An economic evaluation of surgery for temporal lobe epilepsy

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I,J T T E R W 0 R T H IE I N E a A N N

An Economic Evaluation of Surgery for Temporal Lobe Epilepsy Samuel Wiebe, 1Amiram Gafni, Warren T. Blume, and John P. Girvin

We wished to determine whether surgery in adults with difficult to control temporal lobe epilepsy (TLE) is more effective and less costly than medical therapy. We evaluated the costs and consequences of surgical versus medical treatment of TLE, using decision-analysis modeling and an intention-to-treat approach. Data on outcome probabilities and resource utilization were obtained from critical appraisal of the literature, local experience, a panel of experts, and community patient survey. Surgically treating 100 patients for 35 years results in 57 seizure-free patients and a cost of $8,117,911. Medically treating 100 patients results in 12 seizure-free patients and a cost of $10,741,425. Surgery required a larger initial expenditure than medical treatment ($2,775,640 vs. $856,970), but cost-time curves intersect at 8.5 years and surgery remained cheaper thereafter. Results were unchanged by extensive sensitivity analyses. The major determinant of surgical dominance is its greater effectiveness (seizure-free rate) as compared with medical treatment. Surgery remained less costly, with concurrent effectiveness rates >41 and <30%, respectively, for surgical and medical treatment. Available evidence indicates that TLE surgery is more effective and cheaper than medical treatment, a win-win situation. However, adequately designed, controlled trials are necessary to determine more accurately and comprehensively the effectiveness of each therapeutic alternative. Key Words: Economic evaluation-Temporal lobe epilepsy--Surgery--Cost-effectiveness~Decision analysis.

Scarcity in health care is r e s h a p i n g the w a y medicine is practiced in the 1990s. B u d g e t a r y constraints n o w d e m a n d e v i d e n c e of efficient resource use. Policy m a k e r s a n d resource-allocating agen-

Received March 20, 1995; accepted April 5, 1995. From the University Hospital, The University of Western Ontario, London, Ontario, and 1Centre for Health Economics and Policy Analysis, Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada, L8N 3Z5. Address correspondence and reprint requests to Dr. S. Wiebe, University Hospital, 339 Windermere Road London, Ontario, Canada, N6A 5A5. J. Epilepsy 1995;8:227-235 © 1995 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010

cies threaten to cut inefficient programs, i.e., those incapable of p r o d u c i n g a particular o u t c o m e using the least costly quantity and mix of resources (1). Costly interventions such as epilepsy s u r g e r y m a y be a prime target for such b u d g e t a r y restrictions. A l t h o u g h epilepsy surgery is not n e w (2), surgical interest has escalated with the a d v e n t of imp r o v e d surgical, anesthetic, imaging, a n d EEG technology. T e m p o r a l lobe epilepsy (TLE), o w i n g to its resistance to antiepileptic d r u g s (AEDs) a n d its relatively high prevalence, is the most f r e q u e n t type of surgically treated epilepsy. The lifetime p r e v a l e n c e of e p i l e p s y is e s t i m a t e d at 650 in 100,000 population; 40% of these patients have

0896-6974/95/$10.00 SSDI 0896-6974(95)00039-G

S. WIEBE ET AL. complex partial seizures (CPS), and most originate in the TL (3-5). The effectiveness of TLE surgery is supported by large series of cases (6-17) and it has been suggested that the procedure is underutilized (18-20). On the other hand surgery is costly, requiring a team approach in highly specialized units. A recent National Institutes of Health (NIH) consensus statement estimated the median charges for presurgical evaluation and surgery in the United States to be $25,000-$100,000 (20). However, we know of no published formal economic evaluations comparing TLE surgery with medical treatment. Assessing the efficiency of a health care program entails comparing its cost and consequences with an alternative course of action. The typical alternative to epilepsy surgery is medical treatment with AEDs. Using existing data on effectiveness, we conducted an economic evaluation of TLE surgery as compared with currently accepted medical treatment.

