The Lone Dog :: Our Friends and Protectors at the FDA

[Note: This article was initially drafted over 4 years ago when the Lone Dog was barking more loudly, but it was never posted on lasermyeye.org due to canine exhaustion and a feeling that the moment wasn't right. The current moment seems more right, especially after the recent ODP meeting. For those of you clicking to this link from the FDA's petition web site, be advised that the Lone Dog is a disreputable dog. He writes mostly for his own amusement. If you don't like his style, don't read it. The earlier Lone Dog articles are still on-line at this link .]

The Lone Dog has taken to perusing the Food and Drug Administration’s online document archives. All good citizens should understand how their government works. An ultra-compressed version of “getting your excimer laser approved” is as follows:

1] The manufacturer submits an application for an Investigational Device Exemption (IDE), which allows the laser to be used on live human eyeballs to see what will happen (at this point nobody really knows); details of how the laser will be used, what types of eyeballs will be blasted, safety monitors, efficacy monitors, etc. are all hammered out and they’re off to the clinical trial! The IDE research protocol is typically extremely specific, and if investigators note some problems during the trial which can be ameliorated by changing the protocol they may not bother to do so because of the hassle factor. This led, among other things, to the approval of a 5.5x7.5 mm optical zone for the Alcon Summit Autonomous LADARvision laser despite the fact that the investigators quickly learned that it was too small and could wreck night vision, with more than a few patients refusing to have their second eyes done because of vision quality loss.

2] Having collected its data, with interim disaster reports to the FDA, the manufacturer then submits a Premarket Approval Application (PMA); at this point the manufacturer is converted to a higher governmental life form and becomes the “sponsor” of the PMA.

3] The PMA is sent to the Ophthalmic Devices Panel (ODP), a group of concerned and mostly qualified citizens educated in the same general field as the device in question (i.e., optometrists and ophthalmologists). These are not FDA employees and (supposedly) have no financial conflicts of interest. Their job is to represent and protect the public interest, which means sniffing out the bullshit. Since the manufacturer has control of all the original data the LD can assure you that data-morphing is rampant. What is typically presented is slide after slide of charts, graphs, and teeny print stuff with the express purpose of showing the pretty side of the cake.

To its credit, the ODP seems generally tuned in to this behavior. If you care to slog through 300+ pages of transcribed minutes per meeting, you will detect some of the smarter people questioning and complaining about the sponsor’s data presentation. However, by the time the laser gets to the PMA stage, a huge amount of someone’s money has been sunk into the project, the FDA proper has agreed to let the PMA be submitted, and there’s a lot of momentum for approval. Plus, the ODP members all have day jobs, aren’t being paid for this work, and may not have the background necessary to detect garbage-in-garbage-out data. Remember, garbage out data is data that seems appropriate to collect, looks good, but means nothing because the method of obtaining the information or measuring the outcome was invalid. There are two big GIGOs in laser vision correction clinical trials: a) the use of refractive error as a limited proxy measurement of the primary effect of the laser, which is to reshape the cornea; and b) the use of unvalidated patient satisfaction surveys that did not effectively determine the frequency and functional severity of side effects such as glare, arcs, starbursts and halos (GASH), loss of contrast sensitivity, or dry eye symptoms.

4] The ODP can approve the PMA as is, can reject it, or can approve it with stipulations about the labeling. You know those package inserts in pill bottles? Excimer lasers have package inserts. I kid you not. The Panel’s major weapon in the public defense is to force the manufacturer to include specific statements in the product labeling that restrict the approved uses of the laser. A simple example is age range: the manufacturer will ask for approval down to 18 years old, the Panel will point out that they didn’t study any 18 year old patients, and the labeling will have to reflect the approved age range of 21+ years. Does this stop anyone from using the laser on younger patients? No.

However, the Panel can insist on statements about contraindications and can require manufacturers to present to surgeons and patients the safety and efficacy data in a certain format that is, ideally, more honest and easier to understand.

As a sidebar, the specific individuals that compose the Ophthalmic Devices Panel at any one time obviously influence the proceedings. The LD has passing knowledge of the wits and personalities of some of the recent Panel members and you are about to meet one yourself.

