Cost-Effectiveness of Treatment for Threshold Retinopathy
of Prematurity
Gary C. Brown, MD, MBA*‡; Melissa M. Brown, MN, MD, MBA*§; Sanjay Sharma, MD, MSc(Epid)*\; William Tasman, MD‡; and Heidi C. Brown*
ABSTRACT. Objective. Retinopathy of prematurity (ROP) is a leading cause of adverse visual outcomes in premature infants. Both laser photocoagulation and cryo-therapy have been demonstrated in clinical trials to be efficacious in reducing the incidence of visual loss occur-ring secondary to threshold ROP. Visual data recently have become available concerning the long-term clinical efficacy of both treatments, as have data concerning the utility value of visual states in general. Accordingly, we undertook an analysis to ascertain the cost-effectiveness of laser photocoagulation and cryotherapy in the treat-ment of threshold ROP.
Design. A computer simulation economic model is presented to evaluate the cost-effectiveness of cryother-apy and laser photocoagulation thercryother-apy, compared with the natural course of the disease, for treating premature infants with threshold ROP. The model applies long-term visual data from previous clinical trials, utility anal-ysis, decision analanal-ysis, and economic principles, such as present value analysis, to account for the time value of money to arrive at a cost per quality-adjusted life-year (QALY) gained.
Outcome Measures. Cost per QALY gained from laser therapy and cryotherapy.
Results. Laser photocoagulation therapy for thresh-old ROP costs $678 1998 US dollars (at a 3% discount rate to account for the time value of money) for each QALY gained from treatment. Cryotherapy for the same disease costs $1801 per QALY at a similar discount rate.
Conclusions. From the point of view of cost-effective-ness, laser therapy seems to have an advantage over cryotherapy for the treatment of threshold ROP.
Pediatrics 1999;104(4). URL: http://www.pediatrics.org/
cgi/content/full/104/4/e47; threshold retinopathy of
pre-maturity, laser therapy, cryotherapy, cost-effectiveness. ABBREVIATIONS. ROP, retinopathy of prematurity; HCFA, Health Care Financing Agency; CPT, Current Procedural Termi-nology; QALY, quality-adjusted life year; $/QALY, cost per qual-ity-adjusted life-year.
R
etinopathy of prematurity (ROP) is the leading cause of blindness among premature infants.1 It occurs in some form in;32% of infants with birth weights #1000 g.1 Among those infants with birth weights,1251 g, 7% to 8% will develop thresh-old ROP.2Threshold ROP is defined as proliferative retinal vascular disease that is located in zone 1 or 2 in conjunction with plus disease and associated with 5 contiguous or 8 cumulative clock hours of extrareti-nal neovascularization.1Of those who are treated for threshold disease, the long-term survival is;88%.3The Multicenter Trial of Cryotherapy for ROP ini-tially demonstrated that retinal cryotherapy for threshold ROP decreased the incidence of an unfa-vorable anatomic outcome from 51% to 31%.2 Subse-quently, the Laser ROP Study Group4showed with a meta-analysis that the risk of an unfavorable out-come in eyes with threshold ROP was 19% with cryotherapy and 8% with laser therapy.
Now that children who were treated for threshold ROP are maturing, data concerning the long-term visual acuity results from prospective clinical trials are available.5–7It seems that the mean visual acuity in eyes treated for threshold ROP may be better in those children treated with laser photocoagulation than in those treated with cryotherapy. Although systemic complications can be associated with cryo-therapy8 and laser therapy,9 the incidence of such complications seems to be low.
Cost-effective analyses that involve utility theory are being reported with increasing frequency.10 –13 Utility analysis incorporates patient-based prefer-ences that allow the quality of life associated with a health (disease) state to be quantified. In view of recent data concerning utility values in patients with visual loss14 and new information on visual results after therapy for ROP,5–7we undertook an analysis of the cost-effectiveness of laser photocoagulation and cryotherapy for the treatment of threshold ROP.
