Clinical Device-Related Article The power of disruptive technological innovation: Transcatheter aortic valve implantation David B. Berlin,1 Michael J. Davidson,2 Frederick J. Schoen3 1
Covidien, Boulder, Colorado 80503 Division of Cardiac Surgery, Department of Surgery, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts 02115 3 Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts 02115 2
Received 12 August 2014; revised 21 October 2014; accepted 2 December 2014 Published online 24 December 2014 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/jbm.b.33352 Abstract: We sought to evaluate the principles of disruptive innovation, defined as technology innovation that fundamentally shifts performance and utility metrics, as applied to transcatheter aortic valve implantation (TAVI). In particular, we considered implantation procedure, device design, cost, and patient population. Generally cheaper and lower performing, classical disruptive innovations are first commercialized in insignificant markets, promise lower margins, and often parasitize existing usage, representing unattractive investments for established market participants. However, despite presently high unit cost, TAVI is less invasive, treats a “new,” generally high risk, patient population, and is generally done by a multidisciplinary integrated heart team.
Moreover, at least in the short-term TAVI has not been lowerperforming than open surgical aortic valve replacement in high-risk patients. We conclude that TAVI extends the paradigm of disruptive innovation and represents an attractive commercial opportunity space. Moreover, should the longterm performance and durability of TAVI approach that of conventional prostheses, TAVI will be an increasingly attracC tive commercial opportunity. V 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 103B: 1709–1715, 2015.
Key Words: valves, aortic stenosis, prosthesis, transcatheter implantation
How to cite this article: Berlin DB, Davidson MJ, Schoen FJ. 2015. The power of disruptive technological innovation: Transcatheter aortic valve implantation. J Biomed Mater Res Part B 2015:103B:1709–1715.
INTRODUCTION
The convergence of technological progress and medical care has yielded impressive advances in health outcomes and standard of care, and, often yielded economic benefit.1,2 In particular, technology development has enabled the use of implantable cardiovascular medical devices, including pacemakers and cardioverter/defibrillators, prosthetic heart valves, endovascular stents and stent-grafts, cardiac assist devices, and widely used non-cardiovascular implants, as exemplified by total joint replacements and intraocular lenses. However, the adoption into medical practice of new technologies contributes to the economic challenges associated with providing modern comprehensive care to patients through increasingly powerful, yet complex and often very costly medical procedures and devices. As health providers are increasingly pushed to provide high quality care to expanded patient populations at lower incremental cost, and “value” considerations dominate, understanding the dynamics of healthcare innovation through development
and commercialization of medical technology likely will be increasingly important.3 We believe that an evaluation of the applicability of the theory of disruptive innovation to a new and powerful yet expensive cardiovascular technology should be instructive to addressing the challenge of providing technology-intensive quality care to expanding patient populations. This report explores the paradigm of disruptive innovation and the applicability and impact of this concept to the development, commercialization, and implementation of new medical devices and other technologies. After focusing on general concepts, we will examine a specific example where effective clinical implementation of disruptive medical device innovation has occurred, namely transcatheter aortic valve implantation (TAVI). With this procedure, the combination of device design, route of implantation, provider team, and the composition of the patient population so treated is novel. Our analysis and conclusions are intended to be of particular relevance to both those
Correspondence to: F. J. Schoen; e-mail: [email protected]
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interested in developing, commercializing, and using advanced medical devices as well as those interested in fostering a regulatory environment that encourages the ongoing advancement and implementation of medical technology for high quality, effective, and efficient but affordable care.
DISRUPTIVE INNOVATION—OVERVIEW OF THE CONCEPT
The concept of disruptive innovation was elucidated by Harvard Business School Professor Clayton Christensen in his 1997 book, The Innovator’s Dilemma.4 Christensen’s more recent book, The Innovator’s Prescription: A Disruptive Solution for Health Care, published in 2009, extends the disruptive innovation paradigm to medical devices and diagnostic equipment.5 Christensen’s framework characterizes typical innovation as sustaining innovation, the process of improving technology along traditionally accepted performance standards, and generally through iterative, focused modifications that enhance performance, patient outcomes, and/or utility. Developers and manufacturers generally excel at sustaining innovation to the point where their products increase performance more rapidly than customer demands increase, ultimately leading to products that outperform market demands. In contrast, disruptive innovation fundamentally shifts the metrics against which performance and utility are measured. Indeed, Christensen defines disruptive innovations (quite generically) through the following characteristics: Simpler, cheaper, and lower performing. Promise lower margins, not higher profits. Often initially shunned by leading customers who can’t use and don’t want them. First commercialized in emerging or insignificant markets. Given these characteristics, disruptive innovations in their infancy usually represent unattractive investments for incumbent market participants (as they often parasitize existing usage), and initially do not satisfy the needs of current end-users (who don’t know how to optimize benefit from the “disruption”). However, once disruptive innovations reach the market, their performance often improves at a rate faster than market demands increase, while the product costs remain below that of incumbent products. Through this dynamic, disruptive innovations may provide acceptable performance, often at lower cost and greater utility than legacy products, procedures, and other technologies, ultimately allowing them to reach broad application. The combination of lowered costs, adequate performance and/or outcomes, and potentially enhanced access allows disruptive innovations to reach a large base of users who were previously priced out of or otherwise excluded from the market. TAVI is a timely choice of a product being introduced rapidly into clinical practice and has many attributes of a disruptive technology in which risk stratification and costs
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will be significant concerns in selecting therapy. Other disruptive technologies developed to manage serious cardiovascular disease are also under evaluation to compare outcomes and economics with those of their more invasive counterparts. For example, the percutaneous coronary intervention (i.e., stenting) vs. coronary artery bypass graft surgery debate has entered a critical stage of evaluating cost and outcomes. Recently, open surgical coronary artery bypass grafting (CABG) has been confirmed to be the procedure of choice for patients with complex disease, while stents have been shown to be an acceptable alternative, both clinically and economically, for those with less complex disease.6,7 Moreover, for endovascular stent graft versus open surgical repair of abdominal aortic aneurysms, longterm survival and costs have been demonstrated to be approximately equivalent (albeit with a greater reintervention rate in the endovascular group).8,9 We expect that the discussions and data concerning these and other technological innovations, particularly in the realm of less invasive options for serious cardiovascular disease, will yield ongoing lessons learned that will inform the TAVI versus surgical valve placement discussion.
