Volume 19, Issue 7 , Pages 1007-1016, July 2008
Economic Evaluation of Uterine Artery Embolization versus Hysterectomy in the Treatment of Symptomatic Uterine Fibroids: Results from the Randomized EMMY Trial
Article Outline
Purpose
To investigate whether uterine artery embolization (UAE) is a cost-effective alternative to hysterectomy for patients with symptomatic uterine fibroids, the authors performed an economic evaluation alongside the multicenter randomized EMMY (EMbolization versus hysterectoMY) trial.
Materials and Methods
Between February 2002 and February 2004, 177 patients were randomized to undergo UAE (n = 88) or hysterectomy (n = 89) and followed up until 24 months after initial treatment allocation. Conditional on the equivalence of clinical outcome, a cost minimization analysis was performed according to the intention to treat principle. Costs included health care costs inside and outside the hospital as well as costs related to absence from work (societal perspective). Cumulative standardized costs were estimated as volumes multiplied with prices. The nonparametric bootstrap method was used to quantify differences in mean (95% confidence interval [CI]) costs between the strategies.
Results
In total, 81 patients underwent UAE and 75 underwent hysterectomy. In the UAE group, 19 patients (23%) underwent secondary hysterectomies. The mean total costs per patient in the UAE group were significantly lower than those in the hysterectomy group ($11,626 vs $18,563; mean difference, −$6,936 [−37%], 95% CI: −$9,548, $4,281). The direct medical in-hospital costs were significantly lower in the UAE group: $6,688 vs $8,313 (mean difference, −$1,624 [−20%], 95% CI: −$2,605, −$586). Direct medical out-of-hospital and direct nonmedical costs were low in both groups (mean cost difference, $156 in favor of hysterectomy). The costs related to absence from work differed significantly between the treatment strategies in favor of UAE (mean difference, −$5,453; 95% CI: −$7,718, −$3,107). The costs of absence from work accounted for 79% of the difference in total costs.
Conclusions
The 24-month cumulative cost of UAE is lower than that of hysterectomy. From a societal economic perspective, UAE is the superior treatment strategy in women with symptomatic uterine fibroids.
Abbreviations: CI, confidence interval, EMMY, EMbolization versus hysterectoMY, EuroQOL 5, EuroQOL 5 dimension 3 level version, HUI-3, Health Utilities Index Mark 3, MOS SF-36, Medical Outcome Study Short Form 36, UAE, uterine artery embolization
UTERINE fibroids are benign tumors arising from smooth muscle cells of the uterine wall. Fibroids are clinically apparent in approximately 25% of women of reproductive age and are found in approximately 77% of surgically excised uteri at histopathologic examination (1). Fibroids may cause several symptoms (eg, menorrhagia, pain, and bulk-related complaints) that may compromise women's health status. For symptomatic uterine fibroids, a wide variety of both medical and surgical treatment options are available (1). Hysterectomy is the final option whenever other treatments (eg, pharmaceutical treatment or myomectomy) are either unsuitable or ineffective and when there is no desire for future pregnancy.
Concerns about the invasiveness of hysterectomy and its treatment-related morbidity have prompted the development of various less-invasive alternatives. As a consequence, uterine artery embolization (UAE) has been proposed as a promising alternative for the treatment of heavy menstrual bleeding since 1995 (2). Several large case series have indeed suggested UAE to be advantageous over surgery (3, 4, 5, 6), but those studies were hampered by the inclusion of patients with strong treatment preferences and the lack of a control group.
From a societal perspective, the preferred treatment strategy is the one that yields favorable health gains relative to associated costs (‘value for money'). To make a proper comparison in terms of effectiveness and costs-effectiveness, we initiated a prospective, multicenter, randomized clinical trial comparing UAE with hysterectomy in the treatment of menorrhagia caused by uterine fibroids, the EMMY (EMbolization versus hysterectoMY) trial. Results so far indicate that UAE is a safe procedure that is able to avoid hysterectomy in 76.5% of cases with no difference in quality of life at 24 months, justifying the conclusion that UAE is a valuable alternative for hysterectomy (7). Herein, we address the question as to whether UAE is a cost-effective alternative to hysterectomy in the treatment of uterine fibroid–related menorrhagia, thereby using data from our randomized clinical trial.
Materials and Methods
Clinical Study Design
The EMMY trial is a multicenter randomized clinical study comparing UAE with hysterectomy as a treatment for heavy menstrual bleeding caused by uterine fibroids. Twenty-eight hospitals in The Netherlands participated in the trial. The study was approved by the Central Committee Involving Human Subjects (www.ccmo.nl) and by local ethics committees of participating hospitals. The inclusion and exclusion criteria for trial participation were as follows: (a) the clinical diagnosis of uterine fibroids had been confirmed with ultrasonography (US); (b) menorrhagia (subjectively reported by the patient as increased or prolonged menstrual blood loss causing dysfunction in daily life) was the predominant complaint; (c) patients were premenopausal; (d) hysterectomy was thought to be the ultimate solution as other treatment options were unsuitable or had failed to provide symptomatic relief; (e) patients had no desire for future pregnancy; and (f) there was absence of the following disorders: renal failure (creatinine level >150 μmol/L), active pelvic infection, clotting disorders, allergy to contrast fluid, (suspected) uterine malignancy, submucosal fibroids protruding by more than 50% within the uterine cavity, or pedunculated abdominal fibroids.
After written consent was obtained by the attending gynecologist and patients had completed an extensive questionnaire, patients were randomly assigned 1:1 to undergo either UAE or hysterectomy by using a computer-based minimization scheme, stratified for each study center.
Treatment Strategies
Preintervention periodBefore both interventions, all patients completed a questionnaire addressing baseline characteristics (health-related quality of life questionnaires, status of menorrhagia symptoms, and socio-demographic characteristics). They visited the outpatient gynecology clinic for an extensive case history and physical examination. All patients underwent a pelvic US examination—either transvaginally or transabdominally—as well as various laboratory investigations.
