Transcatheter aortic valve replacement for inoperable severe, symptomatic aortic stenosis will create significant social value in the next decade, mostly accruing to patients versus manufacturers.
Objectives: To project the social value of transcatheter aortic valve replacement (TAVR) for inoperable patients with severe, symptomatic aortic stenosis (SSAS).
Study Design: This study used an economic model with parameters obtained from the literature and from US Census Bureau population projections.
Methods: Our model estimated the economic value that will accrue to inoperable patients with SSAS and to device manufacturers as a result of TAVR utilization. We estimated individual patient value as the monetized gain in quality-adjusted life-years as estimated in the cost-effectiveness literature, net of device costs and cost offsets. We estimated manufacturer value by applying an assumed profit margin to revenue from device sales. We created population-level estimates by combining these individual-level estimates with age-stratified Census Bureau population projections and estimates of the incidence of AS. We assessed model uncertainty through the use of probabilistic sensitivity analyses.
Results: Between 2018 and 2028, approximately 465,000 inoperable Americans with SSAS will be treated with TAVR. These procedures will yield a cumulative social benefit of up to $48 billion, with roughly 80% of that benefit accruing to patients and 20% accruing to device manufacturers.
Conclusions: Policy makers and payers should take this social value into account when considering decisions related to the care of inoperable patients with SSAS.
Am J Manag Care. 2020;26(2):e50-e56. https://doi.org/10.37765/ajmc.2020.42401
Considering the US population between 2018 and 2028, we estimated the annual and cumulative social value accruing to patients and to manufacturers as a result of uptake of transcatheter aortic valve replacement (TAVR) for the treatment of severe, symptomatic aortic stenosis (SSAS) in inoperable patients.
Aortic stenosis (AS) is a common disease, affecting 2% to 7% of the global population older than 65 years.1 Although the condition can be asymptomatic for years, when symptoms do appear, untreated patients with severe AS have high mortality (up to 50% within 2 years).2,3 Surgical aortic valve replacement (SAVR), in which the sternum is opened to replace the aortic valve, has been shown to improve survival and quality of life in patients with severe, symptomatic AS (SSAS).4,5 Despite data supporting the use of SAVR for the treatment of SSAS, at least 30% of patients do not undergo SAVR, because of either patient preference to avoid invasive surgery or ineligibility for surgery as a result of advanced age and associated comorbidities (the latter referred to as inoperable patients).6,7 Historically, this population of untreated patients was treated with medical management alone, resulting in 3-year mortality rates as high as 80%.8,9 Transcatheter aortic valve replacement (TAVR) is a less invasive method of AVR in which the aortic valve is replaced through either the femoral artery or a small incision in the chest. Clinical trial data have demonstrated that TAVR for inoperable patients extends median survival by approximately 19 months and significantly improves quality of life compared with medical therapy alone,10,11 thereby offering an alternative treatment for this patient population. Accordingly, TAVR was first approved for commercialization in Europe in 200712 and by the US FDA in 2011 for the treatment of SSAS in inoperable patients.
With commercial approval of TAVR, the volume of these procedures in the United States has grown dramatically. Within Medicare, TAVR grew from 8.9% of all AVR procedures (across all risk groups) in 2012 to 50.3% in 2017.13 This rapid growth suggests a need for an analysis of the aggregate economic impact of TAVR treatment on the distribution of social welfare for inoperable patients; this type of study is referred to as social value analysis.14 These types of studies provide a useful complement to traditional cost-effectiveness analyses, as they incorporate the value to consumers, as well as the value to innovators, allowing policy makers to consider new technologies in a context that is both broad and deep. Inoperable patients who are treated with TAVR realize benefits in the form of increased quantity and quality of life relative to medical management. In addition, firms that manufacture TAVR devices realize benefits by way of profits earned on units sold. Payers may realize both costs (eg, via incremental new spending on TAVR devices) and benefits (eg, cost offsets realized through the avoidance of downstream events, such as postoperative inpatient readmissions). Assessing the value of TAVR to both payers and manufacturers allows for the estimation of the relative share of economic surplus returning to manufacturers (as opposed to consumers), therefore informing a broader discussion regarding optimal incentives for future innovation.