METHODS Overview
Software produced by Treeage, Inc (Williamstown, MA)15was used to perform decision analysis to simulate the clinical situation involving laser therapy, cryotherapy, and no therapy for patients with threshold ROP. This microcomputer model takes into ac-count the mortality within this group of patients, as well as the treatment results expressed in utility form. The numbers of uni-lateral and biuni-lateral cases also were factored into the analysis. Utility values were used at the terminal nodes at the right side of the decision tree to provide the most probable utility value out-comes given the different possible clinical scenarios. The utility
From the *Center for Evidence-Based Healthcare, Flourtown, Pennsylvania; the ‡Retina Service and the §Cataract and Primary Eye Care Service, Wills Eye Hospital, Jefferson Medical College, Philadelphia, Pennsylvania; and the\Epidemiology Unit, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts.
Received for publication Dec 31, 1998; accepted Apr 26, 1999.
Reprint requests to (G.C.B.) Center for Evidence-Based Healthcare, Suite 210, 1107 Bethlehem Pike, Flourtown, PA 19031. E-mail: gary0514@aol.com PEDIATRICS (ISSN 0031 4005). Copyright © 1999 by the American Acad-emy of Pediatrics.
values were based on the visual acuity in the better seeing eye with lower levels of visual acuity yielding correspondingly lower utility values.14
The clinical data used for the analysis are described below. Additional clinical data and assumptions used in the analysis are shown in Table 1.
Treatment
Per the criteria of the Multicenter Trial of Cryotherapy for ROP,2 data were included in the present analysis only if the information involved patients with threshold ROP1 who were treated within 72 hours of the discovery of the threshold disease. Cryotherapy was performed by confluently freezing all avascular retina anterior to the mesenchymal ridge or extraretinal neovas-cularization in affected eyes.1,2,6In a similar manner, only those eyes receiving laser in which all avascular anterior retina was treated with full scatter photocoagulation1,4,16were included.
Mortality and Morbidity
The Cryotherapy for ROP Cooperative Study Group followed a cohort of 291 infants with birth weights,1251 g who entered a prospective randomized clinical trial and were treated in one eye with cryotherapy for threshold ROP.2,3Data obtained on the same cohort at 31⁄2years after randomization revealed that there were 256 survivors among the original cohort of 291 infants.3The av-erage infant was randomized and treated at;3 months of age. Thus, the mortality rate within 33⁄4years after birth was 12% (35 deaths of 291 infants).
It was assumed that children who survived to this stage had a normal life expectancy, although confirmatory data are not avail-able. Data on life expectancy were obtained using 1994 statistics obtained from the Centers for Disease Control and Prevention and the National Center for Health Statistics.17
The incidence of postoperative retinal detachment, cataract, or other ocular complications attributable to cryotherapy or laser therapy is unknown but is likely very low. The systemic morbidity associated with the treatments is low but present. Brown and associates8found that cryotherapy induced cardiorespiratory ar-rest in 1 of 80 consecutive patients, and Vander and associates9 noted approximately the same results for laser therapy.
Bilaterality Versus Unilaterality of Threshold Disease
The Cryotherapy for ROP Cryotherapy Group found that 82.5% of the patients in the cohort of 291 infants developed bilateral threshold disease. For the purposes of our report, those patients with bilateral disease were assumed theoretically to have a similar visual result if they were to be treated with laser therapy in both eyes, have cryotherapy in both eyes, or have no treatment in both eyes. Because it is rare for ROP eyes to convert from a
subthresh-old state to threshsubthresh-old disease at 6 months after birth, which is when the data were reported, it was assumed that none of the unilateral cases would progress to bilateral threshold disease.
The patients with unilateral threshold ROP were presumed to have a normal eye with normal vision on the unaffected side. Thus, their vision was converted to a utility value by the method shown in the next two sections.
Visual Results
Visual results are emerging from clinical trials involving long-term follow-up of patients treated for threshold ROP.5,6The most specific results for treated eyes come from the data of Connolly et al,6who were able to quantify vision in Snellen form in threshold ROP eyes treated with laser therapy or cryotherapy and with a mean follow-up of 5.8 years. The most complete visual data on the natural course of untreated threshold ROP come from the Cryo-therapy for ROP Cooperative Group7that gathered data on sur-vivors from a cohort of 291 patients with threshold ROP.
The assumption was made that once children were$5 years of age, the visual acuity would be stable in each eye. The incidence of long-term complications associated with ROP is unknown. It was assumed that the long-term complications (after 5 years of life) are equal in eyes that underwent laser therapy, cryotherapy, or no treatment.
