AMD Therapies: Comparing Costs and Quality of Life

This article is from October 2006 and may contain outdated material.

The recent windfall in promising therapies for AMD is most welcome. Next comes the job of weighing their relative costs and benefits.

The first treatment option is observation,” said Sharon Fekrat, MD, associate professor of ophthalmology at Duke University.

She was speaking about age-related macular degeneration, and her restraint may set the right pace for assessing the exciting and newly rich spectrum of AMD therapies: the anti-VEGF agents Macugen (pegaptanib), Avastin (bevacizumab) and Lucentis (ranibizumab), as well as combination approaches such as photodynamic therapy (PDT) with Visudyne (verteporfin), PDT with Visudyne plus Kenalog (triamcinolone acetonide), and PDT with Visudyne plus an anti-VEGF treatment. “In some cases,” Dr. Fekrat added, “there’s full macular translocation surgery.”

“I’ve been in practice for 11 years,” said Nancy M. Holekamp, MD, associate professor of clinical ophthalmology at Washington University in St. Louis. “In the past, it was either thermal laser or observation. Now we have choices.”

Choices aren’t always cheap, however, and that’s a shadow hanging over an otherwise bright horizon. In fact, the consensus among some retina specialists is that Avastin and Lucentis, the only treatments shown to prevent vision loss and improve visual acuity, will outshine the others. But the difference in their respective costs is looming over their respective benefits.

Here is the emerging picture on cost-effectiveness for AMD therapy.

The Value of Value?

“Most companies in the business world talk about value,”Dr. Holekamp said. Medicine, on the other hand, talks about outcomes based on the best scientific data available. While Dr. Holekamp agreed that evidence-based medicine is how we need to practice ophthalmology, she said value also matters.

Dr. Holekamp is a proponent of the work of Gary C. Brown, MD, MBA, and Melissa M. Brown, MD, MN, MBA, a husband-and-wife team that hopes to revolutionize the practice of ophthalmology by quantifying the value of particular treatments. They measure total improvement in quality of life from a particular intervention, taking into account efficacy and all the side effects. Value-based analyses identify the best interventions across all fields of health care while integrating the relevant costs.

How it works. First, a “utility” value is assessed. This assessment of value takes into account:

• the visual improvements demonstrated by the treatment in clinical studies,
• the adverse effects of the treatment, and
• the patients’ perspective on how the treatment affects the quality of life.

Extensive research has been done to measure the quality of life of patients at different visual abilities. This may sound elusive, but one approach has been to ask a large number of patients with varying levels of visual acuity how much time of their remaining life they would trade in return for perfect vision. In the case of moderate vision loss, for example, the average patient is typically willing to trade four to 10 years to achieve perfect vision. These data are converted to a “utility” value by a standard formula.

From there, the length of time that the effects of the intervention are expected to last (often the rest of the patient’s life) is factored in, as well as the effects due to adverse events of treatment. The resulting “total utility gained” is measured in quality-adjusted life years (QALYs).

Finally, the cost of the treatment is considered in order to arrive at a cost-utility ($/QALY) assessment.

How value is interpreted. The parameters for what is cost-effective depend largely on what society is willing to pay for health care, said Dr. Melissa Brown, principal and director of the Center for Value-Based Medicine, Flourtown, Pa. By convention, an intervention is deemed very cost-effective if it costs less than $50,000/QALY. Anything over $100,000 is thought of as not cost-effective. A gray area exists between $50,000 and $100,000. Thus, cataract surgery, the most common major operation in ophthalmology, is very cost-effective at $2,020/ QALY.

PDT, on the other hand, was not cost-effective, when calculations were done with early trial data. A more recent calculation, using new data based on longer treatment time, found PDT with verteporfin for classic subfoveal CNV to be very cost-effective.¹ “Over time, the clinical trials showed that PDT became more cost-effective because the results were better,” Dr. Brown said.

Now the Browns are awaiting the publication of a number of clinical trials to analyze other AMD treatments. The analyses should be published within a year. Value-based medicine, in essence, provides a Consumer Reports to all stakeholders in health care, Dr. Brown said.

Or the Quality of Quality?

On a different front, some ophthalmologists assess the value of a treatment by measuring the effect of a particular treatment on quality of life. The most common assessment tool, the NEI’s Visual Function Questionnaire-25, a 25-question survey tool used in most clinical trials, captures those perceptions.

This measure, said Tom S. Chang, MD, associate professor of clinical ophthalmology, University of Southern California, determines whether a treatment improves a patient’s visual function by asking about activities of daily living—such as the ability to see things up close and in the distance—and how they rate their sense of dependence.

Dr. Chang called the VFQ-25 results from the MARINA study, which tested Lucentis vs. sham, “very robust.”²He said that for the first time in ophthalmology, there is a pharmacologic agent that demonstrated a clinically meaningful difference, as well as a statistically significant improvement in quality of life. “This is directly related to the large treatment effect of the drug,” he said, adding that the results were consistent across two randomized trials.

While quality of life assessments are used extensively in oncology and orthopedics, ophthalmology embraces visual acuity as the standard metric, Dr. Chang said. But that may not be as important for patients. Patients want to know how their function will change. Will they be able to drive, knit or recognize a friend from across the street? By that measure, he said, Lucentis is a breakthrough.

Variables. How often does a treatment have to be given? That’s another cost-effectiveness consideration, said Barbara A. Blodi, MD, associate professor of ophthalmology and visual sciences, University of Wisconsin, Madison. For example, PDT with intravitreal steroids is very cost-effective because even though one PDT treatment costs around $2,000, the use of the adjuvant steroid treatment (Kenalog is $5 to $10 for a single treatment) appears to prolong the therapy’s effectiveness, Dr. Blodi explained. “We find we may only have to give the treatment once or twice, if we do this combination,” instead of more than six treatments of PDT alone over two years.

Frequency of treatment could become an issue with Lucentis, despite its good trial performance. In the phase 3b PIER study findings, patients treated with Lucentis showed, on average, an improvement after three monthly injections. But those benefits dwindled after additional doses, and visual acuity drifted back toward baseline.

Dr. Blodi sees her highest risk patients—those who have lost central vision in one eye—every four to six months. She also noted that retina specialists are relying more on optical coherence tomography, which is more cost-efficient than fluorescein angiography. In fact, a small study (n = 40) out of Bascom Palmer Eye Institute found that by monitoring Lucentis patients with OCT, fewer injections were needed.

Seeing is believing. At the end of the day, if a treatment works well, it will be considered cost-effective by many people even if it is expensive. But if it performs poorly, it will not be cost-effective at virtually any price. “People fear going blind even more than death,” said Dr. Holekamp. “We’re fortunate to be in a specialty where our interventions tend to be cost-effective, because people so greatly value their vision.”

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1 Am J Ophthalmol 2005;140:679.

2 Miller, J. et al. Randomized, controlled phase 3 study of ranibizumab (Lucentis) for minimally classic or occult neovascular age-related macular degeneration. MARINA Study Group data presented to the American Society of Retina Specialists 23rd Annual Meeting, July 16–20, 2005, Montreal, Canada.