| Category Reference | |||
|---|---|---|---|
| BEC | Behavioral Economics | ESP | Applied Health Economics, Services, and Policy Research |
| DEC | Decision Psychology and Shared Decision Making | MET | Quantitative Methods and Theoretical Developments |
* Candidate for the Lee B. Lusted Student Prize Competition
Purpose: The FAME Study, an international multicenter RCT (n=1005), demonstrated significant health benefits for patients undergoing multivessel percutaneous coronary intervention (PCI) guided by fractional flow reserve (FFR) measurement compared with PCI guided by angiography alone (ANGIO). The aim of our study was to determine the cost-effectiveness as well as the public health and budget impact for six European countries.
Method: All analyses were performed for patients with multivessel disease comparing FFR vs. ANGIO, based on the original patient-level data of the FAME Study (Tonino et al., NEJM2009). The following analyses were performed for Germany, UK, Italy, France, Belgium and Switzerland. In the prospective cost-effectiveness analyses, we calculated the incremental cost-effectiveness ratios (ICER) in Euro/QALY gained during 1 year adopting the societal perspective. Utilities were measured with country-specific EQ-5D or Torrance-transformed European weights, respectively. Costs were based on country-specific prices and DRGs. The public health and budget impact analysis was based on national PCI registries and performed from the national payer’s perspective over a budget period of two years. Variability was estimated using the Bootstrap method (n=5000 samples) and extensive sensitivity analysis.
Result: In the FAME trial, major adverse cardiac events at 1 year occurred in 13.2% of patients in the FFR arm and 18.3% of patients in the ANGIO arm (p=0.02). For all six countries, FFR was cost-saving compared to ANGIO. Bootstrap simulation indicated FFR being cost saving in 52-73% and cost effective in 89-92% at a threshold of 50,000 EUR/QALY gained. Mean savings per patient range from 300 EUR (Germany) to 900 EUR (France). The 2-year public health impact due to the use of FFR ranged was largest for Germany with more than 500 deaths avoided, more than 2000 major cardiac events avoided, and 380 QALYs gained. The 2-year budget impact ranges from less than 1 million to more than 27 million EUR total cost savings depending on the country. Sensitivity analyses showed that prices of FFR pressure wire and drug-eluting stents were most influential, determining whether FFR is cost-effective or cost-saving.
Conclusion: In the health care systems of Germany, UK, Italy, France, Belgium and Switzerland, FFR-guided PCI in patients with multivessel coronary disease substantially reduces cardiac events, improves QALYs and is cost saving.
Purpose: Pre-exposure prophylaxis with oral antiretroviral treatment (oral PrEP) for HIV-uninfected injection drug users (IDUs) is potentially useful in controlling HIV epidemics with a significant injection drug use component. The role oral PrEP in portfolios of interventions including methadone maintenance therapy (MMT) for drug users and antiretroviral treatment (ART) for infected individuals is unknown. We estimated the effectiveness and cost effectiveness of strategies for using oral PrEP (up to 50% of uninfected IDUs) in various combinations with MMT (25% of IDUs) and ART (80% of all eligible patients) in Ukraine, a representative case for mixed HIV epidemics.
Method: We expanded a previously developed dynamic compartmental model of the HIV epidemic in a population of non-IDUs, IDUs who inject opiates, and IDUs on methadone, adding an oral PrEP program (tenofovir, 50% susceptibility reduction) for uninfected IDUs. The model was populated with data from Ukraine. We modeled 1,000,000 individuals aged 15-49 stratified by HIV status and injection drug use. We analyzed packages of interventions consisting of MMT, ART and oral PrEP. We measured health care costs, quality-adjusted life years (QALYs), HIV prevalence, HIV infections averted, and incremental cost effectiveness.
Result: Without incremental interventions, after 20 years HIV prevalence reached 67.3% in IDUs and 0.9% in non-IDUs. A combination of MMT and oral PrEP for 25% of IDUs lowered HIV prevalence the most in both IDUs (46.2%) and the general population (0.7%). ART (80% access for eligible infected individuals), combined with MMT (25% of IDUs) and oral PrEP (25% of uninfected IDUs) averted the most infections (10,700), followed by ART (80% access) and oral PrEP (50% access), with 8,900 infections averted. The most cost-effective strategy was MMT (25% of IDUs), gaining 76,000 QALYs versus no intervention, at $530/QALY gained. The next most cost-effective strategy consisted of MMT (25% of IDUs) and ART (80% access), at $1,120/QALY gained. Further adding oral PrEP (25% access) was also cost-effective, at $12,240/QALY gained. Oral PrEP alone became cost-effective for annual PrEP costs comparable to annual HIV care costs.
Conclusion: Oral PrEP can be part of cost-effective intervention packages to control HIV epidemics where injection drug use is significant. Where budgets are limited, focusing on MMT and ART access should be the priority. Oral PrEP alone may become highly cost-effective if costs decline significantly.
Purpose: International guidelines recommend early HIV treatment initiation (i.e., at CD4 <350) for HIV-infected individuals in resource-limited settings. However, funding availability for early or deferred HIV treatment (i.e., at CD4 <200) in Haiti is uncertain. We aimed to internally validate and calibrate a user-friendly model of HIV disease in Haiti that will assist policy makers in forecasting treatment need and capacity.
