News

An article in the recent issue of Heptaology illustrates an insightful application of hepatitis C viral dynamic modeling and clinical pharmacology. Guedj et al. (Hepatology 2012 55: 1030-1037) present an HCV dynamic model of viral load versus time during mericitabine therapy. Rather than seeing the clear bi-phasic viral load profile we see with interferon and the protease inhibitors (with characteristic sharp initial drop in viral load), the viral load decline during mericitabine therapy is more complicated: either a slower bi-phasic profile or mono-phasic profile. The authors propose an interesting modeling solution to gain insight into mericitabine’s antiviral activity.

Recently, I was asked to speak at this year’s PaSiPhIC conference about different approaches to meta-analysis. As I was putting together my presentation, I began to wonder: How can we best leverage traditional meta-analysis methods in a model-based drug development framework?

The primary rationale for model-based meta-analysis (MBMA) is to improve decision-making by better leveraging prior information from multiple sources. Decision-makers generally attempt to consider such prior information, but it is usually done in a relatively qualitative manner, and each individual decision-maker is usually aware of only a subset of the prior information. MBMA seeks to make the process more quantitative and comprehensive. The process and results of MBMA may be made visible (aka transparent) to the decision-makers. The end result is that the decision-makers are better informed, and they can contribute their knowledge to the modeling process leading to better, more trusted models and model-based inferences.

I recently returned from the 2013 PAGE meeting in Glasgow. As usual, the scientific presentations were some of the best in the field of pharmacometrics. At this year’s meeting I was offered an opportunity to present some of our recent thoughts about model-based drug development in oncology.

In recognition and support of Rare Disease Day, 2014, the scientists and staff at Metrum Research Group have focused the weekly journal club on articles related to this topic, for the month of February…

Though deemed “rare”, approximately 25—30 million Americans, and 300 million people worldwide, have been diagnosed with one of >6,800 known rare diseases. An estimated 50% of those affected are children. The prevalence of individual rare diseases can range from dozens in the US (progeria, hypophosphatasia, Niemann-Pick, for example), to thousands globally (such as, Crohn’s disease and cystic fibrosis). Although traditionally considered impractical for big pharma development, innovation and development of therapeutics for rare diseases have led to promising treatments for some diseases in recent decades. In the period of time from the passage of the Orphan Drug Act of 1983 until May 2010, the FDA approved 353 orphan drugs and granted orphan designations to 2,116 compounds. As of 2010, at 200 orphan diseases have become treatable (Armstrong). Still, rare diseases pose a critical unmet medical need.

Jonathan Sidi, Metrum Research Group

We are pleased to announce the release of the ggedit package on CRAN.