TRANSCATHETER AORTIC VALVE IMPLANTATION
Aortic stenosis (AS) is the most common valvular heart disease in Western countries, and has serious consequences.10 The prevalence of AS increases with age, reaching about 3% after the age of 75 in the US. Thus, the global burden of AS is expected to double within the next 50 years as life expectancy lengthens. The limited available understanding of AS mechanisms and pathobiology has precluded development of effective non-invasive medical treatments.11 Symptomatic severe AS not treated promptly by corrective surgery has a high mortality as well as high and accelerating symptom burden. Valve replacement surgery (consisting of open chest aortic valve replacement [AVR] done by cardiac surgeons under cardiopulmonary bypass) has a relatively low mortality in uncomplicated cases (3%), generally alleviates symptoms and markedly prolongs survival.12 Existing valve replacement devices have undergone substantial sustaining innovation since early clinical use >50 years ago, by incremental improvements in biomaterials and design, yielding predictable long-term results.13,14 In practice, however, AVR is often denied to elderly and other high-risk patients with severe symptomatic AS, who would be at high risk with conventional surgery owing to extensive co-morbidities or frailty.15,16 TAVI, first performed in humans in 2002, is accomplished through peripheral arterial access, is a less invasive alternative to conventional AVR, and extends the opportunity for effective mechanical correction to a potentially large population of otherwise untreatable individuals.17,18 Clinical experience with TAVI is growing rapidly, with an estimated 80,0001 TAVI procedures performed worldwide to date. Early mortality in a meta-analysis of 25 studies involving over 8800 patients was 7.5%.19 Randomized and observational clinical trials comparing TAVI to classical open
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surgical AVR suggest that survival following TAVI in highrisk patients is equivalent to or better than that of AVR at 1–2 years.12,20,21 Indeed, TAVI is not only considered a disruptive innovation in this space, but also has rapidly been adopted as the new standard of care for many patients with symptomatic AS who would otherwise be deemed inoperable. The design of the devices used in TAVI is necessarily different than that of conventional substitute heart valves. Valves used in TAVI generally consist of a bioprosthetic tissue valve, typically fabricated from bovine pericardium, mounted on a compressible metallic stent. The valve is inserted within the diseased native aortic valve, and without the use of cardiopulmonary bypass. Access is obtained either through a peripheral artery (femoral or subclavian) or directly through the aorta or left ventricular apex. Once located at the level of the aortic valve, the device requires balloon dilatation or self-expands (if fabricated from a shape memory alloy such as Nitinol). The patient’s native aortic valve is not removed in TAVI (as in AVR) but rather is pushed aside to the periphery of the annulus, and compressed against the aortic root. During TAVI, delivery, positioning, and permanent fixation in the optimal location are guided by a combination of fluoroscopy and echocardiography and are critical to procedural success. Complications have been observed in approximately one-third of patients, and may include vascular injury, paravalvular leak, and stroke.22 A variety of prostheses developed specifically for TAVI are currently in use, and many other models are in preclinical and clinical stages of development.23 Two transcatheter aortic-valve devices have been and are currently approved by the FDA for use in the United States: the Edwards Sapien aortic valve (2011, Edwards LifeSciences, Irvine, CA) and the Medtronic CoreValve (2014, Medtronic, Minneapolis, MN). Long-term complications associated directly with the tissue interactions with the leaflets would be expected to be similar to those of bioprosthetic valves implanted surgically,24 but this has not yet been confirmed.
APPLICATION OF THE DISRUPTIVE INNOVATION FRAMEWORK TO TAVI
As a significant deviation from the current surgical techniques for treating AS, TAVI exemplifies elements of Christensen’s “disruptive” framework.25,26 However, the implantation procedure and the associated technology of TAVI have both similarities to and differences from those described by the formal framework of disruptive innovation established by Christensen.27 The dynamics of disruptive innovation have been previously examined with regard to the systemic delivery of healthcare services; however, there is limited literature rigorously examining the application of these dynamics to surgical technology, and particularly novel medical devices and procedures.28 The disruptive features of TAVI have significant implications for the unit cost of care, the manner in which medical services are provided, the long-term applicability of this technology to enlarging and diverse patient populations, and the incentives for commercializing novel cardiac medical device technology. Thus, the paradigm
of disruptive innovation characteristics delineated by Christensen may require modification when applied to TAVI. Target patient population and market size A tenet central to Christensen’s model of disruptive innovation is that disruptive technologies are initially limited to emerging or insignificant markets. For TAVI, the addition of a “new” patient population not at the expense of those undergoing AVR is a crucial feature. The current expert guidelines for clinical use of transcatheter valve implantation, published in the European Heart Journal in 2008, recommend restriction of TAVI to “high-risk patients or those with contraindications for surgery.”29 However, the statement also notes that “[indications for use] may be extended to lower risk patients if the initial promise holds to be true after careful evaluation.” The sentiment of this European statement is echoed in a similarly timed 2008 AHA Scientific Statement, which concluded, “. . .percutaneous AVR . . .should be limited in use to patients considered to be high risk or to inoperable surgical candidates. In this context, even after FDA approvals, percutaneous devices should be used in only a small number of centers. . .until they are thoroughly tested in the clinical arena.”30 Superficially, it would appear that transcatheter valves are indeed restricted initially to a small or potentially insignificant market, in that their use is initially limited to nonsurgical candidates or patients at unacceptably high risk for conventional surgery. However, epidemiologic studies of the target demographic indicate that this is in fact not a small or insignificant market. Approximately, 85,000 AVRs are done in the US each year. It is estimated that at least 30% of patients with severe symptomatic AS are inoperable.31 Previously, incumbent surgical valve manufacturers offered no effective surgical intervention suitable for these patients. Moreover, TAVI may also be a suitable approach to management of some patients with a failed bioprosthetic valve replacement.32 Cost vs. performance Analyzing the cost and performance characteristics of TAVI adds an additional level of complexity. While equipment costs vary by institution, a transcatheter aortic valve device is estimated to cost $30,000 while a traditional prosthetic mechanical or tissue valve is estimated to cost $5,000. The calculated total admission cost of open AVR is $74,067; similarly, the cost of a TAVI procedure is calculated at $73,219.33 Clearly, from the perspective of an incumbent valve manufacturer, TAVI does not meet the “cheaper” characteristic. However, this evaluation of cost might reach a different conclusion if viewed from the different perspectives of the provider, the hospital or the broader healthcare system, especially with respect to the device costs, procedure costs, or longitudinal systemic total healthcare costs of a patient. For instance, in mature TAVI systems (i.e., Europe) increasing number of procedures are being performed without the use of general anesthesia and with short hospital stays, potentially reducing hospital costs significantly (and this approach is beginning to be applied in the US). The
