Read pages 23-25: Then page 40-41 to see clinical study percentages.  Page 64 about how only one Micro Keratome was approved for LASIK.  Page 67-70 makes a good case as to why more follow up is needed with unhappy patients saying they didn’t come back (maybe they didn’t want them to come back and didn’t want them to complain about the halos, starbursts, dry eye, and headaches??    Page 81, they’re stating the 80% patient cut off was set by the sponsor, going on to say that they had a 43 success rate with 7 myopes like myself at the smaller centers blaming that on “physician learning curve.”  Page 76, they’re dismissing the “non-pma group” of only 43% success, saying that the PMA justified LASIK’s safety anyway.  Page 81, they’re talking about the “high retreatment rates” and how this should be dealt with in the labeling and that it’s important.  Need for patient satisfaction to be defined by a questionnaire (I never was asked anything after LASIK if I was satisfied with halos, burning, dry eye, double vision, nothing, this of course would happen with almost every eye at some point).  Page 84, they talk about this again, so it “doesn’t come back and haunt us in the future.”  (and I hope I’m haunting all of these bastards). They’re stating accountability is only at 57%.  This is shit!  Page 88, and I agree:  “perceived is that there are different standards for investigator-sponsored PMAs brought to this Panel than for industry-sponsored PMAs, and I think that is something the Panel should be aware of.”  Page 89, every doctor has a learning curve.  (great where is this on the FDA website and why weren’t any of us informed??)  Page 90, retreatment rates at 40% then lowered to 10%, but yet this isn’t so, just look at the Alcon Documentary I showed you and Morris Waxler confirmed this was a huge problem. Page 91, read about the “missing information” and their concern if it is 1%, 5%, or greater since so much data is missing.  Dr. Rick Ferris is talking about his concern that the studies are “biased” excluding the worst LASIK cases, which skews the numbers.  Page 92-95, the guidance document says 90% is the goal, confirmed by Dr. Matoba. Dr. Macsai “I have difficulty with accountability at 50-76% at six months.”  Since when is the eye stable and stabilized only measured at 3 months?  Who in the hell’s idea of this law started this idiotic thinking, and for these idiots to not ask this question just shows the lack of talent there that day involved.  I would have asked, how are these 2 eyeballs doing at 2,4, 6, 8, 10 years later? (Jim and Larry, read how much these guys are distraught and confused about labeling/guidance for this PMA).  Page 95, Dr. Rosenthal interjects “guidance is guidance” and 80% accountability is okay.  Page 96:  Now, this is a procedure that is being, and I am not arguing one way or the other.  I am just presenting something to you.  This is a procedure that is being done quite extensively throughout this country in which there is no information publicly available except what doctors want to give to patients based upon off-label use. It is the practice of medicine.  It is not being done one or two times. It is being done thousands of times, and I think part of your deliberation has to be you have to weigh the issue, that is it important to have some information even though it is not perfect science, and that is your decision that one has to make.  Page 97:  Ming Wang, “put something in the PMA so the FDA shows concerns about accountability of THIS study and need for a better study to be done.  Page 97, Dr. Ferris: “I have heard advertisements suggesting that there are no side effects to laser and I take it that if this was approved and there are documented levels of side effects that those advertisements would no longer be appropriate. So, I think we have to be careful about going too far in the other direction and trashing this because there is a public health implication of saying nothing, and if we defer saying something the only comment I would have is that my concern is that I don't know what the complication rate truly is lurking out there.  Page 111:  ‘the doctor left the clinic and the clinic was shut down.”  Why would a good LASIK doctor/clinic shut down unless they had really bad results?  Page 113-118:  “20%  complained of worsening glare, 26% of patients were complaining of Halos and 26% complaining of fluctuating vision.”  Page 121:  Wang:  “Specifically regarding halo, we know that clinically the halo experience after LASIK tends to be more visually significant and affecting the quality of vision than halos that occur naturally in patients without ever having surgery.”  Page 122, Dr. Casebeer/Dr. McCulley:  “pupil size important?”  Basically, they didn’t research this it appears. (No wonder Dean Kantis with 10mm pupils is so miserable daily especially at night).  Suggestion was made to randomly sample 20% of patients, and it was quickly shot down by Dr. McCulley saying: “I don't think we care whether they do if we think that is appropriate.  It may be a very good suggestion, but whether they think that they can do it or not or it is appropriate on their part is not relevant. We decide.”  Page 124:  “only one microkeratome shaper (Chiron ACS) was used for this study, but many are out there.”  Dr. Casebeer confirmed this.  Page 126:  “DR. LEPRI:  Mr. Chairman, there is one point I would like to address one of the questions regarding the labeling in pupil size.  The current VISX labeling states that astigmatic patients between the ages of 21 and 30 should be reminded that due to their larger pupils they are more likely than the over 30-year-old population to experience a degradation in visual performance under these conditions.”    Page 127:  Dr. Mannis:  “When I came to the meeting I didn't feel as uncertain about the missing 43 percent as it were as I do now, and I would like to recommend that the obstacles notwithstanding that the sponsor turn back to its cohort and try to provide us with additional follow-up data.”  Up to Page 134, they still don’t have an answer to the “patients done as a Non PMA” and wanted answers suggesting “to contact both the patients and the doctors, and that this is vital missing data.”  So, they moved on to the next question.  Page 135:  “PARTICIPANT;  In the guidance document it is 1 year, 90 percent at 1 year. I mean is that what you are getting at?  DR. MC CULLEY:  No, that has been clarified at another meeting before.  I thought the same thing, but the way it reads and it was Morris that corrected it, it was that stability at two points 3 months apart.” (this decision by Morris, made the standard of care much lower in my opinion).  (again, who made any of these guys GOD even thinking there is stability at 3, 6 or 12 months with the human eye??)  Page 140:  “In addition there are other treatment modalities out there even outside of spectacles to correct these patients and this doesn't mean that they cannot have LASIK, but I am not sure that we should approve the higher range based on the information that we have now.        We can get around this with appropriate informed consent.  DR. MC CULLEY:  What we decided before when we discussed whether to add specifics to the guidance document for the higher ranges is that we would not try to create artificial numbers but take into consideration our realization and the reality that those patients typically do less well, and we would make a judgment as to what the performance was whether it was acceptable or not.  So, we left it soft so that we would bring judgment to it and did not change the guidance but with the understanding that those patients would typically not respond as well as the lower ranges.  Up to page 153, they talk about the “labeling ranges that should set the standard of care.” 

