHSI database’s estimated indication.

There was 100 percent alignment between the HTD’s proposed indication and the estimated indication generated in the IHSI database for five of the eight included technology records. There was 83 percent alignment for two records and 67 percent alignment for one record. Across all records there was full alignment on condition, combination therapy details, patient-specific subgroup, disease-specific subgroup, and place in treatment. Stage of disease was the only element where data was either not generated for the IHSI database’s estimated indication, not aligned with the HTD’s proposed indication, or reported in an incorrect field.

There is a high degree of alignment between an HTD-proposed indication and the IHSI-estimated indication. The processes for generating an estimated indication will involve both NLP-generation and human co-curation. The current (curator-selected) elements are being used to train the NLP engine. Thereafter, the engine will process clinical trial data to surface tags for human selection to generate the structured inputs.

Real-world data can help inform policymaking in health care by facilitating the evaluation of realistic treatment protocols. To generate robust evidence, analysts must address time-dependent confounders—variables influenced by past treatment decisions and affecting future treatment. Double-robust methods can help in eliminating bias by modeling both the treatment and the outcome mechanisms, using machine learning to improve model specification.

Longitudinal targeted minimum loss-based estimation (LTMLE) is a double-robust method that handles time-varying confounding, currently with only a few applications on real-world data. We demonstrate the use of LTMLE to evaluate realistic treatment protocols by applying it on longitudinal registry data to compare various treatment protocols that involve the use of erythropoiesis-stimulating agents (ESA) for myelodysplastic syndromes patients. We define dynamic regimes that trigger initiating ESA when relevant criteria (e.g., low hemoglobin levels) are met and require continuing/stopping ESA based on the response to treatment. We estimate the effect of these protocols on survival and EuroQol 5-dimension questionnaire (EQ-5D) scores.

We study static treatment regimes where we compare patients always on treatment with patients always not on treatment, and we find the average effects of always administering ESA versus never administering it are positive but not significant on patients’ EQ-5D scores or on survival probabilities across all treatment time periods. We also study dynamic treatment regimes where decisions to initiate and continue/discontinue treatment over time depend on changing patient characteristics and responses to treatment. We find that patients following dynamic treatment regimes are predicted to score higher in EQ-5D and have longer survival probabilities than patients under static treatment regimes.

The paper provides a tutorial and case study demonstration of the LTMLE model that can evaluate realistic treatment protocols using longitudinal observational data. It accounts for time-varying confounding in estimating treatment effects and can incorporate machine learning in improving accuracy of outcome prediction. The model has been applied in the setting of long follow-up times and gradually reduced sample size.

In response to the intricate challenges posed by high-cost, one-shot curative therapies, this study explores what hinders the wide implementation of innovative payment schemes across Europe. Drawing insights from the Belgian social healthcare system, this study focused on defining the necessary and sufficient conditions for implementing outcome-based spread payments in the context of market access to advanced medicinal products

Semi-structured interviews (n=33) were conducted with physicians (n=2), hospital pharmacists (n=4), hospital managers (n=2), patient representatives (n=3), industry representatives (n=5), Belgian policymakers (n=6), sickness fund representatives (n=4), legislative experts (n=2), and accounting experts (n=5) to elicit opinions and insights on stakeholders’ responsibilities and roles, and identify the necessary and sufficient conditions to establish outcome-based spread payments for the reimbursement of innovative therapies. The interviews took place between July 2020 and October 2020. The framework method analysis was performed using NVivo software (version 20.4.1.851). Statements were allocated into six main topics: payment structure, spread payments, outcome-based agreements, governance, transparency, and regulation.

Interviewees across stakeholder groups endorsed the idea of implementing outcome-based spread payments. However, opinions varied on practical and legal feasibility, especially regarding long-term follow-up for patients, data collection burden on physicians, and implications on the financing flow of health technology developers, hospitals, and the government. Concerns were also raised regarding the potential need for new governance structures, enhanced transparency on agreements and pricing mechanisms, as well as defining data requirements to address uncertainties often seen with this type of therapy. All interviewees emphasized the importance of increasing stakeholders’ understanding of these agreements to foster broader acceptance and successful implementation.

The effective implementation of outcome-based spread payments falls behind because consensus on how this reimbursement method can be a sustainable solution is missing. Leveraging the concepts of necessary and sufficient conditions from organizational research, this study provides guidance on resolving challenges and defines stakeholders’ roles for successfully implementing this reimbursement approach.

