A kidney transplant gives patients with end-stage kidney disease a clear survival benefit compared with patients who remain on dialysis (1, 2). Kidney transplantation improves both the length and the quality of life. Kidneys for transplantation may be obtained from both deceased and living donors. The number of patients developing kidney failure continues to increase, whereas the supply of organs from deceased donors has been stagnant for many years (3).
Living-donor transplantation provides an alternative supply of kidneys. In fact, kidneys transplanted from living donors are more likely to function immediately and have a longer organ life expectancy than those transplanted from deceased donors (4). The major disadvantage of using living donors is that a healthy patient must undergo a major surgical procedure in the form of open living-donor nephrectomy (LLDN). Live-donor nephrectomy should be performed under optimal conditions with minimal risk and discomfort to the donor. Although the open LLDN is considered to be a safe procedure with mortality in the range of 0.03% (5), donors suffer significant morbidity with acute and chronic wound pain, wound infection, prolonged hospital stay, late return to full activity, and risk of incisional hernia (6).
Laparoscopic LLDN has been introduced as an alternative to open LLDN to reduce postoperative pain and discomfort in the convalescence period. With a laparoscopic approach, the donor avoids the traditional flank incision (with extensive muscular tissue trauma, and close proximity to intercostal nerves), and may have a shorter postoperative recovery period (7). Other things equal, less surgery-related discomfort and pain would potentially increase the organ donor rates (8, 9).
In addition to shorter hospital stays, the duration of sick leave, amount of postoperative pain, and need for narcotic analgesics are reported to decrease with the laparoscopic approach (10–12). However, there is a potential trade-off in cost. Laparoscopic procedures generally last longer than the corresponding open procedures, resulting in greater use of costly operating room resources. Further, laparoscopic procedures require a number of disposable surgical instruments that are not needed during the open one (13, 14). Such differences, however, may or may not be offset by potential cost savings from shorter hospital stays and more rapid return to productive work (6).
Several studies have compared these two methods. Most studies report better clinical outcomes (e.g., shorter convalescence, less postoperative pain) with laparoscopic LLDN than with open LLDN (8, 10, 11, 15). Some studies, however, indicate that the two methods are equivalent in health-related quality of life (16–18). Furthermore, some studies conclude that patients undergoing laparoscopic nephrectomy experience substantially higher quality of life (13, 19). There are few studies on costs, especially with respect to the comparison of cost and outcomes of these two methods. Overall, the nonrandomized studies conclude that the laparoscopic technique is associated with longer operating time and higher cost of surgical equipment and personnel (13, 7, 12, 14).
In the largest trial ever, Andersen et al. (20, 21) and Øyen et al. (22), investigated objective and patient-reported outcomes among donors undergoing laparoscopic versus open approach during the period 2001 to 2004. The “endpoints” of our study were postoperative pain, narcotic analgesic requirement, complications and safety of kidney donation, and quantitative measurement of quality of life by means of the short form (SF)-36 instrument.
In addition to patient-related outcomes, cost may be an important factor in the choice of technology (23). Because there is uncertainty regarding the health benefits to the donor and the potential for increased costs to society and the health care system, it was of great interest to perform cost utility analysis as a continuation of the previous study in our hospital. The aim of this study was to measure the differences in costs between open and laparoscopic nephrectomy, and to compare this difference with patient outcomes and quality-adjusted life years (QALYs).
PATIENTS AND METHODS
We conducted an economic evaluation based on a randomized clinical trial of living-kidney donation (20–22) in a single national center. The study was carried out from February 2001 to May 2004.
A total of 122 living kidney donors were randomized for this study: 63 laparoscopic and 59 open. Donors with a single, left renal artery, and who intended to donate the left kidney were considered eligible for study. All 122 donors underwent surgery according to the randomization, without any selection regarding body mass index, fat distribution, or age (22). The last 46 laparoscopic procedures were completed using a modified/partial hand-assisted technique, and only during the final harvesting stage and without hand-port (22).
Sociodemographic variables, including age, gender, occupation, and relation to the recipient, were obtained from the patients’ medical records, which have been published previously (20–22).
The length of stay in hospital was counted in whole days from the day of donation to the day of discharge. Hospitalization costs were estimated by multiplying the mean length of patient stay in hospital by the average cost of 1 day of hospitalization.
The costs of surgeons, operating room nurses, and anesthetic services were estimated by multiplying the relevant Norwegian wage rates for each group by the number of hours (as extracted from the medical records), and the number of personnel involved in each operation.
The costs of the disposable instruments were derived from the specific price lists of instruments used for each technique in our hospital’s operating rooms.
The amount of postoperative analgesic required on the day of surgery and the first two postoperative days was obtained from medical records. The total analgesic cost was calculated by multiplying the mean analgesic requirement for each technique by the unit price according to the Norwegian drug catalog (based on Felleskatalogen, www.felleskatalogen.no).