Whenever a patient was allocated to undergo UAE, pelvic magnetic resonance (MR) imaging was performed. No additional visit with the interventional radiologist was planned. Patients' allocated to undergo hysterectomy visited the anesthesiology department preoperatively. In the present economic analysis, these visits and procedures were part of the preprocedural work-up costs.
UAEUAE was performed with the patient under local or epidural/spinal anesthesia by an interventional radiologist under supervision of an experienced interventional radiologist (J.A.R.) with ample experience in UAE (>50 procedures).We advised the use of the following pain protocol to all participating units during admission: acetaminophen (three doses at 1,000 mg) and nonsteroidal anti-inflammatory drugs (diclofenac, three doses at 50 mg), and opiates (morphine 10 mg, a maximum of six times per day) or epidural anesthesia whenever pain control was insufficient. The use of antibiotics was not standardized. A 4- or 5-F catheter was introduced into the femoral artery and advanced over the aortic bifurcation to the contralateral internal iliac artery. During the procedure, digital subtraction angiography was performed to identify the origin of the uterine artery. When catheters were in the correct position, actual embolization was carried out with polyvinyl alcohol particles (355–500 μm) (Contour; Boston Scientific, Maastricht, The Netherlands). Microcatheters were allowed but not used routinely in this study. UAE was considered successful when parenchyma filling of the fibroids had stopped (target embolization) or until the main uterine artery was blocked (selective embolization).
After the procedure, women were admitted to the gynecology ward for further care. All patients were advised to stay in the hospital for at least one night.
HysterectomyThe type of hysterectomy and the route of access were left at the discretion of the attending gynecologist. The following procedures were allowed: abdominal hysterectomy, vaginal hysterectomy, laparoscopic hysterectomy, and laparoscopically assisted vaginal hysterectomy. Both supravaginal and total hysterectomies were permitted. We used no uniform standardized guidelines for antibiotic prophylaxis, type of anesthesia, analgesics during admission, and hospital discharge criteria.
Postintervention periodAfter the primary interventions, patients were seen at the gynecology outpatient clinic for clinical follow-up. Furthermore, they received a self-report questionnaire by mail (which contained, among others, the Medical Outcome Study Short Form 36 [MOS SF-36] [8], the EuroQOL 5 dimension 3 level version [EuroQol 5] [9], the Health Utilities Index Mark 3 [HUI-3] [10], and an out-of-hospital resource use survey to be filled in at home at 6 weeks and 6, 12, 18, and 24 months. Analyses of survey responses (MOS SF-36, EuroQol 5, and HUI-3) were performed according to accepted scoring algorithms.
Economic Analysis
Our aim in the present economic evaluation was to provide a decision-analytic framework to support medical decision-making as a trade-off between incremental health gains (clinical effectiveness) versus incremental costs in the comparison between UAE and hysterectomy (11).
EffectivenessClinical effectiveness was evaluated from the perspective of the Quality-Adjusted Life Years (QALY) Utility model, which combines mortality and morbidity in one outcome measure (12). In our study, no mortalities occurred. Results of the randomized controlled trial showed UAE to be clinically noninferior to hysterectomy (ie, the observed mean difference in clinical effectiveness was less than our predefined cut-off value of 25%), meaning that hysterectomy is 100% and UAE is more than 75% clinically effective in the treatment of menorrhagia (7). Furthermore, no systematic difference in health-related quality of life or in health state valuations (utilities) between strategies were found at up to 24-month follow-up, a consistent finding for all measures of Health-Related Quality of Life that were studied (MOS SF-36 [8], EuroQol 5 [9], and HUI-3 [10]) (13) (Table 1). Furthermore, we found no evidence for any differences in the subsequent occurrence of menopausal symptoms between the two strategies (14).
Table 1. Health-Related Quality of Life Outcome: 24-mo Change Score with the MOS SF-36, EuroQol-5, and HUI-3 Forms
| Questionnaire | Mean Change Score Compared with Baseline | Mean Difference in Change Score | P Value | |
|---|---|---|---|---|
| UAE Group (n = 81) | Hysterectomy Group (n = 75) | |||
| MOS SF-36 MCS | 5.80 | 7.26 | 1.47 (−2.78,5.71) | .50 |
| MOS SF-36 PCS | 9.42 | 9.32 | −0.096(−2.98,2.79) | .95 |
| EuroQoL-5 | 0.086 | 0.102 | 0.016(−0.046,0.077) | .62 |
| HUI-3 | 0.068 | 0.094 | 0.026(−0.043,0.095) | .46 |
Because no difference was found in clinical effectiveness and quality of life between the treatment strategies, a cost-minimization analysis was considered to be the appropriate economic evaluation framework.
Cost-minimization analysisCosts were defined as the volumes of resources used during 2 years of follow-up multiplied by the price per unit of each resource. By using the societal perspective, we considered four cost categories: (a) direct medical in-hospital costs (eg, preprocedural costs, in-hospital costs related to the intervention, any additional in-hospital medical costs during follow-up), (b) direct medical out-of-hospital costs (eg, unscheduled general practitioner visits and use of medication out of hospital), (c) direct nonmedical costs (patient expenses such as travel costs and sanitary measures), and (d) indirect costs (productivity related costs due to absence from work).
Data on resource use were collected prospectively in a case record form and as part of the patient's self-report questionnaires at 6 weeks and 6, 12, 18, and 24 months after the primary intervention.
The costs per unit of used resources were obtained from various data sources. The unit costs of direct medical in-hospital cost volumes were based on ‘true' economic cost calculations as obtained from the hospital management system in the Academic Medical Center, Amsterdam (15). True economic costs include a share of fixed costs as well as shares of departmental and hospital overhead costs. The use of these unit costs as standard valuations eliminated cost variability due to differences between hospitals. The cost volumes of UAE and hysterectomy were based on detailed micro-costing by using data recorded in the case record forms and patient records in all participating hospitals. The cost volumes related to complications were recorded prospectively in the case record form (eg, type of complication, unscheduled outpatient visit, subsequent diagnostic and therapeutic measures) and afterwards graded with use of the classification system of the Society of Interventional Radiology, as recommended in the Standard of Practice (16).
