Clinical pharmacology and therapeutics
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Clin. Pharmacol. Ther. · Dec 2010
Comparative StudyConditional approval and approval under exceptional circumstances as regulatory instruments for stimulating responsible drug innovation in Europe.
The need for fast drug innovation and the public demand for risk-free drugs creates a dilemma for regulatory authorities: less restrictive procedures involve uncertainties about benefit/risk profiles of new drugs. The European Union has introduced two instruments that regulate early market access: conditional approvals (CAs) and approvals under exceptional circumstances (ECs). We have studied whether these instruments compromise the safety of new drugs and whether they lead to earlier access to innovative drugs. ⋯ However, the CA pathway shortens the clinical development period. Approvals under ECs are associated with longer clinical development periods, but this regulatory pathway may open up opportunities for specific drugs to be admitted into the market because less comprehensive data are required. Despite the fact that these advanced approvals are based on limited safety databases, there are no special safety issues associated with using these pathways.
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Clin. Pharmacol. Ther. · Dec 2010
Randomized Controlled Trial Comparative StudyAcute alertness-promoting effects of a novel histamine subtype-3 receptor inverse agonist in healthy sleep-deprived male volunteers.
The alertness-promoting effect of MK-0249 (10 or 50 mg), a histamine subtype-3 receptor (HRH3) inverse agonist (IA), was evaluated in the stimulant reference sleep deprivation model (SRSDM) using a double-blind, double-dummy, placebo- and modafinil- (200 mg) controlled, four-period crossover design in 24 healthy young men. The two primary hypotheses were related to sleep latency (first appearance of one epoch of stage 2, 3, or 4 or REM sleep, as detected using polysomnography (PSG)) at 8:00 AM on day 2. ⋯ Sleep latency was higher when averaged over all MWT time points (P < 0.0001 for modafinil and for both doses of MK-0249). The alertness-promoting effect with the use of MK-0249 in the SRSDM suggests that HRH3 IAs may be effective in disorders involving excessive somnolence.
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Clin. Pharmacol. Ther. · Dec 2010
ReviewThe clinical utility of precision medicine: properly assessing the value of emerging diagnostic tests.
Assessments of the clinical utility of biomarkers and genomic tests often ignore individual utility and fail to account for downstream changes to the care delivery model. Tests that identify outliers are often undervalued in favor of those that help direct treatment for the "average" patient. By reducing uncertainty, these tests also enable lower-cost providers and even patients to assume increased responsibility for care in more convenient and affordable settings.