My name is Dr. Margaret Dayhoff-Brannigan and I am a senior fellow at the National Center for Health Research. Our research center scrutinizes scientific and medical data and provides objective health information to patients, providers and policy makers. We do not accept funding from device companies, and therefore I have no conflicts of interest.
Thank you for the opportunity to speak here today.
I completed my Ph.D. in Biochemistry and Molecular Biology at the Johns Hopkins School of Public Health. Prior to receiving my doctorate, I conducted research at the Wilmer Eye Institute at Johns Hopkins. I bring a perspective as both a researcher and an advocate for improved safety of medical devices here today.
It is clear that patients suffering from Keratoconus or Corneal ectasia need treatment options. The risk-benefit analysis may support approval of corneal cross-linking for those patients, however we are very concerned about the data presented here showing limited efficacy. More than 25% of patients treated showed Kmax values that did NOT improve or stabilize. We are also extreemly concerned about off-label use of this risky technology. The incidence of adverse events from the cross-linking procedure is very high, so this procedure should NOT be used except for those diseases/conditions. We are already seeing Lasik procedures that include cross-linking in Europe, where standards are lower than in the US. This puts patients at unnecessary risk. Approving cross-linking could be a slippery slope that we need to avoid in our country to keep patients safe.
If cross-linking is approved, there are a few ways to prevent or at least greatly reduce off label use:
- A black box warning that specifies that the benefits are not proven to outweigh the risks for Lasik patients, and that the device is only approved for progressive Keratoconus or corneal ectasia. The black box should explain the risk of decreased vision, eye pain, irritation, infection, and severe chronic dry eyes. It should also explain that at least 25% of patients have NO improvement after treatment.
- FDA approval should be limited to patients over 16. Adolescence is a time of rapid eye development, and it is inappropriate to extrapolate the results from adults to adolescents.
- We urge the committee to recommend that FDA strictly limit the marketing of the cross-linking procedure to its approved purposes: progressive keratoconus and corneal ectasia on patients over 16.
The FDA has the authority to provide a black box warning warning about off label use. I urge you to ask the FDA this question: Can the FDA limit and enforce advertising, including in-office marketing?
In addition, we strongly recommend two other safeguards:
- FDA should require data on the off label use of this device.
- FDA should require the company to immediately start a post approval study to determine the long-term effect of the treatment particularly on teens and young adults. The data presented by Avedro cannot confirm if the procedure merely delays progression of the disease, or if it is a permanent solution. If the procedure is not a permanent solution, then it is important that patients use that information in determining if the risk of adverse events is worth the delayed progression.
In conclusion, it is crucial that patients have a safe and effective treatment option for progressive keratoconus and corneal ectasia. But the evidence indicates this treatment would do more harm than good for Lasik patients.
To protect the patients who would benefit and those who are likely to be harmed, the FDA needs to use a black box warning and minimize the off-label use of the product. Post market approval studies will also provide valuable information about the risk benefit for undergoing the procedure.
Thank you for your time.
Committee Vote:
First indication, Keratoconus: 10 Yes, 4 No, 1 Abstain
Second indication, Corneal ectasia: 6 Yes, 4 No, 4 Abstain, 1 No Voting