The visual results for both treated eyes and untreated eyes were reported using the Snellen method, which is the most commonly used method for measuring visual acuity in clinical practice. For the purposes of this report, the Snellen visual acuity results in the eyes were converted to decimal form: 20/205 1; 20/25 5 0.8; 20/305 0.67; 20/40 5 0.5; 20/50 5 0.4; 20/60 5 0.66; 20/70 5 0.29; 20/805 0.25; 20/100 5 0.2; 20/200 5 0.1; and 20/400 5 0.05. For a vision of counting fingers, a value of 0.025 was assigned, and for hand motions, a value of 0.0125 was assigned. No light per-ception was given a value of 0.0.
For the natural course of the disease,7those eyes classified in the 20/40 or better range were assigned a mean acuity of 0.67 (20/30), those in the 20/40 to 20/60 range were assigned an acuity of 0.4 (20/50), those in the 20/60 to 20/200 range were given a mean acuity of 0.2 (20/100), those with 20/200 or worse were assigned an acuity of 0.05 (20/400), and those who had vision that was not quantifiable were given a mean acuity of 0.0125 (hand motions).
For those few patients with laser or cryotherapy treatment6 who did not have specific Snellen vision measurement, a value of 0.025 (counting fingers) was assigned to fix-and-follow or cen-tered, steady, and maintained vision, whereas the one eye in the series with unsteady and unmaintained vision was assigned a value of 0.0125 (hand motions).
Conversion of Visual Acuity to Utility Values
It has been noted that the mean utility values of individuals with ocular disease diminish in proportion to the severity of visual loss in the better seeing eye.14Recent data derived via multivariate regression analysis come from a large series of patients with visual loss from various ocular diseases.14These data have allowed the conversion of Snellen visual acuity in the better eye to a mean utility value. The formula derived by this analysis is:
Utility5 0.374x 1 0.514.14
Medical Costs
The costs obtained from this analysis were representative of those paid by the Health Care Financing Agency (HCFA) for provider services classified according to Current Procedural Ter-minology (CPT) data.18The data utilized were from the state of Pennsylvania.19The costs are summarized in Table 2.
The costs themselves included the mean expense to the payer of treatment with laser photocoagulation therapy (CPT code 67228) or cryotherapy (CPT code 67227) in both eyes for 82.5% of patients, and treatment with laser photocoagulation therapy or cryotherapy in one eye in 17.5% of patients. These percentages directly reflect the percentages of premature infants in the Multicenter Trial of Cryotherapy for ROP Study with bilateral and unilateral threshold disease, respectively.2The cost of an initial hospital consultation was taken from the same HCFA data using CPT code 99254. Because the laser therapy and cryotherapy codes most commonly have a 3-month postoperative period, no costs were attributed to TABLE 1. Clinical Assumptions of the ROP Therapy
Econo-metric Model of Cost-Effectiveness
1. Additional cryotherapy is needed in 6.4% of cases and additional laser therapy is required in the same number. Nevertheless, because it is performed within a 30- to 90-day postoperative period (depending upon the insurer), there is no charge by the treating physician.2
2. There is no mortality from either laser therapy or cryotherapy.1,8,9
3. One of 80 patients who undergoes cryotherapy or laser therapy will experience a transient cardiorespiratory arrest8,9 that does not change the utility outcome in decision analysis; it only impacts upon costs.
4. Those cases with bilateral threshold retinopathy of
prematurity are considered to have a similar treatment result in each eye.
5. Those with unilateral threshold ROP are presumed to have normal vision (20/20) in the opposite eye. In this instance, the utility is based upon the formula found for patients with normal vision in one eye and visual loss to at least 20/40 in the second eye.14
6. Preservation of vision is assumed to be as valuable in children with neurologic deficits associated with prematurity as in those with normal psychomotor and social development parameters.
this postoperative period, despite the fact that retreatment might have been necessary in some cases within the first few weeks of initial treatment. Additional laser photocoagulation or cryother-apy for threshold ROP after this 3-month postoperative period is virtually nonexistent.1
Incremental hospital costs are not associated routinely with the treatment of ROP, because the treatment now is performed rou-tinely under local anesthesia,1and the patients are already typi-cally inpatients because of the risks of marked immaturity in the nonhospital setting. Nonetheless, when transient cardiorespira-tory arrest occurred secondary to either cryotherapy or laser ther-apy, the assumption was made that this would add 1 day to an infant’s stay in an intensive care bed. The expense for the day was calculated from a survey of the average per diem cost for an intensive care hospital bed in Pennsylvania.
