Preclinical Studies & Clinical Trials

Introduction and Necessary of Preclinical Studies & Clinical Trials

The process of developing new drugs is always time-consuming and costly. Thorough in vitro and in vivo preclinical testing is essential to evaluate aspects of pharmacodynamics, pharmacokinetics, and toxicology for new drugs. To better mimic the complex mechanisms of human diseases, it is necessary to optimize current standard preclinical and clinical approaches.

Further clinical trials refer to the clinical studies on human participants. The data on dosage, safety, and efficacy can be obtained. Generally speaking, clinical trials must be approved by the health authority/ethics committee in the corresponding country/region before proceeding. According to statistics, only 10% of all drugs in human clinical trials become approved drugs.

Fig 1. From basic research to an approved drug. (Honek, 2017)

Introduction of Preclinical Studies

Preclinical research aims to provide information about the safety and effectiveness of drug candidates before they are tested in humans. Furthermore, preclinical studies have to follow guidelines dictated by Good Laboratory Practice to ensure reliable results.

• Pharmacodynamics

Pharmacodynamics describes what does the drug affects the body. The relationship between the drug concentration and its dose-response shows the doses causing therapeutic effect and toxicity.

• Pharmacokinetics

Pharmacokinetics describes what does the body affects the drug. The drug effect is determined by its absorption, distribution, metabolism, and excretion (ADME). The distribution of the drug in the body can be determined by the drug’s affinity for plasma proteins, the drug’s molecular properties and polarity, as well as tissue vascularization.

• Toxicology

Toxicology describes whether the drug is safe in the body. The preclinical toxicology studies allow the determination of safe and suitable starting doses for clinical trials. Furthermore, the carcinogenicity, genotoxicity, and reproductive toxicity can be evaluated using yeast-based in vitro systems or rats.

The Ideal Preclinical Models

• In vitro models - a relatively fast, simple, and cost-efficient way to study the drug in a Petri dish.
• In vivo models - to study the drug using complete organism based on various animal models, including the novel patient-derived xenograft (PDX) models, orthotopic tumor models, and genetically engineered mice (GEM).
• In silico models - to predict how the drug might behave in subsequent in vitro and in vivo experiments.

Phases of Clinical Trials

• Phase 0 clinical trials: Exploring if and how a new drug may work?
• Phase I clinical trials: Is the treatment safe?
• Phase II clinical trials: Does the treatment work?
• Phase III clinical trials: Is it better than what’s already available?
• Phase IV clinical trials: What else do we need to know?

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Reference

1. Honek, J. Preclinical research in drug development. Medical Writing. 2017, 26: 5-8.