Want Quality Care for Wet Macular Degeneration:
Patients Know Little About MD Biases, Experience

How a person might see with age-related macular degeneration, National Eye Institute, National Institutes of Health

Just about a year ago, I reported the one-year results for the Comparison of AMD Treatments Trial (CATT), which compared Lucentis, the high-cost injectable medication made by Genentech with Avastin, also made by Genentech. A lot has happened in the past year in macular degeneration, including the release of two-year CATT results and the approval of a new drug, Eyelea, by Regeneron.

Your Ophthalmologist’s Biases

Doctors talk about patient-centered care, but I am starting to think that patients are out in the cold in terms of picking the best doctors for themselves. We know zero about physician biases, use of data, and involved with pharma and medical device manufacturers.

If you’ve got wet macular degeneration and are a candidate for drug therapy, you may find yourself lost when you search for an ophthalmologist to treat you.:

  • How do you pick a top-quality ophthalmologist?
  • Are the drugs affordable?
  • What are your preferences?
  • Does your ophthalmologist have preferences for specific drugs and are those preferences aligned with your’s?
  • Will your ophthalmologist recommend therapy, based on the best science and safety data?
  • Is affordability important to you? Your out-of-pocket costs can be substantially higher with Lucentis, for example.

Much harder to discern is what your doctor’s biases are. For all the talk about ratcheting up patient literacy, patients know next to nothing about ophthalmologists’ biases. There are no uniform standards. I’d like to see more transparency. For example,  is your ophthalmologist going to pick a brand name on principle? Pharmaceutical sales reps will press safety buttons, making your physician go with brand. Is your ophthalmologist a paid consultant for the eye industry and could this bias his or her perspective? Are ophthalmology sales reps sitting in the waiting room? Are promotional literature, pens, and tissue boxes cluttering up the waiting room?  It would be nice to know their involvement with industry: speakers’ bureaus, patents, involvement with drug and device companies.

It’s not just your ophthalmologist.

Your Doctor and the Pharmaceutical Industry

According to a report in the Nov. 3, 2010 New York Times, Genentech used a secret rebate program for eye doctors dispensing a high-volume of Lucentis, and rebates rose as quarterly usage increased.

I am not naïve enough to think that I can find a pure eye doctor not involved with industry in any way, shape, or form. I have been to too many ophthalmology meetings and read the disclosures to expect it. I want an eye doctor attentive to my out-of-pocket costs and not recommending a drug because s/he is on a speakers’ bureau or because a drug rep promoted it as the only safe option, when it is disputable.

Is it too much to ask for patients to have the same information on industry involvement available to us that medical journals require?

5 Fast Facts on Wet Macular Degeneration Drugs

1. Currently, there are 3 drugs available demonstrated to improve vision: Avastin, Lucentis, and Eyelea.

2. “Lucentis accounts for 10% of Medicare Part B,” state the CATT authors in the two-year trial results, a higher proportion than I ever expected.

3. Medicare reimburses ophthalmologists 6% of the average wholesale price of the injected drug, or $120 for each Lucentis injection, versus $3 for each Avastin injection.

4. Avastin (Genentech) is the cheapest, at $50 per dose, compared with Lucentis (Genentech), at $2,000 per dose. Both are designed to be given monthly, or on an as-needed basis (stopping the injection if no fluid builds up in the eye.

5. Eyelea (Regeneron) became FDA-approved about six months ago. Eyelea is administered every 2 months at about $1800 per injection. Eyelea is potentially half as cheap as Lucentis.

The Avastin-Lucentis Data

Here’s my summary of the key findings at one year:

In comparison with previous treatments, Avastin and Lucentis are the first treatments to ever improve vision in patients with age-related macular degeneration;
2.    Drugs used in the past (Macugen and Visodyne) only slowed the progression of age-related wet macular degeneration.
3.    Testing various regimens, including monthly injections versus variable (stopping the injection if no fluid builds up in retina), investigators learned that they could give injections into the eye less frequently than once a month because patients getting the injections did not build up fluid that quickly.  On average, patients needed injections into their eye 7 times during the year, instead of monthly (or 12 times).
4.    The two drugs had about the same effects on visual acuity, when administered on the same schedule.
5.    The drug’s cheaper formulation (Avastin), cost $50 per injection, compared with Lucentis, at $2,000 per dose.
6.    Safety considerations are still being evaluated. Serious adverse events (primarily hospitalizations) occurred in 24 percent of patients for patients on Avastin, compared with 19 percent for patients on Lucentis. According to the study, these safety concerns were not identified in previous studies of Avastin, when used to treat colon cancer. Patients are now being followed for a second year and safety will continue to be monitored.

Safety Signal Fails to Materialize

Since the one-year data was released, industry has been pushing hard to press safety issues with Avastin. The one-year trial results made the cheaper Avastin look like a reasonable first-line drug choice.

An industry-sponsored safety analysis done in conjunction with Johns Hopkins researchers using Medicare claims data came out when the first-year NEI study data surfaced, showing an 11% higher mortality risk and 57% higher risk of cerebral hemorrhage in patients using Avastin. Even though Genentech pressed hard with the results, the results didn’t fly because the study was not able to ascertain other patient factors, including stroke, hypertension, and cardiovascular risks.

Notably, at two years, the trial investigators, the American Academy of Ophthalmology, and many other authorities concluded that both Avastin and Lucentis had strong efficacy. The AAO no longer describes differences in serious adverse events with the two drugs as worrisome. The investigators wrote: “There were no differences in rates of death or arteriothromotic events. The interpretation of the persistence of higher rates of serious adverse events with bevacizumab [Avastin] is uncertain because of the lack of specificity to conditions associated with inhibition of VEGF.”

