Thirdly, assuming no patient switch after discontinuation of initial treatment yielded to an incremental ratio of 5,507 per QALY gained while the opposite scenario assuming all patients switch, yielded to an incremental ratio of 6,228 per QALY gained. life-years (QALY) and life-years (LY) gained, incremental cost per QALY, and incremental cost per LY. Sensitivity analyses were performed to test the robustness of the model and to better understand the results drivers. Results In the base-case analysis, the incremental total cost was 714 and the total incremental QALYs and LYs were 0.12 and 0.16, respectively. The resulting incremental cost/QALY and incremental cost/LY were 6,006 and 4,586, respectively. The results were more sensitive to the inclusion of treatment-specific utility decrements and clinical event rates. Conclusions Although there is no official willingness-to-pay threshold in France, these results suggest that rivaroxaban is likely to be cost-effective compared to VKA in French patients with AF from a national insurance perspective. Introduction/Background Atrial fibrillation (AF) is a cardiac arrhythmia with structural and/or electrophysiological abnormalities that induce remodelling in the atria; it is the most common cardiac arrhythmia [1C3]. Worldwide, an estimated 3% of adults aged 20 years or older suffer from AF, approximately 20.9 million men and 12.6 million women [2]. Due to the aging of the population, the worldwide prevalence is predicted to at least double in many countries during the next several decades [4, 5]. AF is associated with substantial morbidity and mortality [2]. Compared to otherwise healthy individuals, men and women with AF are at a 1. 5-fold and 2-fold increased risk for all-cause mortality, respectively [2], and the risk for strokes increased by 2-to-7-fold [4]. Strokes are associated with significant financial burden [6]; in 2015, the total costs of stroke care in the European Union (EU) was estimated to be 45 billion euros [7]. It is expected that between 2015 and 2035, there will be a 34% increase in total number of stroke events in the European Union [7]. Oral anticoagulants including vitamin K antagonists (VKAs) or non-VKA oral anticoagulants (NOACs) such as rivaroxaban, dabigatran, apixaban, and edoxaban, have been established as a cornerstone of management in patients with AF and to reduce stroke incidence and mortality [2] in randomized clinical trials (RCTs) [2]. Many uncertainties remain regarding the relevance of the results of RCTs in a real-world setting. Real-world evidence (RWE) may provide additional information to decision-makers [8]. Indeed, RWE sample size is not limited as it is the case of RCTs. RCTs have to respect inclusion/exclusion criteria regarding population selection. Also, RWE can offer long-term outcomes while the timeframe of RCT is usually shorter with only a few outcomes [9]. A meta-analysis comparing NOACs with VKAs and reporting effectiveness, safety, and persistence using RWE has recently been published [10]. It confirmed the findings of rivaroxaban pivotal RCT [11] and concluded that rivaroxaban is a suitable alternative to VKAs in routine clinical practice. Health Technology Assessment (HTA) agencies are frequently requesting manufacturers to prove the benefits of their health technology in the real-world, not only in terms of clinical RWE but also in terms of RWE cost-effectiveness. Indeed, RWE is of interest since it reflects more closely what happens in a real-world setting. While many initial protection and reimbursement decisions are based on cost-effectiveness models using RCT effectiveness and security data, the use of RWE can provide more realistic estimations of cost-effectiveness based on how the drug is being used in medical practice, its performance, safety, and connected costs. The availability of a RWE meta-analysis provides a good opportunity to evaluate the RWE cost-effectiveness of rivaroxaban compared to VKAs for the prevention of stroke in individuals with AF. In France, NOACs are acknowledged as an important component of the national stroke strategy, but there is an increasing scrutiny regarding the cost of these treatments; consequently, a French national healthcare insurance (NHI) perspective was regarded as relevant to.Individuals enter the model initiating a first-line treatment with either rivaroxaban or VKA, and could progress between health claims according to transition probabilities. VKA. Model results included costs (drug costs, medical event costs, and VKA monitoring costs), quality-adjusted life-years (QALY) and life-years (LY) gained, incremental cost per QALY, and incremental cost per LY. Level of sensitivity analyses were performed to test the robustness of the model and to better understand the results drivers. Results In the base-case analysis, the incremental total cost was 714 and the total incremental QALYs and LYs were 0.12 and 0.16, respectively. The