As progress toward treatment grows, keeping track of clinical trials in neuromuscular diseases has become more important — and more daunting — than ever. These days, it's fairly easy to find scientific reports about clinical trials, but wading through the technical jargon in those reports can be difficult.
If you're considering enrolling in a clinical trial, you'll probably want to understand the trial's design and purpose. To make it easier, we've put together this list of common concepts and terms that describe how clinical trials are set up and analyzed.
Clinical trials are studies done in humans to evaluate potential medical treatments, such as drugs and devices, or techniques, from physical therapy to stem cell transplantation. By a loose definition, studies that examine one group of people before and after treatment could be considered clinical trials.
But by the strictest definition, a clinical trial compares a group of people receiving the experimental treatment, the treatment group, to a similar group of people who don't receive the treatment, the control group. Usually, the control group is given an inert substance called a placebo, so that any expectations participants may have about the experimental treatment will be the same in both groups and therefore theoretically won't influence the results. When the trial is finished, health differences between the two groups can be attributed to the treatment being tried instead of other factors, such as the natural course of a disease, positive expectations of a drug's effects, age or gender of the participants, and so forth.
Crossover trial design
Sometimes, midway through the trial, the group receiving the treatment switches to the placebo, and vice versa, with neither group knowing which substance is which. This crossover is done to address ethical concerns about depriving one group of a possibly beneficial treatment for the duration of the trial. Crossover trial designs encourage trial participation by promising all participants access to the experimental treatment for half the trial's duration.
Open-label trial design
In an open-label trial, everyone involved "sees the label" on the drug container and knows what he's taking. In this trial, there's no placebo group.
Single- and double-blinded
In a single-blinded trial, the participants don't know whether they're receiving a treatment or placebo until the trial is over. In a double-blinded trial, neither the participants nor the researchers know who's receiving treatment or placebo until the trial is over.
Both of these designs are meant to eliminate expectations that could bias the trial results. Placebo-controlled, double-blinded trials are the gold standard of clinical trials.
When reading about a clinical trial, it's important to recognize the trial's goals. Of course, the ultimate goal of clinical trials is to develop effective treatments for disease, but it's also important to uphold the physician's oath, "First, do no harm."
Trials usually take place in phases that move from ensuring safety to proving efficacy.
Phase 1 trials are designed primarily to evaluate the safety of an experimental treatment, given at a small dose. They're also used to smooth out potential problems in how the treatment is administered; for example, they can reveal whether or not a drug has access to the right cells in the body, and whether the drug triggers desired changes in those cells.
A phase 1 trial usually focuses on a small number of participants, sometimes healthy volunteers.
Phase 2 trials are meant to test safety and therapeutic efficacy, and usually involve an escalation of the treatment dose. The number of participants increases and is limited to people who have the disease under study.
Phase 3 trials are large-scale trials designed to establish the final word on therapeutic efficacy. Sometimes, a range of treatment doses is investigated to identify the optimal dosage. If the treatment proves beneficial, its developers will ask the U.S. Food and Drug Administration for permission to market it.
How do researchers use clinical trial data to determine whether a treatment is safe and effective? Ideally, they use statistical methods to determine if the treatment caused a difference between the control group and the treatment group.
Measures and means
Long before a clinical trial begins, researchers select one or more outcome measures or endpoints as indicators of the treatment's effects. For neuromuscular diseases, common outcome measures are muscle strength, quality of life and survival. Once the trial has stopped, the researchers compare the average (or mean) outcome measure in the treatment group to that in the control group.
A significant difference between the outcomes of the treatment group and the control group is taken as evidence that the treatment had some effect. To statisticians, "significant" doesn't mean "important"; it means that it's unlikely the difference could have occurred by chance. The numerical measure of significance is called the p-value.
Statisticians and researchers recognize two standard cutoffs for a significant difference — the .01 (1 percent) and .05 (5 percent) significance levels. A p-value below one of these levels means the difference would have been observed by chance less than 1 percent of the time, or less than 5 percent of the time.
Although p-values are arguably the most important data in a scientific study, they're reported in parentheses, like this: (p < .01), meaning the p-value is less than 1 percent.
A clinical trial is a test, in humans, of an experimental medication or other therapy.
Clinical trials are not treatments, but experiments. Although it's possible that benefit may be derived from participating in a clinical trial, it's also possible that no benefit — or even harm — may occur. Therefore, the decision about whether to participate in a clinical trial requires careful consideration. Keep your MDA clinic doctor informed about any clinical trial participation.
Please be aware that MDA has no ability to influence who is chosen to participate in a clinical trial.
Editor's Note: The above section, "About Clinical Trials," was added to this article on December 16, 2010.