Background: Trans-arterial radio-embolization (TARE) is an emerging treatment for the management ... more Background: Trans-arterial radio-embolization (TARE) is an emerging treatment for the management of hepatocellular carcinoma (HCC). TARE may compete with systemic chemotherapy, sorafenib, in intermediate stage patients with prior chemoembolization failure or advanced patients with tumoral macrovascular invasion with no extra-hepatic spread and good liver function. We performed a budget impact analysis (BIA) evaluating the expected changes in the expenditure for the Italian Healthcare Service within scenarios of increased utilization of TARE in place of sorafenib over the next five years. Methods: Starting from patient level data from three oncology centres in Italy, a Markov model was developed to project on a lifetime horizon survivals and costs associated to matched cohorts of intermediate-advanced HCC patients treated with TARE or sorafenib. The initial model has been integrated with epidemiological data to perform a BIA comparing the current scenario with 20 and 80% utilization rates for TARE and sorafenib, respectively, with increasing utilization rates of TARE of 30, 40 and 50% over the next 1, 3 and 5 years. Results: Compared to the current scenario, progressively increasing utilization rates of TARE over sorafenib in the next 5 years is expected to save globally about 7 million Euros. Conclusions: Radioembolization can be considered a valuable treatment option for patients with intermediateadvanced HCC. These findings enrich the evidence about the economic sustainability of TARE in comparison to standard systemic chemotherapy within the context of a national healthcare service.
Aim This study examined the outputs of research papers in diabetes from 31 European countries bet... more Aim This study examined the outputs of research papers in diabetes from 31 European countries between 2002 and 2013, and their funding. Methods Diabetes research papers in the Web of Science were identified by means of a filter based on journals and title words. For 2009-2013 papers, the funders were coded to show their sector and nationality. Results Europe published 40 547 diabetes papers in the 12 years between 2002 and 2013. Denmark, Sweden and Finland published the most relative to their wealth, but the UK published the most absolutely despite an apparently low burden (as measured by disability-adjusted life years). The largest source of funding was government (30%), followed by the non-profit sector (18%) and industry (13%). The European Commission supported 2.7% of papers, but more in Latvia (33%) and Estonia (16%). Based on an estimated cost per paper of €260 000, the annual research expenditure in Europe was approximately €986 million in 2013. Conclusions The European diabetes burden in disability-adjusted life years increased by one third between 2002 and 2012, but its output of research papers has decreased from 44% to 36% of the world total. This decrease needs to be reviewed in the context of European non-communicable disease research policy.
Objectives: Surgical bleeding can become problematic depending on factors such as bleeding intens... more Objectives: Surgical bleeding can become problematic depending on factors such as bleeding intensity, anatomic location, and coagulation status. Problematic surgical bleeding is frequently associated with important clinical and cost burden. The objective of this study was to conduct a hospital budget impact analysis of a novel fibrin sealant matrix (EVARREST®) versus standard of care (SoC) in severe soft-tissue surgical bleeding in France. MethOds: A hospital budget impact model quantified 30-day cost impact of EVARREST® in France. The severe soft-tissue bleeding trial (n= 91) collected resources including quantity of initial treatment, re-treatment, surgery time, transfusions, and hospitalization (including ICU and ward stay). SoC was composed of oxidized regenerated cellulose (88%) and conventional methods such as manual compression. The surgical analysis included resources clinically related to the significant hemostasis benefit of EVARREST® vs. SoC (i.e., initial and re-treatment, operating time, transfusion). A hospital analysis included all resources collected. Published France unit costs were applied to resource use. Value-added tax was added to product costs. A subgroup analysis (n= 19) was conducted in potentially coagulopathic patients of the trial, defined as those meeting criteria for abnormal coagulation parameters. Results: In severe soft-tissue bleeding, the analysis predicted that the cost of EVARREST® was substantially offset by averted resources, leading to an overall cost impact of only € 771 (hospital analysis) to € 1,496 (surgical analysis) per patient. In the subgroup analysis of potentially coagulopathic patients, EVARREST® no longer had a cost impact, rather was predicted to be cost saving in both the surgical (€ 730) and hospital (€ 2,368) analyses versus SoC. cOnclusiOns: This analysis of a severe soft-tissue bleeding trial predicts EVARREST® may result in important cost efficiencies for hospitals compared with SoC. The findings suggest results may depend on bleeding type, with increased benefit predicted in more problematic (i.e., potentially coagulopathic) bleeding situations. Further study is needed to confirm findings.
