Dwell and dakrina testing

[brd888]

Has there been any clinical testing of these drops?
I know there are many fans on here but what evidence have we they are better than the scores of other formulae on the market?
Ta
Bruce

[Terri]

Bruce: Doc Holly's lecture notes and other information on his site references clinical tests for the drops. You might want to post this on his forum, and I'm sure he'd be happy to add details about the protocols, sample sizes and results.

Terri

[Rojzen]

testing for efficacy: relates to objective

Hi, brd888. . .This is such an important question, because it helps to distinguish across the objectives of the various products out there. . .

The now-large selection of artificial tears on the market are not, to my knowledge, considered drugs that need to be tested for efficacy. Because their ingredients (mostly the hypromelloses, carboxymethylcelluloses, low-oncotic povidone and PVA, mineral salts, mineral oils, castor oil, bicarbonate, boric acid, etc.) have been in opthalmic use for decades, and are generally considered to be safe, I believe that new products containing these same old ingredients can be sold without new safety testing. None of these products comes with claims of actually treating dry eye, and so efficacy testing in that context is also not required, to the best of my understanding. All are marketed simply as "lubricants." I think that the guar gum in Systane went through some testing, but not in the nature of clinical trials associated with Rx products, though I'm not sure of that.

The Dr. Holly drops, I believe, except for the prescription product FreshKote (aka Clinitas Ultra 3) currently fall within the same regulatory framework, to the best of my knowledge. Their ingredients do not depart from the usual collection, and they can most assuredly be said to lubricate the eyes. Because, however, the high oncotic pressure achieved by their formulae have the real, scientifically-based possibility of doing a lot more than lubricating, the non-Rx drops (Dakrina, NutraTear, and Dwelle) will, I think, be tested for efficacy some time in the near future. I believe that an effort is under way to arrange clinical trials for Dwelle, for example. And, as Dr. Holly has pointed out, the B12 in NutraTear has been known, for decades, to promote corneal healing, and B12 has, accordingly been in use, within other products, for that purpose. As for the Rx drops (FreshKote/Ultra 3), I am not sure exactly what kind of testing was required for these, in order for them to become part of Rx formularies, but I believe that these drops do not yet come with therapeutic claims, and so precise testing for corneal healing and tear film stabilization may not yet have taken place on these. . .

Anyway, brd888, Dr. Holly may chime in on this, and his web site may explain more (See http://www.dry-eye-institute.org/), but I vote for using the Dr. Holly drops even if they have not been tested any more so than have products like Refresh, Systane, HypoTears, TheraTears, etc., for they have surely been conceived far more carefully than these other drops, and haveproven themselves at least as safe as the others.

I am reminded here that when FDA finally approved Restasis (which was rejected many times before approval issued), Allergan was, if I recall, able to demonstrate only a 15% efficacy rate in patients, in regard to increased tear production and/or comfort. Don't quote me on that. . .but I think the package insert for Restasis will bear me out. . .Personally, I did OK (no adverse effects, a tiny bit of improvement) on Restasis, but it was not because the statistics in my favor were great. . .and so, if you find a safe product, like the Dr. Holly drops, I vote for trying it, all the while continuing to probe the testing and statistical issues. . .

Hope that helps. . .

[Rebecca Petris]

There actually was quite a bit of testing done on the drops back around 8-10 years ago - at a time when no one ever bothered to do any with any OTC drops. Seems like I used to have summaries of those posted. The problem is that anything comparing with other drops is out of date because the range of drops available back then was totally different from what it is now.

Getting some really well structured clinical trials done on these drops to assess not merely symptomatic relief but therapeutic effects is my dream. The problem, of course, is money. But where there's a will, there's a way.

There are a couple of different ways this kind of testing can be done, by the way. Anybody can do a little clinical trial and document it. Doing a GOOD study and publishing it is another ballgame altogether. Have you ever seen an ad for an artificial tear where a claim is made about its benefits and there was a footnote? The footnote references either a study published in a peer-reviewed medical journal or... "Data on file [Company name]". Personally, I stake little to nothing in any data of the latter style (that's not to say of course that peer-reviewed means it's infallible either, but that's a different story for another day) and it's one of the reasons I've been hesitant to attempt any clinical trial short of "the real thing". I don't want to ask anybody to believe my in-house company data any more than I would believe anybody else's in-house company data. The peer review process may be flawed but it's a lot better than nothing.

