TESTIMONY Regarding Hylaform
Before the General and Plastic Surgery Advisory Panel
Food and Drug Administration
November 21, 2003
Good morning. My name is Elizabeth Santoro, and I am a Health Policy Fellow at the National Center for Policy Research for Women & Families. I am reading the testimony of our President, Dr. Diana Zuckerman, who regretfully could not be here today.
Our Center is a think tank that translates scientific research findings into meaningful information for the public. We use that research information to advocate for policies that benefit the health and safety of women, children, and families.
As I stated this morning, it is difficult for us to testify before the data are presented. We are basing this testimony on the information that was made available on the FDA website yesterday.
We have several concerns about Hylaform.
One concern about Hylaform is the lack of data for African Americans and Asian Americans. Only three of the patients are African American and only five are Asian American.
Our concerns about this are the same as those for Restylane, and to those that the National Medical Association and our Center expressed more generally to the FDA Commissioner a few months ago. Research clearly shows that African Americans and Asian Americans are more likely to produce keloids and can respond differently to procedures involving the skin. In addition, African Americans are more likely to develop autoimmune diseases than white women. The company has not studied a reasonable number of African Americans or Asian Americans to approve the product for those populations.
It is not appropriate to require studies of minority populations on a postmarket basis, since the FDA does not have the authority to enforce such requirements. The company should be required to do the studies before the product is approved.
It is similarly inappropriate to label the product “For Whites Only.” This would be acceptable if a product was found to be safe for whites but unsafe for other racial or ethnic groups. But, such a label is not appropriate as a way around a sponsor’s failure to conduct research on people of color. And, of course, if the product was approved it would probably be used off label for people of color, and that could potentially be dangerous. Research is needed, it won’t take long to do it, and it should be done.
We are also concerned about the sample size. The sample starts with only 133 people and only 123 are still in the study after 12 weeks. Since this is a cosmetic procedure that is likely to be used by hundreds of thousands – perhaps millions– of people, the product should be tested on a larger sample to determine if there are rare adverse reactions that are serious enough to consider before approval.
The study only lasted for 12 weeks, which is a major concern. According to the FDA’s slides, safety data for immunological responses were at 4 weeks. This is obviously too short a time to prove whether this product is safe.
Since this product doesn’t last long, women would need to undergo the procedure multiple times. It is clear from published reports that women who have a good outcome the first or second time they use this product may have serious adverse reactions after the third or later procedure. This needs to be studied before approval since it is clear that the product will be used more than once or twice.
The sponsor excluded women who had other procedures within the previous 6 months. This is not how the product would be used in the real world. Again, this raises safety questions.
A major shortcoming of this research is the high adverse reaction rate. I don’t consider this necessarily a problem of the product, but rather of the study design. It is not helpful for the sponsor to evaluate “adverse reactions” in a way that almost all the women using this product or Zyplast all have adverse reactions. The addition of “serious” or severe” adverse reactions is helpful, but it seems likely that there is a continuum of problems between what is listed as an adverse reaction (which almost everyone experiences) and what is listed as a serious adverse reaction (which almost nobody experiences). The standard needs to be set in a way that is more meaningful. For example, it should measure adverse reactions lasting more than a day or two. That would enable the FDA to determine how safe this product is compared to other products.
I don’t think the FDA should be approving a cosmetic product where 88 percent of the patients have adverse reactions. Either the FDA should reject such a product, or require the company to provide a more meaningful measure of adverse reactions.
In conclusion, I have even more concerns about this product than about Restylane. According to the company’s own data, the product is not necessarily better than the comparison product, Zyplast, and apparently may not last as long. For that reason, I believe rushing this product to market without gathering the additional data listed above is unwarranted.