Model-Driven Development Strategies

What Should Your Dose Be?

Confidence with Model-informed Dose Selection Support

For first-in-human studies, the next phase of development, pediatric dose selection, or for commercialization and labeling support, Simulations Plus uses a model-informed approach to guide the selection of an optimal dose and regimen for your compound. Population PK, PK/PD and exposure-response models are developed to describe and quantify relationships between drug dosing, observed exposure, safety and efficacy outcomes, as well as to identify predictors of variability in these relationships.

PK and Exposure-Response Model Development

With population-based pharmacokinetic models, we can characterize drug disposition using sparse drug concentration data collected from patients with the condition of interest, and assess whether intrinsic and extrinsic factors may be predictive of exposure. Relationships between individual drug exposure and patient efficacy and safety outcomes are characterized using exposure-response models. By gaining understanding of these critical relationships, we can support the selection or justification of dosing regimens, determine the maximum tolerated dose or the minimum effective dose, and characterize sub-population differences or drug-drug interaction effects to guide appropriate dosing strategies.

Pharmaceutical and Clinical Pharmacology Consulting

We can assist your development team in all aspects of pharmacology, from recommendations regarding the study design of preclinical studies to gap analyses for the overall clinical pharmacology development plan to non-compartmental pharmacokinetic and toxicokinetic analyses to the preparation of the clinical pharmacology sections of your regulatory submission. Our expert consultants can support your team as a dedicated, embedded team member or engage on an as needed basis, along with an experienced team, including programming, operations, project management, and administrative support, for specified activities.

Clinical Trial Simulations

Population PK, PK/PD and exposure-response models can be used as a basis for simulations of next-phase clinical trials. With this type of in silico approach, the impact of dose and a myriad of other study design features can be systematically evaluated on trial outcomes in advance of clinical testing. Multiple “what-if” scenarios can be evaluated quickly and efficiently, with replication to provide confidence in designing future trials and assessing risk: benefit for go-forward strategies.

Strategic Gap Analyses and Analysis Planning

In order to fully integrate model-based drug development into development programs, pharmacometricians must become highly skilled in strategically implementing modeling and simulation approaches across the entire development program, as well as in effectively communicating the value of modeling and simulation findings to support the decision-making and regulatory milestones of research and development project teams. Simulations Plus will work with your pharmacometric development teams by providing the best tools and techniques for strategic and operational gap analyses that assess the readiness of franchise programs in specific therapeutic areas to adopt model-based informed drug development.