producing incremental cost/QALY and incremental cost/LY were 6,006 and 4,586, respectively. The results were more sensitive to the inclusion of treatment-specific energy decrements and medical event rates. Conclusions Although there is no established willingness-to-pay threshold in France, these results suggest that rivaroxaban is likely to be cost-effective compared to VKA FM19G11 in French individuals with AF from a national insurance perspective. Intro/Background Atrial fibrillation (AF) is definitely a cardiac arrhythmia with structural and/or electrophysiological abnormalities that induce remodelling in the atria; it is the most common cardiac arrhythmia [1C3]. Worldwide, an estimated 3% of adults aged 20 years or older suffer from AF, approximately 20.9 million men and 12.6 million ladies [2]. Due to the ageing of the population, the worldwide prevalence is expected to at least double in many countries during the next several decades [4, 5]. AF is definitely associated with considerable morbidity and mortality [2]. Compared to normally healthy individuals, men and women with AF are at a 1.5-fold and 2-fold increased risk for all-cause mortality, respectively [2], and the risk for strokes increased by 2-to-7-fold [4]. Strokes are associated with significant monetary burden [6]; in 2015, the total costs of stroke care in the European Union (EU) was estimated to be 45 billion euros [7]. It is expected that between 2015 and 2035, there will be a 34% increase in total number of stroke events in the European Union [7]. Dental anticoagulants including vitamin K antagonists (VKAs) or non-VKA oral anticoagulants (NOACs) such as rivaroxaban, dabigatran, apixaban, and edoxaban, have been established like a cornerstone of management in individuals with AF and to reduce stroke incidence and mortality [2] in randomized medical tests (RCTs) [2]. Many uncertainties remain concerning the relevance of the results of RCTs inside a real-world establishing. Real-world evidence (RWE) may provide additional information to decision-makers [8]. Indeed, RWE sample size is not limited as it is the case of RCTs. RCTs have to respect inclusion/exclusion criteria concerning human population selection. Also, RWE can offer long-term results while the timeframe of RCT is usually shorter with only a few results [9]. A meta-analysis evaluating NOACs with VKAs and confirming effectiveness, basic safety, and persistence using RWE has been released [10]. It verified the results of rivaroxaban pivotal RCT [11] and figured rivaroxaban is the right option to VKAs in regular scientific practice. Wellness Technology Evaluation (HTA) agencies are generally requesting producers to prove the advantages of their wellness technology in the real-world, not merely with regards to scientific RWE but also with regards to RWE cost-effectiveness. Certainly, RWE is normally of interest because it shows more closely what goes on within a real-world placing. While many preliminary insurance and reimbursement decisions derive from cost-effectiveness versions using RCT efficiency and basic safety data, the usage of RWE can offer more realistic quotes of cost-effectiveness predicated on how the medication is being found in scientific practice, its efficiency, safety, and linked costs. The option of a RWE meta-analysis offers a good possibility to measure the RWE cost-effectiveness of rivaroxaban in comparison to VKAs for preventing stroke in sufferers with AF. In France, NOACs are known as an important element of the nationwide heart stroke program, but there can be an raising scrutiny regarding the expense of these remedies; as a result, a French nationwide health care insurance (NHI) perspective was regarded highly relevant to demonstrate the real-world worth of the therapies. Strategies Model strategy An already released Markov cost-effectiveness model [12] was modified to measure the incremental costs and wellness final results of rivaroxaban in comparison to VKA in sufferers with AF in real-world configurations (Fig 1). Sufferers enter the model initiating a first-line treatment with either rivaroxaban or VKA, and may progress between wellness states regarding to changeover probabilities. Health state governments included steady AF, severe and post main ischaemic stroke (Is normally), post and severe minimal Is normally, severe and post myocardial infarction (MI), severe and post intracranial haemorrhage (ICH), gastrointestinal (GI) bleed, and loss of life. Sufferers were in a threat of a meeting always; nevertheless, the model assumed that only 1 event could take place.2015 [16]Post key IS8.12%[7.35%; 8.92%]Beta (390; 4,410)Lip et al. and LYs had been 0.12 and 0.16, respectively. The causing incremental price/QALY and incremental price/LY had been 6,006 and 4,586, respectively. The outcomes were more delicate towards the inclusion of treatment-specific tool decrements and scientific event prices. Conclusions