Emerging role of pharmacoeconomics in the research and development decision-making process.

OBJECTIVES: This study examines the organisational structure of pharmacoeconomics departments in major pharmaceutical and biotechnology companies, the impediments to optimal use of pharmacoeconomic evaluations by companies and the integration of pharmacoeconomic analysis with research and development decision making. DATA AND METHODS: The heads of the pharmacoeconomics departments of 40 companies were surveyed on the structure of pharmacoeconomics departments in their companies, the roles that pharmacoeconomic analyses are playing in the new drug development decision-making process, and the initiation of pharmacoeconomic studies during the development process for a random sample of their companies' investigational new drugs. RESULTS: 45 department heads from 31 parent companies responded to the survey. The pharmacoeconomics function in pharmaceutical and biotechnology companies is relatively new and growing rapidly. Most pharmacoeconomics department heads preferred a different reporting structure than what they currently have and indicated that the strategic role that pharmacoeconomics can play is not well understood within the organisation. Pharmacoeconomic analyses have been increasingly initiated early in clinical development and have been a factor in clinical trial design and in key decisions made during the development process. CONCLUSIONS: Given the continued emphasis on containing healthcare costs worldwide, demand will increase for evidence that drugs provide good value for the money spent on them. Companies will likely respond not only with more economic evaluations for purchasers, but also with greater use of pharmacoeconomics early in the development process to aid in rationalising key research and development decisions, and in guiding final pricing decisions and reimbursement planning, thereby improving resource allocations.

Successful cryopreservation of microvenous allografts.

Vein grafts are used in approximately 20% of microsurgical cases. Although autogenous veins currently form the major source, they are associated with increased operating time and donor site scars. Cryopreserved allograft veins may serve as an alternative source. To our knowledge, cryopreservation of veins (1 mm or less) has not been reported. In this article we have described the process of cryopreserving rat veins (less than 1 mm in diameter) and their preliminary use as interpositional vein grafts.

Mechanisms of vein graft atherosclerosis: LDL metabolism and endothelial actin reorganization.

We have explored the effect of arterial hemodynamics on endothelial cell morphology and low-density lipoprotein metabolism in human saphenous vein segments harvested from tissue donors. An arterial pulsatile perfusion system was used to impose physiologic pressures and flows for 20 hours on saphenous vein and companion (control) femoral artery segments. A venous perfusion apparatus was also employed for the perfusion of a second (control) saphenous vein segment for the same period of time. Calculations of fluid shearing and wall tensile stresses were performed and related to induced changes in endothelial cell geometry and cytoskeletal actin organization and the incorporation, degradation, and localization of intact low-density lipoprotein within the vessel wall. Our results indicate that, compared with native arteries and veins, a 20-hour exposure of test saphenous veins to arterial hemodynamics induced (1) a significant increase in endothelial cell luminal surface area and perimeter independent of alignment with flow, (2) disassembly of the dense peripheral band of actin with a concomitant assembly of stress fibers, and (3) a two- to fourfold elevation in the undegraded low-density lipoprotein content, localized primarily within the subendothelial intima. Although the exact mechanisms underlying these results are uncertain, the focal accumulation of intramural low-density lipoprotein may be related to the loss of normal barrier function during endothelial cell enlargement, which is accompanied by transient cytoskeletal reorganization during the adaptation to arterial flow.