Resource use and costs related to study purposes only, which were not part of routine clinical care (eg, part of laboratory investigations; additional US and MR imaging performed after the primary procedure) were excluded from the present analysis. Two follow-up visits after UAE (at 1 week and 6 weeks after the primary intervention) and one follow-up visit after hysterectomy (at 6 weeks after the intervention) were considered as standard care and were included in our cost analysis. Any further follow-up visits conducted for study purposes were excluded from our analysis unless these were unscheduled follow-up visits for medical problems related to the primary intervention.
The unit costs of direct medical out-of-hospital costs, direct nonmedical costs, and indirect costs were based on Dutch guidelines for cost calculations in health care (17, 18). Indirect costs due to absence from work were estimated as the actual working time lost (hours) multiplied by the reported average net income according to the friction cost method (17). Travel costs per patient were based on mean distances to hospitals (7.0 km) and to general primary care units (1.8 km) (17). Costs were originally calculated in Euros, updated to the 2005 price level by using the Dutch Consumer Price Index (www.cbs.nl) and then converted into U.S. dollars (€1.00 = U.S. $1.34). A 4% discount rate was applied to costs that occurred after 12 months (17).
Sensitivity Analysis
One-way sensitivity analysis was performed to examine the effect of a chosen variable on the total cost difference between strategies by varying it across a range of plausible values (19). We varied four parameters that represented the largest and/or most variable costs: (a) duration of in-hospital stay, (b) duration of absence from work, (c) minor complication rate during follow-up, and (d) frequency of secondary hysterectomies after UAE for insufficient symptomatic relief. The low and high values in the sensitivity analysis correspond to the lower and upper limit values of the 95% CI of the respective variables as found in our study population.
Parameters a and b are subject to differences between various health care systems across different countries, that is, associated costs may not reflect those in other centers over the world. Parameters c and d might change in time due to improved techniques/materials or expertise.
Statistical Analysis
Data were recorded and analyzed by using statistical software (SPSS version 11.5.1; SPSS, Chicago, Illinois). Study outcomes were analyzed according to original treatment assignment (intention to treat). Costs were described with descriptive statistical measures: means, mean differences, and 95% CIs. The 95% CI of the differences in mean costs between strategies were obtained with the nonparametric bootstrap method, including the correction for bias and acceleration (20) applied to the following six cost categories: (1) costs from the preprocedural work-up, the primary intervention, and the postprocedural care; (2) costs from discharge until 2-year follow-up; (3) direct medical in-hospital costs (=[1]+[2]); (4) direct medical out-of-hospital costs plus direct nonmedical costs; (5) indirect costs; and (6) total costs (=[3]+[4]+[5]). The analyses were based on a 1,000 bootstrap samples of the two separate groups. A P value less than .05 (two-tailed) was considered statistically significant.
Results
Patients
Patients were included between March 2002 and February 2004 in 28 Dutch hospitals (21). Of 349 eligible patients, 177 were randomized: 88 were allocated to undergo UAE and 89 were allocated to undergo hysterectomy. After withdrawal, 81 women underwent uterine artery embolization and 75 underwent hysterectomy (Figure).
Figure.
Flowchart used for study.
The mean age of the participating patients was 44.6 years (UAE group) and 45.4 years (hysterectomy group). Participants were predominantly white: 61.4% and 64.0% for UAE and hysterectomy groups, respectively. Most patients (85.3%) had undergone at least one treatment before study enrollment. Patients had menorrhagia for a median of 24 months. Although the main inclusion criterion was menorrhaghia complaints, most patients also had pain (UAE: 82.9%; hysterectomy: 68.5%) and bulk-related complaints (UAE: 77.3%; hysterectomy: 75.3%). Logistic regression analysis did not reveal baseline characteristics that could predict randomization outcome, thereby confirming successful randomization (Table 2).
