Cost-effectiveness analysis of Next generation sequencing tests in critically ill pediatric patients

Rare genetic diseases in the pediatric population constitute an urgent global public health issue; overall, more than 300 million people are affected worldwide. Next Generation Sequencing techniques, as Whole genome sequencing (WGS) and Whole exome sequencing (WES), have proven to be significantly supportive in diagnosing these complex conditions. The aim is to evaluate the cost-effectiveness of WGS versus WES in pediatric patients with suspected genetic disorders. A Bayesian Markov model was calibrated among this target population, comparing WGS to WES. Model parameters were retrieved from the scientific literature. Costs and benefits were discounted at a rate of 3%. A lifetime time horizon and the National Health Service perspective was chosen. The Eurozone threshold, ranging from €30,000 to €50,000, was adopted. Markov Chain Monte Carlo was used as the simulation method for Bayesian inference. Uncertainty was explored through a probabilistic sensitivity analysis (PSA) and a value of information analysis (VOI), illustrated through Cost-Effectiveness Acceptability Curve (CEAC) and Expected Value of Perfect Information (EVPI). Results were reported as Incremental Cost-Effectiveness Ratio (ICER), expressed as euros per additional diagnosis. The base case findings highlighted that WGS was cost-effective with an ICER of €31,973. The CEAC showed that for all thresholds over the ICER, WGS had the highest probability of being cost-effective. The EVPI per patient was estimated to be €6,535 on a threshold of €50,000/diagnosis. In addition to being cost-effective, WGS could allow early genetic diagnosis shortening the diagnostic odyssey. The use of WGS in the diagnostic workup has the potential to revolutionise personalised medicine and to play a significant role in achieving SDG 3 by providing personalised healthcare, identifying genetic risk factors for diseases, and informing public health policies for a target population that represents the human capital of the future

Cost-Effectiveness of Whole-Genome vs Whole-Exome Sequencing Among Children With Suspected Genetic Disorders

Importance The diagnosis of rare diseases and other genetic conditions can be daunting due to vague or poorly defined clinical features that are not recognized even by experienced clinicians. Next-generation sequencing technologies, such as whole-genome sequencing (WGS) and whole-exome sequencing (WES), have greatly enhanced the diagnosis of genetic diseases by expanding the ability to sequence a large part of the genome, rendering a cost-effectiveness comparison between them necessary. Objective To assess the cost-effectiveness of WGS compared with WES and conventional testing in children with suspected genetic disorders. Design, Setting, and Participants In this economic evaluation, a bayesian Markov model was implemented from January 1 to June 30, 2023. The model was developed using data from a cohort of 870 pediatric patients with suspected genetic disorders who were enrolled and underwent testing in the Ospedale Pediatrico Bambino Gesu, Rome, Italy, from January 1, 2015, to December 31, 2022. The robustness of the model was assessed through probabilistic sensitivity analysis and value of information analysis. Main Outcomes and Measures Overall costs, number of definitive diagnoses, and incremental cost-effectiveness ratios per diagnosis were measured. The cost-effectiveness analyses involved 4 comparisons: first-tier WGS with standard of care; first-tier WGS with first-tier WES; first-tier WGS with second-tier WES; and first-tier WGS with second-tier WGS. Results The ages of the 870 participants ranged from 0 to 18 years (539 [62%] girls). The results of the analysis suggested that adopting WGS as a first-tier strategy would be cost-effective compared with all other explored options. For all threshold levels above euro29 800 (US $32 408) per diagnosis that were tested up to euro50 000 (US$54 375) per diagnosis, first-line WGS vs second-line WES strategy (ie, 54.6%) had the highest probability of being cost-effective, followed by first-line vs second-line WGS (ie, 54.3%), first-line WGS vs the standard of care alternative (ie, 53.2%), and first-line WGS vs first-line WES (ie, 51.1%). Based on sensitivity analyses, these estimates remained robust to assumptions and parameter uncertainty. Conclusions and Relevance The findings of this economic evaluation encourage the development of policy changes at various levels (ie, macro, meso, and micro) of international health systems to ensure an efficient adoption of WGS in clinical practice and its equitable access

COVID-19 Vaccination Campaign among the Health Workers of Fondazione Policlinico Universitario Agostino Gemelli IRCCS: A Cost–Benefit Analysis

