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Keywords:

  • centralized care;
  • cost-effectiveness;
  • ovarian cancer;
  • quality-adjusted life years

Abstract

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgements
  7. REFERENCES

BACKGROUND.

The objective of this study was to evaluate the cost-effectiveness of centralized referral of patients with advanced-stage epithelial ovarian cancer who underwent primary cytoreductive surgery and adjuvant chemotherapy.

METHODS.

A decision-analysis model was used to compare 2 referral strategies for patients with advanced-stage ovarian cancer: 1) referral to an expert center, with a rate of optimal primary cytoreduction of 75% and utilization of combined intraperitoneal and intravenous adjuvant chemotherapy, and 2) referral to a less experienced center, with a rate of optimal primary cytoreduction of 25% and adjuvant treatment that consisted predominantly of intravenous chemotherapy alone. The cost-effectiveness of each strategy was evaluated from the perspective of society.

RESULTS.

A cost-effectiveness analysis revealed that the strategy of expert center referral had an overall cost per patient of $50,652 and had an effectiveness of 5.12 quality-adjusted life years (QALYs). The strategy of referral to a less experienced center carried an overall cost of $39,957 and had an effectiveness of 2.33 QALYs. The expert center strategy was associated with an additional 2.78 QALYs at an incremental cost of $10,695 but was more cost-effective, with a cost-effective ratio of $9893 per QALY compared with $17,149 per QALY for the less experienced center referral strategy. Sensitivity analyses and a Monte Carlo simulation confirmed the robustness of the model.

CONCLUSIONS.

According to results from the decision-analysis model, centralized referral of patients with ovarian cancer to an expert center was a cost-effective healthcare strategy and represents a paradigm for quality cancer care, delivering superior patient outcomes at an economically affordable cost. Increased efforts to align current patterns of care with a universal strategy of centralized expert referral are warranted. Cancer 2007. © 2007 American Cancer Society.

Worldwide, 204,449 women are newly diagnosed with ovarian cancer each year, and there are an estimated 124,860 disease-related deaths.1 Approximately 65% of patients will be diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage III (T3N0/N1M0) or stage IV (any T, any N, M1) disease.2 For this group, the most important clinician-driven prognostic factors are the extent of residual disease after primary cytoreductive surgery and the administration of adjuvant platinum-based chemotherapy.3, 4 The association between initial surgical care by a gynecologic oncologist and a higher likelihood of optimal primary cytoreductive surgery, close adherence to recommended chemotherapy treatment guidelines, and resultant superior clinical outcomes has been well documented.5–10

In addition to subspecialty surgical care, recent attention has focused on centralized referral of patients with ovarian cancer to high-volume expert centers that offer a multidisciplinary expertise to the global treatment program.5, 9, 11, 12 However, to date, the clinical benefits and associated costs of centralized care have not been quantified precisely. With current concerns over the escalating economic burden of healthcare and a concomitant desire to optimize clinical outcomes, such information would be of value to public policy and healthcare administrators as well as third-party payers. Therefore, the objective of the current study was to simulate the projected clinical benefits and economic costs associated with referral to an expert center with a high rate of optimal primary surgical cytoreduction and utilization of intraperitoneal (IP) chemotherapy measured against referral to a less experienced center with a comparably low rate of optimal surgical resection and treatment with intravenous (IV) chemotherapy alone in the majority of patients.