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several perspectives may offer different conclusions regarding the costs of TAVI as compared with those of traditional surgical AVR (or non-treatment of high-risk populations who could not be candidates for AVR). In the United States, hospitals and providers may be reimbursed at a lower rate for TAVI than for surgical AVR, and these rates may vary among geographic regions. Thus, TAVI may be financially unattractive as this procedure can incur a net loss. Although reimbursement patterns may evolve, this currently impacts adoption in the United States. The evaluation of performance of TAVI in the context of disruptive innovation requires the delineation of suitable performance metrics. A widely adapted view of ideal prosthetic valve performance is described by Dr. Dwight Harken’s “ten commandments,” initially formulated in 1962, but largely relevant today.34 Traditional valve development and performance metrics have focused on incremental improvements intended to limit thrombosis and propagation of emboli, durability, enhancing surgical fixation and healing in the annulus, lack of infection and hemolysis, and improving other physiologic and mechanical determinants of performance. However, a transcatheter valve offers its most significant value directly through avoiding sternotomy, cardiopulmonary bypass, and aortic clamping, features of open AVR which are undesirable in the population suited for TAVI. The existing framework of disruptive innovation would imply that this new performance would come at the cost of inferior traditional performance metrics, such as those just mentioned. Nevertheless, the clinical trial results demonstrate noninferiority of transcatheter valves relative to surgically implanted valves in terms of mortality and in some cases hemodynamics, thereby contradicting the “lower performing” tenet of the disruptive innovation framework, at least in the short term. The performance dynamics of disruptive innovation in the clinical environment are worthy of additional evaluation, specifically due to the associated regulatory structure. The current regulatory structure for approval of medical devices in the United Sates creates significant hurdles for the introduction of technologies that offer a novel value proposition, as these new products are often held to the performance standards of existing marketed technologies.35,36 This dynamic may restrain the forces of innovation that have been so powerful in propelling the advancement of technology in other industries by limiting the introduction of technology that requires a trade-off between new and existing performance metrics. Nevertheless, both the Edwards LifeSciences Sapien Valve and the Medtronic CoreValve TAVI devices have been granted approval by the FDA for use in patients with severe AS who are at high mortality risk if they undergo traditional open-heart procedures. Although the long-term structural performance of transcatheter valves is unknown at this time, they may represent a performance dynamic more in line with the expected dynamics of disruptive innovations. TAVI will be done predominantly in elderly patients with AS, and, as previously demonstrated, bioprosthetic valves implanted in older patients have a better outcome than those in younger patients.37 Thus, long-term durability will be difficult to
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document. Moreover, if the durability of first-generation transcatheter valves in the long-term is poor, then iterative developments in design and potentially biomaterials will likely focus on enhancing durability. Commercial incentives for disruptive innovators As described previously, disruptive innovations generally represent economically unattractive initiatives for established market participants because they cannibalize existing high margin products with new low margin products. However, the incentives for commercialization essential for successful propagation of medical innovation are much greater for incumbent manufacturers of traditional surgical valves than the incentives described for incumbent manufacturers from other industries. As detailed above, the addition of a “new” patient population (i.e., previously inoperable patients) not at the expense of those undergoing traditional valve replacement is attractive. Moreover, the ability to offer a percutaneous procedure without the need for cardiopulmonary bypass will further expand (rather than segment) the pool of potential patients. Although the selling price of transcatheter valves is currently approximately six times the cost of a traditional biologic valve, it is reasonable to assume that the manufacturing cost of a transcatheter valve is not six times that of a traditional valve (exact costs of production are not available to these authors). This evaluation of margin and profitability is an important deviation from the classic analysis of disruptive innovation as it suggests that significant economic incentives exist for investment into, and commercialization of, transcatheter valves by incumbent device manufacturers, even when sales of the new product could lead to decreased sales of legacy surgical valves. Thus, even if sales of transcatheter valves were to be directly cannibalistic to surgically implanted valve sales, the transcatheter valve would continue to represent a significant commercial opportunity for incumbent device manufacturers. This feature stands in contrast to the stated characteristic that disruptive innovations “promise lower margins, not higher profits.” While specific pricing varies among institutions, and costs of production are both variable between manufacturers and closely guarded trade secrets, the average selling price of a transcatheter valve in the US has been estimated at $30,000 while the average selling price of a surgically implanted valve is approximately $5,000. If we consider most conservatively that the surgically implanted valve yields all profit, then we may deduce that a transcatheter valve sold at the average selling price of $30,000 and gross margin of at least 17% (i.e., $5,000/ $30,000) would be a more profitable product than a mechanical valve. While gross margins for specific products are not disclosed by manufacturers, the two largest transcatheter valve companies in the US, Medtronic and Edwards Lifesciences, are publicly traded entities and therefore report an aggregated gross margin that reflects their full product portfolio. For fiscal year 2013 both Edwards Lifesciences and Medtronic, the two companies with TAVI devices approved by the FDA in the US, reported gross profit margins of 75%.38 Thus, it is likely that transcatheter
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FIGURE 1. Evaluation of performance metrics with TAVI.
