Tuesday, October 26, 2010: 10:15 AM
Grand Ballroom West (Sheraton Centre Toronto Hotel)

* Candidate for the Lee B. Lusted Student Prize Competition

Session Chairs:
Y. Claire Wang, MD, ScD and Nilay D. Shah, PhD
10:15 AM
Hla-Hla Thein, MD, MPH, PhD1, Murray D. Krahn, MD, MSc2, Alex Hoare, BSc, (Hons)3, Gregory J. Dore, MD, MPH, PhD3 and David Wilson, PhD3, (1)University of New South Wales and University of Toronto, Sydney, Australia, (2)University of Toronto, Toronto, ON, Canada, (3)University of New South Wales, Sydney, Australia

Purpose: The public health burden of hepatitis C virus (HCV) infection is considerable. We evaluated the current and future burden of HCV in Australia from a societal perspective over the period 2010-2039.

Method: A dynamic mathematical transmission model was developed to simulate HCV transmission among injecting drug users (IDUs) and non-IDUs and to track the natural history of disease progression of infected people. Healthcare costs for hepatitis C were estimated from activity-based analysis and national databases. Patient/family time costs were estimated based on Canadian estimates. Productivity losses were estimated using the friction cost method. All costs were adjusted to 2008 Australian dollars. A cost-effectiveness and cost-utility analysis was performed to compare the costs and benefits associated with five alternative HCV treatment scenarios.

Result: Under current levels of treatment, where ~3,500 HCV cases are treated each year, it was estimated that there would be ~11,700 new HCV infections in Australia in 2010, which would remain relatively stable over the next 30-year period. Our model estimated 228 new cases of liver failure, 121 new cases of liver cancer, 44 liver transplant cases and 241 liver-related deaths, and 4,759 potential years of life lost in 2010. These numbers would increase by 11-13% in 2039 under current conditions. We estimated that there would be $1.1 billion cost of HCV in 2010; of which, 17% would be attributed to healthcare costs, 44% to patient/family time costs, and 39% to productivity costs. HCV-related chronic liver disease contributes ~90% of the costs, and HCV-related liver failure, liver cancer and liver transplant contributes the remaining 10%. The total costs would increase by 75% in 2039 under current conditions. If treatment rates are increased by 250% (to ~12,000 per year), the number of new cases of liver failure, liver cancer, and the number of liver transplant cases and liver-related deaths are expected to decrease by ~20%, with substantial long-term total cost savings ($274m, 5% discount) and gains in life years (20,353) and quality-adjusted life years (QALYs) (80,614) (undiscounted). Incremental cost-effectiveness ratios ranged between $16,000-$17,000/QALY, and were most sensitive to assumptions about drug costs, utilities for early disease stage, and discount rate.

Conclusion: Strategies to improve treatment uptake is critical in order to mitigate the future burden of hepatitis C and our results help inform policy decision-making.

10:30 AM
Elisabeth A.L. Fenwick, PhD1, Nathalie A. Kulin, MSc2, Deborah Marshall, PhD2 and Kirsten Hall Long, Ph.D.3, (1)University of Glasgow, Glasgow, United Kingdom, (2)University of Calgary, Calgary, AB, Canada, (3)Mayo Clinic College of Medicine, Rochester, MN
Purpose: It has yet to be determined whether earlier detection of lung cancer with screening translates into reduced mortality. Trials have been initiated, but in the interim, debate continues over the implications given uncertain efficacy and risks of screening in practice.  We address this lack of information with a decision-analytic model.

Method: We developed a probabilistic Markov model of cost-effectiveness for lung cancer screening with helical computed tomography (hCT) compared with chest x-ray (CXR) and no screening (NS).  The base case was 55-year old US current/former smokers screened annually until age 74. Data were from published literature, Surveillance Epidemiology and End Results database, and Lung Screening Study (LSS), a nationally representative trial.  We assumed that stage shifts observed with screening translate into survival benefits.  Analyses explored the impact of alternative cohort ages for starting and stopping screening, smoking status, overdiagnosis, compliance, and false positive (FP) rates. We estimated incremental cost-effectiveness ratios (ICERs) for life years (LYs) and quality-adjusted LYs (QALYs), and cost-effectiveness acceptability curves.  We performed value of information analysis to estimate the potential value of further research to reduce uncertainty.

Result: no In the base case: (a) CXR cost $362,291/LY vs. NS; (b) hCT cost $634,982/LY vs. CXR; and (c) both CXR and hCT were dominated by NS in the QALY analyses.  The probability that NS is cost-effective was 91% at a maximum acceptable ratio of $100,000/QALY (7% and 2% for CXR and hCT, respectively).  When only current smokers were screened, screening was performed once, screening was initiated at either age 45 or 65, or there was no overdiagnosis, CXR and hCT remained dominated by NS when QALYs were the outcome.  If hCT were associated with FPs, false negatives, or overdiagnosis, hCT cost $144,671/QALY vs. NS, and CXR was dominated by NS.  Replacing the base case LSS FP rates for hCT with those from the Early Lung Cancer Action Program resulted in an ICER of ~$1.3M/QALY for hCT vs. NS.  When the FP rate for hCT was set at 0, this ICER decreased to $297,759/QALY.