The ODP proceedings contain an open public hearing at the very end of a hard two days, when most of the brains in the room are slush. In 1999, a very brave guy, Rick Kwiecinski, traveled to DC at his own expense and addressed the ODP during the public hearing. Speaking as a clinical trial human subject, he told the panel numerous true things about the GIGO nature of the PMA for the Summit Excimer laser system. He got squashed like a bug, because many of the panel members were mostly ignorant of his concerns and couldn’t relate what he was saying to all those snazzy slides from the sponsor. He was a terrified, semi-articulate regular guy and they snobbed him out of the room.

The LD is going to let Mr. Kwiecinski speak for himself through the minutes of the July 23-24, 1999 ODP meeting. The minutes are first presented in the original, and then presented again with LD commentary inserted.

AGENDA ITEM: Open Public Hearing [of the Ophthalmic Devices Panel, July 23, 1999].

MR. KWIECINSKI: Dear panel members, FDA, those in attendance, I am not a speaker at all.

DR. MC CULLEY: And also give what your affiliation is, any conflicts of interest, economic and otherwise, that you might have.

MR. KWIECINSKI: With knees shaking, I am Rick Kwiecinski. I paid my own way here. I have been here for two days. I have a financial interest in a number of eye companies, including this one.

My personal opinion is, it would be great financially if you did something great from this. But I am here to speak hopefully on a much higher cause than this.

I have been represented a couple times in the last two days. I am a LASIK patient and have been misrepresented quite a bit in the last two days, and I feel I should speak up and tell you something about that, fill in on some of that data.

Yesterday morning, when we started this whole thing, I was in awe and respect of everyone here for their credentials and their intelligence. It is absolutely amazing.

Now, after today, I am just in awe of your power and I am definitely intimidated here.

As far as the data, I was a perfect case on your charts. I was extremely lucky. I went for a free evaluation one day in July last summer and the doc said, yes, you are a perfect patient, you might end up with reading glasses, but that is the extent of it. You know, go for it.

I was really lucky. I had to take off for a trip soon, so they fit me in, actually, the next day. So, I had a free evaluation one afternoon and I was going to have LASIK done on both eyes the next afternoon.

After the surgery or whatever, I was astounded. It was a phenomenal thing. There were tons of halos and stars everywhere and at night time it was impossible, but luckily, I had only done one eye. I could live with that and the doc assured me that that stuff would go away.

Because of my lines of work, the glasses weren't going to be an option for me, so I thought the risk/reward was worth it to have this surgery done on my eyes.

It certainly was. I am ecstatic. Even with the starring, in November of last year, I had the second eye done.

I thought that was almost as great. When I left there, it was perfect. Yes, there was starring and halos, but when I fill out the form, I tell everybody how ecstatic I am. I definitely am.

I can see now and my right eye is 20/20 on the chart, and sometimes my left eye is almost that good. It really varies.

You know, all of a sudden, I have had lots of problems with that one, and I definitely have a foreign body sensation in there, the vision comes and goes in the day. I do have the halos.

It is not as easy to accommodate with the starring when you have both eyes, I found out. One thing that I can definitely tell you, the starring will go away after six months, because you accommodate. You learn things.

When you are driving a boat, and you can't see any of the lights out there and it is really important, you accommodate. You stare into a light for a little while, and without the dilation of the pupil, you can get rid of the starring for a while, until you have to stare at the bright light again.

When you drive in traffic, you stare at the bright lights. As long as you don't let your pupil dilate, you are a perfect patient.

When I hear what we are trying to approve today, I am lost on where I actually stand. See, I am a citizen of the country here.

For me to go to a free evaluation one day, and walk in with confidence the next day to get this operation is because the FDA -- thank you -- this is the country that is harder than any other country to get approved in.

My point, because I realize your time is important, I think we have a critical issue here. The fact is that the machine is not the problem. It is the use of this machine.

Unfortunately, I am in awe of your power, but I have to say that I feel sorry and forgive you for that, because of the situation we seem to be in here today.

Yesterday I heard, the train is moving. The fact is that you have less control over the train if you don't approve it, because you can't put any restrictions on it.

If we go with one and we don't go with the other, boom, we blow a lot of people's confidence in some things that may be good, and boost confidence in other things that may be very equal. I don't know.

I am just a person on the street. I am Mr.Cohort. I am Mr. Cohort, Mr. Perfect Cohort, except for one thing. I was misrepresented on these charts.

