Clinical pharmacology and therapeutics
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Clin. Pharmacol. Ther. · Apr 2012
Comparative StudyPrediction of codeine toxicity in infants and their mothers using a novel combination of maternal genetic markers.
Substantial variation exists in response to standard doses of codeine ranging from poor analgesia to life-threatening central nervous system (CNS) depression. We aimed to discover the genetic markers predictive of codeine toxicity by evaluating the associations between polymorphisms in cytochrome P450 2D6 (CYP2D6), UDP-glucuronosyltransferase 2B7 (UGT2B7), P-glycoprotein (ABCB1), mu-opioid receptor (OPRM1), and catechol O-methyltransferase (COMT) genes, which are involved in the codeine pathway, and the symptoms of CNS depression in 111 breastfeeding mothers using codeine and their infants. ⋯ A novel combination of the genetic and clinical factors predicted 87% of the infant and maternal CNS depression cases with a sensitivity of 80% and a specificity of 87%. Genetic markers can be used to improve the outcome of codeine therapy and are also probably important for other opioids sharing common biotransformation pathways.
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Clin. Pharmacol. Ther. · Mar 2012
Is it possible for FDA regulatory scientists and industry scientists to work together?
The US Food and Drug Administration (FDA) was established as a regulatory agency to protect the public health by ensuring that foods, medications, devices, and many other products are safe, effective, and properly labeled. William Abrams demonstrated that scientists from the pharmaceutical industry and the FDA can work together with integrity and synergy to develop scientific and educational programs, thus paving the way for more recent precompetitive collaborations between the "regulators" and the "regulated."
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Clin. Pharmacol. Ther. · Mar 2012
ReviewThe innovative medicines initiative: a European response to the innovation challenge.
The Innovative Medicines Initiative (IMI) was launched in 2008 as a large-scale public-private partnership between the European Commission and the European Federation of Pharmaceutical Industries and Associations (EFPIA). With a total budget of €2 billion, the IMI aims to boost the development of new medicines across Europe by implementing new collaborative endeavors between large pharmaceutical companies and other key actors in the health-care ecosystem, i.e., academic institutions, small and medium enterprises, patients, and regulatory authorities. Projects conducted by IMI consortia have already delivered meaningful results, providing proof-of-concept evidence for the efficiency of this new model of collaboration. In this article we review recent achievements of the IMI consortia and discuss the growing interest in the IMI as a best-practice model to reinvigorate drug development.
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Clin. Pharmacol. Ther. · Mar 2012
The critical path initiative: leveraging collaborations to enhance regulatory science.
Since 2004, the Critical Path Initiative has prompted industry, academia, and government agencies to work together to share the information, technology, and expertise critical to modernize and transform our approach to drug development and review. Various collaborations have been sharing data in a precompetitive space, establishing data standards, and facilitating collective tool development. As a result, the organization is making progress toward developing knowledge and tools that can reduce uncertainty in medical product development.
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Clin. Pharmacol. Ther. · Mar 2012
FDA review divisions: performance levels and the impact on drug sponsors.
Sponsors of new drug applications (NDAs) confront a host of uncertainties, one of the more vexing of which is negotiating the differing and inconsistent policies and standards among the various US Food and Drug Administration (FDA) drug review divisions. The FDA faces many challenges as well, internal and external, that confound its efforts to provide a consistent and timely review process. In this article, we examine various input factors, such as the number of regulatory filings, that contribute to fluctuations in the annual FDA workload, as well as output factors, such as NDA approval times, that are often viewed by sponsors as measures of the FDA's performance. Interdivisional differences at the FDA, in both input and output factors as well as other process-related factors, such as issuance of complete response letters, division staff levels, and quality of the sponsor's application, are considered in light of their contribution to the vagaries of the sponsors' experiences with the regulatory process.