Anesthesia services were utilized for a percentage of patients enrolled in the Multicenter Trial of Cryotherapy for ROP.2 Nev-ertheless, since that time, patients are treated routinely without the aid of general anesthesia.1For this reason, the cost of anesthe-sia services was not factored into the analysis.
Present Value Analysis
The benefits derived from laser therapy and cryotherapy for threshold ROP are spread out over the lifetime of the treated individual, but the cost required to deliver laser therapy or cryo-therapy is delivered during the first year of life (typically within the first 3 months of life). Therefore, some compensatory mecha-nism must be instituted to validate the economic analysis.
The time value of money is not constant.20,21A dollar spent now can be reinvested to yield more real dollars in the future. A dollar spent in the year 1999 will purchase more goods and services than a dollar spent in the year 2009. To account for the changing time value of money, we discounted the quality-adjusted life-years (QALYs) obtained yearly from the therapy over the life expectancy of the average individual to their present value. Alternatively, the future value of the dollars spent at the time of therapy also could have been calculated over the life of the patient (leaving the initial QALYs derived a constant) to arrive at the same analysis.
The discount rate is variable depending on the discretion of investors or other interested stakeholders. For the purpose of this analysis, we chose to use a discount rate representative of the yearly return on funds that an investor could obtain from the safest investment of capital over and above the yearly inflation level. In essence, this is accounting for the Fisher effect,22which adjusts the nominal return on investment for inflation, thereby yielding the real return. The approximate nominal return on one
of the safest investments (a United States government 1-year treasury bill) at the time of the preparation of this article was 4.5% per year,23and the current inflation rate in the United States was ;1.48% per year.24Thus, the yearly discount rate or return on investment in real dollars (calculated according to the Fisher ef-fect) used in our analysis is 1.045/1.01485 1.03, or 3% per year.
RESULTS Utilities
The mean visual results expressed in decimal equivalents using the Snellen system for acuity in premature infants with birth weights ,1251 g who develop threshold ROP are shown in Table 3. The average eye with laser photocoagulation therapy has a mean acuity of 0.49 at 5.8 years after treatment, whereas the average eye after cryotherapy has a mean acuity of 0.31 at a similar time after therapy.6 Untreated eyes with threshold ROP have a mean acuity of 0.237 at approximately the same time (5.5 years after treatment).
When the Snellen decimal equivalents were con-verted to utility values, the results were as follows: the mean utility for patients in the laser-treated group was 0.70, the mean for those in the cryother-apy group was 0.63, and the mean utility for the threshold retinopathy group that received no treat-ment was 0.60.
In the patients with threshold ROP in one eye, the mean utility was 0.89. This was calculated by insert-ing the Snellen decimal visual acuity for 20/20 or 1.0 into the Utility5 0.374x 1 0.514 formula.14
Decision Analysis
Three arms were used in the decision analysis tree for dealing with threshold ROP: 1) treatment with photocoagulation laser therapy; 2) treatment with cryotherapy; and 3) no therapy. The assumptions were made that the long-term survival in each of the arms was 88%, and that 82.5% of cases had bilateral threshold ROP.
Taking into account the above variables with the utility values described in the previous section ap-plied to the terminal nodes of the decision analysis tree, the mean decision analysis utility value for a patient with threshold ROP treated with laser ther-apy was 0.65. The mean utility value for a patient treated with cryotherapy was 0.59, and the mean utility value for patients in the group without treat-ment was 0.57.