Vaccinations generate health, economic and social benefits in both vaccinated and unvaccinated populations. The aim of this study was to conduct a cost–benefit analysis to estimate the costs and benefits associated with the COVID-19 vaccination campaign for health workers in Fondazione Policlinico Universitario Agostino Gemelli IRCCS (FPG). The analysis included 5152 healthcare workers who voluntarily received the Pfizer–BioNTech COVID-19 vaccine, divided into physicians, nurses and other health workers. Data about vaccine cost, administration and materials were derived from administrative databases of the FPG from 28 December 2020 to 31 March 2021. The costs associated with the COVID-19 vaccination campaign amounted to EUR 2,221,768, while the benefits equaled EUR 10,345,847. The benefit-to-cost ratio resulted in EUR 4.66, while the societal return on investment showed a ratio of EUR 3.66. The COVID-19 vaccination campaign for health workers in FPG has high social returns and it strengthens the need to inform and update decision-making about the economic and social benefits associated with a vaccination campaign. Health economic evaluations on vaccines should always be considered by decision-makers when considering the inclusion of a new vaccine into the national program

Evaluation of the Strategies to Control COVID-19 Pandemic in Four European Countries

On March 11, 2020, the World Health Organization (WHO) has officially declared the novel coronavirus outbreak a pandemic. The national governments deployed a series of severe control measures and a set of public health policies in order to stop the spread of COVID-19 pandemic. The aim of this study is to investigate the correlation between specific interventions and incident cases during the second wave in multiple and specific countries. The observational study was based on data from the Oxford COVID-19 Government Response Tracker (OxCGRT) source retrieved from October 1st, 2020 to January 10, 2021. Thirteen specific indicators related to measures adopted were considered. Four European countries were taken into account: Italy, German, Spain and UK. A vector autoregression (VAR) model and the Granger Causality test were performed to allow for an assessment of any possible effect induced by each control measure against the overall pandemic growth. Wald test was conducted to compute p-values. No correlation between the applied measures and incident cases in the four countries was shown by the Granger causality test. Only closings of workplaces (C2) and limits on private gatherings showed (C4) a significant correlation with incident cases in UK and restrictions on internal movement between cities/regions in Germany. The Granger causality also tested that C2 and C4 forecasted the decrease of incident cases after a time lag of 6–30 days in UK and Germany, respectively. Policy makers must analyze the context in which policies are set because of effectiveness of interventions can be influenced by local context and, especially, by socio-economic and demographic characteristics, and make a proper communication to support the resilience of the population capable of guaranteeing adherence to the interventions implemented

Analisi di minimizzazione dei costi dell'ablazione transcatetere della fibrillazione atriale eseguita mediante TactiFlex o TactiCath

Introduzione L’ablazione transcatetere è una terapia efficace per il controllo del ritmo nella fibrillazione atriale (FA). L’obiettivo dello studio è confrontare i costi dell’ablazione transcatetere della FA eseguita rispettivamente con TactiFlex e TactiCath in uno scenario ospedaliero reale. Metodi Assunta la medesima efficacia e sicurezza cliniche per le due alternative, è stata effettuata un'analisi di minimizzazione dei costi per valutarne l’impatto economico. Le durate medie delle due proce- dure sono state calcolate su un campione di pazienti trattati presso un ospedale italiano. Le analisi dei costi medici diretti e non medici diretti sono state effettuate adottando la prospettiva dell'ospe- dale. È stata condotta un'analisi di sensibilità univariata per valutare l’incertezza nei parametri scelti. Risultati Dalla prospettiva dell'ospedale, si stima preliminarmente che la procedura con TactiFlex costi €168 in più rispetto all'alternativa, con un guadagno medio di 57.3±9.5 minuti nella disponibilità della sala operatoria impiegata e del personale coinvolto nell’ablazione. I parametri maggiormente deter- minanti l’incertezza nei risultati sono i salari orari del personale e i costi dei cateteri ablatori. Conclusioni L’adozione del catetere TactiFlex può aumentare l'efficienza nell’impiego delle sale operatorie e del personale coinvolto nelle ablazioni della FA, e ridurre il rischio di complicanze attribuibile alla maggior durata dell’anestesia

Health technology assessment of whole genome sequencing in the diagnosis of genetic disorders: a scoping review of the literature

Objective: The aim of this scoping review is to map the available evidence about the use of health technology assessment (HTA) in the assessment of whole genome sequencing (WGS).Methods: A scoping review methodology was adopted. The population, concept, and context framework was used to build up the research question and to establish the eligibility criteria. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews was adopted to implement a comprehensive search strategy. Evidence was retrieved from scientific databases and HTA organizations Web sites. Reports were classified as full HTA, mini-HTA, rapid reviews or other.Results: The search strategy identified seven reports. Five HTA organizations from five countries elaborated the reports: one full HTA, four rapid reviews, and two classified as others. The reports were mainly focused on the evaluation of the clinical utility and cost-effectiveness of genome-wide sequencing as well as informing policy questions by providing analyses of organizational and ethical considerations.Conclusions: Few HTA organizations are drafting reports for WGS. It is essential to stimulate a critical reflection during the elaboration of HTA reports for WGS to steer choices of decision makers in the establishment of priorities for research and policy and reimbursement rates