Conclusion: As expected, both CXR and hCT were associated with increased LYs and costs. However, the associated negative quality-of-life effects of FPs and overdiagnosis resulted in both screening options being dominated by NS when QALYs were the outcome.

10:45 AM
Michael B. Nichol, PhD1, Joanne Wu, MD, MS1, Julie L. Priest, MSPH2, Tara K. Knight, PhD1 and C. Ron Cantrell, Ph.D.2, (1)University of Southern California, Los Angeles, CA, (2)GlaxoSmithKline, Research Triangle Park, NC

Purpose: Patients with diabetes and comorbid cardiovascular disease (CVD) require polypharmacy to control both conditions and prevent complications. Few studies investigate the impact of multiple medication compliance on healthcare utilization. The study objective was to assess the relationship of multiple medication compliance with healthcare utilization.

Method: We identified patients ≥40 years of age with a diagnosis of type II diabetes and comorbid CVD  including hypertension, coronary artery disease, and heart failure from California Medicaid claim data between 2002 and 2004. Proportion of days covered ≥0.8 was used to assess medication compliance. Finite mixture models (FMMs) with negative binomial density were used to estimate healthcare utilization in 2004 and its association with multiple medication compliance.

Result: A total of 21,740 patients were analyzed. Only 18% of patients were compliant with both diabetes and CVD medications, 32% compliant with only diabetes medication, 7% with only CVD medication, and 43% did not fill any appropriate medication or were non-compliant with any medication. FMMs classified patients to two latent classes (low- vs. high-users). Approximately 57% of patients were low-users and 43% were high-users for number of emergency room (ER) visits and prescription fills; while 80% were low-users vs. 20% high-users for number of hospitalizations and outpatient visits. High-users had 1.3 (prescription fills) to 4.0 (outpatient visits) times higher utilization than low-users. As compared to patients who did not fill or were non-compliant with both diabetes and CVD medications, those adherent to both diabetes and CVD medications in low-users class were significantly associated with increased 2.215±0.154 outpatient visits (p<0.001) and increased 15.470±0.835 prescription fills (p<0.001); but decreased 0.033±0.016 ER visits (p=0.04) and decreased 0.015±0.008 hospitalizations (p=0.09); while those adherent to both medications in high-users class were significantly associated with increased 21.005±2.151 outpatient visits (p<0.001) and increased 38.614±2.014  prescription fills (p<0.001), but decreased 0.050±0.024 ER visits (p=0.03) and decreased 0.081±0.030 hospitalizations (p=0.01).

Conclusion: Compliance with multiple medications had a significant impact on the increased utilization of outpatient visits and prescription fills, and the decreased utilization of ER visits and hospitalizations in a California Medicaid population with type II diabetes and comorbid CVD.  Further study is needed to investigate whether an appropriate number of outpatient visits and prescription fills can help offset ER visits and hospitalizations.

11:00 AM
Ulrike Haug, German Cancer Research Center, Heidelberg, Germany, Amy B. Knudsen, Ph.D., Massachusetts General Hospital, Boston, MA and Karen M. Kuntz, ScD, University of Minnesota, Minneapolis, MN

Purpose: Adherence with colorectal cancer (CRC) screening using fecal occult blood tests (FOBTs) is low. Accordingly, researchers are actively pursuing the development of a blood test (BT) for CRC screening. Pilot studies have focused on the BT’s sensitivity for detecting invasive CRC, while there is limited evidence regarding its sensitivity for detecting precursor lesions (i.e., adenomas). We assessed the cost-effectiveness of a hypothetical BT that does not detect precursor lesions (beyond chance detection) in comparison to the currently recommended FOBTs.

Method: We used a previously-developed microsimulation model, SimCRC, to calculate life-years and lifetime costs (payers’ perspective) for a cohort of US 50-year-olds to whom non-invasive CRC screening is offered annually from age 50 to 75. For FOBTs (i.e., Hemoccult II, Hemoccult SENSA and fecal immunochemical test) we used established estimates regarding test performance and costs (respectively, specificities of 98%, 93%, 95%, sensitivities for small adenomas of 5%, 12%, 10%, sensitivities for large adenomas of 12%, 24%, 22%, sensitivities for CRC of 40%, 70%, 70% and per test costs of $5, $5, $22). For the BT we assumed a specificity of 95%, a sensitivity of 90% for CRC, a sensitivity of 0% for adenomas of all sizes, and a base-case per test cost of $22. We performed sensitivity analyses on the screening interval, test characteristics and screening adherence and performed threshold analysis on the cost of the BT.

Result: At the base-case cost estimate of $22, the BT was dominated by the FOBTs in all scenarios, even when its sensitivity for CRC was assumed to be 100% or when adherence for BT strategies was assumed to be substantially higher than for FOBTs (80% versus 50%). Compared with Hemoccult SENSA and the fecal immunochemical test, BT strategies saved 13-18 fewer life-years while the costs were about $450,000 to $600,000 higher (outcomes expressed per 1000 50-year-old individuals, discounted at 3% annual rate). The BT remained dominated even when the unit cost of the test was lowered to zero.

