Discussion: NICE consultation on CXL

[Andrew MacLean]

Lynn

You make a good point, but raise another question: what criteria would lead to the conclusion that the normal scientific procedures ought to be abandoned.

At the moment we have a haphazard situation where practitioners have cherry-picked patients and published data that is worse than useless. On the forum we have heard to two patients who have required grafts after CXL, but I have never met a practitioner who would concede that this was significant.

If they select from the KC population only those patients who would not progress, and they then claim 'success' when their patients did not progress then they have demonstrated nothing except the willingness of people to pay over very large sums of money to prevent something that was not going to happen. This is hardly a sound basis for the adoption of a new therapy.

At first I was tremendously enthusiastic about CXL and the promise it held; now I am less so, largely because of the failure of practitioners to proceed in an orderly and scientific manner.

Andrew

[Andrew MacLean]

I owe Gareth, and the rest of the forum an apology.

Earlier today Gareth posted a thoughtful and balanced response to my post (above). I was trying to respond, in turn to his latest contribution, but instead of quoting from his text, I managed to delete much of it. I have no idea how I managed to do what I did, but rather than leave a post that made no sense, I have sent him a pm asking him to repost his contribution so that we can start again from where we would have been if I was not such a klutz.

**Note to self: remember to turn on your computer screen when visiting the KC forum!

Andrew

[GarethB]

Appology accepted, PM responded to, will do my best to do another thoughtful and balanced response tonight

[Lynn White]

Andrew...

Hoping you have your computer screen on and so glad you joined the debate!

OK - I think you misunuderstand me. First of all, the Dresden study is not one where " where practitioners have cherry-picked patients and published data that is worse than useless", it is a proper, scientific study. So are the studies being undertaken in the US and elsewhere in the UK already. My point was that the present consultation seems to ignore the scientific studies already available in the field simply because they do not originate in the UK. I also make the point that it is going to be very difficult for the UK to embark on long term studies that have scientific meaning because some "subjects" will simply not put up with being part of an "experiment" and take matters into their own hands. In other words, a study that sets out to be scientific may end up being just as meaningless because it ceases to be random. I am not advocating abandoning scientific research, I am just questioning what will be gained by insisting more research takes place when there is a lot of research out there already, completed.

As to practitioners imparting CXL - I am not quite sure what you are saying here? I beg to differ with your opinion because I actually fit patients who have had CXL performed by such practitioners and therefore do have actual professional experience of what is happening in this field, rather than anecdotal hearsay?

The overwhelming majority of practitioners appear to be ethical and proper and do not gratuitously CXL people just for monetary gain. They are often under great pressure from desperate individuals who are clutching at any straws to try and halt their keratoconus progression. Actually, many who consult surgeons are very advanced and progressing rapidly and of these many DO stop progressing - and as I monitor them post op, I do know this for a fact. So your view of surgeons claiming success for patients who are not progressing anyway is a little harsh, I should say?

There are also a good number of patients who want CXL whatever the prognosis. I have personally spent hours (literally) talking to patients to explain that in their case it is probably better waiting to see if anything changes before going ahead - or at least wait a few weeks to make a decision. The surgeon often says the same thing. Said patient has agreed - only for them to ring up a few weeks later for their post op CL fitting! "Oh well," they explain "I was just worried that it would get worse and I decided it was just better to go ahead and have it done!" In other words, people WANT this procedure whatever stage of KC they are at - and many do have this when they are really at the point of grafting anyway - something the procedure is not exactly designed for.

The stark truth is that if you are faced with your child being at risk from a debilitating condition, you have done the research, you are sure in your own mind it will work - and the NHS assigns your child to the group that "takes its natural course", what are you going to do, if you have the wherewithal to go privately? I am not saying this is wrong or right, I am just explaining human nature and that it can thwart the best laid plans for a totally scientific experiment. And who are we to say people should be denied this choice?

I am not averse to the NHS going into this cautiously and under strict conditions, I am just saying that assigning people to a group who do not have any treatment is morally questionable and may not even be scientifically possible. There is research evidence that shows that badly fitting RGP lenses actually accelerate keratoconus - so if your control group are still in lenses, this may make the CXL outcomes look TOO favourable. You would have to have BOTH groups forswear contact lenses for the duration of the study to be absolutely scientific. Not sure anyone would volunteer for THAT!

Lynn

[Lizb]

from a personal point of view i would rather pay privately and definitely get CXL that should stop/slow the progression of KC than take a chance on further trials within the NHS that may or may not treat me with CXL. yes it will cost me in monetary terms but if it means i remain able to manage KC (at least in one eye) with glasses then for me it is money more than well spent.
Yes there is a long term risk that is as yet unknown, but from the current data available the results are very positive in slowing/stopping the progression of KC.

[Andrew MacLean]

Lynn

Again you make some good points that raise more questions than they provide answers.

