Assessing the prognostic utility of hematologic response for overall survival in patients with newly diagnosed AL amyloidosis: results of a meta-analysis.

OBJECTIVES: Amyloid light-chain (AL) amyloidosis is a rare disease characterized by amyloid fibril deposits made up of toxic light chains causing progressive organ dysfunction and death. Recent studies suggest that hematologic response may be an important prognostic indicator of overall survival (OS) in AL amyloidosis. The aim of this study was to evaluate the trial-level association between hematologic complete response (CR) or very good partial response or better (≥ VGPR) and OS in newly diagnosed patients. METHODS: Studies were identified via systematic literature review. Pooled effect estimates were generated by a random-effects model. RESULTS: Nine observational studies reporting hematologic CR or ≥VGPR and OS hazard ratios (HRs) were included in the meta-analysis. Achieving hematologic CR was associated with improved OS (HR, 0.21; 95% confidence interval [CI] 0.13-0.34). Achieving ≥ VGPR was also associated with improved OS (HR 0.21; 95% CI 0.17-0.26). Results of a sensitivity analysis excluding one outlier study revealed no heterogeneity and a better overall HR estimate. Potential limitations of this meta-analysis include the small number of eligible studies (consistent with the rarity of the disease) and inconsistencies in reporting of results. CONCLUSIONS: Overall, our findings support the use of deep hematologic response (CR or ≥VGPR) as a clinical trial endpoint in newly diagnosed AL amyloidosis. This study provides evidence that early hematologic response is a strong patient-level surrogate for long-term OS in patients with AL amyloidosis receiving frontline therapy. Structured data collection of depth of response in future trials will further strengthen these observations.

A Review of Current Approaches to Defining and Valuing Innovation in Health Technology Assessment.

OBJECTIVES: The growing focus on the value of new drugs for patients and society has led to a more differentiated notion of innovation in the context of pharmaceutical products. The goal of this article is to provide an overview of the current debate about the definition and assessment of innovation and how innovation is considered in reimbursement and pricing decisions. METHODS: To compile the relevant literature, we followed a 2-step approach. First, we searched for peer-reviewed literature that deals with the definition of pharmaceutical innovation. Second, we reviewed health technology assessment (HTA) guidelines of 11 selected countries (Australia, Belgium, Canada, England, France, Germany, Italy, Japan, Norway, Sweden, and The Netherlands) regarding aspects of innovation that are currently considered as relevant by the respective HTA bodies. RESULTS: All countries in our sample use 1 of 2 types of reward mechanism for novel drugs that they consider provide some sort of benefit. Generally, the focus is on the therapeutic benefit of a drug, whereas, depending on the exact arrangement, other aspects can also be taken into account. A reduction in side effects and aspects of treatment convenience can be invoked in some of the countries. Mostly, however, they are not considered unless they are already captured in the clinical outcomes used to measure the therapeutic benefit. CONCLUSION: Our review shows that although the health economic literature discusses a range of aspects on how innovation may generate value even without providing an immediate added therapeutic benefit (or on top of it), these are only selectively considered in the reviewed HTA guidelines. For most part, only the added therapeutic value is crucial when it comes to pricing and reimbursement decisions.

Budget impact analysis of the use of oral and intravenous therapy regimens for the treatment of relapsed or refractory multiple myeloma in Germany.

BACKGROUND: In Germany, several triplet therapies for treating relapsed or refractory multiple myeloma (rrMM) patients have recently been approved. While most of them are administered intravenously, ixazomib-based combination is the only orally bioavailable regimen. OBJECTIVE: To conduct a 1-year and 3-year budget impact analysis (BIA) of different novel triplets to treat patients with rrMM in second or subsequent therapy lines accounting for costs covered by German statutory health insurance (SHI). METHODS: A 3-state partitioned survival model (PSM) was developed to evaluate the budget impact of the following regimens: carfilzomib plus lenalidomide plus dexamethasone (KRd), elotuzumab plus lenalidomide plus dexamethasone (ERd), daratumumab plus lenalidomide plus dexamethasone (DRd), and ixazomib plus lenalidomide plus dexamethasone (IRd). The analysis included direct medical costs such as drug acquisition, comedication and preparation for parenteral solutions, drug administration and other 1-time costs, adverse event management costs and direct non-medical costs, such as transportation costs. RESULTS: Based on current drug market shares in German healthcare market, the estimated costs after 1 year of treatment was €551 million (KRd), €163 million (ERd), €584 million (DRd), and €95 million (IRd). The total budget impact of €1393 million is mainly driven by drug acquisition and subsequent therapy costs. CONCLUSION: Among the regimens of interest, the oral-based therapy regimens offered cost advantages over intravenous-based therapy regimens. The higher overall costs of intravenous therapy regimens were attributed primarily to higher drug acquisition costs.

Hospital utilization and expenditures among a nationally representative sample of Medicare fee-for-service beneficiaries 2 years after receipt of an Annual Wellness Visit.

