Progressive Reporting and Model Based Drug Development

Over the years, our relationships with clients have deepened and Cognigen is often asked to begin working on projects at the earliest stages of development and to continue to refine a model as new data arrives from ongoing clinical development programs.  Consequently, if a assets continues to show promise, we have the opportunity to provide modeling and simulation results at decision-making milestones over the lifecycle of clinical development. Typically, these activities culminate in a comprehensive synthesis of exposure-response relationships for efficacy and safety endpoints that are included in the regulatory submission.

Cognigen enjoys a reputation for providing comprehensive documentation of the analysis process, results from interim steps in the analysis, and, in the case of simulations, careful documentation of the decision tree used to generate simulation scenarios and the accompanying results. The technical reports describe a broad range of activities including data assembly methods and data disposition, model development strategies, and analytic results derived from the accumulation of data from Phase 1, 2, and 3 clinical trials.

The preparation of a technical report involves a significant effort on the part of a number of functional groups. The analyst must identify relevant content to be included in the report, data programming must modify the analysis datasets and re-generate many of the graphical displays, and the document preparation group spends many hours, assembling, formatting, and checking the final product. Required quality documentation is then generated by each functional group, as dictated by SOPs.

While these cumulative activities put a satisfactory end to a project the process is costly and time-consuming. It is one thing if the report is all-inclusive of the modeling and simulation effort at the end of a development program; it is quite another if a comprehensive report is produced each time a model is updated. Consider the following typical scenario:

• Cognigen receives data from Phase 1 SAD and MAD studies and asked to develop an initial PK model and perform simulations to support the design of a Phase 2 trial
• The Phase 2 trial is positive and we are asked to do 3 things:
  • Incorporate the PK data into our database and re-run the PK model,
  • Perform a PK/PD analysis of the safety and efficacy endpoints, and
  • Perform simulations to support the design of the Phase 3 clinical trials
• If the Phase 3 trials are positive we can anticipate receiving these data and develop an overall synthesis  of the PK, efficacy, and safety data for inclusion in the regulatory submission

The primary goal of our work at each of the above-mentioned stages is to provide results that are useful for advancing a development program. An important question for these multi-phase analyses is how to best document the emerging interim results so that future analyses can proceed efficiently, but without the need to unnecessarily complicate the documentation produced for each stage of the modeling process.