Organizational Aspects of the Implementation and Use of Whole Genome Sequencing and Whole Exome Sequencing in the Pediatric Population in Italy: Results of a Survey

This study explores the organizational aspects of whole genome sequencing (WGS) implementation for pediatric patients with suspected genetic disorders in Italy, comparing it with whole exome sequencing (WES). Health professionals’ opinions were collected through an internet-based survey and analyzed using a qualitative summative content analysis methodology. Among the 16 respondents, most were clinical geneticists performing only WES, while 5 also used WGS. The key differences identified include higher needs for analyzing genome rearrangements following WES, greater data storage and security requirements for WGS, and WGS only being performed in specific research studies. No difference was detected in centralization and decentralization issues. The main cost factors included genetic consultations, library preparation and sequencing, bioinformatic analysis, interpretation and confirmation, data storage, and complementary diagnostic investigations. Both WES and WGS decreased the need for additional diagnostic analyses when not used as last-resort tests. Organizational aspects were similar for WGS and WES, but economic evidence gaps may exist for WGS in clinical settings. As sequencing costs decline, WGS will likely replace WES and traditional genetic testing. Tailored genomic policies and cost-effectiveness analyses are needed for WGS implementation in health systems. WGS shows promise for enhancing genetics knowledge and expediting diagnoses for pediatric patients with genetic disorders

Pediatric post COVID-19 condition: an umbrella review of the most common symptoms and associated factors

Background: Although the long-term consequences of the Coronavirus Disease-2019 (COVID-19) pandemic are yet to be fully comprehended, a syndrome symptomatically akin to the COVID-19 disease has been defined, for children and adolescents, in February 2023 by the World Health Organization (WHO) as ‘post COVID-19 condition’ (PCC). Potential consequences of COVID-19 that affect developmental milestones in children and adolescents should be comprehended in their magnitude and duration. The aim is to investigate the most common symptoms and predictors or risk factors for pediatric PCC. Methods: In this umbrella review, the population of interest was defined as children and adolescents from 0 to 19 years old presenting PCC symptoms as defined by the WHO in the International Classification of Diseases. The intervention considered was general follow-up activity to monitor the patients’ recovery status. No comparator was chosen, and the outcomes were symptoms of PCC and predictors or risk factors of developing PCC. Methodological quality, risk of bias and the level of overlap between studies were assessed. A random- effects meta-analytic synthesis of respective estimates with inverse variance study weighting was carried out, for the primary studies included by the reviews retrieved, regarding predictors or risk factors reported. Results: We identified six eligible systematic reviews, five with meta-analyses, from three databases. The most common symptoms reported were fatigue and respiratory difficulties; female sex and older age were the most reported factors associated with the development of pediatric PCC. Conclusions: A deeper understanding of pediatric PCC requires well- designed and clearly defined prospective studies, symptom differentiation, and adequate follow-up

Community-based participatory research to engage disadvantaged communities: Levels of engagement reached and how to increase it. A systematic review

Community-based participatory research (CBPR) is one of the most used community engagement frameworks to promote health changes in vulnerable populations. The more a community is engaged, the more a program can impact the social determinants of health. The present study aims to measure the level of engagement reached in randomized controlled trials (RCTs) using CBPR in disadvantaged populations, and to find out the CBPR components that better correlate with a higher level of engagement. A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Embase, Web of Science, MEDLINE, Cochrane and Scopus databases were queried. Engagement level was assessed using the revised version of IAP2 spectrum, ranging from "inform" to "shared leadership" . Fifty-one RCTs were included, belonging to 36 engagement programs. Fourteen CBPR reached the highest level of engagement. According to the multivariate logistic regression, a pre-existing community intervention was associated with a higher engagement level (OR = 10.08; p<0.05).The variable "institutional funding" was perfectly correlated with a higher level of engagement. No correlation was found with income status or type of preventive programs. A history of collaboration seems to influence the effectiveness in involving communities burdened with social inequities, so starting new partnerships remains a public health priority to invest on. A strong potentiality of CBPR was described in engaging disadvantaged communities, addressing social determinants of health.The key findings described above should be taken into account when planning a community engagement intervention, to build up an effective collaborative field between researchers and population