orthopedics (2) and other indications (5). 79% (23/29) were positive recommendations; 96% (22/23)... more orthopedics (2) and other indications (5). 79% (23/29) were positive recommendations; 96% (22/23) of which included cost-saving claims, with the sole exception being based on comparable resource utilization. Nevertheless, for the 6 not recommended appraisals, the level of clinical evidence was cited as key. ConClusions: To date, relatively few devices have been appraised under MTEP. Outcomes have been mostly positive but, unlike Technology Appraisal Guidance, MTEP guidance is non-binding. Importantly, being cost-saving is a criteria for consideration under MTEP, precluding inclusion of high-cost innovative technologies for which timely access may be particularly challenging. France has a national assessment body (CNEDiMTS) targeted to the appraisal of new/innovative medical technologies, which may form a better model for involvement of national appraisal bodies in device reimbursement.
A729 oncologists in a two-round Delphi survey both, from the NHS and the society perspective. Uni... more A729 oncologists in a two-round Delphi survey both, from the NHS and the society perspective. Unit costs were obtained from national databases. Direct costs included medication and healthcare resources costs (including visits, tests, hospitalizations, surgery, adverse events management and treatment of specific metastases). Indirect costs were estimated using the human-capital approach. Direct and total costs were described for patients with LR and/or MR and for an average patient from a hypothetical cohort of individuals with a BC recurrence. Uncertainties were explored in an univariate sensitivity-analysis. Results: Within a 100-patients'cohort, 7 would have an LR, 90 an MR, and 3 an LR followed by an MR. All patients with an LR would receive targeted therapies combinations. Patients estimated to have an MR received up to 5 treatment lines (5% no treatment; 10%:1L; 13%:2L; 20%:3L; 21%:4L and 31%:5L). Tthe most common treatments in each line were pertuzumabtrastuzumab-taxane (1L), trastuzumab emtansine (2L), lapatinib-capecitabine (3L) and trastuzumab combinations (4-5L). Depending on the type of recurrence and the number of lines received, estimated direct and total costs per patient ranged between € 38,511 (1L) and € 308,869 (5L); total costs between € 50,908 and € 358,000. Direct and total costs for an average patient were € 208,682 and € 235,138 respectively. ConClusions: Direct and indirect costs of treating recurrences need to be integrated in the cost-analysis involving the incorporation or novel targeted agents in the early BC setting to prevent recurrence. Strategies reducing the recurrences risk such as targeted therapies in earlier stages of HER2+ BC would result in significant economic savings for the Spanish NHS and the society.
A767 with poor survival prospects, with mean survival estimates ranging from 5.0-12.7 months. Con... more A767 with poor survival prospects, with mean survival estimates ranging from 5.0-12.7 months. ConClusions: Whilst the approach adopted does not adjust for differences in trial patient populations and is particularly data-intensive, use of such sophisticated methods of evidence synthesis may be more informative for subsequent costeffectiveness modelling and may have greater impact when considering an indication where observed data is particularly immature or survival prospects are more positive, which may then lead to more informative decision-making for drug reimbursement.
Background Nonfatal myocardial infarction (MI) is commonly included as an endpoint in studies of ... more Background Nonfatal myocardial infarction (MI) is commonly included as an endpoint in studies of treatment or prevention of coronary artery disease driven by the assumption that MI is a surrogate for downstream mortality and that preventing MI will reduce mortality. Though biologically plausible and frequently associated in epidemiological studies, the validity of MI as a surrogate marker for all-cause mortality in randomized controlled trials (RCTs) has not been previously demonstrated with trial-level meta-analytic evidence. Purpose To assess MI as a surrogate endpoint for all-cause mortality in RCTs Methods In December 2020, PubMed was searched for all RCTs reporting all-cause mortality and MI published in the New England Journal of Medicine, the Lancet, or the Journal of the American Medical Association. RCTs with a minimum sample size of 1000 patients and 24 months of follow up were included. Trial-level correlation between MI and all-cause mortality was then assessed for surro...