Table 2. Summary of Baseline and Procedural Characteristics
| UAE Group (n = 88) | Hysterectomy Group (n = 89) | |
|---|---|---|
| Baseline characteristics | ||
| Mean age ± standard deviation (y) | 44.6 ± 4.8 | 45.4 ± 4.2 |
| Mean body mass index ± standard deviation (kg/m2) | 26.7 ± 5.6 | 25.4 ± 4.0 |
| Parity | ||
| 0 | 30(34) | 20(22) |
| 1/>1 | 58(66) | 69(78) |
| Ethnicity | ||
| White | 54(61) | 57(64) |
| Black | 24(27) | 20(22) |
| Other | 10(11) | 12(13) |
| Smoking status | ||
| Current smoker | 21(24) | 23(26) |
| Former smoker | 11(12) | 14(16) |
| Nonsmoker | 56(64) | 52(58) |
| Highest educational level⁎ | ||
| Elementary school | 3(3.4) | 6(6.9) |
| Lower vocational, lower secondary school | 29(33) | 32(37) |
| Intermediate and higher vocational, higher secondary school | 26(30) | 27(31) |
| College/university | 28(32) | 22(25) |
| Other | 2(2.3) | 0(0) |
| Employed | 68(78) | 70(79) |
| Previous treatment† | ||
| None | 11(12) | 15(17) |
| Hormonal | 59(67) | 59(66) |
| Nonsteroidal anti-inflammatory drugs/tranexaminacid | 45(51) | 41(46) |
| Iron supplement/blood transfusion | 50(57) | 52(58) |
| Surgical procedures | 17(19) | 11(12) |
| Myomectomy | 13(15) | 13(15) |
| Hysteroscopic endometrium resection | 3(3.4) | 1(1.1) |
| Curettage | 3(3.4) | 0(0) |
| Symptoms | ||
| Menorrhagia | 88(100) | 89(100) |
| Anemia | 43(49) | 42(47) |
| Lower abdominal pain | 73(83) | 61(68) |
| Bulk-related complaints | 68(77) | 67(75) |
| Median symptom duration (mo)‡ | 24(3–250) | 24(4–240) |
| Median duration of menstruation‡ | ||
| Total days | 7(4–28) | 8(3–42) |
| Heavy days | 3(1–28) | 4(1–21) |
| Modified pictorial blood loss assessment chart‡ | ||
| Median (IQR) | 850(429–1483) | 952(475–1453) |
| Mean no. of fibroids‡§ | 2(1–20) | 2(1–9) |
| Procedural characteristics | ||
| Type of UAE | ||
| Target embolization | ||
| Left uterine artery | 65 | — |
| Right uterine artery | 59 | — |
| Selective embolization | ||
| Left uterine artery | 8 | — |
| Right uterine artery | 12 | — |
| Type of hysterectomy⁎⁎ | ||
| Abdominal hysterectomy | 2 | 63 |
| Vaginal hysterectomy | 1 | 8 |
| Vaginal hysterectomy with morcellator | 1 | 1 |
| Laparoscopic hysterectomy with morcellator | 0 | 2 |
| Laparoscopic assisted vaginal hysterectomy | 0 | 1 |
| Conservation of cervix | 2 | 22 |
⁎Data are missing for two patients in the hysterectomy group. |
†Two patients may have undergone more than one previous treatment or had more than one fibroid-related symptom. |
‡Numbers in parentheses are ranges. |
§Data are missing for five patients in the UAE group and 11 in the hysterectomy group. |
⁎⁎Embolization failed in 4 patients and hysterectomy was performed. |
Resource Use
Table 3 details the main volumes of resource use as well as the unit costs per resource. In the UAE group, four of 81 embolizations (4.9%) were bilateral technical failures, resulting directly in a secondary hysterectomy. In the 75 patients who underwent hysterectomy, an abdominal hysterectomy was performed in 63 (84%), vaginal hysterectomy in nine (12%), laparoscopic hysterectomy in two (3%), and laparoscopically assisted vaginal hysterectomy in one (1%).
Table 3. Resource Use from Randomization until 24-mo Follow-up
| Resource Use | UAE Group (n = 81) | Hysterectomy Group (n = 75) | ||
|---|---|---|---|---|
| No. | Unit Cost ($) | No. | Unit Cost ($) | |
| Direct medical in-hospital costs | ||||
| Before primary procedure | ||||
| Preprocedural work-up⁎ | 81 | 668 | 75 | 462 |
| Primary procedure | ||||
| Successful embolization | 77 | 2,356 | 0 | 2,356 |
| Bilateral failed embolization | 4 | 2,090 | 0 | 2,090 |
| Hysterectomy | 0 | 3,829 | 75 | 3,829 |
| Epidural anesthesia | 13 | 388 | 21 | 388 |
| Periprocedural minor complications | 5 | 0 | 2 | 0 |
| Periprocedural major complications | 0 | 0 | 0 | 0 |
| Postprocedural admission nursing ward | ||||
| Admission to nursing ward (mean duration of hospital stay/days) | 81 (1.7) | 987 | 75 (5.1) | 2,952 |
| Minor complications during admission | 92 | 904 | 112 | 271 |
| Major complications during admission | 1 | 6,328 | 1 | 6,328 |
| From discharge until 24-mo follow-up | ||||
| Scheduled outpatient visit | 162 | 168 | 75 | 168 |
| Unscheduled outpatient visits | 107 | 168 | 63 | 168 |
| Minor complications during follow-up | 168 | 251 | 104 | 243 |
| Major complications during follow-up | 4 | 134 | 1 | 2,072 |
| Re-admission to nursing ward (mean duration of hospital stay/days) | 27 (5.4) | 3,165 | 6 (4.6) | 2,680 |
| Repeat intervention: secondary hysterectomy | 19 | 3,829 | 0 | 3,829 |
| Repeat intervention: other | 4 | 1,675 | 6 | 2,770 |
| Direct medical out-of-hospital costs | ||||
| Unscheduled general practitioner visits | 18 | 27 | 18 | 27 |
| Prescribed medication | 36 | 155 | 5 | 5 |
| Direct nonmedical costs | ||||
| Travel costs | 81 | 39 | 75 | 26 |
| Tampons and sanitary napkins | 73 | 112 | 0 | 0 |
| Indirect costs | ||||
| Absence from work (mean duration of absence of work/days) | 61 (21) | 6,368 | 50 (46) | 15,384 |
⁎Included were the out-patient visit, blood work, pelvic US, pelvic MR imaging (only UAE group), and consultation with anesthesiologist (hysterectomy group). |
All secondary hysterectomies but one were performed because of persistence or relapse of menorrhagia. In one patient, menorrhagia resolved but pain and bulk-related complaints worsened, necessitating a secondary hysterectomy. These hysterectomies were evenly distributed over the 2-year follow-up period.
The following repeat interventions, apart from secondary hysterectomies, were performed: hysteroscopic fibroid resection (n = 1), manual fibroid resection (n = 1), diagnostic hysteroscopy with curettage (n = 1), adhesiolysis via laparotomy (n = 1), bilateral adnexal extirpation (n = 1), fistula repair (Latzko technique) (n = 1), (laparoscopic) cicatrix reconstruction surgery (n = 2), adhesiolysis combined with ovarian cystectomy via laparotomy (n = 1), and diagnostic laparoscopy (n = 1).
