Article Date: 5/1/2005

Bringing Macugen into Practice
Planning is key to providing this new AMD treatment.
BY ROCHELLE NATALONI, CONTRIBUTING EDITOR

Macugen (pegaptanib sodium, Eyetech/Pfizer) is not the first injectable drug to make its mark on the vitreoretinal world, but it just might end up being the most remarkable, if not in terms of clinical outcomes, then perhaps in terms of practice patterns. It is the first approved treatment that is indicated for all forms of neovascular AMD, including minimally classic and occult vessels, and its recommended course of treatment is every 6 weeks for 2 years.

In this article, several retinal physicians who have already begun to provide Macugen injections describe the logistical and financial impact the new treatment has had on their practices, talk about adherence to course-of-treatment and clinical protocols, and address topics ranging from scheduling to comanagement to reimbursement.

While their commentary on most of these topics is as divergent as their practices, they all agree on one thing: offering Macugen fulfills their ethical imperative to provide treatment that is in the best interest of the patient.

CREATING AN INFRASTRUCTURE

Iowa retina specialist David D. Saggau, MD, of the Wolfe Eye Clinic, near Des Moines, has made distinct changes to efficiently bring Macugen into his large group practice. "The age of pharmacological treatment of the retina is here, and we're all going to have to create the infrastructure to accommodate it," he says. To this end, Dr. Saggau has created a "parallel practice," dedicated solely to injections. "I hired a new nurse, and we have a separate schedule and separate paperwork for Macugen patients, and I've folded my Kenalog patients into that, as well," explains Dr. Saggau. He sees his injection patients in the same facility as his other patients, but most administrative aspects are kept separate.

The general recommendation for intravitreal injection follow-up is that patients should be educated to know the symptoms of endophthalmitis, and should be contacted within 1 week of the injection. Some physicians interviewed for this article are following that recommendation, others are contacting patients after 3 days and then again at 7 days post-treatment, still others are bringing the patient in for a follow-up visit, or having the patient see the referring ophthalmologist -- or an optometrist -- for follow-up. Dr. Saggau relies on this final option for about half of his patients. "We are even holding seminars to educate our referring doctors about Macugen and what to look for before and after injections," says Dr. Saggau. "This is somewhat analogous to comanagement after cataract surgery."

The frequency of Macugen treatments, along with follow-up visits and/or follow-up phone calls suggests that, from an administrative standpoint, the process can be tricky. "There is a fair amount of paperwork, so we generated a master schedule to track when each injection was given, when the follow-up was performed and when the consent was signed," says Dr. Saggau. Every time the patient returns, the consent needs to be reviewed and signed again. The patient leaves with a post-injection form that contains instructions and the time of the 2- to 7- day follow-up appointment, as well as with a pre-injection form with the instructions and times for his or her 6-week re-injection. "You have to have a strong coordinator to make sure all of the details are worked out," Dr. Saggau explains.

He stresses the importance of developing a workable system early in the process. "If you plan to provide this treatment, and you don't set up an infrastructure, you'll have to piece together a system over time in a patchwork manner. You need to take the time to do this now because pharmacotherapy for retinal disease is here to stay and we're all going to spend more time doing it," he asserts.

University of California at Los Angeles (UCLA) retinal specialist Steven Schwartz, MD and the Group at UCLA have developed a plan to keep his Macugen program running efficiently. "We have found that patients do not mind coming in for injections, but they do mind a long waiting time in the office," says Dr. Schwartz. "In response to this, we have created injection clinics twice a week. We dedicate lanes and a few technicians. We deliver a number of injections with a goal of keeping average office waiting time below 30 minutes. We have found this approach both efficient and attractive to patients and families."

Others are taking a wait-and-see approach. For instance, Paul Tornambe, MD, a clinical investigator in the Macugen trials and director of the San Diego Retinal Research Foundation, says although his 2-physician practice is essentially at capacity now, he does not foresee having to make any changes to accommodate the provision of Macugen. "A couple of years ago, when we began doing Visudyne treatments, it looked like that was going to pyramid, and that I was going to have to spend 3 days a week doing just that. But that never panned out because doctors didn't follow the protocol and provide the treatments every 3 months," he says.

Similarly, David S. Boyer, MD, associate clinical professor at the University of Southern California, has rolled the Macugen injections into his existing practice, which he says is already heavy on Kenalog. "If our use of Macugen begins to rise exponentially, then we would consider setting aside a specific time to do the injections," he says. A critical variable in Macugen's place in his practice, he notes, will be patient tolerance. "We had a 92% patient retention rate in the clinical trials, but those were people who wanted to be in the trial and who were very motivated, and not representative of your average patient at all."

TREATMENT FREQUENCY AND DURATION

Another important variable regarding Macugen's impact on a practice is how closely the clinical trial protocol is followed. Some doctors say they will commit to the 2-year program and follow its recommendations strictly, while others plan to test after every injection, or after several injections, to evaluate the drug's efficacy and then make treatment decisions based on their findings.

