Pharmaceuticals Licensing and Reimbursement in the European Union, United States, and Japan.

This article describes recent developments in licensing and reimbursement policies in the EU, US, and Japan, examines causes of changes and compares differences and projects trends. With respect to licensing, the European Medicines Agency (EMA), US Food and Drug Administration (FDA), and Japan's Pharmaceuticals and Medical Devices Agency (PMDA) are committed to rigorous evaluation of pharmaceuticals in advance of market access with feedback from postmarket experience. The EMA is exploring integrated adaptive pathways for licensing, with formal pilot tests to provide a practical proof of concept. The FDA is augmenting traditional licensing procedures through reforms including Breakthrough Product Designation. The PMDA is implementing reforms to foster innovation and earlier patient access through its Sakigake strategy and licensing reforms on regenerative medicines. With respect to reimbursement, several generalizations emerge. Relative to US counterparts, EU payers typically set higher standards for evidence of effectiveness as a condition of reimbursement, impose tougher limits on reimbursement by indication, and drive harder deals in negotiations over prices.

Does limb angular motion raise limb arterial pressure?

AIM: Mechanical factors such as the muscle pump have been proposed to augment flow by several mechanisms. The potential for limb angular motion to augment local perfusion pressure (pressure = (1/2)rhor(2)omega(2), where rho is the fluid density, r the radius and omega the angular velocity) has been overlooked. We sought to test the hypothesis that limb angular motion augments limb arterial pressure. METHODS: Nine human subjects performed horizontal shoulder flexion ( approximately +/-90 degrees at 0.75 Hz for 30 s). We measured finger arterial pressure (photoplethysmography) in the moving (Trial 1) and non-moving arm (Trial 2) in separate trials along with the pressure (strain gauge) generated at the fingers within a length of water-filled tubing mounted on the moving arm in both trials. RESULTS: Arm swinging raised (P < 0.05) the mean pressure measured in the tubing by 11 +/- 2 and 14 +/- 2 mmHg (Trials 1 and 2 respectively). In response to exercise, the rise in mean finger arterial pressure in the swinging limb (18 +/- 3 mmHg, Trial 1) exceeded (P < 0.05) the rise in the resting limb (8 +/- 2 mmHg, Trial 2) by an amount similar to the 11 mmHg rise in pressure generated in the tubing in Trial 1. CONCLUSIONS: We conclude that the swinging of a limb creates centrifugal force (a biomechanical centrifuge) which imparts additional pressure to the arteries, but not the veins owing to the venous valves, which further widens the arterial-venous pressure difference.