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Knee osteoarthritis (OA) is a prevalent and debilitating condition with a significant impact on patient quality of life and healthcare costs. Intra-articular glucocorticoid injections (IAGI) are used in Switzerland for conservative management. A systematic literature review identified one existing economic evaluation on this topic globally. Therefore, the aim of this study was to evaluate the cost effectiveness of IAGI in knee OA (relative to standard care) within the Swiss healthcare context.
Methods
A cost-utility analysis was conducted using a healthcare payer perspective. Health outcomes were measured using quality-adjusted life year (QALY) estimates. Clinical outcomes were mapped into a preference-based utility measure. The clinical data showed IAGI only improved pain at one month but not beyond. Only direct costs in 2024 CHF were considered. A time horizon of six months was used to capture differences in costs and outcomes. Given the short-term clinical improvement, only a single IAGI injection was modeled. Both costs and outcomes were discounted at three percent per annum. Both deterministic sensitivity analyses (DSA) and probabilistic sensitivity analyses (PSA) were conducted. The research project was funded by the Swiss Federal Office of Public Health.
Results
The base case incremental cost-effectiveness ratio for IAGI in knee OA was CHF12,456 (USD15,735) per QALY gained. PSA showed a 71.9 percent probability of cost effectiveness at a hypothetical willingness-to-pay (WTP) threshold of CHF50,000 (USD63,164) per QALY gained and 75.0 percent at CHF100,000 (USD126,322). There was a 22.0 percent chance that IAGI is dominated by standard care (i.e., IAGI is more costly and less effective). The DSA identified the key model drivers as IAGI administration costs and changes in health-related quality of life post-treatment.
Conclusions
IAGI for knee OA appeared to be a cost-effective adjunct to standard care under hypothetical thresholds of CHF50,000 (USD63,164) and CHF100,000 (USD126,322) per QALY gained. Incorporating both DSA and PSA allowed for a robust exploration of uncertainties, highlighting critical drivers of cost effectiveness. Future research should refine long-term effectiveness estimates, particularly the impact of IAGI on progression to joint replacement, and evaluate real-world outcomes to ensure optimal resource allocation.
Health technology assessment (HTA) has increasingly shaped public health insurance reimbursement decisions across many countries during the last 10 years. As countries implement and expand their use of HTA in determining recommendations for reimbursement, patient access to new medicines is affected. This study analyzed the impact of HTA, and HTA expansion, on patient access to new medicines across OECD countries.
Methods
New medicines were identified as new active substances approved by the European Medicines Agency, the United States Food and Drug Administration, or Japan’s Pharmaceuticals and Medical Devices Agency and launched globally between 1 January 2014, and 31 December 2023. Public health insurance reimbursement was determined by reviewing HTA recommendations by the appropriate HTA bodies and public reimbursement listings in each country. Patient utilization of new medicines was measured by estimating the number of patients treated with new medicines in each country, on a per capita basis, using sales and volume data adjusted for expected treatment durations.
Results
During the past 10 years, HTA continued to play no official role in public health insurance reimbursement decisions for new medicines in the USA but played an expanding role in other OECD countries. New medicines increasingly launched first in the USA, with patients having access through public health insurance to 85 percent of new medicines in 2023. Patients in other OECD countries were far less likely to access new medicines within a year of first launch, and on average had access through public health insurance to less than a third of new medicines in 2023.
Conclusions
The use of HTA contributes to patient access inequality across countries by limiting and delaying public health insurance reimbursement of new medicines. In the USA, which does not use HTA, patients have access to far more new medicines. Patients in countries where HTA bodies have become gatekeepers of determining which new medicines are cost effective tend to have worse access.
Budget impact analyses are essential for decision-making processes regarding the incorporation of technologies into healthcare systems. Despite advancements driven by the National Committee for Health Technology Incorporation (CONITEC), the Brazilian Network for Health Technology Assessment (REBRATS), and the National Supplementary Health Agency (ANS), challenges persist in evaluating the economic impact of new technologies, including methodological inconsistencies in submitted dossiers.
