The FDA

Most of the public believes the mission of the FDA is to protect the public health. What people don't realize is how incredibly ineffective the FDA can be, and how the approval process for new devices can be corrupted by special interests. This occurs because the individuals who presumably have the expertise to conduct clinical trials and evaluate new technology have an interest in seeing it approved.

Lasers used for LASIK, PRK and other forms of refractive surgery are under the purview of the FDA. Clinical trials are conducted under an FDA Investigational Device Exemption. Laser manufacturers (and stockholders) have a huge financial stake in the clinical trials. Typically only "top" surgeons in the country are recruited as clinical trial investigators. The "top" surgeons "cherry-pick" the patients they enroll... patients that they know are likely to have a good result. Patients are meticulously screened for inclusion in clinical trials.

When a surgeon uses a laser for a procedure that is not FDA approved or performs a treatment that falls outside the approved indications, the treatment is considered "off label". Such uses fall under "practice of medicine," and are not regulated by FDA.

The FDA relies on advisory committees to provide independent advice from outside experts on new medical devices that are under deliberation at FDA. Although the committee provides advice to the Agency, final decisions are made by FDA. The committee that reviews data for refractive surgery lasers is called the Ophthalmic Devices Panel. Some panel members, particularly Dr. Michael Grimmett and Dr. Arthur Bradley, are honest scientists with a dispassionate interest in honestly evaluating the potential of new devices to serve or harm the public. Some other members of the panel appear to be brain dead, or simply "yes men," whose job it is to rubber stamp new technology without much critical inquiry. Unfortunately, Dr. Michael Grimmett and Dr. Arthur Bradley are no longer members of the panel, which represents a huge loss for patients everywhere.

The advisory committee meetings are open to the public. Transcripts of advisory committee meetings are published on the FDA website. Some very interesting exchanges can be found in the FDA transcripts -- exchanges which foreshadowed problems that the victims of refractive surgery knew about, but couldn't get anyone to pay attention to, because no one was interested.


Read excepts of testimony from FDA Ophthalmic Devices Panel meetings:


The testimony of Morris Waxler, former FDA official, sheds some light on why many, if not all, LASIK complications are under-reported. It appears that there is also a disconnect between the industry and the FDA. Dr. Waxler talks about the problem of under-reporting.

MR. HARRIS: And if the doctors were never told by Alcon that 10.5 percent, operating above 10.5 percent retreatment rate was a problem, they might not even know that, true?

DR. WAXLER: That's true. It's really an interesting situation where the, both the panel and Dr. Rosenthal explicitly stated in their panel meeting that the retreatment rate was an important part, and it was required of all manufacturers in response to panel members questions, and it was in the labeling, and it is in the labeling for all the machines, not just Alcon's. And the fact that neither Alcon nor apparently the agency or apparently the docs have emphasized that feature of the requirements doesn't mean it's not a problem. It means that there's been some serious problem in communication about the importance of retreatment and a lack of understanding of, of paying attention to it. And I think the manufacturer, you know, it's their machine. I mean, to be honest with you, I mean, the manufacturer incurs a heavy responsibility, and I feel for them because they really, you know, anybody can use their machine. They sell it to people. They don't -- they can't keep track of their outcomes. It's quite true. They depend on these docs to report to them. But they also -­- those docs depend on accurate information from the company about what was expected in terms of, you know, what's an acceptable retreatment rate. And I don't know from firsthand knowledge what, what Alcon communicated to its docs about what is an acceptable retreatment rate.

The Lastest Hype: What About Wavefront Results? There is a 9% dissatisfaction rate. See the FDA Alcon Meeting link just above for even more information.

DR. GRIMMETT: Dr. Michael Grimmett. I just had an observation and would like to hear if you have a comment. You may have none. There may be no answer. I found it curious that despite a very comprehensive analysis and sophisticated technology, that the patients that were unsatisfied or extremely unsatisfied approximated 9 percent. It's notable that the PERK study (A study of radial keratotomy patients) by comparison, using bear skins and stone knives, had an 11-percent dissatisfaction rate, and I found it curious that one in 10 patients are unsatisfied, despite a phenomenal amount of technology and analysis, and I would like to commend you on a superb analysis and presentation. Do you have a comment why it's still one in 10 despite all the sophisticated technology or is there no answer to that, sir?

DR. PETTIT: No. Well, I don't know everything.

DR. GRIMMETT: Dr. Bradley stated wavefront-guided LASIK does not reduce the level of higher-order aberrations of the preoperative eye, and he also wrote there's no way wavefront-guided LASIK can correct higher-order aberrations and render super-normal vision. That's the second statement. Is that not correct?