Page 155:   “DR. SUGAR:  I would like to add that there be a statement concerning the possible adverse effect of pupil size on patient's symptoms and that this be taken into account and this be placed both in the patient brochure and the physician labeling.

            DR. MC CULLEY:  Okay, and Dr. Bullimore you had, we had a couple that you were scribing. Dr. Matoba had one, and then we had one other that brought product labeling in line.  You didn't write it, huh?  Okay, he will write it this time, Alice.

            DR. MATOBA:  My suggestion was that the labeling be modified to be consistent with the exclusion criteria that were used for the clinical trial, specifically previous intraocular procedures, surgery.  Patients with that indication were excluded.

            DR. MC CULLEY:  Why?

            DR. MATOBA:  I don't know why, but I think that there should be a warning.  It shouldn't necessarily be an exclusion criterion in the labeling, but it should be a caution that this procedure was not investigated for those subgroups.

            DR. MC CULLEY:  And the why is you can blow the wound, but anyway let us not.  I should just shut up.

            Dr. Wang?

            DR. WANG:  I would like to suggest in the same paragraph Dr. Sugar suggested adding a sentence saying that cautionary statements such as for high range of correction visually significant halo or glaring may be present.

Page 156:  Importance of Pupil Size to have sufficient warnings in the Labeling:

MS. MORRIS: Lynn Morris.  I wanted to be clear that pupil size was included. I thought I heard the sponsor say that that wasn't part of the study.  They didn't collect that data.