MATERIALS AND METHODS

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgements
  7. REFERENCES

Overall Model

A decision-analysis model was created to evaluate 2 management strategies for patients with advanced-stage epithelial ovarian cancer from primary cytoreductive surgery through completion of front-line chemotherapy (Fig. 1). The 2 strategies were: 1) referral to an expert center, with achievement of optimal residual disease (≤1 cm) in 75% of patients and administration of initial chemotherapy using a combination of IP cisplatin and IP and IV paclitaxel (IP/IV) in the majority (80%) of optimally cytoreduced patients, and 2) referral to a less experienced center, with a 25% rate of optimal primary cytoreduction and with adjuvant chemotherapy consisting predominantly (90%) of IV carboplatin and IV paclitaxel (IV/IV). Within each strategy, it was assumed that patients had undergone an attempt at maximal cytoreductive surgery followed by a planned 6 cycles of chemotherapy. For patients who underwent optimal cytoreductive surgery, chemotherapy could consist of either the IP/IV regimen or the IV/IV regimen. For patients who were left with suboptimal residual disease, chemotherapy consisted of the IV/IV regimen. The model and analyses conformed to the 10 basic principles that should be incorporated into a cost-effectiveness analysis identified by the Panel on Cost-Effectiveness in Health and Medicine convened by the U.S. Public Health Service.13 The model was generated from the perspective of society and incorporated all relevant cost associated with primary management of advanced-stage epithelial ovarian cancer.

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Figure 1. Decision-analysis model for the referral of patients with advanced-stage ovarian cancer to either an expert center or a less experienced center. IP indicates intraperitoneal; IV, intravenous.

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Model Estimates: Clinical Assumptions

Clinical assumptions were obtained from a review of the published English-language literature. Whenever possible, data from Phase III trials was utilized; however, when such data were unavailable, clinical assumptions were generated from Phase II trials, case-control studies, retrospective case series, and expert opinion (Table 1).

Table 1. Model Estimates: Clinical Assumptions
Clinical parameterModel estimate, %Reference(s)
  • IP indicates intraperitoneal; IV, intravenous.

  • *

    Among patients with residual disease that measured ≤1 cm.

  • IP cisplatin plus IP and IV paclitaxel.

  • Survival time was discounted at 3% per year.

  • §

    IV carboplatin plus IV paclitaxel.

Expert center
 Rate of optimal primary cytoreduction756, 14–23
 Rate of complete cytoreduction*5022, 24–28
 Proportion receiving IP/IV chemotherapy*80 
 Operative mortality of primary surgery3 
Less experienced center
 Rate of optimal primary cytoreduction255, 7, 29–34
 Rate of complete cytoreduction*105, 7, 29–34
 Proportion receiving IP/IV chemotherapy*10 
 Operative mortality of primary surgery3 
IP/IV chemotherapy
 Median survival: No gross residual, mo
  Undiscounted113.335
  Discounted84.3 
 Median survival: Residual 0.1–1.0 cm, mo
  Undiscounted52.635
  Discounted46.7 
 Quality of well-being index: Mo 1–50.6635
 Quality of well-being index: Mo 6–120.7135
 Incidence of hospitalization for fever935
 Incidence of hospitalization for infection835
 Incidence of hospitalization for gastrointestinal toxicity1235
 Incidence of hospitalization for metabolic events735
 Incidence of hospitalization for thrombocytopenia335
 Incidence of hospitalization for renal or genitourinary event235
IV/IV chemotherapy§
 Median survival: No gross residual, mo
  Undiscounted78.235
  Discounted65.6 
 Median survival: Residual 0.1–1.0 cm, mo
  Undiscounted39.135
  Discounted35.8 
 Median survival: Residual >1.0 cm, mo
  Undiscounted26.636
  Discounted25.1 
 Quality of well-being index: Mo 1–50.7335
 Quality of well-being index: Mo 6–120.7635
 Incidence of hospitalization for fever335, 36
 Incidence of hospitalization for infection335, 36
 Incidence of hospitalization for gastrointestinal toxicity635
 Incidence of hospitalization for metabolic events2.035
 Incidence of hospitalization for thrombocytopenia1.035
 Incidence of hospitalization for renal or genitourinary event0.535

For the expert center strategy, the rate of optimal primary cytoreduction (residual disease measuring ≤1 cm) was estimated at 75%.6, 14–23 Among the patients who underwent optimal resection, the rate of complete cytoreduction (no gross residual disease) was estimated at 50%.22, 24–28 For patients who received treatment at a less experienced center, the rate of optimal primary cytoreduction was estimated at 25%, and 10% of patients who underwent optimal resection were left with no gross residual disease.5, 7, 29–34 An operative mortality rate of 3% was derived from a review of 200 consecutive patients with ovarian cancer from the Maryland Health Services Cost Review Commission (HSCRC) database who underwent hysterectomy with salpingo-oophorectomy (All Patient Diagnostic-Related Groups [APDRG] 684, 686, 687, and 688) and cytoreduction (APDRG 544) between fiscal years (FY) 2004 and 2006.

