Learn more about clinical trials
Video: The Gold Standard
What are randomised controlled trials and why are they important?
In this short video, the UK Medical Research Council Clinical Trials unit explains how clinical trials are set up and why they are important:
How are clinical trials structured?
The first step in human testing is Phase 1, which mainly looks at the safety of a potential drug. The drug is given to a small number of healthy people at various doses for a short time to make sure they don’t develop any serious side effects. These trials usually last several months. About 25%1 of all HD drugs and interventions tested in Phase 1 trial make it to the next step.
Phase 2 trials are designed to further evaluate safety and make sure that the drug doesn’t cause problems in a larger group of people who actually have the disease, and to look at what dose can be given to people. Often a Phase 2 trial is also designed to give an early hint about efficacy, meaning whether or not it is effective—does the drug show signs that it might be beneficial to patients? These trials typically last from several months to two years. About 20%1 of HD drugs and interventions tested in Phase 2 trials make it to the next step.
Most Phase 2 trials are very choosy about which people will be included in this stage, and often seek volunteers in a narrow age range with a specific set of symptoms and no other health problems. This is so that the analysis won’t be clouded by other factors—they want to try to isolate any effect the drug may have and keep everything else the same.
Phase 2 trials are almost always randomized and blinded, meaning that the trial participants are randomly assigned to treatment groups, with some given the active drug at different doses and others given a placebo—a sugar pill or something else known to be inactive—without anyone knowing what kind of treatment they are getting (this is the ‘blinded’ part). This is to prevent people’s hopes or subconscious biases from influencing the results. Even the staff who run the study don’t know which people are getting the experimental drug—only the people who analyze the data get to know who got what.
Phase 3 trials are the real acid test, when the drug is given to a larger and more diverse group of people. The goal is to see if the drug or treatment is effective, that is, does it offer a clinical benefit to patients and improve their course of disease or signs/symptoms. These trials usually last one to four years and also provide further safety data, monitoring for adverse reactions or side effects.
If the drug is effective, and if the side effects are not dangerous, the company or other institution sponsoring the trial will apply to regulatory authorities (like the US FDA and/or the EMA in Europe) for approval. These agencies review the data and judge whether the balance of benefit and risk to patients is reasonable. About 14%1 of the HD drugs or interventions that enter Phase 3 trials are successful and gain approval. Given the drugs that don’t make it past Phase 1 or Phase 2, that means that only about 3.5%1 of HD drugs or interventions that begin testing in humans are eventually approved and available for use by doctors for clinical use.
1 Travessa AM, Rodrigues FB, Mestre TA, Ferreira JJ. Fifteen Years of Clinical Trials in Huntington’s Disease: A Very Low Clinical Drug Development Success Rate. J Huntingtons Dis. 2017;6(2):157-163. doi: 10.3233/JHD-170245. PMID: 28671135.