Methods
Reports on the critical analysis of dossiers submitted to the ANS prepared by a health technology assessment center between December 2022 and December 2024 were analyzed. Criticisms of the submitted dossiers were categorized into eleven topics: (i) analytical model; (ii) reference scenario; (iii) alternative scenario; (iv) time horizon; (v) target population; (vi) direct costs; (vii) market behavior; (viii) sensitivity analysis; (ix) input data; (x) output data; and (xi) final decision. Descriptive and quantitative data were used to identify patterns and methodological gaps.
Results
The critical analysis identified recurring issues, including underestimated target populations in 50 percent of cases and inadequate direct cost evaluations in 40 percent. These inadequacies were often linked to outdated data sources, such as the Painel dos Dados do TISS database. Analytical models were deemed adequate in 70 percent of cases, whereas sensitivity analyses were insufficient in 30 percent of cases. Market behavior projections were conservatively estimated in 60 percent of dossiers, affecting the accuracy of budget impact projections. These methodological inconsistencies hindered the reproducibility of analyses and compromised evidence-based decision-making.
Conclusions
The findings highlighted the need for methodological standardization in dossiers submitted to the ANS, emphasizing the need to update data sources and ensure transparency in budget impact calculations. These improvements could enhance evaluation validity and support better decision-making for technology incorporation. Future research should address strategies to reduce uncertainties and inconsistencies in analytical models and cost estimations.
Da Vinci robot-assisted surgery (dV-RAS) has been around for more than 20 years and has become the standard of care for select procedures in specific countries. Recently, health technology assessment agencies have used local evidence to inform their evaluation of dV-RAS. We aimed to compare global, Pan-European (Pan-EU), and Pan-Asian systematic literature reviews on dV-RAS for seven malignant procedures.
Methods
The PubMed, Scopus, and Embase databases were systematically searched through to 31 December 2022 following PRISMA and PROSPERO guidelines (CRD42023466759). Studies that compared dV-RAS with laparoscopic or video-assisted thoracoscopic surgery (lap/VATS) or open oncologic surgery and reported on relevant clinical outcomes were included. Studies were checked for the source of clinical data and categorized as being either Pan-EU or Pan-Asian. The global analysis included all eligible studies. Pooled odds ratios or mean differences were calculated for randomized, prospective, and database studies using R software and a fixed-effect or random-effects (when heterogeneity was significant) model. The revised Cochrane risk-of-bias and ROBINS-I tools were used to assess bias.
Results
The global systematic literature review identified 230 studies (34 randomized, 74 prospective, 122 database), including 78 Pan-EU and 35 Pan-Asian studies. Results from the global and regional studies agreed on rates of conversions and blood transfusions and lengths of hospital stay. The global, Pan-EU, and Pan-Asian studies did not align on: operative time (Global: dV-RAS longer; Pan-EU: dV-RAS longer versus open; Pan-Asian: dV-RAS longer versus lap/VATS); 30-day complications (Global and Pan-Asian: dV-RAS lower; Pan-EU: dV-RAS lower versus open); 30-day readmissions (Global and Pan-EU: dV-RAS lower; Pan-Asian: dV-RAS lower versus open); 30-day reoperations (Global: dV-RAS lower versus open; Pan-EU and Pan-Asian: dV-RAS similar); 30-day mortality (Global: dV-RAS lower; Pan-EU: dV-RAS lower versus open; Pan-Asian: dV-RAS longer versus lap/VATS).
Conclusions
Our analysis highlighted that global and regional evidence aligned on select outcomes. The differences we observed might be associated with surgeon experience, limited evidence, or other unknown regional biases. These findings should be considered by health technology assessment agencies when looking at regional data versus global evidence.
A state is luminous if and only if, whenever one is in it, one is in a position to know that one is. A state is bright if and only if, whenever one is in it, one is in a position to believe that one is. Beliefs have long been regarded, both historically and from a contemporary perspective, as luminous and bright. This paper evaluates Timothy Williamson’s influential anti-luminosity arguments as they apply to the luminosity and brightness of belief. While his margin-for-error argument may effectively challenge the luminosity of knowledge, it cannot be straightforwardly extended to undermine either the luminosity or the brightness of belief. Some authors responded to the more general anti-luminosity argument based on a constitutive connection between states and attitudes. An influential reply on Williamson’s behalf by Srinavasan in terms of degrees of confidence opens way to the claim that there is a constitutive connection between confidence and belief. The more general argument, in the specific case of belief, can then be resisted by drawing on independently defensible views of how we form beliefs about our own beliefs.
