The Impact of Generic Substitution on Health and Economic Outcomes: A Systematic Review.

BACKGROUND: Generic drugs are considered therapeutically equivalent to their original counterparts and lower in acquisition costs. However, the overall impact of generic substitution (GS) on global clinical and economic outcomes has not been conclusively evaluated. OBJECTIVE: To test whether (1) generics and original products yield the same health outcomes, and (2) generic therapies save economic resources versus original therapies. METHODS: We performed a systematic literature review in Medline, Embase, and the Cochrane Database of Systematic Reviews to identify original studies that examine clinical or economic outcomes of GS. After standardized data extraction, reported outcomes were categorized as supporting or rejecting the hypotheses. Each reported outcome was assessed and accounted for supporting and opposing GS. One publication could provide multiple outcome comparisons. RESULTS: We included 40 studies across ten therapeutic areas. Fourteen studies examined patients on de novo therapy; 24 studies investigated maintenance drug therapy, and two studies considered both settings. Overall, 119 outcome comparisons were examined. Of 97 clinical outcome comparisons, 67% reported no significant difference between generic drugs and their off-patent counterparts. Of 22 economic comparisons, 64% suggested that GS increased costs. Consequently, hypothesis (1) was supported but hypothesis (2) was not. We found no major differences among studies that investigated clinical outcomes with de novo or maintenance therapy. CONCLUSION: The review suggests that clinical effects are similar after GS. However, economic savings are not guaranteed. More systematic research comparing clinical and economic outcomes with or without GS is needed to inform policy on the use of generic substitution.

Nuclear fragmentation of high-energy heavy-ion beams in water.

As a part of the physical-technical program of the heavy-ion therapy project at GSI we have investigated the nuclear fragmentation of high-energy ion beams delivered by the heavy-ion synchrotron SIS, using water as a tissue-equivalent target. For a direct comparison of fragmentation properties, beams of 10B, 12C, 14N, and 16O were produced simultaneously as secondary beams from a primary 18O beam and separated in flight by magnetic beam analysis. The Z-distributions of beam fragments produced in the water target were measured via energy loss in a large ionisation chamber and a scintillator telescope. From these data we obtained both total and partial charge-changing cross sections. In addition we have performed Bragg measurements using two parallel-plate ionization chambers and a water target of variable length. The detailed shape of the measured Bragg curves and the measured cross sections are in good agreement with model calculations based on semi-empirical formulae.

Neonatal and adult patterns of lectin binding to rat small intestinal microvillus membranes.

To investigate postnatal developmental changes of rat small intestinal microvillus membrane (MVM) sugar components, binding studies were done using peanut agglutinin (PNA) and soybean agglutinin (SBA). MVM were prepared from rats of different ages (new-borns to 12 weeks). The Airfuge method was used for separation of unbound material. Characteristics of sugar ligand specificity were different for PNA and SBA, although D(+)galactose was used as an inhibitor for both lectins. Concentration curves and Scatchard plots showed partial saturation of total binding, and at least two groups of MVM ligands. Differences in lectin binding between newborn and adult MVM were opposite for PNA and SBA (newborns bound more PNA, but less SBA). During the first few postnatal weeks in rats, SBA binding changed early, and PNA binding exhibited an intermediate change, not related to weaning. Changes in MVM glycoproteins shown by lectin binding appear to be part of a complex postnatal maturational process in rats, involving different biochemical, functional, and biophysical membrane characteristics.