Thursday, October 18, 2012: 4:30 PM-6:00 PM
Regency Ballroom C (Hyatt Regency)

Session Chairs:
David W. Hutton, PhD and Jane J. Kim, PhD
4:30 PM
Lauren E. Cipriano, MS, Stanford University, Stanford, CA and Thomas A. Weber, PhD, Ecole polytechnique federale de Lausanne, Lausanne, Switzerland

Purpose: Several recent analyses (e.g., Ann. Intern. Med. 156(4):263, 2012) indicate that universal one-time screening for hepatitis C (HCV) is likely cost-effective for individuals currently aged 40-60.  Since the prevalence of HCV is decreasing with birth-year, screening future cohorts will be less cost effective.  Maximizing social value of a HCV screening program requires lifecycle evaluation of its costs and benefits in the presence of the options to continue with or without costly information collection or to terminate the program.

Methods: We apply a Markov decision process framework to evaluate a policy of universal HCV screening.  The incremental net monetary benefit of screening a single cohort is linear in the uncertain time-varying parameter, cohort prevalence.  We estimated the lifetime cost and benefit of each screening outcome using an HCV natural history model (Liu et al., in prep.), HCV prevalence dynamics using regression to birth-cohort specific prevalence in NHANES, and the cost of information from the US National HIV Behavioral Surveillance System.  The willingness-to-pay threshold is assumed $75,000/QALY.  Value iteration yields the optimal HCV screening and information collection policy for US men and women.

Results: Without any information collection, the optimal time to stop universal one-time hepatitis C screening is in 36 years (95%CI: 30-41 years) for men and in 15 years (95%CI: 7-21 years) for women.  For men, the value of collecting sample information about the HCV prevalence immediately likely does not exceed the cost of collecting information.  For women, immediate sampling (n*WOMEN=2400) increases the expected value of an HCV screening policy from $259.2 million to $261.4 million. However, provided a standing option to collect sample information about prevalence the optimal policy is to screen men and women without information collection for 31 years and 11 years, respectively, and then to collect sample information (n**MEN=2000, n**WOMEN=2250) to inform the next action.  The expected value of this strategy is $1.149 billion (cf. $1.145 billion with no information collection) and $265.1 million. 

Conclusions: Maximizing social value from a health program, such as HCV screening, requires a complete policy lifecycle analysis.  By incorporating the expected prevalence dynamics and solving the problem as a Markov decision process we were able to increase the expected value of an HCV screening program by identifying the optimal time to collect HCV prevalence information.

4:45 PM
David D. Kim, MS1, Joshua D. Stein, MD, MS2, Paula Anne Newman-Casey, MD2, Kristen Harris Nwanyanwu, MD2, Mark W. Johnson, MD2 and David W. Hutton, PhD1, (1)University of Michigan School of Public Health, Ann Arbor, MI, (2)University of Michigan, Ann Arbor, MI

Purpose: To determine the most cost-effective treatment option for patients with newly-diagnosed clinically significant diabetic macular edema (CSDME): focal laser photocoagulation (L), focal laser plus intravitreal triamcinolone (L+T) injections, and intravitreal ranibizumab injections with the focal laser (L+R) or delayed laser with ranibizumab injections (DL+R).


We developed a Markov decision analysis model to compare the incremental cost effectiveness ratio (ICER) of treating newly-diagnosed CSDME with L, L+R, DL+R or L+T.  The model followed a hypothetical cohort of patients, 57 years of age with CSDME over a 25 year time horizon. Different levels of best corrected visual acuity (BCVA) were used as health states.  The distribution of BCVA at the baseline, year 1 and year 2 or later were obtained from a recent DRCRnet randomized controlled trial.  We used a societal perspective, measuring direct medical costs of treatment and long-term care of CSDME as well as quality-adjusted life years (QALYs) gained with 3% annual discount rates.  Sensitivity analysis was conducted to test uncertainty in the model assumptions.


Under the base model with the use of ranibizumab, over 25 years the expected cost for a single patient with newly-diagnosed CSDME receiving L, L+R, DL+R, and L+T were $15505, $53750, $56917, and $19369, while the effectiveness were 10.43, 10.83, 10.99, and 9.57 QALYs, respectively.  The ICER of DL+R over L was $71271/QALY, L+R over L was $89903/QALY and L dominated L+T.  With the use of bevicizumab instead of ranibizumab, The ICER of DL+B over L was $11138/QALY and L continued to dominate L+T. L+B provided fewer QALYs at a higher cost per QALY than DL+B.

Conclusion: An interesting finding from our analysis is the impact of using bevicizumab  instead of ranibizumab in the model.  Although not approved by the FDA, many providers will treat CSDME using bevicizumab  since it is considerably cheaper than ranibizumab ($348 vs. $2337 per injection) and is assumed to have similar efficacy.  Given similar effectiveness, the price differential between these two anti-VEGF agents can have a dramatic impact on the incremental cost effectiveness as observed in our analysis. The risk of cerebrovascular accident would need to be at least 1.5% greater among patients receiving bevicizumab  relative to ranibizumab for ranibizumab to become the more cost-effective treatment alternative.