Although there is absolutely no public willingness-to-pay threshold in France, these outcomes claim that rivaroxaban may very well be cost-effective in comparison to VKA in French sufferers with AF from a nationwide insurance perspective. Launch/History Atrial fibrillation (AF) is normally a cardiac arrhythmia with structural and/or electrophysiological abnormalities that creates remodelling in the atria; it’s the most common cardiac arrhythmia [1C3]. Worldwide, around 3% of adults aged twenty years or old have problems with AF, around 20.9 million men and 12.6 million females [2]. Because of the maturing of the populace, the world-wide prevalence is forecasted to at least dual in lots of countries through the following several years [4, 5]. AF is certainly associated with significant morbidity and mortality [2]. In comparison to in any other case healthful individuals, women and men with AF are in a 1.5-fold and 2-fold improved risk for all-cause mortality, respectively [2], and the chance for strokes improved by 2-to-7-fold [4]. Strokes are connected with significant economic burden [6]; in 2015, the full total costs of heart stroke care in europe (European union) was approximated to become 45 billion euros [7]. It really is anticipated that between 2015 and 2035, you will see a 34% upsurge in final number of heart stroke events in europe [7]. Mouth anticoagulants including supplement K antagonists (VKAs) or non-VKA dental anticoagulants (NOACs) such as for example rivaroxaban, dabigatran, apixaban, and edoxaban, have already been established being a cornerstone of administration in sufferers with AF also to decrease stroke occurrence and mortality FM19G11 [2] in randomized scientific studies (RCTs) [2]. Many uncertainties stay about the relevance from the outcomes of RCTs within a real-world placing. Real-world proof (RWE) might provide more information to decision-makers [8]. Certainly, RWE test size isn’t limited since it may be the case of RCTs. RCTs need to respect addition/exclusion criteria relating to inhabitants selection. Also, RWE can provide long-term final results as the timeframe of RCT is normally shorter with just a few final results [9]. A meta-analysis evaluating NOACs with VKAs and confirming effectiveness, protection, and persistence using RWE has been released [10]. It verified the results of rivaroxaban pivotal RCT [11] and figured rivaroxaban is the right option to VKAs in regular scientific practice. Wellness Technology Evaluation (HTA) agencies are generally requesting producers to prove the advantages of their wellness technology in the real-world, not merely with regards to scientific RWE but also with regards to RWE cost-effectiveness. Certainly, RWE is certainly of interest because it demonstrates more closely what goes on within a real-world placing. While many preliminary insurance coverage and reimbursement decisions derive from cost-effectiveness versions using RCT efficiency and protection data, the usage of RWE can offer more realistic quotes of cost-effectiveness predicated on how the medication is being found in scientific practice, its efficiency, safety, and linked costs. The option of a RWE meta-analysis offers a good possibility to measure the RWE cost-effectiveness of rivaroxaban in comparison to VKAs for preventing stroke in sufferers with AF. In France, NOACs are known as an important element of the nationwide heart stroke program, but there can be an raising scrutiny regarding the expense of these remedies; as a result, a French national healthcare insurance (NHI) perspective was.2019 [10] applied to tree-month probabilities of VKA armMajor IS0.180%
(HR: 0.83)[0.163%; 0.202%]
(HR: [0.75;0.93])Beta (343; 185,544)MI0.185%
(HR: 0.96)[0.154%; 0.220%]
(HR: [0.80;1.14])Beta (135; 73,678)GI bleed0.495%
(HR: 1.22)[0.455%; 0.540%]
(HR: [1.12;1.33])Beta (472; 94,947)ICH0.137%
(HR: 0.69)[0.104%; 0.179%]
(HR: [0.52;0.90])Beta (69; 51,161)Discontinuation????0C3 months18.04%
(HR: 0.62)[17.46%; 18.92%]
(HR: [0.60;0.65])Beta (1462; 6,268)????3C6 months10.58%
(HR: 0.62)[10.24%; 11.09%]
(HR: [0.60;0.65])Beta (1603; 12,849)????6C12 months9.60%
(HR: 0.62)[9.29%; 10.06%]
(HR: [0.60;0.65])Beta (1622; 14,492)????12+ months6.74%
(HR: 0.62)[6.53%; 7.07%]