Methods: We used patient-level data from Haitian observational cohorts and a randomized trial conducted in Haiti to develop a computer-based, mathematical model of HIV disease. Incidence density analysis was used to derive model parameters for untreated HIV disease progression (HIV seroconverters cohort, n=41; asymptomatic HIV disease, n=436) and HIV treatment (early 1st-line treatment, n=408, deferred 1st-line treatment, n=910; deferred 2nd-line treatment, n=194). Model predictions were compared to observed data to assess internal validity. Goodness of fit measures included visual assessment of Kaplan-Meier survival curves, comparisons of 5-year event probability, and percentage deviation between the predicted estimates and observed data at discrete time points, averaged over time. When model predictions did not exhibit a good fit due to model structure simplifications that would enhance usability, an internal calibration algorithm was applied to improve goodness of fit between predicted and observed outcomes. The model was implemented in Microsoft Excel, and results evaluated over a 5-and 10-year policy time horizon.
Results: For a cohort of newly HIV-infected individuals with no access to HIV treatment, the model predicts median AIDS-free survival of 9.0 years pre-calibration and 5.6 years post-calibration versus 5.8 years (95% CI 5.1, 7.0) observed (Figure 1). For a cohort of patients initiating deferred treatment, the model estimates 23.2% would die by 5 years (versus 23.5% in the observed data), 7.3% would be lost from care (versus 7.8%), and 11.7% would initiate a second treatment regimen (versus 10.8%). In 12 out of 14 comparisons assessing different natural history and treatment-related outcomes, mean percentage deviation between the model predictions and observed data does not exceed 5% over both 5 and 10 years.
Conclusions: Internal validation and calibration results were sufficient for 5- and10-year health policy decision making. Using local data in a model-building process can improve validity and acceptability of policy models in resource-limited settings.
Purpose: Adjuvant chemotherapy decisions for women with early-stage breast cancer are complex. the 21-gene assay, a gene expression profiling test, is validated at predicting distant recurrence-free response in patients with ER+ LN- early-stage breast cancer. This enables chemotherapy to be better targeted at higher risk patients than is possible through the use of Adjuvant! Online (AOL) or clinical judgement alone. However, existing cost-effectiveness analyses of the 21-gene assay have numerous limitations: in particular, they consider a limited range of strategies and do not separately consider intermediate risk patients identified through either AOL or the 21-gene assay. Our objective was to build an Ontario-based cost-effectiveness analysis which comprehensively addresses these limitations.
Method: We built upon a Markov model developed by Tsoi and colleagues, using data from the NSABP B-14 and B-20 clinical trials. We assumed that AOL and the 21-gene assay may be provided separately or sequentially and considered the chemotherapy decision separately for every possible risk group, resulting in 1000 unique strategies for the provision of AOL, the 21-gene assay and chemotherapy.
Result: The 21-gene assay appears cost-effective for all patients, regardless of a patient’s initial AOL risk assessment. The highest ICER is in patients at low AOL risk ($29,000 per QALY), while the 21-gene assay dominates in patients at high AOL risk. Chemotherapy appears cost-effective only in patients at intermediate or high 21-gene assay risk. The highest ICER is in patients at low AOL and intermediate 21-gene assay risk ($64,000 per QALY). Chemotherapy is dominated in patients at low 21-gene assay risk.
Conclusion: The 21-gene assay appears to be cost-effective for all Ontario women with ER+ LN- early-stage breast cancer, regardless of the woman’s initial AOL risk assessment. These results have informed the Ontario Health Technology Advisory Committee’s recent deliberations regarding the funding of the 21-gene assay in Ontario.
Purpose: To compare four previously-published methods of transforming Short Form 36 and 12 Item Health Surveys (SF-36 /SF-12) data into utilities, using survey responses from veterans with diabetes (DM) and chronic kidney disease (CKD); to determine if these transformations are valid for discriminating utility losses (disutilities) as CKD severity increases; and to estimate the disutility associated with progressive CKD.
Methods: Veterans with DM were selected who responded to the Large Veterans Health Survey in 1999 and divided into those with recent-onset DM (duration of ≤3 years) and prevalent DM (duration >3 years). Surveys were merged with data from the Diabetes Epidemiology Cohort, a well-established longitudinal cohort of veterans with diabetes. ICD-9 and procedure codes determined if respondents were on dialysis or had end-stage renal disease (ESRD). If subjects did not have ESRD/dialysis, serum creatinines were used to stage CKD. Four previously-published SF-36 /SF-12-to-utility transformations (A = SF-12 to SF-6D, B = SF-36 to SF-6D, C = SF-36 to HUI2, D= SF-12 to VR-6D) were used to estimate utilities (U) for each respondent. Generalized linear regression models estimated the disutility associated with each CKD stage, after adjustment for demographics, socio-economics, and co-morbidities.
Results: Of 67,694 diabetic patients, 22,273 had recent-onset and 45,691 patients had prevalent DM. The figure gives mean utilities by each method for recent-onset DM patients; results were similar for prevalent DM. Method A did not discriminate utility by CKD stage, among either recent-onset or prevalent diabetics. The remaining three methods showed a stepwise decline in utility as CKD stage increased. The rank order was consistently U(A)>U(C)>U(B)>U(D). In recent-onset DM, mean disutilities associated with increasing CKD stage differed significantly by transformation method (p<0.0001) and ranged between 0.0017 - 0.0042, -0.0067 - -0.0019, -0.0256 - -0.0041, and -0.0116 - -0.0091 for CKD stages 2, 3, 4/5, and ESRD/dialysis respectively; results were similar for prevalent DM.
Conclusions: In a cross-sectional analysis of diabetic veterans, systematic differences were found in utilities estimated using four transformations of SF-36 /SF-12 data. In particular, method A may not capture all available SF-36 information, resulting in inconsistent utility estimates relative to other methods. CKD-associated disutility values differed significantly between methods at each CKD stage, suggesting that selection of transformation method requires careful consideration of potential floor and ceiling problems.