[Rebecca Petris]

p.s. Rojzen did a great job of summing up the safety/regulatory side. In the US it's called the FDA's OTC monograph for ophthalmic demulcents. There's a pre-approved list of ingredients and concentrations and if you stay within that list, your product is basically automatically deemed acceptable for over-the-counter sales. The FDA lays out every last word that can be used on the labels in terms of claiming what the drops do (e.g. "for relief of...")

The only reason anyone selling drops in this category would do any testing of such products is if you wish to make marketing claims of benefits beyond those stated in the FDA's monograph for these types of products. What's different about Dr. Holly's drops is that his science was developed for therapeutic use (read up on history of Dehydrex for example) but Dwelle & Dakrina were essentially re-formulating that concept to make it possible to sell them over the counter. Which makes great sense as a strategy if you want something to be widely available, and/or if there aren't $millions available to do the kind of clinical studies necessary preparatory to filing a new drug application for Rx sales. However, there are downsides to selling them on an OTC basis. Among other things, when you sell something labelled as a palliative lubricant, that's the level of expectation you set for them. We all think very differently about Rx drops than we do about OTC drops.

[brd888]

Ta

Cheers,
It was a hard question to ask due to conflict of interest in this site.
BTW I am not concerned about safety of the products - I'd just like clinical proof of performance. However I can see how difficult it is to get accurate results in testing due to the complexity of patient's symptoms and severity.

I did find a dated reference on "The Thai Journal of Ophthalmology" which you can google if interested. Compares Dakrina to "Tears Naturale"...
"In general, Dakrina showed a superior effect. Due to the small number of subjects however, the difference found between the two eye drops was not statistically significant at the p = 0.05 level. "

Regards,
Bruce

[Rojzen]

wondering what effect was tested

Thank you, brd888, for that reference to the comparative study. . .I will be interested to see what objectives were being tested for, since Tears Naturale and Dakrina are so vastly different in their actions. . .If patients were simply asked whether they feel better, after a short period, I would not find that study very meaningful, since my goal is not merely short-term relief. . .But if measurements of TFBUT and cornea topography were taken, that will be quite interesting to compare. . .Thanks again. . .

[Rebecca Petris]

Cheers,
It was a hard question to ask due to conflict of interest in this site.
BTW I am not concerned about safety of the products - I'd just like clinical proof of performance.

Totally understand. And while it's easy for me to say "hey guys, don't be shy about tossing tough questions my way" - realistically it's probably not the easiest thing in the world to do in this forum. Honestly though, I encourage people to question everything. I only wish I were in a position to do more in the way of providing answers!! I took on the job of keeping these drops alive just based on what little I understood of the science, on faith, personal experience and the anecdotes of people who had used them for ages (some up to 15 years).

However I can see how difficult it is to get accurate results in testing due to the complexity of patient's symptoms and severity.

Quite. It takes years to structure, recruit for and conduct decent clinical studies even if you have the resources for it. Then allow a couple more years for the peer review process and... well, it's all very slow and very expensive.

The Thai article is the only one of which I'm aware that was published in the peer-reviewed press. I think that probably the most interesting study conducted was done by Gary Foulks at Duke University measuring change in goblet cell density of Sjogrens patients taking Dakrina. Dr. Foulks moved to U of Louisville and the study was never completed. He remains a big fan of the drops tho - whenever I get a new customer from Louisville I know why. Usually post transplant or other severe patients.

[dianat]

Do you think he would revisit the idea of a trial?

[Terri]

I feel like I am a clinical trial. I was thinking about all of the drops I've tried, and I began to feel like an eyedrop ho. Bion Tears, Celluvisc, Endura (and its BFF Restasis), Genteal (liquid, gel, whatever), Lacrilube, Lacriserts (I know, very retro), Refresh (in all its regular, plus, ointment and gel permutations), Systane, Tears Naturelle, TheraTears (in all flavors), regular Visine ( desperate purchase at the Grand Canyon when I ran out of PF vials of whatever I was carrying at the time), Visine Pure Tears (for the cool new dispenser). Have I left anybody out?

So, now that I've proven to myself in my one-woman clinical trial that Doc Holly's drops rule, I'm trying to figure out what to do with my inventory of rejected drops. I've tried giving them away in the swap meet (no takers), and I'm too environmentally conscious (aka cheap) to just pitch them in the trash. Maybe we can start a forum on creative alternate uses for ineffective eye drops?