QALYs
The number of QALYs is calculated by multiply-ing the improvement in utility conferred by a treat-ment modality by the number of expected years the modality will be in effect. For the 88% of children who survived to the 31⁄2-year level, the mean total life expectancy is 76.4 years.17 Because treatment was administered at 3 months of life, and because
stabi-TABLE 2. Cost Data Associated with Treatment of Threshold ROP
1. The cost of laser therapy for threshold ROP is $794 per eye. It is calculated according to CPT code 67228 [destruction of extensive or progressive retinopathy (e.g., diabetic retinopathy); one or more sessions: photocoagulation]. 2. The cost of laser therapy per patient is the weighted average
of 82.5% of patients treated in both eyes (23 $794) and 17.5% of patients treated in one eye (13 $794).2Thus, the weighted average cost per patient is $1450.70.
3. The cost of cryotherapy for threshold ROP is $498 per eye. It is calculated according to CPT code 67227 [destruction of extensive or progressive retinopathy (e.g., diabetic retinopathy); one or more sessions: cryotherapy].
4. The cost of cryotherapy per patient is the weighted average of 82.5% of patients treated in both eyes (23 $498) and 17.5% of patients treated in one eye (13 $498).2Thus, the weighted average cost per patient is $908.85.
5. The cost of the initial examination to decide upon treatment (either laser therapy or cryopexy) is CPT code 99254 (Initial inpatient consultation5 $140).
6. The per diem cost of an intensive care hospital bed is $1200. 7. There is no cost attributable to the follow-up examinations
after treatment because of the 3 month postoperative period for laser therapy and cryotherapy.
8. The improvement in quality of life is discounted at a rate of 3% over the remaining life expectancy of the long-term surviving infants who were treated;3 months after birth.
TABLE 3. Visual Outcome (in Snellen Decimal Equivalent) of an Eye with Threshold ROP
Laser therapy6 0.49 Mean of 5.8 years after treatment Cryotherapy6 0.31 Mean of 5.8 years after treatment No treatment7 0.23 Mean of 5.5 years after treatment
lization or progression occurs within weeks at most after treatment, the treatment effect was assumed to last for a total of 76 years.
Overall, cryotherapy conferred a 10.02 utility value treatment effect (0.59 – 0.57) per year over no treatment. Therefore, the number of nondiscounted, QALYs obtained by cryotherapy over no treatment for threshold ROP was 1.52 (0.02 3 76 years).
Laser therapy conferred a10.08 utility value treat-ment effect (0.65– 0.57) over no treattreat-ment. Thus, the corresponding gain in nondiscounted QALYs for this therapy over no treatment was 6.08 (0.073 76 years). As mentioned in a previous section, the number of QALYs obtained by a treatment regimen need to be discounted to provide a valid economic analysis. Employing a 3% discount rate over 76 years to the QALYs obtained with cryotherapy, the number of discounted QALYs obtained from cryotherapy over the natural course of the disease was 0.59 (Table 4). The number of QALYs obtained from laser therapy over the natural course of the disease was 2.37.
Sensitivity analysis of the values using varying discount rates revealed that with a 1% discount rate over the 76-year benefit period, cryotherapy deliv-ered 1.06 QALYs and laser therapy delivdeliv-ered 4.26 QALYs. When the discount rate was increased to 5% for the 76-year period of benefit, the numbers of QALYs gained by cryotherapy and laser therapy were 0.40 and 1.58, respectively. With a substantially higher discount rate of 10% over the 76 years, cryo-therapy showed a gain of 0.20 QALY, and laser ther-apy showed a gain of 0.79 QALY.
Medical Costs
The cost of an initial inpatient consult to examine a threshold child was $140 for both cryotherapy- and laser-treated patients. Assuming that 1 of 80 cryo-therapy- or laser cryo-therapy-treated patients would re-quire an extra day in intensive care attributable to the sequelae of transient cardiorespiratory arrest, the av-erage cost per patient at a per diem hospital day ($1200 per day) was $15.
The cost of laser therapy for one threshold eye was $794, and the cost for two eyes was $1592. Thus, the weighted average cost of laser therapy per patient (assuming bilateral threshold disease in 82.5% of threshold cases) was $1452. With the additional $140 for consultation and $15 for the risk of cardiorespi-ratory arrest, the total expense related to the treat-ment was $1607 for the average infant.
The cost of cryotherapy for one eye was $498, and for two eyes was $996. Using the same weighted average that takes into account the 82.5% of bilateral cases, the mean cost for cryotherapy of a threshold infant was $908. Therefore, with the additional $140
inpatient consult fee and the cardiorespiratory arrest assessment of $15, the total cost for cryotherapy for the average infant was $1063.