valves represent a more profitable commercial opportunity, on a marginal basis, than surgically implanted valves. These results imply that the TAVI technology represents a profitable business opportunity for incumbent manufacturers due to improved gross margins, higher selling prices, and increased volume. The higher selling prices are related to a manufacturer’s ability to capture value created in disrupting ancillary procedural expenses and, as with most medical devices, are not driven by the costs of production. It is interesting to speculate how market dynamics may change, should the long-term performance (particularly durability and freedom from stroke or paravalvar leak) of transcatheter valves improve and ultimately approach that of surgical valves. If this occurs, the indications for the use of transcatheter valve implantation technology may expand to include lower risk patients who would potentially be surgical AVR candidates.39 This dynamic is already emerging in Germany whereas long ago as 2004, 20% of aortic valve procedures were already being performed using transcatheter techniques.40 This expansion of utilization is consistent with the characteristics of disruptive innovation, which repeatedly identifies technologies that start in a niche market and, through sustaining technological improvements, steadily march into the mainstream. Impact on providers and health care costs Examination of TAVI from the perspective of the physician provider is also particularly interesting in the contemporary
era of changing health care economics. Particularly important will be the accumulating data that examines TAVI in the context of the overall impact of a particular patient’s care on the total accumulated cost of care to the hospital and to insurers. The analysis described above suggests that the cost of TAVI for one patient is presently comparable to the cost of open AVR. However, since the patient population receiving TAVI tends to be older and have a higher incidence of frailty, avoidance of a major invasive procedure (obviating sternotomy and cardiopulmonary bypass) has the potential to reduce stays in hospital, and in long-term care facilities and potentially hospital readmissions. Though unproven, it is possible that these downstream effects could potentially offset some of the cost of the procedure. An interesting potential consequence of the use of TAVI in highrisk patients is the decrease in mortality and adverse postoperative events in the lower risk patients now selected for surgical valve replacement.41 Moreover, the treatment environment, technology, and procedure associated with TAVI are dramatically different from traditional surgical AVR such that leading customers for surgically implanted prosthetic valves will generally not be capable of using transcatheter technology without specific supplemental training.42 Therefore, the required skill set for TAVI is distinct from the skill set historically utilized by cardiothoracic surgeons. Thus, while certain forms of transcatheter technology exist amenable to use by cardiac surgeons, specifically transapical (rather than peripheral)
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implantation, the main developmental focus for transcatheter valve manufacturers is transfemoral implantation devices, which are most typically used by interventional cardiologists, or cardiothoracic surgeons with specific crosstraining in the techniques of implantation. These specialists (i.e., cardiac surgeons and interventional cardionalists) have traditionally competed with one another. Therefore, to date, implementation of TAVI, especially in the United States, has centered around integrated “heart teams” comprised of both interventional cardiologists and surgeons, primarily at large academic medical centers. This is due to the fact that initial rollout of this technology was to clinical investigation sites, all of which had large and active valve programs prior to TAVI. After the devices were approved by FDA for limited commercial use, the Medicare National Coverage Decision mandated that TAVI must be performed conjointly by interventional cardiology and cardiac surgery and only be available at centers that meet volume metrics for heart valve surgery and interventional cardiology. This has limited implementation to centers which can achieve these metrics. However, the quality and cost advantages of TAVI may extend beyond large academic medical centers. As the procedure becomes more routine and, importantly, if these constraints change, it is possible that the technology will migrate to smaller, non-academic centers and potentially to underserved areas. Indeed, a recent study in Germany suggested that performing TAVI in highly selected patients at hospitals without cardiac surgical capabilities is feasible.43 Additionally, a recent analysis from South Africa suggested that TAVI as an alternative to conventional surgery in highrisk patients was feasible and cost-effective at a group of eight private cardiac hospitals.44 Thus, the model of implementation may ultimately reflect that of existing advanced heart failure/transplant centers, with regional referral “Centers of Excellence” for TAVI. Another potential disruptive effect is in developing countries where access to cardiac surgery and other resources are more limited. Though AS tends to represent a smaller disease burden in the developing world, this less-invasive technology could potentially offer therapy to patients otherwise untreatable.
CONCLUSIONS
Our discussion shows that TAVI exemplifies some but not all characteristics of classical disruptive innovation, as formulated by Christensen. In particular, transcatheter valves are not cheaper than surgical valves, TAVI is generally not considered lower performing than surgical valve replacement (in the short-term), and the development and commercialization of transcatheter valves can represent an attractive commercial opportunity for the incumbent medical device manufacturer. However, the technology is not directly applicable to the traditional customer for surgically implanted valves and is first being commercialized in an expanded market for surgical valve manufacturers, particularly patients with a contraindication to surgical intervention. Clearly, additional research, development, and analysis of the impact of TAVI are warranted. Questions remain