The purpose of this study was to estimate the present and future economic impact of TAVR adoption for inoperable patients with SSAS and for TAVR device manufacturers in the United States, using recently developed approaches for the assessment of economic value.15-20 Using an analysis time frame of 2018 to 2028, we aimed to project the size of the inoperable population with SSAS, estimate the fraction of this population who will receive TAVR, and calculate the economic returns of that utilization, for both the patients and the device manufacturers.
Projecting TAVR-Eligible Population From 2018 to 2028
To estimate the future economic impact of TAVR adoption for patients with inoperable SSAS and for TAVR manufacturers, we began by projecting the size of the inoperable population eligible for TAVR treatment.
To determine the number of inoperable patients with SSAS between 2018 and 2028, we first projected the number of patients with SSAS nationally, regardless of surgical risk status. We did this by multiplying current estimates of severe AS incidence rates (stratified by age) by the proportion of patients with severe AS whose disease is symptomatic,21,22 and then multiplying the resulting quantity by age-stratified US population projections for each year in the analysis period.23 Finally, we multiplied the values described earlier by the estimated fraction of patients with SSAS considered inoperable.7 The parameters used to perform these calculations are presented in Table 1.7,21,22,24-26
Projecting TAVR Utilization From 2018 to 2028
Only a fraction of incident inoperable SSAS cases are treated with TAVR.21,27 As such, we estimated the number of inoperable patients using TAVR in the future as the product of (1) the projected eligible inoperable population in each year (described previously), and (2) an estimate of the fraction of eligible inoperable patients who ultimately receive TAVR, extracted from the literature.21 As a conservative assumption, we assumed that this fraction remains constant over time. We also assumed that individuals can receive the treatment only once.
Calculation of Industry Value
TAVR market share estimates were available for the population with SSAS but not specifically for the inoperable population with SSAS. In addition, the prices of the different TAVR devices for the different SSAS risk groups (inoperable, high risk, and intermediate risk) are very similar.24 As such, for the purposes of this analysis, we used the best peer-reviewed cost-effectiveness evidence available, without regard to TAVR device type, and assumed that these results applied to all inoperable patients treated with TAVR.25 Cost-effectiveness results were then employed to calculate patient value (discussed later). As most contemporary TAVR procedures are performed using transfemoral (TF) access, we used cost-effectiveness results from a TF cohort.
We calculated industry revenue by multiplying the device price by the number of TAVR procedures on inoperable patients projected to occur annually between 2018 and 2028. We assumed that device cost would remain constant across years (Table 17,21,22,24-26).25 In addition, we conservatively assumed profit—analogous to welfare gains in the context of social value analysis—to be 80% of revenue.28 This is substantially larger than the profit margins of 18% to 29% reported by device manufacturers in recent years.29,30 Formally, (undiscounted) industry value in year t was calculated as Nt × P × p, where Nt denotes the number of procedures, P denotes the device price, and p denotes the profit margin.
Computation of the Monetized QALY Benefit of TAVR
We estimated the monetized value of the quality-adjusted life-year (QALY) gain for each treated inoperable patient by assuming a QALY willingness-to-pay (WTP) value of $150,000 (Table 17,21,22,24-26).26,31 A threshold of $150,000 was chosen because incremental cost-effectiveness ratios (ICERs) above this cutoff are considered low economic value as defined by the American Heart Association and the American College of Cardiology.32 We estimated the total monetized QALY gain for the US inoperable SSAS population in each year as the product of the individual monetized QALY value and the number of TAVR procedures on inoperable patients in each year.
