Relative Cost of a Line of Vision in Age-Related Macular Degeneration

Results 

Extrafoveal choroidal neovascularization treatment by argon laser was found to be efficacious in the first report of the Macular Photocoagulation Study Group.1 From that study, the WLS was 2.43 and VPP was 2.25 from Figure 3 from 18-month follow-up data. The MLVC (estimated from Table 3 of the follow-up report3) was 1.9 lines (Table 1). The Macular Photocoagulation Study Group also reported on treatment of juxtafoveal neovascularization utilizing krypton laser photocoagulation.2 The WLS was 1.05 (from Table 6), the VPP was 0.84 (from Fig 3), and the MLVC was 1.5 (from Fig 4) from that reference.2 The WLS was derived from 5-year Macular Photocoagulation Study follow-up data.3 The treatment of subfoveal neovascularization was also reported.4 From Table 5 of that reference, the WLS was 1.70 and the MLVC was 1.4; from Figure 5, the VPP was 0.3.4 The WLS and MLVC data were available for only 24 months of follow-up.

The Treatment of Age-Related Macular Degeneration with Photodynamic Therapy study group first reported the efficacy of PDT with subfoveal neovascularization that had mostly or minimally classic components.5 From Table 3 of that reference, the WLS was 2.31 and the MLVC was 1.4; from Figure 2, the VPP was 0.6. A subsequent study reported the use of PDT for exclusively occult lesions.6 From Table 3 of that reference, the WLS was 1.34 and the MLVC was 0.84 at 12 months; VPP was 0.09 (from page 547). The WLS (1.75) and VPP data were more favorable for 24 months of follow-up (0.84 for 3 lines and 1.02 for 6 lines), so these numbers were used.

The first treatment study combining PDT with intravitreal triamcinolone was reported by Spaide et al.7 Only MLVC could be estimated from this study for comparative purposes; the subgroup analysis was important in that the MLVC from baseline was 2.5 for patients with no previous PDT and 0.44 for those with previous PDT. This result should be compared with expected visual loss, which using controls for the Treatment of Age-Related Macular Degeneration with Photodynamic Therapy5 and Verteporfin in Photodynamic Therapy6 studies was estimated at 2.6 lines, yielding 5.1 lines saved. A subsequent study corroborated these findings, but the results were not reported in the same format.22 Although cataract extraction is probably needed more (27% in the Augustin and Schmidt-Erfurth study22 vs. 13% in nonsteroid injection studies), this was not factored into the cost models. Spaide et al7 found the need for retreatment in 24% in the first year.

The first report of an anti–vascular endothelial growth factor agent for AMD was pegaptanib8; there was no subtype analysis as in the photodynamic therapies. Utilizing the results only for the most effective dose (0.3 mg), the WLS was 0.90 (from Table 3, Table 4 of that reference), the VPP was 0.72 (from Table 3), and the MLVC was 1.5 (from Fig 1). The Age-Related Eye Disease Study was also analyzed.9 The only comparative parameter was the VPP, which at 1 year showed 0.04 lines (from Fig 6). Only categories 3 and 4 were utilized, from Figure 6 of that reference. Because therapy with Age-Related Eye Disease Study vitamins is very different in its intent, this VPP was calculated as 0.18 for 5 years.

Discussion 

The data and calculations that proceed from this paper are based on the seminal studies for each principal treatment for AMD. Although the analysis proceeds from many assumptions, these err on the side of favoring the cost effectiveness of newer AMD treatments. Clearly, many steps in this analysis could be argued as inaccurately reflecting the visual value or costs, but the comparisons in this analysis yield large differences, so the trend is likely real and at least is worthy of attention. The observation that costs are high is indisputable. Furthermore, costs are being increasingly distributed to pharmaceutical expenses, and pricing (unlike professional fees) is being set corporately (at least initially) rather than by free market– or even government–regulated payor mechanisms. A health care system has many constraints that limit what diseases it chooses to cover or exclude. Within a broad distribution of disease, it is not generally ethically or politically feasible to trade out the high cost per line conditions such as AMD for low cost per line conditions such as RDs or other chronic disease care for more limited problems. Therefore, the challenge is to determine how to cope with the diagnoses that involve expensive treatments.

There are many assumptions that likely underestimate the disparity in costs. Long-term follow-up information for AMD treatment is lacking; the amount of vision preserved by AMD treatments probably does not continue to improve and how well it is maintained awaits confirmation. Clearly, the nature of diseases can differ; AMD requires more chronic, ongoing care compared with most of the comparison conditions cited in this study. However, this preliminary analysis has examined only the acute phases of treatment. Second-year costs of most new AMD treatments may approximate first-year costs, and costs in subsequent years have not been defined, but are likely substantial. The point at which treatment may be discontinued (end point) is also nebulous. In contrast, the ongoing costs for the comparison diagnoses are, at most, a small fraction of initial costs.

This study showed that the costs for AMD treatments are further amplified when considering that the life expectancy of the typical patient with AMD is substantially shorter than for many comparison conditions, such as RD.

In addition, the visual benefits calculated from the cited AMD studies are derived from optimized, “study” patients; broader application to “all comers” likely yields less benefit, because the clinical eligibility criteria for treatment are less strictly defined for intravitreal therapies in the first place and are likely to be even more broadly applied in the second place.