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regarding the impact of medical device regulation upon the characteristics of disruptive innovation in this industry and the conclusions reached regarding cost and performance may also differ if evaluated from a long-term and comprehensive health care economics perspective. DISCLOSURES
Mr. Berlin is currently an employee of Covidien. This paper is based upon research completed while he was a student in the Harvard-MIT Division of Health Sciences and Technology, prior to and independent from his current employment. This paper is the work of the attributed author, and does not necessarily represent the views of, and should not be attributed to, Covidien. Dr. Davidson is a paid consultant to Edwards LifeSciences, and Sorin. Dr. Schoen is a paid consultant to Boston Scientific, CardiAQ, Direct Flow Medical, Edwards LifeSciences, Medtronic, Sorin, St Jude Medical, and Symetis. REFERENCES 1. Kramer DB, Xu S, Kesselheim AS. Regulation of medical devices in the United States and European Union. N Engl J Med 2012;366: 848–855. 2. Chatterjee A, King J, Kubendran S, DeVol R. Healthy savings: Medical technology and the economic burden of disease. Milken Institute Report; Santa Monica, CA, July 2014. 3. Porter EM, Lee TH. The strategy that will fix health care. Harvard Business Review October, 2013. pp 50–70. 4. Christensen CM. The Innovator’s Dilemma: When New Technologies Cause Great Firms to Fail. Boston, MA: Harvard Business School Press; 1997. 5. Christensen CM, Grossman JH, Hwang J. The Innovator’s Prescription: A Disruptive Solution for Health Care. New York: McGraw-Hill; 2009. 6. Mohr FW, Morice M-C, Kappetein AP, Feldman TE, Stahle E, Colombo A, Mack MJ, Holmes JR DR, Morel M-a, van Dyck N, Houle VM, Dawkins KD, Serruys PW. Coronary artery bypass graft surgery versus percutaneous coronary intervention in patients with three-vessel disease and left main coronary disease: 5-year follow-up of the randomised, clinical SYNTAX trial. Lancet 2013; 381:629–638. 7. Cohen DJ, Osnabrugge RL, Magnuson EA, et al. Cost-effectiveness of percutaneous coronary intervention with drug-eluting stents vs. bypass surgery for patients with 3-vessel or left main coronary artery disease. Final results from the SYNTAX trial. Circulation 2014;130:1146–1157. 8. Dangas G, O’Connor D, Firwana B, et al. Open versus endovascular stent graft repair of abdominal aortic aneurysms. J Am Coll Cardiol Interv 2012;5:1071–1080. 9. Stroupe KT, Lederle FA, Matsumura JS, Kyriakides TC, Jonk YC, Ge L, Freischlag JA. Cost-effectiveness of open versus endovascular repair of abdominal aortic aneurysm in the OVER trial. J Vasc Surg 2012;56:901–910. 10. Carabello BA, Paulus WJ. Aortic stenosis. Lancet 2009;373:956– 966. 11. Rajamannan NM, Evans FJ, Aikawa E, Grande-Allen KJ, Demer LL, Heistad DD, Simmons CA, Masters KS, Mathieu P, O’Brien KD, Schoen FJ, Towler DA, Yoganathan AP, Otto CM. Calcific aortic valve disease: Not simply a degenerative process. A Review and Agenda for Research from the National Heart and Lung and Blood Institute Aortic Stenosis Working Group. Circulation 2011;124: 1783–1791. 12. Chiang YP, Chikwe J, Moskowitz AJ, Itagaki S, Adams DH, Egorova NN. Survival and long-term outcomes following bioprosthetic vs mechanical aortic valve replacement in patients aged 50–69 years. JAMA 2014;312:1323–1329. 13. Rahimtoola SH. The next generation of prosthetic heart valves needs a proven track record of patient outcomes at > or =15 to 20 years. J Am Coll Cardiol 2003;42:1720–1721.
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14. Chaikof EL. The development of prosthetic heart valves—Lessons in form and function. N Engl J Med 2007;357:1368–1371. 15. Iung B, Cachier A, Baron G, Messika-Zeitoun D, Delahave F, Tornos P, Gohlke-Barwolf C, Boersma E, Ravaud P, Vahanian A. Decision-making in elderly patients with severe aortic stenosis: why are so many denied surgery? Eur Heart J 2005;26:2714–2720. 16. Charlson E, Legedza AT, Hamel MB. Decision-making and outcomes in severe symptomatic aortic stenosis. J Heart Valve Dis 2006;15:312–321. s-Cabau J. Transcatheter aortic valve implantation: current 17. Rode and future approaches. Nat Rev Cardiol 2012;9:15–29. ne reux P, Head SJ, Wood DA, Kodali SK, Williams MR, Paradis 18. Ge JM, Spaziano M, Kappetein AP, Webb JG, Cribier A, Leon MB. Transcatheter aortic valve implantation 10-year anniversary: review of current evidence and clinical implications. Eur Heart J 2012;33:2399–2402. 19. Giordana F, D’Ascenzo F, Nijhoff F, Moretti C, D’Amico M, Biondi Zoccai G, Simming JM, Nickenig G, Van Mieghem NM, Chieffo A, Dumonteil N, Tchetche D, Barbash IM, Waksman R, D’Onofrio A, Lefevre T, Pilgrim T, Amabile N, Cogner P, Kornowski R, Yong ZY, Baan J, Colombo A, Latib A, Salizzoni S, Omede P, Conrotto F, La Torre M, Marra S, Rinaldi M, Gaita F. Meta-analysis of predictors of all-cause mortality after transcatheter aortic valve implantation. Am J Cardiol 2014;114:1447–1455. 20. Kodali SK, Williams MR, Smith CR, Svensson LG, Webb JG, Makkar RR, Fontana GP, Dewey TM, Thourani VH, Pichard AD, Fischbein M, Szeto WY, Lim S, Greason KL, Teirstein PS, Malaisrie SC, Douglas PS, Hahn RT, Whisenant B, Zajarias A, Wang D, Akin JJ, Anderson WN, Leon MB; PARTNER Trial Investigators. Two-year outcomes after transcatheter or surgical aorticvalve replacement. N Engl J Med 2012;366:1686–1695. 21. Tice JA, Sellke FW, Schaff HV. Transcatheter aortic valve replacement in patients with severe aortic stenosis who are at high risk for surgical complications: Summary assessment of the California Technology Assessment Forum. J Thorac Cardiovasc Surg 2014;148:482–491. 22. Fassa AA, Himbert D, Vahanian A. Mechanisms and management of TAVR-related complications. Nat Rev Cardiol 2013;10:685–695. 23. Ielasi A, Latib A, Tespili M. Current and new-generation transcatheter aortic valve devices: An update on emerging technologies. Expert Rev Cardiovasc Ther 2013;11:1393–1405. 24. Schoen F, Levy RJ. Tissue heart valves: Current challenges and future research perspectives. J Biomed Mater Res 1999;47:439– 465. 25. Svensson LG. Evolution and results of aortic valve surgery, and a ‘disruptive’ technology. Cleve Clin J Med 2008;75:802–804. 26. Gilad R, Somogyi R. Percutaneous heart valves: the emergence of a disruptive technology. Univ Toronto Med J 2005;82:199–201. 27. Berlin DB. Characteristics of disruptive innovation within the medical device industry. Masters Dissertation, Massachusetts Institute of Technology, 2011. 28. Lim WL, Hang CC, Neo KB. Discontinuous innovations framework: A review of automatic external defibrillators in the healthcare industry. In: 4th IEEE International Conference on Management of Innovation and Technology, 2008. ICMIT 2008. 29. Vahanian, A, Alfieri O, Al-Attar N, Antunes M, Bax J, Cormier B, Cribier A, De Jaegere P, Fournial G, Kappetein AP, Kovac J, Ludgate S, Maisano F, Moat N, Mohr F, Nataf P, Pierard L, Pomar JL, Schofer J, Tornos P, Tuzcu M, van Hout B, Von Segesser LK, Walther T; European Association of Cardio-Thoracic Surgery; European Society of Cardiology; European Association of Percutaneous Cardiovascular Interventions. Transcatheter valve implantation for patients with aortic stenosis: A position statement from the European Association of Cardio-Thoracic Surgery (EACTS) and the European Society of Cardiology (ESC), in collaboration