5:00 PM
Zachary J. Kastenberg, MD1, Michael P. Hurley, MS1, Anna Luan, BS1, Vidya Vasu-Devan, BA1, Douglas K. Owens, MD, MS2 and Jeremy D. Goldhaber-Fiebert, PhD1, (1)Centers for Health Policy & Primary Care and Outcomes Research, Stanford University, Stanford, CA, (2)Veterans Affairs Palo Alto Health Care System and Stanford University, Stanford, CA

Purpose:  Appendicitis is the most common indication for non-obstetric surgery in pregnant women with nearly 10,000 cases of appendicitis during pregnancy occurring annually. Displacement of the abdominal anatomy and the physiological changes of the second and third trimester decrease the accuracy of clinical diagnosis with reported negative appendectomy rates of approximately 40%. Diagnostic laparoscopy, CT, and MRI are the commonly employed strategies to confirm the diagnosis of appendicitis and are assessed here with a cost-effectiveness analysis.

Methods:  We developed a decision-analytic Markov model to quantify the health outcomes and costs for the mother and fetus. Pregnant women who were suspected of having appendicitis underwent one of three diagnostic strategies:  1) Diagnostic laparoscopy; 2) MRI scan; 3) CT scan. All women with a positive MRI or CT and all women in the laparoscopy strategy then underwent an appendectomy with the risk of incurring a perioperative complication, including preterm delivery or fetal loss. Finally, due to fetal radiation exposure in the CT strategy, the model included the subsequent health outcomes and costs for children experiencing radiation-associated pediatric cancer. All model inputs were derived from the published literature. The analysis adopted a societal perspective, considering a lifetime horizon, and expressed outcomes in terms of discounted costs, quality adjusted life years (QALY) for the mother and fetus, and incremental cost-effectiveness ratios.

Results:  MRI cost $789 per additional QALY gained compared to diagnostic laparoscopy. The MRI strategy cost less and was more effective than CT when the cost of performing an MRI was below $5,395. In a setting where MRI was unavailable, CT cost $1,264 per QALY gained compared to diagnostic laparoscopy. Unless the prevalence of appendicitis was >98% in the screened population, imaging of any type prior to surgery was more cost-effective than diagnostic laparoscopy. 

Conclusions:  A high level of clinical diagnostic certainty must be reached prior to proceeding to operation without pre-operative imaging in the pregnant patient given the risks of preterm labor and fetal loss associated with operation. Depending on imaging costs and resource availability, both CT and MRI are potentially cost-effective strategies, with the risk of radiation-induced childhood cancer from CT having little impact on population-level outcomes.

5:15 PM
Malek B. Hannouf1, Richard M. Zur, Ph.D2, C. Elizabeth McCarron, Ph.D1, Alexander V. Louie, BSc, MD3, George B. Rodrigues, MD, FRCPC, MSc3 and Gregory S. Zaric1, (1)University of Western Ontario, London, ON, Canada, (2)The Hospital for Sick Children, Toronto, ON, Canada, (3)London Regional Cancer Program, London, ON, Canada

Purpose: Currently, lobectomy (surgical resection) is the treatment of choice for medically operable Stage I non–small cell lung cancer (NSCLC) patients. A growing body of evidence suggests that stereotactic body radiation therapy (SBRT) may be considered as an option for these patients. We sought to investigate the cost effectiveness of using SBRT versus lobectomy for the management of patients with medically operable Stage I NSCLC from the perspective of the Canadian public healthcare system.

Methods: We developed a Markov model to project the lifetime clinical and economic consequences of operable Stage I NSCLC. We considered 12 scenarios corresponding to male and female patients aged 65 or 70 with minor comorbidity and standard life risk, average comorbidity and light smoking, and major comorbidity and heavy smoking. We assumed that lobectomy is associated with short term postoperative mortality risk and reduction in quality of life. We assumed SBRT is associated with minimal treatment related toxicity and maintenance of quality of life as it has been shown in recent analyses. The model was parameterized using data from clinical trials, 10 year cost data obtained by linking Ontario Cancer Registry with administrative databases in Ontario, and secondary sources. Costs are presented in 2012 CAD. Future costs and benefits were discounted at 5%.

Results: In all scenarios, SBRT led to an increase in quality adjusted life years of survival (QALYs) and a decrease in cost resulting in SBRT being cost saving compared to lobectomy. QALYs gained and cost saving ranged from 0.018 QALY and $25,900 per person for a 65 year old female with minor comorbidities, and up to 0.032 QALY and $26,400 per person for a 70 year old male with major comorbidities and heavy smoking. Results were most sensitive to the changes in the quality of life associated with SBRT.

Conclusions: Our results suggest that SBRT is clinically and economically a promising treatment for patients with operable Stage I NSCLC. These results suggest that SBRT should be considered for adoption for operable Stage I NSCLC. However, ongoing assessment of SBRT effectiveness in real-world Canadian clinical practice is warranted especially with regards to quality of life in these patients.

