The power of phase II end-points for different possible mechanisms of action of an experimental treatment.

BACKGROUND: The high failure rate in phase III oncology trials is partly because the signal obtained from phase II trials is often weak. Several papers have considered the appropriateness of various phase II end-points for individual trials, but there has not been a systematic comparison using simulated data to determine which end-point should be used in which situation. METHODS: In this paper we carry out simulation studies to compare the power of several Response Evaluation Criteria in Solid Tumours (RECIST) response-based end-points for one-arm and two-arm trials, together with progression-free survival (PFS) and testing the tumour-shrinkage directly for two-arm trials. We consider six scenarios: (1) short-term cytotoxic therapy; (2) continuous cytotoxic therapy; (3+4) cytostatic therapy; (5+6) delayed tumour-shrinkage effect (seen in some immunotherapies). We also consider measurement error in the assessment of tumour size. RESULTS: Measurement error affects the type-I error rate and power of single-arm trials, and the power of two-arm trials. Generally no single end-point performed well in all scenarios. Best observed response rate, PFS and directly testing the tumour-shrinkages performed best for a number of scenarios. PFS performed very poorly when the effect of the treatment was short-lived. In scenario 6, where the delay in effect was long, no end-point performed well. CONCLUSIONS: A clinician setting up a phase II trial should consider the likely mechanism of action the drug will have and choose an end-point that provides high power for that scenario. Testing the difference in tumour-shrinkage is often powerful. Alternative end-points are required for therapies with a long delayed effect.

Isolation and characterization of bioactive compounds from plant resources: the role of analysis in the ethnopharmacological approach.

The phytochemical research based on ethnopharmacology is considered an effective approach in the discovery of novel chemicals entities with potential as drug leads. Plants/plant extracts/decoctions, used by folklore traditions for treating several diseases, represent a source of chemical entities but no information are available on their nature. Starting from this viewpoint, the aim of this review is to address natural-products chemists to the choice of the best methodologies, which include the combination of extraction/sample preparation tools and analytical techniques, for isolating and characterizing bioactive secondary metabolites from plants, as potential lead compounds in the drug discovery process. The work is distributed according to the different steps involved in the ethnopharmacological approach (extraction, sample preparation, biological screening, etc.), discussing the analytical techniques employed for the isolation and identification of compound/s responsible for the biological activity claimed in the traditional use (separation, spectroscopic, hyphenated techniques, etc.). Particular emphasis will be on herbal medicines applications and developments achieved from 2010 up to date.

[Occupational exposure to inhalation anesthetics: 10 years of measurements at hospitals in Puglia]. / Esposizione professionale ad anestetici inalatori: 10 anni di misure in ospedali pugliesi.

The Authors provide the data gathered from measurements of nitrous oxide in the operating room of Puglia during the period between 1993 and 2003. They prove significant reductions of pollution according with time and they verify lower pollution levels in the operating rooms of private hospitals with respect to public facilities. The importance of the maintenance of gas distribution and evacuation systems is shown and a method of environmental and biological monitoring is provided. Finally, the Authors prove the utility of the graphic representation of the measurements, conduced utilising dedicated instrumentation.