Methods Study Setting and Description of Alternatives Our analysis targeted adults with difficult-tocontrol epilepsy of presumed TL origin. The setting was the Epilepsy Unit at University Hospital, University of Western Ontario, London, Ontario, Canada, where epilepsy surgery has been performed since 1974. On the average, 50 temporal lobectomies for epilepsy are performed yearly. The unit has eight monitored beds and serves as a referral center for Ontario and Canada (21). The medical alternative consists of one or more AEDs, chosen according to seizure type and severity as determined by clinical and laboratory evaluation. The surgical alternative involves admission to an epilepsy unit for one- or two-stage presurgical evaluation (PSE) to determine operability. The first stage consists of tapering AEDs under careful medical supervision and continuous scalp EEGclinical recording, brain magnetic resonance imaging (MRI), and psychological, psychiatric, and neuropsychological evaluation. When necessary, patients proceed to the second stage, consisting of depth-subdural electrode EEG recordings, and intracarotid sodium amytal injection for speech and memory lateralization. Patients w h o are not operable after PSE are treated with the medical alternative. Operable patients undergo TL resection with 228

J EPILEPSY, VOL. 8, NO. 3, 1995

intraoperative electrocorticographic (ECoG) recording. Postoperatively, they are treated as in the medical alternative.

Data Sources Using Medline, epilepsy experts, and standard epilepsy textbooks, we searched and critically appraised the existing English language literature from 1965 to 1993 for probability estimates of clinical outcomes, patient management, and sequela of medical and surgical treatment of TLE. Only studies with ~50 patients were included for analysis of effectiveness (seizure-free rates). For less frequently reported outcomes and management variables, all the available literature was analyzed. A group of experts (epilepsy specialists and field workers) reviewed these data and provided consensus for conflicting information on clinical outcomes and probabilities, inpatient and outpatient management, and outcomes for which reliable information was not available in the literature. The resources required to treat a typical case with each alternative were estimated from three main sources: First, using a standardized questionnaire, we surveyed 33 outpatients in Southwestern Ontario w h o typified the relevant clinical outcomes. Second, the expert panel was canvassed for consensus on resource use. Third, we obtained detailed standard costs of presurgical evaluation, surgery, and postoperative care for 30 consecutive patients w h o underwent temporal lobectomy for epilepsy from August 1992 to March 1993 at the study setting.

Analytic Techniques Using existing methodological standards (2224), we evaluated the hypothesis that surgery reduces seizure frequency more effectively and at a lower cost than medical treatment. Effectiveness was defined as seizure-free status because this is always a relevant outcome in epilepsy therapy and because in the absence of quality of life (QOL) or seizure severity measurements, seizure-free status is the best surrogate. We used an intention-to-treat approach; i.e., all patients undergoing preoperative evaluation were analyzed in the surgical program, regardless of the final surgical decision. Stable outcomes were assumed based on our published experience (17) and projected for 35 years

ECONOMIC EVALUATION OF EPILEPSY SURGERY

the approximate life expectancy for a typical patient at the time of surgery. The viewpoint of the study was that of a third-party payer or health insurer. We performed extensive one- and two-way sensitivity analyses for important variables that entailed uncertainty.

in recent series (33-35), in the form of hemorrhage, infection, or cortical contusions. Operative morbidity occurs in 1% of patients (12), and mortality has been nonexistent in our experience (17) and was nonexistent in a recent larger series (36). Decision A n a l y s i s

Critical A p p r a i s a l of the L i t e r a t u r e

No controlled trials have assessed the effectiveness of epilepsy surgery. The existing data are derived from uncontrolled series of cases with "before and after" analyses. Considerable uncertainty is expressed in the literature with respect to probabilities of long-term seizure-free status and significant improvement with medical treatment (19,2529). Variation exists among surgical centers' deftnition of surgical candidacy; some operate only on the most medically refractory patients, whereas others operate on the basis of "remediability." Information is scarce with respect to AED requirements in surgically treated seizure-free patients (10,26,30-32) and with respect to the proportion of inoperable patients after presurgical evaluation. Morbidity of invasive EEG was estimated at ~1%

