How a Research Idea Transforms Into a Clinical Trial

A brilliant idea in the lab sometimes can lead to therapeutic breakthroughs, but the journey from an idea to a product is a long and often arduous one. It takes roughly 10 to 15 years for a drug to get from the lab to clinical use.^{1, 2}

Much of that work occurs before the first clinical trial participant is enrolled.

Drug discovery and development

The drug discovery process generally starts with target identification, which involves finding a gene or protein that plays a significant role in a disease. That means scientists need to know what factors contribute to the disease. Is it tied to a specific gene or protein? Are there potential biomarkers?

At this stage in the process, thousands of compounds may be possible therapeutic candidates, so researchers narrow this down and those that merit additional study. This process can take years. Once a new candidate looks promising, it must go through preclinical testing to ensure that it’s safe to test in humans.

Preclinical research

Once scientists identify a promising drug candidate, research continues into a wide range of issues, including its mechanism of action; how it’s absorbed, distributed, metabolized and excreted; potential toxicity; and the optimal methods of administration (pill, infusion, etc.)³

Preclinical research typically involves in vitro and in vivo models — and sometimes, in silico — models. The goal is to obtain basic information about the safety and biological efficacy of a drug candidate before testing it in humans. If you’re not familiar with these three terms, here are brief explanations:

• In vitro (literally, “within the glass”) takes place in a lab and typically involves human or animal cells grown on a dish. Researchers will expose cells to the drug candidate to assess the effects. This approach can be especially useful in identifying any toxic or carcinogenic effects. However, in vitro tests cannot replicate the conditions that occur inside a living organism.⁴
• In vivo (literally, “within the living”) refers to experiments that are carried out using a whole, living organism, such as a mouse. In vivo studies enable scientists to better evaluate the safety and efficacy of a drug candidate. They also help in determining dosage and gender differences, and effectiveness on mitigating pathologies recapitulated into these disease models.^{5, 6}
• In silico, or testing performed on computer or via computer simulation, is relatively new. Researchers often use these tests to predict how potential therapies interact with the body and with pathogens.⁷

Only after a drug candidate passes pre-clinical testing will human clinical trials begin.

Translation Into Clinical Trial

Moving from an idea to a clinical trial represents translational research — taking scientific discoveries made in the lab and “translating” them into new treatments. It bridges the gap between the basic science (at the lab bench) and their incorporation into clinical application (at the patient bedside).⁸ That bridge can be a long and frustrating one. We’re still crossing it.

Notes

1. Lansdowne, L. E.: Exploring the Drug Development Process. Drug Discovery from Technology Networks (2020)
2. Pascoe, E. M. et al.: Explainer: how do drugs get from the point of discovery to the pharmacy shelf? Conversation (2017)
3. The Drug Development Process, FDA. 2018
4. In vitro vs. In vivo: Is One Better?, UHN Research, University of Toronto.
5. Differences between in vitro, in vivo, and in silico studies,” The Marshall Protocol Knowledge Base, last modified Sept. 1, 2019
6. In vitro vs. In vivo: Is One Better, op.cit.
7. “Differences between in vitro, in vivo, and in silico studies,” op. cit.
8. Seyhan, A.A. Lost in translation: the valley of death across preclinical and clinical divide – identification of problems and overcoming obstacles. transl med commun 4, 18 (2019), https://doi.org/10.1186/s41231-019-0050-7