EVIDENCE-BASED DERMATOLOGY: ORIGINAL CONTRIBUTION. Direct Medical Costs for Surgical and Medical Treatment of Condylomata Acuminata

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1 Direct Medical Costs for Surgical and Medical Treatment of Condylomata Acuminata Murad Alam, MD; Matthew Stiller, MD EVIDENCE-BASED DERMATOLOGY: ORIGINAL CONTRIBUTION Objective: To determine which treatment modalities for condylomata acuminata are associated with the lowest direct medical costs. Design: Cost-effectiveness analysis. Setting: Ambulatory private practice, primary or specialty care. Patients or Other Participants: Adults with no presenting complaints other than condylomata acuminata. Interventions: Construction of a cost-effectiveness model. From a literature review, extraction of commonly accepted guidelines regarding duration and frequency as well as reports of efficacies of typical treatment regimens; from Medicare physician fee schedules, costs of physician visits and physician-administered treatments; from published data, average wholesale prices of medications. Main Outcome Measure: Estimated direct medical costs per complete clearance associated with different treatment options for condylomata acuminata. Results: Mean direct medical costs per complete clearance are lowest for surgical excision ($285). Other lowcost modalities are loop electrosurgical excision procedure ($316), electrodesiccation ($347), carbon dioxide laser ($416), podofilox ($424), and pulsed-dye laser ($479). Higher-cost modalities are cryotherapy ($951), trichloroacetic acid ($986), imiquimod ($1255), podophyllum resin ($1632), and interferon alfa-2b ($6665). Conclusion: Surgical modalities, including excision, electrodesiccation, loop electrosurgical excision procedure, and laser, as well as podofilox are low-cost options for the treatment of condylomata acuminata. Arch Dermatol. 2001;137: From the Department of Dermatology, College of Physicians and Surgeons, Columbia University, New York, NY. THE TREATMENT of condylomata acuminata entails costs for patients and insurers. While many studies have attempted to compare the efficacy of various treatments against placebo and each other, limited data exist regarding the costs of each therapeutic option. In this article, we estimate and compare the direct medical costs of each of several commonly used treatment modalities: podophyllum resin, podofilox, trichloroacetic acid, imiquimod, interferon alfa-2b, cryotherapy, electrodesiccation, cold steel excision, loop electrosurgical excision procedure (LEEP), and laser surgery. RESULTS Brief treatment for simple condylomata (Table 6) can be accomplished with podofilox, cryotherapy, electrodesiccation, surgical excision, LEEP, or laser for costs ranging from approximately $200 to $300. Podophyllum resin is more expensive, at $385 for a similar treatment regimen, and trichloroacetic acid and imiquimod are yet more expensive at $513 and $607, respectively. Interferon alfa-2b would entail much higher cost, $2744, by the predictions of this model. In the case of extensive condylomata requiring prolonged treatment (Table 6), LEEP would be the most affordable treatment modality ($294), followed by surgical excision ($318), podofilox ($334), and electrodesiccation ($415). ($535) and imiquimod ($649) are slightly more expensive. Cryotherapy and podophyllum resin are several times the cost of the least expensive modalities, at $1449 each. Again, interferon alfa-2b treatment is the most expensive alternative ($5803). Adjusting the costs of each type of treatment to reflect differences in efficacy results in a slightly different cost distribution (Table 7). Comparing the costs to achieve 100% clearance reveals that surgical excision is the lowest-cost modality 337

2 MATERIALS AND METHODS A cost model was constructed for each treatment modality (Table 1) by reviewing the literature for estimates of the typical frequency and duration of treatment courses (Table 2), obtaining a set of physician fee schedules (Table 3), approximating the wholesale costs of medications (Table 4), and considering the relative efficacy of the treatments in clearing condylomata (Table 5). For simplicity, combinations of treatments that may commonly be used in clinical practice are not studied. Direct medical costs are taken to include the aggregate costs of any physician visits and procedures as well as costs for medications and medical devices not provided at the office visits. Office visit and physician-administered treatment costs are estimated from the November 1999 Medicare fee schedule for participating providers, and the costs of medications and medical devices are average wholesale prices quoted in the 2000 Drug Topics Red Book. While some practitioners may administer similar medications or procedures in different ways, we use commonly accepted guidelines reported in the medical literature to determine the duration and frequency of typical treatment regimens. Whenever newer published empirical data on the duration and frequency of treatment regimens associated with a given treatment modality are available, this information has been used to supersede manufacturer guidelines. All of the treatment types considered in this study except LEEP are specifically classified by a 1997 report of the American Medical Association on external genital warts as patient-applied, health care provider administered, or alternative treatments. 