Surgical Endoscopy

, Volume 21, Issue 7, pp 1184–1189

Health economic evaluation of therapeutic strategies in patients with idiopathic achalasia: results of a randomized trial comparing pneumatic dilatation with laparoscopic cardiomyotomy

Authors

    • Department of General SurgeryBorås Central Hospital
  • E. Johnsson
    • Department of SurgerySahlgrenska University Hospital
  • A. Kjellin
    • Department of SurgeryKarolinska University Hospital
  • M. Ruth
    • Department of SurgerySahlgrenska University Hospital
  • H. Lönroth
    • Department of SurgerySahlgrenska University Hospital
  • M. Andersson
    • Department of RadiologySahlgrenska University Hospital
  • L. Lundell
    • Department of SurgeryKarolinska University Hospital
Article

DOI: 10.1007/s00464-007-9310-0

Cite this article as:
Kostic, S., Johnsson, E., Kjellin, A. et al. Surg Endosc (2007) 21: 1184. doi:10.1007/s00464-007-9310-0
  • 129 Views

Abstract

Background

We have prospectively collected information concerning the costs incurred during the management of patients allocated to either forceful dilatation or to an immediate laparoscopic operation because of newly diagnosed achalasia.

Methods

Fifty-one patients with newly diagnosed achalasia were randomized to either pneumatic dilatation to a diameter of 30–40 mm or to a laparoscopic myotomy to which was added a posterior partial fundoplication. Follow-ups were scheduled at 1, 3, 6, and 12 months after inclusion. At each follow-up visit a study nurse interviewed the patients regarding symptoms and their quality of life (QoL) and a health economic questionnaire was completed. In the latter questionnaire, patients were asked to report the presence and character of contacts with the healthcare system since the last visit.

Results

In the dilatation group six patients (23%), including the patient who was operated on because of perforation, were classified as failures during the first 12 months of follow-up compared to one (4%) in the myotomy group (p = 0.047). Five of those classified as failures in the dilatation group subsequently had a surgical myotomy and the sixth patient was treated with repeated dilatations. The patient classified as failure in the myotomy group was treated with endoscopic dilatation. The initial treatment cost and the total costs were significantly higher for laparoscopic myotomy compared to a pneumatic dilatation-based strategy (p = 0.0002 and p = 0.0019, respectively) When the total costs were subdivided into the different resources used, we found that the single largest cost item for pneumatic dilatation was that for hospital stay and that for laparoscopic myotomy was the actual operative treatment (operating room time) The cost-effectiveness analysis, relating to the actual treatment failures, revealed that the cost to avoid one treatment failure (incremental cost-effectiveness ratio) amounted to €9239.

Conclusion

The current prospective, controlled clinical trial shows that despite a higher level of clinical efficacy of laparoscopic myotomy to prevent treatment failure in newly diagnosed achalasia, the cost effectiveness of pneumatic dilatation is superior, at least when a reasonable time horizon is applied.

Keywords

AchalasiaBalloon dilatationMyotomySymptomsTreatment failureHealth economic evaluationLaparoscopy

Although achalasia is an uncommon disease [13], it usually is diagnosed at a fairly late stage of the disease process. Accordingly, achalasia patients have suffered from the disease-specific symptoms for many years, the consequence of which is a profoundly impaired quality of life [4, 5]. When the diagnosis is obtained, effective therapy can be instituted in the form of either pneumatic endoscopic dilatation or surgical myotomy [6]. Over the years firm opinions have been expressed regarding the pros and cons of respective management strategy [7]. Before the launch of laparoscopic myotomy most clinicians seemed to advocate balloon dilatation as the obligatory initial step and thereafter rely on surgical referral at the time of therapeutic failure. This was mainly the result of the attractiveness of the forceful dilatation strategy due to availability, ease, comfort, reliable safety profile, and reassuring results in terms of swallowing control [8, 9]. During recent years it seems as if the opinions have deviated toward a more liberal use of a laparoscopic operation as soon as the diagnosis has been confirmed [10]. This has occurred despite a complete lack of corresponding scientific evidence to support this drift in the therapeutic management. We have conducted a randomized clinical trial comparing pneumatic dilatation with laparoscopic myotomy and partial fundoplication in the treatment of newly diagnosed cases of idiopathic achalasia. To get a comprehensive view of the merits of respective therapeutic strategy, health economic assessments are of pivotal importance. In the present study we therefore prospectively collected information concerning the costs incurred during the management of patients allocated to either forceful dilatation or to an immediate laparoscopic operation. We report the outcome of such analyses with the time frame limited to the first year after randomization.

