Determining appropriate dosage for your first in human (FIH) clinical trials is critical. Conventional methods rely on animal studies and allometric scaling, which can be imprecise and lead to inaccurate clinical starting doses. That’s why many pharmaceutical companies now use physiologically based pharmacokinetic (PBPK) modeling—the mechanistic approach offers a more accurate translation of preclinical data to inform the FIH starting dose.
There are multiple software platforms available for PBPK modeling to support FIH, but they are not created equal. Although every platform commercially available should technically be able to provide data for determining FIH dosage, there may be limitations in what is offered in the platforms to fully support your company’s requirements.
In this blog post, we’ll walk through key considerations for vetting your options and determining which FIH modeling and simulation platform will best suit your team’s needs.
It’s crucial to have a clear idea of what you need out of the technology you’re considering. Before selecting a FIH software, you should understand the formulation and population you want to run your trial in and the dosing regimen you want to simulate. Combining this with the key assumptions and constraints to be tested and methods for model validation and verification will allow you to set a clear objective for selecting the right modeling software.
Consider Modeling Environment
Evaluate the ease of creating, modifying, and running models, as well as available libraries of predefined populations and compounds.
For example, commercial FIH simulators should come pre-loaded with animal and human models for your use—but will they have the ones you need to support your future studies? Some platforms come with only a few animal models and a limited healthy human population model. That may be fine, but if your drug needs different dosing for pediatric populations, genders, or disease states, you will want to inquire about what models are included with your license.
You’ll also want the ability to import and export data to and from external sources to fully power your FIH simulations. No matter the quality of your FIH predictions, it is of limited use if you can’t easily access it and incorporate it into your workflows.
Identify Support and Training
Consider the availability of support and training options provided by the software vendor.
- Do they have bespoke courses to help your team learn how to translate nonclinical data to a clinical FIH starting dose?
- Is there dedicated consultant support available to help your in-house experts understand the software and evaluate your data?
- Is there documentation and other forms of support you can leverage if needed?
No matter how great the technology and models, the FIH simulation platform you choose will be used by the people on your team and it’s important to assess what kind of support will be available.
Understand True Costs
A sticker price rarely tells the whole story. You need to evaluate the initial cost of the software and determine if there are any hidden costs.
- Does the package offer all that you need to support your FIH simulation or are there add-ons (aka upsells) required just to obtain basic functionality?
- If questions arise during your program, will you be able to answer them with your software configuration?
- As your compound progresses in the development lifecycle, can the platform “grow” with additional modules as you expand your modeling and simulation approaches?
Understanding the total cost of ownership and potential additional expenses is essential for budget planning.
Translation of preclinical exposure data to humans can make or break the success of your Phase 1 clinical trials—it’s critical to get it right, and the FIH simulator you choose plays a big part in doing so.