I have no doubt that CXL is a valuable innovation, but I would be at a loss to say how valuable it is. Surely the NICE study would resolve the issue of quantifiable value once and for all? As I understand the situation, it was the failure of practitioners to engage with the science that made the FDA so reluctant to approve CXL in the United States; but they do now seem to have some studies underway on the same basis as would be proposed by NICE.

By the way, I agree about the contact lens thing.

Lizb, I fully understand why people would want to pay money to get the real thing rather than enter a properly controlled study; the PR for CXL has been very effective indeed.

[Lynn White]

Andrew

NICE is NOT doing a study!! That is not its function. It is currently recommending that CXL be available only under certain restrictions. I quote again from the documents on the website:

1. Provisional recommendations

1.1 Current evidence on the safety and efficacy of photochemical corneal collagen cross-linkage using riboflavin and ultraviolet A (UVA) for keratoconus is inadequate in quantity and quality. Therefore this procedure should only be used with special arrangements for clinical governance, consent and audit or research.

Also
1.5 NICE encourages further research into photochemical corneal collagen cross-linkage using riboflavin and UVA for keratoconus. Research should take the form of studies that allow comparison with the natural history of the disease, and should define patient selection criteria based on estimated risk of disease progression. Outcomes should include measurement of visual acuity, topographic assessment of corneal stability, prevention of progression to transplant, and long-term safety. NICE may review the procedure on publication of further evidence.

This means it is saying that the NHS should offer it under "special arrangements" and that it "encourages" more research - by other poeple. So this is NOT one study that will solve the issue once and for all..... in many ways, this is what the Dresden study is doing as it has been running 9 years now. To replicate that in the UK, any NHS study would have to run an equal amount of time. Studies cost time and money and individual establishments or researchers all have a different take on it. NICE is not attempting to control the direction of research even. So it may be 5 years down the line we still have a rag tag and bobtail of small research projects and we are no further on.

I am not saying what is right or wrong here.. this is a discussion and from this I hope we all can contribute to submissions to NICE.

Lynn

[GarethB]

Take 2, I'll try and remembre what I wrote before

At the moment we have a haphazard situation where practitioners have cherry-picked patients and published data that is worse than useless.

This has been discussed amt times on the forum and the NICE consultation gives us a chance to adress the balance. In doing so we need to be ethical and ensure that those who receive the placebo and then go on to progress get the CXL before it is too late. If post CXL the progress further then both of these factors will be valuble information to capture in the report as to the effectiveness of this treatment as it does not preclude the ability of the patient to have the graft at a later data. So not only does the selection criteria need to be such that it captures the widest population of patients but the follow up is controlled swo that those who require it can get follow up and alternative therapy if required such as intacs or grafts.

On the forum we have heard to two patients who have required grafts after CXL,

I know one person who had the treatment in Dresden with the epithelium intact at their own request, their reasoning was the healing would be quicker and they accepted that the halting process migght be slower. Their aim of having the treatment was to buy time while they sorted some issues within their personal life before they had the graft and considers both achieved what they set out to do. As to the other case I can not recall.

I know I made a comment about being pro-graft but only as a last resort but as to why I put this my poor old brain is strugling to recall.

[Andrew MacLean]

Lynn

You re right. The use of "NICE" study is a careless shorthand, but it does make the point that NICE is asking for research within set parameters. I am not opposed to this, indeed I would welcome it.

Also, NICE has no remit in my jurisdiction, so the whole question is academic for me. NICE does not cover the whole of the UK, although its decisions are sometimes informative for decisions in the other 'home nations' jurisdictions.

Gareth, well done; I am sorry to have put you to so much trouble. You did also say at the end of the post that I mangled that you were an enthusiast for grafts, but only as a last resort. I wholeheartedly agree with that sentiment.

All the best

Andrew

[Ali Akay]

Unfortunately it is a fact of life that when there is hope of a "miracle cure" there are always people out there trying to exploit the vulnerable patients. I recently saw a patient in his mid thirties with very early cones and no evidence of progression for some years. He saw an eminent Harley St corneal surgeon a few months ago to discuss CXL and apparently the surgeon was very keen to treat him there and then! He came to ask my advice which was that as his cones are very early, his corneas are getting naturally tougher through the ageing process, and there was no evidence of progression, I wondered if it was appropriate for him. I am not suggesting this surgeon acted improperly as I am only going by what the patient told me. I am not against the procedure in principle, but we need to realise that it's not approporiate for everyone and time will tell how effective it is and what long term issues (if any) there are. Thanks to Lynne for bring this consultation document into our attention. Hopefully sensible guidelines will eventually be reached. Interestingly, I saw another patient recently who had CXL under NHS. He apparently saw the surgeon privately for consultation who was then able to treat him through the NHS hospital where he works. I am not sure how this was possible,but he was very clear about it! Could this be a way getting CXL on NHS?