(HR: [0.60;0.65])Beta (1676; 22,032)Proportion of switch among discontinued patients12.00%[7.64%; 16.36%]Beta (25; 187)Collings et al. to VKA. Model outcomes included costs (drug costs, clinical event costs, and VKA monitoring costs), quality-adjusted life-years (QALY) and life-years (LY) gained, incremental cost per QALY, and incremental cost per LY. Sensitivity analyses were performed to test the robustness of the model and to better understand the results drivers. Results In the base-case analysis, the incremental total cost was 714 and the total incremental QALYs and LYs were 0.12 and 0.16, respectively. The resulting incremental cost/QALY and incremental cost/LY were 6,006 and 4,586, respectively. The results were more sensitive to the inclusion of treatment-specific utility decrements and clinical event rates. Conclusions Although there is no official willingness-to-pay threshold in France, these results suggest that rivaroxaban is likely to be cost-effective compared to VKA in French patients with AF from a national insurance perspective. Introduction/Background Atrial fibrillation (AF) is a cardiac arrhythmia with structural and/or electrophysiological abnormalities that induce remodelling in the atria; it is the most common cardiac arrhythmia [1C3]. Worldwide, an estimated 3% of adults aged 20 years or older suffer from AF, approximately 20.9 million men and 12.6 million women [2]. Due to the aging of the population, the worldwide prevalence is predicted to at least double in many countries during the next several decades [4, 5]. AF is associated with substantial morbidity and mortality [2]. Compared to otherwise healthy individuals, men and women with AF are at a 1.5-fold and 2-fold increased risk for all-cause mortality, respectively [2], and the risk for strokes increased by 2-to-7-fold [4]. Strokes are associated with significant financial burden [6]; in 2015, the total costs of stroke care in the European Union (EU) was estimated to be 45 billion euros [7]. It is expected that between 2015 and 2035, there will be a 34% increase in total number of stroke events in the European Union [7]. Oral anticoagulants including vitamin K antagonists (VKAs) or non-VKA oral anticoagulants (NOACs) such as rivaroxaban, dabigatran, apixaban, and edoxaban, have been established as a cornerstone of management in patients with AF and to reduce stroke incidence and mortality [2] in randomized CSF2RA clinical trials (RCTs) [2]. Many uncertainties remain regarding the relevance of the results of RCTs in a real-world setting. Real-world evidence (RWE) may provide additional information to decision-makers [8]. Indeed, RWE sample size is not limited as it is the case of RCTs. RCTs have to respect inclusion/exclusion criteria regarding population selection. Also, RWE can offer long-term outcomes while the timeframe of RCT is usually shorter with only a few outcomes [9]. A meta-analysis comparing NOACs with VKAs and reporting effectiveness, safety, and persistence using RWE has recently been published [10]. It confirmed the findings of rivaroxaban pivotal RCT [11] and concluded that rivaroxaban is a suitable alternative to VKAs in routine clinical practice. Health Technology Assessment (HTA) agencies are frequently requesting manufacturers to prove the benefits of their health technology in the real-world, not only in terms of clinical RWE but also in terms of RWE cost-effectiveness. Indeed, RWE is definitely of interest since it displays more closely what happens inside a real-world establishing. While many initial protection and reimbursement decisions are based on cost-effectiveness models using RCT effectiveness and security data, the use of RWE can provide more realistic estimations of cost-effectiveness based on how the drug is being used in medical practice, its performance, safety, and connected costs. The availability of a RWE meta-analysis provides a good opportunity to evaluate the RWE cost-effectiveness of rivaroxaban compared to VKAs for the prevention of stroke in individuals with AF. In France, NOACs are acknowledged as an important component of the national stroke strategy, but there is an increasing scrutiny regarding the cost of these treatments; consequently, a French national healthcare insurance (NHI) perspective was regarded as relevant to demonstrate the real-world value of these therapies. Methods Model approach An already published Markov cost-effectiveness model [12] was adapted to assess the incremental costs and health results of rivaroxaban compared to VKA in individuals with AF in real-world settings (Fig 1). Individuals enter the model initiating a first-line treatment with either rivaroxaban or VKA, and could progress between FM19G11 health states relating to transition probabilities. Health claims included stable AF, acute and post major ischaemic stroke (Is definitely), acute and post small IS, acute and post myocardial infarction (MI), acute and post intracranial haemorrhage (ICH), gastrointestinal (GI) bleed, and death. Individuals were constantly at a risk of an event; however, the model assumed that only one event could happen per cycle. Additionally, long term consequences of an event were regarded as until death or until the occurrence of a subsequent event with long-term effects..2014 [25], based on Cotte et al. costs (drug costs, medical event costs, and VKA monitoring costs), quality-adjusted life-years (QALY) and life-years (LY) gained, incremental cost per QALY, and incremental cost per LY. Level of sensitivity analyses were performed to test the robustness of the model and to better understand the results drivers. Results In