Speaker’s Corner

Merit Cudkowicz, M.D., is an expert in designing clinical trials. An associate professor of neurology at Harvard Medical School, she co-directs the ALS clinic at Massachusetts General and often collaborates with Center scientists in setting up human therapy studies. Here, she answers our questions about ALS drug trials.

Q. How do ALS trials differ from, say, those for blood pressure drugs?

A. One catch in designing ALS trials arises because the disease can approach patients in different ways. In some people, speaking and breathing are affected first. In others, leg weakness heralds the disease. The speed of progression of symptoms also may differ. So it takes many measures to capture the “flavor” of the illness at the moment of study. For example, we follow muscle strength, breathing ability and the overall ability to function.

Q. What about looking at survival?

A. That’s one of the most important measures.

Q. But, then, won’t trials have to last years?

A. Not necessarily. To measure survival, a key principle is that the longer you follow people, the fewer you need to study. Because we’ve no time to waste, however, we’re planning trials with more people for a shorter time. With the ceftriaxone trial (see Three Drugs), we’re proposing up to 600 patients. It’s a placebo-controlled study we’ll submit to the FDA for review next month.

Q. And there’s no way around the placebo?

A. Not if you want to tell if a drug is effective. Because patients vary so widely in disease progression, it’s difficult to detect meaningful change without a comparison group. If you think your drug might deliver a 20 percent improvement in survival, you wouldn’t be able to detect that—to separate it from the usual life span differences people with ALS have—without a placebo group.

Also, sometimes drugs that we think are worth testing unexpectedly end up causing harm. Again, it could be hard to observe that without a placebo group. In fact, we recently saw this in an ALS trial—a negative effect we wouldn’t have detected otherwise.

Q. When you’re starting a new study, how do you pick subjects fairly?

A. We think carefully about this issue for every study and have discussed it broadly with patients, patient advocates and ethicists. There are no firm guidelines here, but fairness and openness are essential. One typical approach is “first come, first served,” assuming people meet a trial’s criteria. Once we get FDA and hospital approval to conduct a study, we tell our patients about it. At the same time, we work with patient foundations like ALSA or MDA to get out the word to everyone. We strive to encourage discussions with the ALS community on the fairest way to enroll trials.

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