24 Estimates of the short-term efficacy of the examined treatments are used to weight the relative costs of different treatment approaches. 25 Perfect (100%) efficacy in this context is defined as clearance of all condylomata at the end of therapy. Long-term efficacy, recurrence rates, and figures for sustained clearance of treated warts are not considered in the cost analysis. This simplification is used since extremely limited information is available regarding posttreatment efficacy beyond a few months; the medium-term posttreatment efficacy data are disparate and difficult to interpret. Other patient-related considerations for selecting one treatment type over another are also not endogenous to this cost analysis: these may include patient pain tolerance, preference for self- or physician-administered treatment, desire for rapidity of treatment, concern regarding scarring, and previous treatment failure. Excluding subsequently mentioned exceptions, all physician visits in this model are treatment visits. Initial and follow-up visits are included for patient-applied treatments, in which the initial visit is the prescription visit and the final visit is required for discontinuation of treatment. A follow-up visit is also included for surgical options requiring only a single treatment visit. Physician visits were either evaluation and management (E/M) initial or follow-up visits without physicianadministered treatments, or treatment visits during which no other service was performed. Initial visits at which physicianadministered treatments were not provided were considered initial level 2 (99202) or 3 (99203) outpatient E/M visits. Follow-up visits at which physician-administered treatments were not provided were considered as follow-up level 2 (99212) or 3 (99213) outpatient E/M visits. Treatment visit costs were derived by averaging the costs associated with the appropriate Current Procedural Terminology (CPT) destruction codes for lesions, including condylomata, located on the penis, vulva, or anus, respectively. For instance, the cost of a hypothetical cryotherapy treatment was defined as the mean of the costs of cryosurgery of the penis (54056), cryosurgery of the anus (46916), and simple destruction at the vulva (56501). For treatment of extensive condylomata, level 3 E/M codes and extensive destruction CPT codes were used; more limited treatments were represented by level 2 E/M codes and simple destruction CPT codes. ($285), followed by LEEP ($316), electrodesiccation ($347), carbon dioxide laser ($416), podofilox ($424), and pulsed-dye laser ($479). Cryotherapy ($951) and trichloroacetic acid ($986) are about 3 times as expensive as the lowest-cost treatment. Imiquimod ($1255) and podophyllum resin ($1632) are more expensive still. Interferon alfa-2b has an efficacy-adjusted cost of $6665. The mean direct medical costs (medication and physician) per clearance for treating condylomata for each of the modalities are shown in the Figure. COMMENT Our estimates suggest varying costs to patients and insurers depending on the therapeutic options selected by physicians. In our model, after adjusting for efficacy, surgical treatments appear to be lowest cost. Surgical excision, LEEP, and electrodesiccation are the most inexpensive, followed closely by carbon dioxide and pulsed-dye laser. The only medical treatment at this end of the cost distribution is podofilox, which has a cost comparable to that of laser. Physician-administered medical therapies are approximately 2 (trichloroacetic acid), 4 (podophyllum resin), or more than 10 (interferon alfa-2b) times the cost of laser treatment. Cryotherapy is also more than twice as expensive as podofilox or the surgical modalities. Overall, the low costs associated with surgical treatments derive from the high levels of clearance that may be achieved with few treatments. Imiquimod, by virtue of its higher medication cost and protracted duration of treatment, and podophyllum resin, because of the numerous physician-administered treatments required, are relatively more expensive. Notably, the model also stratifies aggregate costs by the intensity of the treatment regimen. For treating specific types of disease, treatments that are usually more expensive may be relatively more affordable. Efficacyadjusted costs for a brief course of cryotherapy to treat simple condylomata ($339) are thus comparable to those for the low-cost modality for the same indication (surgical excision, $228). For a prolonged course to treat extensive condylomata, imiquimod ($1298) is less expensive than cryotherapy ($1834) and approximately the same cost as trichloroacetic acid ($1288). One important reservation about the aggregate cost estimates derived herein is that the underlying assump- 338

