Questions and answers about clinical trials for Huntington’s Disease
What is a clinical trial?
Why are clinical trials needed?
Should you participate in a clinical trial?
How are research participants protected in a clinical trial?
Why does it take so long to test new treatments and are there ways to accelerate the process?
What is an observational trial?
Who sponsors, conducts, and oversees clinical and observational trials?
Why does it take so long to test new treatments and are there ways to accelerate the process?
What are the steps involved in getting a new treatment approved for people?
Are all drugs tested in clinical trials?
How can I learn more about clinical trials?
How can I find out about clinical trials for HD?
What is a clinical trial?
In a clinical trial (sometimes called a clinical study), patients receive experimental treatments that have not been thoroughly tested and approved for a particular indication. A clinical trial is set up to determine whether a treatment is safe and effective.
There are also clinical trials that do not involve taking experimental treatments. These are called observational trials
and are designed to gather information to gain a better understanding of all the factors that affect the disease or condition.
Why are clinical trials needed?
Clinical trials are the only reliable and objective way to determine if a treatment is safe and effective. In a clinical trial, the experimental treatment is compared to either the standard treatment or to a placebo (an inactive substance or procedure designed to mimic the drug or procedure that is being tested). The reliability of the trial is maximized by including large numbers of participants from diverse backgrounds. The objectivity of the trial is maximized by “blinding,” in which patients and clinicians do not know who is getting the experimental treatment or a placebo (this is called a “double blind study”). Both reliability and objectivity are ensured by collecting and analyzing data from all participants.
Should you participate in a clinical trial?
It’s your decision. In a clinical trial, you may be taking a drug for which the risks and benefits are not known, in contrast to taking drugs that are already approved, for which the risks and benefits have largely been determined. Before agreeing to be a part of a clinical trial, you should learn all you can about the possible risks known to be associated with the drug you would be taking. But you must also be aware that there may be unforeseen risks that are not known or predictable.
Risks and benefits have to be evaluated in the context of your disease and according to your personal values and preferences. Some people may be prepared to tolerate greater risks or more serious types of risks because they have a serious disorder. You, as the research participant, are the only person who can make this decision.
Some of the reasons you may want to participate are:
· Hope that the treatment being studied will slow your disease or lessen your symptoms.
· To advance research that may lead to a better understanding of the disease, future treatments, or preventive measures.
· To reduce your feelings of helplessness (feeling like you are DOING something).
· To get regular attention from the research team; this may have other benefits.
Some of the reasons you may not want to participate are:
· Concern that the trial will make your disease worse.
· Concern that you will experience adverse effects of treatments.
· Concern that participating in the trial will be inconvenient, requiring too much time to go to the clinic or hospital.
How are research participants protected in a clinical trial?
The regulatory agencies that oversee clinical trials have established systems for protecting subjects in clinical trials:
Informed Consent. All subjects in clinical trials must give informed consent, which is a process that helps provide full and complete understanding of the risks and benefits of the study before and after research participation begins. You should have an opportunity to discuss with the research team all of your questions and concerns regarding the study. You should also be given a document that spells out, in detail, all of the risks, whether minor or major. You will be required to sign this document, which should also include this information:
· Why the study is being done
· What will happen during the trial and over what period of time
· Anticipated benefits, including if no benefit can be expected
· Alternative treatments
· Your rights, including your right to leave the trial at any time
Institutional Review Board (IRB). The institution where the research is conducted will have an IRB that reviews the study plan to make sure it meets ethical and scientific standards. The informed consent document that you sign should specify that the study has been approved by the institution’s IRB.
Data Monitoring Committee. Most trials have an independent committee of specialists in the research area of interest that meet on a regular basis to review the progress of the trial and the data that has been gathered. This Data Monitoring Committee may recommend that a trial be stopped early if interim data indicate that there is either too high an incidence of adverse reactions or if the benefits of the trial are substantial.
Why does it take so long to test new treatments and are there ways to accelerate the process?
The process of testing new treatments and getting them approved for use by governmental regulatory agencies is a long one, taking anywhere from 8-12 years (see "What are the steps involved in getting a new treatment approved for people?” below). There have been several attempts to streamline this process; however, cutting corners increases the risk that questions will remain unanswered or adverse effects will not be detected. Some ways that the process can be streamlined include:
· Searching for drugs that have already been tested for other conditions to find agents that might be effective for HD. In the SET-HD process, for example, many of the drugs that are being evaluated for early entry into clinical trials already have been proven safe in persons who have other conditions.
· Conducting different phases of studies concurrently rather than sequentially. For example, sometimes phase I and II studies that look at safety, tolerability, toxicity, dosage, and effectiveness can be combined.
· Making decisions about how to proceed at interim points after independent data monitoring committee have reviewed results. Treatments that appear promising might be able to proceed to the next level of testing, while those that have no apparent benefit or high risks could be dropped, thus allowing resources to be concentrated on those treatments with the greatest potential.
Other efforts aimed at streamlining the search for effective treatments include searching for objective biological markers of disease progression that would indicate whether a treatment is having the desired effects. Identification of such “biomarkers” could greatly speed the testing of new treatments.
What is an observational trial?
