Tuesday, January 7, 2014: 1:30 PM-3:00 PM
Tanglin IV (The Regent Hotel)

Session Chairs:
Yee Wei Lim and Douglas K. Owens, MD, MS
1:30 PM
Beate Jahn, PhD1, Ursula Rochau, MD, MSc1, Christina Kurzthaler, Bsc1, Marjan Arvandi, MS1, Felicitas Kuehne1, Martina Kluibenschaedl, Bsc.1, Murray D. Krahn, MD, MSc2, Mike Paulden, MA., MSc.3 and Uwe Siebert, MD, MPH, MSc, ScD4, (1)UMIT - Institute of Public Health, Medical Decision Making and HTA/ Area 4 HTA and Bioinformatics, Hall in Tyrol/ Innsbruck, Austria, (2)University of Toronto, Toronto Health Economics and Technology Assessment (THETA) Collaborative, Toronto, ON, Canada, (3)University of Toronto, Toronto, ON, Canada, (4)UMIT/ ONCOTYROL/ Harvard School of Public Health/ Harvard Medical School, Hall, Austria
Purpose: A Breast Cancer Outcomes model was developed at the ONCOTYROL research center, to evaluate the cost-effectiveness of personalized test-treatment strategies in Austria. The goal of this study was to build a model that allows evaluation of combinations of innovative tests, biomarkers and new treatments early in the development process. In a first application, we evaluate the cost effectiveness of the new 21-gene assay (ODX) when it is applied in addition to the Adjuvant! Online (AOL) decision aid to support personalized decisions on adjuvant chemotherapy in Austria

Method: We developed a discrete event simulation model to run a hypothetical cohort of 50 year old women over a lifetime time horizon. The main outcomes were life-years gained, quality-adjusted life-years (QALYs), costs and cost-effectiveness. Based on the new ISPOR-SMDM recommendations, the model was validated. Eight test-treatment strategies were evaluated. Each strategy was defined by three letters. The first letter indicates whether patients with a low risk according to AOL were tested using ODX (Y-yes; N-no), the second and the third letters provide this information for AOL intermediate and high-risk patients, respectively. Robustness of the results was tested in a sensitivity analysis. Results were compared to a Canadian analysis by the Toronto Health Economics and Technology Assessment Collaborative (THETA).

Result:  Five out of eight strategies were dominated (i.e. more costly and less effective: NNY, NYN, YNN, YNY, YYN). The base-case analysis shows that only the strategies in which ODX is provided to patients with an intermediate or high AOL risk (incremental cost-effectiveness ratio (ICER) NYY = 1,600 EUR/QALY) and where all patients get ODX (ICER YYY 15,700 EUR/QALY) are cost-effective. These results are sensitive to changes in the probabilities of distant recurrence, age and costs of chemo that lead to further non dominated strategies. The base case analysis was comparable to the THETA results. Our discrete event simulation using a modular structure provides the flexibility to test various sequential tests, additional biomarker and treatments.

Conclusion: Our study showed that ODX, when used in addition to the AOL, is cost-effective in two test-treatment strategies (NYY, YYY) in Austria. Our simulation tool provides the flexibility to evaluate combinations of two or more tests that can complement each other and respective treatment.

1:45 PM
Cheng-Yang Hsieh, MD, Jason C. Hsu, PhD and Yea-Huei Kao Yang, National Cheng Kung University, Tainan, Taiwan
Purpose: Intravenous tissue-type plasminogen activator (t-PA) is the only effective treatment for acute ischemic stroke in current practice. Recently, it has been used at lower dose in Asian countries due to the concerns of the safety and cost of the standard dose approved in the westerns countries. We aimed to evaluate the risk-benefit ratio of t-PA for the Asian stroke patients at diverse dosages of: (1) standard-dose (0.9 mg kg-1) and (2) low-dose (0.7 mg kg-1) to provide evidence for decision making of prescribing and reimbursement.

Method: A decision model was created to compare the risk-benefit of the standard- and low- doses of t-PA. The risk measures were the occurrence of symptomatic intracerebral hemorrhage (SICH) and mortality respectively and in combination; the efficacy measures was the proportion of patients with a modified Rankin Scale (mRS) score ≤ 1 at 3 months. The estimates were obtained from the published meta-analysis literature about Asian population. The risk and benefit of both dosages were compared in the form of incremental risk-benefit ratios (IRBRs). Probabilistic sensitivity analysis and one-way sensitivity analysis were conducted to incorporate uncertainty in model parameters and to estimate the impact of changing each key parameter individually.

Result: When SICH was used as the risk measure, low-dose t-PA (IRBR = 0.3729) showed increased risk and benefit as compared to standard-dose t-PA. However, standard-dose t-PA was dominated over by low-dose t-PA (IRBR = -2.3333), when mortality was used as the risk measure. Furthermore, the result of combined SICH and mortality revealed that the standard-dose t-PA was favorable as compared with low-dose t-PA with the IRBR of -0.3529. In sensitivity analyses, the IRBR ratios were robust to variations in utility of effectiveness and mortality of low-dose t-PA.

