A Clinical Trials Primer

First, the obvious: everyone wishes there were more effective ALS treatments found already. Progress is being made, with five new genes discovered and two new treatments in the last five years—we are closer than ever to the possibility of a cure. But, even as we talk about how there have been real, tangible discoveries in ALS research, we cannot yet point to a reliable treatment to dramatically slow progression of the disease, let alone a treatment that stops progression or acts as a cure. It is heartbreaking for people with ALS and their families.

But for people with ALS, there is an active role they can take in fighting the disease: by participating in a clinical trial. For while the search new therapies begins in the laboratory, where ideas for new treatments are tested in cell cultures or test tubes, if a treatment shows enough promise it must eventually be tested on the intended end user, meaning human beings—living, breathing people.

While a clinical remains the best method researchers have developed to find effective treatments, they are not easy undertakings, and not without risks. Equally important to finding new effective treatments, clinical trials allow researchers to identify useless or harmful treatments before they are introduced to a large number of patients. Clinical trials are costly, can last for months, and when the treatment being tested proves to not be effective or inconclusive, it is disappointing for all involved. Still, clinical trials have proven to be the most reliable, fastest way to discover treatments that really work.

Right here in St. Louis, Dr. Tim Miller from Washington University is using clinical trials to identify biomarkers that will help identify other treatments from other clinical trials faster. As Dr. Miller says in this video, he considers those people with ALS who take part in clinical trials brave volunteers who are helping to advance the cause for everyone diagnosed with ALS and those yet to be diagnosed:

So far we’ve used the words “clinical trial” to cover all varieties of tests, but in research circles there are three distinct types, or phases, of clinical trials that each have unique goals and outcomes.

In a Phase I trial, a drug or treatment is given to a small number of people to see if it is safe and does not in fact have adverse or negative effects. The number of subjects in this phase is intentionally small to expose as few people as possible to an untried treatment, even though by the time a Phase I trial begins there is high confidence that the treatment is safe. While a Phase I trial may begin to show if the drug or treatment is effective in treating a disease, the testing of safety is main purpose of this phase. Further testing is necessary to determine the true effect of the treatment.

If a treatment’s Phase I trial is deemed successful, it can move to a Phase II trial. This trial begins to assess the treatment’s effectiveness as well as determine the correct dose, frequency and method of administration (pill, injection, etc.). While larger than a Phase I trial, a Phase II trial is still usually relatively small, involving less than 100 participants. In most cases in a Phase II trial the drug or treatment is tested against a placebo—an identical treatment that does not contain the drug. This type of test is called a double-blind trail, meaning neither the researcher nor the ALS patient knows if they are receiving the experimental treatment or the placebo.

The use of double-blind, placebo-controlled trials for a disease like ALS is troubling to some, given the fear that possibly successful treatments might at first be given to only a portion of the test group. However, such tests are in fact a necessary part of the process to control for the placebo effect—the tendency all of us have to feel better for a while when we think we are receiving a treatment that will help us. In fact, these double-blind tests speed the process of bringing prove effective treatments to the greater public.

If the drug shows positive signs of being both safe and effective in phase II, it will move to a Phase III trial. The Phase III trial is much larger than the proceeding two, almost always involving multiple researchers at different sites across the country and even the world. Phase III trials are always placebo-controlled, and incredibly expensive to conduct, sometimes costing billions of dollars. As such the ALS Association only provides funding through Phase II trials, to allow resources to be directed to promising treatments that stand the best chance to help the largest number of people with ALS. Because a successful Phase III trial allows the manufacture of the drug to apply to the United States Food and Drug Administration to bring the drug to market as an approved treatment, Phase III trials are almost always funded by pharmaceutical companies

So any breakthroughs in the treatment of ALS will progress through the clinical trial process. But the process cannot succeed without those willing to take part. The national ALS Association website describes those people with ALS who take part in clinical trials in this way:

“A person with ALS that participates in clinical trials is a hero. They give their precious time and could be exposed to possible hardships, even though it may be unlikely that they will not live to see its potential benefits, but know the trial could potentially help people in the future. In addition, even if a candidate fails to hold promise, the results of any clinical trial give new insight and direction to those working to solve the mysteries of ALS.”

If you are interested in participating in an ALS clinical trial or would like to learn more about the current research being done, the ALS Association partners with the Northeast ALS Consortium (NEALS) to provide the most accurate and up-to-date resource for information on both federally and privately funded clinical studies. Though a robust set of search tools you can find trials by location, type or phase.

We can’t know if a breakthrough treatment for ALS is in clinical trial now, or might begin soon, or is still years away. Indeed, the entire point of a clinical trial is by rigorous, unemotional study to make a research team prove they have found an effective treatment. But when such treatments are found they will be because in no small part of every person with ALS who has made the choice to a part of a clinical trial throughout the years. For that we all say thank you.

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