Evaluation of the clinical utility of the PromarkerD in-vitro test in predicting diabetic kidney disease and rapid renal decline through a conjoint analysis.

BACKGROUND: Early identification of patients at risk of developing diabetic kidney disease or rapid renal decline is imperative for appropriate patient management, but traditional methods of predicting renal decline are limited. OBJECTIVE: This study evaluated the impact of PromarkerD, a biomarker-based blood test predicting the risk of diabetic kidney disease (DKD) and rapid renal decline. METHODS: Conjoint analysis clarified the importance of PromarkerD and other patient attributes to physician decisions for type 2 diabetes patients. Forty-two patient profiles were generated, with varying levels of albuminuria, estimated glomerular filtration rate (eGFR), blood pressure, hemoglobin A1c (HbA1c), age, and PromarkerD result. A web-based survey asked each physician to make monitoring/treatment decisions about eight randomly selected profiles. Data were analyzed using multivariable logit models. RESULTS: Two hundred three primary care physicians and 197 endocrinologists completed the survey. PromarkerD result was most important for increasing the frequency of risk factor monitoring. PromarkerD was second to HbA1c in importance for deciding to prescribe sodium/glucose cotransporter-2 inhibitors (SGLT2s) with a DKD indication, second to blood pressure for increasing the dose of lisinopril, and second to eGFR for replacing ibuprofen with a non-nephrotoxic medication. Compared with no PromarkerD results, a high-risk PromarkerD result was associated with significantly higher odds of increasing monitoring frequency (odds ratio [OR]: 2.56, 95% confidence interval: 1.90-3.45), prescribing SGLT2s (OR: 1.98 [1.56-2.52]), increasing lisinopril dose (OR: 1.48 [1.17-1.87]), and replacing ibuprofen (OR: 1.78 [1.32-2.40]). A low-risk PromarkerD result was associated with significantly lower odds of increasing monitoring frequency (OR: 0.48 [0.37-0.64]), prescribing SGLT2s (OR: 0.70 [0.56-0.88]), and replacing ibuprofen (OR: 0.75 [0.57-0.99]). CONCLUSION: PromarkerD could increase adoption of renoprotective interventions in patients at high risk for renal decline and lower the likelihood of aggressive treatment in those at low risk. Further studies are needed to assess patient outcomes with PromarkerD in real-world practice.

US payer budget impact of a microarray assay with machine learning to evaluate kidney transplant rejection in for-cause biopsies.

AIM: This study evaluates the economic impact to US commercial payers of MMDx-Kidney used in conjunction with histologic evaluation of for-cause kidney transplant biopsies. MATERIALS AND METHODS: An Excel-based model was developed to assess the cost impact of histology plus MMDx-Kidney versus histology alone for the evaluation of potential rejection in kidney transplant patients who receive a for-cause biopsy. Different model time periods were assessed, ranging from 1 to 5 years post-biopsy. A targeted literature review was used to identify parameter estimates, validated by two external clinicians with expertise in managing kidney transplant rejection. A sensitivity analysis was conducted to evaluate the relative impact of key clinical and cost parameters. In particular, the model identified the magnitude of MMDx-Kidney's impact on graft failure from rejection that would be required for MMDx-Kidney to be cost-neutral. RESULTS: By more accurately characterizing rejection, MMDx-Kidney is estimated to increase antirejection treatment costs by $1,126 per test. Nevertheless, a break-even analysis shows that the costs of MMDx-Kidney and anti-rejection medication, as well as the costs associated with an increase in the number of patients with functioning transplants, may be offset by reductions in costs associated with graft failure (i.e. costs of hospitalizations, dialysis, and repeat transplants) over 5 years, assuming MMDx-Kidney reduces annual graft failure from rejection by at least 5%. For the base case, with a 25% relative reduction in annual rate of graft failures from rejection, MMDx-Kidney increases overall costs incurred in the first year of the model but starts generating savings by the second year of the model. CONCLUSIONS: Compared with histologic evaluation of for-cause kidney transplant biopsies alone, the use of MMDx-Kidney in conjunction with histologic evaluation improves the diagnoses of graft dysfunction and may have the potential to generate overall savings from reductions in rejection-related graft failure.

Assessment of motivating factors associated with the initiation and completion of treatment for chronic hepatitis C virus (HCV) infection.

BACKGROUND: Infection with hepatitis C virus (HCV) is associated with high morbidity and increased mortality but many patients avoid initiation of treatment or report challenges with treatment completion. The study objective was to identify motivators and barriers for treatment initiation and completion in a community sample of HCV-infected patients in the United States. METHODS: Survey methods were employed to identify factors reported by patients as important in their decision to start or complete HCV treatment. Study participants included 120 HCV-infected individuals: 30 had previously completed treatment with pegylated interferon/ribavirin (PR), 30 had discontinued PR, 30 were treated with PR at the time of the survey, and 30 were treatment‒naïve. Telephone interviews occurred between May and August of 2011 and employed a standardized guide. Participants assigned factors a rating from 1 (not at all important) to 5 (extremely important). Trained researchers coded and analyzed interview transcripts. RESULTS: Of 33 factors, expected health problems from not treating HCV infection was reported as most encouraging for treatment initiation and completion, while treatment side effects was most discouraging. Sixty-nine percent of participants reported that the ability to obtain information during treatment on the likelihood of treatment success (i.e., results of viral load testing) would motivate them to initiate therapy. Median preferred timing for learning about test results was 5 weeks (range: 1-23 weeks). CONCLUSION: Understanding challenges and expectations from patients is important in identifying opportunities for education to optimize patient adherence to their HCV treatment regimen.

