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

What You Should Know About Joining a Clinical Trial

Q: I’m thinking about joining a clinical trial testing a possible new medication to treat ALS, but I’m not sure I like the idea of potentially being put on just the placebo drug. What should I know or consider?

A: This is a common question that comes up with every single trial -- why do we need a placebo group? Everyone goes into a clinical trial with high hopes that the drug being tested is going to be better than the placebo, an inactive drug. But that’s not always the case. Sometimes after the study is completed, it turns out that the test drug actually made patients worse. So the people who actually do the best can end up being the ones who are taking the placebo. For example, several years ago there was an important clinical trial of Lithium for ALS, but it turned out it was actually harmful to some ALS patients.

So what exactly is a clinical trial? You have to remember that it is simply a scientific experiment. Although clinical trials are based on a great deal of previous research, they are experiments in humans to prove that a test drug either helps, or does not help real people with ALS. Many of the drugs have been tested with success in animals, or in smaller observational studies in people. When you give a test drug into a large number of people with ALS, you don’t know for certain if it is safe or if it will effectively treat the disease.

Keep in mind that the people who work to develop effective drugs for ALS do so with great commitment and significant expense. Everyone is highly motivated to figure out a treatment that works. But to determine that a drug is effective, a randomized double-blinded clinical trial remains the "gold standard."

Let me explain what that means. A randomized study means that once you meet the criteria for being included in the clinical trial, you are placed in either the placebo group or a group getting the test drug under evaluation. Typical inclusion criteria might be age, sex, other medical conditions, how long you’ve had ALS, or your muscle strength and breathing capacity.

The decision of "drug or placebo" is made solely by chance almost like flipping a coin. The research pharmacist is the only person who knows what each research participant is getting. Nothing in the drug’s container or packaging will convey whether it is a placebo or the active drug -- they will look identical.

When a study is double blinded, it means neither the patient nor the research team knows what treatment the patient is taking (either placebo or active test drug). The double blind ensures that all people involved in the trial from the patient and the family, to the people administering the drug, to the trial leaders will be completely unbiased as they record drug side effects or potential improvements (in areas such as grip strength, or breathing capacity, for example). Without having a “blinded” system, staff would naturally be rooting for the person taking the active drug, hoping for a big discovery. And that could affect the quality and objectivity of the results.

In a clinical trial, patients are asked to take the medication faithfully according to directions and report any side effects they might have. It’s a big responsibility, especially considering patients and their families know that they may be doing all this and still just taking a placebo.

Developing successful new drugs for any condition can be very frustrating. Most studies are based on rock-solid preliminary data and are flawlessly done, but at the end of the day the test drug simply may not work. That was the case with the recent trial of Ceftiraxone.

Researchers know that patients and families typically only have one shot at a drug trial and they understand how frustrating it can be when a trial fails. But it may help to know that just participating in a clinical trial provides a positive psychological benefit. It gives participants a true sense of purpose since they are making a contribution to the global understanding of ALS. We always learn something.

The scientists may gain new insights into which classes of drugs might work for ALS, or could get information that helps them better understand how the disease works.

Although the slow march to new findings can be frustrating, it’s important to remember that all our understanding of science has been extremely incremental. I make this point with medical students and residents all the time. The amount of effort it takes to learn one solid fact in clinical medicine is monumental. It’s rare that there are big paradigm shifts or major insights from any single study or experiment.

To better understand this, consider how many iterations the concept of a cell phone has gone through. Watch the early James Bond movies and see the “portable” phones they were using. Those clunky machines have now evolved in everyday life into little computer-phones you can put in your pocket.

When it comes to developing new drugs for ALS, the pace of progress is also incremental. So while I am not satisfied with the pace of drug development, I encourage everyone with ALS to participate in any type of research dealing with the disease. We should all pay attention to the lyrics of the song from West Side Story, Something's Coming--"...the air is humming, and something great is coming!" In ALS, this won't happen without you.

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.