Model estimates for the proportion of optimally resected patients who received a contemporary IP/IV chemotherapy regimen were 80% for patients who attended an expert center based on the current utilization rate at The Johns Hopkins Medical Institutions (JHMI), and 10% for patients who attended a less experienced center, based on HSCRC data for the administration of IP chemotherapy for ovarian cancer at non-JHMI hospitals during FY 2006. The treatment completion rate for IP/IV chemotherapy was modeled after the experimental arm of Gynecologic Oncology Group (GOG) protocol 172: 6 cycles (42%), 5 cycles (5%), 4 cycles (5%), 3 cycles (7%), 2 cycles (15%), 1 cycle (19%), and 0 cycles (8%).35 The balance of incomplete IP treatment cycles was substituted with cost estimates for the IV treatment regimen up to a total of 82.9% of patients completing 6 cycles of adjuvant chemotherapy.35 For optimally resected patients who received the IV/IV chemotherapy regimen, the treatment completion rate was modeled after the control arm of GOG protocol 172: 6 cycles (90%), 5 cycles (2%), 4 cycles (2%), 3 cycles (2%), 2 cycles (2%), and 1 cycle (2%).35 The treatment completion rate for patients with suboptimal residual disease who received IV/IV chemotherapy was modeled after GOG protocol 132: 6 cycles (81%), 5 cycles (2%), 4 cycles (5%), 3 cycles (4%), 2 cycles (3%), and 1 cycle (5%).36

Treatment-related complications that were most likely to result in hospitalization were assumed to be fever, infection, gastrointestinal toxicity, metabolic events, renal or genitourinary events, and thrombocytopenia. The frequencies of hospitalization for these events, according to residual disease and treatment regimen, were calculated at 50% of the incidence of grade 3 or 4 fever and infectious morbidity and 25% of the incidence of grade 3 or 4 gastrointestinal toxicity, metabolic events, renal or genitourinary events, and thrombocytopenia in GOG protocols 172 and 132 (Table 1).35, 36

All survival estimates were generated from the actual or projected median survival from Phase III trials of patients with advanced-stage ovarian cancer (GOG protocols 172 and 132) and were incorporated into cost-effectiveness analysis first as undiscounted outcomes and then discounted at a rate of 3% per year according to the estimated median survival for each treatment program (Table 1).27, 28, 35, 36

Quality-of-life adjustments for the toxicity of chemotherapy during the first year of survival were estimated from longitudinal quality-of-life assessments using the Functional Assessment of Cancer Treatment-Oncology (FACT-O) survey in GOG protocol 172.35 Quality-of-life index values were calculated based on a maximum FACT-O score of 156, with quality-adjusted life years (QALYs) adjusted for differences between the IP/IV regimen and the IV/IV regimen during the initial 5-month period and the subsequent 7 months after diagnosis.

Model Estimates: Costs

Model estimates for the costs of care were derived from the Maryland HSCRC database for hospital charges and from the common-use JHMI administrative databases for professional fee charges for patients who underwent initial surgical management and received primary chemotherapy for FIGO stage IIIC and IV ovarian cancer between FY 2004 and FY 2006. All charges were adjusted to 2006 U.S. dollars using the consumer price index, and estimated costs were calculated as 60% of total hospital charges and 40% of professional fees (based on the average ratio of total hospital direct and indirect costs to charges and the average departmental professional fee-collection rate) (Table 2).

Table 2. Model Estimates: Costs
Clinical parameterModel estimate, $
  • IP indicates intraperitoneal; IV, intravenous.

  • *

    Costs based on 40% collection rate for professional fee charges and 60% collection rate for hospital charges.

