Economic impact of industry-sponsored clinical trials of pharmaceutical products in Austria.

Aims: Modern pharmaceutical product development is a long and complex process associated with significant investments by pharmaceutical companies. The innovative pharmaceutical industry accounts for the vast majority of expenditures in clinical trials of potential new pharmaceuticals and therefore generates economic activity within a country. The aim was to assess the far-reaching economic impact of industry-sponsored clinical-trials (ISCTs) of pharmaceutical products for the healthcare system and the national economy.Materials and methods: The study approach was based on three analytical steps. First, a survey among 15 pharmaceutical companies in Austria was conducted to evaluate the annual number of ISCTs subdivided according to trial phase, therapeutic areas and associated employees. Second, the monetary value of treatments performed in ISCTs was calculated based on a sample of clinical-trial protocols. Finally, the macroeconomic impact, measured in terms of value-added and jobs created by the conducted ISCTs, was calculated using Input-Output analysis by applying an extended Leontief-model.Results: The study demonstrated that €116.22 million spent in ISCTs generated a total value added of €144 million, €74 million direct, in 2018. Each year a medical treatment value of €100 million was financed through 463 ISCTs, with an average value of medical treatment of €37,068 per recruited patient. This represents a significant 0.3% of annual current health-expenditures. In summary, each Euro invested by the pharmaceutical industry in ISCTs generates €1.95 for the Austrian economy. ISCTs also created and secured employment in the extent of 2,021 full-time-equivalents, thus resulting in an employment multiplier of 1.66.Conclusions: In conclusion, conducting clinical-trials by pharmaceutical industry-beside its importance in its own domain-results in tangible benefits and a positive macroeconomic impact that contribute to the sustainability of the Austrian healthcare system by complementing its limited resources. Furthermore, it is a non-negligible factor in locational and industrial policy.

Hemostatic efficacy, safety, and pharmacokinetics of a recombinant von Willebrand factor in severe von Willebrand disease.

This phase 3 trial evaluated the safety and hemostatic efficacy of a recombinant von Willebrand factor (rVWF) for treatment of bleeds in severe von Willebrand disease (VWD). rVWF was initially administered together with recombinant factor VIII (rFVIII) and subsequently alone, as long as hemostatic factor VIII activity (FVIII : C) levels were maintained. Pharmacokinetics (PK) were evaluated in a randomized cross-over design (rVWF vs rVWF:rFVIII at 50 IU VWF:ristocetin cofactor activity [RCo]/kg). Bleed control for all treated bleeds (N = 192 bleeds in 22 subjects) was rated good or excellent (96.9% excellent; 119 of 122 minor, 59 of 61 moderate, and 6 of 7 major bleeds) on a 4-point scale (4 = none to 1 = excellent). A single infusion was effective in 81.8% of bleeds. Treatment success, defined as the number of subjects with a mean efficacy rating of <2.5, was 100%. The PK profile of rVWF was not influenced by rFVIII (mean VWF:RCo terminal half-life: 21.9 hours for rVWF and 19.6 hours for rVWF:rFVIII). FVIII : C levels increased rapidly after rVWF alone, with hemostatic levels achieved within 6 hours and sustained through 72 hours after infusion. Eight adverse events (AEs; 6 nonserious AEs in 4 subjects and 2 serious AEs [chest discomfort and increased heart rate, without cardiac symptomatology] concurrently in 1 subject) were associated with rVWF. There were no thrombotic events or severe allergic reactions. No VWF or FVIII inhibitors, anti-VWF binding antibodies, or antibodies against host cell proteins were detected. These results show that rVWF was safe and effective in treating bleeds in VWD patients and stabilizes endogenous FVIII : C, which may eliminate the need for rFVIII after the first infusion. This trial was registered at www.clinicaltrials.gov as #NCT01410227.

A prospective randomized study comparing fibrin sealant to manual compression for the treatment of anastomotic suture-hole bleeding in expanded polytetrafluoroethylene grafts.