With regard to the direct medical cost volumes, noticeable results were as follows: Additional epidural anesthesia was more often applied in the hysterectomy group (13 of 81 patients vs 21 of 75 patients); patients in the hysterectomy group were hospitalized for a significantly longer time (1.7 vs 5.1 days); re-admissions occurred more frequently in the UAE group (27 of 81 patients vs six of 75 patients); in total, 19 secondary hysterectomies were performed in the UAE group because of bilateral technical failure (n = 4) or clinical failure (n = 15); and nearly twice as many unscheduled outpatient visits occurred in the UAE group (107 of 81 patients vs 63 of 75 patients).
With regard to the direct nonmedical costs, the mean number of tampons and sanitary napkins used in the UAE group were 163 and 442 per woman, respectively. The average number of days absent from work was 21 for UAE patients and 46 for hysterectomy patients. The costs of a successful embolization and a bilaterally failed embolization differed only slightly ($2,356 vs $2,090, respectively), mainly based on polyvinyl alcohol particles.
Resource Costs per Patient
Table 4 shows the mean costs per patient for each cost parameter and for each cost category (direct medical in-hospital, direct medical out-of-hospital, direct nonmedical, indirect) and in total. The average total costs of the UAE strategy consisted of direct medical in-hospital costs (58%), direct medical out-of-hospital costs (0.6%), nonmedical costs (1.2%), and absence from work (41%). In the hysterectomy group, these proportions were 45%, 0.2%, 0.1%, and 55%, respectively. The mean total costs of UAE were significantly lower than those of hysterectomy (mean cost difference: −$6,936 [−37%]; 95% CI: −$9,548, −$4,281). The difference in total costs (−$6,936) could be attributed chiefly to the difference in direct medical in-hospital costs (−$1,624; 95% CI: −$2,605, −$586) and indirect costs (−$5,453; 95% CI: −$7,718, −$3,107) between the procedures, which were both significantly lower for the UAE strategy. The costs related to the primary interventions, including pre- and postprocedural care, were also significantly lower for the UAE group ($4,157) than for the hysterectomy group ($7,538; mean cost difference: −$3,381; 95% CI: −$3,772, −$2,860). The cost advantage for UAE was partly offset by the subsequent costs generated during 2 years of follow-up, which were significantly higher after UAE than after hysterectomy (mean cost difference: $1,757; 95% CI: $781, $2,629).
Table 4. Average Costs per Patient at 2-year Follow-up ($)
| Parameter | Mean Costs | Mean Difference | 95% CI Mean Difference⁎ | |
|---|---|---|---|---|
| UAE Group (n = 81) | Hysterectomy Group (n = 75) | |||
| Direct medical in-hospital costs | ||||
| Costs of preprocedural work-up | 668 | 462 | 206 | |
| Costs of primary procedure | 2,417 | 3,945 | −1,528 | |
| Costs of postprocedural care | 1,071 | 3,130 | −2,059 | |
| Subtotal: prepreprocedural, primary procedure, and postprocedural costs | 4,156 | 7,537 | −3,381 | −3,772,−2,860 |
| Costs from discharge until 2-year follow-up | 2,532 | 775 | 1,757 | 781,−2,629 |
| Subtotal: direct medical in-hospital costs | 6,688 | 8,313 | −1,625 | −2,605,−586 |
| Direct medical out-of-hospital costs | 74 | 33 | 41 | |
| Direct non-medical costs | 140 | 26 | 114 | |
| Subtotal: direct medical out-of hospital and non-medical costs | 214 | 59 | 155 | 99,−237 |
| Indirect costs | 4,723 | 10,176 | −5,453 | |
| Subtotal: indirect costs | 4,723 | 10,176 | −5,453 | −7,718,−3,107 |
| Overall total costs | 11,626 | 18,563 | −6,937 | −9,548,−4,281 |
⁎95% CIs were obtained with the nonparametric bootstrap method. The 95% CIs presented include adjustment for bias and acceleration. |
Significant cost differences between both groups for the separate cost parameters were as follows: Costs of preprocedural outpatient visits were higher for UAE (mean difference, $206). With regard to costs of postprocedural unscheduled outpatient visits, re-admissions, and secondary hysterectomies as repeat intervention, UAE was more costly than hysterectomy (mean difference, $170, $721, and $898, respectively). Costs of the primary procedure (ie, UAE and hysterectomy) were lower for UAE than for hysterectomy (mean difference, −$1,528).
Sensitivity Analysis
Table 5 displays the effect of alternative assumptions about four cost parameters on the mean total cost difference between both treatment modalities. The total cost difference was relatively insensitive to variations in the length of hospital stay and to the variation of minor complication rates. Two parameters were somewhat sensitive to variation across values different from base-case values: the duration of absence from work and the rate of secondary hysterectomies. For all assumed variations, however, a difference in total costs remained in favor of UAE.
Table 5. Results of Sensitivity Analysis
| Variable⁎ | UAE Group | Hysterectomy Group | Mean Difference in Total Costs ($) | % Change | |||
|---|---|---|---|---|---|---|---|
| Value | Total Mean Costs ($) | Value | Total Mean Costs ($) | ||||
| Duration of hospital stay (d) | Observed | 1.7 | 11,626 | 5.1 | 18,563 | −6,937 | |
| Low | 1.3 | 11,394 | 4.8 | 18,389 | −6,995 | +0.8% | |
| High | 2.0 | 11,800 | 5.4 | 18,737 | −6,937 | 0% | |
| Absence from work (d) | Observed | 21 | 11,626 | 46 | 18,563 | −6,937 | |
| Low | 16 | 10,110 | 36 | 15,219 | −5,109 | −35.8% | |
| High | 27 | 13,445 | 56 | 21,907 | −8,462 | +22.0% | |
| Minor complications during follow-up | Observed | 2.1% | 11,626 | 1.4% | 18,563 | −6,937 | |
| Low | 1.8% | 11,590 | 1.1% | 18,511 | −6,921 | −2.3% | |
| High | 2.4% | 11,662 | 1.7% | 18,615 | −6,953 | +2.3% | |
| Secondary hysterectomy rate (including duration of hospital stay) | Observed | 23.5% | 11,626 | — | 18,563 | −6,937 | |
| Low | 14.8% | 11,037 | — | 18,563 | −7,526 | +8.5% | |
| High | 34.2% | 12,358 | — | 18,563 | −6,205 | −11.8% | |
⁎Low and high values of the variables correspond to the lower and upper limits of the 95% CI of the respective variables. |
A threshold analysis showed that direct medical and nonmedical costs of the strategies were equal at a 55.2% overall clinical success rate of UAE. At success rates beneath this level, hysterectomy became the cheapest treatment.
