Clinical drug development is a systematic process designed to ensure new medicines are safe and effective. This intricate process spans many years, involving rigorous testing and evaluation. It requires significant scientific, financial, and human resources, all aimed at improving public health.
Before Human Trials
Before a potential drug is tested in people, it undergoes preclinical research. This stage involves laboratory studies, often conducted in test tubes (in vitro) and animals (in vivo). Researchers aim to understand how the drug interacts with biological systems, including its mechanism of action.
A key focus is pharmacodynamics, which explores what the drug does to the body, and pharmacokinetics, which investigates how the body handles the drug (absorption, distribution, metabolism, and excretion). Toxicology testing is also performed to identify potential toxic effects and determine a safe starting dose for human trials. On average, only about one in every 5,000 compounds that begin drug discovery eventually becomes an approved drug.
Testing in People
Once preclinical data supports a drug candidate’s safety, it may advance to human clinical trials. These trials are conducted under strict protocols to gather information on the drug’s safety, dosage, and effectiveness, while protecting participants.
Phase I
Phase I trials are the first human tests of a new drug. These studies involve a small group of 20 to 100 participants, who may be healthy volunteers or patients with the target disease. The primary goal is to assess the drug’s safety, determine a safe dosage range, and understand how the body processes it (pharmacokinetics). Researchers gradually increase doses while monitoring for side effects, aiming to find the maximum tolerated dose.
Phase II
If a drug demonstrates an acceptable safety profile in Phase I, it progresses to Phase II trials. These trials evaluate the drug’s effectiveness and further assess safety in a larger group of several dozen to several hundred patients with the specific condition. Phase II studies aim to determine if the drug has any biological activity or effect on the disease. Many are randomized, controlled studies where participants receive the new drug, a placebo, or standard treatment to minimize bias and ensure reliable results.
Phase III
Following successful Phase II results, a drug enters Phase III. These trials confirm the drug’s efficacy and safety, comparing it against existing treatments or a placebo. Phase III studies involve hundreds to several thousands of patients and are conducted at multiple sites. These trials are almost always randomized and blinded, meaning participants and sometimes researchers do not know who is receiving the new drug, which reduces bias. The data collected from Phase III trials provides evidence of the drug’s benefits and risks for regulatory approval.
Bringing New Medicines to Patients
After a drug successfully completes Phase III clinical trials, the manufacturer compiles all the gathered data into a submission for regulatory review. In the United States, this is typically a New Drug Application (NDA) for small-molecule drugs or a Biologics License Application (BLA) for biological products like vaccines or gene therapies. In Europe, a similar submission is made as a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA). These applications are extensive, containing detailed information from preclinical studies, all clinical trial results, manufacturing processes, and proposed labeling.
Regulatory bodies like the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) then rigorously review this submitted data. Their role is to assess the drug’s safety and efficacy, weighing its benefits against any potential risks. This review process involves expert evaluation by teams of scientists, clinicians, and statisticians. The time and resources involved in this regulatory review can be substantial, often taking several months to over a year, depending on the complexity of the drug and the completeness of the application. If the regulatory agency determines that the drug meets the required standards for safety and efficacy, it grants approval, allowing the medicine to be marketed and made available to patients.
After Approval
Drug development does not conclude with regulatory approval; instead, it transitions into a stage known as post-market surveillance, often referred to as Phase IV studies. This ongoing monitoring ensures the drug’s continued safety and effectiveness once it is widely available to the general public. Unlike the controlled environment of clinical trials, Phase IV collects real-world data from diverse patient populations, which can reveal rare side effects or long-term effects that may not have been apparent during earlier, smaller trials.
Pharmacovigilance systems are in place to collect and analyze reports of adverse events, enabling regulatory bodies and manufacturers to identify and address any new safety concerns promptly. This continuous oversight helps to refine the understanding of the drug’s risk-benefit profile in broader use. Additionally, Phase IV studies can explore new indications for the drug, evaluate its use in specific patient subgroups, or gather further data on its long-term benefits. This persistent monitoring is an integral part of ensuring patient safety and optimizing the use of approved medicines.