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Accelerating Therapeutic Development for Huntington's Disease

Model-HD

Model-HD: Collaborative modeling of clinical data on Huntington’s disease

MODEL-HD is a collaboration between CHDI, the Food and Drug Administration’s (FDA) Office of Clinical Pharmacology, and the wider Huntington’s disease (HD) research community that will build consensus disease-progression models for HD using data from longitudinal observational studies and clinical trials in both prodromal and manifest disease. It is similar to the collaboration announced in March 2008 between the FDA and the American Association of Pharmaceutical Scientists that is modeling Alzheimer’s disease.The aim of the collaboration is to simulate HD clinical trials under alternative designs. A disease-progression model will be particularly useful in planning trials for compounds that are intended to modify disease. Modeling of this type has previously been applied to Parkinson’s disease and non-small cell lung cancer (Gobburu JV and Lesko LJ, Annu. Rev. Pharmacol. Toxicol.2009;49:291). The systematic study of the onset and progression of HD clinical signs and symptoms may also shed light on the mechanisms of HD.

MODEL-HD has the following objectives:

  • Construct and maintain the modeling database
  • Determine the general form of the base models for potential clinical endpoints and biomarkers
  • Find and incorporate covariates and progression modifiers into the base models
  • Develop predictive models for potential clinical endpoints as functions of selected biomarkers
  • Fit path analysis and other multivariate models
  • Model dropout rates and placebo effects in HD clinical trials

Currently, the modeling database contains data from the following clinical studies:

  • Clinical observational studies: PREDICT-HD, TRACK-HD, COHORT, REGISTRY
  • Clinical interventional trials: CARE-HD, HORIZON

Other clinical datasets will become available in the near future, and the project will also benefit from the results of genome-wide association (GWA) scans that have been conducted on many patients in the MODEL-HD database. Models will be generated by a working group of statisticians and expert modelers who will report to an advisory committee of senior clinical and scientific experts. This collaboration began in January 2012 with a kick-off meeting at the FDA. Regular meetings of the working group began in May 2012. Important intermediate findings and the final model (or models) will be published in peer-reviewed journals.