Diffusion of a new drug among ambulatory physicians-The impact of patient pathways.

When drugs enter the market, physicians' prescribing behavior plays a crucial role in the diffusion process. Although regulations to foster economically efficient prescribing exist, physicians have some degree of freedom in choosing medication and are subject to various influencing factors. The aim of the present analysis is to investigate how interaction among patients and physicians affects the diffusion. We look at two different ways that patient pathways might influence physicians and examine these effects for Sacubitril/Valsartan (S/V), a new drug for patients with heart failure. Using administrative data from Germany, we identify physicians who prescribed S/V in the first 2 years of its availability. We apply survival models to estimate the impact of the patient-physician interaction on the physicians' adoption time. To this end, we determine whether individual physicians treated patients that had been prescribed S/V, and how many other physicians already prescribing S/V were connected in patient-sharing networks. Our main findings are that patients with a previous prescription seem to induce adoption by demanding repeat prescriptions. Moreover, patients establish connections between physicians that may lead to prescriptions for new patients. Our results therefore suggest that patient pathways play a significant role in the diffusion of a new drug.

Human caspases in vitro: expression, purification and kinetic characterization.

A number of strategies and protocols for the expression, purification and kinetic characterization of human caspases are described in the literature. We have systematically revised these protocols and present comprehensive optimized expression and purification protocols for caspase-1 to -9 as well as improved assay conditions for their reproducible kinetic characterization. Our studies on active site titration revealed that the reproducibility is strongly affected by the presence of DTT in the assay buffer. Furthermore, we observed that not all caspases show a linear relationship between enzymatic activity and protein concentration, which explains the discrepancy between published values of specific activities from different laboratories. Our broad kinetic analysis allows the conclusion that the dependency of caspase activities on protein concentration is an effect of concentration-dependent dimerization, which can also be influenced by kosmotropic salts. The protocol recommendations as an outcome of this work will yield higher reproducibility regarding expression and purification of human caspases and contribute to standardization of enzyme kinetic data.