Understanding the Cost of Pharmacokinetic & Pharmacodynamic Analyses

How much does PK/PD cost?

While a very common question, it is not one that is easy to answer. The cost of PK/PD depends on many factors but, in general, as complexity increases then so does cost. The complexity of PK/PD depends on actual data collected and the manner in which data are collected during the conduct of nonclinical and clinical studies. For example, if PK and PD samples and dosing parameters are not properly collected, documented, and reported during the conduct of a nonclinical study or a clinical study, then the complexity of determining PK/PD parameters, and the cost, increase. Other factors affecting the complexity and cost of PK/PD include the number of:

• Analytes assessed (i.e., parent drug, metabolites, etc.);
• Dosing regimens or crossover phases;
• Individual samples collected (e.g. number of PK/PD blood samples collected); and
• PK/PD relationships that must be analyzed to produce and report a complete PK and PD profile

Studies with multiple analytes, dosing regimens, crossover dosing phases, and many PK/PD samples collected can be very complex and require a significant amount of time to properly analyze and report. Often there are complexities that cannot be accurately predicted without seeing the final data. As such, the cost associated with PK/PD analyses are difficult to predict because it all depends on the actual data.

TK = Toxicokinetics; NCA = Noncompartmental; PK = Pharmacokinetics; PD = Pharmacodynamics; PK/PD = Correlation of concentration (PK) to effect (PD) AKA ‘exposure-response’; Population PK/PD = sparse sampling and modeling of PK/PD data

Toxicokinetic (TK) Analysis

Due to the nature of sample collection in a TK study, TK parameters are typically restricted to peak concentration (Cmax), time to peak concentration (Tmax), and exposure (AUC). As such, TK analysis is generally the least complex and typically the least expensive. If a GLP audit of the study report is necessary, the cost will increase.

Noncompartmental (NCA) Pharmacokinetics (PK)

NCA PK analysis is typically done for healthy volunteer studies with rich sample PK collection (i.e., multiple blood samples collected for concentration determination). A noncompartmental PK study such as a single-ascending dose, multiple ascending dose, food-effect, drug-drug interaction (DDI), bioavailability, bioequivalence, etc. can cost more than TK analyses but generally costs less than more complex analyses such as those done for population PK or exposure/response (PK/PD) relationships.

Pharmacodynamic (PD) Analyses

PD analysis (e.g., blood clotting parameters for an anticoagulant drug) can be complex and require significant time for a Pharmacokineticist to properly analyze and interpret the data.

Compartmental PK and PK/PD Analyses

Compartmental PK analysis and PK/PD exposure/response relationships generally require more effort and time compared to noncompartmental PK analysis leading to increased costs.

Population PK (popPK) and Modeling of Pharmacodynamics (PD)

Population PK analysis and PD modeling requires the use of complex mathematical models to describe the behavior of a drug in a population of subjects from a clinical study. Population PK typically relies on sparse sampling of the drug concentrations across a population of subjects enrolled in larger Phase 2 and Phase 3 studies. Fitting sparse sampling popPK data to a mathematical model is very labor intensive and is performed by highly trained consultants called pharmacometricians. The cost of a popPK analysis reflects the expertise and efforts of the pharmacometricians performing this work. Model selection for popPK analysis and PD modeling, using a forward-backward elimination approach, requires a large time commitment from pharmacometricians. Allucent has developed a model selection tool based on a genetic algorithm to automate model selection. This algorithm runs in a high-end computing environment and allows for more objective results, faster run times, and a more reliable/robust model for population PK analyses.

Model-Based Drug Development

Model-based drug development is an iterative process that starts with selecting a model to describe the characteristics of a drug. The model is refined over time as additional data are gathered on the drug’s characteristics from nonclinical and clinical studies. Model-based drug development is used to improve decision making ability for each step in a drug’s development pathway by leveraging both modeling and simulation. As an iterative process that essentially begins with nonclinical data and is refined through clinical development from Phase 1 to 3, the costs for this type of analysis can be high relative to other types of PK/PD analyses.

The Cost of Sub-optimal PK/PD Data

One factor that can result in significantly higher costs in drug development is sub-optimal PK/PD data and PK/PD analysis done incorrectly. PK/PD analysis done improperly or not optimally can cause significant delays in drug development, which increases overall costs, and can increase time-to-market for promising therapeutics. Allucent can help significantly reduce sub-optimal PK/PD data. Contact a Senior Consultant  to discuss your clinical pharmacology program.