Developing and Testing Theories
Scientists working at universities, pharmaceutical or biotechnology companies, and research centers are constantly testing out theories for how to make new or better HIV vaccines and prevention products. Initially, ideas can be tested in labs or tried out in mathematical models and computer simulations. Ideas are refined, and from the best approaches an experimental vaccine is developed.
Preclinical Testing
Preclinical testing is done to see if the product is safe in animals, and whether it may be appropriate to continue studies in people. The most common animals that are used in preclinical tests of HIV prevention products are mice, rabbits, and rhesus macaque monkeys. Even if a product looks safe in animals, the same may not be true in people. And no matter how much we learn in preclinical tests, only people can get HIV — human immunodeficiency virus, the virus that causes AIDS. Since animals’ immune systems are different from those of people, the only way to prove a new product's safety and effectiveness in people is to test it in people. If the product looks promising in animals, we have to make a decision about whether to move the product forward into human studies, called clinical trials.
Clinical Trials: Phases of Testing
Studies in human volunteers come in 3 main steps, or phases.
Phase 1 studies involve a small number of healthy volunteers, meaning they are HIV-negative and free of any significant medical problems. The main purpose of a Phase 1 study is to test the safety of the product, making sure that people do not experience significant side effects and do not become too uncomfortable following injections. We can also get a first look at whether the vaccine causes the desired immune responses.
Phase 2 studies involve larger numbers (hundreds) of volunteers. The purpose of Phase 2 studies is usually to understand more about the safety of the product and any immune responses it causes by studying it in more people. Questions about the right dose and the scheduling of the doses can usually be further sorted out at this stage.
Phase 2b and 3 studies involve several thousand volunteers who are considered to have a higher likelihood for acquiring HIV because of their sexual behavior or drug use. They are followed over time to determine if the study product actually works to prevent HIV. In HIV vaccine trials, the follow-up time is often 3-5 years.
In Phase 1 and Phase 2 clinical studies, we are not testing to see if a product protects anyone against getting HIV. We are only testing how the body responds to the products. To see if a product actually protects against HIV, an efficacy study is needed, which is often a Phase 3 study. However, sometimes the HVTN may use a special step called a Phase 2b study. A Phase 2b study is designed to test the concept of whether a product shows promise and should advance to a full Phase 3 study, or it should be scrapped. It is a quicker way to test the promise of an HIV study product. Phase 2b trials are larger than Phase 2 (involving thousands of participants), but smaller than a Phase 3 study, and can usually be done in 2-3 years.
It's complicated!
The process described above is the most simplified and streamlined. Vaccine and other prevention product development often works this way, but there can be more to it. For example, after a product is tested in a Phase 1 or 2 trial, it may be reformulated in a slightly different way, which would mean that it has to go back to Phase 1 again. Or, instead of a single new vaccine product being tested, researchers may invent a new vaccine strategy or use new combinations of vaccines, or identify new ways of giving the products besides traditional injections. Some studies may not involve new products at all, but are done to learn more about a certain part of the immune system or how the body works. In all cases, study volunteers play a crucial role. Progress toward finding effective prevention methods, and ultimately a safe and effective vaccine, could not be made without them.