Can Generalized Cost-Effectiveness Analysis Leverage Meaningful Use of Novel Value Elements in Pharmacoeconomics to Inform Medicare Drug Price Negotiation?

OBJECTIVES: Decision makers considering using cost-effectiveness analysis (CEA) to inform health-technology assessment must contend with documented and controversial shortfalls of CEA, including its assumption of disease severity independence and static pricing. ISPOR has recently introduced novel value elements besides direct healthcare cost and effectiveness for the patient, and these should be captured in CEA. Although novel value elements advance our understanding of "what" should be measured (value of hope, severity of disease, health equity, etc), there is limited direction on "how" to measure them in conventional CEA. Furthermore, with Medicare empowered to set drug prices under the Inflation Reduction Act, it is not clear what role CEA might have on where prices are set, given objections to the quality-adjusted life year in conventional approaches. METHODS: We critically reviewed the evidence for expanding conventional CEA methods to a more generalized approach of generalized CEA (GCEA). RESULTS: GCEA accounts for methods that address objections to the quality-adjusted life year and incorporate novel value elements. Although GCEA offers advantages, it also requires further research to develop "off-the-shelf" resources to help inform, for example, maximum fair price in the context of Medicare drug price negotiation. CONCLUSIONS: Should a shift toward GCEA reveal that the societal value of novel medicines exceeds their market-based costs, which will raise the key question of what market failure Medicare negotiation is meant to solve, if any, and therefore what the appropriate role of such negotiation might be to maximize the value society might garner from the development of novel medicines.

Dehydrated human amnion/chorion membrane to treat venous leg ulcers: a cost-effectiveness analysis.

OBJECTIVE: To evaluate the cost-effectiveness of dehydrated human amnion/chorion membrane (DHACM) in Medicare enrolees who developed a venous leg ulcer (VLU). METHOD: This economic evaluation used a four-state Markov model to simulate the disease progression of VLUs for patients receiving advanced treatment (AT) with DHACM or no advanced treatment (NAT) over a three-year time horizon from a US Medicare perspective. DHACM treatments were assessed when following parameters for use (FPFU), whereby applications were initiated 30-45 days after the initial VLU diagnosis claim, and reapplications occurred on a weekly to biweekly basis until completion of the treatment episode. The cohort was modelled on the claims of 530,220 Medicare enrolees who developed a VLU between 2015-2019. Direct medical costs, quality-adjusted life years (QALYs), and the net monetary benefit (NMB) at a willingness-to-pay threshold of $100,000/QALY were applied. Univariate and probabilistic sensitivity analyses (PSA) were performed to test the uncertainty of model results. RESULTS: DHACM applied FPFU dominated NAT, yielding a lower per-patient cost of $170 and an increase of 0.010 QALYs over three years. The resulting NMB was $1178 per patient in favour of DHACM FPFU over the same time horizon. The rate of VLU recurrence had a notable impact on model uncertainty. In the PSA, DHACM FPFU was cost-effective in 63.01% of simulations at the $100,000/QALY threshold. CONCLUSION: In this analysis, DHACM FPFU was the dominant strategy compared to NAT, as it was cost-saving and generated a greater number of QALYs over three years from the US Medicare perspective. A companion VLU Medicare outcomes analysis revealed that patients who received AT with a cellular, acellular and matrix-like product (CAMP) compared to patients who received NAT had the best outcomes. Given the added clinical benefits to patients at lower cost, providers should recommend DHACM FPFU to patients with VLU who qualify. Decision-makers for public insurers (e.g., Medicare and Medicaid) and commercial payers should establish preferential formulary placement for reimbursement of DHACM to reduce budget impact and improve the long-term health of their patient populations dealing with these chronic wounds. DECLARATION OF INTEREST: Support for this analysis was provided by MiMedx Group, Inc., US. JLD, and RAF are employees of MiMedx Group, Inc. WHT, BH, PS, BGC and WVP were consultants to MiMedx Group, Inc. VD, AO, MRK, JAN, NW and GAM served on the MiMedx Group, Inc. Advisory Board. MRK and JAN served on a speaker's bureau. WVP declares personal fees and equity holdings from Stage Analytics, US.