Patients and methods

Between 2000 and 2005, 51 patients with newly diagnosed achalasia were randomized to either pneumatic dilatation to a diameter of 30–40 mm or to laparoscopic myotomy to which was added a posterior partial fundoplication. No patient had previously received disease-specific treatment such as Botox injection, myotomy, or dilatation to more than 18 mm. The patients were recruited from two university hospitals and three local hospitals. All patients had a typical clinical history together with characteristic findings on esophageal manometry consistent with achalasia, i.e., high pressure of the lower esophageal sphincter (LES) together with insufficient relaxation of the sphincter. To be eligible for inclusion in the trial patients had to have a general condition that allowed both treatment alternatives to be completed.

Fifty-one patients were available for the intention-to-treat (ITT) analysis (Fig. 1). There were no apparent differences in demographic background characteristics between the treatment groups. Of importance for the adherent indirect medical costs, the following baseline recordings were obtained regarding the patients’ social and working situation: In the dilatation group five were already preoperatively on sick leave, one was retired, one was on disability pension, and the rest were in the working force. The corresponding figures for those allocated to surgical myotomy were; four, none, and one, respectively; in addition, one operated patient was a college student. Because of incomplete follow-up in this respect, we lack robust data on the length of post-treatment sick leave in the large group of patients who were in the work force.
https://static-content.springer.com/image/art%3A10.1007%2Fs00464-007-9310-0/MediaObjects/464_2007_9310_Fig1_HTML.gif
Fig. 1.

Number of randomized patients and treatment failures during the 12 months of follow-up.

Treatment

Pneumatic dilatation was performed in all centers by experienced endoscopists. Patients allocated to pneumatic dilatation were treated either under conscious sedation with midazolam and pethidine or under general anesthesia. Fluoroscopy was used to allow an exact positioning of the dilatation balloon (RIGIFLEX, ABD achalasia balloon dilatator, Boston Scientific, Natick, MA). A predefined dilatation protocol was followed (balloon inflated to 10 psi for 60 s) which comprised an initial eventual two-stage procedure by which patients with insufficient symptom relief from one dilatation had another one within ten days. Further dilatations were performed if symptoms relapsed during follow–up, but if more than three dilatations were needed not counting the initial two, the patient was classified as a treatment failure (see below). The initial dilatation was to 30 mm in females and 35 mm in males, eventually followed by a balloon with a diameter of 35 and 40 mm in females and males, respectively. Each patient was discharged as soon as he/she had recovered from the conscious sedation/general anesthesia and after having swallowed fluid without significant complaints and symptoms.

All patients allocated to surgical myotomy were operated on or the operation was supervised by two experienced laparoscopic surgeons and all procedures could be completed laparoscopically. To prevent gastroesophgeal reflux each myotomy was completed by adding a partial fundoplication. During the procedure a minimum package consisting of five trocars, a dissecting instrument, a liver retractor, and a rotating grasper was used and all dissections were completed by use of Ultracision technology (Ethicon Endo-Surgery).

Follow-up

Follow-ups were scheduled at 1, 3, 6, and 12 months after inclusion. At each follow-up visit a study nurse interviewed the patients regarding symptoms and their quality of life (QoL) and a health economic questionnaire was completed. In the latter questionnaire, patients were asked to report the presence and character of contacts with the healthcare system since the last visit. A secondary data evaluation procedure was performed to minimize the risk for recall bias. Consequently, a survey of records in the hospital administration systems from the area where the patient lived was completed and all charts from visits and hospital stays during the 12 months after randomization were extracted to obtain a most objective and comprehensive assessment for healthcare resource consumption.

The presence of treatment failure was judged at all contacts, scheduled or nonscheduled, during follow-up and was considered if one or more of the following occurred: (1) incomplete symptom control or symptom relapse that required more than three treatments other than those already given initially, (2) treatment required for a relapse within three months after the initial treatment series (at least two sessions), (3) serious complication after a treatment that required a switch to the alternative strategy, (4) the patient required an alternative treatment because of lack of satisfaction with the allocated therapy, (5) the doctor responsible decided that the patient should undergo another treatment after consulting the trial committee.

QoL was recorded using one generic instrument and one more disease-specific. The generic instrument used was the psychological well-being index (PGWB), which includes 22 items divided into six dimensions: anxiety, depressed mood, positive well-being, self-control, general health, and vitality. Each dimension contains three to five items, which are graded using a six-point scale. The higher the score the greater the well-being. The disease-specific instrument was the gastrointestinal symptom rating scale (GSRS). This instrument includes 15 items divided into six dimensions: diarrhea syndrome, indigestive syndrome, intestinal obstruction, abdominal pain syndrome, reflux syndrome, and swallowing difficulties. GSRS uses a seven-point scale and a higher score means more pronounced symptoms [1116]. Corresponding instruments have been acknowledged in the assessment of patients with achalasia [17].

