Clinical Trials in a Dish: A Perspective on the Coming Revolution in Drug Development.

The pharmaceutical industry is facing unprecedented challenges as the cost of developing new drugs has reached unsustainable levels, fueled in large parts by a high attrition rate in clinical development. Strategies to bridge studies between preclinical testing and clinical trials are needed to reduce the knowledge gap and allow earlier decisions to be made on the continuation or discontinuation of further development of drugs. The discovery and development of human induced pluripotent stem cells (hiPSCs) have opened up new avenues that support the concept of screening for cell-based safety and toxicity at the level of a population. This approach, termed "Clinical Trials in a Dish" (CTiD), allows testing medical therapies for safety or efficacy on cells collected from a representative sample of human patients, before moving into actual clinical trials. It can be applied to the development of drugs for specific populations, and it allows predicting not only the magnitude of effects but also the incidence of patients in a population who will benefit or be harmed by these drugs. This, in turn, can lead to the selection of safer drugs to move into clinical development, resulting in a reduction in attrition. The current article offers a perspective of this new model for "humanized" preclinical drug development.

Challenges in designing and executing clinical trials in a dish studies.

The ever-increasing cost of drug discovery and development represents a significant challenge for the pharmaceutical industry and new strategies to bridge studies between preclinical testing and clinical trials are needed to reduce the knowledge gap prior to first human exposures, and to allow earlier decisions to be made on the further development of drugs. A number of studies have demonstrated that various cell types differentiated from human induced pluripotent stem cells (iPSCs) do not just respond similarly to human tissues in general, but rather recapitulate the drug response of their specific donor's, when exposed to the same drug in vivo. This recapitulation opens the doors to Clinical Trials in a Dish (CTiD), a platform which involves testing, in vitro, medical therapies for safety on cells collected from a sample of human patients, before moving into clinical trials. However, the science behind CTiD is complex, and every element of the process from tissue acquisition to data generation must be assessed and designed to meet quality metrics and standards. Without such rigorous assessment and design, the basic scientific integrity of CTiD constructs is likely compromised, and the results questionable. Given the lack of standard process and/or quality metrics in place for the use of stem cell-based products for in vitro testing per se, we discuss here the key elements that one needs to consider when designing, implementing and executing CTiD studies, in order to ensure an approach that will reliably mimic clinical trials, and allow obtaining reproducible and reliable experimental data.