The AAO press release lauded the study as “seminal” in “comparative effectiveness research,” a marked departure from AAO’s defensive stance at year one, when they stressed the importance of MD choice and autonomy.

Donald S. Fong, MD, MPH, Director of Clinical Trials Research, Kaiser Permanente  Southern California, Pasadena, CA, told Patient POV: “As far as I am concerned, Avastin is first line. If it doesn’t work, I will go to Eyelea, which is half as expensive as Lucentis.”

There were a few isolated issues with compounding of Avastin and industry tried to use this as a lesson in going for brand.

Patients Need to Know More About Their Doctor

Patients would benefit from knowing a lot more about their eye doctors and all other doctors that  just isn’t out there. In a previous article on Patient POV, Ricki Lewis told the story of a patient with osteogenesis imperfecta, a condition which has eye manifestations. Some ophthalmologists are unfamiliar with the disorder.

I don’t mean to single out ophthalmology. These issues are relevant to knowing all of your doctors.  Why should journals be the only place where physician disclosures are mandated? Why can’t patients find reliable data on physician experience as well?

Clarification: The following was inadvertently left out of the original piece. Genentech has purposely not sought FDA approval for Avastin for the treatment of wet macular degeneration.  Lucentis is a fragment of the Avastin.

On Disclosure, Transparency, and Firewalls: A Call for Uniform Standards

Since Patient POV was launched March 29, I have been struggling with how to deal with the issue of industry-supported patient advocacy groups. On Thursday, ProPublica released its paper: “Financial Ties Bind Medical Societies to Drug and Device Makers” with a splash. A billboard from a medical device company near the Moscone Center, site of the Heart Rhythm Society convention, opens the piece, stating that “thousands of cardiologists” attending the meeting have been “bombarded with pitches for drugs and medical devices.”I don’t doubt it. I have attended scores of medical meetings as a reporter and when I first started going to the meetings, I found the industry influence stunning.

Last Tuesday, I reported the American Academy of Ophthalmology’s (AAO) response to the finding that the cheaper Genentech age-related macular degeneration drug, Avastin, at $50 a dose, worked just as well as their high-cost drug, Lucentis, at $2,000 per injection. The AAO would not recommend for or against Avastin over Lucentis and cautioned that the drugs seem to work differently, that a safety signal must be explored further.
It is pretty easy, to say that we know where they are coming from. In fact, one of several stories on AAO’s website about the trial states emphatically—albeit near the bottom of one of the stories: “Congratulations to Genentech for developing the drugs and getting them to market, congratulations to all in Washington and particularly at the NEI who allowed the trial to go forward, and congratulations to the trials leaders (particularly Dan Martin, MD) and the investigators for designing and conducting a benchmark piece of science. And, finally, thank you to the 1,200 patients whose commitment to the importance of answering critical clinical questions led them to participate in the trial.”

There has already been spin from industry since this study was released in the New England Journal of Medicine, flagging of a possible safety signal in Avastin. That mounted to a crescendo last week. Genentech must be betting on safety throwing Avastin out of the water.
Nevermind, that Genentech flaunted a non-peer-reviewed study out of Johns Hopkins, claiming the “largest worldwide experience” and potential worrisome safety concerns with the cheaper drug. Not disclosed was that it was an unvetted study run primarily by Genentech authors.

But this wasn’t entirely my purpose in writing this today. I think big pharma and the medical device industry are out there. Medical apps, mobile, and software are also big and promoted by some patient advocates. Exactly what their relationships are to these companies is often obscure. I want patients to have transparent information to review, especially if someone is claiming to help them.

It hasn’t escaped me that big pharma and the medical device industry have their hand in media today. You can see ads for Novadisk and more sitting on top of NPR stories; Cleveland Clinic is up on Slate. They are not alone. Peer-reviewed medical journals get tons of money from industry.

Patient Advocacy Groups and Nonprofits

When it comes to patient advocacy and nonprofits, there is often even less transparency. Some don’t mention a single contributor on their website. Others openly provide the information. This raises so many questions. Do we reject them out of hand if they have money from industry? What is appropriate?

This inconsistency may result in pretty unreliable reporting. And sometimes I remember having read that company X operated outrageously in marketing a particular drug, and then I see that same company prominently advertised on a patient advocacy website. Should I discard that organization’s information out of hand?

If I ask some sites to speak with a patient on a disease condition, how do I know where that patient is coming from? What makes an honest patient anyway? Last week, I was working on a story on the NIH Stem Cell decision. The story was never written, but I spoke with the head of research at the Parkinson’s Disease Foundation in New York. I asked whether they could connect me with a patient. It turns out that they provided a patient, a cell biologist with Parkinson disease who was on disability, and had retired from the medical technology company Becton Dickinson. I wasn’t told this from the get-go, but I asked. Perhaps PDF gave me this person because this patient could answer questions about stem cells articulately. There was no incentive for PDF to tell me this, and I don’t fault them. You don’t have to be an investigative reporter to realize that patients with Parkinson’s disease might see limits with existing therapies. And you don’t need a brain surgeon or genius reporter to show you that a company like Becton Dickinson would benefit from the stem cell reprieve.

I am all for physician societies disclosing industry support. But that is just one aspect of the problem. How should media report? Can you watch a PBS show on the brain and not view it tainted because of financial support from a relevant funder? These issues need to be thought through.

I think that whether you are a physician society, media, or a patient advocacy or nonprofit group, the same rules should apply. In addition, if funding is given, the same firewalls should apply, and be transparent for all to see.