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with the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J 2008;29:1463–1470. King SB III, Smith SC Jr, Hirshfeld JW Jr, Jacobs AK, Morrison DA, Williams DO. 2007 focused update of the ACC/AHA/SCAI 2005 guideline update for percutaneous coronary intervention: A report of the American College of Cardiology/American Heart Association task force on practice guidelines: 2007 writing group to review new evidence and update the ACC/AHA/SCAI 2005 guideline update for percutaneous coronary intervention, writing on behalf of the 2005 writing committee. Circulation 2008;117: 261– 295. Leon MB, Smith CR, Mack M, Miller DC, Moses JW, Svensson LG, Tuzcu EM, Webb JG, Fontana GP, Makkar RR, Brown DL, Block PC, Guyton RA, Pichard AD, Bavaria JE, Herrmann HC, Douglas PS, Petersen JL, Akin JJ, Anderson WN, Wang D, Pocock S; PARTNER Trial Investigators. Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery. N Engl J Med 2010;363:1597–1607. Dvir D, Barbanti M, Tan J, Webb JG. Transcatheter aortic valvein-valve implantation for patients with degenerative surgical bioprosthetic valves. Curr Probl Cardiol 2014;39:7–27. Reynolds MR, Magnuson EA, Wang K, Lei Y, Vilain K, Walczak J, Kodali SK, Lasala JM, O’Neill WW, Davidson CJ, Smith CR, Leon MB, Cohen DJ; PARTNER Investigators. Cost-effectiveness of transcatheter aortic valve replacement compared with standard care among inoperable patients with severe aortic stenosis Clinical Perspective Results From the Placement of Aortic Transcatheter Valves (PARTNER) Trial (Cohort B). Circulation 2012;125:1102–1109. Harken DE. Heart valves: Ten commandments and still counting. Ann Thorac Surg 1989;48 (3 Suppl):S18–S19. US Food and Drug Administration. Heart Valves—Investigational Device Exemption (IDE) and Premarket Approval (PMA) Applications, Draft Guidance. January 20, 2010. US Food and Drug Administration [Internet]. Device Classification. [Last reviewed April 27, 2009]. Available from: http://www.fda. gov/MedicalDevices/DeviceRegulationandGuidance/Overview/ClassifyYourDevice/default.htm. Last accessed December 19, 2014. Rahimtoola SH. Choice of prosthetic heart valve for adult patients. J Am Coll Cardiol 2003;41:893–904. http://ycharts.com/companies/MDT/gross_profit_margin and http:// ycharts.com/companies/EW/gross_profit_margin Mack MJ. Does transcatheter aortic valve implantation mean the end of surgical aortic valve replacement? Texas Heart Inst J 2010; 37:658–659. Fish RD. Percutaneous heart valve replacement: Enthusiasm tempered. Circulation 2004;110:1876–1878. Rozen G, Fefer P, Shinfeld A, Sternik L, Guetta V, Malachy A, Levin S, Feinberg M, Raanani E, Segev A. The changing characteristics and outcomes of patients undergoing surgical aortic valve replacement in the transcatheter aortic valve implantation era. J Cardiovasc Med. Forthcoming. Walther T, Simon P, Dewey T, Wimmer-Greinecker G, Falk V, Kasimir MT, Doss M, Borger MA, Schuler G, Glogar D, Fehske W, Wolner E, Mohn FW, Mack M. Transapical minimally invasive aortic valve implantation multicenter experience. Circulation 2007; 116 (Suppl):I240–I245. Eggebrecht H, Mehta RH, Haude M, Sack S, Mudra H, Hein R, Brachmann J, Gerckens U, Kuck KH, Zahn R, Sechtem U, Richardt G, Schneider S, Senges J. Transcatheter aortic valve implantation (TAVI) by centres with and without an on-site cardiac surgery programme: preliminary experience from the German TAVI registry. EuroIntervention 2014;10:602–608. Mabin TA, Candolfi P. An analysis of real-world cost-effectiveness of TAVI in South Africa. Cardiovasc J Afr 2014;25:21–26.
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Covidien, Boulder, Colorado 80503 Division of Cardiac Surgery, Department of Surgery, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts 02115 3 Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts 02115 2
Received 12 August 2014; revised 21 October 2014; accepted 2 December 2014 Published online 24 December 2014 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/jbm.b.33352 Abstract: We sought to evaluate the principles of disruptive innovation, defined as technology innovation that fundamentally shifts performance and utility metrics, as applied to transcatheter aortic valve implantation (TAVI). In particular, we considered implantation procedure, device design, cost, and patient population. Generally cheaper and lower performing, classical disruptive innovations are first commercialized in insignificant markets, promise lower margins, and often parasitize existing usage, representing unattractive investments for established market participants. However, despite presently high unit cost, TAVI is less invasive, treats a “new,” generally high risk, patient population, and is generally done by a multidisciplinary integrated heart team.
Moreover, at least in the short-term TAVI has not been lowerperforming than open surgical aortic valve replacement in high-risk patients. We conclude that TAVI extends the paradigm of disruptive innovation and represents an attractive commercial opportunity space. Moreover, should the longterm performance and durability of TAVI approach that of conventional prostheses, TAVI will be an increasingly attracC tive commercial opportunity. V 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 103B: 1709–1715, 2015.
Key Words: valves, aortic stenosis, prosthesis, transcatheter implantation
How to cite this article: Berlin DB, Davidson MJ, Schoen FJ. 2015. The power of disruptive technological innovation: Transcatheter aortic valve implantation. J Biomed Mater Res Part B 2015:103B:1709–1715.
