- What are clinical research studies?
- What are the best types of clinical research studies?
- What are the important things to consider when designing a clinical trial?
- What is a Phase 1 study?
- What is a Phase 2 study?
- What is a Phase 3 study?
- What happens after a Phase 3 study is complete?
- Who determines if a clinical trial can be initiated?
Participating in a Clinical Trials:
- Who can participate in a clinical trial?
- Why should I participate in a clinical trial?
- Will participating in a clinical trial interfere with my current MS treatment?
- What would be my responsibility if I participated in a clinical trial?
- What are my rights as a participant of a clinical trial?
- What questions do I need to ask my doctor if they ask me to participate in a clinical trial?
MS Drugs in the News:
- I hear about new MS drugs in the news, yet it seems like it take years for new those drugs to be available. Why is that?
- What should I be listening for when I hear about a new MS drug in the news?
General Information About Clinical Research Studies
What are clinical research studies?
Clinical research studies are the basis of modern medicine and provide doctors with vital information on who would benefit from a medication. A therapy must first be proven by a series of properly designed clinical trials regulated by the Food and Drug Administration before someone can promote it. The Food and Drug Administration is a governmental agency that reviews the available information on a pharmaceutical, gives approval for the manufacture and specific marketing claims, and continues to survey the drug after the therapeutic has gone to market.
In this country, we do not prescribe medicine based upon speculation, casual observation, or personal experience. It is not adequate to say, “If it sounds good then it must be good.” It is also not adequate to think that if it worked for one person then it will work for all people. All therapies, regardless of how simple or safe they may sound, can have negative aspects. For example, side effects can vary from being mildly troublesome to dangerous and life-threatening. All treatments cost money and can take up your time. And an unproven treatment can interact with another medication you are taking. That is why it is important to distinguish those that truly work.
What are the best types of clinical research studies?
The best clinical study is called a randomized, double-blind, placebo-controlled trial. That’s a long name, but we will break down each component. Participants are typically given one of two possible therapies. If the trial is designed to compare the effects of drug A versus drug B, then this is called a head-to-head study. If one is trying to determine the effect of a drug versus no drug, then that is a placebo-controlled study.
Placebo is a substance that has no biologic activity (i.e., a sugar pill), making it a sham treatment. It should appear identical to the therapy being tested so that the participant will not know what they are getting. Having a placebo is important to show that the therapy being studied is better than nothing. There is a phenomenon called the “placebo-effect” which occurs in about one out of three people, and is associated with a true improvement despite not taking the medicine.
Another reason why placebo is important is because the study is “double-blinded.” This means that neither the participant nor the investigator knows who is getting which therapy. This is important because if you knew you were receiving the treatment, you might be more inclined to report an improvement because you want to be optimistic. Also, if the doctor knew what you were receiving, they might encourage you and suggest that you are doing better.
Finally, randomized means that neither the participant nor the investigator of the study is able to select which treatment is received. This allows the people from each group to have an equal chance at being assigned to either therapy. For example, if the investigator was able to select, they might give the treatment to those with worse disease, making it difficult to know if this group is doing better than the placebo group who is less affected.
What are the important things to consider when designing a clinical trial?
Clinical studies need to answer a question and must have a final result. The question is a hypothesis, which means a theory that has not been proven. For example, the hypothesis for the original Betaseron treatment trial that came out in 1993 was, “Is Betaseron better than placebo in reducing the number of relapses over 2 years?” For this the final result was relapse rate. Once a good question is formulated, and the final result decided upon, one has to determine how big the study will be and how long it will last. This is done by mathematical modeling based on previous knowledge which then indicates if a certain number of people have to be enrolled, and the certain number of years they are to be followed to show that the therapy in question will be worthwhile.
What is a Phase 1 study?
To paraphrase from the Food and Drug Administration website:
Phase 1 includes the initial introduction of an investigational new drug into humans. These studies are closely monitored and may be conducted in patients, but are usually conducted in healthy volunteers. These studies are designed to determine the metabolic and pharmacologic actions of the drug in humans, the side effects associated with increasing doses, and, if possible, to gain early evidence on effectiveness. During Phase 1, sufficient information about the drug's dosing and biologic effect should be obtained to permit the design of well-controlled, scientifically valid, Phase 2 studies. The total number of subjects included in Phase 1 studies varies with the drug, but is generally in the range of 20 to 80.
What is a Phase 2 study?
To paraphrase from the Food and Drug Administration website:
Phase 2 includes the early, controlled clinical studies conducted to obtain some preliminary data on the safety and sometimes the effectiveness of the drug for a particular indication in patients with the disease. This phase of testing also helps determine the common short-term side effects and risks associated with the drug. Phase 2 studies are typically well-controlled, closely monitored, and conducted in a relatively small number of patients, usually involving several hundred people.
What is a Phase 3 study?
To paraphrase from the Food and Drug Administration website:
Phase 3 studies are expanded controlled and uncontrolled trials. They are performed after preliminary evidence suggesting effectiveness of the drug has been obtained in Phase 2, and are intended to gather the additional information about effectiveness and safety that is needed to evaluate the overall benefit-risk relationship of the drug. Phase 3 studies usually include several hundred to several thousand people.
Why are clinical research studies important?
Clinical research forms the basis for how we determine whether a medicine is effective and safe. One needs to only look through the history of medicine to realize that treatments without evidence can be a very dangerous problem. People have come to have high expectations that the medicines physicians prescribe are effective, appropriate, and have a favorable benefit-risk profile. None of this would be possible without a clinical trial.
Who determines if a clinical trial can be initiated?