Calculation of Patient Value
To circumvent the complexities of the US insurance market, this analysis used a societal perspective to estimate patient value. In this framework, we computed the net value that an individual obtains from TAVR as the difference between the monetized valuation of the QALY benefit (described previously) and the incremental difference in costs, including differences in the device cost, as well as differences in postprocedural medical expenses. The concept of patient value is thus an amalgamation of value returning to the patient (in the form of improved quality and/or quantity of life) and the change in medical costs borne by payers, which may be either patients themselves or, more typically, commercial or government insurers. For convenience, we refer to this construct as patient value. We extracted the values for cost offsets (including device cost) from the literature (Table 17,21,22,24-26)25 and converted them to 2017 US$ using the Medical Consumer Price Index.33 We assumed a discount rate of 3% consistent with US guidelines.34 Formally, (undiscounted) patient value in year t was calculated as Nt × (Q × WTP — P — C), where Nt denotes the number of procedures, Q denotes the QALY gain of TAVR relative to medical management, WTP denotes the WTP value for a QALY, P denotes the device price, and C denotes the estimated cost offsets of TAVR relative to medical management.
Sensitivity and Scenario Analyses
We assessed the model’s sensitivity to the joint uncertainty of all input parameters by implementing a probabilistic sensitivity analysis (PSA). In a PSA, model results are iteratively regenerated following resampling of input parameters from assumed statistical distributions, which are derived from published or assumed values (eg, means and CIs) describing the uncertainty of parameter point estimates. We varied QALY gains, lifetime cost offsets, incidence rates, the proportion of severe AS that is symptomatic, the proportion of SSAS that is inoperable, and the proportion of inoperable patients with SSAS who receive TAVR. Table 17,21,22,24-26 shows the assumed statistical distributions of the uncertainty parameters and assumptions that governed the PSA. We performed 1000 replications of the model and computed the fraction of these in which estimated societal value exceeded estimated industry value. We also separately present results from a scenario analysis, which uses a WTP value of $100,000 per QALY in place of the base-case parameter value of $150,000.
TAVR Uptake Projections
Between 2018 and 2028, approximately 465,000 Americans with inoperable SSAS were projected to receive TAVR. Because the gradual aging of the US population will slowly increase the annual incidence of SSAS, regardless of risk status, the number of inoperable patients with SSAS receiving TAVR was also projected to grow over time. Full projection results are presented in Table 2.
Annual Social Value
In 2018, approximately 39,000 inoperable patients with SSAS were estimated to receive TAVR, resulting in a cumulative gain of about 50,000 QALYs (Table 2). After accounting for device costs and cost offsets, and using a WTP value of $150,000 per QALY, approximately $3.7 billion in patient value was created. By contrast, assuming that firms retain 80% of revenues as profits, approximately $940 million of the social value accrued to manufacturers. When these values were projected to 2028, we estimated that these undiscounted benefits would increase to $4.4 billion and $1.1 million ($3.2 billion and $810 million discounted) in patient value and manufacturer value, respectively.
Cumulative Social Value
Between 2018 and 2028, we projected the total QALY gain among inoperable patients with SSAS to be 600,486 QALYs and the cumulative social value of TAVR (summing over inoperable patients and manufacturers) to be $48.1 billion. Roughly 80% of that value ($38.5 billion) accrued to patients and roughly 20% ($9.6 billion) to manufacturers (Table 2). Furthermore, we projected that the undiscounted social value will grow over time as the incidence of SSAS increases (Figure 121).
Sensitivity and Scenario Analysis Results
Figure 2 depicts repeated simulations of the model results following joint draws from the statistical distributions that describe the uncertainty in each of the model parameters (shown in Table 17,21,22,24-26). The base-case (deterministic) result is indicated as a single light blue point; the results of each of the 1000 replications are represented as dark blue points. Points appearing above the orange line represent instances in which the value accruing to patients is greater than the value accruing to manufacturers, and points below it indicate the reverse. In 99.8% of the replicated simulations, the economic value to inoperable patients was greater than the economic value to manufacturers.
When the WTP for a QALY was assumed to be $100,000, the cumulative patient value was estimated to fall from $38.5 billion to $12.6 billion, and the estimated share of value accruing to manufacturers would rise from 20.0% to 43.3% (Table 3). When the PSA was conducted using this lower valuation, patient value exceeded manufacturer value in 67.8% of the simulations.
