The Touchstone in Drug Development: How Preclinical Studies Ensure the Validity and Safety of Clinical Trials

Each year the Food and Drug Administration (FDA) approves around 50 drugs for human use, some of which are submitted for consideration years in advance. It is a widely known fact that it can take a long time for drugs and vaccines to be approved for entering the market. Have you ever wondered why? In part, the answer is the rigorous three-phase clinical trial process.

The clinical trial process aims to ensure the efficacy and safety of the drug. However, it is both risky and unethical to test novel, unproven drugs that could bring potential adverse effects on humans as the initial step. Therefore, animal testing serves as an effective safety measure before conducting trials on humans. Animal studies are part of the drug development process and they are also used to study various aspects of the human body. For example, researchers have studied fruit flies to advance understanding in human genetics. However, there are inherent physiological differences between animal models and humans. In order to ensure the results are translatable between animals and humans, it is crucial to select the right animal model.

Animal testing commonly takes place during the preclinical phase of drug development. During this phase, a drug or a procedure is tested on animals for its efficacy and safety before it is administered to humans. A researcher must only resort to animal testing if there are no alternatives. They must use the smallest number of animal subjects that yield results. When selecting an animal model, ones with a less sensitive nervous system are preferred as this tends to decrease animal suffering.

Upon studying a specific concept, researchers use simple models that revolve around one signature idea or mechanism. For instance, one of the model organisms used for researching human diseases is a parasitic worm commonly referred to as C. elegans. It has 302 neurons, a mere fraction of the 86 billion that humans possess. The animal’s anatomy is extremely simplistic, consisting of the pharynx, intestines, gonads, and anus, all packed inside a streamlined body barely one millimeter in length. Despite the simplicity, it shares plenty of similarities with humans at a molecular level, making it an ideal model for studying various diseases and understanding the immune system.

Many research projects that involve animal subjects are funded by the National Institutes of Health (NIH), the primary agency for biomedical and public health research in the United States. At the NIH, a group of dedicated scientists with various fields of expertise under the Office of Science Policy meticulously inspect proposals involving animal research to ensure their efficacy.

“Science is collaborative. The best science is done when people with different lenses on the same issue come together,” said Dr. Jessica Creery, Health Science Policy Analyst at the NIH Office of Science Policy.

In addition to exploring the frontiers of science and health, one of the NIH’s primary concerns is animal welfare. To address this, researchers are required to use the simplest model possible to answer their complex research questions. Less complex models can ensure the obtainment of insightful data regarding one single notion or mechanism. Additionally, they can also indirectly reduce the number of animals involved due to inconclusive testing.

However, efforts to improve animal welfare do not stop here. NIH has been actively seeking novel replacements for animal testing that could further minimize ethical concerns.

An uprising alternative at the moment is the “organ-on-a-chip platform,” also known as micro-physiological systems. These chips are able to mimic human physiology in extreme environments. One of the primary areas of application for this piece of technology is in outer space research. When humans are exposed to zero gravity for a prolonged period, their tissues demonstrate an accelerated process of aging. Health concerns such as osteoporosis, a condition where the bones become fragile, and muscle deterioration accompany this aging process, placing astronauts at great risk. However, with this chip, researchers will be able to better understand how human tissues interact with microgravity environments without having to send anybody into space. This could be the paving stone for future technology that minimizes the aging process for astronauts.

Organ-on-a-chip technologies and animal testing essentially share the same purpose. Both are non-human alternatives for studies that have implications for human subjects, which could help humanity become better. However, there is still a long way to go before they become mature enough to fully replace animal testing. Animals, at the moment, are still the most ideal subjects for preclinical study due to their similarity to humans in various aspects.