DR. BRADLEY: Your memory is better than mine, but I can look at the slide.

DR. GRIMMETT: No, I believe I transcribed it correctly.

DR. BULLIMORE: I agree. This is Dr. Bullimore. I agree with the sentiments of both of those statements. Exactly how the second one is worded, we could come back to, but the first one adequately ??

DR. WEISS: Can you repeat the first one again?

DR. GRIMMETT: Sure. Wavefront-guided LASIK does not reduce the level of higher-order aberrations of the preoperative eye.

DR. WEISS: Would that not be confusing to someone? Wouldn't that be confusing?

DR. GRIMMETT: Michael Grimmett. It may suggest somehow wording in that wasn't it that the higher-order aberrations were 20 percent higher than the preop eye in the wavefront-guided versus what, 80 percent was the number?

PARTICIPANT: Seventy-seven percent.

DR. WEISS: In here, is there any place saying that LASIK itself increases aberrations and that customized corneal ablation increases them less than conventional treatment?

DR. GRIMMETT: I think that's the idea.

DR. WEISS: So maybe we could put that wavefront-guided ablation ??

DR. GRIMMETT: Conventional LADARVision LASIK increases higher-order aberrations by that figure 77 percent while wavefront-guided LASIK increases them by whatever, 20 percent, whatever the number is, or you can say reduces them to a 20-percent level, if you want to use the word "reduces."

DR. BULLIMORE: I would avoid the term "reducing."

DR. WEISS: I would say each of them increases it because basically whether or not you're treating the preexistent or what's induced, the bottom line is you still have more aberrations than you did when you started off.

DR. GRIMMETT: Well, the intent is telling the traffic cop that you're speeding less than the other speeders.

In the following testimony, Ralph Rosenthal, M.D., Director, Division of Ophthalmic Devices, admits that patients don't do as well in the real world as they do in clinical trials. This meeting was called to review clinical trials of phakic intraocular lenses, another elective eye surgery to correct myopia.

Link to transcript

October 3, 2003

DR. WEISS: I think we have to be careful about this best physicians talking about lack of data. I'm sure these were good docs and good surgeons, but creating this extra god‑like category, I think we should take out of the discussion.

DR. BANDEEN‑ROCHE: That's a point well‑taken. That's a point well‑taken. Nonetheless, I mean, we hardly expect better performance in the field than we do in a clinical trial.

DR. McCULLEY: You don't have data to support that statement, do you? Do you have data to support that statement? You do. Okay.

DR. ROSENTHAL: With all kinds of devices.

DR. McCULLEY: All right.

DR. WEISS: What I would then like to lead to is since there's agreement ‑‑

DR. ROSENTHAL: Wait.

DR. WEISS: Yes.

DR. ROSENTHAL: I want to make sure I said the right thing. Once they go out in the field, they tend to have more problems than they do within the clinical trial.

DR. McCULLEY: But you don't have data to support that the people who do the trials are the best of the best.

DR. ROSENTHAL: No.

DR. McCULLEY: I think that is opinion ‑‑

DR. MACSAI: That's my opinion.

DR. McCULLEY: That is Marian's opinion, and it should not be in our discussions.

DR. WEISS: So we're going to take out the "god" factor out of the discussion.

(Laughter.)

This device causes a loss of endothelial cells, which are vital for the health of the cornea. These cells do not regenerate. If too many cells are lost, the cornea will become cloudy and result in vision loss. In the discussion that follows, you will see that panel members were concerned about the potential on-going loss of endothelial cell density with this device. Dr. Rosenthal, FDA Division Director, speaks up to protect physicians at the expense of patients' well-being. From the transcript:

DR. MATHERS: I would agree that it is important to patient care. There are some patients here that had very substantial loss in cell count, and you would want to pick those up. And it would be important for that patient's well‑being that you do so at some not short interval after surgery, perhaps a year or something like that.

DR. WEISS: So if you're going to give guidance as far as when repeat specular microscopy would be done, what would you suggest?

DR. MATHERS: As early as three months, possibly six, and at latest, one year.

DR. WEISS: Somewhere between six months and a year. Dr. Macsai.

DR. MACSAI: That's not what I intended by my comment.

DR. WEISS: What did you intend?