"Some retinologists have thought about starting and stopping Macugen based on either vision or funduscopic findings; however, there are no data to support this strategy," says Dr. Schwartz. "No single paper correlates fundus findings with visual acuity. The data are clear and support chronic VEGF suppression with Macugen. To me, this creates a sort of imperative for the treating community to learn more about the therapy by frequently evaluating patients with examinations and diagnostic tests."

While Dr. Boyer readily concedes that there is an inherent risk in tweaking the prescribed protocol, he says he'll begin to monitor patients after 3 injections. "After any study is released, we look to see if we could improve upon it. I don't think there is hard and fast data indicating that every 6 weeks is absolutely critical. It may end up being every 4 or 5 weeks or every 7 or 8 weeks, but the only way to find out is for doctors to modify the protocol in their own practices and then report the outcomes."

Dr. Saggau suggests that following the 2-year plan lends some simplicity to an otherwise complicated endeavor. "Macugen presents new challenges to the clinical practice. It makes it a little more complicated and creates a new level of systems, but it simplifies patient care a great deal, as well. Once patients understand that they are going to undergo a specific course of therapy (after the initial OCT and angiogram to confirm the diagnosis), we don't need those diagnostic tests anymore, unlike PDT where every time they came back we had to check the test results to decide what we were going to do next. With Macugen, we know that once they start, it's a 2-year program, so it simplifies things."

Kirk H. Packo, MD, says he will probably follow the prescribed every 6 weeks for 2 years protocol in 'ideal' cases. "I think of an ideal case as a small lesion where I'm going to have a good chance of saving useful visual acuity," says Dr. Packo, who is a professor and the chairman of Rush University Medical Center in Chicago, as well a partner in Illinois Retina Associates. In cases with larger lesions, particularly those that are not otherwise eligible for PDT, Dr. Packo says, "If vision starts to fall off, I may back off on following the protocol. Depending on the patient's visual prognosis and progress, I may begin testing with OCT and fluorescein in making a decision on whether or not I want to continue."

According to Dr. Tornambe, the data strongly suggest that the Macugen program should be followed for at least 1 year, if not the full 2 years. "I'll follow the protocol unless I see something in the eye that turns into a disciform scar, and it turns out that to continue with the injections would be like beating a dead horse. It's important to keep in mind that this is maintenance therapy for a chronic disease with exacerbations. I think once you begin Macugen, you have to commit to it, which is why I'm a little more cautious about starting [a patient on] Macugen," he says.

Lawrence J. Singerman, MD, president of Retina Associates of Cleveland, and clinical professor of ophthalmology, Case Western Reserve University, who was among the leading recruiters for the Macugen clinical trials, says it is too soon to make a firm commitment to recommended frequency and duration of treatment. "I don't think we can make a firm commitment to that yet. I think we'll follow it in the vast majority of cases, since the data are compelling, but we certainly won't follow it blindly in all cases," he says. "We'll use patient satisfaction, visual acuity, distortion, leakage on fluorescein angiography, OCT. We'll use every available option to determine efficacy. Also, there's the possibility of combining it with PDT, which may alter the frequency of one or the other or both," he adds.

Reginald J. Sanders, MD, of the Retina Group of Washington and also clinical associate professor of ophthalmology at Georgetown University School of Medicine, is looking at the question of frequency and duration of a treatment from a different perspective. "Although the Macugen study -- including its treatment protocol of every 6 weeks for 2 years -- was approved by the FDA, there's no better study than the collective experience of the physician community. As physicians, we have to be vigilant about making these decisions based on our own clinical observations," says Dr. Sanders.

FINANCIAL ASPECTS

The initial expenditures associated with incorporating Macugen into practice are minimal according to those who have done so. A refrigerator to maintain the drug's appropriate temperature, a monitor to ensure the continuous operation of the cooling system, and perhaps a few extra speculum represent the initial outlay. The financial burden lies elsewhere.

"This is a very expensive procedure and if for some reason we don't collect the copay we are at risk. Fortunately, in this instance, the Eyetech/Pfizer team has put together stopgaps to help docs circumvent these potential losses, but ultimately the risk is ours," says Dr. Boyer.

Approximately 75% of patients for whom the treatment is indicated are Medicare beneficiaries. Medicare has set the reimbursement rate at the Average Sales Price (ASP) plus 6% or $1054.70.

"Medicare has left it up to the local carriers whether to reimburse part of it, all of it or none of it," says Dr. Sanders. "Eyetech has done a superb job of getting local coverage." The treatment is covered by Medicare in all 50 states, according to Dr. Sanders, a board member of the American Society of Retinal Specialists (ASRA) and its federal liaison for reimbursement issues.

