Phase IV Clinical Trials → Safety and adverse effects

Rigorous Phase I-III studies are required before a therapeutic can be marketed, however safety profiles of these new therapeutics may be incomplete due to limitations such as small sample sizes, short durations of study, and strict inclusion/exclusion criteria. A phase IV clinical trial overcomes some of these boundaries, as sample sizes are often much larger and studies are often much longer, with no set duration. Furthermore, the ‘real-world’ setting phase IV trials exist to ensure the safety profile of these therapeutics can be assessed in the broader population.

Phase IV studies can uncover serious side effects that were not uncovered in earlier phase trials. In the US, it was found that through post-marketing studies, approximately 20% of drugs acquired new black box warnings. Furthermore, 4% of drugs were eventually withdrawn due to safety concerns that emerged from these trials.

As phase IV trials incorporate significantly larger patient populations (sometimes 1000’s), this presents a unique opportunity to uncover rare side effects that may only present through large populations. If a side effect only presents in 1 in every 5000 patients, it will require a larger sample size than in most phase III trials to be discovered.

A drug will continue to have its safety monitored for the entire time it is available on the market. Pharmaceutical companies will have systems set in place to continually track and investigate side effects as they present and report them to the relevant regulatory authorities. This ensures therapies are continually evaluated, helping to keep patients safe.