Generative artificial intelligence (AI) is revolutionizing real-world evidence generation in health care. This study compared chemotherapy recommendations for women with breast cancer across different clinical risk profiles and Oncotype DX Breast Recurrence Score® test results, as obtained from a Delphi panel of experts, with recommendations generated by ChatGPT. The objective was to analyze concordances and differences between AI-generated and expert-driven insights.
Methods
An online survey of 10 independent breast cancer experts, blinded to each other’s responses, assessed chemotherapy recommendations for patients with early stage, node-negative breast cancer. Responses were analyzed by clinical risk (high versus low), age group (≤50 versus >50 years), and recurrence score (RS) (<11, 11 to 25, >25) from Oncotype DX. ChatGPT, using automated prompt engineering, addressed the same scenarios as agent-based oncologists. Expert recommendations were summarized as arithmetic means, while ChatGPT responses were analyzed for concordance. A one-sample t-test compared mean estimates between the Delphi panel and ChatGPT results, highlighting differences in recommendations across groups.
Results
The Delphi panel and ChatGPT provided clinically similar chemotherapy recommendations for patients evaluated with Oncotype DX, with no statistically significant differences in eight out of 12 scenarios. Both agreed on zero percent chemotherapy for patients with low clinical risk (RS<11) and showed comparable results for high clinical risk (RS>25), including patients under 50 years (8% versus 10%) and over 50 years (6% versus 5%). The largest divergence, which was statistically significant, was observed for patients with low clinical risk (RS 11 to 25) who were over 50 years (1% versus 20%). High-risk patients consistently received strong recommendations, with near perfect agreement for those with high clinical risk (RS>25) who were under 50 years (98% versus 95%).
Conclusions
From a decision-making perspective, the responses from ChatGPT and the Delphi panel were very similar, suggesting that AI can effectively support the health technology assessment process. This alignment highlights AI’s potential to accelerate decision-making, offering a faster alternative to the traditional, time-consuming Delphi model while maintaining reliable chemotherapy recommendations.
Despite the significant impact of the media on individuals with mental illness, newspaper articles related to antidepressants have not been systematically studied. The present study aimed to analyze Brazilian journalistic coverage on the use of antidepressants to understand how the news presents and shapes the topic of antidepressants for its readers.
Methods
This qualitative study evaluated journalistic content on antidepressant use from Folha de São Paulo, a newspaper available in digital format. Articles published between 1 January 2019 and 31 December 2023 were collected and stored in a database for analysis. Natural language processing (NLP) techniques, combined with machine learning, were applied. The R software (version 4.3.3) with tidytext, tm, tidyverse, and stringr packages was used for the analyses. The study identified patterns and trends in language usage, focusing on frequently occurring terms to understand how antidepressants are portrayed in media content.
Results
The initial research was conducted using the keyword “antidepressants” in the search engine of the Folha de São Paulo. Of the articles assessed for eligibility, 182 were included in the study. Across all the articles, the analysis aimed to identify the most frequently used words, resulting in a word cloud. The most used words in the text body were “treatment,” followed by “years,” “anxiety,” “women,” and “pandemic.” Regarding the most frequent words in the titles, they were “depression,” “health,” and “study.” On average, there was no significant change in the total number of n-grams used.
Conclusions
The findings illustrated how Brazilian media frames antidepressant use, revealing potential misinformation or stigma. Understanding these representations can guide strategies for improving public awareness and reducing stigma around mental health. By highlighting trends in journalistic narratives, this study contributes to public health policies that promote accurate, responsible communication about antidepressant use.