Information on perioperative incidents, postoperative complications, and reoperations was taken from the patients’ medical records. The cost of a serious perioperative complication was calculated for each individual donor. Reoperation personnel cost was calculated as described above. Blood transfusions cost was based on the number of blood units and the unit cost (U.S. $198 per saline-adenine-glucose–blood unit). The intensive care unit (ICU) cost was estimated by multiplying the total number of days spent in the ICU by the average cost of an ICU day as estimated from the hospital accounting system. The cost estimates for physiotherapy were time based. The costs of diagnostic procedures were estimated from the price lists of diagnostic procedures at the radiology department (Rikshospitalet, 2003). Data on the use of other pharmaceuticals were extracted from the patients’ records, and the costs were calculated on the basis of current drug prices (Felleskatalogen).
Data on sick leave were collected by telephone interviews approximately 1 year after the donation (20). Production losses (indirect costs) were estimated by multiplying the number of weeks of sick leave by the national average weekly wage rate including holiday pay and the employers’ pension contributions.
To quantify other economic losses from the donation, a questionnaire was mailed to patients 12 months postoperatively. The donors were asked to estimate their economic losses in hired home work (babysitter and housework, etc.), transportation costs, and patient copayments for health care.
One patient who was converted from laparoscopic to open surgery was classified as laparoscopic according to the intention-to-treat principle (20). Because there were no significant differences in the length of hospitalization between the two groups, running costs and administrative costs were not included. Because of the retrospective collection of cost data, the outpatient follow-up cost and the clinical cost after transfer to other hospitals were excluded. All costs were expressed in 2003 Norwegian Kroner and converted into US$ ($1.00≈NOK 6.50).
Quality of Life
QALY is a common measure of health benefit in economic evaluation. Here, quality of life is measured on a 0 to 1 scale, where death is equal to zero and perfect health is equal to 1. To obtain the values, we used the SF-36 data as collected by Andersen et al. (21). The SF-36 questionnaires were completed on admission 1 to 2 days before surgery, and were sent to the donors by mail at 1, 6, and 12 months after donation. The timing of data collection was based on the expected profiles of recovery from surgery (22). The SF-36 has been found to be sensitive when used to compare open and laparoscopic LLDN (15, 16).
Although SF-36 scores provide an excellent means for judging the effectiveness of health care interventions, they have only a limited value in economic evaluation because they are not based on preferences. Consequently, the SF-36 scores (range from 0 to 100) were converted into a specific SF-6D single index, and this index was translated into 0 to 1 scale by means of an algorithm developed by Brazier et al.(24, 25).
A QALY is a composite health benefit measure that captures effects in both quality of life (utility) and duration of the health state (26). Therefore, the time-integrated summary score, the area under the curve of the utilities, was calculated to define the quality of life per period, based on the assumption that utilities followed a linear course over time between the assessments (27).
Cost Utility Analysis and Sensitivity Analysis
To quantify the differences in cost and health outcome between the surgical approaches, we conducted a cost utility analysis. This is a special form of cost effectiveness analysis that evaluates incremental costs and effects of an intervention by measuring health outcomes in QALYs (26). The main outcome of a cost utility analysis is the cost per QALY gained. This ratio expresses the difference in (incremental or marginal) health benefits (expressed in QALYs) from one therapy to another divided by the difference in costs between therapies.
To explore the uncertainty of the costs and outcomes, we used one-way sensitivity analyses. Each parameter estimate (the so-called base case value) was varied, individually, within reasonable bounds to investigate the impact on costs or QALYs.
We used the SPSS statistical package version 13.0 (SPSS, Chicago, IL) for all statistical analyses. We used unpaired t test to compare groups with respect to continuous variables and Fisher’s exact test for categorical variables. Values of P less than 0.05 were considered to be significant.
The randomization was successful in that the two patient groups were similar regarding age, gender, relation to recipient, body mass index, and employment situation (Table 1).
Intraoperative and Postoperative Clinical Outcomes
For procedures performed laparoscopically, gross anesthesia time (285 vs. 228 min; P<0.05) and operative time (180 vs. 140 min; P<0.05) were longer than with open surgery (Table 2, Supplemental Table 1). The use of opioid analgesics was different on the day of surgery (13.1 vs. 17.8 mg; P=0.010).
In the laparoscopic donor group, seven major postoperative complications (11%) resulted in reoperations and one patient in the laparoscopic group required conversion to the open technique. These included the following: bleeding from a port site (n=1), a forgotten sponge through an infraumbilical incision (n=1), incarceration of bowel in a port site (n=1), intestinal perforation (n=2) of which one required more than 2 weeks observation in the ICU before recovering, and in the long term, incisional/port hernias (n=2). There was no reoperations in the open surgery group (P<0.05) (Fig. 1).