In the absence of substantial differences in measured Snellen visual acuity outcomes, other studies have proposed alternate parameters of visual benefit. These include contrast sensitivity,23 disability avoidance,24 impairment rating,25, 26, 27 quality of life,28, 29 and utility value.29, 30, 31, 32, 33, 34, 35, 36 Most methods either are largely based on visual acuity or correlate fairly well with visual acuity. Snellen visual acuity is the most intuitive, quantitative, and universal approximation in the clinician’s experience for evaluating therapeutic treatments. Alternative measures are commonly based on qualitative patient judgments, which are less intuitive to the physician’s assessment.

The most comprehensive cost analysis study was a diabetic retinopathy model based on reasonable assumptions in a model of detecting and treating patients with diabetes to avoid disability associated with severe visual loss.24 The conclusion of that study was that the level of effectiveness of treatments compounded by the frequency and youth of type 1 diabetes yielded an enormous saving ($9571 for each newly diagnosed patient) to society by avoiding disability. A similar cost analysis for AMD may yield surprisingly high societal cost savings, but because the AMD population is more commonly at or past retirement age, the magnitude would, no doubt, be less.

Others have evaluated the cost utility of photodynamic treatment in the group of patients with predominantly classic choroidal neovascularization owing to AMD.37 That study utilized the concept of quality-adjusted life years, which has been developed by other investigators.30, 31, 32, 33 Other investigators have attempted to quantitate quality of life rather than Snellen visual acuity for conditions such as macular degeneration, macular holes, and other macular disorders.25, 26, 27, 28 Whereas it is well understood that central, Snellen visual acuity is not a universally applicable standard, its accuracy is still formidable.27

Newer, probably more efficacious treatments for macular degeneration are on the horizon38 and although these may represent substantial improvements in preserving and even restoring visual acuity, they promise to be more expensive than existing pharmacologic treatments. In addition, strategies involving combinations of existing therapies are being investigated. Although these might further escalate costs, they could sum to a more cost-effective strategy; the results of ongoing studies in this area are pending.

Recently, an innovative intravitreal application of a systemic anti–vascular endothelial growth factor agent has shown promise in both efficacy and especially in cost reduction.30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41 It might be that a marginal benefit of more expensive therapies must be weighed against therapies that might be markedly less expensive. The published data for ranibizumab and bevacizumab are preliminary and involve shorter follow-up intervals. With those provisos, an estimated cost calculation similar to the current study could be applied. If one estimates 5.4 lines saved (3 lines average improvement and 2.6 lines visual loss avoided as in PDT controls)5, 6 with 12 applications of ranibuzamab,42 a similar clinical and testing regimen, and a $2000/dose price, the cost for treatment works out to $9000/line or $900/line-year. Similarly, for bevacizumab an assumption of 4 treatments (as has been a common first year frequency, the author’s experience), 3.6 lines saved (1-line average improvement—30.3% × 3 line improvement—plus avoidance of 2.6 lines lost from PDT studies5, 6) yields $600/line or $60/line-year. Even if applied for 8 or 12 doses, a doubling or tripling of costs is still an order of magnitude below that of other strategies. Assumptions in this analysis are even less well established than in the foregoing analysis and should be considered even rougher estimates until longer term data are published.

Others have reported potential repercussions from the high costs of newer AMD treatments.29

Intuition questions the sustainability of delivering such expensive therapeutic interventions for a condition with such a high prevalence as macular degeneration. The marginal benefits and broadly advocated indications compound this issue. Yet, this situation is not unique to ophthalmology; there are counterparts in many fields such as oncology, orthopedics, infectious diseases, and cardiology. If the disproportionate pharmaceutical costs are at the expense of reimbursements for more cost-effective treatments as outlined in this paper (the “single pool” of health care resource allotment) the greater good could be threatened.43 This author confesses naivety regarding relative value units allocation at a government payor level, but the principle of meeting escalating pharmaceutical costs at the expense of professional reimbursement poses a severe risk to health care delivery. In the extreme case, the scope of the specialty could be redefined in a distorted way. Certainly, cost recoupment is necessary to sustain research, development, and approval of new therapies, but innovation and effective treatment delivery across the broader range of disease may be threatened or biased unless these issues are reconciled.

The means to quantitate differences is a necessary first step in opening any cost-containment debate. Quantifiable measures have been previously proposed, but do not have universal acceptance, possibly because of their subjective component. Possible strategies that are ethically appropriate and politically feasible might come from 2 directions. Scientifically, studies might identify subgroups with better or nonefficacious responses, explore combination regimens that allow a less expensive chronic-phase therapy, or find similar efficacy with a reduced number of treatment sessions. Health care policy might be able to create incentives to decrease drug cost, share the costs with individuals, or police usage without creating new, undue burdens. A fair, unbiased, and educated organization (or the closest approximation to that ideal) might be empowered to guide, define, and direct the applicability of such treatments. The difficulty of this strategy is the lack of precedent for its efficacy. A good measure of physician responsibility, as protected by the authority of clear guidelines, seems a necessary component for implementing what could be hard, even conflicting treatment patterns. The individual practitioner’s intuition and the business bias of pharmaceuticals leave a vacuum of responsible stewardship. However, without a fundamental change, market forces may severely harm both providers and patients.