Incorporating patient preferences into health technology assessment represents a promising avenue for its enhancement. However, the complexity and diversity of methods for evaluating preferences, coupled with uncertainties regarding their impact on decision-making processes, present significant challenges to their effective integration. Consequently, the objective of this study was to evaluate the application of the MaxDiff analysis methodology for determining patient preferences, with a focus on pharmaceutical services as a case study.
Methods
The experimental design for scaling MaxDiff was developed using Sawtooth Lighthouse software. The design parameters included 12 pharmaceutical services. Descriptive statistics, hierarchical Bayesian analysis, latent class analysis, and logistic regression methods were employed to generate preference results.
Results
The most preferred services were identified as follows: the creation of a personalized list of safe medications to address patient needs, with a quantitative contribution of 0.5; and the provision of rapid tests (for influenza and Helicobacter) and stroke risk assessment (quantitative contribution of 0.31). In contrast, patients did not prioritize services related to contraception selection or weight control and weight loss program development. Descriptive statistics, hierarchical Bayesian analysis, and logistic regression methods sequentially identified the most preferred services. Latent class analysis revealed two distinct consumer segments: Segment 1 (39%) and Segment 2 (60%), which differed in their sociodemographic characteristics and preferred services.
Conclusions
The obtained results can be utilized as patient-based evidence to understand patients’ unmet needs in the assessment of technologies such as pharmaceutical services, taking into account the local context. Despite the simplicity of the MaxDiff analysis methodology, the resource intensity and the level of knowledge among specialists and patients regarding preference collection methods remain significant barriers to its implementation.
Over the years many researchers have sought to understand the decision-making process of CONITEC, the Brazilian health technology assessment (HTA) agency. The emergence of high-cost technologies, such as monoclonal antibodies (mAbs), has heightened the importance of delineating the decision-making criteria. This study aimed to elucidate the criteria employed by CONITEC for the incorporation of mAbs in Brazil.
Methods
All CONITEC reports published between 2019 and 2024 on mAbs were included. Descriptive statistics were utilized to summarize the data. The statistical significance between outcomes and covariates was assessed using the Kruskal-Wallis test for continuous variables and the chi-square test for categorical variables. Logistic regressions were produced to evaluate the impact of each covariable on the recommendations. Results with a p-value of less than 0.10 were considered statistically significant due to the small sample size. All analyses were conducted using R software.
Results
After cleaning the database, 53 reports were included, encompassing 37 mAbs evaluated for 45 indications. Sixteen submissions (30.1%) received a positive recommendation. Efficacy (p=0.009) and the preliminary decisions (p<0.001) were significantly associated with the final recommendation. Further analysis showed that an incremental cost-effectiveness ratio (ICER) below BRL150,000 (USD65,020) was associated with a higher chance of a positive recommendation (p=0.050). Logistic regression revealed that the logarithm of the ICER was significantly associated with recommendations (odds ratio 0.618; p=0.031), indicating that increasing the ICER by 2.7 times was associated with a 38.2 percent lower chance of listing.
Conclusions
Efficacy is important for decision-makers in Brazil. However, the results of economic analyses also influence the recommendation of mAbs. An ICER above BRL150,000 (USD65,020) per quality-adjusted life year significantly reduced the chances of a mAb being listed.
The healthcare and rehabilitation processes for individuals with low back pain impose significant costs on healthcare systems worldwide. Understanding the economic burden of this condition can help policymakers implement preventive strategies and promote a more rational allocation of health resources. The aim of this study was to investigate the costs of managing low back pain in Brazil between 2010 and 2019.
Methods
This study evaluated the costs of low back pain from the perspective of the Brazilian Unified Health System (SUS) in the outpatient setting. Data were collected from the Ambulatory Information System and analyzed by sex, age group, and health condition (low back pain). Ambulatory care data were presented as number of visits, total annual cost, and number of procedures performed. In addition, linear regression analysis using generalized linear models (gamma distribution with identity link) was performed to examine the association between total outpatient care costs and predictors such as age, gender, and race.