Discussion
Our study shows that, as a treatment for heavy menstrual bleeding, UAE is a cost-saving alternative to hysterectomy in women with uterine fibroids. Health outcomes did not differ between strategies, but mean total costs per patient were 37% lower for UAE compared with hysterectomy. Differences in direct medical in-hospital costs contributed to this difference to a considerable extent; the costs of the embolization procedure were lower than those of a hysterectomy. Surprisingly, indirect costs were an even more important contributor to the difference in total costs. Absence from work accounted for 79% of the overall difference in total costs. According to the sensitivity analysis, overall cost differences were relatively insensitive to variations in four important cost parameters, implying that the cost difference in favor of UAE was robust.
The few available published reports about the costs and cost-effectiveness of UAE have been limited to retrospective, single-center studies that only reported direct medical in-hospital costs (22, 23, 24). Only one of those studies concluded that the in-hospital costs of UAE were higher for UAE than for hysterectomy in the treatment of uterine fibroids (25). The increased costs of UAE in that study were mainly related to complications: One patient was re-admitted for severe pain and another patient went into respiratory arrest after UAE. Furthermore, postprocedural pelvic MR imaging for study purposes was included in the total costs as well. In agreement with our results, most of the other reports suggested UAE to be associated with lower costs than hysterectomy (22, 23, 24).
One report has also performed an economic evaluation from the societal perspective, including both direct and indirect costs (23). That study was based on a decision model using assumptions and estimates as input, rather than being based on real observations from a prospective randomized trial. Despite the methodologic differences between that study and ours, the results were very similar and also confirmed UAE to be a cost-effective alternative to hysterectomy.
Only recently was another empirical cost-effectiveness analysis comparing UAE and hysterectomy or myomectomy in a randomized trial design published: the Scottish REST trial (26). In that study, after 1 year of follow-up, UAE was found to be less costly than surgery (mean difference, $1,712). This is comparable to our findings, where these costs differed by $1,625 in favor of UAE. However, as illustrated by our findings, the true difference in costs between UAE and hysterectomy is much larger when a longer follow-up is considered and when absence from work is entered in the equation.
When comparing the results of economic evaluations between countries, researchers are confronted with the issue of external validity (generalizability). Various factors cause differences in costs of medical treatments between countries, which are related to either healthcare resource use or cost per units of provisions and performances (17). On the whole, published reports on costs of UAE and/or hysterectomy suggest direct medical in-hospital costs for both UAE and hysterectomy to be strikingly lower than the direct medical in-hospital costs as calculated in our study (22, 23, 24, 25, 27, 28, 29). Studies comparing hysterectomy with other treatment alternatives, including both direct medical in-hospital and out-of-hospital costs, also seem to suggest lower costs for hysterectomy (30, 31). Similarly, lower costs of hysterectomy were reported in two studies that considered both direct and indirect costs (32, 33).
There are several explanations for the apparently lower costs of both UAE and hysterectomy as reported by others in comparison to our findings. First, most previous reports used cost estimations in their economic evaluation. Part of the fixed costs and shares of departmental and hospital overheads that should be allocated in part to the cost volumes are vulnerable to being easily overlooked when costs are estimated instead of being calculated. Cost estimations may therefore systematically underestimate ‘true' economic costs, as used in our analysis (15). Second, several resource volumes were not included in earlier studies due to retrospective data collection, which is prone to underestimation of used resources.
Absence from work accounted for 79% of the difference in total costs between UAE and hysterectomy. This implies that performing an economic evaluation from a societal perspective may lead to unexpected, yet very important, findings. Only one other study comparing UAE and hysterectomy included indirect costs or productivity costs in its economic evaluations (23). This is surprising because indirect costs contribute substantially to the costs for society when a particular treatment choice is being made.
One potential limitation is that our findings may be typical for the Dutch healthcare system and insurance legislation regarding absence from work, which differs from those in the United States and other countries within Europe. When assuming 16 days absence for UAE and 36 days for hysterectomy in the sensitivity analysis, the differences in total costs decreased by 17%. Even with these assumptions, the total cost difference changed; however, the mean total costs of UAE were still lower than those of hysterectomy.
An important limitation of our economic evaluation is that UAE was performed according to the state of the art at the onset of the study. Since then, the technique of UAE has been further developed, and, in some institutions, direct postprocedural MR imaging is sometimes being performed to detect the fibroid infarction rate, thus indicating the need for any repeat embolizations in case of unsatisfactory technical or clinical (34, 35). These developments may increase the clinical success rate of UAE even further, at the expense, however, of extra costs. Furthermore, in this study we solely used polyvinyl alcohol particles. Nowadays, not only polyvinyl alcohol particles, but also the more expensive spherical particles are commonly used, thereby increasing the overall costs.
Another limitation of our evaluation is that data were not collected beyond 2 years of follow-up. Relief of symptoms related to fibroids usually occurs after menopause (1). Hence, follow-up of patients until menopause would seem more appropriate. Reassuringly, any differences in clinical outcome, health status, and health-related quality of life were absent between 6 and 24 months of follow-up. It remains unclear, however, whether our results will remain stable beyond this observation window, until menopause. Longer follow-up the EMMY trial cohort is warranted to determine long-term cost differences. Long-term follow-up of two other case series showed the 5-year success rate of UAE to range from 73% to 75% (36, 37). Until today, no economic evaluation comparing UAE and hysterectomy has been published with a follow-up exceeding 12 months, except for one decision-analytic approach that estimated costs and effects until menopause (23).
