December 7, 2010
Thank you for the opportunity to speak today.
The National Research Center for Women & Families is dedicated to improving the health of adults and children. Our nonprofit center does not accept funding from companies that make medical products, so I have no conflicts of interest.
My perspective is as a researcher trained in epidemiology at Yale Med School, with experience doing research at Vassar and Harvard. I am also a fellow at the University of Pennsylvania Center for Bioethics.
We all know that obesity can kill, and that most weight loss strategies don’t work. The track record for diet pills is not impressive, and there is a great need for safe and effective treatments. But that doesn’t mean any diet pill that works for any patients should have FDA approval. I was sorry to hear this panel criticized for not recommending approval of several other diet pills in recent years, and for votes that encouraged the FDA to take Meridia off the market. Those votes reflected appropriate concerns about the lack of evidence to support FDA approval. This panel has done its job well, and that is to ensure that diet pills are safe and effective as a requirement for FDA approval. Thank you for sticking with those essential criteria.
I commend the sponsor for their large studies, including 4,500 patients. But, even so, the studies provide no information about the long-term risks or benefits of this drug for obesity, which is a long-term and often life-long condition.
It’s much easier to get statistically significant results when you have a large sample, even with modest benefits, and that is the situation with these data. NB patients were more likely to lose weight than the placebo group, but that represented only a few more pounds on average – only 7-9 pounds lighter for a person weighing 200 pounds. NB met some but not all of the weight loss effectiveness criteria set by the FDA. Diabetics were least likely to benefit from NB, unfortunately.
Most worrisome, the weight lost occurred during the first 6 months, with no additional weight loss in the second 6 months, on average. Progress was not made after 6 months. Would people stay on the drug when the pounds stop dropping and they have to pay for the drug? What would happen after they go off the drug? There are no data to answer those essential questions.
Those questions are especially important because almost half the patients assigned to NB chose to go off the drug in less than a year. I think I am correct that the statistics for weight loss at one year are based only on the patients who completed one year – not to total sample of patients who took NB.
Regarding safety, there were clear problems with blood pressure and pulse rates for all patients, although those that lost weight had improvements in blood pressure, especially compared to patients who didn’t lose weight. There were psychiatric-related events that could be serious. There were more cognitive problems, including attention disorders. There were modest health benefits among the NB patients who lost weight, but we don’t know the long-term risks or benefits to a patient’s health or even to their weight.
NB consists of two well-know drugs, with established safety profiles – and risk profiles. One of these drugs is the antidepressant Wellbutrin, which like all antidepressants, carries warnings about the risk of suicide for teens and young adults. However, unlike most antidepressants, it also includes black box warnings about suicide and depression for all adults, as well as seizures. Those risks are a high price to pay to lose an additional 3 or 4 pounds for every 100 pounds a person weighs, compared to placebo. Although many of us would like to lose 7 pounds or 10 pounds, obese patients won’t have much health benefit from that kind of weight loss, especially in the context of adverse reactions for the drug.
Antidepressants can be life-saving for people with debilitating depression. However, these mind-altering drugs have serious side effects that must not be taken lightly, especially for teens and young adults who might want to take a weight loss pill. Moreover, when people who were on antidepressants go off them, there can be problems as well.
In summary, we need better research before the FDA should consider approving this drug. We need to know how long people are likely to stay on NB, how much they would benefit if they stay on the drug for more than one year, and how would their weight and health be effected when they go off the drug.
We do patients no favors by allowing a drug to go on the market and be widely advertised, when we know the benefits are modest and the risks can be deadly. In these studies, most patients were healthy even though they were obese. In the real world, the patients will be less healthy and will certainly be less carefully monitored than they were in a clinical trial.
FDA Advisory Committee members often ask for post-market studies. In this case, that could be dangerous. This drug has modest benefits, and appears to have substantial potential for risks – such as high blood pressure and suicide. Studies of the two component drugs, as used for depressed patients, alcoholics, or drug addicts, are not sufficient. Better pre-market studies are needed – waiting for post-market studies raises ethical questions, because you would be exposing tens of thousands of patients – perhaps millions — to substantial risks. Cosmetic benefits are not enough to merit approval. I urge you to vote against approval until long-term data are available on NB specifically as a weight loss drug.