Cost per QALY ($/QALY)
The nondiscounted US dollars expended per QALY for cryotherapy were $699 ($1063/1.52 QALYs), and for laser therapy they were $264 ($1607/6.08 QALYs). Nevertheless, these figures do not take into account the time value of money. Thus, a discount rate must be applied to QALYs. When the discount rate of 3% per year is applied to the QALYs over the 76-year period of life expectancy of the average surviving infant, the $/QALY for cryother-apy is $1801 and for laser thercryother-apy is $678 (Table 4). Sensitivity analysis for $/QALY at a discount rate of 1% per year yields a $/QALY for cryotherapy of $1003 and for laser therapy of $377. With a discount rate of 5% per year, the $/QALY for cryotherapy is $2658 and for laser therapy is $1017. With a large discount rate of 10% per year, the corresponding figures are $5315 for cryotherapy and $2030 for laser therapy.
DISCUSSION
The results of this study suggest that both cryo-therapy and laser cryo-therapy are exceedingly cost-effec-tive treatments for threshold ROP. Both treatments result in a substantial improvement in mean quality of life that lasts over the lifetime of the average patient with threshold ROP. Although this study noted that the actual patient treatment costs associ-ated with cryotherapy ($1063) are less than those associated with laser therapy ($1607), evidence from a randomized clinical trial6 has shown that eyes treated with laser therapy have better long-term visual results than those treated with cryotherapy. These recent results were not completely unexpected by those well versed in treating threshold ROP. Re-sults from the Laser ROP Study Group4previously suggested the increased clinical efficacy of laser ther-apy over cryotherther-apy from the anatomic point of view.
Overall, using a 3% discount rate over the 76-year period of life expectancy of a patient with threshold ROP, the cost for laser therapy is $678/QALY and the cost for cryotherapy is $1801/QALY. The greater long-term clinical efficacy of laser therapy and the subsequent increased improvement of quality of life conferred by the better visual results suggest that it should be considered to be the preferred treatment if a clinician must choose between laser therapy and cryotherapy. Nevertheless, in instances with cloudy media (such as from vitreous hemorrhage or a marked tunica vasculosa lentis), laser therapy may not be possible, and cryotherapy may be the only option.
When comparing the cost-effectiveness of one medical interventional treatment with another, care must be taken to minimize the number of confound-ing factors.25If possible, utility valuation should be undertaken with the same investigational methodol-ogy (using the time trade-off method, the standard gamble method, or another method),26,27because the TABLE 4. QALYs Gained and Cost-Effectiveness of Therapy
for Threshold ROP Yearly
Discount Rate (%)
Cryotherapy Laser Therapy N of QALYs $/QALY N of QALYs $/QALY
0 1.52 699 6.08 264
results of these different methods can differ substan-tially.28,29Utility values obtained from different pop-ulations (eg, patients, physicians, administrators, and the general public) also can differ substantially for the same disease state.27,30We believe, as do oth-ers,31–33 that, when possible, preferences obtained from patients should be used, because those who have experienced diseases firsthand are best able to assess the degree to which the disease impairs qual-ity of life. The utilqual-ity values used in the present study were derived solely from patient preferences.14 Sim-ilar discounting methods and rates also should be used to account for differences in the time value of money caused by inflation, opportunity costs, or cur-rency exchange differences. The sensitivity analysis in the present study demonstrates the vast differ-ences in results that can occur from altering the discount rate alone, particularly when the treatment benefit effect occurs over many years and/or in the distant future. These substantial differences reflect the effect of compounding that occurs when calcu-lating discount rates. Finally, comparing medical costs should reflect a uniform scale, such as the scale used by the HCFA.19Comparing cost-efficiency from one country to another is particularly difficult be-cause of the lack of standard costs and the effect of currency exchange fluctuations.34
Keeping the above inexactitudes in mind, for com-parison we have calculated that a single vessel cor-onary artery bypass procedure for left main corcor-onary artery disease is associated with an incremental, 1998 US dollar cost-effectiveness of $6880/QALY30 and that a liver transplant is associated with an incremen-tal cost-effectiveness of $327 500/QALY.36 To our knowledge, data concerning the incremental cost-effectiveness of most interventional procedures asso-ciated with the sequelae of prematurity are not pres-ently available. Although there are no absolute standards for cost-effectiveness, it has been sug-gested arbitrarily that interventional therapies cost-ing.$100 000/QALY are not particularly cost-effec-tive, whereas those costing ,$20 000/QALY are cost-effective.35,36
Thus, both laser therapy and cryotherapy for ROP seem to be excellent values. The permanent improve-ment in vision that translates to improved quality of life from these treatments, which are of moderate cost, explains why they are especially cost-effective. In essence, laser therapy and cryotherapy are clini-cally efficacious treatments with long-standing ben-eficial effects that are not prohibitively expensive by modern health care standards.
