What are Clinical Trials?

How Does a Clinical Trial Work?


A clinical trial is a way to systematically test whether a new drug or other kind of therapy can prevent, treat or cure a disease in people; they are sometimes called “interventional” trials (which are different from “observational” studies like Enroll-HD). Clinical trials often test drugs, but all kinds of other treatments—different diets, exercise and physiotherapy regimens, deep brain stimulation, surgical procedures, etc.—may also be tested this way.

Why do clinical trials?

No matter how good a new drug or treatment seems to be in animal models, it needs to be tested in a large group of people to show that it really works and to find out what side effects it might cause. Sometimes only a small percentage of people benefit, or sometimes dangerous side effects show up in only a minority.

In a short video, the UK Medical Research Council Clinical Trials unit explains how clinical trials are set up and why they are important:

Why do clinical trials move slowly?

Recruitment has a lot to do with it. Finding the right people to volunteer for a clinical trial is time-consuming, especially for rare diseases like HD. According to one estimate, getting enough volunteers typically takes twice as long as originally planned. Another reason that clinical trials can take so long is that safety is paramount and there are lots of regulations that must be complied with, meaning lots of paperwork and bureaucracy, for very good reasons.

What protects my safety in a clinical trial?

No international organization supervises clinical trials, but nearly all must get approval from either the US Food and Drug Administration, the European Medicines Agency, or both. In the US and Europe, almost all clinical trials also have oversight from an Institutional Review Board or IRB. This board includes doctors and scientists as well as community members. All trials involve some risk, but this board reviews the protocol for how the study will be conducted to make sure that the risks are reasonable and in proportion to the potential benefit. The informed consent form that you sign before you begin a clinical trial will clearly spell out the potential risks and benefits.

Will I get better care if I sign up for a clinical trial?

Not necessarily. Most trials don’t include complete medical care—you will still go to your regular doctors. Also, while sometimes the new drug or treatment is a real improvement over current alternatives, it may turn out not to be very effective, or it may cause side effects.

If I’m thinking about joining a clinical trial, what questions should I ask?

You should know whether you will have to modify your current medications or therapies, and who will be in charge of your health care. It’s good to know at the outset how long the study is expected to last, although you always have the right to withdraw from any study at any time.

You might ask why the research team thinks this treatment will be effective, or whether it’s been studied before. Another good question might be whether, if the experimental medicine works for you, you’ll be able to keep getting it after the study is done.

The US National Institutes of Health has more comprehensive lists of questions you might consider asking (en Espanol), as does the Medical Research Council of the UK.

How would I hear about trials if I join Enroll-HD?

When you sign up for Enroll-HD, you have the option to be contacted by your site staff should a suitable trial start up that is looking for volunteers like you. Read more about how that works here.

For more information:

Clinicaltrials.gov, run by the US National Institutes of Health, has more information about the clinical trial process and what volunteers should know. You can also search all the current clinical trials for Huntington’s disease.

The US National Institutes of Health has in-depth descriptions of what happens in a clinical trial.

European Huntington Disease Network (EHDN) provides information to people living with HD; finding clinics and support.

FAQ on clinical trials from the Huntington Study Group, which is involved in coordinating some studies for HD.

How are they structured?

researchDrugs are almost always first tested in animal models to get a sense of what the correct dosage should be, to look for dangerous side effects, and to get hints about whether it might help people with the disease.

Phase I

The first step in human testing is Phase I, 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.

Phase II

About 70 percent of all studies make it to the next step, a Phase II trial. Usually, people who have the disease in question are given the drug over a period of weeks or months. Phase II trials are designed to further evaluate safety—to 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 II 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?

Many trials are very choosy about which people will be included in this stage. This is so that the analysis won’t be clouded by other factors—they want to try to isolate the effect of the drug, and keep everything else the same. Trials often seek volunteers in a narrow age range with a specific set of symptoms, and no other health problems.

This type of trial is almost always randomized and blinded, meaning that the trial participants are randomly assigned to treatment groups, with some given the active treatment 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 know which is which.

Phase III

About one third of all drugs make it to a Phase III trial. This is the real acid test, when the drug or treatment is given to a larger and more diverse group of people. More than half of the drugs that have made it this far are successful in Phase III testing. The upshot is that the overall success rate for drugs that begin clinical trials is only about 20 percent.

If the treatment works, and if the side effects are not dangerous, the company or other institution or group sponsoring the trial will apply to regulatory authorities, like the US Food & Drug Administration and/or the European Medicines Agency, for approval. These agencies review the data and judge whether the balance of risk and benefit to patients is reasonable.