Conclusion: The detection of adenomas appears to be a crucial aspect in the development of BTs that are aimed to improve non-invasive screening for CRC. Sequentially-designed diagnostic studies focusing first on adenomas, which are more prevalent, rather than on CRC could be a resource-saving approach to identify promising marker candidates.

11:15 AM
Shelby D. Reed, PhD1, Charles D. Scales Jr., MD2, Suzanne B. Stewart, MD2, Judd W. Moul, MD2, Jielin Sun, PhD3, Kevin A. Schulman, MD1 and Jianfeng Xu, PhD3, (1)Duke Clinical Research Institute, Durham, NC, (2)Duke University Medical Center, Durham, NC, (3)Wake Forest University School of Medicine, Winston-Salem, NC

Purpose:   Targeted strategies for chemoprevention of prostate cancer with finasteride toward higher risk groups could be more cost-effective than untargeted chemoprevention.   Recently published risk prediction models by Xu et al. can predict a man's risk of prostate cancer as a function of family history and 14 genetic markers.  In this study, we estimated the cost-effectiveness of chemoprevention strategies across risk groups defined by family history and number of inherited risk alleles.

Method:   We developed a probabilistic Markov model with 8 health states using data from SEER databases, US life tables, the published medical literature and other on-line sources to estimate costs and quality-adjusted survival to model the impact of chemoprevention with finasteride on the prevention of prostate cancer.  We incorporated a decision tree to integrate the prevalence of different risk groups based on family history and genetic risk factors to evaluate the cost-effectiveness of various prevention strategies. 

Result:   In men 50 years of age, chemoprevention with finasteride for 25 years is estimated to increase (discounted) quality-adjusted life expectancy by 0.101 QALYs (95% CI: 0.006-0.151) at an incremental (discounted) cost of $9,043 (95% CI: 8,549-9,498) relative to no chemoprevention; an incremental cost-effectiveness ratio of $89,300 per QALY (95% CI, 58,800-149,800).  Among men with a negative family history, the cost-effectiveness of chemoprevention ranged from $128,600 per QALY (95% CI; 78,000-248,700) in men with 7 or fewer risk alleles to $65,200/QALY (95% CI: 43,900-114,800) in men with 14 or more risk alleles.  Across all men with a positive family history (and no genetic testing), the cost-effectiveness of chemoprevention was estimated at $64,200 per QALY.  At an estimated cost of $400 per individual with a negative family history, the cost-effectiveness of targeting chemoprevention based on genetic information ranged from $98,100 per QALY when restricting chemoprevention to men with 14 or more risk alleles to $103,200 per QALY when expanding chemoprevention to men with 8 or more risk alleles.

Conclusion:   In men with a negative family history of prostate cancer, there was little gain in cost-effectiveness when targeting chemoprevention to men on the basis of this set of genetic risk factors.

11:30 AM
Ivar Sønbø Kristiansen, MD, PhD1, Oddvar Solli, Cand., polit.1, Kåre I. Birkeland2 and Anne-Marie Aas2, (1)University of Oslo, Oslo, Norway, (2)Oslo University Hospital, Oslo, Norway

Purpose: The purpose of this study was to estimate the (quality-adjusted) life-year gains and lifetime costs of 2-year, 5-year and lifelong lifestyle intervention (diet and exercise) compared to immediate switch to insulin in patients with poorly controlled type 2 diabetes.

Method: We simulated the disease course including complications, quality-adjusted survival, and lifetime costs of the three durations of lifestyle intervention and of immediate switch to insulin using the UKPDS Outcomes Model. A randomized trial provided data on impact of lifestyle changes on risk factors. Unit costs were taken from various local data sources. The costs of intervention, medication, equipment and GP-visits were calculated in a separate spreadsheet. Quality-of-life data were taken from a survey of patients with diabetes in Norway. 

Result: The quality-adjusted life-expectancy with immediate switch to insulin and with 2-year, 5-year and lifelong lifestyle intervention was 7.67, 7.71, 7.75, 7.86, respectively, with lifelong discounted costs of $44,318, $80,084, $124,882 and $221,407. The incremental cost per quality-adjusted life-year (QALY) for lifestyle intervention versus immediate switch to insulin were $943,905, $992,210 and $916,104 for 2-year, 5-year and lifelong treatment. The largest cost driver was indirect costs incurred by the patients' participation in diet and exercise sessions and time spent on travel to these sessions. When disregarding indirect costs, the incremental costs per QALY gained for the respective strategies were $6,353, $8,637 and $5,258.

Conclusion: The results from this study indicate that the cost-effectiveness of lifestyle intervention in patients with poorly controlled type 2 diabetes is largely dependant on how time costs are valued. Lifestyle interventions are cost-effective only if indirect costs or the value of time is set to zero or nearly zero.