Conclusion: Our results indicated that the standard-dose t-PA might be preferred over low-dose t-PA considering both risks and benefits. Selecting appropriate dosage of t-PA according to both risk and benefit simultaneously is suggested in order to achieve better treatment goals for acute ischemic stroke in Asian population.

2:00 PM
Kine Pedersen1, Sveinung Wergeland Sørbye, MD, PhD2, Stefan Lönnberg, MD, PhD3, Emily Burger, MPhil1 and Ivar Sønbø Kristiansen, MD, PhD, MPH1, (1)University of Oslo, Oslo, Norway, (2)University Hospital of North Norway, Tromsø, Norway, (3)Cancer Registry of Norway, Oslo, Norway
Purpose:  Norwegian health authorities are considering implementing primary human papillomavirus (HPV) testing in screening for cervical cancer for women 34-69 years. We aim to compare the current screening algorithm (i.e., primary cytology every three years) with primary HPV-testing every six years to enumerate resource trade-offs in terms of detection of high-grade cancer precursors (CIN2+) and number of colposcopies performed.

Method:  We developed a probabilistic decision tree simulation model to estimate outcomes associated with different screening algorithms. The model uses epidemiologic data from the Cancer Registry of Norway and follows individual women attending primary screening at baseline through subsequent six years, allowing for loss-to-follow-up and spontaneous regression of CIN2+. We compared the current Norwegian strategy (Strategy 1) entailing primary cytology with co-testing (HPV and cytology) for delayed triage of atypical and low-grade cytology results (ASC-US/LSIL), with two alternative HPV strategies. Both HPV strategies involve primary HPV testing followed by reflex cytology for any HPV-positive result. For Strategy 2, the threshold for diagnostic colposcopy/biopsy is high-grade atypical cells or worse (ASC-H+), while Strategy 3 involves a lower threshold on the cytology result, i.e., any atypical cells (ASC-US+). Primary outcomes were CIN2+ detected and number of colposcopies/biopsies performed.

Result:  Among 100,000 women, we project the three strategies would detect 503, 338 and 715 CIN2+, and require respectively 2685, 1925 and 3696 colposcopies. Consequently, the number of colposcopies per CIN2+ detected were 5.34, 5.70 and 5.17 for Strategy 1, 2 and 3, respectively. Strategy 2 results in a 32% reduction in detected CIN2+ while simultaneously increasing the number of colposcopies per CIN2+ by 7% compared to the current strategy, thus providing a less efficient algorithm. Conversely, Strategy 3 may increase detection of CIN2+ by 42% at a cost of 38% more colposcopies, and detect CIN2+ more efficiently than the current strategy (i.e., decreasing the colposcopy to CIN2+ ratio by 3%).

Conclusion:  There is a potential for improving the current screening algorithm by implementing screening with primary HPV-testing. However, unless the lower threshold for referral to colposcopy/biopsy is utilized, primary HPV-testing may detect fewer cancer precursors and require more colposcopies per detected case. The differential effectiveness of the three algorithms in terms of preventing invasive cancer will depend on the extent to which cancer precursors regress or progress into cancer.

2:15 PM
Yin Wan, MS1, Qiang Li, MSc2, Yixi Chen, MSc3, Seema Haider, PhD4, Sizhu Liu, MS1 and Xin Gao, PhD1, (1)Pharmerit, Bethesda, MD, (2)Surgical Intensive Care Unit, Department of General Surgery, Jiangsu Province Hospital, Nanjing, China, (3)Pfizer Inc., Beijing, China, (4)Pfizer Inc., Groton, CT

Purpose: To assess the healthcare resource utilization (HCRU) and costs from a Chinese payer's perspective (Nanjing city) for MRSA-NP in hospitalized adults treated with linezolid or vancomycin, including the economic impact of renal failure.

Method: A post-hoc analysis was conducted using data from a phase IV, randomized, double-blind, global multicenter study (Wunderink, CID: 2012, NCT00084266) in culture-proven MRSA-NP patients [microbiologic confirmed intent-to-treat (MITT) cohort]. Renal failure was defined by ≥1 of the following: 1) investigator-reported renal failure adverse events; 2) acute kidney injury defined renal failure using RIFLE criteria; 3) initiated dialysis after study drug started. HCRU from treatment initiation through end of study visit (EOS) included study drug use, mechanical ventilator (MV) days, intensive care unit (ICU) days, length of stay (LOS), and dialysis days. Chinese costs were calculated by applying Nanjing-specific unit costs (2012 ¥) to the HCRU collected from the global trial. Between-group differences were tested using chi-square test for renal failure rates and t test for HCRU/costs, and the non-parametric Wilcoxon rank-sum test for comparisons with sample size < 30.