INTRODUCTION
The convergence of technological progress and medical care has yielded impressive advances in health outcomes and standard of care, and, often yielded economic benefit.1,2 In particular, technology development has enabled the use of implantable cardiovascular medical devices, including pacemakers and cardioverter/defibrillators, prosthetic heart valves, endovascular stents and stent-grafts, cardiac assist devices, and widely used non-cardiovascular implants, as exemplified by total joint replacements and intraocular lenses. However, the adoption into medical practice of new technologies contributes to the economic challenges associated with providing modern comprehensive care to patients through increasingly powerful, yet complex and often very costly medical procedures and devices. As health providers are increasingly pushed to provide high quality care to expanded patient populations at lower incremental cost, and “value” considerations dominate, understanding the dynamics of healthcare innovation through development
and commercialization of medical technology likely will be increasingly important.3 We believe that an evaluation of the applicability of the theory of disruptive innovation to a new and powerful yet expensive cardiovascular technology should be instructive to addressing the challenge of providing technology-intensive quality care to expanding patient populations. This report explores the paradigm of disruptive innovation and the applicability and impact of this concept to the development, commercialization, and implementation of new medical devices and other technologies. After focusing on general concepts, we will examine a specific example where effective clinical implementation of disruptive medical device innovation has occurred, namely transcatheter aortic valve implantation (TAVI). With this procedure, the combination of device design, route of implantation, provider team, and the composition of the patient population so treated is novel. Our analysis and conclusions are intended to be of particular relevance to both those
Correspondence to: F. J. Schoen; e-mail: [email protected]
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interested in developing, commercializing, and using advanced medical devices as well as those interested in fostering a regulatory environment that encourages the ongoing advancement and implementation of medical technology for high quality, effective, and efficient but affordable care.
DISRUPTIVE INNOVATION—OVERVIEW OF THE CONCEPT
The concept of disruptive innovation was elucidated by Harvard Business School Professor Clayton Christensen in his 1997 book, The Innovator’s Dilemma.4 Christensen’s more recent book, The Innovator’s Prescription: A Disruptive Solution for Health Care, published in 2009, extends the disruptive innovation paradigm to medical devices and diagnostic equipment.5 Christensen’s framework characterizes typical innovation as sustaining innovation, the process of improving technology along traditionally accepted performance standards, and generally through iterative, focused modifications that enhance performance, patient outcomes, and/or utility. Developers and manufacturers generally excel at sustaining innovation to the point where their products increase performance more rapidly than customer demands increase, ultimately leading to products that outperform market demands. In contrast, disruptive innovation fundamentally shifts the metrics against which performance and utility are measured. Indeed, Christensen defines disruptive innovations (quite generically) through the following characteristics: Simpler, cheaper, and lower performing. Promise lower margins, not higher profits. Often initially shunned by leading customers who can’t use and don’t want them. First commercialized in emerging or insignificant markets. Given these characteristics, disruptive innovations in their infancy usually represent unattractive investments for incumbent market participants (as they often parasitize existing usage), and initially do not satisfy the needs of current end-users (who don’t know how to optimize benefit from the “disruption”). However, once disruptive innovations reach the market, their performance often improves at a rate faster than market demands increase, while the product costs remain below that of incumbent products. Through this dynamic, disruptive innovations may provide acceptable performance, often at lower cost and greater utility than legacy products, procedures, and other technologies, ultimately allowing them to reach broad application. The combination of lowered costs, adequate performance and/or outcomes, and potentially enhanced access allows disruptive innovations to reach a large base of users who were previously priced out of or otherwise excluded from the market. TAVI is a timely choice of a product being introduced rapidly into clinical practice and has many attributes of a disruptive technology in which risk stratification and costs
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will be significant concerns in selecting therapy. Other disruptive technologies developed to manage serious cardiovascular disease are also under evaluation to compare outcomes and economics with those of their more invasive counterparts. For example, the percutaneous coronary intervention (i.e., stenting) vs. coronary artery bypass graft surgery debate has entered a critical stage of evaluating cost and outcomes. Recently, open surgical coronary artery bypass grafting (CABG) has been confirmed to be the procedure of choice for patients with complex disease, while stents have been shown to be an acceptable alternative, both clinically and economically, for those with less complex disease.6,7 Moreover, for endovascular stent graft versus open surgical repair of abdominal aortic aneurysms, longterm survival and costs have been demonstrated to be approximately equivalent (albeit with a greater reintervention rate in the endovascular group).8,9 We expect that the discussions and data concerning these and other technological innovations, particularly in the realm of less invasive options for serious cardiovascular disease, will yield ongoing lessons learned that will inform the TAVI versus surgical valve placement discussion.
TRANSCATHETER AORTIC VALVE IMPLANTATION
Aortic stenosis (AS) is the most common valvular heart disease in Western countries, and has serious consequences.10 The prevalence of AS increases with age, reaching about 3% after the age of 75 in the US. Thus, the global burden of AS is expected to double within the next 50 years as life expectancy lengthens. The limited available understanding of AS mechanisms and pathobiology has precluded development of effective non-invasive medical treatments.11 Symptomatic severe AS not treated promptly by corrective surgery has a high mortality as well as high and accelerating symptom burden. Valve replacement surgery (consisting of open chest aortic valve replacement [AVR] done by cardiac surgeons under cardiopulmonary bypass) has a relatively low mortality in uncomplicated cases (3%), generally alleviates symptoms and markedly prolongs survival.12 Existing valve replacement devices have undergone substantial sustaining innovation since early clinical use >50 years ago, by incremental improvements in biomaterials and design, yielding predictable long-term results.13,14 In practice, however, AVR is often denied to elderly and other high-risk patients with severe symptomatic AS, who would be at high risk with conventional surgery owing to extensive co-morbidities or frailty.15,16 TAVI, first performed in humans in 2002, is accomplished through peripheral arterial access, is a less invasive alternative to conventional AVR, and extends the opportunity for effective mechanical correction to a potentially large population of otherwise untreatable individuals.17,18 Clinical experience with TAVI is growing rapidly, with an estimated 80,0001 TAVI procedures performed worldwide to date. Early mortality in a meta-analysis of 25 studies involving over 8800 patients was 7.5%.19 Randomized and observational clinical trials comparing TAVI to classical open
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surgical AVR suggest that survival following TAVI in highrisk patients is equivalent to or better than that of AVR at 1–2 years.12,20,21 Indeed, TAVI is not only considered a disruptive innovation in this space, but also has rapidly been adopted as the new standard of care for many patients with symptomatic AS who would otherwise be deemed inoperable. The design of the devices used in TAVI is necessarily different than that of conventional substitute heart valves. Valves used in TAVI generally consist of a bioprosthetic tissue valve, typically fabricated from bovine pericardium, mounted on a compressible metallic stent. The valve is inserted within the diseased native aortic valve, and without the use of cardiopulmonary bypass. Access is obtained either through a peripheral artery (femoral or subclavian) or directly through the aorta or left ventricular apex. Once located at the level of the aortic valve, the device requires balloon dilatation or self-expands (if fabricated from a shape memory alloy such as Nitinol). The patient’s native aortic valve is not removed in TAVI (as in AVR) but rather is pushed aside to the periphery of the annulus, and compressed against the aortic root. During TAVI, delivery, positioning, and permanent fixation in the optimal location are guided by a combination of fluoroscopy and echocardiography and are critical to procedural success. Complications have been observed in approximately one-third of patients, and may include vascular injury, paravalvular leak, and stroke.22 A variety of prostheses developed specifically for TAVI are currently in use, and many other models are in preclinical and clinical stages of development.23 Two transcatheter aortic-valve devices have been and are currently approved by the FDA for use in the United States: the Edwards Sapien aortic valve (2011, Edwards LifeSciences, Irvine, CA) and the Medtronic CoreValve (2014, Medtronic, Minneapolis, MN). Long-term complications associated directly with the tissue interactions with the leaflets would be expected to be similar to those of bioprosthetic valves implanted surgically,24 but this has not yet been confirmed.