  • Not all patients completed 6 cycles of specified regimen; incorporates costs of surgery and chemotherapy.

  • Based on an average hourly wage of $16.68 adjusted for a 5-day work week and a 57.5% employment rate.

  • §

    According to the Bureau of Labor Statistics.37, 38

Primary surgery*21,133
Placement of IP catheter and first cycle of IP chemotherapy*6080
Inpatient IP/IV chemotherapy cycle*2860
Outpatient IP/IV chemotherapy cycle*1655
Removal of IP catheter*1957
Outpatient IV/IV chemotherapy cycle*1494
Total cost surgery and IP/IV therapy (treatment received)45,172
Total cost optimal surgery and IV/IV therapy (treatment received)29,633
Total cost suboptimal surgery and IV/IV therapy (treatment received)29,184
Cost of each hospitalization for fever or infection*6830
Cost of each hospitalization for gastrointestinal toxicity*7184
Cost of each hospitalization for metabolic event*6654
Cost of each hospitalization for thrombocytopenia*13,756
Cost of each hospitalization for renal or genitourinary event*14,730
Lost wages8440§
Caregiver support IP/IV chemotherapy1381§
Caregiver support IV/IV chemotherapy1036§
Primary cytoreductive surgery

Direct and indirect hospital charges were obtained for patient services with an International Classification of Disease, 9th Revision, Clinical Modification (ICD-9-CM) code of 183.0 and Common Procedural Terminology (CPT) codes of 58951, 58952, 58953, or 58954. Total hospital charges (mean, $32,889; median, $26,541; range $18,686-85,430) were calculated for the index admission of 40 consecutive patients undergoing primary cytoreductive surgery. The mean total hospital charge was used to generate model cost estimates. Professional fee surgeon charges were estimated as 40% of $3500 ($1400) to approximate the contractual Medicare reimbursement of $1379 for a CPT code of 58951 during FY 2006.

IP chemotherapy regimen

The IP/IV chemotherapy regimen was based on the treatment program reported in GOG protocol 172 and currently in use at the JHMI.35 Each cycle consisted of a 24-hour infusion of paclitaxel on Day 1; an IP infusion of cisplatin in Day 2, which required a 2-day inpatient hospitalization; and IP paclitaxel administered in the ambulatory setting on Day 8. Charges were incorporated for placement of an IP infusion port as a separate procedure (CPT code 44942) and coinciding with the first cycle of chemotherapy (CPT code 99221). Mean hospital and professional fee charges for these procedures were calculated at $9284 and $1275, respectively. For each subsequent treatment cycle, mean inpatient hospital and professional charges were $4584 and $275, respectively, for treatment on Days 1 and 2, whereas the mean ambulatory hospital and professional charges were $2665 and $140, respectively, for treatment on Day 8. Removal of the intraperitoneal catheter on an ambulatory basis was associated with a mean hospital charge of $2261 and a professional charge (CPT code 44942) of $1000. The total cost of surgery and IP/IV chemotherapy based on treatment received, excluding hospitalization for treatment-related toxicity, was $45,172.

IV chemotherapy regimen

The IV/IV chemotherapy treatment regimen consisted of IV carboplatin and IV paclitaxel (as a 3-hour infusion) administered on an ambulatory basis on Day 1 of a 21-day treatment cycle. For this calculation, mean hospital charges were $2396 per treatment cycle. The professional charge associated with each treatment was $140. The total costs of surgery and IV/IV chemotherapy, based on treatment received, excluding hospitalization for treatment-related toxicity, were $29,633 after optimal cytoreduction and $29,184 after suboptimal cytoreduction.

Hospitalization for treatment-related toxicity

All cost estimates for treatment-related toxicity were obtained from a review of the Maryland HSCRC database for patients who were admitted to JHMI during FY 2005 to FY 2006 for neutropenic fever (ICD-9-CM code 288.0) resulting from chemotherapy, gastrointestinal toxicity (ICD-9-CM code 560.81), chemotherapy-related metabolic events (ICD-9-CM code 276.9), and chemotherapy-induced thrombocytopenia (ICD-9-CM code 287.5).