Medicare's Annual Wellness Visit (AWV) provides an opportunity to link beneficiaries to cancer screenings and immunizations, however, research has not examined its effectiveness. The aim of this study was to examine the effect of receiving an AWV on outcomes while accounting for the healthy user effect. This study used 2013-2017 Medicare claims data to compare hospital utilization and total expenditures among a 5% random sample of Medicare fee-for-service (FFS) beneficiaries with and without AWV use in 2014 (228,053 AWV users were propensity-score matched to 228,053 nonusers). Linear fixed effects regression models examined differences in study outcomes 12 and 24 months after AWV use, controlling for baseline differences in sociodemographics, health status, utilization, and accountable care organization attribution. The proportion of Medicare FFS beneficiaries that used the AWV increased from 13% in 2013 to 24% in 2017. Users of the AWV had a marginally significant reduction in Medicare spending 12 months (-$122, 95% CI -$256, $11, p = 0.073) and significant reductions (-$162, 95% CI, -$310, -$14, p = 0.032) 24 months after the visit, relative to non-users. However it remains unclear what is driving these savings as there was no change in hospital-related utilization and results may still be biased due to inherent differences between users and non-users. The AWV provides an opportunity for providers to focus on prevention and geriatric needs not covered in typical office visits. Practices adopting AWVs have noted increased revenue, more stable patient populations, and stronger provider-patient relationships. While utilization remains low, it is steadily increasing over time.

Use of Welcome to Medicare Visits Among Older Adults Following the Affordable Care Act.

INTRODUCTION: To encourage greater utilization of preventive services among Medicare beneficiaries, the 2010 Affordable Care Act waived coinsurance for the Welcome to Medicare visit, making this benefit free starting in 2011. The objective of this study was to determine the impact of the Affordable Care Act on Welcome to Medicare visit utilization. METHODS: A 5% sample of newly enrolled fee-for-service Medicare beneficiaries for 2005-2016 was used to estimate changes in Welcome to Medicare visit use over time. An interrupted time series model examined whether Welcome to Medicare visits increased significantly after 2011, controlling for pre-intervention trends and other autocorrelation. RESULTS: Annual Welcome to Medicare visit rates began at 1.4% in 2005 and increased to 12.3% by 2016. The quarterly Welcome to Medicare visit rate, which was almost 1% at baseline, was increasing by 0.06% before the 2011 Affordable Care Act provision (p<0.001). Immediately following the 2011 Affordable Care Act provision, the rate increased by about 1% in the first quarter of 2011 (intercept, p<0.001), followed by an increase of 0.13% every subsequent quarter (slope, p<0.001). This general trend was observed in subgroup analyses, although this trend varied by subgroups where the pre-Affordable Care Act trends of lower utilization persisted over time for non-whites and improved less quickly for men, regions other than Northeast, and beneficiaries without any supplemental insurance. CONCLUSIONS: The Affordable Care Act, and perhaps the removal of cost sharing, was associated with increased use of the Welcome to Medicare visit; however, even with the increased use, there is room for improvement.

Congestive heart failure: who is likely to be readmitted?

Readmission for congestive heart failure (CHF) is the most common reason for readmission among Medicare fee-for-service patients. Yet CHF readmissions are not just a Medicare problem. This study examined who is likely to be readmitted for CHF, using all-payer hospital discharges from 14 of the states participating in the Healthcare Cost and Utilization Project. Patients with the strongest positive association with readmission were discharged against medical advice, covered by Medicaid, and had more severe loss of function and certain comorbidities such as drug abuse, renal failure, or psychoses. Weak negative relationship between readmission and cost of index admission provides some evidence that hospitals with higher readmission rates do not systematically use fewer resources in treating patients in initial encounters. High readmission rate for Medicaid patients suggests that state and federal governments should target Medicaid populations and drug abuse treatment for better care coordination to reduce readmissions and health care costs.

Impact of the HealthChoice program on cesarean section and vaginal birth after C-section deliveries: a retrospective analysis.

OBJECTIVE: To assess the impact of the HealthChoice program in Maryland on cesarean section and vaginal birth after C-section deliveries. STUDY DESIGN: Pre-post design using a comparison group with Maryland State Inpatient Databases, part of the Healthcare Cost and Utilization Project, developed by the Agency for Healthcare Research and Quality. Although the combined 1995 and 2000 database contained over 1.2 million inpatient discharge records, the analysis included all hospital discharge abstracts for women in labor. To identify the delivery, Diagnoses-Related Groups (DRGs) 370-375 were used from the discharge data. Together, there were 128,743 births identified in both years. METHODS: Pregnant women enrolled in Medicaid managed care were compared pre-implementation and post implementation with pregnant women delivering babies under private insurance. The analysis computed difference-in-differences estimates using a logistic regression model that controlled for maternal characteristics, payment source, labor and delivery complications, and hospital characteristics. The outcome variables included Primary Cesarean, Repeat Cesarean, and Vaginal Birth after C-section. RESULTS: These results suggest that Medicaid managed care enrollees were less likely to undergo cesarean section deliveries relative to privately insured beneficiaries. Medicaid MCOs may have done a better job of limiting the growth in overused procedures than did MCOs and providers for privately insured women. CONCLUSION: This study has shown that there has been an overall increase in the use of primary and repeat cesarean sections in Maryland hospitals. However, HealthChoice limited this increase for Medicaid enrollees relative to privately insured women. On the other hand, vaginal births after C-section have declined in Maryland.