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Using data from the literature, local experience, and expert panel consensus, we developed a decision-analysis model of typical TLE management with the two therapeutic alternatives (Fig. 1). With the medical alternative, patients may become seizure-free or may or may not improve significantly. As in previous reports, significant improvement was operationally defined as a >75% reduction in seizure frequency from baseline (7,15,17,26,37). With the surgical alternative, nonoperable patients have the same outcomes as those in the medical alternative; operable patients may become seizurefree without AEDs, i.e., not requiring AEDs after the first postoperative year and not having seizures other than auras; they may become seizurefree with AEDs, i.e., AEDs required after the first postoperative year; or they may or may not im-

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Figure 1. Decision tree of therapeutic alternatives in temporal lobe epilepsy. Probabilities are expressed per 100 patients in each alternative using an intention-to-treat approach. Patients who are inoperable are treated with the medical alternative. Decision nodes (squares); chance nodes (circles). J EPILEPSY, VOL. 8, NO. 3, 1995

229

S. WIEBE ET AL. prove significantly. Probability estimates of clinical outcomes for the typical case and for best-worse scenarios are shown in Table 1.

Cost Identification and Measurement We estimated the resource requirements for a typical case with each alternative. Hospital costs are expressed as standard costs, and outpatient resources reflect current market prices based on 1993 Canadian dollars (Canadian $1.00 = U.S. $0.76). All costs were projected for 35 years, and all were discounted to obtain present (1993) values. We used the customary 5% discount rate to account for differential timing of some costs, and as a measure of society's time preferences (52). Physicians' costs were obtained from the Ontario Health Insurance Plan's fee schedule (53). Fees may not reflect opportunity cost, but they have been used successfully in previous studies (54,55). Other costs included in the analysis are AEDs, blood tests, dental services, c o m m u n i t y , social, a n d s u p p o r t services, transportation, ambulance, emergency room, EEG studies, imaging, nonsurgical epilepsyrelated hospitalizations, presurgical evaluation, and surgery (detailed cost itemization available on request).

Results

Costs and Consequences of Therapeutic Alternatives The existing data on effectiveness indicate that - 1 2 in 100 medically treated patients with difficultT a b l e 1.

Outcome Medical program Seizure-free Significantly improved Not significantly improved Surgical program Not operable Operable Seizure-free Seizure-free without AEDs Seizure-free with AEDs Significantly improved Not significantly improved

to-control epilepsy may become seizure-free, as compared with 57 with surgical treatment, i.e., with intention to treat surgically. For the baseline scenario, the total cost per 100 patients treated for 35 years is $8,117,911 with the surgical program as compared with $10,741,425 with the medical program. The total cost per seizure-free patient is 6.3 times higher with the medical than with the surgical program, i.e., $895,119 ($10,741,425/12) versus $142,419 ($8,117,911/57), respectively (Table 2), clearly indicating a win-win situation for surgery. The average cost per patient for PSE and surgery was $26,520 (SD = $9,400). Although savings of $2,623,524 can be expected by surgically treating 100 patients in 35 years, surgery requires a larger initial expenditure. Thirtyeight percent of the total costs in the surgical program are incurred in the first year of treatment, as compared with only 8% of the total medical costs (Table 2). Total medical and surgical costs equalize by the ninth year of treatment; thereafter, medical treatment is more costly (Fig. 2). Therefore, surgery is efficient due to its ability to avert costs of long-term medical treatment. With the medical alternative, three elements account for 88% of the cost of follow-up: AEDs and blood tests (43%), hospitalization and emergency room visits (27%), and social and community services (18%). The same components account for only 60% of the costs of the surgical alternative (Table 3). Only 32% of the total costs of the surgical program are due to the actual presurgical evaluation and surgery ($26,520 per patient on the average). The main elements of such costs per patient are hospital stay, $7,566; epilepsy unit and EEG