To investigate whether joint modelling of two candidate surrogate endpoints, the tumour response ... more To investigate whether joint modelling of two candidate surrogate endpoints, the tumour response (TR) and progression free survival (PFS), improves their predictive value of the final clinical endpoint, the overall survival (OS), in advanced colorectal cancer. Study Design and Setting: Data were obtained from a systematic review of randomised control trials investigating effectiveness of a broad range of pharmacological therapies in advanced colorectal cancer. The treatments included systemic chemotherapies, antiepidermal growth factor receptor (anti-EGFR) therapies, anti-angiogenic agents, other multi-targeted antifolate (MTA) treatments and intra-hepatic arterial chemotherapy (IHA). Multivariate meta-analysis was used to model the association patterns between treatment effects on the surrogate endpoints (PFS and TR) and the final outcome (OS). The surrogate relationships were explored by the use of regression parameters (intercept, slope and conditional variance) and adjusted R-squared. Analyses were conducted on data from all trials reporting relevant outcomes and in subgroups defined by the type of therapy. Results: Analysis of 33 trials which reported treatment effects on all three outcomes (TR, PFS and OS) showed that there was association between treatment effects on OS and the treatment effect on both candidate surrogate endpoints, TR and PFS, when modelled individually and jointly. The surrogate association was particularly strong between treatment effect on PFS and OS, with the positive slope 0.28 (95% CrI: 0.12, 0.45) and relatively small conditional variance 0.003 (95% CrI: 0.00, 0.01). The adjusted R-square was also relatively high but obtained with a large uncertainty; 0.66 (0.2, 0.97). This relationship was not improved by inclusion of the treatment effect on the second surrogate
Background: Trans-arterial radio-embolization (TARE) is an emerging treatment for the management ... more Background: Trans-arterial radio-embolization (TARE) is an emerging treatment for the management of hepatocellular carcinoma (HCC). TARE may compete with systemic chemotherapy, sorafenib, in intermediate stage patients with prior chemoembolization failure or advanced patients with tumoral macrovascular invasion with no extra-hepatic spread and good liver function. We performed a budget impact analysis (BIA) evaluating the expected changes in the expenditure for the Italian Healthcare Service within scenarios of increased utilization of TARE in place of sorafenib over the next five years. Methods: Starting from patient level data from three oncology centres in Italy, a Markov model was developed to project on a lifetime horizon survivals and costs associated to matched cohorts of intermediate-advanced HCC patients treated with TARE or sorafenib. The initial model has been integrated with epidemiological data to perform a BIA comparing the current scenario with 20 and 80% utilization rates for TARE and sorafenib, respectively, with increasing utilization rates of TARE of 30, 40 and 50% over the next 1, 3 and 5 years. Results: Compared to the current scenario, progressively increasing utilization rates of TARE over sorafenib in the next 5 years is expected to save globally about 7 million Euros. Conclusions: Radioembolization can be considered a valuable treatment option for patients with intermediateadvanced HCC. These findings enrich the evidence about the economic sustainability of TARE in comparison to standard systemic chemotherapy within the context of a national healthcare service.
Aim This study examined the outputs of research papers in diabetes from 31 European countries bet... more Aim This study examined the outputs of research papers in diabetes from 31 European countries between 2002 and 2013, and their funding. Methods Diabetes research papers in the Web of Science were identified by means of a filter based on journals and title words. For 2009-2013 papers, the funders were coded to show their sector and nationality. Results Europe published 40 547 diabetes papers in the 12 years between 2002 and 2013. Denmark, Sweden and Finland published the most relative to their wealth, but the UK published the most absolutely despite an apparently low burden (as measured by disability-adjusted life years). The largest source of funding was government (30%), followed by the non-profit sector (18%) and industry (13%). The European Commission supported 2.7% of papers, but more in Latvia (33%) and Estonia (16%). Based on an estimated cost per paper of €260 000, the annual research expenditure in Europe was approximately €986 million in 2013. Conclusions The European diabetes burden in disability-adjusted life years increased by one third between 2002 and 2012, but its output of research papers has decreased from 44% to 36% of the world total. This decrease needs to be reviewed in the context of European non-communicable disease research policy.