I tell you, when you go into the office, they say, yes, you have got starring. They say it is going to go away.

You say, well, doc, thanks, I can see. I couldn't see before. I lose my contact, I am in dire danger, because I couldn't see two feet in front of my face.

MR. KWIECINSKI: Okay. To wrap it up, folks, you have given your opinion to the FDA. I am glad in this country that they get to go on their own accountability.

Hopefully, I plead, I implore the FDA to listen to all the data, and the fact is, what I see as a lack of data on a lot of this thing, I see some folks here that are stuck without data.

The fact is, we are picking on those who build the machines and we are throwing the responsibility on the patients, and there is a big gap in between.

The company that built the laser that did my eyes, I mean, they are way on one end. The other guy, when I walk in there -- this is the thing that blows me away -- is the fact that you realize when I go in there and I say, doc, I am not really seeing that great from my left eye and it comes and goes, and maybe in this light it is a little better, accommodation again.

He says, wait, if you put your hand in front of your left eye, you realize that you only see with your right eye anyhow. It doesn't matter.

DR. MC CULLEY: Excuse me, I do need to ask you to wrap up. I have been tolerant and you have gone way beyond your five minutes. Please wrap up.

MR. KWIECINSKI: Right. My conclusion for this whole thing, that the labeling on this machine should require that whoever uses presents valid data for the privilege of using that machine and, more importantly, so that you have more factual data, is the fact that a test has to be done, a scientific test, not a little handout sheet that is the responsibility of the patient to fill out, to tell you whether starring and halo is a problem.

With the data that is being collected, nobody even spoke up here today except me, and I am scared as hell. But there were folks who spoke yesterday in the morning.

The fact is that they are a little blip on that chart, and it is very hard for you to tell at this distance how crucial a factor that is in someone's life.

Yet, I can walk to my doctor tomorrow and have him do this all over again. I implore the FDA of this country to do something for the safety of these folks and to find out this data that is needed.

Please do not protect me from necessarily the machine. I have seen other things that were safe, or protect me from me, whether I choose to have it done to correct me from 2400 to 2100. Hey, if my vision went back to 2100, I would still write ecstatic down on the survey sheet.

DR. MC CULLEY: Thank you. Is there anyone else in the audience that would like to come forward to speak?

AGENDA ITEM: Open Public Hearing [of the Ophthalmic Devices Panel, July 23, 1999]. Annotated by the LD.

MR. KWIECINSKI: Dear panel members, FDA, those in attendance, I am not a speaker at all.

DR. MC CULLEY: And also give what your affiliation is, any conflicts of interest, economic and otherwise, that you might have.

MR. KWIECINSKI: With knees shaking, I am Rick Kwiecinski. I paid my own way here. I have been here for two days. I have a financial interest in a number of eye companies, including this one. He doesn’t understand precisely what is meant by financial interest, and is making this statement to establish that he is not anti-laser-manufacturer, as will become clearer below.

My personal opinion is, it would be great financially if you did something great from this. But I am here to speak hopefully on a much higher cause than this. And he is right, the ethics of human subjects research is one of the highest causes there is, and that’s the real issue here.

I know, and I certainly don't have the fancy charts and that sort of thing. Please forgive me. One thing that I did notice in all the data is, it clearly shows that the surgeon expertise is very critical in this. This will come down to more than just technical expertise, but honesty, appropriate decision making, and concern for the patient’s quality of life.

Yesterday morning, when we started this whole thing, I was in awe and respect of everyone here for their credentials and their intelligence. It is absolutely amazing.

Now, after today, I am just in awe of your power and I am definitely intimidated here. He’s scared and the LD would be too.

I guess I am a little bit of a chicken. I only went with one. From that, everything went fantastic. I am a high myopic patient. I don't know all the numbers, but basically, over 20/400 or so. I have lived in contact lenses for about 25 years. The definitions of ‘moderate’ and ‘high’ are critical, because ‘high’ myopes have poorer outcomes: 20/400 vision uncorrected is usually not a ‘high’ myope but Mr. Kwiecinski may have inadvertently dumped himself into a data category that the ODP equates with poorer outcomes anyway.