Cost-effectiveness model of use of genetic testing as an aid in assessing the likely benefit of aspirin therapy for primary prevention of cardiovascular disease.

BACKGROUND: Aspirin use for the primary prevention of cardiovascular disease (CVD) is controversial because of the need to balance the risk of major bleeding events caused by aspirin with the benefit of CVD events prevented by aspirin. The United States Preventive Services Task Force (USPSTF) proposed guidelines that use CVD risk thresholds, based on the Framingham Risk Score, to identify patients likely to benefit from aspirin use. Genetic information could be used to modify this CVD risk assessment; for example, 2 variants of the LPA gene, which encodes apolipoprotein(a), are associated with increased risk of CVD. OBJECTIVES: To estimate the incremental cost-effectiveness of using genetic test results for 2 LPA variants to derive modified Framingham Risk Score estimates and to use these estimates to identify patients likely to benefit from aspirin use according to USPSTF guidelines for aspirin use in the primary prevention of CVD. METHODS: A cost-effectiveness model of 1 million patients representative of the US population was developed based on the association of 2 LPA variants (rs3798220 and rs10455872) with CVD. The cost of testing was estimated for patients whose 10-year CVD risk would exceed the USPSTF treatment threshold if they were to test positive for the LPA variants. Patient utility estimates for myocardial infarction and stroke, and cost estimates (using a 3.5% annual discount rate) for myocardial infarction, stroke, and gastrointestinal bleeding events were based on published estimates. RESULTS: Recommending aspirin to patients whose CVD risk surpassed the risk threshold when LPA information was included in their risk assessment would prevent an estimated 65 CVD events over 10 years. At a genetic test cost of $150, the incremental cost-utility of testing for LPA variants is estimated at $24,942 per quality-adjusted life-year. CONCLUSIONS: LPA genotyping in the context of the aspirin use guidelines for primary prevention of CVD could be cost-effective.

A structured literature review of the direct costs of adult systemic lupus erythematosus in the US.

OBJECTIVE: A structured review of the literature was undertaken to examine the direct costs of adult systemic lupus erythematosus (SLE) in a US population. METHODS: English-language studies published from January 2000 to April 2010 were systematically reviewed from both Medline's PubMed and the Cochrane databases. Studies were included if they reported direct medical costs of SLE among adults in the US. RESULTS: Seven studies published since January 2000 that reported direct medical costs associated with SLE in the US were identified. Studies examined main cost categories of inpatient, outpatient, and pharmacy services; each contributed substantially to total costs. Wide SDs were reported, consistent with variability in disease manifestation. Mean annual direct costs of SLE patients ranged from $13,735-$20,926; the costs of those with and without nephritis ranged from $29,034-$62,651 and $12,273-$16,575, respectively. Across studies of a general SLE population, pharmaceutical costs composed 19-30% of total expenditures, with inpatient costs accounting for 16-50% and outpatient costs accounting for 24-56% of overall costs. Methodologies varied across studies, with patient self-reported resource utilization generating the lowest estimates versus claims-based analyses; Medicaid claims analyses generated lower incremental cost estimates for SLE patients versus control patients compared to estimates based on commercial claims analysis. CONCLUSION: SLE is associated with substantial annual direct cost burden in the US; however, little research has been done examining costs associated with specific treatments or cost variation by disease severity and disease manifestations. Future research elucidating the causes in variation of costs will help in the appraisal of emerging therapies and in developing clinical management strategies.

Assessment of the influence of test characteristics on the clinical and cost impacts of methicillin-resistant Staphylococcus aureus screening programs in US hospitals.

OBJECTIVE: To compare the impacts of different methicillin-resistant Staphylococcus aureus (MRSA) screening test options (eg, polymerase chain reaction [PCR], rapid culture) and program characteristics on the clinical outcomes and budget of a typical US hospital. METHODS: We developed an Excel-based decision-analytic model, using published literature to calculate and compare hospital costs and MRSA infection rates for PCR- or culture-based MRSA screening and then used multivariate sensitivity analysis to evaluate key variables. Same-day PCR testing for a representative 370-bed teaching hospital in the United States was assessed in different populations (high-risk patients, intensive care unit [ICU] patients, or all patients) and compared with other test options. RESULTS: Different screening program populations (all patients, high-risk patients, ICU patients, or patients with previous MRSA colonization or infection only) represented a potential savings of $12,158-$76,624 per month over no program ($188,618). Analysis of multiple test options in high-risk population screening indicated that same-day PCR testing of high-risk patients resulted in fewer infections over 1,720 patient-days (2.9, compared with 3.5 for culture on selective media and 3.8 for culture on nonselective media) and the lowest total cost ($112,012). The costs of other testing approaches ranged from $113,742 to $123,065. Sensitivity analysis revealed that variations in transmission rate, conversion to infection, prevalence increases, and hospital size are important to determine program impact. Among test characteristics, turnaround time is highly influential. CONCLUSION: All screening options showed reductions in infection rates and cost impact improvement over no screening program. Among the options, same-day PCR testing for high-risk patients slightly edges out the others in terms of fewest infections and greatest potential cost savings.