OBJECTIVE: The ideal hemostatic agent for treatment of suture-line bleeding at vascular anastomoses has not yet been established. This study evaluated whether the use of a fibrin sealant containing 500 IU/mL thrombin and synthetic aprotinin (FS; marketed in the United States under the name TISSEEL) is beneficial for treatment of challenging suture-line bleeding at vascular anastomoses of expanded polytetrafluoroethylene (ePTFE) grafts, including those further complicated by concomitant antiplatelet therapies. METHODS: Over a 1-year period ending in 2010, ePTFE graft prostheses, including arterio-arterial bypasses and arteriovenous shunts, were placed in 140 patients who experienced suture-line bleeding that required treatment after completion of anastomotic suturing. Across 24 US study sites, 70 patients were randomized and treated with FS and 70 with manual compression (control). The primary end point was the proportion of patients who achieved hemostasis at the study suture line at 4 minutes after start of application of FS or positioning of surgical gauze pads onto the study suture line. RESULTS: There was a statistically significant difference in the comparison of hemostasis rates at the study suture line at 4 minutes between FS (62.9%) and control (31.4%) patients (P < .0001), which was the primary end point. Similarly, hemostasis rates in the subgroup of patients on antiplatelet therapies were 64.7% (FS group) and 28.2% (control group). When analyzed by bleeding severity, the hemostatic advantage of FS over control at 4 minutes was similar (27.8% absolute improvement for moderate bleeding vs 32.8% for severe bleeding). Logistic regression analysis (accounting for gender, age, intervention type, bleeding severity, blood pressure, heparin coating of ePTFE graft, and antiplatelet therapies) found a statistically significant treatment effect in the odds ratio (OR) of meeting the primary end point between treatment groups (OR, 6.73; P < .0001), as well as statistically significant effects for intervention type (OR, 0.25; P = .0055) and bleeding severity (OR, 2.59; P = .0209). The safety profile of FS was excellent as indicated by the lack of any related serious adverse events. CONCLUSIONS: The findings from this phase 3 study confirmed that FS is safe and its efficacy is superior to manual compression for hemostasis in patients with peripheral vascular ePTFE grafts. The data also suggest that FS promotes hemostasis independently of the patient's own coagulation system, as shown in a representative population of patients with vascular disease under single- or dual-antiplatelet therapies.

Use of fibrin sealant as a hemostatic agent in expanded polytetrafluoroethylene graft placement surgery.

BACKGROUND: The low thrombogenicity, porosity, and limited elasticity of expanded polytetrafluoroethylene (ePTFE) vascular grafts, although beneficial, may exacerbate the problem of suture-line bleeding at vascular anastomoses and consequently lead to increased operating times. The overall objective of this prospective, randomized, controlled, subject-blinded, multicenter phase 2 study was to evaluate the efficacy and safety of a fibrin sealant containing 500 IU/mL thrombin and synthetic aprotinin (FS; marketed in the United States under the name TISSEEL) for hemostasis in subjects undergoing vascular surgery and receiving prosthetic ePTFE vascular grafts. METHODS: FS was compared with manual compression with surgical gauze pads, a standard of care for hemostasis in vascular surgery. Two FS polymerization/setting times (60 and 120 seconds) were investigated to evaluate influence on the efficacy results. Patients undergoing ePTFE graft placement surgery (N = 73) who experienced bleeding that required treatment after surgical hemostasis were randomized to be treated with FS with clamps opened at 60 seconds (FS-60; N = 26), with FS with clamps opened at 120 seconds (FS-120; N = 24), or with manual compression with surgical gauze pads (control; N = 23). The proportion of subjects achieving hemostasis at 4 minutes (primary endpoint) as well as at 6 and 10 minutes (secondary endpoints) in the three treatment groups was analyzed using logistic regression analysis, taking into account gender, age, type of intervention, severity of bleeding, systolic blood pressure, diastolic blood pressure, heparin coating of the ePTFE graft, and platelet inhibitors. RESULTS: There were substantial differences in the proportion of subjects who achieved hemostasis at the study suture line at 4 minutes from treatment application between FS-120 (62.5%) and control (34.8%) groups (a 79.6% relative improvement). Logistic regression analyses found a statistically significant treatment effect at the 10% level in the odds ratio (OR) of achieving hemostasis at 4 minutes between the FS-120 and control groups (OR = 3.98, p = 0.0991). Furthermore, it has been shown that the perioperative administration of platelet inhibitors significantly influences (OR = 3.89, p = 0.0607) hemostasis rates at the primary endpoint. No statistically significant treatment effects were found for the other factors. Logistic regression analyses performed on the secondary endpoints demonstrated a significant treatment effect of achieving hemostasis at 6 minutes (OR = 9.92, p = 0.0225) and at 10 minutes (OR = 6.70, p = 0.0708) between the FS-120 and control groups. Statistically significant effects in the logistic regression analyses were found at the 10% level in the OR of achieving hemostasis at 6 and 10 minutes, respectively, for the following factors: FS-120 versus control group (OR = 9.92; p = 0.0225 and OR = 6.70; p = 0.0708, respectively), type of intervention (OR = 0.3; p = 0.0775 and OR = 0.25; p = 0.0402, respectively), and heparin coating of the ePTFE prosthesis (OR = 4.83; p = 0.0413 and OR = 3.65; p = 0.0911, respectively). FS was safe and well-tolerated, as indicated by the lack of any related serious adverse events. CONCLUSION: The findings from this phase 2 study support the strong safety profile of FS and suggest that it is an efficacious hemostatic agent in ePTFE graft placement surgery, as well as a useful tool in peripheral vascular surgery applications.