Physicians for Clinical Responsibility

From 2014-

The conquest of retinal medicine-


Introduction-

Endless articles and “studies”, real or marketing department driven, endless “roundtable discussions” by the same “experts” over and over, whose only distinction from the rest of the retinal community is that they are paid by the very companies that sponsor the “expert panels”. It’s all circular reasoning.

And it is all moot.

Real science (the independent studies that have already shown that Avastin has the same or better efficacy and with PRN dosing better safety from geographic atrophy) is ignored by these “Key Opinion Leaders”, who tout corporate sponsored data as the only “normative” data for evidence based medicine. They have transmogrified “evidence based medicine” into “marketing based evidence”. They ignore the well-established equivalence of Avastin to Lucentis AND Eylea at 1/100
th the cost. They then claim that the obscene financial inducements to do so have no bearing and that they are doing “what’s best” for their patients. They dismiss Avastin as an acceptable choice for those willing to settle for “discount therapy” (actually claimed in a recent “expert panel”) and decry infection risk, which is actually the same for any injection and could be rendered moot simply by Genentech acknowledging the obvious and packaging Avastin for the eye.

The simple fact is that Avastin came along and set the standard, not only for efficacy and safety,
but for cost as well, upsetting a carefully planned agenda by Big Pharma to loot the healthcare budget.

About financial incentives-

Nine or ten years ago, I saw many of the high dollar docs on the CMS list as advocates for patients, and specifically for Avastin use for patients’ benefit.  Some now appear to be among the top users of high frequency Lucentis, in spite of the overwhelming body of data against the practice.  They should speak for themselves, but the question is what brings one to be among the 800 or so docs who account for almost all Lucentis (and Eylea) use (and cost).  

There are 17,000 other US ophthalmologists who don’t.  Of those 17,000, about 2,500 are retina docs caring for the same patients as the 800 with identical or better success at about 1/100th the cost.  So, what has driven this schism in ophthalmology, and what are the 800 or so costing?


    Through the Looking Glass- An editorial redux of recent history in the retinal world

    The following is a redux of the last ten years, focused for the nonmedical reader.  It is rough and only an opinion of a concerned observer, but it is good background and as the CMS numbers show in graphic detail, this single story is enough to tip the medicare scales across
    all specialties.  It is the single biggest scandal in Medicare history, and the minority cashing in, only 850 or so out of over 17,000 ophthalmologists, seem to think they are on firm ground.  They celebrate the new age of “partnership” between industry and profession, and industry is only too happy to own the very market from which they profit. This “partnership” has created a schism which is bringing down our profession of eye medicine at the hands of regulators desperate to reign in the financial beast, even if they have to slay the sheep with the goats. This is a topic that requires a patient and unblinking look at realities that many involved wish to ignore, conceal, and deny.

    After the CMS data release on physician payments in 2012, a major news outlet ran a story about the CMS releasing physician payment data entitled “The Eyes Have It”. The thrust of the article was that many of the leading marauders on medicare and seniors were ophthalmologists. The reporter focused on 5.6 billion dollars paid as if this was all overpayment, apparently without realizing that this included the 4.7 billion dollar budget for eye care. That, of course, leaves another billion or so, which in the ophthalmology world pretty much all goes to Genentech for Medicare’s cut for the Lucentis bill, but the reporter missed that too. Completely. As a result 17000 are tarred and feathered for the profiteering of a company and a small minority of the eye care world.

    A billion for Lucentis? It’s actually more like 2 billion, and that’s just because 75 or 80% of the retina doctors refuse to be intimidated or induced to use Lucentis. If we all used Lucentis according to the company instructions, it would cost over 10 billion dollars per year,
    just for the drug and just for the new cases of macular degeneration, never mind the ongoing cases, or the many other diseases that can be treated the same way. Include those, and the costs have been estimated as high as 38 billion per year, just for the drug cost of Lucentis.

    Why is this? It is the extension of a status quo, a legacy that began with the promotion and marketing of another drug called Visudyne. This was a drug used as part of a treatment called photodynamic therapy. The drug was given IV, followed after 15 minutes with what was euphemistically called a “cold laser” that would activate the drug, treat the abnormal vessels and according to the claims, not harm normal tissue. The price: $1500.00 per dose, to be repeated about 4 times per year.