Lost wages and caregiver support

Lost patient wages were calculated based on an average hourly earning of $16.68 and were adjusted for a 5-day work week and an employment-to-population ratio of 57.5%, as reported by the Bureau of Labor Statistics as of April 2006 for female residents of the United States aged ≥20 years.37, 38 Lost wages were estimated for a 6-week period surrounding surgery plus an additional 16 weeks to complete the full treatment program. Caregiver support costs were calculated similarly by using estimates of 2 hours per day during the postoperative recovery period, 14 hours per IP/IV treatment cycle, and 8 hours per IV/IV treatment cycle.

Cost-Effectiveness and Sensitivity Analyses

Cost effectiveness was calculated as the overall cost per patient, in terms of economic impact and effect on quality-adjusted survival time, of implementing each of the 2 strategies. The cost-effectiveness ratio was calculated as the overall cost per QALY associated with each strategy, and the incremental cost-effectiveness ratio was calculated as the additional cost per QALY for the more costly strategy. A series of 1-way sensitivity analyses of each relevant variable across a reasonable range was performed, and a tornado diagram was developed for the entire model. Both cost-effectiveness analyses and 1-way sensitivity analyses were conducted from the perspective of society. Probabilistic sensitivity analysis was performed with Monte Carlo simulation with 10,000 repetitions, and triangular distributions were assumed for all variables. For cost estimates and survival time assumptions, 95% confidence intervals (95% CIs) were used to define variable distributions, whereas baseline values ±25% were used to define the distributions for rates of optimal and complete cytoreductive surgery. All modeling and calculations were performed using a commercially available decision-analysis software program (TreeAge Pro Healthcare module; Treeage Software Inc., Williamston, Mass), and all costs are reported as 2006 U.S. dollars.

RESULTS

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgements
  7. REFERENCES

Cost-Effectiveness Analysis

Cost-effectiveness analysis revealed that the strategy of referral to an expert center had an overall cost per patient of $50,652 and effectiveness of 5.12 QALYs (Table 3). The strategy of referral to a less experienced center carried an overall cost of $39,957 and effectiveness of 2.33 QALYs. The expert center referral strategy was associated with an additional 2.78 QALYs at an incremental cost of $10,695 but was more cost effective, with a cost-effectiveness ratio of $9893 per QALY compared with $17,149 for the less experienced center referral strategy. The incremental cost-effectiveness ratio (ICER) of the more effective option is the ratio of the mean incremental cost and mean incremental effectiveness (in terms of $ per QALY). Expert center referral, which was the more effective strategy, had an ICER of $3809. In other words, each additional QALY gained by referral to an expert center cost $3809. Repeating the cost-effectiveness analysis with survival time discounted at a rate of 3% per year yielded similar findings, with the strategy of expert center referral associated with an incremental gain of 2.11 QALYs at an additional cost of $10,476 per patient (Table 3).

Table 3. Cost-effectiveness Comparison of Expert Center Referral Strategy Versus Less Experienced Center Referral Strategy
StrategyCost, $Incremental cost, $Effectiveness, QALYsIncremental Effectiveness, QALYsC/E, $Incremental C/E, $
  • QALYs indicates quality-adjusted life years; C/E, cost-effective ratio.

  • *

    Survival time discounted at 3% per year.

Undiscounted survival time
 Less experienced center39,957 2.33 17,149 
 Expert center50,65210,6955.122.7898933809
Discounted survival time*
 Less experienced center40,116 2.14 18,746 
 Expert center50,59210,4764.242.1111,9325029

Sensitivity Analyses

The tornado diagram depicted in Figure 2 shows that the variables with the most influence on the cost of the different strategies in the overall model were the cost of IV/IV chemotherapy for optimally and suboptimally resected patients, the cost of IP/IV chemotherapy, and the probability of IP/IV chemotherapy at a less experienced center. The only threshold value was observed for the cost of treatment with IP/IV chemotherapy; at a cost of $28,000, IP/IV chemotherapy and IV/IV chemotherapy would have an equivalent value total cost of $39,000. For a cost of initial treatment <$28,000, the IP/IV chemotherapy strategy would dominate (less costly and more effective) the IV/IV chemotherapy strategy. There were no threshold values for any of the other clinically relevant variables that were evaluated. In other words, for each variable and within the range of values evaluated, the strategy of less experienced center referral had a higher cost-effectiveness ratio (higher cost per QALY) and, thus, was less cost effective than the expert center referral strategy.