Healthcare costs

An assessment of total costs for the healthcare system was performed. Costs for all variables included in the analyses were taken from the hospital administration charts for in-hospital debits at Sahlgren’s University Hospital, Göteborg, Sweden, for the 2006 (Table 1). Solid data on costs for visits to general practitioners and drug consumption outside the hospital was not possible to capture in this study because of practical reasons and legal obstacles. Charges in Swedish crowns (SEK) were converted to euro (€) at a rate of 9.20 SEK to €1. Costs and benefits both were for one year, so no discount rate was applied. The total healthcare costs during 12 months from randomization was calculated for each patient, as well as the sums of initial treatment costs and costs during follow-up. An incremental cost-effectivness ratio was calculated with regard to treatment failure.
Table 1.

Background data for the health economic analysis

 

Costs (€)

In-hospital stay

654/day

Outpatent visit

396

Inpatient rehabilitation

434/day

Balloon dilatation with Rigiflex® including fluoroscopy

523

Charge per minute at operating theatre

20.70/min

Nonreusable material during laparoscopic myotomy

489

Charge per hour at postoperative recovery ward

40.00/h

Upper gastrointestinal endoscopy

358

Upper gastrointestinal endoscopy with dilatation

523

Additional charge for endoscopic procedure under general anesthesia

999

Intensive care

2991/day

24-h pH measurement

175

Esophageal manometry

347

Chest X-ray

60

Esophageal swallowing study

228

Chest computerized tomography

469

Abdominal computerized tomography

508

Abdominal ultrasound

182

Initial treatment costs included all costs from randomization into the trial to discharge from the hospital after cessation of the initial treatment, i.e., after the patient had his/her initial one or two dilatations within 10 days or laparoscopic myotomy. These costs included costs for the initial treatment, for endoscopic procedures with additional charge if endoscopy was performed under general anaesthesia, for in-hospital stay, for outpatient visits including the emergency ward, and for X-ray examinations.

Follow-up costs included all costs from the time of discharge from the hospital after cessation of the initial treatment until 12 months from randomization. These costs included costs for alternative treatment because of treatment failure, for endoscopic procedures with additional charge if endoscopy was performed under general anaesthesia, for in-hospital stay, for outpatient visits including the emergency ward, and for X-ray examinations.

Total costs included all costs for healthcare consumption during 12 month from randomization, i.e., the sum of the intitial costs and the follow-up costs. Examinations (X-ray, esophageal physiologic studies) and outpatient visits made for study purposes only were not taken into account.

Threshold analyses were conducted with regard to the cost of one pneumatic dilatation and the cost of the laparoscopic myotomy. The purpose of these analyses was to see how much the cost for one pneumatic dilatation and laparoscopic myotomy could be changed with a remaining difference in total lifetime cost.

Randomization

The study was a prospective randomized multicenter trial where randomization was performed in a 1:1 fashion by a computer-based algorithm stratifying for age, gende, and previous medical treatment by a so-called minimization technique. A study nurse at Sahlgren’s hospital, Gothenburg, Sweden, conducted the randomization centrally.

Statistics and ethics

A sample size of 70 patients in each treatment arm was calculated from 30% difference in dysphagia score with a power of 80% at a 0.05 significant level. An interim analysis was planned after 50 evaluable patients. After this analysis the inclusion was stopped.

All analysis was performed according to an ITT approach and accordingly patients remained in their initial treatment group for all analyses throughout the study. Patients lost to follow-up were given the highest rank in significance testing regarding costs and in failure analysis given an outcome that diminished the difference between treatment groups. Data are presented as mean and median values to which ranges are added and p < 0.05 was considered significant. Comparison between groups for categorical variables was made by chi-squared and Fisher’s exact tests as appropriate. For comparison of numerical and ordered categorical variables, a Mann-Whitney test was used. Statistical analyses of the data were done using the Statistica-99 software package (Statsoft Inc., Tulsa, OK)

The study was performed according to the declaration of Helsinki and had been approved by the local ethics committee. Informed consent was obtained from each participating patient before inclusion into the trial.