An important piece of the puzzle is that the Centers for Medicare & Medicaid Services (CMS) has determined that as of 2006, all medication that is injected by physicians in the care of Medicare patients will be reimbursed 6% plus the ASP of the drug. Previously, CMS paid 95% of the Average Wholesale Price (AWP). This meant that if the drug manufacturer discounted its drug, the physician stood to earn more of a profit and therefore had an incentive, beyond the best possible care of the patient, to provide the drug. Dr. Sanders says it looks as though the local carriers will follow Medicare's lead and reimburse the usual 80%; patients or secondary insurance are responsible for the remaining 20%.

"Seventy-five percent of patients who have macular degeneration have Medicare, which means that most of our patients will be covered by their primary insurance," notes Dr. Sanders. "Medicare covers 80%. If you don't collect the other 20% from secondary personal insurance or Medicaid or the patient, you can lose about $200 per patient per shot, which equates to about $9000 per year if 50 patients in your practice are on Macugen or double that if you have 100 Macugen patients."

Dr. Sanders advises having the patient sign a waiver indicating that it is not certain if their secondary insurance will cover the copay, and that if it the copay is not covered the patient is responsible. "Typically, the commercial insurers reject a new procedure or medication a couple of times before they get on board. Unless someone's dogging them, it's not in their best interest to cover it. Once they agree to cover it, it takes another 18 months to get reimbursed. So the risk is greatest in that first 18 months," he says. "Eyetech has done an exhaustive job of getting commercial carriers on board."

If insurance coverage and the copay both come through without a hitch, the physician stands to earn $300 per injection, but no one is adding Macugen to their armamentarium with the idea that it will be a profit center. "No practice that I know of in the country collects 100% of their 20% copays or secondaries. Just to break even in a case like Macugen where you are paying for the product up front, you need to collect 95% of copays," says Dr. Sanders.

The reimbursement scenario varies if the injections are performed in a hospital or ASC. In these settings, the facility is responsible for purchasing the drug, which alleviates the cash flow dynamic associated with performing the injections in the office. All physicians who were interviewed for this article say they will provide the treatments in their offices. "There's a big difference in risk if you do it in an ASC or hospital vs. in your office," says Dr. Sanders. "You get reimbursed less if you do it in an ambulatory surgery center (ASC), but the advantage is that you don't have to buy the drug. Although you make less profit in that scenario, you also avoid a lot of the financial risk."

Dr. Saggau echoes the sentiments of others quoted in this article when he said, "Macugen offers people with wet AMD an advantage over the natural history of the disease. We finally have something to offer a lot of people that we didn't have to offer in the past, so we're going to offer it regardless of what the profit and loss picture is." Dr. Tornambe points out that the manufacturer is doing everything possible to help. "While I'm concerned that, at the outset, physicians will end up eating some of the cost of the drug, Eyetech is bending over backwards to make it as atraumatic as possible. I think that Eyetech has anticipated these problems and really has made a great effort to get around it," he says.

ASEPTIC TECHNIQUE

In addition to possible retinal toxicity and mechanical damage to the lens and retina by a misdirected injection, the rare but serious risk of endophthalmitis demands adherence to controlled aseptic conditions. Dr. Schwartz describes his aseptic technique at UCLA as being 100% on label. "We use a drape, speculum, and gloves, and all patients receive a telephone call 2 to 3 days after the injection, as well as a slit lamp exam within a week of injection. Often, the referring physician is happy to participate and will perform the 1-week exam," he said. "We have found that by involving patients in endophthalmitis prevention, lid scrubs, and 3 days of preoperative fourth-generation fluoroquinolones, they are not only happy to come back for the injection, but they are truly engaged in the process and this seems to add to their satisfaction."

Dr. Tornambe says he plans to continue using the aseptic technique that he's been using. "I've given thousands of injections in the office because I've done a lot of pneumatic retinopexy since the mid 80s, and I will use the same protocol for Macugen as I use for pneumatic retinopexy. I always use a speculum, always use a 10% betadine prep, and although this is not in the recommended protocol, I always give about 20 milligrams of gentamicin in the subconjunctival manner near the injection site. As I said, I've been doing this for 20 years and I've never had an infection so I'm not about to stop."

Everyone agrees on the necessity of using a speculum and liberal povidone iodine, but they part ways on whether to administer antibiotics just before the procedure or several days prior, as well as on the use of topical or subconjunctival anesthesia. Additionally, no consensus exists on the use of gloves or a drape.

Dr. Packo says his large group practice had as much difficulty in standardizing their technique as the Consensus Panel had on creating its "Evolving Guidelines for Intravitreal Injections," (Aiello, et al., Retina 2004). "We didn't standardize the anesthesia because we couldn't come to agreement as a group," says Dr. Packo. "I use a subconjunctival injection, but most of my partners are using topical anesthesia. They say most of the time the patient hardly feels anything. But the way I see it is if it were my eye, I wouldn't want to ever feel anything."

 



Retinal Physician, Issue: May 2005