Survey on the Situation of Medical Departments in the Pharmaceutical Industry in Spain.

INTRODUCTION: Medical departments have evolved from a position of support to one of strategic leadership. The number of tasks and the complexity of interactions in which they are involved is increasing. However, the spectrum of their activity in the sector differs significantly from one company to another. Therefore, the aim of this study was to describe their situation within the pharmaceutical industry, analyzing the positions, functions, and profiles of their professionals. METHODS: This study consisted of an online survey containing 25 questions grouped into four blocks (structure, medical direction, training, and activities and responsibilities). Medical departments in the Spanish pharmaceutical industry of different sizes and scope were invited to participate. The survey took place in 2021, with a designated response period of three months. It is important to note that all responses collected during this time were treated as anonymous. RESULTS: Thirty companies participated. A total of 93.3% of respondents worked for an international laboratory, with a size of 0-5 or 11-20 people (20.7%). For 27.6% of the companies, the number of medical advisors per medical department was 1 or 4, with varying numbers of medical scientific liaisons (1, 6-10, and > 20). A total of 56.7%, 33.3%, and 6.7% indicated that the country manager, head of regional medical affairs, and head of global medical affairs, respectively, had a solid-line reporting relationship with the medical directorate. Medical directors were mostly graduates in medicine (86.2%) with a doctorate (34.5%), and medical managers were mainly graduates in medicine (77.8%) and pharmacy (66.7%). CONCLUSIONS: This study reveals that respondents predominantly work in internationally focused laboratories, with professionals ranging from experienced medical directors to managers with 6-20 years of experience, each with distinct roles.

Pharmacodynamics assessment of Bemiparin after multiple prophylactic and single therapeutic doses in adult and elderly healthy volunteers and in subjects with varying degrees of renal impairment.

INTRODUCTION: Aging and renal impairment may prolong the half-life and lead to accumulation of low molecular weight heparins. Correct dosing is critical to prevent bleeding or thrombosis. MATERIALS AND METHODS: Open, parallel study. Healthy adult [n=13] and elderly (>65yrs) [n=12] volunteers; and subjects with mild (ClCr≥50 to ≤80mL/min, n=8), moderate (ClCr≥30 to <50mL/min, n=7), and severe (ClCr<30mL/min, n=8) renal impairment received four prophylactic doses (3,500IU/24h) and a single therapeutic dose (115IU/kg) of bemiparin with an interim washout period. Anti-FXa activity and the potential need for dose adjustment were evaluated. RESULTS: There were statistically significant differences in the severe renal impairment group vs. adult volunteers in all anti-FXa related parameters, but no significant differences in any of the anti-FXa related parameters between the adult and the elderly. Anti-FXa simulations after 10 prophylactic doses predicted mean Amax=0.59IU/mL in subjects with severe renal impairment and 0.33-0.39IU/mL in the rest. Simulations in the severe renal impairment group with dose adjustment (2,500IU/24h) predicted all individual Amax<0.60IU/mL (mean Amax=0.42IU/ml). Simulations after 10 therapeutic doses predicted mean Amax=1.22IU/mL in severe renal impairment group and 0.89-0.98IU/mL in the rest. Simulations in the severe renal impairment group with 75% dose adjustment predicted individual Amax≤1.60IU/mL (mean Amax=0.91IU/mL). CONCLUSIONS: No dose adjustments are required in elderly with preserved renal function. A dose adjustment of bemiparin is only advisable in patients with severe renal impairment when using prophylactic or therapeutic doses.

Safety assessment and pharmacodynamics of a novel ultra low molecular weight heparin (RO-14) in healthy volunteers--a first-time-in-human single ascending dose study.

INTRODUCTION: RO-14 is a novel ultra low molecular heparin. The purpose of this study was to evaluate the safety and pharmacodynamic profile of RO-14 in healthy males. MATERIALS AND METHODS: We conducted a two-stage, single-center, open-label, randomized study. Two cohorts of 6 volunteers were randomly assigned to 12 single, ascending subcutaneous doses (1750-19950IU of anti-FXa activity) in an alternating crossover fashion. Safety was assessed by spontaneous/elicited adverse events, medical examination and laboratory tests. Anti-FXa activity and anti-FIIa activity were assessed throughout the 24hours after dosing. Dose proportionality and linearity of the anti-FXa activity were evaluated. RESULTS: All doses were well tolerated and there were no bleeding events. At the lowest dose, anti-FXa activity A(max) was 0.16 (±0.02) IU/mL and AUC(0-24) was 1.11 (±0.24) IU*h/mL, At the highest dose anti-FXa activity A(max) was 1.67 (±0.15) IU/mL; AUC(0-24) was 21.48 (±4.46) IU*h/mL and t½ was 8.05h. Mean T(max) (all doses) was 2.86 (±0.39) h. RO-14 showed proportional and linear pharmacodynamics [normalized A(max) among doses (p=0.594) and normalized AUC(0-24) (p=0.092), correlations between A(max-)dose (R(2)=0.89, p<0.001) and AUC(0-24)-dose (R(2)=0.86, p<0.001)]. Anti-FIIa activity was below the detection limit (0.1IU/ml) at all dose levels. No clinically significant changes were observed in the platelet count, APTT, PT, TT, fibrinogen and antithrombin. CONCLUSIONS: In this phase I study, RO-14 exhibited a good safety profile, anti-FXa activity for either prophylaxis or treatment of venous thromboembolism, linear pharmacodynamics, a longer elimination half-life than currently marketed low molecular weight heparin and no anti-FIIa activity.