Well, one of the things I should tell you is the reason that I had this surgery is that my contacts were not correcting me after all those years. I was increasing in astigmatism and that sort of thing, and I could not get 20/20 vision. See the extensive Panel debate and ultimate labeling requirements for stable refractive error before surgery – Mr. Kwiecinski’s experience was that his best corrected vision was declining and his astigmatism was increasing pre-op.

Because of my lines of work, the glasses weren't going to be an option for me, so I thought the risk/reward was worth it to have this surgery done on my eyes. The LD thinks Mr. Kwiecinski might pilot a boat for a living, frequently at night.

It certainly was. I am ecstatic. Because of the uncorrected visual acuity. Even with the starring, in November of last year, I had the second eye done. Why? Because his surgeon told him the starring and halos would go away, and because he had no practical experience of what life would be like with starring and halos from both eyes.

I thought that was almost as great. When I left there, it was perfect. Yes, there was starring and halos, but when I fill out the form, I tell everybody how ecstatic I am. I definitely am. Yes, whenever he fills out that patient questionnaire either 1) there is no way for him to indicate the functional severity of his night-time vision problems, or 2) he feels that he should respond to the questions in terms of his uncorrected visual acuity only, or 3) he thinks his surgeon is a nice guy and doesn’t want to hurt his feelings, or 4) all of the above.

I can see now and my right eye is 20/20 on the chart, and sometimes my left eye is almost that good. It really varies.

You know, all of a sudden, I have had lots of problems with that one, and I definitely have a foreign body sensation in there, the vision comes and goes in the day. I do have the halos.

It is not as easy to accommodate with the starring when you have both eyes, I found out. Yeah, he had to learn it the hard way because his surgeon didn’t pay any attention to his complaints after eye #1, and probably neither knew nor cared what he did for a living. One thing that I can definitely tell you, the starring will go away after six months, because you accommodate. You learn things. No, it doesn’t always go away, it didn’t go away for Mr. Kwiecinski. Accommodate in this sense means ‘adapt’, rather than the ophthalmic definition of accommodation which means ‘to focus on up close objects’.

When you drive in traffic, you stare at the bright lights. As long as you don't let your pupil dilate, you are a perfect patient. Here is it…a wonderful data point on the sponsor’s graph because Mr. Kwiecinski’s uncorrected visual acuity is 20/20 in his right eye when tested in a doctor’s office. In fact, his functional vision is dreadful. How would you like to live like this, driving your car or piloting a boat at night and continuously sneaking a peek at the closest bright light source to keep your pupils constricted? This procedure was a life disaster for Rick Kwiecinski and he ends up on the PMA as a great data point.

The other way that I was misrepresented in this, and I should tell you that I have been told that luckily, my right eye, which turned out very well -- thank you very much -- that was in the study, but my left eye isn't in the study. Enter the ethics…Rick Kwiecinski thought he was part of the clinical trial for both eyes and he is no dummy. He knows that either 1) he was lied to, or 2) the manufacturer has dumped the data on the left eye because of the poorer acuity outcome and refractive instability.

When I hear what we are trying to approve today, I am lost on where I actually stand. See, I am a citizen of the country here.

Of course, they have looked out after me. I am an intelligent man. I read the fine print. I realized there were complications. Have you ever read the complications on some of this stuff that the public is exposed to. But he knows intuitively the difference between medical misadventure and bad care - keep reading.

My point, because I realize your time is important, I think we have a critical issue here. The fact is that the machine is not the problem. It is the use of this machine. His surgeon told him the GASH would go away but it didn’t. It was severe and it hadn’t improved by the time he went in for his left eye 4 months later. Nothing being done differently for the left eye, the surgeon could easily have surmised that permanent GASH in both eyes would result, which would be a major functional problem for a guy who drives cars and boats at night.

Unfortunately, I am in awe of your power, but I have to say that I feel sorry and forgive you for that, because of the situation we seem to be in here today.

Yesterday I heard, the train is moving. The fact is that you have less control over the train if you don't approve it, because you can't put any restrictions on it.

I am just a person on the street. I am Mr.Cohort. I am Mr. Cohort, Mr. Perfect Cohort, except for one thing. I was misrepresented on these charts.