An observational trial is different from a clinical or treatment trial in a number of ways. In an observational trial, no specific treatment is being studied. Subjects are not randomized into different groups and are not given either an experimental treatment or placebo. Instead, subjects are enrolled and observed over a period of time. Different types of data are collected from the participants and analyzed to look for trends and correlations that may inform us better about the disease and how to conduct a clinical trial involving experimental treatments. For example, data collected may include biological (e.g., blood or tissue analyzed for genetic factors or other biological substances), imaging (e.g., magnetic resonance imaging (MRI) or computed tomography (CT), family history, medical history (e.g., what treatments are being or have been used), clinical, behavioral, etc. Observational studies can be very powerful in terms of defining the natural history of a disease and gathering, in a systematic way, information about patients’ experiences with different forms of treatment. However, because observations studies are not controlled as in a treatment trial, they cannot make conclusions about cause and effect of particular treatments.
Two observational studies of HD are currently underway. The PREDICT-HD study: Neurobiological Predictors of Huntington's Disease is still accepting volunteers who are healthy but who have undergone DNA predictive testing and are known to carry the HD gene. Another study, PHAROS: Prospective Huntington At Risk Observational Study, has completed enrollment of 1001 individuals who are at risk for HD but have chosen not to be tested for the HD gene. Read more about the PREDICT-HD and PHAROS and studies at the NIH web site.
Who sponsors, conducts, and oversees clinical and observational trials?
Clinical trials may be sponsored or funded by pharmaceutical companies or by physicians, medical institutions, foundations, voluntary groups, or federal agencies such as the National Institutes of Health (NIH), the Department of Defense (DOD), and the Department of Veteran's Affairs (VA). The United States, Canada, Japan, Australia, and countries in Europe all have regulatory agencies and institutional review boards that review and regulate clinical trials. In the United States, the Food and Drug Administration (FDA) also sponsors some clinical trials for new treatments for orphan diseases like HD that affect a small percentage of the population.
What are the steps involved in getting a new treatment approved for people?
Every country has different regulatory agencies that oversee the approval of new treatments. While the exact procedure may vary from country to country, in general;
· Pre-clinical studies are the first step. This involves testing the compound in animals such as mice, rats, dogs, and monkeys. The purpose of these studies is to show that the compound does not cause cancer or other disease in humans, and to learn more about how the compound works and what happens to it in the body. Once it is shown to the regulatory agency that the compound appears to be safe and possibly effective in animals, testing in humans can begin.
· The first human studies that are done (Phase I studies in the United States) are designed to make sure the compound is safe and not toxic. These studies are typically done in a small number of healthy volunteers (20-50), usually in a hospital setting where they can be closely watched and treated should there be any side effects. The purpose of these studies is to determine how the experimental drug is absorbed, metabolized, and excreted in humans. Additionally, these studies seek to determine what types of side effects occur as the dosage of the drug is increased.
· Once a compound has been shown to be safe in healthy volunteers, studies in people that have the disease can begin. These studies (Phase II) are designed to evaluate the safety of the drug in the target population, the effectiveness of the drug, and the correct dose to use. Several hundred subjects may take part in Phase II trials, which may last for several weeks or months. For compounds being tested in HD patients, Phase II trials may enroll fewer (20-100) subjects. These trials are usually designed to compare the new drug with a standard treatment or placebo. Subjects are assigned randomly (as if by the flip of a coin) to either the experimental group or the control group. Often these studies are double-blinded.
Only about one third of new treatments successfully complete both Phase I and Phase II testing.
· Compounds that have been shown to be safe and effective in these early studies are then tested in larger groups of patients, sometimes numbering several hundred to several thousand, with the disease/condition of interest. These studies (Phase III) continue to be randomized and blinded. This large-scale testing provides the sponsors as well as the regulatory agencies with a more thorough understanding of the drug's effectiveness, benefits/risks, and range/severity of possible adverse side effects. These studies typically last several months or years.
· Following the successful completion of these studies, the sponsor submits the results of all of the studies to the regulatory agency (the FDA in the U.S.) If the regulatory agency approves, the sponsor may be allowed to market the compound as a drug, but only using evidence resulting from the studies.
· Even after the drug is on the market, the sponsor and regulatory agencies continue to monitor patients who are taking the drug to make sure there are no long-term safety concerns. In the U.S., these post-marketing studies are called Phase IV clinical trials. The data from these post-marketing studies may not be collected as rigorously or systematically as in other phases of the clinical trials process.
Are all drugs tested in clinical trials?
There are many drugs that are already on the market for other conditions. Once a drug is available, physicians may use it to treat conditions other than the one in which it has been studied. However, the drug may not work as well or may have unexpected side effects if it is used for other conditions. The same is true for many natural remedies, vitamins and herbal preparation. Their effects in people with HD may be unknown.
How can I learn more about clinical trials?
See the href="http://www.clinicaltrials.gov/ct/info/resources;jsessionid=4174FFA2447D6BB9D67E919E8168681B">NIH web site for more information about clinical trials or the FDA Center for Drug Evaluation Review web site.
How can I find out about clinical trials for HD?
Read about HD trials that are currently enrolling patients on this web site. More information may also be found on the Huntington Study Group web site. Other clinical trials may be listed at the NIH Clinicaltrials.gov web site. At this site, you can search for clinical trials for HD by typing “Huntington's disease” into the search box.