            DR. MC CULLEY:  That is correct. They did not study it, but the fact that they did not study it does not alleviate our concern that it might be an issue. So, we are saying that we want that in.

            MS. MORRIS:  Oh, no, I want you to assure me that that is going to be in the labeling.

            DR. MC CULLEY:  Yes, that was added.

Part Two: Coming Next….

Part 2:

Page 159:  MS. MORRIS: Lynn Morris.  I wanted to be clear that pupil size was included. I thought I heard the sponsor say that that wasn't part of the study.  They didn't collect that data.

            DR. MC CULLEY:  That is correct. They did not study it, but the fact that they did not study it does not alleviate our concern that it might be an issue. So, we are saying that we want that in.

            MS. MORRIS:  Oh, no, I want you to assure me that that is going to be in the labeling.

            DR. MC CULLEY:  Yes, that was added.

Page 275:  DR. WANG:  I think my answer is yes.  In particular, the treatment is circular.  The fact we are going to use 65 percent against-the-rule, I'm just wondering if that is suggesting in any way a weakening of the cornea. Again, the context of examining refractive stability.  So the answer is yes.

            DR. MC CULLEY:  Next question.

            DR. EYDELMAN:  Question 5, visual symptoms data reveal photophobia and double vision to be the symptoms with the greatest change from pre-operative levels.  Do increases in these visual symptoms constitute a safety concern?

(symptoms, they meant to say:  AE/Complications correct?)

            DR. MACSAI:  Well, it seems the sponsor has tried to address this by questioning these patients with a phone questionnaire.  But it's my understanding that this data wasn't submitted for FDA review, the tabulations.  Were they, of the phone questionnaire, or weren't they?

            DR. EYDELMAN:  The summary of this was submitted.

            DR. MACSAI:  Sorry.  Got it.

(great, they couldn’t reach people via phone so they rounded it up again, saying LASIK was safer than it really is).

DR. EYDELMAN:  What was not submitted was the information on the updated cohort.  But the phone questionnaire, the original was submitted.

            DR. MACSAI:  The original, but not the updated.

            DR. MC CULLEY:  Again, if we're going the route that we're going, which is requesting more, it's a moot point; 5b.

            DR. EYDELMAN:  Is the analysis of the updated patient questionnaire necessary prior to making a recommendation regarding approvability of this device?

            DR. MACSAI:  Yes.

            DR. GRIMMETT:  It seems to redundant to me to the last question.  Didn't we just agree that we would like the updated questionnaire information?  So certainly we would like that information on the review.

            DR. MC CULLEY:  Next question.

Page 276:

DR. JURKUS:  I am also wondering if a more detailed analysis about near-front acuity would be available.

            DR. MACSAI:  I would like to expand on Dr. Higginbotham's request for gender analysis in that this is the patient population at high risk for dry eyes and keratoconjunctivitis and that may have an influence on the efficacy of the laser.  So if they could make an analysis of that as a barrier.

            DR. PULIDO:  I'd like to thank again the sponsor for supplying, one, good accountability, and number two a good data set from which we could see the strengths and weaknesses.

            DR. FERRIS:  I'd like to follow-up on something Dr. Wang said.  That is although I know we are not going to rewrite the guidance document, I'm concerned if the data at two years is showing a decrease, whether at least with the other laser system we have asked about documenting stability, and so I worry that we may or may not find two years to be the endpoint.

            At some point you need to go until you document stability, or at least it would seem to me that I would I might know about stability, because my patients would probably want to know more than a two year effect.  Is it going to level off or is it not.  If hasn't leveled off, I think there may be concern bringing it back here.

            DR. MC CULLEY:  So what one would say if we were writing the guidance document would be minimum of two years for a new device, assuming that stability is demonstrated at two years?

            DR. PULIDO:  And stability being what?

            DR. MC CULLEY:  It would have to be redefined for this group, as has been pointed out.  That would be to be determined in the guidance.  We don't have that.