    There were some interesting aspects of the Visudyne story. The claim was that it would help people, but the study redefined visual “success” to include 3 lines of vision loss. The claim was that the drug and the treatment would not cauterize (burn) normal tissue, but patients were advised to stay out of the sun for at least 3 days so that Visudyne in the skin would not cause severe burns. The claim was that the treatment would not harm normal tissue, but OCT studies that easily show swelling and damage were not included in the original studies and the first post-treatment visit was delayed for three months, after the acute swelling phase. It was little wonder that about 9 out of 10 patients got worse or that there was a common complaint about perfectly circular blind spots or noticing perfectly circular macular atrophy in the shape of the stimulating laser spot and the pool of Visudyne that leaked out of the membrane.

    So the paradigm was set: obscenely expensive therapy, approved based upon favorably crafted, company-sponsored research with little or no regard for cost or patient benefit. This paradigm was followed in 2004 with Macugen, the first approved VEGF inhibitor, which did next to nothing, helping only about 1/8th of patients at $1000.00 per dose every 6 weeks. Retisert steroid inserts came along at over $18,000.00 for a dose that would last 6 months or so and accomplish the same thing as about 80 bucks worth of triamcinolone but with far more risk of blinding side-effects. Triessence is another very expensive steroid with little or no real benefit over existing choices which cost far less. Same thing for Osurdex, another $2000.00 per dose steroid with more side effects and no advantage.

    And then there’s the ultimate “me-too” drug story: Lucentis. On the heals of this financial coup, a new drug, Eylea, is marketed at a similar cost to Lucentis, with no demonstrated “head-to-head” benefit over Avastin. The VIEW studies from which it was approved only showed that it was “noninferior” to monthly Lucentis, which has been shown in multiple studies to be ‘nonsuperior’ to Avastin.

    The Avastin-Lucentis story

    Avastin was approved in 2003 for the treatment of colorectal cancer. It was found to be safe and effective at shrinking tumors and to some degree prolonging life. There were extensive safety studies with only wound healing identified as a notable issue and only in high dosage. There was a slight increase in thromboembolism (from 0.2% to 0.4% only in cancer patients and
    only with concurrent use of 5- Fluorouracil. Genentech CMO Hal Barron, MD was very specific about this, explaining in print and that Avastin was safe in very large doses IV, directly into the blood stream.

    Prominent ophthalmologists including Genentech board members urged Genentech to expand the testing and indications to include eye care, but they refused. The thinking here is a matter of speculation for those of us on the outside, but the logical inconsistencies are difficult to ignore:

    1. Genentech knew that, in Avastin, they had a true wonder drug for cancer.

    2. They knew that it would be priced appropriately for 500 to 1500 mg doses every two weeks, guaranteeing them billions in revenue. The price point was around $50,000.00 per patent for an average course of treatment.

    3. They knew or could figure out (it's simple arithmetic) that IF Avastin would work in the eye, we'd only need 1 mg or so, meaning that, at the pricing they would be stuck with from the cancer indication, they wouldn't make as much money as with cancer patients.

    4. They knew that at the time Novartis was making billions with the pricing precedent they set with Visudyne, and it doesn't even work that well. Same thing with the absurd pricing of Macugen, also following the precedent carefully nurtured by the Pharma lobby for exorbitant pricing without regard to efficacy.

    So, here's the questions:

    1. Is it possible that the oncology pricing could have been seen as a problem for ophthalmology marketing?

    2. As a for-profit company, what would have been the motivation to even see if Avastin worked for AMD? Might there have been greater motivation to NOT look at Avastin and instead just claim that the molecule was too big, creating a plausible excuse to cut off an active site and rename it?

    3. Would that have cleared the way to take a drug with an active site that they KNEW was good, alter it, give it a new name, and bring it out as "something else", with, of course, a new price, once again guaranteeing billions more in profit from essentially the same molecular active site?

    4. Since they paid for the MARINA study, which got Lucentis through the FDA, they could arbitrarily set the protocol at 25 injections (every 4 weeks for 2 years). At the equally arbitrary choice of $2000.00 per half milligram, this replicates the Avastin price point of $50,000.00 per patient for a course of treatment. That’s quite a coincidence.

    These are NOT accusations, just musings on the seeming illogic of the brilliant folks at Genentech missing something so obvious, and the odd coincidence that missing this could result in up to 10 billion per year in additional revenue. Even with the revelation that Avastin and Lucentis work equivalently, the company continues to ignore and even disparage Avastin and push expanding the market for Lucentis. I was told by a company executive that they were doing the “ethical thing” since they had a “moral obligation to their shareholders to make as much money as possible.” A “moral obligation” to lie and obfuscate data to the detriment of patients and society? As a company that benefits from serving the public interest, they also have a moral obligation to the public trust, so what of that?