The length of postoperative hospital stay was similar in the two groups (6.2 vs. 6.7 days). The resumption of employment was more rapid in the laparoscopic group than the open surgery group (7.1 vs. 9.5 weeks; P=0.010). Complete description of preoperative and postoperative clinical outcomes has been published previously (20–22).
The mean operating room cost (personnel cost; see Table, Supplemental Digital Content 1,http://links.lww.com/A901, and disposable instruments cost; see Table, Supplemental Digital Content 2, http://links.lww.com/A902) was 72% less in the open surgery group than in the laparoscopic group ($3,471 vs. $962; P<0.05) (Table 4). This difference appears to reflect longer operating and anesthesia time (see Table, Supplemental Digital Content 3,http://links.lww.com/A903) and the extra equipment required for laparoscopic surgery. Disposable supplies accounted for 79% of the operating room cost for laparoscopy compared with 38% for open surgery (see Table, Supplemental Digital Content 2,http://links.lww.com/A902).
Postoperative analgesic cost was similar in laparoscopic and open surgery groups ($96 vs. $120) (Table 4, see Table, Supplemental Digital Content 4,http://links.lww.com/A904).
Because average length of stay was similar in two groups, there was no substantial difference in the mean hospitalization cost between the two groups ($6734 vs. $7277).
The mean cost of complications in the laparoscopic group was greater than for the open surgery group ($33,162 vs. $4573; P<0.05). The most striking difference was the cost attributed to intensive care (for one of the patients with intestinal perforation). Contributing most to complication costs in the laparoscopic group were intensive care cost (45% of all complication costs), rehospitalization (23%), and diagnostic cost (18%); whereas in the open surgery group, rehospitalization (79%) constituted the dominant complication-related cost (see Table, Supplemental Digital Content 5,http://links.lww.com/A905).
Because the open surgery patients returned to work later, the production loss (indirect cost) during their convalescence was 40% greater ($14,062 vs. $10,032). Other economic costs (such as patient co-payment, hired home work, and transport) during 1 year were 61% greater in the open surgery group ($1797 vs. $2892). Hired home work cost was the major cost in both groups. The majority of this disparity reflected more pain after donation and longer sick leave in the open surgery group (Table 3).
The mean total cost was $55,292 vs. $29,886, respectively, for laparoscopic and open surgery group, with a mean difference of $25,406. Complications cost and production loss (indirect cost) were the main elements of the total cost (Table 4).
Quality of Life
The health utility scores (SF-6D utility) generally favored the laparoscopic group but the differences were small and not statistically significant throughout the evaluation period (Table 5). The scores improved from 1 to 6 months after donation in both groups. At 12 months, both groups had a mean SF-6D score at almost the same level as at baseline.
The mean number of QALYs was 0.780 and 0.765 in the laparoscopic and open surgery group, respectively. This results in a mean QALY gain of 0.015 in favor of laparoscopy.
Cost Utility Analysis and Sensitivity Analysis
The additional cost of laparoscopic surgery was $25,406 per patient with 0.015 additional QALYs, implying a cost per QALY of $1,693,733 after 12 months of follow-up.
In the one-way sensitivity analyses, the cost of the major complications and reoperation in the laparoscopic group had the greatest impact on the incremental cost. If the cost of major complications from laparoscopic procedure had been avoided, the mean cost per patient would have been $27,788 and laparoscopy would have been the dominant strategy (lower costs, greater benefits). In contrast, higher rates of major complications and reoperations in the laparoscopic group would result in the highest incremental cost per QALY ($2,766,800). Finally, the magnitude of QALY gain had a major impact on the cost effectiveness ratio. For the remaining parameters, realistic changes in values made little differences to the results (Table 6).
In this study, as in other similar studies, we have documented considerable advantages of the laparoscopic approach for live donor nephrectomy with regard to convalescence and postoperative pain. Laparoscopic donors required less pain medication and returned to activity and work sooner. This has resulted in lower indirect costs (lower wage loss) and a lower financial burden to the laparoscopic donors. However, longer operating time and more costly disposable consumables resulted in greater operating room cost for the laparoscopic group. This is broadly consistent with findings of other studies (13, 7, 12, 14, 28). The length of hospital stay was similar for both groups in this study and reflects the current practices in Europe, where early discharge is not a prioritized issue (14, 28–31). It should be noted that in Norway, living donors have been offered a generous length of stay irrespective of whether they have been subjected to laparoscopic or open procedure, and the small difference in hospital stay evidently reflects this policy. The postoperative recovery is much faster after laparoscopic procedure, and donors may be discharged within 24 hr of surgery; the United States, in particular, uses an early discharge policy (28). Thus, our study may overstate the direct cost differential between the two procedures by not capturing the potential for reduced costs for laparoscopic LLDN with regard to length of hospital stay.