Involving patients in the health technology assessment (HTA) lifecycle is a core principle at the National Institute for Health and Care Excellence (NICE). To achieve this, NICE has adopted a mixed approach to patient and public involvement and engagement (PPIE) spanning the entire appraisal process. To ensure the PPIE approach enables meaningful involvement, NICE engaged with stakeholders to review its effectiveness and identify areas for improvement.

In 2023, an independent consultant reviewed NICE’s PPIE approach and engaged with NICE staff and external stakeholders from patient organizations, individual patient contributors, and engagement leads at national health and social care organizations. The engagement included interviews with NICE staff (n=19) and external stakeholders (n=13), and an online survey that received 83 responses from patient organizations and patient contributors. Using this feedback, NICE’s patient and public involvement program conducted four focus groups to develop a framework of improved methods and processes for PPIE with NICE staff, patient organizations, and patient contributors.

The engagement identified many positives in NICE’s approach to PPIE, including:

• • lay members sitting on each HTA committee as equal members

• • patient organizations providing written evidence to HTA committees

• • patient experts providing written and verbal testimony to HTA committees

• • support provided by NICE.

The engagement also identified areas where PPIE could have a greater impact, including:

• • improved methods for collecting patient evidence and insight

• • strengthening the role of lay members

• • collating and reusing previously collected patient evidence

• • taking a proportionate approach to involving small organizations

• • allocating staff resources to focus on impactful PPIE practices.

NICE has developed a draft framework for an improved approach to increase the impact of PPIE in HTA decision-making. In 2024, NICE will publicly consult with NICE staff and external stakeholders to review the framework, agree the strategic aims, and develop metrics for measuring success. Following this consultation, the findings and NICE’s updated approach to PPIE will be presented.

Publicly funded cancer services face significant financial and capacity challenges. It is estimated that 40 percent of medicines used to treat cancer are outside their marketing authorization or “off-label.” These uses are usually outside the remit of health technology assessment (HTA) groups. Accessing emerging off-label uses is mostly through individual patient requests, which are resource intensive, delay patient treatment, and produce inequity.

A program providing national HTA review of off-label and off-patent cancer medicine uses has been established by Healthcare Improvement Scotland. Processes include horizon scanning, support for proposing clinicians, and engaging patient groups. Relevant published and unpublished clinical and cost-effectiveness information—identified through systematic literature searches, engagement with pharmaceutical companies, academic and health service data groups—supports independent appraisal and decision-making. Where cost-effectiveness information is unavailable, a value-judgment framework, including magnitude of clinical benefit, uncaptured benefits, and budget and service impact, is utilized to standardize review. The decision-making Council includes public partners, and advice is shared across NHSScotland.

From July 2022 to October 2023, the program has published advice on nine proposals—eight off-label uses and one on-label off-patent use. Health economic models from a pharmaceutical company and an academic group supported decision-making on two proposals, value-judgment frameworks for two proposals, and real-world evidence for one proposal. Eight proposals were supported, and one was not supported. Each supported proposal slowed cancer, prolonged life, or reduced toxicity compared to standard treatment options. Four were cost-saving and three had a low medicines budget impact. Three were service-saving and three had no significant impact on services.

Novel HTA programs can address gaps in medicines governance to improve patient outcomes and support sustainability. Clinical connections, patient group engagement, health economic collaborations and linkage to national cancer data teams and academics have facilitated bespoke approaches to evidence-gathering despite limited resources. Our agile and adaptive approach has enabled robust review and decision-making on varied and impactful proposals.

The value-based healthcare (VBHC) concept links dollars spent to outcomes that matter to patients, rather than to the volume of services. A health technology assessment (HTA) was carried out to determine if the VBHC model could be effective to improve care delivery in colorectal cancer at the CHU de Québec-Université Laval.

A systematic review on VBHC models implemented in oncology was conducted in indexed databases and grey literature between January 2000 and January 2022. Semistructured interviews were conducted from various key informants in our hospital (n=19), including three patients, to characterize the colorectal cancer care organization. HTA was conducted with an interdisciplinary group including surgeons, nurses, hospital managers, and patients.

Key factors to consider in the implementation of VBHC include organizing care around the same medical condition, measuring outcomes and costs for every patient, and tracking data through information technology platforms. Results from case studies suggest that VBHC may have promising effects on clinical, patient-reported, and process outcomes measures. Several issues regarding the degree of agreement with the VBHC principles have been identified in our facility, including a non-uniform care trajectory, a lack of an integrated interdisciplinary team, and the absence of efficient information technologies.

It was recommended that the CHU de Québec-Université Laval initiates an organizational transformation in colorectal cancer care to implement a VBHC model. An effective care transformation will require a significant culture change with impacts on organization and practices but also with positive spin-offs by creating value and patient-centered care.