Lumping rare diseases sharing similar etiologies into broader clinical trials

Noam Y. Harel; originally posted 8/21/2008; updated 3/31/2013

(Inspired by conversations at the Clinical Trials Methods Course sponsored by NINDS and Univ. of Rochester 8/2008; special thanks to Dr. John Marler)
(Reinforced by publications that have appeared since originally posting this entry: Dobkin 2009; Hodes et al., 2013)

  • Many neurological diseases are extremely rare.
  • Some of these diseases fall into broader groups such as muscular dystrophies, lysosomal storage disorders, or neurodegenerative diseases.
  • Each of these broad groups of neurological diseases share several putative pathologic mechanisms - for example, protein aggregation in various neurodegenerative diseases; apoptosis in almost all of these diseases.
  • In many cases, similar drugs are tested in clinical trials for various different diseases in the same broader group - for instance, Coenzyme Q10 in ALS, Parkinson's, and Huntington's disease.

  • To increase recruitment, cut administrative costs, and expand generalizability, conduct larger trials recruiting patients with various diseases within broader groups, with fewer exclusion criteria.
  • Would need to normalize outcome measures on disease-specific scales - the new NIH Toolbox provides the perfect set of tests to do this.
  • Use pre-specified subgroup analyses to determine if a drug shows efficacy for one or more of a group of diseases.