the base-case analysis, the incremental total cost was 714 and the total incremental QALYs and LYs were 0.12 and 0.16, respectively. The producing incremental cost/QALY and incremental cost/LY were 6,006 and 4,586, respectively. The results were more sensitive to the inclusion of treatment-specific energy decrements and medical event rates. Conclusions Although there is no established willingness-to-pay threshold in France, these results suggest that rivaroxaban is likely to be cost-effective compared to VKA in French individuals with AF from a national insurance perspective. Intro/Background Atrial fibrillation (AF) is definitely a cardiac arrhythmia with structural and/or electrophysiological abnormalities that induce remodelling in the atria; it is the most common cardiac arrhythmia [1C3]. Worldwide, an estimated 3% of adults aged 20 years or older suffer from AF, approximately 20.9 million men and 12.6 million ladies [2]. Due to the ageing of the population, the worldwide prevalence is expected to at least double in many countries during the next several decades [4, 5]. AF is definitely associated with considerable morbidity and mortality [2]. Compared to normally healthy individuals, men and women with AF are at a 1.5-fold and 2-fold increased risk for all-cause mortality, respectively [2], and the risk for strokes increased by 2-to-7-fold [4]. Strokes are associated with significant financial burden [6]; in 2015, the total costs of stroke care in the European Union (EU) was estimated to be 45 billion euros [7]. It is expected that between 2015 and 2035, there will be a 34% increase in total number of stroke events in the European Union [7]. Oral anticoagulants including vitamin K antagonists (VKAs) or non-VKA oral anticoagulants (NOACs) such as rivaroxaban, dabigatran, apixaban, and edoxaban, have been established as a cornerstone of management in patients with AF and to reduce stroke incidence and mortality [2] in randomized clinical trials (RCTs) [2]. Many uncertainties remain regarding the relevance of the results of RCTs in a real-world setting. Real-world evidence (RWE) may provide additional information to decision-makers [8]. Indeed, RWE sample size is not limited as it is the case of RCTs. RCTs have to respect inclusion/exclusion criteria regarding populace selection. Also, RWE can offer long-term outcomes while the timeframe of RCT is usually shorter with only a few outcomes [9]. A meta-analysis comparing NOACs with VKAs and reporting effectiveness, safety, and persistence using RWE has recently been published [10]. It confirmed the findings of rivaroxaban pivotal RCT [11] and concluded that rivaroxaban is a suitable alternative to VKAs in routine clinical practice. Health Technology Assessment (HTA) agencies are frequently requesting manufacturers to prove the benefits of their health technology in the real-world, not only in terms of clinical RWE but also in terms of RWE cost-effectiveness. Indeed, RWE is usually of interest since it reflects more closely what happens in a real-world setting. While many initial coverage and reimbursement decisions are based on cost-effectiveness models using RCT efficacy and safety data, the use of RWE can provide more realistic estimates of cost-effectiveness based on how the drug is being used in clinical practice, its effectiveness, safety, and associated costs. The availability of a RWE meta-analysis provides a good opportunity FM19G11 to evaluate the RWE cost-effectiveness of rivaroxaban compared to VKAs for the prevention of stroke in patients with AF. In France, NOACs are acknowledged as an important component of the national stroke plan, but there is an increasing scrutiny regarding the cost of these therapies; therefore, a French national healthcare insurance (NHI) perspective was considered relevant to demonstrate the real-world value of these therapies. Methods Model approach An already published Markov cost-effectiveness model [12] was adapted to assess the incremental costs and health outcomes of rivaroxaban compared to VKA in patients with AF in real-world settings (Fig 1). Patients enter the model initiating a first-line treatment with either rivaroxaban or VKA, and could progress between health states according to changeover probabilities. Health areas included steady AF, severe and post main ischaemic stroke (Can be), severe and post small IS, severe and post myocardial infarction (MI), severe and post intracranial haemorrhage (ICH), gastrointestinal (GI) bleed, and loss of life. Individuals were often at a threat of an event; nevertheless, the model assumed that only 1 event could happen per routine. Additionally, long-term consequences of a meeting were regarded as until loss of life or before occurrence of the following event with long-term outcomes. All individuals could either become on-treatment (rivaroxaban, preliminary VKA or additional VKA after a change) or off-treatment (once all remedies.