Understanding the Clinical Trial Process

By Brett Drummond

When we talk about basic science discoveries related to multiple sclerosis, we often finish the article by explaining that this finding is likely to be 5-10 years away from potentially making it into the marketplace as a new treatment.  This timeframe is obviously frustrating for people living with MS, especially seeing as during this period, a lot of research may fail or run out of funding, and these discoveries then just disappear.  To help better understand the process that happens, we thought it would be beneficial to give a breakdown of the four different phases a clinical trial progresses through.

Phase 1:

This stage of the clinical trial process is undertaken to determine the safety of the new treatment.  This is performed in a small group of people (often less than 50) and seeks to identify any potential side-effects and the most well tolerated dose.  As this stage isn’t to assess the effectiveness of the treatment, it is often performed in healthy individuals.  News stories, such as the recent one in France, regarding serious problems in clinical trials are rare, but they are almost always during this phase.

Phase 2:

This stage is often the first time that the treatment will have been tested in people with the disease of interest and the number of people included in this trial will be much larger than any Phase I studies (often several hundred).  You will often hear the terms randomised and placebo-controlled when discussing Phase 2 studies.  This means that participants in the trial will be randomly placed into one of two groups, where they will either receive the treatment or a ‘fake’ treatment (known as the placebo).  These trials will be ‘blinded’ to both the participants and the researchers, which means that no one involved in the study is aware of whether each individual is taking the drug or the placebo.  This helps ensure that there is no bias, and so maximises the validity of results.

The purpose of these studies is to assess whether the therapy is effective – this is determined by designing and measuring a number of outcomes that relate to the expected benefits of the drug.  These can range from pathological signs (such as lesion formation or brain atrophy on MRI) to clinical outcomes (such as fatigue, walking speed or quality of life).  Safety continues to be monitored during this phase with any side-effects or adverse events recorded.

Phase 3:

Based on a successful Phase 2 trial, treatments move into this much larger study.  The number of participants in these studies can reach the thousands.  The main difference in the Phase 3 study is that the new treatment is tested in comparison to other therapeutic options.  As always, safety information is recorded to allow for the new medication to be administered safely if it becomes widely available.  A successful Phase 3 study is the last hurdle for a therapy to clear before it is released onto the market.

Phase 4:

Once the drug is on the market, Phase 4 studies are often performed.  These studies allow for the safety and efficacy of the treatment in the general population.  As earlier studies are often performed over a shorter period of time, long-term effects are also monitored during this trial.

There are many factors that can impact on the length of each of these phases, such as the time necessary to recruit appropriate numbers of participants for the study, and the desired length of the trial to assess the effectiveness.  As you can see, there is a considerable process that a treatment must go through from the point of discovery until it is released on the market.  However, this is done in the best interests of the community, as it is vital that the safety is properly assessed before it becomes available to the public.  Even with this process, we have seen a number of safety concerns with current MS medications, such as the development of PML, that have arisen from long-term use of these treatments.