Result: MITT patients (224 linezolid/224 vancomycin) were followed for 23.3±10.1 days (linezolid 23.0±10.0, vancomycin 23.6±10.2), with 39% hospitalized at EOS for both linezolid and vancomycin. Linezolid vs. vancomycin had similar total costs: ¥77,089±¥51,211 vs. ¥77,695±¥52,450, p=0.90. Linezolid patients had a significantly lower incidence of renal failure vs. vancomycin (4% [n=9] vs. 15% [n=34], p<0.001). Patients with renal failure (vs. no renal failure) had significantly more MV days (12.0±9.9 vs. 7.8±9.0, p=0.004) and ICU days (13.5±9.9 vs. 10.0±8.5, p=0.013), similar LOS (18.8±9.8 vs. 18.2±9.6, p=0.74) and incurred higher total costs ¥100,449±¥65,080 vs. ¥74,944±¥49,632, p=0.002, Table 1). linezolid-treated (vs. vancomycin-treated) patients who developed renal failure trended towards lower HCRU (MV days: 7.6±3.6 vs.13.2±10.7, p=0.21; ICU days: 9.9±6.6 vs. 14.4±10.5, p=0.30; LOS: 16.1±11.0 vs. 19.5±9.5, p=0.26) and, when correcting for mortality differences using a per-person day approach tended to incur lower per person-day total cost (¥4,805±¥1,930 vs. ¥5,347±¥2,395, p=0.32). Table 1 reports the unadjusted mean costs for various cohorts.

Conclusion: Linezolid was associated with a significantly lower incidence of renal failure than vancomycin. HCRU and costs from a Chinese (Nanjing) payer perspective were similar between linezolid and vancomycin. Patients who developed renal failure incurred more HCRU and greater costs versus those who did not.


2:30 PM
Murray D. Krahn, MD, MSc1, Karen E. Bremner, BSc2, Jin Luo, MSc3, Jeffrey Hoch, PhD4, Gary Naglie, MD5 and Shabbir MH Alibhai, MD, MSc2, (1)Toronto Health Economics and Technology Assessment (THETA) Collaborative, Toronto, ON, Canada, (2)University Health Network, Toronto, ON, Canada, (3)Institute for Clinical Evaluative Sciences, Toronto, ON, Canada, (4)Cancer Care Ontario, Toronto, ON, Canada, (5)Baycrest, Toronto, ON, Canada

To estimate and compare real-world total health care costs for clinically relevant androgen deprivation therapy (ADT) regimens and indications for prostate cancer (PC).


Using a cancer registry and health care administrative databases in the province of Ontario, Canada, PC patients who started >90 days of ADT at age >66 in 1995 to 2005 were selected and classified by ADT regimen and indication. We used an outpatient prescription drugs database and hospital records to determine ADT regimen: medical castration; orchiectomy; anti-androgen monotherapy; combined androgen blockade (CAB) medical (medical castration plus anti-androgen); CAB surgical (orchiectomy plus anti-androgen). We used prescription drug data, hospital procedure codes, and diagnostic codes to determine indications for ADT: neoadjuvant, adjuvant, metastatic disease, biochemical recurrence, primary (non-metastatic). Using nonparametric regression methods we computed first-year, five-year, and ten-year longitudinal total direct medical costs (CAD2009).


The cohort numbered 21,818 (mean age 75 years; 54% alive on December 31, 2007). Mean first-year costs were highest among metastatic patients: from $24,403 for orchiectomy to $32,221 for anti-androgen monotherapy. Mean first-year costs for all other regimens and indications were below $20,000 except for medical castration for recurrence ($24,716). Primary treatment with orchiectomy was the least costly ($14,218). CAB medical was the most costly regimen in the first year for primary, neo-adjuvant, and adjuvant indications. Mean five-year and ten-year costs were lowest for neo-adjuvant treatment, with differences of <$3,000 between regimens. Orchiectomy regimens were the least costly, but limited to primary and metastatic indications. CAB Medical was generally more costly than anti-androgen monotherapy or medical castration alone. Annual costs were highest in the first year of ADT, likely due to drug/orchiectomy and costs associated with indication (radiation, metastases, recurrence). Outpatient drugs, including pharmacological ADT, accounted for 17% to 65% of total first-year costs.


Surgical castration, if clinically relevant, represents considerable cost savings over pharmacological ADT. Monotherapies are more economical than CAB. Metastatic disease is the most costly indication. Administrative data allow estimation of costs in large population-based cohorts over long periods of time. Their lack of detailed clinical data can be overcome by developing algorithms, eg. for treatment regimens and indications. Our real-world costs provide high quality data for PC cost-effectiveness and decision models.