Results

In total 51 patients were randomized, of whom 26 were allocated to pneumatic dilatation. Eighteen of these had one dilatation as the primary treatment and the remaining eight required two initial treatment sessions. One patient underwent one dilatation session but thereafter refused further contacts and consequently was lost to follow-up. We noticed two perforations after dilatation; one was initially treated conservatively and the other had an immediate operation, whereupon the perforation was repaired and a myotomy was completed together with a partial fundoplication. Twenty-five patients had a laparoscopic operation without any conversion. No major complications were noted in these patients.

In the dilatation group six patients (23%), including the patient who was operated on for perforation, were classified as failures during the first 12 months of follow-up compared with one (4%) in the myotomy group (p = 0.047). Five patients of those classified as failure in the dilatation group subsequently had a surgical myotomy and one was treated with repeated dilatations. The patient classified as failure in the myotomy group was treated with endoscopic dilatation.

Quality of life, as assessed by use of PGWB, revealed a significant improvement and normalization in the total score as a response to dilatation and to surgical myotomy (84 ± 20 to 101 ± 16 and 92 ± 20 to 105 ± 18, respectively). The pre- and post-treatment GSRS scores in respective groups revealed a significant improvement in dysphagia (p = 0.002, p = 0.003) by either therapy, but again with no significant difference between the groups.

The median number of in-hospital days was 0 (range = 0–43) for the dilatation group and 3 (range = 2–21) for the surgical myotomy group (p = 0.023).

The results of the cost assessments are summarized in Table 2. The initial treatment cost and the total costs were significantly higher for those who had laparoscopic myotomy compared with those who underwent a pneumatic dilatation-based strategy (p = 0.0002 and p = 0.0019, respectively). The difference in initial treatment cost was caused by higher costs for the therapeutic procedure and for the in-hospital stay. There was no statistically significant difference in costs for interventional procedures during the year of follow-up. When the total costs were subdivided into the different resources used during 12 months (Table 3), we found that the single largest cost item for pneumatic dilatation was that for hospital stay and that for laparoscopic myotomy was the actual operative treatment (operating room time). It can also be noted that the costs for the subsequent follow-up after initiation of respective therapeutic strategy did not differ.
Table 2.

Direct medical costs during the first year after randomization to either pneumatic dilatation or surgical myotomya

 

Dilatation (n = 26)

Myotomy (n = 25)

p value

Total costs (€)

6713/1969 (523–67,119)

8488/7545 (5325–30,696)

0.0019

Initial treatment costs (€)

2969/1046 (523–18,535)

7270/7310 (5160–11,081)

0.0002

Follow-up costs (€)

3738/399 (0–4888)

1218/399 (0–19,615)

0.80

a Values are mean/median and range in parenthesis

Table 3.

Total costs divided into used resourcesa

 

Dilatation

Myotomy

(n = 26)

(n = 25)

Primary treatment (€)

839/523 (523–5288)

4781/4893 (3554–6056)

Failure treatment (€)

969/0 (0–5368)

21/0 (0–523)

In-hospital stay (€)

2617/0 (0–28,127)

2721/1962 (1308–13,737)

Out patient visits (€)

352/0 (0–1598)

268/399 (0–1198)

Other endoscopic procedures (€)

72/0 (0–358)

85/0 (0–523)

Additional costs for endoscopic procedure under general anesthesia (€)

651/0 (0–4997)

0/0 (0–0)

Rehablitation care (€)

434/0 (0–10,851)

0/0 (0–0)

Radiology and esophageal manomety/pH metry (€)

148/0 (0–2984)

125/0 (0–3136)

Other costs (€)

648/0 (0–17,036)

486/0 (0–7472)

Total lifetime cost (SEK)

6713/1969 (523–67,119)

8488/7545 (5325–30,696)

a Values are mean/median and range in parenthesis

The cost-effectiveness analysis, relating to the actual treatment failures, revealed that the cost to avoid one treatment failure (incremental cost-effectiveness ratio) amounted to €9239. A threshold analysis focusing on the cost of the actual surgical procedure showed that a statistically significant difference in total costs remained in favor of the pneumatic dilatation strategy as long as the cost of the surgical procedure was 15% or more of the actual cost. In analogy, charges for the one pneumatic dilatation could be increased to €2600 (500% of actual cost) with an unchanged difference. If the costs were less than 5% of the actual cost for laparoscopic myotomy, there would be a statistically significant difference in favor of the myotomy strategy regarding total cost.

