Toward Inclusivity in Preclinical Drug Development: A Proposition to Start with Intestinal Organoids.

Representation of humans from diverse backgrounds in the drug development process is key to advancing health equity, and while clinical trial design has recently made strides toward greater inclusivity, preclinical drug development has struggled to make those same gains. One barrier to inclusion is the current lack of robust and established in vitro model systems that simultaneously capture the complexity of human tissues while representing patient diversity. Here, the use of primary human intestinal organoids as a mechanism to advance inclusive preclinical research is proposed. This in vitro model system not only recapitulates tissue functions and disease states, but also retains the genetic identity and epigenetic signatures of the donors from which they are derived. Thus, intestinal organoids are an ideal in vitro prototype for capturing human diversity. In this perspective, the authors call for an industry-wide effort to leverage intestinal organoids as a starting point to actively and intentionally incorporate diversity into preclinical drug programs.