Mathews et al constructed a 5-year computer model basedon data from the literature to compare antibiotic manage-ment to early surgery.4 Their results indicate a total cost ofantibiotic management for 5 years of $11,100. This cost ishigher than what we estimate for a 6-year period, despite thefact that Mathews et al used a somewhat lower unit cost forsurgery and a higher discount rate (10%). However, our es-timates are based on a proportion of 5% of patients whorequire surgery every year, while Mathews et al used aproportion of 8% for grade III reflux. Thus, a higher propor-tion of patients will undergo re-implantation (30%) in theirmodel, leading to higher costs. Also, as a consequence of thisrather high surgical rate, the strategy with early surgery wasfound to save costs compared to surgery for patients withbreakthrough injections while on antibiotics (approximately$1,000 for grade III reflux) before discounting. However, thesaving was lost when costs were discounted 10%.

We took a similar approach in scenario 3 in our modelbased on the hypothesis that, with the availability of a safeand less invasive procedure, the proportion of parents optingfor early injection rather than chronic antibiotic treatmentand injection for breakthrough infection would increase. Weassumed that about 70% of children would undergo injectionafter 1 to 2 years of unsuccessful antibiotic therapy. Thisassumption increases costs during the 6 years slightly com-pared to current practice but reduces the failure rate by morethan 30%.

It must be borne in mind that all of our results are based ona model that combines data from different sources, and there-fore, should be considered with caution. However, this is awell accepted methodology in economic analysis of new treat-ments, as actual clinical practice data are usually not avail-able when decisions about resource allocations have to bemade. Such models aim at supporting decision making, not atreplacing it, and thus provide information that can be com-bined with other data and knowledge.

One might ask, “what does all of this mean for the clini-cian?”. While costs analyses are attractive and important forpayers, individual patients (and parents) are under littlefinancial pressure in the United States to make selectionsabout therapy based on cost savings. However, this analysissuggests that endoscopic injection is not only less costly, butalso more effective given the assumptions of this model. Thetherapeutic assumptions of the model are not meant to rep-resent a rigid approach to the treatment of vesicoureteralreflux. They are instead meant to serve as illustrations ofwell accepted strategies that were endorsed by a panel ofpediatric urologists, surgeons and nephrologists with repre-sentative from all major regions of the United States.13

CONCLUSIONS

We believe that endoscopic injection with dextranomer/hyaluronic acid copolymer is a viable treatment option whenconsidering open ureteral reimplant. We further believe thatendoscopic treatment as first line therapy for patients withvesicoureteral reflux that persists for at least 1 year is anoption that is attractive not only from the perspective of costaccounting, but also in terms of effectiveness. For each childwith grade III reflux open ureteral reimplantation conveys ahigher initial success rate for a single anesthetic (98% openversus 70% initial injection, see figure). However, this modelshows that a persistent approach to endoscopic surgery witha commitment to 1 or more anesthetics results in overallsuccess that equals or exceeds open surgery. This result isparticularly true if open reimplant is reserved as it is at mostcenters in the United States for patients with high grade orpersistent vesicoureteral reflux.

REFERENCES

1. Elder, J. S., Peters, C. A., Arant, B. S., Jr., Ewalt, D. H.,Hawtrey, C. E., Hurwitz, R. S. et al: Pediatric Vesicoureteral

Reflux Guidelines Panel summary report on the managementof primary vesicoureteral reflux in children. J Urol, 157: 1846,1997

2. Elder, J. S., Snyder, H. M., Peters, C., Arant, B., Hawtrey, C. E.,Hurwitz, R. S. et al: Variations in practice among urologistsand nephrologists treating children with vesicoureteral reflux.J Urol, 148: 714, 1992

3. Jodal, U., Hansson, S. and Hjalmas, K.: Medical or surgicalmanagement for children with vesico-ureteral reflux? ActaPaediat Suppl., 88: 53, 1999

4. Mathews, R., Naslund, M. and Docimo, S.: Cost analysis of thetreatment of vesicoureteral reflux: a computer model. J Urol,163: 561, 2000

5. Lebowitz, R. L., Olbing, H., Parkkulainen, K. V., Smellie, J. M.and Tamminen-Mobius, T. E.: International system of radio-graphic grading of vesicoureteric reflux. International RefluxStudy in Children. Pediatr Radiol, 15: 105, 1985

6. Edwards, D., Normand, I. C., Prescod, N. and Smellie, J. M.:Disappearance of vesicoureteric reflux during long-term pro-phylaxis of urinary tract infection in children. Br Med J, 2:285, 1977

7. Bellinger, M. F. and Duckett, J. W.: Vesicoureteral reflux: acomparison of non-surgical and surgical management. ContribNephrol, 39: 81, 1984

8. Arant, B. S., Jr.: Medical management of mild and moderatevesicoureteral reflux: followup studies of infants and youngchildren. A preliminary report of the Southwest Pediatric Ne-phrology Study Group. J Urol, 148: 1683, 1992

9. Tamminen-Mobius, T., Brunier, E., Ebel, K. D., Lebowitz, R.,Olbing, H., Seppanen, U. et al: Cessation of vesicoureteralreflux for 5 years in infants and children allocated to medicaltreatment. J Urol, 148: 1662, 1992

