PK/PD Drug and Disease Modeling and Simulation

Quantifying Drug, Disease, and Trial Information to Aid Efficient Drug Development

For almost 20 years, our pharmacometricians have combined insight and innovation to build quantitative models of the interactions between the human body, drug effects, and diseases. Our team develops models that are fit-for-purpose and meet strategic objectives, are aligned with regulatory authority requirements and expectations, and are updated and adjusted based on program evolution.

Here are some of the approaches that we have used to support hundreds of drug approvals in a range of therapeutic areas in recent years:

  • Drug models—PopPK, exposure-response models, concentration QT models, etc—describe the exposure-response relationship for both drug efficacy and safety
  • Disease progression models describe the relationship between biomarkers and clinical outcomes, time course of disease and placebo effects; we have particularly deep experience in tumor growth modeling and viral kinetic modeling
  • Trial models are used to determine the effect of inclusion/exclusion criteria, drug adherence, and protocol deviations on the probability of trial success

As a member of your development team, we leverage the wide range of Certara’s model-informed drug development (MIDD) capabilities to answer key technical, regulatory, and commercial challenges.

Pharmacometrics Strategy Aligned to Development Cycle and Regulatory Goals

A well-designed pharmacometrics regulatory strategy satisfies multiple goals. First, the strategy prioritizes the needs of the program and details when and how they will be met. Next, a strategic road map provides direction that ensures that studies and analyses will be fit-for-purpose and add value to the program. Finally, a robust strategy facilitates positive interactions with regulators, commercial partners, and payers.

Pre-clinical

  • Support first-in-human (FIH) designs by bridging pre-clinical PK/PD data and predecessor compounds
  • Translation from animal to human data for safety and efficacy
  • Assess cardiac safety risk
  • Identify exposure-safety, exposure-PD, and exposure-activity relationships
  • Establish early view on drug-drug interactions (DDI) using PBPK models
  • Determine FIH dose justification rationale

Phase 1 through Proof-of-Concept

  • Clinical pharmacology quantitative PK/PD evaluation
  • Support Proof-of-Concept (PoC) designs by modeling the time-course of disease, the compound effect, and the effect of patient variables; evaluate PoC success criteria
  • Support strategies to evaluate Proof-of-Mechanism
  • Support conduct of clinical pharmacology programs through quantitative pharmacology services (data management, non-compartmental analysis, clinical study report contributions)
  • Drug metabolism consultancy (eg, to optimize drug-drug and drug-food interaction strategy)

Proof-of-Concept through pre-NDA activities

  • Support dose and regimen selection trials by bridging Phase 1 PK/PD data and predecessor compounds
  • Support expansion into new indications by bridging across indication
  • Define the efficacy and/or safety margin vs. comparators by performing a comprehensive safety/efficacy evaluation utilizing literature data
  • Develop and implement strategic modeling and simulation plans that are integrated into the clinical development plan
  • Develop criteria for interim analysis—evaluate innovative designs
  • Assess drug-drug interactions and other safety concerns
  • Optimize alternative drug formulations
  • Comparison to competitor compounds—comparative effectiveness
  • Population PK and exposure-response design
  • Support regulatory interactions

Registration activities

  • Dose justification
  • Population PK analysis
  • Exposure-response analysis
  • Support response to regulatory questions
  • Author clinical pharmacology and pharmacometric components of registration files

Post-marketing

  • Comprehensive safety/efficacy evaluation, including comparison of double-blind and open-label trials
  • Support publication strategy
  • HEOR modeling
  • Market access—value strategy

Other

  • Special populations—support pediatric and orphan drug trial designs
  • Special populations—hepatic and renal impairment, co-morbidities
  • Special populations—PK/PD bridging to Asian and other ethnic populations
  • IVIVC
  • OTC, generics
  • Global health

Contact us to learn how we can provide you with a reliable, reproducible and predictable decision support system, inform and optimize your drug’s label, and understand all dimensions of your drug’s efficacy and safety profile.

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