5:30 PM
Kevin F. Erickson, M.D.1, Sohan Japa, MBA2, Douglas K. Owens, MD, MS3, Glenn M. Chertow, M.D., MPH4, Alan M. Garber, MD, PhD5 and Jeremy D. Goldhaber-Fiebert, PhD2, (1)Stanford University School of Medicine, Stanford, CA, (2)Stanford University, Stanford, CA, (3)Veterans Affairs Palo Alto Health Care System and Stanford University, Stanford, CA, (4)Stanford University School of Medicine, Palo Alto, CA, (5)Office of the President and Provost, Cambridge, MA

Purpose: Patients with chronic kidney disease (CKD) have an elevated risk for myocardial infarction (MI) and stroke. Although HMG Co-A reductase inhibitors (“statins”) are effective at preventing cardiovascular (CV) events in patients with non-dialysis-requiring CKD, guidelines conflict on the use of statins in this population. The purpose of this study was to determine the cost-effectiveness of statins for primary cardiovascular prevention in patients with non-dialysis-requiring CKD.

Method: We developed a decision-analytic Markov model.  Main outcomes included rates of MI and stroke, discounted quality adjusted life years (QALYs) and life time costs (2010 USD) and associated incremental cost-effectiveness ratios (ICER).  Rates of CKD progression were modeled using longitudinal studies of patients with CKD.  The possibility of myotoxicity from statins was included in the analysis.  Costs of statin therapy included the cost of monthly generic pravastatin along with biannual laboratory monitoring.

Result: For 65 year-olds with mild hypertension and mild-moderate (stage 3) CKD, statin therapy increased lifetime costs in men by $6,210 and in women by $6,855 and led to a gain of 0.12 and 0.07 QALYs in men and women, respectively.  Statin therapy reduced the combined rate of MI and stroke, improving outcomes at a cost of $53,085 per QALY for men and $105,788 per QALY in women.  The health and economic benefits of statins varied according to age and baseline cardiovascular risk, with the cost per QALY gained higher in younger patients with lower cardiovascular risk.

Conclusion: Use of statins could lead to modest absolute reductions in cardiovascular disease in patients with CKD due to their high underlying risk of cardiac events; however, these gains are partially offset by a modest elevated risk of statin-induced rhabdomyolysis .  Statin use in older men with CKD compares favorably to other interventions considered cost effective.  In younger men and women with CKD, use of statins is less efficient due to their lower risk of CV events.  Statin use is more favorable in all cohorts when low cost generics are available.

5:45 PM
Monisha Sharma, ScM1, Muhieddine Seoud, MD2 and Jane J. Kim, PhD1, (1)Harvard School of Public Health, Boston, MA, (2)American University of Beirut Medical Center, Beirut, Lebanon

Purpose: While the estimated age-standardized cervical cancer (CC) rate in Lebanon is relatively low (3.8 per 100,000 women years), most cases are detected at later stages.  There is no national organized CC screening program in Lebanon. Rather, screening is opportunistic and limited to women who can afford to pay out-of-pocket for exams.  As a result, a small percentage of women receive frequent screening with annual cytology while the majority are never screened.  We evaluated the health and economic effects of expanding screening coverage and extending screening intervals in Lebanon.

Method: We used an individual-based Monte Carlo simulation model that simulates the natural history of HPV and cervical disease, as well preventive interventions. Using a likelihood-based approach, we calibrated the model to primary epidemiological data from Lebanon, including CC incidence and HPV type distribution among women with lesions and cancer.  Analyses were conducted using the 50 best-fitting parameter sets. We evaluated cytology screening strategies for women aged 25 to 60 years, varying coverage from 20-80% and frequency from annual to every five years.  Lifetime costs included direct medical costs associated with screening, diagnosis, and treatment, as well as patient time and transportation. Sensitivity analyses were conducted to explore the effects of screening performance, screening modality, and cost.  

Result: Repeated annual cytologic screening among 20% of screen-eligible women reduced CC incidence by only 14% and cost I$52,740 per quality-adjusted life year (QALY) gained, compared to triennial screening of the same population; this far exceeded Lebanon’s gross domestic product (GDP) per capita (I$12,610), a common threshold for identifying strategies that are good value for money.  Increasing screening coverage to 50% at triennial intervals resulted in a greater CC reduction (26%) and was cost-effective at I$8,040 per QALY.  Further raising coverage levels to 70% with triennial screening yielded the highest CC reductions (43%) and was associated with a cost per QALY that fell just below Lebanon’s GDP per capita.  Increasing coverage of annual cytology was not found to be cost-effective under plausible scenarios.

Conclusion: Current screening practice in Lebanon of repeated cytology in a small percentage of women is very inefficient.  Increasing screening coverage to 70% with extended screening intervals provides greater health benefits at a reasonable cost and will likely lead to more equitable distribution of health gains.