Initiatives aimed at increasing organ donation can be considered health care interventions, and will compete with other health care interventions for limited resources. We have developed a model capable of calculating the cost-utility of organ donor initiatives and applied it to Donor Action, a successful international program designed to optimize donor practices. The perspective of the payer in the Canadian health care system was chosen. A Markov model was developed to estimate the net present value incremental lifetime direct medical costs and quality adjusted life years (QALYs) as a consequence of increased kidney transplantation rates. Cost-saving and cost-effectiveness thresholds were calculated. The effects of changing the success rate and time frame of the intervention was examined as a sensitivity analysis. Transplantation results in a gain of 1.99 QALYs and a cost savings of Can$104,000 over the 20-year time frame compared with waiting on dialysis. Implementation of an intervention such as Donor Action, which produced as few as three extra donors per million population, would be cost-effective at a cost of Can$1.0 million per million population. The cost-effectiveness of Donor Action and other organ donor initiatives compare favorably to other health care interventions. Organ donation may be underfunded in North America.
To investigate the population pharmacokinetics of mycophenolic acid (MPA) in adult kidney transplant recipients during the crucial first week after transplantation.
Data were collected from 117 patients. MPA plasma concentrations were determined at t=0, 1, 2, 3 and 4 h after mycophenolate mofetil dosing on days 3, 5 and 7. Population analysis was performed using NONMEM. Covariates screened were sex, age, body weight, serum creatinine, creatinine clearance, serum albumin, days of therapy, diabetes mellitus, organ source (live or cadaveric) and co-therapy (tacrolimus or cyclosporine). Final model validity was evaluated using 200 boot strapped samples from the original data. Bias and precision were determined through comparison of observed and predicted concentrations.
Individual concentration-time profiles showed evidence of an absorption lag time and enterohepatic recirculation of MPA in some patients on some occasions. The best base model had bi-exponential elimination with a typical population (SE%) apparent clearance (CL/F) of 29 l/h (5%) and apparent volume of the central compartment of 65 l (7%). CL/F decreased significantly with increasing serum albumin (1.42 l/h reduction in total plasma CL/F with each 1 g/l increase in albumin) and was 27% greater in patients receiving cyclosporine than in those receiving tacrolimus. Evaluation of the final model showed close agreement between pairs of boot strapped and final model parameter estimates (all differences