Previous authors have studied the cost-effective-ness of screening and cryotherapy for threshold ROP. Javitt and associates37wrote an excellent trea-tise on the subject in 1993 and noted that appropriate ophthalmic screening of premature infants and sub-sequent cryotherapy treatment for threshold disease produce a substantial overall saving for the United States at a cost of $2488 to $6045/QALY, depending on the screening strategy. There are several impor-tant differences between that paper and the present study. Javitt and associates37took into account gen-eral ROP-screening costs in addition to those of
cryo-therapy, whereas the present study concentrated ba-sically on interventional treatment for threshold disease. Neither the Javitt paper nor this paper took into account the long-term follow-up costs associated with ROP over a lifetime. More importantly, how-ever, was the fact that long-term visual acuity data after cryotherapy and laser treatment for threshold ROP were not available for Javitt and colleagues.37 They assumed that good and bad anatomic fundus results correlated with either excellent vision or blindness, respectively, which is not the case.7Thus, the utility assumptions were substantially different in that paper, compared with the present paper. De-spite the differences, both the Javitt paper and the present study demonstrate the substantial cost-effec-tiveness of treatment for ROP.
The present study has theoretical drawbacks that should be noted. The study by Connolly et al,6 on which the follow-up visual acuities were based, had a relatively small cohort of patients, and the fol-low-up period was only 5.8 years; the visual sequelae of laser therapy and/or cryotherapy after 5.8 years are not known. Additionally, the utility values that we used were calculated from a formula derived by multivariate analysis from a large sample of adults with visual loss.14 It can be argued that, because visual loss from ROP typically occurs earlier in life, these patients might adapt better and have a higher utility score associated with visual loss than do adults who lose vision later in life. Nonetheless, it has been demonstrated in a large study that there is not a correlation between the length of time of visual loss and utility values.14
Although an overestimation utility impairment in ROP patients may bias the results toward decreased cost-effectiveness, the visual data used in our study may actually underestimate the cost-effectiveness of treatment for threshold disease. The mean age of patients from who the visual data were obtained was ,6 years. The difficulty in coaxing children of that age with perfect eyes to read beyond the 20/30 or 20/25 line is well appreciated by ophthalmologists. Therefore, it is likely that if the visual results were measured 5 years later, the mean vision would be improved at the upper end of the scale.
It should be noted that premature children who develop neurologic impairment were included in the economic analysis in the present study. It has been estimated that ;22% of infants with a birth weight ,1250 g have a major handicap with neurologic involvement.38 Other authors37 have excluded this group in cost-effectiveness analysis for ROP, but we believe that vision is just as valuable to those with neurologic impairment, and perhaps even more so, as to those without neurologic impairment.
Also of note is the fact that our analysis did not include Markov modeling in the decision analysis aspect. Markov modeling is a useful tool when a decision analysis involves risk that is continuous over time.39Although the software program that we used has substantial Markov process capability,15the incidence of long-term complications associated with ROP are unknown. Because assumptions are often the most important part of economic modeling, we
chose to ignore this issue rather than use subjective and potentially misleading information. Nonethe-less, we believe that the incidence of serious ocular complications (eg, retinal detachment, cataract, and glaucoma) after 53⁄4years of age is relatively low1and that the difference in the late ocular complication rates between those who are treated for ROP and those who are not is likely to be minimal.
ACKNOWLEDGMENTS
This work was supported in part by the Retina Research and Development Foundation, Philadelphia, PA, and by the Princi-pal’s Initiative and Research Fund, Kingston, Ontario, Canada.
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