Objectives: Surgical bleeding can become problematic depending on factors such as bleeding intens... more Objectives: Surgical bleeding can become problematic depending on factors such as bleeding intensity, anatomic location, and coagulation status. Problematic surgical bleeding is frequently associated with important clinical and cost burden. The objective of this study was to conduct a hospital budget impact analysis of a novel fibrin sealant matrix (EVARREST®) versus standard of care (SoC) in severe soft-tissue surgical bleeding in France. MethOds: A hospital budget impact model quantified 30-day cost impact of EVARREST® in France. The severe soft-tissue bleeding trial (n= 91) collected resources including quantity of initial treatment, re-treatment, surgery time, transfusions, and hospitalization (including ICU and ward stay). SoC was composed of oxidized regenerated cellulose (88%) and conventional methods such as manual compression. The surgical analysis included resources clinically related to the significant hemostasis benefit of EVARREST® vs. SoC (i.e., initial and re-treatment, operating time, transfusion). A hospital analysis included all resources collected. Published France unit costs were applied to resource use. Value-added tax was added to product costs. A subgroup analysis (n= 19) was conducted in potentially coagulopathic patients of the trial, defined as those meeting criteria for abnormal coagulation parameters. Results: In severe soft-tissue bleeding, the analysis predicted that the cost of EVARREST® was substantially offset by averted resources, leading to an overall cost impact of only € 771 (hospital analysis) to € 1,496 (surgical analysis) per patient. In the subgroup analysis of potentially coagulopathic patients, EVARREST® no longer had a cost impact, rather was predicted to be cost saving in both the surgical (€ 730) and hospital (€ 2,368) analyses versus SoC. cOnclusiOns: This analysis of a severe soft-tissue bleeding trial predicts EVARREST® may result in important cost efficiencies for hospitals compared with SoC. The findings suggest results may depend on bleeding type, with increased benefit predicted in more problematic (i.e., potentially coagulopathic) bleeding situations. Further study is needed to confirm findings.
orthopedics (2) and other indications (5). 79% (23/29) were positive recommendations; 96% (22/23)... more orthopedics (2) and other indications (5). 79% (23/29) were positive recommendations; 96% (22/23) of which included cost-saving claims, with the sole exception being based on comparable resource utilization. Nevertheless, for the 6 not recommended appraisals, the level of clinical evidence was cited as key. ConClusions: To date, relatively few devices have been appraised under MTEP. Outcomes have been mostly positive but, unlike Technology Appraisal Guidance, MTEP guidance is non-binding. Importantly, being cost-saving is a criteria for consideration under MTEP, precluding inclusion of high-cost innovative technologies for which timely access may be particularly challenging. France has a national assessment body (CNEDiMTS) targeted to the appraisal of new/innovative medical technologies, which may form a better model for involvement of national appraisal bodies in device reimbursement.