In summary, we can state that the 24-month mean costs of UAE were lower for UAE compared to hysterectomy, mainly due to the differences in direct medical in-hospital costs and indirect costs. According to the sensitivity analysis, overall cost differences were relatively insensitive to variations in four important cost parameters, implying that the cost difference in favor of UAE was robust. Therefore, we conclude that, from an economic perspective, UAE is the superior treatment strategy for patients with symptomatic uterine fibroids.
Acknowledgments
Contributors. The EMMY-trial was initiated by J. Reekers, W. Ankum, and G. Bonsel. The steering committee comprised the following persons: J. Reekers, W. Ankum, M. Burger, G. Bonsel, E. Birnie, G. Veldhuyzen van Zanten, H. van Overhagen, S. de Blok, and H. Vervest. The safety committee had the following members: J. Evers, M. Prins, and J. van Engelshoven, Academic Hospital Maastricht, The Netherlands (nonparticipating center). W. Hehenkamp, N. Volkers, P. Smit, E. Birnie, W. Ankum, and J. Reekers contributed to and edited the manuscript. All members of the EMMY trial group supplied, treated, and evaluated participating patients. W. Hehenkamp, N. Volkers, P. Smit, and E. Birnie managed and analyzed data. All authors had access to all data in the study and held final responsibility for the decision to submit for publication. We are indebted to all participating patients, EMMY trial group members and nurses, and other contributors who made the trial possible. We are grateful to M.G.W. Dijkgraaf, PhD, Department of Clinical Epidemiology Biostatistics and Bioinformatics, Academic Medical Center, and to K.W. Redekop, PhD, Institute of Health Policy and Management, Erasmus Medical Center, Rotterdam, for assistance in performing the bootstrap method. We thank M. Nuberg, H. van Welsum, and M. Cornet for their administrative efforts. The EMMY trial was funded by ZonMw ‘'Netherlands Organisation for Health Research and Development' and sponsored by Boston Scientific. EMMY trial group and investigators:
Clinical Centers (the number of randomized patients is given in parentheses): Academic Medical Center, Amsterdam (32) — J. Reekers, W. Ankum, M. Burger, G. Bonsel, E. Birnie, W. Hehenkamp, N. Volkers; Onze Lieve Vrouwe Gasthuis, Amsterdam (40) — S. de Blok and C. de Vries; Atrium Medical Center, Heerlen (4) — T. Salemans and G. Veldhuyzen van Zanten; Groningen University Hospital, Groningen (3) — D. Tinga and T. Prins; Bosch Medical Center, Den Bosch (1) — P. Sluijffers and M. Rutten; Bronovo Hospital, The Hague (1) — M. Smeets and N. Aarts; Medical Center Rijnmond-Zuid, Rotterdam (2) — P. van der Moer and D. Vroegindeweij; St. Elisabeth Hospital, Tilburg (6) — F. Boekkooi and L. Lampmann; Flevo Hospital, Almere — G. Kleiverda; Gooi-Noord Hospital, Laren — R. Dik and J. Marsman; Kennemer Gasthuis, Haarlem (4) — C. de Nooijer, I. Hendriks and G. Guit; Leyenburg Hospital, The Hague (4) — H. Ottervanger and H. van Overhagen; St. Lucas/Andreas Hospital, Amsterdam (4) — A. Thurkow; Martini Hospital, Groningen (10) — P. Donderwinkel, J. Wijma and C. Holt; Medical Center Alkmaar, Alkmaar (4) — A. Adriaanse and J. Wallis; Medical Center Leeuwarden, Leeuwarden (9) — J. Hirdes, J. Schutte and W. de Rhoter; Hospital Midden-Twente, Hengelo (6) — P. Paaymans and R. Schepers-Bok; Medisch Spectrum Twente, Enschede (5) — G. van Doorn, J. Krabbe and A. Huisman; Reinier de Graaf Gasthuis, Delft (2) — M. Hermans and R. Dallinga; Slingeland Hospital, Doetichem (4) — F. Reijnders and J. Spithoven; St. Jans Gasthuis, Weert (1) — W. de Jager and P. Veekmans; Twenteborg Hospital, Almelo (6) — P. van der Heijden, M. Veereschild and J. van den Hout; University Medical Center Utrecht, Utrecht (4) — I. van Seumeren, A. Heintz, R. Lo and W. Mali; Westeinde Hospital, The Hague (2) — J. Lind and Th. de Rooy; Diakonessenhuis Utrecht, Utrecht (5) — M. Bulstra and F. Sanders; De Heel Hospital, Zaandam (1) — J. Doornbos; Rijnstate Hospital, Arnhem (3) — P. Dijkhuizen and M. van Kints; Slotervaart Hospital, Amsterdam (4) — Ph. Engelen and R. Heijboer; BovenIJ Hospital, Amsterdam (5) — A. Dijkman. Midden-Twente, Hengelo (6) — P. Paaymans and R. Schepers-Bok; Medisch Spectrum Twente, Enschede (5) — G. van Doorn, J. Krabbe and A. Huisman; Reinier de Graaf Gasthuis, Delft (2) — M. Hermans and R. Dallinga; Slingeland Hospital, Doetichem (4) — F. Reijnders and J. Spithoven; St. Jans Gasthuis, Weert (1) — W. de Jager and P. Veekmans; Twenteborg Hospital, Almelo (6) — P. van der Heijden, M. Veereschild and J. van den Hout; University Medical Center Utrecht, Utrecht (4) — I. van Seumeren, A. Heintz, R. Lo and W. Mali; Westeinde Hospital, The Hague (2) — J. Lind and Th. de Rooy; Diakonessenhuis Utrecht, Utrecht (5) — M. Bulstra and F. Sanders; De Heel Hospital, Zaandam (1) — J. Doornbos; Rijnstate Hospital, Arnhem (3) — P. Dijkhuizen and M. van Kints; Slotervaart Hospital, Amsterdam (4) — Ph. Engelen and R. Heijboer; BovenIJ Hospital, Amsterdam (5) — A. Dijkman.