Results
Between 2010 and 2019, the SUS spent more than USD189 million to treat low back pain in adults. During this period, more than 16 million physical therapy sessions, 7,000 surgeries, and one million imaging studies were performed. These procedures accounted for approximately 85 percent of total spending on low back pain in Brazil. Despite the high number of physical therapy sessions, significant expenditures were still observed for surgical procedures. Regression analysis showed that men had higher costs per procedure than women.
Conclusions
The study revealed significant costs for low back pain in Brazil, with higher expenditures for men and those aged 34 to 63 years. Major expenditures were associated with surgery and physical therapy, whereas the prescription of imaging studies decreased, which is in line with recommendations. These findings highlight the need for targeted strategies to effectively manage resources for low back pain in the ambulatory care setting.
Diabetes is a condition that affects public health based on its increased incidence, prevalence, morbidity, and mortality. According to the latest Atlas of the International Diabetes Federation, it is estimated that there are 537 million adults with the condition; for Brazil, the estimate is 16 million. Investment in diabetes and its complications exceeds USD42 billion in Brazil.
Methods
This national study was conducted from 1 July to 22 August 2024. Interviews were conducted online with 1,843 Brazilians over 18 years of age with diabetes. The study’s objective was to identify barriers to diabetes treatment in Brazil after the incorporation of health technologies in the Unified Health System (SUS) aimed at diabetes. Data were processed according to the profile of reported diabetes diagnosis in the National Health Survey 2019, conducted by the Brazilian Institute of Geography and Statistics.
Results
The preliminary study indicated that 56 percent of those diagnosed with diabetes are over 60 years of age, 58 percent have elementary education, 54 percent have a monthly family income of up to two minimum wages, 75 percent have type 2 diabetes, 67 percent say they have hypertension, and 63 percent have high cholesterol. Obesity was reported by 39 percent, 82 percent use oral medication, 67 percent undergo tests through the SUS, and 84 percent obtain free medication through the SUS. Of those interviewed, 60 percent cite the availability of medication as the main factor in monitoring the condition, followed by attention from doctors (53%).
Conclusions
The aging population poses challenges for diabetes control in Brazil and will further strain the public health system. Current barriers, such as bottlenecks in care and lack of medicines and doctors, are likely to worsen. Vulnerable groups with lower levels of education and income are currently the most affected. With the increasing age of the population, the system will spend more resources and may have difficulty sustaining itself in a few years.
Skin-related neglected tropical diseases (skin NTDs) are very prevalent in endemic areas. Resources to manage them are very scarce. The World Health Organization’s Skin NTDs app is designed to help frontline health workers in identifying skin NTDs (n=13) and common skin conditions (n=24). A beta version including artificial intelligence (AI) was developed, and its accuracy and usability was assessed in real life conditions.
Methods
The Skin NTDs app usability and user experience was assessed in frontline healthcare workers (n=38) in Kenya. Participants answered the user Mobile App Rating Scale (uMARS) questionnaire. Focus group discussions (n=4) and semi-structured interviews (n=15) were used to get an in-depth understanding of the user experience. To assess accuracy of the AI algorithm, 40 participants from five counties in Kenya used the app for five months, uploading photographs of the skin lesion (n=605) to an external platform. AI algorithm accuracy was calculated based on the gold standard of consensus diagnosis reached by three independent dermatologists.
Results
The Skin NTDs app received high scores on the uMARS questionnaire (mean app quality 3.82/5 and perceived impact 4.1/5; n=38). Focus group discussions and interview responses aligned with the uMARS findings, reinforcing the positive assessment of the app. It helped to empower professionals, increased their knowledge about skin diseases, and improved their communications skills with patients. The app was time saving and reduced referral of patients to specialists. Some features to be improved were identified. Overall accuracy of the app was found to be 80 percent in diseases where AI has been trained with a higher number of photos of endemic skin conditions.
Conclusions
The Skin NTDs app showed commendable quality and holds potential to be scaled up and implemented at the national level in Kenya and globally. It performs well as a clinical decision support system to help frontline healthcare workers identify potential skin diseases that patients suffer from and to reduce the number of referrals to dermatologists in contexts where there is a lack of specialized professionals.