    Wait a second! 10 Billion with a "B"?

    Sure. 200,000 new cases of wet AMD per year in the US alone times 25 injections (half for patients in the first year of MARINA protocol and half from the previous year for patients completing the 2 year course) X 2000.00 per injection = $10,000,000,000.00, yep 10 BILLION dollars with a “B”, over twice the entire 4.7 billion budget for all of eye care. And that’s just for
    new AMD cases and just for the drug itself. Add in the other ongoing cases of wet AMD, retinal vein occlusions, diabetics, neovascular glaucoma, and other things, and the number for treating by MARINA protocol is closer to 38 billion per year, just for the cost of the drug. Given that there is a very costly minority of retina doctors willing to adhere to the myth that MARINA is the protocol to use, and it is not hard to see why those doctors occupy the top of the CMS payment lists or to see how this is defaming the entire specialty of ophthalmology and bleeding US healthcare dry for no patient benefit at all.

    Behavior Modification 101-

    Why would doctors do that? Perhaps out of a combination of fear and financial incentive.

    Fear tactics:


          Financial incentives:



                                So, just how expensive are these “me-too drugs? Lucentis is the poster child but, incredibly, some doctors still use the antecedents, Visudyne and Macugen, even though they rarely help and often hurt, by direct toxicity or simply by supplanting better choices. Let’s put the cost of Lucentis in perspective:


                                        Current Day Consequences-

                                        So, just over 800 doctors are responsible for almost 2 Billion in drug cost and even more in kickbacks. As a direct result, out of necessity to prevent catastrophe, Medicare is fighting back. By reigning in drug costs affecting only those 800 doctors and saving the Medicare program? No, negotiating drug costs was made a federal crime by politicians controlled by the drug industry. No, they are fighting back where they are allowed to, by turning the screws on the other 17,000 plus eye providers on E&M codes, 25 modifiers, and surgery billing practices. And where is the retina leadership responding? By fighting against tiered reimbursement for anti-VEGFs, which would be exactly the way to keep Avastin in its position as the standard both in terms of efficacy for well over 95% of cases and also for cost. Why is the leadership concentrating here instead of advocating for the large majority of retina doctors (over 60% in the most recent trends survey) who use Avastin first? Because the leadership is almost exclusively from among the 800 who not only use the outrageously expensive choices, but also relies on PHARMA for funding of meetings and even academic departments and for corporate sponsored research. The enormous majority of eye doctors who are just trying to get it right and get paid an honest reimbursement are left on their own. This has created a schism between them and the 800, between the rank and file and the “leadership, even between reality and the nonsustainable and ruinous gravy train that was set up years ago by industry with the Visudyne boondoggle which has since become Casey Jones’ runaway train.

                                        It is time for the massive majority to work with Medicare and other payers to take back reality.


                                        Solutions-

                                        The problems here are entirely generated by the paradigm created by the disingenuous development and marketing of Visudyne: that retinal pharmacologics should cost around $2000.00 per dose regardless of efficacy, and that they should be given often, and that the market would bear these prices. The PHARMA lobby has worked hard to create and preserve this paradigm.

                                        Avastin up-ended that paradigm, as Genentech and the industry knew that it would, simply because eye patients need so much less drug than cancer patients. At oncology pricing and with its phenomenal efficacy,
                                        Avastin would not only set the new clinical standard but also the standard for cost-effectiveness. Genentech first sought to obscure it and refused to even test it. It was not really “discovered” but rather “uncovered” by Dr. Phil Rosenfeld’s ingenuity, honesty, and leadership, and since then Genentech and the entire Pharma lobby have been seeking to squash it. They have been trying to put the genie back in the bottle though intimidation, financial incentives, racketeering, exerting control over the R&D process and CME activities, and subsidizing academic eye departments and whole professional societies. Through such techniques, they have transmogrified evidence-based-medicine into “marketing-based-evidence”, which is the topic of a separate essay.

                                        The solution is simply to embrace the clinical
                                        and cost-effectiveness standards that Avastin set and to undo the liberties that pharma has taken to redefine the research process to better serve the marketing process. Regaining the standards of the past requires reforming corrupt legacies.