DR. MACSAI: My intention was that in my hands and my practice, if I was to implant this device, which appears to be an efficacious device, we don't have an answer about the long‑term endothelial damage. And I, as alluded to by both Dr. Sugar, Schein and Mathers, would want to know if my patient was getting into trouble. And if they go from 28 to 2000, there's trouble right here in River City, and it's time to decide if that thing is safer in or out. And I don't want to wait until there's microcystic edema and we're transplanting that cornea in a 4 year old.

DR. WEISS: What do you recommend for labeling though? This is what you do when ‑‑

DR. MACSAI: I want to suggest ‑‑

DR. WEISS: You suggest, okay.

DR. MACSAI: ‑‑ that the practitioner follow their patients with endothelial cell counts, because that's all we have.

SPEAKER: For what time?

DR. MACSAI: Well, my personal opinion, I would say five years. And when we got all this long‑term data that comes in, and it shows that I'm off the wall, I'll be the first to stand up and say thank you. I'm wrong, and then we can change the labeling on the device, and that will be a wonderful thing.

DR. WEISS: Well, actually, you know, we don't even have to ‑‑

DR. MACSAI: Annually for five years.

SPEAKER: Oh, annually.

DR. MACSAI: Is that what you want?

DR. WEISS: And actually, we don't even have to ‑‑ and I'll defer to Dr. Rosenthal. We could just say if this was what we're trying to ‑‑ everything is a suggestion here. Even our vote is a suggestion. We could say that ‑‑

DR. ROSENTHAL: If you suggest that you put it in labeling as a suggestion, you put doctors in liability risk if they don't do it. So if it's in the labeling, and it's not done, even as a suggestion, I think it holds greater water than a suggestion.

DR. WEISS: So you might be suggesting to the malpractice attorney to take that case.

DR. ROSENTHAL: Did I make myself clear?

DR. WEISS: Malvina.

SPEAKER: You put people at medical legal risk.

Later in the discussion:

DR. MACSAI:  You may not put it in your eye, but it meets the guidance.

July 1999 FDA Ophthalmic Devices Panel meeting: Dr. Rosenthal comments that it is outside the purview of the Agency if a physician fails to provide adequate informed consent to patients. Patients only recourse is to file a lawsuit against the physician.

DR. ROSENTHAL: We cannot tell them how to write an informed consent. We can tell them what the labeling issues are with respect to the device, the adverse events, the complications, the potential hazards, and we can embolden it in big bright blue letters, but if a doctor does not want to tell it to the patient, we cannot tell him to do so.

DR. MC CULLEY: The check and balance in the system for that physician who does not is our legal system.

DR. ROSENTHAL: I am afraid.

From the same meeting transcript, Dr. James P. McCulley, Chairman of the panel, seems to let Dr. Charles Casebeer off the hook when asked about the importance of pupil size:

DR. BULLIMORE: A couple of very quick questions while he is still at the table. Firstly, do you think pupil size is an important factor in patient satisfaction with this procedure?

DR. CASEBEER: As a personal matter, I mean do I, personally, think that?

DR. MC CULLEY: No, I don't think we want personal --

DR. BULLIMORE: Does the sponsor believe that pupil size is an important determinant in -- okay.

DR. CASEBEER: I want to answer, but it doesn't seem appropriate.

DR. MC CULLEY: No, I think you told us before you did not assess pupil size.

DR. CASEBEER: Correct. So, we have no opinion.

Pupil size measurement was required in the protocol for the clinical trials. So why did the FDA let the investigators get away with this?


The New York Times

Report Assails F.D.A. Oversight of Clinical Trials

By GARDINER HARRIS
Published: September 28, 2007

WASHINGTON, Sept. 27 — The Food and Drug Administration does very little to ensure the safety of the millions of people who participate in clinical trials, a federal investigator has found.

In a report due to be released Friday, the inspector general of the Department of Health and Human Services, Daniel R. Levinson, said federal health officials did not know how many clinical trials were being conducted, audited fewer than 1 percent of the testing sites and, on the rare occasions when inspectors did appear, generally showed up long after the tests had been completed.

The F.D.A. has 200 inspectors, some of whom audit clinical trials part time, to police an estimated 350,000 testing sites. Even when those inspectors found serious problems in human trials, top drug officials in Washington downgraded their findings 68 percent of the time, the report found. Among the remaining cases, the agency almost never followed up with inspections to determine whether the corrective actions that the agency demanded had occurred, the report found.

“In many ways, rats and mice get greater protection as research subjects in the United States than do humans,” said Arthur L. Caplan, chairman of the department of medical ethics at the University of Pennsylvania.

Read the entire article at: Article