Chile has been conducting various efforts toward reforming the healthcare system, yet significant discrepancies persist in the equitable access to and utilization of healthcare resources. The aim of this scoping review was to map the existing literature on hearing health care and treatments for hearing loss (HL) in Chile to identify local determinants that may contribute to stratification of access to hearing health care.
Methods
The Joanna Briggs Institute guidance for scoping reviews was followed. The PCC criteria (Population, Concept, Context) was used to guide development of the search strategy. Searches were conducted in MEDLINE (PubMed), the Cochrane Library, and Science Direct databases and supplemented by a manual search. Searches were limited to publications from 2000 to June 2023, with no restrictions on language or publication type. Two independent reviewers screened all retrieved references, assessed the eligibility following the PCC criteria, and charted data of the eligible publications. Disagreements were solved through discussion with a third reviewer. A structured narrative synthesis of findings was conducted.
Results
The search yielded 506 unique records for screening, of which 104 full-text publications were assessed and 39 were included in the review. The evidence revealed that the treatment of HL is publicly financed for children younger than four years (any type of HL, degree moderate or higher), the elderly aged 65 years or older (bilateral HL requiring a hearing aid) and people at least four years of age diagnosed with total deafness (cochlear implant candidates). However, for individuals aged between four and 64 years who have HL but are not totally deaf, there is not a clear rehabilitation pathway or dedicated public reimbursement.
Conclusions
Age and degree of HL might be the most prominent determinants of access to hearing health care in Chile. Diagnosis and treatment of people aged four to 64 years with moderate to severe HL might incur out-of-pocket expenses or even have no access to care for HL. These findings highlight the need for public health policies to promote equitable access to hearing health care in Chile.
In the face of ever accelerating climate change, the ability to resist such change and work with nature to secure a more environmentally just future poses a striking but necessary challenge. From this perspective, the present article asks: Can a posthuman reimagining of the human, non-human, and more-than-human nexus in the context of a semiotic landscape analysis of the seas (henceforth, seascape) create new possibilities beyond the Anthropocene? This approach, which I call MARA—mapping and applying a rhizomatic assemblage of the seascape—aims to offer an exploratory framework for rethinking the interaction of the multispecies entanglement and the consequences in terms of vulnerability and resilience to climate change. This is achieved through a multisensory semiotic landscape approach to a case study of a blue tourism initiative in Ireland’s seascape. The results of the case study serve to undo the previously accepted binary structure of power which favours human over non-human. (Multisensory semiotic landscape, seascape, rhizomatic assemblage)
Studies on bilingual individuals indicate that both first-language (L1) and second-language (L2) processing recruit linguistic and simulation systems, with L1 processing typically showing greater activation of simulation systems (often referred to as preference systems) and L2 processing relying more heavily on linguistic systems. When bilingual speakers switch between languages, the language used initially may influence the activation of preference systems in the subsequent language. The present study examines whether L2 proficiency moderates this influence. Employing a 2 × 2 × 2 × 2 mixed design, we investigated how L2 proficiency shapes embodied effects during L1 and L2 sentence comprehension under two language-switching conditions (L1 → L2 and L2 → L1) in bilingual participants. Results revealed that low-proficiency bilinguals demonstrated embodied effects in L1 comprehension across both switching directions. In contrast, highly proficient bilinguals showed such effects only when switching from L1 to L2 but not from L2 to L1. These findings suggest that, in the L2 → L1 condition, the linguistic system activated during L2 processing in highly proficient bilinguals exerts a stronger influence on subsequent L1 processing than in low-proficiency bilinguals, highlighting the role of proficiency in modulating cross-linguistic embodied effects.
Rare diseases (RDs) present unique challenges in health technology assessment (HTA) due to small, heterogeneous populations and limited clinical data, which complicate economic modeling and delay access to innovative interventions. This survey, conducted by the HTAi Rare Diseases Interest Group, explored key challenges in economic modeling for RDs, the application of solutions, and the use of evidence assessment frameworks in HTA practice.