I was on these charts in two different ways. One, I was represented on those charts as a perfect outcome, and number two, I was represented on those charts as one of the accountability problems, and I am embarrassed about that. The manufacturer is dumping the left eye data by saying that Mr. Kwiecinski didn’t return for follow-up examinations.

I tell you, when you go into the office, they say, yes, you have got starring. They say it is going to go away.

You say, well, doc, thanks, I can see. I couldn't see before. I lose my contact, I am in dire danger, because I couldn't see two feet in front of my face.

He says, well, how was the halos beforehand, and how was the starring beforehand, compared to now. I thought, should I base that on clean contacts, dirty contacts, or not being able to see two feet in front of my face. And here it is from the heart and mind of an ordinary Mr. Cohort…GIGO on the safety monitoring because, when wearing dirty contacts, Mr. Kwiecinski maybe had some halos, and when wearing nothing he was utterly defocused. But before surgery he had the option of clean contacts or glasses, in which case he could see just fine. Now, under no circumstances can he see just fine. However, his surgeon is eager to remind him that the halos etc. weren’t caused by the surgery, they were there beforehand. So are you better, worse, or the same on that questionnaire?

MR. KWIECINSKI: Okay. To wrap it up, folks, you have given your opinion to the FDA. I am glad in this country that they get to go on their own accountability.

Hopefully, I plead, I implore the FDA to listen to all the data, and the fact is, what I see as a lack of data on a lot of this thing, I see some folks here that are stuck without data. Damned right (the LD is getting raised hackles all over again re-reading this). The ODP has no useful information about safety vis a vis life-disrupting vision quality loss despite good uncorrected high contrast acuity.

The fact is, we are picking on those who build the machines and we are throwing the responsibility on the patients, and there is a big gap in between. Yep, it’s called the surgeon. Mr. Kwiecinski is generous in supposing that there is no collusion between refractive surgeons and manufacturers. But he’s right on target with blame-the-patient.

I heard it yesterday said, hey, even if we put that on there, they don't have to tell the patient. The fact is, what is wrong with the labeling that says something along with, this machine is only allowed to be used by those who give back 90 percent of accountability for the data, so that you folks have some decent information to go on. Mr. Kwiecinski has identified something the manufacturers love, which is that miserable patients have a tendency to quit coming back for protocol follow-up examinations. Investigators often state that it is the super-happy patients who don’t come back because they have busy lives and see just fine. No one knows where the balance lies. But Mr. Kwiecinski has reason to believe his left eye got dumped (or was never enrolled) and the LD has reason to believe that when investigators are trying to dragnet subjects in for longer follow-up visits, they try harder on the happy patients.

He says, wait, if you put your hand in front of your left eye, you realize that you only see with your right eye anyhow. It doesn't matter.

That is kind of good, but he says, don't worry about it. I will do it again, if you want it done again, but he says, you are 42, maybe that is a little better uncorrected, because if you ever need reading glasses -- Mr. Kwiecinski was under-corrected in his left eye with a fluctuating refractive error and chronic pain. His surgeon’s response is to say that he isn’t using that eye for distance anyway so it can’t be a problem for him with his nighttime car and boat driving. Actually it’s a good thing, he can use it to read! Is this guy an asshole or what (the surgeon)? Is this the intellectual and ethical honesty level of the clinical investigators for the Summit IDE? God help us all.

DR. MC CULLEY: Excuse me, I do need to ask you to wrap up. I have been tolerant and you have gone way beyond your five minutes. Please wrap up. Have we been listening?

MR. KWIECINSKI: Right. My conclusion for this whole thing, that the labeling on this machine should require that whoever uses presents valid data for the privilege of using that machine and, more importantly, **so that you have more factual data, is the fact that a test has to be done, a scientific test, not a little handout sheet that is the responsibility of the patient to fill out, to tell you whether starring and halo is a problem.**

With the data that is being collected, nobody even spoke up here today except me, and I am scared as hell. But there were folks who spoke yesterday in the morning.

**The fact is that they are a little blip on that chart, and it is very hard for you to tell at this distance how crucial a factor that is in someone's life.**

Yet, I can walk to my doctor tomorrow and have him do this all over again. **I implore the FDA of this country to do something for the safety of these folks and to find out this data that is needed.**

DR. MC CULLEY: Thank you. Is there anyone else in the audience that would like to come forward to speak?

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