Ask the Doc: Q & A with Edward Kasarskis, MD, PhD

Edward Kasarskis, M.D., Ph.D. is Director of the multidisciplinary ALS Center at the University of Kentucky Neuroscience Center in Lexington, Kentucky, professor in the Department of Neurology at the University of Kentucky, and Chief of Neurology at the VA Medical Center in Lexington KY. 

	Dr. Kasarskis

The Nuts and Bolts of Clinical Trials

Q: What do you tell your patients when they are considering participating in a clinical trial? Is it worth the effort?

A: I can understand your concerns because clinical trials involve your willingness to be part of something without having any idea whether the study will be helpful to you. 

I always tell patients that they should understand that a clinical trial is actually an experiment. The purpose is to discover if a drug that worked on animals can be safe and effective with humans -- and work better than a placebo or the current best treatment.

When patients sign up to be part of a study, they sign a consent form that is actually a legal contract. It usually ranges from 6 to 25 pages long. Signing the “contract” can be a little overwhelming. Usually patients get the consent form to take home, and they come back and sit down with a doctor, nurse, or other member of the clinical trial team to review the form.

Patients agree to put their bodies on the line, volunteering to follow instructions related to the trial, such as faithfully taking medication or following some prescribed regimen.  They also will have blood or urine taken at regular intervals, or whatever else is spelled out in the form; provide personal information; and agree to record side effects.  They come for a study visit regularly, a process which can take up to 6 to 8 hours of poking and prodding. Patients are also informed that they are free to quit the trial at any time, no questions asked.  But for the good of the study and advancing knowledge, we hope that you stay with it to the end.  That means you should really understand what is being asked of you and make the commitment.

At the same time, the people in charge of the trial have responsibilities, too. They are expected to conduct the study to the best of their ability, exposing patients to the new treatment in the safest way possible, and by monitoring them very closely. If there’s a hint of any sort of problem, the trial leaders will do whatever is necessary to resolve it. Patients won’t have to pay for tests, the drug or treatment, or for exams.

So why should you do it? Everybody who participates in a study gets a great psychological benefit just by participating.  Participants are also monitored more than the average ALS patient, a factor which may contribute to better management of ALS.

Yes, it’s true: any trial participant could be placed (randomly, like a coin flip) on a placebo rather than the active test drug. But sometimes people taking the placebos are the lucky ones; the non-active drug may turn out to be no less effective than is the trial medication, or the test drug may actually cause troubling side effects or be harmful.  We have seen this in some ALS drug trials.

It’s helpful to know the three different types of trials involved in testing a potential new drug. Typically in what is called a “Phase 1” clinical trial, healthy humans are exposed to a single dose of the drug and monitored closely to see how quickly the drug is absorbed and how long it stays in the bloodstream.  This will develop information about how safe each dosage seems to be.

Once the nuts and bolts are tested in normal individuals, a “Phase 2” study tests the drug in the target population, with people who would actually need and will take the medication.  In our case, these are patients with ALS.  The researchers need to determine if the drug behaves similarly for these people just as it did in healthy volunteers, whether the dose is correct, and what the side effects are.
 
Actually the process can be sped up a bit since ALS is an uncommon illness.  Trials related to ALS may qualify for "orphan drug status," allowing a drug to be tested right away in ALS patients, bypassing normal volunteers.

Next, there’s a “Phase 3” trial, which takes the drug at the now-determined dose and evaluates it with a larger number of people.  This time, the drug is compared to a placebo or current standard of care to prove that the drug is effective or an improvement over current therapy.  Phase 3 trials are the definitive trial the outcome is critical to the drug approval process -- and have the most patients enrolled.

To get the drug approved by the Federal Drug Administration, (the FDA), the drug maker must provide the results of two independent studies that demonstrate the same results.

When does a patient get to know how the trial turns out? After all the data are gathered from the very last patient and after all the data are sealed so they can’t be tampered with, the test site is notified about which of their patients got the active drug and which got placebos. A patient enrolled early on in the study process may finish the trial early, but all patients usually have to wait until the trial is completed before they’ll learn whether they were taking the active drug or the placebo. (If early data shows the drug is extraordinarily effective, patients on placebo may be placed on the active drug). But typically, the first patient enrolled in a study might have to wait 2 years to know.

Many patients wonder or worry about how all this is regulated. There are actually two levels of protection for clinical trial participants:

    First, the details of how the study will be conducted are submitted to an independent “Institutional Review Board” (IRB) at the trial site, typically a university.  Physicians, nurses, pharmacists and community members are on the boards, and they review all the design and operational details.  You must have IRB approval before the study can start.  The IRB reviews and approves the consent form document that forms the contract between the study site and the research volunteer.

    A “Data Safety Monitoring Board,” a small group of people not connected with the study or the drug company in any way, monitors how the trial is conducted. The members of the board are the only people who know in real time who is taking the active drug and who is on placebo, and they watch for adverse events and other issues. They have the authority to stop the study immediately at any time should that be necessary.

So, now back to your original question: Yes, participating in a clinical trial is not only worth your effort but it is essential. Without people like you, no drug will ever be approved in the U.S. Every one of us benefits from what is learned from clinical trials of drugs, whether the treatments are found safe and effective, or not. 

If you would like to submit questions for a future Q & A, please send your questions to theexchange@alsa-national.org. Please understand that we won’t be able to address all questions and we won’t be able to respond to individuals personally.