Discussion

The present results represent the first comparative health economic analysis with respect to the management of newly diagnosed achalasia that has been carried out within the framework of a randomized clinical trial protocol [1820]. Under these circumstances costs have been captured at the time when they occur in the treatment of each patient. No doubt laparoscopic myotomy is the most effective therapy when it comes to the prevention of treatment failures. However, this result is reached at a comparatively high cost, which is exemplified by the substantially larger initial cost and total cost. The results are interesting and are also somewhat expected based on recent data from a neighboring clinical research field, i.e., gastroesophageal reflux disease. Despite a somewhat smoother postoperative course after a laparoscopic operation, it has been found to be notoriously difficult to show a competitive cost-efficacy profile compared to an open procedure [21]. This is mainly because of the higher costs associated with the actual laparoscopic procedure in the form of longer operating time, costly equipment, and disposable instruments. Moreover, a head-to-head comparison between proton pump inhibitor (PPI) therapy and open antireflux surgery [22] has again emphasized the short-term advantage of medical treatment primarily due to the overwhelming cost burden inflicted by the actual operation.

The question then arises: What are the eventual advantages of the surgical strategy? Because of the rarity of achalasia, we chose to restrict the operating surgeons to those with not only experience in upper GI laparoscopic operations in general but also those from cardiomyotomy in particular. One of the consequences of such a strategy is that the pre- and postoperative courses in each patient might well have been somewhat more favorable than if newly diagnosed cases were treated in less specialized units. Because the second costly item in both strategies was that incurred by postoperative in-hospital care, it can be argued that the initial cost differences recorded in the present study might in fact be biased even more in favor of laparoscopic surgery. Furthermore, it has to be recalled that 5 of our 26 patients, allocated to forceful dilatation, had the procedure completed under general anesthesia, which may inaccurately increase the cost of that treatment. No doubt a substantial proportion of these dilatations can be done in conscious patients under sedation. The reasoning behind the flexibility of our protocol on this point was we wanted to mimic the clinical situation under which these patients are usually managed.

Another interesting part of the current health economic analysis was that the costs associated with the “corrections” of treatment failure had very little impact on the total cost profile, again speaking in favor of the pneumatic dilatation-based strategy. In fact, five of the six treatment failures subsequently underwent a laparoscopic operation, the cost of which were included in the calculations. The cost-effectiveness analysis revealed that the cost to avoid one treatment failure (incremental cost-effectiveness ratio) amounted to €9239, a figure that is considered comparatively high [2325].

When it comes to a direct comparison of medical costs, the relative cost of the operation and dilatation procedure have a paramount impact on the final outcome. It follows from this basic information that the results of a comparison will vary from one country to another and most likely also from one time period to another. The latter aspect has also to be incorporated into the extrapolation of the current one-year follow-up data. We assume for the sake of argument that the annual incidence of treatment failures during respective therapy is constant, i.e., 20% in the dilatation strategy and 4% after allocation to surgical myotomy at the time of the initial diagnosis of achalasia. We introduce a yearly discount rate of 5% and add into the equation that each patient is offered a myotomy in case of failure after dilatation and that eventual failures after surgery are dilated. We then come to the following costs: After three years the cumulative direct medical costs amount €9529 and €9400 when the surgical strategy is followed. Thus, it could be argued that a break-even point is reached after that time period. Again, this is another example of an office-computer-based analysis with many inherent uncertainties [2628]. It must be noted that the long-term outcome of the surgery has to be better clarified in well-designed randomized clinical trials [29, 30]. With our baseline data on the socioeconomic structure of the study population, it can be concluded that the majority of the patients were in the working force. This contrasts with the situation in a study of GERD patients randomized either to PPI therapy or antireflux surgery [22], where a much larger proportion were either retired, on sick leave, or had a disability pension. The consequences of the structure of our study population are therefore that the indirect medical costs would further burden the cost profile of the surgical strategy.

A general problem in health economic evaluations is the uncertainty inherent in cost estimates. One problem with this study is that the cost estimates cannot accurately be separated from charges. However, the sensitivity analysis revealed that even larger changes in the cost estimates did not alter the sign of the recorded differences.

Moreover, it is always questionable which time period should be used for a strict comparison of treatment strategies for a defined disease. It is well known that individual decision makers sometimes take a rather limited time horizon into account. From a societal point of view it may be more significant to cover a limited time period. The main reason for this is that the available healthcare technologies and to the associated costs are prone to change.

It can therefore be concluded from the current prospective controlled clinical trial that despite the higher level of clinical efficacy of laparoscopic myotomy to prevent treatment failure in newly diagnosed achalasia, the cost effectiveness of pneumatic dilatation is superior, at least when a reasonable time horizon is applied.

Copyright information

© Springer Science+Business Media, LLC 2007