Methods
A mixed-method survey was developed with multiple-choice, Likert-scale, and open-text questions using the SurveyMonkey platform. Responses were collected from members of HTAi and the International Network of Agencies for Health Technology Assessment at conference sessions. Additional respondents were recruited via professional networks and direct emails. Options exceeding 50 percent of responses and rate weighted averages guided the interpretation and identification of areas of agreement.
Results
In total, 36 individuals across all continents, mostly from consultancy and HTA agencies, responded to the survey. Key challenges in economic modeling included insufficient quality of clinical trials (duration and sample size), scarcity of robust data, and lack of health-related quality of life metrics. The most common solutions included using proxy diseases, pooled data, and qualitative research. Broader impacts were integrated through societal perspectives, decision modifiers, and deliberative processes. GRADE was the most commonly cited explicit evidence assessment framework. In some cases, implicit approaches dominated HTA practice where challenges such as single-arm trials and reliance on real-world evidence prevailed, though patient-reported outcomes had gained some acceptance.
Conclusions
Scarcity and quality of clinical data remain significant barriers to economic modeling for RDs. Solutions such as qualitative methods and pooling data show promise. The broader impacts of RDs are increasingly being considered, but further research is essential to refine methods, embrace non-traditional data, and develop appropriate frameworks to assess evidence for RDs in HTA.
Chronic lymphocytic leukemia (CLL) is a malignant hematologic disorder that affects older adults. CLL is the most common leukemia in adults in the Western world. The genomic landscape of CLL is heterogeneous. The aim of this report was to identify the clinically relevant molecular alterations in CLL and define the role of targeted next-generation sequencing (NGS) in routine care.
Methods
The evaluation included an analysis of systematic reviews, meta-analyses, clinical guidelines, and relevant molecular alterations using OncoKB™ and TOPOGRAPH classifications. Approvals from the French National Authority for Health Transparency Committee or compassionate use decisions from the French National Agency for Medicines and Health Products Safety were also considered.
Results
Targeted NGS in CLL detected molecular alterations to determine prognosis and guide treatment decisions with a higher sensitivity than Sanger sequencing. The recommended analyses include:
• TP53 and IGHV mutations before first-line treatment;
• TP53 mutation before treatment modification in relapse cases;
• TP53, BTK, and PLCG2 mutations after treatment with BTK inhibitors;
• TP53 and BCL2 mutations after treatment with BCL2 inhibitors; or
• TP53, BTK, PLCG2, and BCL2 mutations after treatment with both BTK and BCL2 inhibitors.
Conclusions
Targeted NGS is essential for managing CLL. The gene panel will be updated dynamically based on new scientific evidence and regulatory approvals.
Internationally, there is a growing drive to integrate patient preference information (PPI) into health technology assessment (HTA) decision-making. However, it is unclear how PPI is used in real-world contexts and the extent to which it can reshape and influence HTA decisions. Understanding how PPI can be meaningfully used in HTA is fundamental for supporting its practical application and increasing trust in its use.
Methods
The aim was to enhance understanding of how HTA committees interpret and incorporate PPI into decision-making. Mock deliberation workshops were conducted by members of the HTAi Patient Preference Project Subcommittee with experts from four HTA agencies. For the workshops, a mock evidence package was developed that included PPI evidence alongside key clinical and economic evidence to simulate decision-making processes. The mock deliberations were analyzed using thematic analysis.
Results
The mock deliberation workshops (25 participants) highlighted both opportunities and challenges in integrating PPI into HTA processes. While PPI was acknowledged as valuable evidence, its influence on decision-making in the scenarios varied from being cited by a few participants as informing the decision to most participants indicating the evidence was not persuasive. Participants pointed out the need for more structured guidance on how to incorporate PPI alongside clinical and economic evidence. The findings highlighted the importance of standardizing the path to integration, as well as the content and format of PPI, to support consistent interpretation and application in HTA.
Conclusions
By examining how PPI is weighed alongside clinical and economic evidence, the project offered valuable insights for stakeholders aiming to generate more pertinent PPI studies for incorporation into the decision-making process. The key takeaways for HTA agencies included strategies for effectively balancing PPI with clinical and economic evidence, highlighting a shift toward incorporating more diverse and inclusive forms of evidence.