Our findings suggest that substantial social value will be created as a result of TAVR treatment for inoperable patients with SSAS over the next decade. Our study projected that up to $48.1 billion in value will be generated between 2018 and 2028, with roughly 80% of that value accruing to inoperable patients and 20% to manufacturers. A PSA suggested that the portion of social value realized by inoperable patients is likely to exceed the value that will return to manufacturers, as this result was obtained in up to 99.8% of the simulated repetitions.
Prior research has found that TAVR is cost-effective compared with medical management in the inoperable population. Using data from the PARTNER B trial (ClinicalTrials.gov NCT00530894), Reynolds et al found that TAVR would generate a lifetime benefit of 1.29 QALYs per patient, at an incremental cost of $79,837, resulting in an ICER of $50,212 per QALY.25 Our study builds on these results by estimating the total social value that TAVR will generate and assessing the distribution of that value between patients and manufacturers. This perspective is useful for payers and policy makers because it extends the decision-making calculus around TAVR adoption beyond a narrow consideration of short-term costs. In addition, our study informs a larger debate in the literature regarding the relationship between the manufacturer share of economic returns from a new medical technology and incentives for future innovation.35,36
Although we observed a large social benefit of TAVR in the inoperable population with SSAS, it is possible that we underestimated the true benefit. First, the data used to inform our study were derived from the use of a first-generation device in the early age of TAVR. Over the past 10 years, there have been substantial improvements in device technology, procedural planning, operator experience, and post-TAVR care, which have been associated with better clinical outcomes and lower resource utilization.37-39 Another factor that may also contribute to underestimating the social benefit of TAVR in the inoperable population is the effect of prior undertreatment of this population on our future projection. Durko et al estimated that roughly one-third of inoperable patients with incident SSAS do not receive TAVR.21 This value aligns closely with our own comparison of the number of AVR procedures performed annually in the United States with our estimates of the number of annual incident cases (results not shown) and is consistent with previous research.40 Furthermore, previous research has suggested that roughly a quarter of patients with SSAS who are offered only SAVR will decline it.41 Accordingly, it is unknown what fraction of patients who are eligible for TAVR either are not offered it or decline it, thereby leading to the undertreatment of this population. To the extent that patient perception of TAVR as a less invasive alternative grows over time, undertreatment of SSAS may be reduced.42 As such, the cost-effectiveness of TAVR in the current era may be greater than previously estimated, and thus our calculations may underestimate the true social value of TAVR in the inoperable population with SSAS.
It is useful to consider our results in the context of other social value studies. Although this study provides the first assessment of the distributional effects on social value for TAVR, informative comparisons are available in the literature. Our estimate of the share of value returning to manufacturers for TAVR (roughly 20%) is nearly identical to the fraction estimated by a recent study on statins.18 A much lower estimate (2%) was obtained for pediatric vaccines,20 whereas another study found that between 25% and 66% of value accrues to manufacturers for 3 therapies treating multiple sclerosis, depending on modeling assumptions.43 This context suggests that, relative to several therapies, TAVR may generate reasonably large returns to inoperable patients and to society per dollar of manufacturer profit.
Of note, TAVR has also been demonstrated to be cost-effective relative to SAVR for operable patients at high44 and intermediate45 surgical risk. Furthermore, recent clinical trials have demonstrated that TAVR yields substantial benefits relative to SAVR for patients at low surgical risk, who comprise the largest proportion of patients with SSAS.46,47 This suggests, first, that the social value of TAVR may extend beyond the inoperable risk group and, second, that this value will be inherently conditional on the degree to which patients and doctors select treatment with TAVR or SAVR. Future research should address these questions directly.