3 Table 1. Usage Protocol and Hypothetical Cost Structure for Each Treatment * Podophyllum resin Usage protocol: physician applied once to twice weekly for total of 3 to 6 applications Physician costs: 3-6 treatment visits at mean of 54050, 56501, and for simple destruction or at mean of 54065, 56515, and for extensive destruction Podofilox Usage protocol: patient applied for 2-4 cycles; in each cycle, twice-daily application for 3 d, then 4 days rest Physician costs: initial visit + follow-up visit, level 2 or level 3 Medication costs: 1 container if continued for 2 wk, 2 containers if 4 wk Trichloroacetic acid Usage protocol: physician applied at varying intervals for a total of 4 applications Physician costs: 4 treatment visits at mean of 54050, and for simple destruction or at mean of 54065, 56515, and for extensive destruction Imiquimod Usage protocol: patient applied at most 3 times/wk for 16 wk Physician costs: initial visit + follow-up visit, level 2 or level 3 Patient medication purchases: at most 4 boxes of imiquimod Interferon alfa-2b Usage protocol: physician-delivered injections for a total of doses Physician costs: treatment visits at mean of 54050, 56501, and for simple destruction or at mean of 54065, 56515, and for extensive destruction Medication costs: vials Cryotherapy Usage protocol: physician performed at 1- to 2-wk intervals for a total of 2-6 applications Physician costs: 2-6 treatment visits at mean of 54056, 56501, and for simple cryotherapy or at mean of 54065, 56515, and for extensive destruction Electrodesiccation Physician costs: treatment visits at mean of 54055, 56501, and for simple electrodesiccation or at mean of 54065, 56515, and for extensive destruction; add 1 follow-up visit, level 2 or level 3 Surgical excision Usage protocol: physician performed for a total of treatments Physician costs: treatment visits at mean of 54060, 56515, and or at mean of 54065, 56515, and for extensive destruction; add 1 follow-up visit, level 2 or level 3 LEEP (loop electrosurgical excisional procedure) Usage protocol: physician performed for a total of 1 treatment Physician costs: 1 treatment at mean of 54055, 56501, and for simple electrodesiccation or at mean of 54065, 56515, and for extensive destruction; add 1 follow-up visit, level 2 or level 3 Usage protocol: physician performed 1-2 treatments for both pulsed-dye and carbon dioxide lasers Physician costs: 1-2 treatment visits at mean of 54057, 56515, and for simple laser surgery or at mean of 54065, 56515, and for extensive destruction; if only 1 treatment, add 1 follow-up visit, level 2 or level 3 *Five-digit numbers in Physicians costs are Current Procedural Terminology codes. Table 2. Average Number of Treatments Required for Clearance of Condylomata Acuminata by Various Modalities* Major Reviews Buetner and Ferenczy, Mayeaux et al, Other Estimates Podophyllum resin , (25%) Podofilox , 5 2-4, Trichloroacetic acid Imiquimod NR NR 3 times/wk for 16 wk 1,8,9 Interferon alfa-2b NR , , Cryotherapy , , , Electrodesiccation , , Surgical excision LEEP NR 1 Carbon dioxide , 14 1, 15 1, 10 1, , Pulsed-dye 1.6, , Nd:YAG 1, *LEEP indicates loop electrosurgical excision procedure; NR, not reported. Treatment cycles (usually in weeks). Maximum treatment course. Table 3. Costs (in Dollars) of Physician Visits* Physician visits without treatment Office visit, new patient, level 2 (99202) Office visit new patient, level 3 (99203) Office visit, established patient, level 2 (99212) Office visit, established patient level 3 (99213) Treatment visits Destruction of lesion(s), penis (eg, condyloma), simple Chemical (54050) Electrodesiccation (54055) Cryosurgery (54056) surgery (54057) Surgical excision (54060) Destruction of lesion(s) penis, extensive, any method (54065) Destruction of lesion(s), vulva; simple, any method (56501) Destruction of lesion(s), vulva; extensive, any method (56515) Destruction of lesion(s), anus (eg, condyloma), simple Chemical (46900) Electrodesiccation (46910) Cryosurgery (46916) surgery (46917) Surgical excision (46922) Destruction of lesion(s) anus, extensive, any method (46924) *Source: Medicare fee schedule (Massachusetts), for participating providers, November Numbers in parentheses indicate evaluation and management codes for physician visits and Current Procedural Terminology codes for treatment visits. Table 4. Average Wholesale Prices (in Dollars) of Medications Purchased by Patients* 0.5% Podofilox gel/solution, 3.5 g/ml % Imiquimod, 12-packet box Interferon alfa-2b, powder for injection, IU, 1 vial *Source: 2000 Drug Topics Red Book, (104th ed, Medical Economics, Montvale, NJ). 339