Outcome probability estimates used in analysis Probability (range)

References

12 (0-25) 13 (8-28) 75 (60-80)

25,27-29,38,39, local experience 20,25,38-40, local experience Complement of the two previous outcomes

15 85 55 (43-68) 30 (19-41) 25 (14-36) 17 (12-22) 13 (8-18)

Expert panel and local experience Expert panel and local experience 6-11,13-17,32,41-48 30,31,49,50, local experience Complement of probability of "without AEDs" 7,8,13-17,47,48,51, local experience 7,8,13-17,47,48,51, local experience

AEDs, antiepileptic drugs. Probability estimates and ranges of clinical outcomes in each therapeutic alternative. Details of sources are described in text. Probabilities are expressed per 100 patients in each alternative, using an intention-to-treat approach.

230 J EPILEPSY, VOL. 8, NO. 3, 1995

ECONOMIC EVALUATION OF EPILEPSY SURGERY T a b l e 2.

Therapeutic alternative (No. seizure-free)

Differential timing of expenditures with each alternative

Total costs during year 1 ($)

Total costs during years 2-35 ($)

Total costs per seizure-free patient ($)

820,552 3,105,646 2,285,094

9,920,873 5,012,265 ( - ) 4,908,608

895,119 142,419

Medical (12) Surgical (57) Surgical minus medical

Total costs of program ($) 10,741,425 8,117,911 ( - ) 2,623,514

Costs are incurred at different times with each therapeutic alternative. Surgical treatment requires a larger initial expenditure, but the total cost of the surgical program is lower than that of the medical program. Costs of alternatives are expressed for the treatment of 100 patients for 35 years, using a 5% discount rate. Minus sign indicates savings with the surgical option. services, $7,298; physician services, $5,580; operating room, $3,543; and neuropsychological services, $3,031. We performed extensive sensitivity analyses on important variables that entailed uncertainty, using a range of plausible values obtained from the literature and the expert panel and making conservative assumptions for uncertain or unavailable data. The surgical strategy remained less costly and more effective in each of the 14 possible situations examined (Table 4). The net incremental savings for each additional seizure-free patient with surgery could be decreased 50% by changing three variables: (a) increasing surgical costs by 2 SD above the baseline; (b) changing probability estimates to favor medical treatment and disfavor surgery at all decision-tree endpoints, other than the number of seizure-free patients; and (c) varying the probability of seizure-free status using the most favorable estimate for the medical strategy and the least favorable estimate for the surgical strategy. 12~

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l~fler.

Discussion

When diagnostic or therapeutic alternatives are compared, those that are more effective are usually also more costly, and one must decide whether implementing the more expensive program is warranted or feasible. This is not an easy task for re-

T a b l e 3.

12

10

2

We assessed the uncertainty surrounding seizure-free status achievement with each strategy by two-way sensitivity analyses using a broad range of plausible probabilities (Table 5). Medical treatment would become cheaper, though less effective than surgery, if the concurrent surgical (intention to treat) and medical seizure-free rates were <41 and >30%, respectively.

Cost category AEDs Hospital and emergency CSS Other PSE and surgery Total cost

Major cost categories of programs Surgical program $ (%)

Medical program $ (%)

2,769,904 ( 3 4 )

4,609,900(43)

1,275,811( 1 6 ) 762,352 ( 9 . 3 ) 707,349 ( 8 . 7 )

2,913,134(27) 1,956,379(18) 1,262,012(12)

2,602,495 (32) 8,117,911 (100)

10,741,425(100)

AEDs, antiepileptic drugs; CSS, community and social services; PSE, presurgical evaluation. Three categories account for the majority of expenditures in both therapeutic alternatives, i.e., AEDs, nonsurgical hospitalizations and emergency room services, and CSS. The total costs of each program are expressed for the baseline scenario per 100 patients treated for 35 years, using a 5% discount rate. J EPILEPSY, VOL. 8, NO. 3, 1995 231