For a clinical trial to move forward, a number of things must be in place for it to start. First, the drug manufacturer often has a large say in the clinical trial because they most often pay for the study. There are some exceptions to this, but most manufacturers are not going to pay for a trial for a drug where they do not have exclusive rights or no competition. It is estimated to take more than $500 million to invent a new drug and bring it to market.
Next, the trial needs to have a well-formulated hypothesis and question. It must have a final result that will answer that question. It should have enough patients, and follow them long enough to show a benefit, if one exists. All of these things are determined by physicians and researchers, and go into the structure of the trial.
Next, the manufacturer needs to find the patients. For MS, this often means the manufacturer will have neurologists sign an agreement to become an investigator in the trial at their center.
Each center has a human studies committee who review the study protocol to ensure it meets governmental requirements, ensures safety, and that the study is ethical. The human studies committee is compromised of physicians, and people from all aspects of society. They continually review the study and need to be notified if there are any adverse reactions of the medication.
Who can participate in a clinical trial?
Clinical trials have “inclusion” and “exclusion” criteria. This is based upon the question being answered and specifics about the therapy. The inclusion and exclusion criteria vary widely among different studies, so who can participate depends on the specifics of a given trial.
- It is educational. That is, when you understand the detail, commitment, and level of involvement on the part of the investigator, then you can better appreciate how these medicines come to market. They also give you an inside view so you can distinguish those claims on the Internet with no proof versus the medicines that have been accepted by the scientific community.
- You can contribute to scientific knowledge. In order to discover new treatments, have them come to market, and learn how to use our available treatments most effectively, we need a great deal of people in clinical trials. Hence, you may be advancing the knowledge of MS, and can be part of something that may turn out to be a great benefit.
- You can receive a therapy not yet accepted or available. For those who are not doing well on standard therapy, it is encouraging to know that there is research trying to find that next great medicine. It can take many years for these things to come out, but you might be getting it before anyone else.
- You will receive exceptional care. People that participate in trials will see an MS specialist on a regular basis.
- People in clinical trials do better than those not in clinical trials. We do not know why this is true, but it is. Even those on placebo do better, so do not be too discouraged if you find out that you did not get the study medicine.
Will participating in a clinical trial interfere with my current MS treatment?
It depends upon the trial. Now that we have proven therapies for MS, people are reluctant to do placebo-controlled trials. However, there are circumstances when our approved therapies do not seem to be working. In these situations, trials can involve add on therapy where you continue to take your long-term therapy. Alternatively, you may need to stop your current therapy to go on the study medicine for a brief period of time. These are all things that would be addressed in specific when you hear about the details for a potential trial you are considering.
What would be my responsibility if I participated in a clinical trial?
Once you enroll in a clinical trial, it is important that you are committed to sticking with the treatment and completing your visits. If too many people drop out it is difficult to interpret the data, and the study may not be able to answer the question initially posed. Even if you do not think the medicine is working for you, you need to still go to your visits. If everyone who did not improve on the medicine dropped out of the study, it might appear as though the medicine worked in the end when it actually did not.
Of course, some people do drop out of every study. If you are having side effects or problems you can withdraw at any point. Also, one may have to drop out if they move away. After all, some of these trials can be lengthy, and one can never be sure where life will take them over a couple years.
What are my rights as a participant of a clinical trial?
First of all, you have the right to decline participation in a study. If you decline, your doctor should in no way make you feel as though this is not acceptable or that your care will be compromised. Once you decide to participate, you have the right to withdraw from the study at any point. However, you should have a valid reason for withdrawing. If too many people withdraw the end results could be compromised. Most studies have a safety committee that periodically reviews the study to ensure that there are no problems.
Understand how long the study is. Be sure to consider:
- Am I planning on moving out of the area soon?
- Am I planning on becoming pregnant soon?
- Find out how many visits will be required, and how long the visits will last. There may be unscheduled visits if you are having a relapse, otherwise, all studies have scheduled visits on a regular basis. Some visits may take several hours, which can be difficult if your work is inflexible. If you dislike MRI scans, you should find out how many are included in the study.
- Find out what are the treatment arms in the study. Is it a head-to-head drug comparison, a placebo-controlled trial, or a cross-over study where you get to receive both treatment arms?
- Find out if the study will pay for your medications. Some post-marketing studies have people continue on their medications from their pharmacy. Also, find out if parking is covered, and whether there is any reimbursement for time. Usually, reimbursement for your time is minimal if provided at all. Return to the questions
I hear about new MS drugs in the news, yet it seems like it take years for new those drugs to be available. Why is that?
Unfortunately, the scientific process takes a long time. It is frustrating, and on occasion may feel as though if they sped up the process there would be many more options for different diseases. This is particularly upsetting when people feel as though the clock is ticking in terms of their own disease.
However, the slowness is because science needs to be careful and meticulous. It is designed to prevent dangerous or ineffective drugs from coming to the market. There is a lot of interest in expediting approval of promising new therapies. This has to be weighed by the public’s interest in ensuring the safety of these therapies.
What should I be listening for when I hear about a new MS drug in the news?
A few words of caution when you hear about something on the news. First of all, usually the person on the news is the investigator or the pharmaceutical company who have an interest in self-promotion. Second, many stories on the news are about therapies that are still many years away from becoming accepted or approved. Third, stories about a recently published trial are often over-simplified or even misinterpreted.
Also, one needs to be cautious when gathering information on the internet. The internet has many anecdotal stories, which means that someone has made a limited observation but has not proven it. Also, the pharmaceutical companies manufacture MS educational sites that are also designed to promote their own product. And finally, be cautious on taking advice from other patients, because their circumstances might be different than yours.
The NMSS website is a reliable source to learn about different therapies, including those that are established and those that are being investigated and up-to-date on MS related press releases. And of course, speak with your doctor to see if an emerging therapy or trial might be suitable for your particular situation.