10. Wennerstrom, M., Hansson, S., Jodal, U. and Stokland, E.: Dis-appearance of vesicoureteral reflux in children. Arch PediatrAdolesc Med, 152: 879, 1998

11. Schwab, C. W., Jr., Wu, H.-Y., Selman, H., Smith, G. H. H.,Snyder, H. M., III and Canning, D. A.: Spontaneous resolutionof vesicoureteral reflux: a 15-year perspective. J Urol, 168:2594, 2002

12. Lackgren, G., Wåhlin, N., Skoldenberg, E. and Stenberg, A.:Long-term followup of children treated with dextranomer/hy-aluronic acid copolymer for vesicoureteral reflux. J Urol, 166:1887, 2001

13. Kobelt, G.: Treatment practices of VUR in the United States. Asurvey. Uppsala: Q-Med, unpublished data, 2001

14. Current Procedural Terminology. Chicago: American MedicalAssociation, 2001

15. Family Care Medical Centers. Physician’s Fee Schedule Soft-ware, version 2.9. Denver: FCMC Professional Software, 2001

16. http://www.eckerd.com/pricing/druglist, 2001. Accessed Janu-ary 26, 2002

17. Gold, M. R., Siegel, J. E., Russell, L. B. and Weinstein, M. C.:Cost-Effectiveness in Health and Medicine. New York: OxfordUniversity Press, 1996

18. Leonard, M. P., Decter, A., Mix, L. W., Johnson, H. W. andColeman, G. U.: Endoscopic treatment of vesicoureteral refluxwith collagen: preliminary report and cost analysis. J Urol,155: 1716, 1996

19. Niklasson, L. and Hojgard, S.: Cost-analysis of managementstrategies for children with vesicoureteral reflux. Acta Paedi-atr, suppl., 431: 79, 1999

EDITORIAL COMMENT

I congratulate the authors on tackling a complicated and poten-tially controversial cost analysis of the management of reflux. Thisarticle deserves careful reading, and an equally careful examinationof the conclusions and their clinical applicability.

In any computer model assumptions have to be made that arebased on the best available data. If the assumptions are substan-tially incorrect, despite the use of a sensitivity analysis, the conclu-sions will be suspect. The most important of these in this analysis isthe long-term effectiveness of a single injection, which is estimatedat 70%. Although this rate is based on a prior study (reference 12 inarticle), the estimate seems high. In the former study the responserate after first injection was 54%. Although this rate is includedpatients with all grades of reflux, 63% had grade III reflux. Ofthe patients who required a second injection or surgery 60%

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initially had grade III reflux. Since the proportion is essentiallythe same, it would follow that failure of the first injection inpatients with grade III reflux must have been similar to the groupoverall. Also, in that study first injection failed in 34% of patientswith grade III or greater post-procedure reflux. In the presentanalysis we are told that 70% will have grade 0 or I reflux longterm after the first injection. It would be important to know thatthe success rate is really as high as is suggested. It is unclear fromthe description of the model whether 12-month voiding cystoure-thrography is obtained in all patients. Of the patients who ini-tially had a negative voiding cystourethrogram after injectiontherapy 22% had grade III or greater reflux at 12 months. Also13% of patients with grade 0 reflux on postoperative voidingcystourethrography who underwent a late voiding cystourethrog-raphy (greater than 12 months postoperatively) for various rea-sons had grade II reflux or higher.

Let us assume that injection therapy really is as good as this reportsuggests. What can we make of the conclusions of this study? Oneway to do an economic analysis is to look at the cost of achieving aspecific end point by 2 or more different pathways. Only if we agreeon the desired end point can we rationally discuss what it costs to getthere. This study takes another route altogether. Based on an un-published survey sponsored by Q-Med, we are told that urologistsand nephrologists are more likely to recommend injection therapythan open surgery. Therefore, 50% of patients with persistent refluxat 6 years in the control group will undergo open surgery, whereas75% will receive injection therapy in the experimental group. In theend, more control patients will have persistent reflux (due to lack oftherapy) than the injection group, provided the estimates of long-term success are accurate. Therefore, we are told that injection

therapy is more effective than open surgery and costs less. Had wechosen a specific end point, such as complete reflux resolution, itshould be clear that injection therapy would not be nearly as effectiveas open surgery, and the cost difference would depend on the as-sumed success of each therapy.

There is a danger in this analysis that must be recognized. Thecontention that injection therapy, if available, would be recom-mended in cases in which open surgery would not suggests that theindications for reflux correction are determined by the therapy in-stead of by the disease. This is generally a recipe for increasedmedical costs. Using the example of coronary artery disease, we seea similar situation. “Balloon coronary angioplasty initially was re-garded as an alternative to CABG, a way to achieve coronary revas-cularization less traumatically, at less cost and with a much shorterrehabilitation period. During the past 2 decades, it has become clearthat angioplasty largely serves as an expensive alternative to med-ical therapy rather than an inexpensive alternative to CABG.”1 Thebottom line is this: if permanent correction of reflux is important ina particular patient or patient group, what is the most cost-effectivemethod to achieve that goal? This paper, unfortunately, does notanswer that question.

Steven DocimoDepartment of Pediatric UrologyChildren’s Hospital of PittsburghPittsburgh, Pennsylvania

1. Mark, D. B. and Hlatky, M. A.: Medical economics and theassessment of value in cardiovascular medicine: part II. Cir-culation, 106: 626, 2002

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