S. WIEBE ET AL.

Table 4. Scenario 2

3

4

5

6

7

8

9

10

11

12

13 14

Scenarios used in sensitivity analyses

Description As in baseline, but using outcomes in decision tree other than seizure-free status in favor of the medical intervention and against the surgical intervention (see Fig. 1) As in baseline, but decreasing AED requirements by 50% in medically and surgically treated patients who become seizure-free As in baseline, but decreasing AED requirements by 35% in medically and surgically treated patients who are not significantly improved As in baseline, but increasing AED requirements by 50% in medically and surgically treated patients who are significantly improved As in baseline, but decreasing epilepsy-related hospitalizations to zero in medically and surgically treated patients who are significantly improved As in baseline, but decreasing epilepsy-related hospitalizations by 50% in medically and surgically treated patients who are not significantly improved As in baseline, but decreasing community and social services by 50% in medically and surgically treated patients who are not significantly improved As in baseline, but decreasing community and social services by 50% in medically and surgically treated patients who are significantly improved As in baseline, but decreasing community and social services by 50% in medically and surgically treated patients who become seizure-free As in baseline, but increasing community and social services by 40% in medically and surgically treated patients who are significantly improved As in baseline, but doubling the amount of community and social services consumed by medically and surgically treated patients who become seizure-free As in baseline, but using the upper range (+ 2 SD) of surgical and presurgical costs As in baseline, but using the lower range ( - 2 SD) of surgical and presurgical costs

We analyzed 14 different scenarios using a range of plausible values. Variables used in the analysis were chosen on the basis of various degrees of uncertainty and mostly favored the medical alternative to test the robustness of our findings.

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source allocators (56). Our evaluation shows that TLE surgery apparently belongs in the u n u s u a l category of therapies that are not only more effective but also cheaper t h a n their alternative course of action. This surgical w i n - w i n situation, unchanged by extensive sensitivity analyses, results from its ability to avert long-term treatment costs. Our analysis has several practical implications. First, in the current climate of fiscal a n d b u d g e t a r y constraint, size a n d t i m i n g of e x p e n d i t u r e s in health care programs are carefully scrutinized. Because epilepsy surgery requires a greater initial expenditure than medical treatment, any decisions to implement a surgical program will have to balance its larger initial expenditure w i t h its long-term lower total costs. Second, AEDs account for a sizable p r o p o r t i o n of surgically a v e r t e d costs; as newer, more expensive AEDs are being used, surgery is expected to have a favorable impact on these expenditures. The same applies to the opportunity cost of social a n d support services, hospitalizations, and medical resources currently devoted to operable epilepsy patients w h o continue to be treated medically. Third, although long-term medical treatment accounts for the greatest expenditure, sensitivity analyses s h o w that surgical costs are also significant. Lowering PSE and surgical costs would shorten the time to intersection of medical and surgical cost curves. Analysis of the least costly quantity a n d mix of resources necessary to perform presurgical evaluation and surgery for epilepsy a d e q u a t e l y r e m a i n s an o p e n area for efficiency and effectiveness research. Fourth, our model suggests that surgical efficiency relates to the timing of operation; the earlier surgery is p e r f o r m e d in life (15,41), the m o r e costs are averted. Epilepsy is more than seizures; QOL plays a major role in this chronic illness (56-58). It is unfortunate that at the time of this publication no comparative data are available in this important field. Research that incorporates QOL as a major outcome should permit its inclusion in future economic evaluations. The need for such comprehensive risk-benefit assessment (59,60) is underscored by the gradual broadening of indications for epilepsy surgery to encompass "surgically remediable" as o p p o s e d to o n l y medically intractable p a t i e n t s (12), a n d by the availability of n e w AEDs with a variety of cost-efficacy/side-effect profiles. Indirect costs, i.e., loss of income a n d leisure time, are i m p o r t a n t in an economic evaluation with a societal perspective, but existing data for

ECONOMIC EVALUATION OF EPILEPSY SURGERY Table

5.