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Figure 2. Sensitivity analyses: tornado diagram for the overall model. IV indicates intravenous; chemo, chemotherapy; IP, intraperitoneal; exper., experienced; cytoreduct., cytoreduction; wtp, willingness to pay.

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Monte Carlo simulation with 10,000 repetitions revealed that the expert center referral strategy had a mean cost of $50,638 (95% CI, $40,384-62,100) and mean effectiveness of 5 QALYs (95% CI, 4–7 QALYs). The mean cost of the less experienced center referral strategy was $40,479 (95% CI, $32,343-48,627) with a mean effectiveness of 2 QALYs (95% CI, 2–3 QALYs). A cost-effectiveness scatterplot of the Monte Carlo simulation that displays the individual cost and effectiveness value pairs for each recalculation of the model revealed moderate variability with respect to the cost of each strategy but no overlap with respect to effectiveness (Fig. 3). The expert center strategy consistently was more effective compared with the less experienced center strategy.

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Figure 3. Monte Carlo simulation cost-effectiveness scatterplot of individual cost and effectiveness value pairs for each of 10,000 recalculations of the model. QALY indicates quality-adjusted life years.

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DISCUSSION

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgements
  7. REFERENCES

For women with advanced-stage ovarian cancer, a large body of retrospective and population-based data consistently has shown that gynecologic oncologists are significantly more likely to achieve optimal residual disease compared with other surgical subspecialists and that this disparity in surgical success mirrors subsequent survival outcome.6–8, 10, 39–44 Recently, attention has focused on the potential for improved healthcare outcomes associated with concentration of cancer services in high-volume or expert centers.45 A number of population-based studies have demonstrated conclusively that the surgical expertise and multidisciplinary care provided to patients with ovarian cancer at high-volume or expert centers are associated with superior survival outcomes compared with low-volume centers.5, 9, 11, 12, 42, 46 Accordingly, the Society of Surgical Oncology provided the following guidelines for ovarian cancer surgery: Surgeons who undertake operations for possible ovarian cancer should have both the necessary technical expertise and a thorough understanding of the management of the disease itself; also, the optimal treatment of ovarian cancer disease requires the skillful and appropriate integration of surgery and chemotherapy and is carried out best in centers where an experienced, coordinated multidisciplinary team is available.47

Two contemporary trends in ovarian cancer treatment underscore the importance of concentrating the care of this patient population in centers with the necessary resources and expertise to deliver high-quality services that are consistent with current professional practice standards. First, advances in surgical techniques have been associated with optimal resection rates ≥75% by experienced centers and surgeons.6, 14–23, 48, 49 In addition, an increasingly robust body of data indicates that complete surgical resection with no gross residual disease should be the benchmark of surgical success, with the reported median survival currently ranging from 76 months to 106 months for patients with completely resected, bulky FIGO stage IIIC ovarian cancer.25, 27, 28 The second important development in ovarian cancer care has been a renewed interest in combined IP and IV combination chemotherapy as front-line treatment after optimal resection for patients who have advanced-stage disease that is confined to the abdominal cavity and retroperitoneum.35 In light of these clinical practice trends, the objective of the current study was to estimate the projected clinical benefits and economic costs associated with referral of such patients to an expert center compared with their referral to a less experienced center.