References
- . Uterine fibroids. Lancet. 2001;357:293–298
- Arterial embolisation to treat uterine myomata. Lancet. 1995;346:671–672
- . The Ontario Uterine Fibroid Embolization Trial (II. Uterine fibroid reduction and symptom relief after uterine artery embolization for fibroids). Fertil Steril. 2003;79:120–127
- . Uterine fibroid embolization: nonsurgical treatment for symptomatic fibroids. J Am Coll Surg. 2001;192(1):95–105
- . Uterine artery embolisation for symptomatic fibroids: clinical results in 400 women with imaging follow up. BJOG. 2002;109:1262–1272
- . Uterine artery embolization for leiomyomata. Obstet Gynecol. 2001;98:29–34
- . Uterine artery embolization versus hysterectomy in the treatment of symptomatic uterine fibroids: 2 years' outcome from the randomized EMMY trial. Am J Obstet Gynecol. 2007;196:519–11
- . SF-36 health survey update. Spine. 2000;25:3130–3139
- . EQ-5D: a measure of health status from the EuroQol Group. Ann Med. 2001;33:337–343
- Multiattribute and single-attribute utility functions for the health utilities index mark 3 system. Med Care. 2002;40:113–128
- . Cost-effectiveness analysis in radiology. Radiology. 2001;219:611–620
- . Cost-effectiveness in health and medicine. New York/Oxford: Oxford University Press; 1996;
- . Symptomatic uterine fibroids: treatment with uterine artery embolization or hysterectomy: results from the randomized clinical Embolisation versus Hysterectomy (EMMY) Trial. Radiology. 2008;246:823–832
- Loss of ovarian reserve after uterine artery embolization: a randomized comparison with hysterectomy. Hum Reprod. 2007;22:1996–2005
- . The distinction between cost and charges. Ann Intern Med. 1982;96:102–109
- Reporting standards for uterine artery embolization for the treatment of uterine leiomyomata. J Vasc Interv Radiol. 2001;12:1011–1020
- . Handleiding voor kostenonderzoek. Diemen: College voor zorgverzekeringen; 2004;
- . Farmocotherapeutisch kompas: medisch farmacotherapeutische voorlichting. Amstelveen: College voor zorgverzekeringen (CVZ); 2004;
- . Handling uncertainty in economic evaluations of healthcare interventions. BMJ. 1999;319:635–638
- . Analysis of cost data in randomized trials: an application of the non-parametric bootstrap. Stat Med. 2000;19:3219–3236
- Uterine artery embolization versus hysterectomy in the treatment of symptomatic uterine fibroids (EMMY trial): peri- and postprocedural results from a randomized controlled trial. Am J Obstet Gynecol. 2005;193:1618–1629
- . Cost analysis of myomectomy, hysterectomy, and uterine artery embolization. Am J Obstet Gynecol. 2002;187:1401–1404
- . Cost-effectiveness of uterine artery embolization and hysterectomy for uterine fibroids. Radiology. 2004;230:207–213
- . Medico-economic approach to the management of uterine myomas: a 6-month cost-effectiveness study of pelvic embolization versus vaginal hysterectomy. Eur J Obstet Gynecol Reprod Biol. 2003;111:59–64
- . Hospital costs of uterine artery embolization and hysterectomy for uterine fibroid tumors. Acad Radiol. 2002;9:1300–1304
- Uterine-artery embolization versus surgery for symptomatic uterine fibroids. N Engl J Med. 2007;356:360–370
- . Estimated costs for uterine artery embolization and abdominal myomectomy for uterine leiomyomata: a comparative study at a single institution. J Vasc Interv Radiol. 2002;13:1207–1210
- . Costs and charges associated with three alternative techniques of hysterectomy. N Engl J Med. 1996;335:476–482
- . Uterine artery embolization for leiomyomata: resource use and cost estimation. J Vasc Interv Radiol. 2001;12:571–574
- . An economic evaluation of transcervical endometrial resection versus abdominal hysterectomy for the treatment of menorrhagia. Br J Obstet Gynaecol. 1993;100:244–252
- . Randomised trial comparing hysterectomy and transcervical endometrial resection: effect on health related quality of life and costs two years after surgery. Br J Obstet Gynaecol. 1996;103:142–149
- . A cost comparison of hysterectomy and hysteroscopic surgery for the treatment of menorrhagia. Eur J Obstet Gynecol Reprod Biol. 1996;70:87–92
- Quality of life and cost-effectiveness of levonorgestrel-releasing intrauterine system versus hysterectomy for treatment of menorrhagia: a randomised trial. Lancet. 2001;357:273–277
- . Repeat uterine artery embolization: indications and technical findings. J Vasc Interv Radiol. 2006;17:1923–1929
- MR imaging evidence of reversal of uterine ischemia after uterine artery embolization for leiomyomata. J Vasc Interv Radiol. 2006;17:1535–1538
- . Long-term outcome of uterine artery embolization of leiomyomata. Obstet Gynecol. 2005;106:933–939
- . Long-term follow up of uterine artery embolisation: an effective alternative in the treatment of fibroids. BJOG. 2006;113:464–468
The EMMY study is funded by ZonMw 'Netherlands Organisation for Health Research and Development' (grant application number 945-01-017) and supported by Boston Scientific Corporation, The Netherlands.None of the authors have identified a conflict of interest.
PII: S1051-0443(08)00275-3
doi:10.1016/j.jvir.2008.03.001
© 2008 SIR. Published by Elsevier Inc. All rights reserved.
Volume 19, Issue 7 , Pages 1007-1016, July 2008