Two-way sensitivity analyses of effectiveness in both therapeutic alternatives Surgical strategy

Medical strategy Effectiveness (No. seizure-free) 12a 5

Cost per seizure-free patient ($) 895,119 2,259,604

12

895,119

20

504,882

25

388,844

30

311,108

Effectiveness (No. seizure-free)

Cost per seizure-free patient ($)

Net incremental cost per seizure free patient (surgical-medical) ($)b

57 37 47 57 67 37 47 67 37 47 57 67 37 43 37 41 47 57 67

142,419 259,837 188,693 2,520 1,103 259,682 188,576 110,041 259,936 188,776 2,585 110,182 259,473 215,561 259,373 226,799 188,333 2,219 109,871

- 58,300 - 52,628 - 57,843 - 61,046 -63,200 - 45,328 - 53,667 - 61,249 - 28,235 - 45,376 - 53,252 - 57,776 - 9,577 - 24,795 37,652 - 3,136 - 28,359 - 45,435 - 53,295

Impact of changing the expected effectiveness of the two alternatives simultaneously (two-way sensitivity analysis). The results are stable up to an effectiveness threshold of 30 and 40% with medical and surgical treatments, respectively; at this point, surgery is no longer cheaper. Effectiveness rates are expressed per 100 patients, using an intention-to-treat approach. Minus sign indicates savings with the surgical program. aBaseline scenario. bObtained by: [(Costs of surgical program) - (Costs of medical program)/(No, of patients seizure-free with surgery) (No. of patients seizure-free with medical treatment)]. e p i l e p s y are l a d e n w i t h u n c e r t a i n t y (61). H o w e v e r , willingness of p a t i e n t s to u n d e r g o either s u r g e r y or m e d i c a l t r e a t m e n t m a y b e i n t e r p r e t e d as revealed p r e f e r e n c e s (62) to forgo i n c o m e or leisure time in e x c h a n g e for the c h a n c e of cure offered b y o n e of the t r e a t m e n t s . Finally, results of e c o n o m i c e v a l u a t i o n s are only as precise as the i n f o r m a t i o n o n w h i c h t h e y are based. O u r o u t c o m e probabilities could gain precision if o b t a i n e d f r o m a d e q u a t e l y d e s i g n e d , rand o m i z e d controlled trials of surgical v e r s u s m e d i cal t r e a t m e n t of TLE as h a s b e e n s h o w n for o t h e r t h e r a p i e s (63-66). Such studies d o n o t exist. H o w ever, the e x t e n s i v e sensitivity a n a l y s e s p e r f o r m e d s u p p o r t o u r results w i t h i n a w i d e r a n g e of plausible situations a n d allow identification of thresholds at w h i c h surgical a n d medical costs c h a n g e significantly. T h e stability of the m o d e l to w i d e variations in PSE a n d surgical costs also m a k e s the results generalizable to different practice settings. Yet o b t a i n i n g accurate data o n the effectiveness of e p i l e p s y s u r g e r y is p a r a m o u n t a n d will require adequately d e s i g n e d controlled trials c o m p a r i n g the

effects of t h e r a p e u t i c strategies o n all r e l e v a n t outc o m e s in epilepsy, including p a t i e n t s ' p r e f e r e n c e s a n d quality of life. Acknowledgment: S. W. w a s the recipient of a n A b b o t t e d u c a t i o n a l g r a n t d u r i n g the a c a d e m i c y e a r 1993-1994. W e t h a n k Barbara Sorin a n d o u r m a n y colleagues w h o p r o v i d e d useful i n f o r m a t i o n a n d critique for this project, the regional e p i l e p s y a g e n cies in S o u t h w e s t e r n Ontario, R a n d y W e l c h for detailed c o s t - a c c o u n t i n g i n f o r m a t i o n , a n d M a r i a Raffa a n d H e a t h e r M u r r a y for t y p i n g the m a n u script.

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