Cost effectiveness of bemiparin sodium versus unfractionated heparin and oral anticoagulants in the acute and long-term treatment of deep vein thrombosis.

INTRODUCTION: Low-molecular-weight heparins (LMWHs) are at least as effective and well tolerated as unfractionated heparin (UFH) in the treatment of deep vein thrombosis (DVT), offering easier administration and obviating the need for anticoagulant monitoring, but have a higher acquisition cost than UFH. OBJECTIVE: To quantify the potential economic impact of two regimens of subcutaneous bemiparin 115 IU/kg/day for 7-10 days (plus oral anticoagulants [OAC] or followed by long-term bemiparin 3500IU) versus dose-adjusted intravenous UFH for 7 days plus OAC for 3 months in the acute and long-term treatment of DVT. The representative patient was a 62-year-old, 77 kg male with proximal DVT of the lower limbs. METHODS: A cost-effectiveness analysis was performed using a decision-tree modelling approach. The results were expressed in terms of costs (euro, 2002 values) and incremental cost effectiveness. The treatment costs (hospital stay, physician services, drug administration) and costs incurred due to complications (pulmonary embolism, recurrent DVT, bleeding events, thrombocytopenia and deaths) during the 3-month study period were considered for the primary analysis. Life expectancy and QALYs were considered for the secondary analysis. The study was performed in the setting of the Spanish National Health System. RESULTS: Bemiparin plus OAC or long-term bemiparin for 3 months provided net cost savings of euro 769 and euro 908 per patient, respectively, compared with UFH plus OAC (UFH plus OAC euro 4128 vs bemiparin plus OAC euro 3359 vs long-term bemiparin euro 3220). Bemiparin plus OAC and long-term bemiparin for 3 months were calculated to avoid 27 and 7 additional VTE events, respectively, per 1000 patients treated. Bemiparin plus OAC or long-term bemiparin increased quality-adjusted life expectancy by approximately 1.72 and 0.74 years, respectively, compared with UFH plus OAC. The univariate sensitivity analysis supported the cost effectiveness of bemiparin in all the ranges tested for complications and costs. CONCLUSIONS: Our model suggests that bemiparin plus OAC or long-term bemiparin for 3 months may be dominant strategies over UFH plus OAC in the treatment of DVT from the Spanish National Health System perspective, offering better outcomes and cost savings. Long-term bemiparin may be a cost-neutral alternative to bemiparin plus OAC.

Pharmacoeconomic analysis of bemiparin and enoxaparin as prophylaxis for venous thromboembolism in total knee replacement surgery.

INTRODUCTION: Low molecular weight heparins are effective and have a good tolerability profile as first-line prophylaxis for venous thromboembolism (VTE) in major orthopaedic surgery. However, pharmacological inequivalence within the class could lead to differences in cost-effectiveness ratios. OBJECTIVE: To quantify the potential economic impact of subcutaneous bemiparin sodium 3500 IU/day compared with enoxaparin sodium 40 mg/day as prophylaxis for VTE in patients undergoing total knee replacement (TKR) surgery, considering both in-hospital and post-discharge outcomes and costs during 6 weeks of postoperative follow-up. METHODS: A cost-effectiveness analysis was performed using a decision modelling approach. The results were expressed in terms of costs and incremental cost effectiveness in Euro (2002 values). The treatment costs (hospital stay, physician services, drug administration) and costs incurred due to complications such as pulmonary embolism and/or proximal deep vein thrombosis, bleeding events, wound haematoma and thrombocytopenia were considered for this analysis. The target population comprised all adult patients undergoing TKR surgery included in a previous clinical trial (n = 381). The study was conducted in the setting of the Spanish National Health System. The time horizon chosen was 6 weeks. RESULTS: Bemiparin provided cost savings of Euro144.48 per patient compared with enoxaparin when costs derived from treatment and complications during the 6-week postoperative period were considered (Euro4675.01 vs Euro4819.49). Pharmacy costs per patient were lower for bemiparin during hospital stay (Euro43.34 vs Euro50.20; difference, Euro-6.86) and for post-discharge prophylaxis (Euro68.63 vs Euro87.78; difference Euro-19.15). Bemiparin was calculated to avoid 42 additional VTE events per 1000 patients treated at 6 weeks. The incremental cost-effectiveness analysis indicated that bemiparin was dominant over enoxaparin, producing better outcomes and cost savings. The sensitivity analysis supported the cost effectiveness of bemiparin in all the ranges tested for complications and costs. CONCLUSIONS: Our model suggests, based on its underlying assumptions and data, that bemiparin may be more cost effective than enoxaparin for thromboprophylaxis in total knee replacement surgery in the Spanish healthcare setting.