From a societal perspective, the production loss was higher in the open surgery group. It seems plausible that the laparoscopic approach affords a quicker return to work compared with the traditional approach. Several studies have reported similar results (10, 12, 15, 19, 29, 30), however, our patients, both in the laparoscopic and the open group, had a longer duration of sick leave than what has been reported in international studies. In principle, the Norwegian social security system covers the donor’s expenses and income loss during sick leave so the incentive to resume work early may be less than in countries with less generous social welfare systems.
In this study, the greatest cost difference was attributable to complications (U.S. $33,162 vs. U.S. $4573). The rate of major laparoscopic complications was relatively high in our study and had a significant impact on donors’ quality of life (21) and the cost of kidney donation. In other laparoscopic series, the major postoperative complications rate has ranged from 1% to 17% (22). Kasiske et al., (32) who summarized several single-center studies on living-donor kidney transplantation, reported a mean overall complication rate of 32% and a major complication rate of 4.4%. Obese donors were overrepresented among our major laparoscopic complications. Furthermore, in the sensitivity analyses, we excluded the patient who had a prolonged ICU stay. This exclusion brought the cost per QALY down to $337,800 (Table 6).
The observation of more complications in the laparoscopy group suggests an important question: when new methods are introduced, at what point should randomized trials be performed? An advanced laparoscopic procedure such as laparoscopic nephrectomy is known to have a steep and difficult learning curve-surgical excellence is achieved only after a considerable number of operations. In the present study, the randomized trial was started approximately 1 year after the introduction of laparoscopic kidney harvesting to be able to assign patients to both groups. At that time, we were still in the learning phase for the method; it is possible that the number of complications could have been lower at a later stage. Furthermore, in this study only two surgeons performed the laparoscopic nephrectomies, one with extensive laparoscopic experience and one with somewhat less experience. Thus, the high rate of major complications might be attributed to the surgeons’ experience/“learning curve stage,” rather than to the surgical technique per se.
After the randomized study was undertaken, we introduced hand-assistance (with hand-port) during the whole laparoscopic procedure to increase donor safety and reduce the risk of intraperitoneal complications. We have also used the retroperitoneal approach. Subsequently, there have been no major complications in the laparoscopic group (data not shown; presented at ESOT, Prague, 2007). It should be kept in mind that the laparoscopic procedure is still evolving with respect to technique and equipment.
Over 1 year of follow-up, the mean number of QALYs was greater in the laparoscopic group. It should be noted, however, that this mean gain (0.015) is based on differences in life quality that were not statistically significant. In health economic evaluation, it is a common practice to account for nonsignificant differences. Our mean effect is similar to other comparisons of laparoscopic and open surgery (33, 34). By using the Euroqol-5D (EQ-5D) instrument, Kok et al. (29) showed in their randomized study a mean gain of 0.03 QALYs. Pace et al. (13) reported an even greater difference of 0.06 QALYs using the time trade-off technique. The difference of 0.015 QALYs in our study is smaller than the two previous studies, which may be explained by the great occurrence of complications in our laparoscopic group. The difference of 0.06 QALYs found by Pace et al. (13) are based on a nonrandomized study. Kok et al. (29) used EQ-5D, which is a less sensitive instrument to measure quality of life than the SF-6D. In addition, they did not include data on the learning curve of laparoscopic series. Consequently, the number of significant postoperative complications was small in their study (29).
To our knowledge, this is the largest randomized cost effectiveness study comparing laparoscopic and open-donor surgery during 1 year follow-up. Still, the results need to be interpreted with caution. Two slightly different laparoscopic techniques were used during the trial. However, the infraumbilical incision and extent of dissection inside the abdominal cavity was the same. We, therefore, consider that the impact on the donors was similar (20–22), also with respect to costs. Cost data were collected retrospectively, however, and this may introduce inaccuracies (e.g., the lack of data after discharge from hospital may introduce some bias). Also, the level of experience may limit the generalizability of our results. For obvious reasons, neither patients nor surgeons were blinded, and preferences for type of procedure may influence the results.
Finally, we sought to address issues only as they pertain to donors. There is no evidence in literature that the costs and outcomes for the renal transplant recipient patients will differ depending on the method of kidney removal (13).
It is well established that living-donor renal transplantation is more cost effective than dialysis for the treatment of renal failure. Our study adds to this knowledge by exploring the choice of surgical procedure for kidney donation. The results indicate that the laparoscopic technique may be cost effective depending, in particular, on the rate of complications. Lower complication rates for the laparoscopic technique may result in cost savings and better patient outcomes.
The authors thank Esther-Cecilie Frydenlund, Heidi Garberg Gule, Karl Sæbjørn Kjellesdal, Trond Aag, and Trude Andreassen for allowing access to data.
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