General questions

What are clinical trials and are they enough to prove a vaccine is safe?


Clinical trials are research studies performed in people to evaluate a medical, surgical, or behavioral intervention. They are the primary way that researchers find out if a new treatment or medical device, including a vaccine, is safe and effective in people.

Clinical trials advance through four phases to test a vaccine, find the appropriate dosage, and look for side effects. If, after the first three phases, researchers find a vaccine to be safe and effective, regulatory agencies can evaluate all the information and may approve it for clinical use while continuing to monitor its effects.

A Phase I trial tests an experimental vaccine on a small group of often healthy people (20 to 80) to judge its safety and side effects.

A Phase II trial uses more people (100 to 300). While the emphasis in Phase I is on safety, Phase II focuses on safety, immunogenicity (the immune response triggered by the vaccine), and efficacy (whether the vaccine prevents the disease). So, this phase gathers data on whether the vaccine generates an immune response in people in various categories of age, ethnicity and gender.

A Phase III trial gathers more information about efficacy and safety, studying different populations and different dosages. The number of subjects usually ranges from several hundred to thousands of people. Phase 3 trial is essential for registration and approval to market of a vaccine. If the regulatory authority agrees that the trial results are positive, it will approve the new vaccine.

Phase IV trials take place after approval of use. Effectiveness and safety are monitored in large, diverse populations. Sometimes, the side effects of a vaccine may not become clear until more people have taken it over a longer period of time.

All of these steps are standard in vaccine development, and all of them have been followed in developing COVID-19 vaccines that have received WHO Emergency Use Listing pre-qualification or authorization from stringent regulatory authorities.