Defects in Value Associated With Hospital-Acquired Conditions: How Improving Quality Could Save U.S. Healthcare $50 Billion.

ABSTRACT: Hospital-acquired conditions in the United States are considered avoidable complications but remain common statistics reflecting on health system performance and are a leading cause of patient fatality. Currently, over 3.7 million patients experience a hospital-acquired condition in the United States each year, which costs the U.S. healthcare delivery system an excess of $48 billion. Evidence-based clinical practice guidelines for common hospital-acquired conditions (e.g., infections, falls, pressure injuries) to reduce risk to the patient. In each of these instances, preventing the outcome with these guidelines costs less than treating the outcome, in addition to keeping the patient safe from harm. By applying the framework of defects in value to hospital-acquired conditions, we estimate that U.S. health systems could avert this $48 billion in spending on treating harmful hospital-acquired conditions; more so, these systems of care could recuperate over $35 billion after investing proportionally in a system that delivers greater quality by preventing hospital-acquired conditions over treating them. Currently, the Centers for Medicare and Medicaid Services only withholds reimbursements for hospital-acquired conditions and penalizes health systems with high rates of these outcomes. However, payers do not offer any reward-based incentives for hospital-acquired condition prevention. A series of policy and health system solutions, including tracking of hospital-acquired condition rates in electronic health records, identifying centers of excellence at reducing rates of harm with the use of clinical practice guidelines, and rewarding them monetarily for reduced rates could create equal-sided risk and opportunity to engage health systems in improved performance.

Cost effectiveness of immunotherapy combination therapies for endometrial cancer.

Over the past five years (2019-2023), several new targeted therapies and immunotherapy has been approved in treating relapsed cervical, ovarian, and endometrial cancers. Concurrently, there has been growing recognition of financial toxicity associated with cancer care during this time period. As such, we reviewed FDA approvals from 2019 to 2013 and identified the following approvals in gynecologic oncology: pembrolizumab plus lenvatinib, pembrolizumab for recurrent endometrial cancer that is MSI-H/dMMR, tisotumab vedotin, dostarlimab as single-agent therapy, and dostarlimab plus chemotherapy. We focused on approvals for endometrial cancer, and conducted a cost-effectiveness analysis for combination options approved in treating recurrent or advanced endometrial cancer (i.e. pembrolizumab plus lenvatinib versus placebo; dostarlimab plus chemotherapy versus placebo), and found neither regimen was cost-effective at a willingness-to-pay of $100,000 per Equal Value of Life Years Gained (evLYG). While these costs may not necessarily be translated to an individual patient, these costs are absorbed by healthcare systems and insurance providers on a larger scale with downstream effects on individuals contributing to healthcare costs a whole.

Predicting pressure injury risk in hospitalised patients using machine learning with electronic health records: a US multilevel cohort study.

OBJECTIVE: To predict the risk of hospital-acquired pressure injury using machine learning compared with standard care. DESIGN: We obtained electronic health records (EHRs) to structure a multilevel cohort of hospitalised patients at risk for pressure injury and then calibrate a machine learning model to predict future pressure injury risk. Optimisation methods combined with multilevel logistic regression were used to develop a predictive algorithm of patient-specific shifts in risk over time. Machine learning methods were tested, including random forests, to identify predictive features for the algorithm. We reported the results of the regression approach as well as the area under the receiver operating characteristics (ROC) curve for predictive models. SETTING: Hospitalised inpatients. PARTICIPANTS: EHRs of 35 001 hospitalisations over 5 years across 2 academic hospitals. MAIN OUTCOME MEASURE: Longitudinal shifts in pressure injury risk. RESULTS: The predictive algorithm with features generated by machine learning achieved significantly improved prediction of pressure injury risk (p<0.001) with an area under the ROC curve of 0.72; whereas standard care only achieved an area under the ROC curve of 0.52. At a specificity of 0.50, the predictive algorithm achieved a sensitivity of 0.75. CONCLUSIONS: These data could help hospitals conserve resources within a critical period of patient vulnerability of hospital-acquired pressure injury which is not reimbursed by US Medicare; thus, conserving between 30 000 and 90 000 labour-hours per year in an average 500-bed hospital. Hospitals can use this predictive algorithm to initiate a quality improvement programme for pressure injury prevention and further customise the algorithm to patient-specific variation by facility.

