Background: Single-arm trial (SAT) data is increasingly reviewed for drug approvals by regulators and Health Technology Assessment (HTA) bodies. Supplementary data in the form of external comparators (ECs) can be used to provide clinical context to support these drug evaluations. In this study we characterized HTAs for SAT-based submissions, the use of supplementary EC data and outcomes from HTA review.Methods: HTA Accelerator database was used to describe SAT-based HTA submissions with decisions (2011-2019).Results: A total of 433 SAT-based HTA submissions were identified between 2011 and 2019 with a 13-fold increase during this period. Around 65%(283/433) were in oncology or hem-oncology. Around 52%(226/433) of submissions contained some type of EC data, including prior clinical trials (24%, 104) and real-world data (RWD) (20%, 87), but 40%(175) contained no EC data. The overall acceptance rate for SAT-based submissions was 48% and with RWD EC data acceptance was 59%. In the latest 5year period (2015-2019), use of RWD ECs increased 22% as a proportion of submissions per year, whereas, prior trial ECs decreased (-14%) and use of no EC remained stable (-2%). Between 2015 to 2017 and 2018 to 2019, acceptance rate for RWD ECs increased by 20% (41% in 2015-2017 to 61% in 2018-2019) whereas prior trial EC use decreased by 10% and no EC submissions decreased 16%. Of 226 submissions using ECs, only 29%(66) used an adjusted indirect treatment comparison method.Conclusions: SAT-based submissions to HTA bodies are rapidly evolving in terms of composition and acceptance. Types of EC and methodological approach used are important determinants of positive outcomes.
Background: Clostridium difficile is associated with 20–30% of cases of antibiotic-associated diarrhoea. The incidence of C. difficile infection (CDI) is higher in Ireland than in other countries in Europe, and it is associated with considerable morbidity. Previously recommended standard therapeutic options were vancomycin and metronidazole, but the macrocyclic antibiotic fidaxomicin has recently been recommended for use in adults with CDI in Ireland. Objectives: To perform a cost-utility analysis of fidaxomicin compared to oral metronidazole (used to treat initial non-severe disease and first non-severe recurrence) and oral vancomycin (used to treat severe disease and any non-severe recurrence beyond the first) for the treatment of CDI. Methods: A Markov model was used to determine the cost-utility of fidaxomicin in the treatment of all adult CDI patients (base case), patients with severe CDI and patients with initial CDI recurrences, respectively. Patients enter the model in the CDI health state and are treated either with fidaxomicin or current standard of care (oral metronidazole for non-severe CDI; vancomycin for severe CDI) for 10 days. The time horizon was 1 year. Deterministic and probabilistic sensitivity analyses were performed. Health state utilities were derived from the literature. The perspective was that of the Irish Health Service Executive (HSE). Results: In the base case, fidaxomicin was dominant to current standard-of-care therapy, with cost savings of €2,904 and incremental quality-adjusted life year (QALY) gain of 0.031. The main drivers of costeffectiveness were recurrence rates and cost of hospitalization. Fidaxomicin was also dominant for all patient subgroups. The probability of fidaxomicin being cost-effective in all patients with CDI at a willingness to pay threshold of €45,000 per QALY gained was 82%. Conclusion: Fidaxomicin was dominant to the current standard-of-care therapy for CDI. Based on this analysis, fidaxomicin has received reimbursement for CDI treatment under the High Tech Drug Scheme in Ireland.
Objectives: Untreated hepatitis C virus (HCV) infection results in chronic liver disease. The prevalence in The Netherlands is estimated at 0.1-0.4% with 50% of patients having HCV genotype 1 (GT1). Sofosbuvir (SOF), a novel Direct Antiviral Agent (DAA), reached high rates of sustained virological response (SVR) when given with pegylated interferon-α and ribavirin (PegIFN-α /RBV) in chronic HCV (all genotypes). This study compares the costs per successfully treated patient with sofosbuvir compared to current standard of care (SoC) in the Netherlands in treatment-naïve GT1 patients. MethOds: A Markov transition cost-utility model was used, reflecting efficacy and safety data from published RCTs with SOF+PegIFNα /RBV, PegIFN-α /RBV, telaprevir (TVR) +PegIFN-α /RBV and boceprevir (BOC) +PegIFN-α /RBV. Medical resource use is based on clinical guidelines and expert opinion. Costs include treatment costs, monitoring costs, costs for treatment of complications and adverse events. The model has a lifetime horizon and costs are discounted with 4% and outcomes with 1.5%. Successfully treated patients are defined as having an SVR. Results are presented for a treatment-naïve GT1 population. Results: The SVR rate for SOF ranged from 91.7% in non-cirrhotic patients to 80.1% in cirrhotic patients. This was 43.6% and 23.6% for PegIFN-α , 75.4% and 61.9% in TVR and 64.1% and 55% for BOC. Total treatment costs ranged from € 55,376 to € 70,336 for SOF (non-cirrhotic and cirrhotic), € 22,240 and € 44,751 for PegIFN-α , € 42,593 to € 60,071 for TVR and € 39,634 to € 57,647 for BOC. The costs per SVR varied from € 60.388 to € 87,050 for SOF (non-cirrhotic and cirrhotic), € 51,009 to € 189,623 for PegIFN-α , € 56,489 to € 97,045 for TVR and € 61,832 to € 104,813 for BOC. cOnclusiOns: The costs per successfully treated patient with sofosbuvir are comparable to current standard of care in GT1 treatment naive patients without cirrhosis and are lower than SoC in cirrhotic patients in The Netherlands.
SummaryIn the present study we have investigated the effect of a 100 mg single oral dose of a newly developed thromboxane A2 receptor antagonist on collagen-induced thrombogenesis in flowing human non-anticoagulated blood. Blood was drawn directly from an antecubital vein over immobilised collagen type III fibrils on a cover slip placed in a parallel-plate perfusion chamber. Shear rates at the collagen surface were characteristic for medium sized (650 s−1) and moderately stenosed (2,600 s−1) arteries. Blood-collagen interactions were morphologically quantified as platelet-collagen adhesion, fibrin deposition and thrombus volume. Activation peptides of coagulation, fibrinopeptide A (FPA), and of platelets, β-thromboglobulin (β-TG), were measured immediately distal to the perfusion chamber.HN-11500 ingestion reduced significantly the thrombus volume by 32% at 2,600 s−1, but not at 650 s−1. However, transmission electron microscopy revealed loosely packed and less degranulated platelets at 650 s−1. The β-TG plasma levels were also reduced at both shear rates by the HN-11500 ingestion. The platelet-collagen adhesion was significantly enhanced at both shear rates. This was apparently a consequence of higher platelet concentrations at the collagen surface, because fewer platelets were consumed by the thrombi after the drug ingestion. In contrast, the coagulation, as measured by fibrin deposition and FPA plasma levels, was not significantly affected by HN-11500.Thus, it appears that the thromboxane A2 receptor antagonist HN-11500 reduces the thrombotic response by primarily impairing the platelet function at arterial blood flow conditions, and particularly at high wall shear rates.
The treatment of mild to moderate psoriasis with a fixed calcipotriol/betamethasone combination is a more cost-effective treatment than a treatment with the single agents or tacalcitol monotherapy.
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