The clinical assumptions in the current decision-analysis model were derived with the intent of representing the polar extremes along the continuum of primary treatment for patients with advanced-stage ovarian cancer. Nevertheless, the comparison of referral strategies to either an expert center or a less experienced center accurately reflects current disparities in clinical practice with respect to the degree of primary cytoreductive surgical success and implementation of contemporary chemotherapy treatment programs. Under these assumptions, the expert center referral strategy was associated with an additional 2.78 QALYs at an incremental cost of $10,695 but was more cost effective, with a cost-effectiveness ratio of $9893 per QALY compared with $17,149 per QALY for referral to a less experienced center. The robustness of the model was confirmed by a series of 1-way sensitivity analyses and probabilistic sensitivity analysis. It is noteworthy that, within the expert center referral strategy, the variables with the strongest influence on cost were the cost of IP/IV chemotherapy and the probability of administering IP/IV chemotherapy in optimally resected patients, suggesting that development of an equally efficacious IP/IV regimen that could be administered on an ambulatory basis and, thus, at reduced cost, could yield an even more favorable cost-effectiveness ratio for the strategy of centralized expert referral.

Like with any cost-effectiveness analysis of this nature, there are a number of limitations that must be considered in interpreting the results. First, the hypothetical nature of the model requires a series of assumptions regarding the probability of specific clinical outcomes and practice patterns. Although some centers certainly have rates of optimal primary cytoreductive surgery that lie somewhere in between those of expert centers and less experienced centers, the model estimates do reflect the finding that contemporary reports show a wide disparity in surgical success rates. In addition, an estimate for the proportion of patients receiving combined IP/IV chemotherapy according to the level of center expertise are not yet available in the published literature, such that these assumptions were based on limited data from the HSCRC database and the personal experience of the authors. A second potential limitation of the current data is that survival time estimates were derived from only 2 studies, albeit randomized, prospective clinical trials, to maximize the homogeneity of the analysis with respect to toxicity and the resulting impact on quality of life. Inclusion of additional studies for survival estimates may have increased the precision of these assumptions but would have come at the expense of less accurate QALY calculations. A third limitation of the current analysis is the use of median survival times, as opposed to mean survival times, which assume a normally distributed attrition rate and do not account for irregularities in the survival curves observed over time. A fourth limitation of the current study is that cost estimates of treatment were generated from a single institution and may not be reflective of costs in other practice settings or geographic regions. Specifically, the model does not account for the potential effects of an upward charge bias for high-technology, tertiary care, teaching hospitals and, consequently, may overestimate the cost of treatment at less experienced centers. Because the rate of optimal primary cytoreductive surgery is an essential component of an expert center and the Maryland HSCRC database contains no information on this key quality characteristic for individual hospitals, adjustment for charge differentials related to institutional demographic factors was impractical. Finally, the model does not account for potentially greater out-of-pocket expenses for individuals and families traveling to an expert center.

Despite these limitations, the current data suggest that, under the current set of clinical and economic assumptions, a strategy of referral to an expert center, where a high proportion of patients undergo optimal primary cytoreduction and receive combined IP/IV chemotherapy, is cost-effective from the perspective of society compared with referral of patients to a less experienced center. Although the expert center strategy was more costly overall, the concomitant extension of survival represents a high-value healthcare commodity based on the modest economic resources consumed. Current patterns of care studies, however, indicate that a minority of patients with ovarian cancer have initial access to expert gynecologic oncologist surgical care at high-volume centers.8, 43, 50–52 For example, in a statewide, population-based study of 2417 patients with ovarian cancer in Maryland, Bristow et al characterized primary surgical care and observed that only 34.5% of patients were treated by high-volume surgeons, and only 22.8% of patients underwent surgery at high-volume centers.53 These data point out prime opportunities to improve the healthcare delivery system for women with suspected advanced ovarian cancer, namely, to expand access to expert care by increasing the number and level of expertise of qualified centers providing multidisciplinary, comprehensive services coupled with consistent adherence to referral guidelines by point-of-contact providers.

Acknowledgements

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgements
  7. REFERENCES

Supported by the Pam McDonald Ovarian Cancer Research Program.

REFERENCES

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgements
  7. REFERENCES