This study has several limitations. First, the results rely on projections of unknown future quantities (eg, the percentage of inoperable patients with SSAS who will receive TAVR). We sought to make realistic projections through analysis of data observed in the recent past. However, to the extent that our projections are inaccurate, our estimates may be biased. For example, we assumed the incidence of AS to remain constant, whereas real-world data show that the age-adjusted population incidence of AS decreased in recent years.48 Second, we estimated base-case results by incorporating several parameters obtained from the literature into a single economic model. Many of these parameters were estimated with uncertainty, including the QALY benefit and cost offset associated with TAVR usage, as well as the fraction of patients with SSAS considered inoperable. We sought to mitigate this limitation by incorporating the uncertainty associated with each input parameter into a joint PSA. Additionally, as noted previously, the estimated benefit of TAVR for inoperable patients (1.29 QALYs) was obtained from a cost-effectiveness study of an early-generation TAVR device (SAPIEN), as these are the only data available for this patient population.25 Because patient outcomes have improved over time and resource utilization has decreased, we may have underestimated the social value of TAVR by using this data. Third, the data that provided our QALY benefit and cost-offset input parameters considered only TAVR procedures conducted via the TF route25 and did not consider TAVR procedures performed via the less common alternative access routes (eg, transapical). Thus, our results cannot be generalized to TAVR performed via alternative access in this population, although we believe that inoperable patients eligible only for alternative access represent a small portion of the overall population, given that the rates of alternative-access TAVR have decreased substantially over time because of the progressively smaller delivery system of newer-generation TAVR devices.49 Finally, our estimate of the cost offsets associated with TAVR for inoperable patients comes from a study that used a 1-year period.25 Thus, our model did not account for any cost differences that might exist beyond this period.
We sought to estimate the value that will accrue to society—both in aggregate and to different segments of society—as a result of expected TAVR uptake by inoperable patients with SSAS between 2018 and 2028. We projected that up to $48.1 billion in social value will be generated, with roughly 80% of that value accruing to patients and the remainder accruing to manufacturers. Future research is needed to assess the social value of TAVR in patients with operable SSAS.Author Affiliations: Precision Health Economics, Oakland (JS, TTS) and Los Angeles (EvE, ABJ), CA; Lahey Hospital and Medical Center (SJB), Burlington, MA; Edwards Lifesciences (CT, SC), Irvine, CA; Harvard Medical School (ABJ), Boston, MA; Massachusetts General Hospital (ABJ), Boston, MA.
Source of Funding: Edwards Lifesciences Inc.
Author Disclosures: Dr Sussell was an employee of Precision Health Economics, a consultancy of the health and life sciences industries, at the time of this study. Ms van Eijndhoven and Mr Schwartz are employees of Precision Health Economics. Dr Baron reports consulting for Edwards Lifesciences, advisory board membership for Abiomed and Boston Scientific Corp, and a pending research grant from Boston Scientific Corp. Dr Thompson and Mr Clancy are full-time employees of and own stock in Edwards Lifesciences, which manufactures transcatheter aortic valve implants. Dr Jena has received consulting fees unrelated to this work from Pfizer, Bristol-Myers Squibb, Novartis, Amgen, Eli Lilly, Vertex Pharmaceuticals, AstraZeneca, Celgene, Tesaro, Sanofi Aventis, Biogen, and Precision Health Economics and has received consulting fees for economic expert testimony from Analysis Group.
Authorship Information: Concept and design (JS, EvE, TTS, SJB, CT, SC, ABJ); acquisition of data (JS, EvE, TTS, SC); analysis and interpretation of data (JS, EvE, TTS, SJB, CT, SC, ABJ); drafting of the manuscript (JS, EvE, TTS, SJB, SC, ABJ); critical revision of the manuscript for important intellectual content (JS, EvE, TTS, SJB, CT, SC, ABJ); statistical analysis (JS, EvE, ABJ); provision of patients or study materials (CT, SC); obtaining funding (SC); administrative, technical, or logistic support (TTS, CT, SC); and supervision (JS, CT, SC, ABJ).
Address Correspondence to: Emma van Eijndhoven, MS, MA, Precision Health Economics, 11100 Santa Monica Blvd, Ste 500, Los Angeles, CA 90025. Email: firstname.lastname@example.org.REFERENCES
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