Generic substitution in the treatment of epilepsy: case evidence of breakthrough seizures.

OBJECTIVE: There are concerns that generic and brand antiepileptic drugs (AEDs) may not be therapeutically equivalent. This study investigated how generic AED substitution may have negative consequences. METHODS: Sixty-nine of 150 physicians who participated in a large survey on generic AED substitution completed a case review form regarding a patient who experienced a loss of seizure control due to a generic AED. Nineteen were excluded from analysis. RESULTS: Fifty patients, well-controlled on a brand AED, subsequently experienced a breakthrough seizure or increased seizure frequency after switching to a generic without other provoking factors. AEDs included phenytoin (15 cases), valproic acid (14), carbamazepine (7), gabapentin (8), and zonisamide (8). Two patients were on a combination of two AEDs, both of which were switched to generics. In 26 cases serum AED levels were known both before and after generic substitution. Twenty-one had lower levels at the time of the breakthrough seizure on the generic medication. Loss of seizure control had a negative impact on quality of life, including loss of driving privileges (n = 30) and missed school/work days (n = 9). CONCLUSIONS: Changing from a brand antiepileptic drug (AED) to a generic may result in seizures. This raises the concern that current Food and Drug therapeutic equivalence testing regulations may not be adequate for AEDs and suggests that more clinical evidence is needed. Physicians, pharmacists, patients, and policy makers should be aware that for some patients there may be risks associated with switching from brand to generic AEDs.

Deep brain stimulation in the treatment of Parkinson's disease: a cost-effectiveness analysis.

BACKGROUND: In treating PD, deep brain stimulation (DBS) has shown great promise in a series of uncontrolled studies. OBJECTIVE: To estimate the incremental cost effectiveness of DBS compared with the best medical management in late-stage PD. METHODS: The authors constructed a decision model to determine the lifetime incremental cost effectiveness between two options in patients with PD aged 50 years and older: 1) best medical management and 2) DBS. As the long-term efficacy of DBS (>3 years) is not known, key assumptions regarding the procedure's long-term durability were made. Costs were in US 2000 dollars, and quality-adjusted life year (QALY) was the effectiveness measure. Base assumptions were that quality of life (QOL) in patients with late-stage PD is 0.55 (0-to-1 scale, 1 is perfect health) and that DBS benefits are constant for 4 years, eroding gradually over the next 5 years until at parity with those produced by best medical management. Incremental cost-effectiveness and sensitivity analyses were performed. RESULTS: Under base-case assumptions, DBS provides an additional 0.72 QALY at an additional cost of $35,000 compared with best medical management that results in an incremental cost-effectiveness ratio (C/E) of $49,000. QOL increases of between 18 and 30% resulted in questionable cost effectiveness. QOL increases of between 6 and 18% resulted in incremental C/E ratios not usually considered cost effective (>100,000/QALY). CONCLUSIONS: The results suggest that DBS may be cost effective in treating PD if QOL improves 18% or more compared with those receiving best medical management. This underscores the need for randomized, controlled, prospective DBS experiments including QOL and economic components.

HMO penetration, competition, and risk-adjusted hospital mortality.

OBJECTIVE: HMOs have been shown to have an effect on the care provided directly to their enrollees. They may also influence the care provided to individuals in fee-for-service plans through a spill-over effect. The objective of this study was to investigate the associations among HMO market penetration, HMO and hospital competition, and the quality of care received by Medicare fee-for-service patients measured by risk-adjusted hospital mortality rates. DATA SOURCES: The 1990 data for 1,927 hospitals in 134 metropolitan statistical areas (with five or more hospitals) included Medicare fee-for-service risk-adjusted mortality rates from the Medicare Hospital Information Reports, hospital characteristics from the American Hospital Association annual survey, and HMO market penetration and competition calculated from InterStudy and Group Health Association of America data. STUDY DESIGN: Statistical regression techniques were used to identify the associations between HMO market penetration, competition, and risk-adjusted mortality, controlling for other hospital characteristics and region. PRINCIPAL FINDINGS: Higher HMO market penetration and to a lesser degree increased HMO competition were associated with better mortality outcomes for fee-for-service Medicare enrollees. Competition between hospitals did not exhibit a significant association. CONCLUSIONS: HMOs may have a spill-over effect on quality of care received by individuals enrolled in fee-for-service plans. These findings may be explained by a positive effect on local practice styles or a preferential selection by HMOs for areas with better hospital care.