4 Table 5. End-of-Treatment Efficacy of Treatment Modalities* Buetner and Ferenczy, Reported Effectiveness in Clearing Condylomata, % Major Reviews Mayeaux et al, Other Estimates Consensus Estimate, % Podophyllum resin (25%) , , , Podofilox , , Trichloroacetic acid , Imiquimod NR NR 50, Interferon alfa-2b NR , Cryotherapy , Electrodesiccation Surgical excision LEEP Carbon dioxide , , , 20 94, Pulsed-dye *LEEP indicates loop electrosurgical excision procedure; NR, not reported. Table 6. Total Costs (in Dollars) per Treatment Course of Simple and Extensive Condylomata by Various Modalities* Simple Condylomata Extensive Condylomata Brief Course Prolonged Course Brief Course Prolonged Course Visits Meds Total Visits Meds Total Visits Meds Total Visits Meds Total Podophyllum resin Podofilox Trichloroacetic acid Imiquimod Interferon alfa-2b Cryotherapy Electrodesiccation Surgical excision LEEP *When there is no range of treatment durations in a hypothetical cost structure for a given modality, the costs of treatment are the same for brief and prolonged treatment. Meds indicates medications; LEEP, loop electrosurgical excision procedure. tions regarding relative efficacies and the number of treatments usually required with the various treatment modalities are based on physician studies and pharmaceutical company recommendations that may be flawed. Few studies have compared multiple treatment modalities on the same patient population. Also, this analysis assumes aggressive billing of patients by physicians and rigorous scheduling of follow-up appointments. In actual situations, follow-up visits may be less frequent. Physicians may in some cases receive substantially less reimbursement than that mandated by the Medicare fee schedule used in this analysis. The present model extends previous work on the costeffectiveness of treatment strategies for condylomata. Earlier cost studies have examined fewer treatment modalities. In some cases, these studies have incorporated assumptions that may be inaccurate, unsupported by the literature, outdated, or otherwise not applicable to US medicine. For instance, Langley and colleagues 21,23 have collaborated on 2 recent articles that discuss the costs of various types of treatment but ultimately provide complete cost models for only 2 modalities, imiquimod and podofilox. They conclude that imiquimod is slightly more costeffective than podofilox in cost per sustained cleared patient. 21 However, as has been discussed previously, sustained clearances associated with different treatment modalities are inherently difficult to compare given different durations of follow-up and the absence of any true longterm studies that track disease remission for periods of greater than several months. The short-term clearance rate for podofilox that Langley and colleagues include in their analysis is 0.283, 23 which is less than half the other estimates in the literature. Even after entering their low rate into our model, our consensus estimate for podofilox efficacy is 0.63 (Table 5). In addition, the Langley cost analyses are based in part on a dated cost model for genital warts constructed by Strauss and colleagues. 26 The earlier article by Strauss et al uses cost data from 1992, and makes unusual cost assumptions, such as costing the second and subsequent treatment visits as follow-up E/M visits rather than as more expensive treatment visits. Strauss et al also explicitly decline to consider relative efficacies of treatment alternatives since their advisory panel concludes that no therapy is consistently more effective than another. 26 In contrast to the analyses of Langley et al, Mohanty s 22 cost comparison of treatment of condylomata with 340

5 Table 7. Total Costs (in Dollars) per Complete Clearance of Simple and Extensive Condylomata by Various Modalities* Simple Condylomata Extensive Condylomata Brief Course Prolonged Course Brief Course Prolonged Course Mean Podophyllum resin Podofilox Trichloroacetic acid Imiquimod Interferon alfa-2b Cryotherapy Electrodesiccation Surgical excision LEEP Carbon dioxide Pulsed-dye *When there is no range of treatment durations in a hypothetical cost structure for a given modality, the costs of treatment are the same for brief and prolonged treatment. LEEP indicates loop electrosurgical excision procedure. Total Direct Medical Costs, $ Medical 6665 Podofilox Trichloroacetic Acid Imiquimod Podophyllum Resin Interferon Alfa-2b Surgical Excision LEEP Electrodesiccation CO 2 Pulsed-Dye Cryotherapy Treatment Modalities Surgical Medication Costs Physician Costs Mean direct medical costs per clearance for treating condylomata by various modalities. LEEP indicates loop electrosurgical excision procedure; CO 2, carbon dioxide. podophyllum resin and podofilox finds podofilox to be highly cost-effective. The overall cure rate 22 with podofilox is found to be 66%, close to the other estimates in the literature. Mohanty s model is limited by its consideration of only 2 treatment modalities. The Mohanty model may also be less relevant to the United States since it examines cost of care in the United Kingdom and computes treatment costs by estimating the cost of physician time in minutes and adding medication costs for physicianadministered medications. In conclusion, the results of this study clarify the direct costs of treatment of condylomata acuminata with different medical and surgical techniques. In particular, surgical modalities, including cold-steel excision, electrodesiccation, LEEP, and laser, appear to be low cost and require few treatments. Of the patientadministered drugs, podofilox is the most affordable. 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