A729 oncologists in a two-round Delphi survey both, from the NHS and the society perspective. Uni... more A729 oncologists in a two-round Delphi survey both, from the NHS and the society perspective. Unit costs were obtained from national databases. Direct costs included medication and healthcare resources costs (including visits, tests, hospitalizations, surgery, adverse events management and treatment of specific metastases). Indirect costs were estimated using the human-capital approach. Direct and total costs were described for patients with LR and/or MR and for an average patient from a hypothetical cohort of individuals with a BC recurrence. Uncertainties were explored in an univariate sensitivity-analysis. Results: Within a 100-patients'cohort, 7 would have an LR, 90 an MR, and 3 an LR followed by an MR. All patients with an LR would receive targeted therapies combinations. Patients estimated to have an MR received up to 5 treatment lines (5% no treatment; 10%:1L; 13%:2L; 20%:3L; 21%:4L and 31%:5L). Tthe most common treatments in each line were pertuzumabtrastuzumab-taxane (1L), trastuzumab emtansine (2L), lapatinib-capecitabine (3L) and trastuzumab combinations (4-5L). Depending on the type of recurrence and the number of lines received, estimated direct and total costs per patient ranged between € 38,511 (1L) and € 308,869 (5L); total costs between € 50,908 and € 358,000. Direct and total costs for an average patient were € 208,682 and € 235,138 respectively. ConClusions: Direct and indirect costs of treating recurrences need to be integrated in the cost-analysis involving the incorporation or novel targeted agents in the early BC setting to prevent recurrence. Strategies reducing the recurrences risk such as targeted therapies in earlier stages of HER2+ BC would result in significant economic savings for the Spanish NHS and the society.
A767 with poor survival prospects, with mean survival estimates ranging from 5.0-12.7 months. Con... more A767 with poor survival prospects, with mean survival estimates ranging from 5.0-12.7 months. ConClusions: Whilst the approach adopted does not adjust for differences in trial patient populations and is particularly data-intensive, use of such sophisticated methods of evidence synthesis may be more informative for subsequent costeffectiveness modelling and may have greater impact when considering an indication where observed data is particularly immature or survival prospects are more positive, which may then lead to more informative decision-making for drug reimbursement.
Background Nonfatal myocardial infarction (MI) is commonly included as an endpoint in studies of ... more Background Nonfatal myocardial infarction (MI) is commonly included as an endpoint in studies of treatment or prevention of coronary artery disease driven by the assumption that MI is a surrogate for downstream mortality and that preventing MI will reduce mortality. Though biologically plausible and frequently associated in epidemiological studies, the validity of MI as a surrogate marker for all-cause mortality in randomized controlled trials (RCTs) has not been previously demonstrated with trial-level meta-analytic evidence. Purpose To assess MI as a surrogate endpoint for all-cause mortality in RCTs Methods In December 2020, PubMed was searched for all RCTs reporting all-cause mortality and MI published in the New England Journal of Medicine, the Lancet, or the Journal of the American Medical Association. RCTs with a minimum sample size of 1000 patients and 24 months of follow up were included. Trial-level correlation between MI and all-cause mortality was then assessed for surro...
To investigate whether joint modelling of two candidate surrogate endpoints, the tumour response ... more To investigate whether joint modelling of two candidate surrogate endpoints, the tumour response (TR) and progression free survival (PFS), improves their predictive value of the final clinical endpoint, the overall survival (OS), in advanced colorectal cancer. Study Design and Setting: Data were obtained from a systematic review of randomised control trials investigating effectiveness of a broad range of pharmacological therapies in advanced colorectal cancer. The treatments included systemic chemotherapies, antiepidermal growth factor receptor (anti-EGFR) therapies, anti-angiogenic agents, other multi-targeted antifolate (MTA) treatments and intra-hepatic arterial chemotherapy (IHA). Multivariate meta-analysis was used to model the association patterns between treatment effects on the surrogate endpoints (PFS and TR) and the final outcome (OS). The surrogate relationships were explored by the use of regression parameters (intercept, slope and conditional variance) and adjusted R-squared. Analyses were conducted on data from all trials reporting relevant outcomes and in subgroups defined by the type of therapy. Results: Analysis of 33 trials which reported treatment effects on all three outcomes (TR, PFS and OS) showed that there was association between treatment effects on OS and the treatment effect on both candidate surrogate endpoints, TR and PFS, when modelled individually and jointly. The surrogate association was particularly strong between treatment effect on PFS and OS, with the positive slope 0.28 (95% CrI: 0.12, 0.45) and relatively small conditional variance 0.003 (95% CrI: 0.00, 0.01). The adjusted R-square was also relatively high but obtained with a large uncertainty; 0.66 (0.2, 0.97). This relationship was not improved by inclusion of the treatment effect on the second surrogate
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