            DR. PULIDO:  Shouldn't we tell the sponsor what we would like for stability, since we were asking for long-term results now?  We need to be able to help them in that regard.  What will we be happy with?

            DR. MC CULLEY:  Dr. Grimmett or Dr. Bullimore, either one.

            DR. BULLIMORE:  Primarily, I would like to see a little more data.  I mean it's very difficult to make decisions on stability with so little data at the 24 months.  I reiterate my impression that at two years the technique appears to be on the order of 50 percent effective.  I base that both on the cross-sectional data that has been presented -- I'm sorry, the longitudinal data that has been presented, but also the pair-wise comparison, looking at the change in the elegant integration of that data that was done in various people's heads.  I think that will remain my primary concern.

Page 285-287:  LOOK AT ALL OF THE DOCTORS THAT WANTED TO “NOT APPROVE” THE LASER and showed concern about the studies saying more “info was needed, not just that 90% of patients attained 20/20 while discrediting the symptoms which should have been AE/Complications, also they all showed concern that the LASIK results were “temporary” and they set the labeling standard at 90% at 2 years.  (NOT GOOD).  Who in their right mind would do LASIK if it only lasted 2 years and then regressed?

DR. VAN METER:  I voted not approvable.  I believe the device is reasonably safe.  I think the sponsors have shown that to my satisfaction.  I have questions about the efficacy because the instability of the refraction and the regression.

            The last table that was shown showed seemingly stability had percent of patients in the Y axis.  And it would be more helpful to have the actual refraction data, ideally a cycloplegic refraction data, and show that to be stable, rather than have a percentage of patients that is 20/20.

            DR. MACSAI:  I voted not approvable.  This is a new refractive laser.  Despite the fact that the sponsor has done a great job in providing data in an organized, reviewable manner, it is just too soon to tell.  The data reviewed to date demonstrates refractive drift and decreased efficacy over time.  There is an increase in astigmatism with a progressive axis shift.  Analysis of the total hyperopia as measured by cycloplegic refraction will determine the true efficacy of this procedure, and with further follow-up we will be able to better determine the safety and efficacy.

            DR. JURKUS:  I voted not approvable for the same reasons that have been indicated.

            DR. HIGGINBOTHAM:  I voted not approvable considering I think the need for additional follow-up as evidenced by the increasing symptoms that patients are complaining about, as well as the lack of refractive stability long-term.  I think we really do need to see what happens with these patients over time.

            DR. PULIDO:  I voted not approvable, again because I think not so much the safety data, but the effectiveness data.  We need to have longer-term results to make sure we're not putting out to the American public, a new technique that is not stable over the long run.

            DR. SUGAR:  I voted not approvable.  I believe the procedure is safe.  I believe that the effectiveness is disappointing and further data will either confirm or refute that.  I disagree with the 90 percent requirement.  I don't think that that is realistic, but otherwise I agree with the vote.

            DR. BULLIMORE:  I voted not approvable.  While I will accept that the device is reasonably safe, the efficacy data is somewhat disappointing.  I believe that both sponsor and reviewers and indeed FDA have been hampered by the lack of a guidance document, but nonetheless one can apply some common sense to this data and look at the degree of change that has been attempted, and place the actual achieved change at different time intervals in the context of what is being attempted.  Based on that, I don't think that the sponsor has to date demonstrated efficacy.

            DR. GRIMMETT:  The average consumer will likely want more than a temporary refractive effect.  Since there is a paucity of reliable, long-term data that cannot reasonably substantiate critical stability issues, I voted that the PMA is not approvable primarily due to effectiveness issues.  I do believe the PMA shows that the procedure is reasonably safe.

            DR. MATOBA:  I voted that this procedure is not approvable for reasons elucidated by Dr. Grimmett and Dr. Macsai.  I also agree with Dr. Sugar's comments regarding the accountability.

            DR. MANNIS:  I voted not approval primarily based on lack of demonstration of efficacy.