Comparative Effectiveness of Placental Allografts in the Treatment of Diabetic Lower Extremity Ulcers and Venous Leg Ulcers in U.S. Medicare Beneficiaries: A Retrospective Observational Cohort Study Using Real-World Evidence.

Objective: To compare the effectiveness of cellular tissue products (CTP) versus standard care in U.S. Medicare beneficiaries with diabetic lower extremity ulcers (DLEUs) or venous leg ulcers (VLUs). Approach: We performed a retrospective cohort study using real-world evidence from U.S. Medicare claims for DLEUs or VLUs between 2016 and 2020. There were three cohorts evaluated: viable cryopreserved placental membrane (vCPM) or viable lyopreserved placental membrane (vLPM); other CTP; and standard care. Claims were collapsed into episodes of care. Univariate and bivariate statistics were used to examine the frequency distribution of demographics and clinical variables. Multivariable zero-inflated binomial regressions were used to evaluate mortality and recurrence trends. Logistic regression compared three adverse outcomes (AOs): amputation; 1-year mortality; and wound recurrence. Results: There were 333,362 DLEU episodes among 261,101 beneficiaries, and 122,012 VLU episodes among 80,415 beneficiaries. DLEU treatment with vLPM was associated with reduced 1-year mortality (-26%), reduced recurrence (-91%), and reduced AOs (-71%). VLU treatment with vCPM or vLPM was associated with reduced 1-year mortality (-23%), reduced recurrence (-80%), and 66.77% reduction in AOs. These allografts were also associated with a 49% and 73% reduced risk of recurrence in DLEU and VLU, respectively, compared with other CTPs. Finally, vCPM or vLPM were associated with noninferior prevention of AOs related to amputation, mortality, and recurrence (95% CI: 0.69-1.14). Conclusions: DLEUs and VLUs treated with vCPM and vLPM allografts are associated with lowered 1-year mortality, wound recurrence, and AOs in DLEUs and VLUs compared with standard care. Decision makers weighing coverage of placental allografts should consider these added short- and long-term clinical benefits relative to costly management and high mortality of Medicare's most frequent wounds.

The impact of a mixed reality technology-driven health enhancing physical activity program among community-dwelling older adults: a study protocol.

Background: Physical inactivity and a sedentary lifestyle among community-dwelling older adults poses a greater risk for progressive physical and cognitive decline. Mixed reality technology-driven health enhancing physical activities such as the use of virtual coaches provide an emerging and promising solution to support healthy lifestyle, but the impact has not been clearly understood. Methods and analysis: An observational explanatory sequential mixed-method research design was conceptualized to examine the potential impact of a user-preferred mixed reality technology-driven health enhancing physical activity program directed toward purposively selected community-dwelling older adults in two senior centers in the Philippines. Quantitative components of the study will be done through a discreet choice experiment and a quasi-experimental study. A total of 128, or 64 older adults in each center, will be recruited via posters at community senior centers who will undergo additional screening or health records review by a certified gerontologist to ensure safety and proper fit. Treatments (live coaching with video-based exercise and mixed reality technology-driven exercise) will be assigned to each of the two senior center sites for the quasi-experiment. The participants from the experimental group shall be involved in the discreet choice experiment, modeling, and usability evaluations. Finally, a qualitative sample of participants (n = 6) as key informants shall be obtained from the experimental group using purposive selection. Discussion: This study protocol will examine the health impact of a promising mixed reality program in health promotion among older adults. The study utilizes a human-centered mixed method research design in technology development and evaluation in the context of developing nations.Clinical trial registration: ClinicalTrials.gov, identifier NCT06136468.