PK in Late Stage Trials Pays Dividends

Editor’s Note: This article is part of a series examining popular peer-reviewed articles from years past called “Peer-Reviews Revisited: Why You Should Read Today.” You can read the other articles in this series here.

Companies that don’t collect pharmacokinetic (PK) data during Phase II and Phase III clinical trials are missing major dividends. Collecting late-phase PK data pays dramatic regulatory dividends as it moves products to market more quickly by reducing drug development time and costs.

Regulators in both the United States and Europe have expressed clear preferences for PK data, but collecting PK data is still the subject of debate within industry. PK data collection adds immediate costs. Decision-makers outside the regulatory realm may not recognize the approval, labeling, financial and clinical benefits over the lifecycle of a drug candidate.

“Our results should support and encourage collection of PK data in late phase clinical trials,” said lead author Nitin Mehrotra, PharmD, Pharmacometrics Team Leader for the Food and Drug Administration. “This can reduce drug development cost and time, helping safe and effective drugs reach the target population in a timely manner and also provide the most appropriate labeling instructions for practicing physicians.”

Researchers analyzed regulatory actions for all of the New Drug Applications and Biological License Applications submitted to FDA between 2002 and 2008 that required pharmacometrics review. They also surveyed clinical pharmacology scientists in industry, academia and contract research organizations and selected case studies illustrating the role of PK data on dose optimization, approval decisions and the need for additional trials.

Their key findings:

• PK data contributed to regulatory decisions for more than half of NDAs/BLAs submitted.

• PK data affected labeling language and approval in 87% of submissions.

• PK data eliminated the need for additional clinical trials in 28% of submissions.

• PK data was used to conduct exposure-efficacy analysis in nearly half of FDA submissions.

“Spending time,  money and resources to collect PK information in late phase clinical trials can help in high-level approval-related regulatory decisions,” Dr. Mehrotra concluded.