I’m Dr. Diana Zuckerman and I am president of the National Research Center for Women & Families. Our nonprofit think tank does not accept funding from pharmaceutical companies, and so I have no conflicts of interest.
Our think tank focuses on scrutinizing research to determine the risks and benefits of various medical products and procedures, and our main interest is promoting evidence-based medicine. My perspective today is as someone who is trained in epidemiology at Yale Medical School and also trained in psychology. I was on the faculty at Vassar and Yale, and a researcher at Harvard, and also a Fellow at the Center for Bioethics at the University of Pennsylvania. Also relevant today is I am on the board of directors of two nonprofit organizations that are dedicated to helping the FDA. That’s the congressionally mandated Reagan-Udall Foundation and the Alliance for a Stronger FDA.
I have spoken at dozens of these meetings, and I try to focus on the products that I think are most important and where I think the expertise that we can bring might be helpful. So I share the frustrations that have been expressed by some of the folks on the panel today. This was a very complicated set of data. I looked at the same materials that you did, I believe, and there was a lot of data. But unfortunately, from our point of view, not enough data on what we really wanted to know more about, which were the low dosage, the 10-milligram dosage. And so I want to just say a couple of things.
Our effort is always to look at the risk/benefit ratio, and I’m sure that’s something that you will also be doing, and certainly that’s what the FDA wants to do. What are the risks of this product, and what are the benefits, and what do we know? Do we know enough about those risks, and do we know enough about those benefits? And I felt that the FDA presentation seemed a little apologetic.
I think their determination to tease out as much information as possible is extremely important, and I think that their focus — not just looking at how many minutes faster do you fall asleep, but to really look at what are the benefits. When people have insomnia, it’s horrible to lie in bed not being able to sleep. I’m sure everyone in this room has had that experience, and I’ve had it too often. But what really matters is how you feel the next day. I am sure I’m not the only person who ever took a sleeping pill because I had a big drive the next day and I wanted to be sure that I got enough sleep. So if in fact the pill makes me sleepier or less able to drive well the next day, that’s really crucially important.
I do want to point out that on page 27 of the clinical review, there is a very clear presentation of what the benefits are in terms of additional sleep time, falling asleep faster, and staying asleep. And those benefits are statistically significant, but they’re often quite modest, especially at these lower dosages where you might have people, on average, falling asleep 5 minutes sooner or staying sleep 20 minutes longer. And that’s a pretty modest benefit if in fact they’re going to also feel tired the next day and more likely to fall asleep while driving.
So in summary, I would say that despite all the data, a tremendous amount of data, as the data came in and as it became increasingly clear that there were serious and substantial risks at the higher dosages, that has left us with a situation where we need better data at the lowest dosage — that’s 10 milligrams — and we don’t have that. Having 60 people in a study is just not sufficient. As frustrating as it was to look at individual patients, and I share the concern that individual patients can tell us just so much, we’re stuck with that kind of information. And it becomes important when you only have such a small number of people taking these low dosages.
So the choice is to either ask for more data before approval is given, and that is what we believe needs to be done; the other choice would be to provide really explicit labeling. But all of you in this room, I think, know the limits of labeling. Labeling is not enough. You could have a great warning. You could even have a black box warning saying, don’t take this drug if you’re planning to drive within 12 hours or 10 hours or whatever number of hours you might be able to come up with. But people are just not going to read it or they’re not going to understand how important it is.
So labeling is important, but not sufficient to protect people from adverse reactions. And postmarket studies aren’t, either. These products — and I don’t want to pick on this one pill because we know that there are problems with Ambien and other pills as well — hadn’t been studied adequately originally, and those drugs are being reviewed now by the FDA. And I congratulate the FDA for doing that.
We need to get a better sense of what the real benefits are, not just 5 minutes or 20 minutes more of uninterrupted sleep, but the actual functioning of a person on the next day. And we should know that information prior to approving a drug that’s clearly going to be used by many, many people.
In conclusion, I just want to say that I don’t envy your work today. It’s very difficult to plow through all this information. But I hope that you’ll be able to focus on the key issues here, which is how do we measure benefit? What is the purpose of sleeping pills? Why do people take them? Is it just that they want to fall asleep 5 minutes faster and don’t want to get up quite as often during the night, or is it a bigger issue than that? Is the real benefit how well they can function the next day, how well they can think, how well they can drive, and how well they can do all the things that we all try to do in our day-to-day life; and whether we need more data — and I believe that we do — more data to find out is 10 milligrams safe and is it effective?
A related issue is whether, if the dosage is high enough to be effective, is that inevitably going to cause problems with safety? In other words, if it works to help you fall asleep, is it more likely to keep you tired the next day, more likely to have you falling asleep while driving?
Thank you very much for the opportunity to speak today, and I’d be glad to answer any questions.
On August 13, 2014, the FDA announced that it approved Belsomra (suvorexant) in four dosages – 5, 10, 15, and 20 milligrams.