APPLICATION OF THE DISRUPTIVE INNOVATION FRAMEWORK TO TAVI
As a significant deviation from the current surgical techniques for treating AS, TAVI exemplifies elements of Christensen’s “disruptive” framework.25,26 However, the implantation procedure and the associated technology of TAVI have both similarities to and differences from those described by the formal framework of disruptive innovation established by Christensen.27 The dynamics of disruptive innovation have been previously examined with regard to the systemic delivery of healthcare services; however, there is limited literature rigorously examining the application of these dynamics to surgical technology, and particularly novel medical devices and procedures.28 The disruptive features of TAVI have significant implications for the unit cost of care, the manner in which medical services are provided, the long-term applicability of this technology to enlarging and diverse patient populations, and the incentives for commercializing novel cardiac medical device technology. Thus, the paradigm
of disruptive innovation characteristics delineated by Christensen may require modification when applied to TAVI. Target patient population and market size A tenet central to Christensen’s model of disruptive innovation is that disruptive technologies are initially limited to emerging or insignificant markets. For TAVI, the addition of a “new” patient population not at the expense of those undergoing AVR is a crucial feature. The current expert guidelines for clinical use of transcatheter valve implantation, published in the European Heart Journal in 2008, recommend restriction of TAVI to “high-risk patients or those with contraindications for surgery.”29 However, the statement also notes that “[indications for use] may be extended to lower risk patients if the initial promise holds to be true after careful evaluation.” The sentiment of this European statement is echoed in a similarly timed 2008 AHA Scientific Statement, which concluded, “. . .percutaneous AVR . . .should be limited in use to patients considered to be high risk or to inoperable surgical candidates. In this context, even after FDA approvals, percutaneous devices should be used in only a small number of centers. . .until they are thoroughly tested in the clinical arena.”30 Superficially, it would appear that transcatheter valves are indeed restricted initially to a small or potentially insignificant market, in that their use is initially limited to nonsurgical candidates or patients at unacceptably high risk for conventional surgery. However, epidemiologic studies of the target demographic indicate that this is in fact not a small or insignificant market. Approximately, 85,000 AVRs are done in the US each year. It is estimated that at least 30% of patients with severe symptomatic AS are inoperable.31 Previously, incumbent surgical valve manufacturers offered no effective surgical intervention suitable for these patients. Moreover, TAVI may also be a suitable approach to management of some patients with a failed bioprosthetic valve replacement.32 Cost vs. performance Analyzing the cost and performance characteristics of TAVI adds an additional level of complexity. While equipment costs vary by institution, a transcatheter aortic valve device is estimated to cost $30,000 while a traditional prosthetic mechanical or tissue valve is estimated to cost $5,000. The calculated total admission cost of open AVR is $74,067; similarly, the cost of a TAVI procedure is calculated at $73,219.33 Clearly, from the perspective of an incumbent valve manufacturer, TAVI does not meet the “cheaper” characteristic. However, this evaluation of cost might reach a different conclusion if viewed from the different perspectives of the provider, the hospital or the broader healthcare system, especially with respect to the device costs, procedure costs, or longitudinal systemic total healthcare costs of a patient. For instance, in mature TAVI systems (i.e., Europe) increasing number of procedures are being performed without the use of general anesthesia and with short hospital stays, potentially reducing hospital costs significantly (and this approach is beginning to be applied in the US). The
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several perspectives may offer different conclusions regarding the costs of TAVI as compared with those of traditional surgical AVR (or non-treatment of high-risk populations who could not be candidates for AVR). In the United States, hospitals and providers may be reimbursed at a lower rate for TAVI than for surgical AVR, and these rates may vary among geographic regions. Thus, TAVI may be financially unattractive as this procedure can incur a net loss. Although reimbursement patterns may evolve, this currently impacts adoption in the United States. The evaluation of performance of TAVI in the context of disruptive innovation requires the delineation of suitable performance metrics. A widely adapted view of ideal prosthetic valve performance is described by Dr. Dwight Harken’s “ten commandments,” initially formulated in 1962, but largely relevant today.34 Traditional valve development and performance metrics have focused on incremental improvements intended to limit thrombosis and propagation of emboli, durability, enhancing surgical fixation and healing in the annulus, lack of infection and hemolysis, and improving other physiologic and mechanical determinants of performance. However, a transcatheter valve offers its most significant value directly through avoiding sternotomy, cardiopulmonary bypass, and aortic clamping, features of open AVR which are undesirable in the population suited for TAVI. The existing framework of disruptive innovation would imply that this new performance would come at the cost of inferior traditional performance metrics, such as those just mentioned. Nevertheless, the clinical trial results demonstrate noninferiority of transcatheter valves relative to surgically implanted valves in terms of mortality and in some cases hemodynamics, thereby contradicting the “lower performing” tenet of the disruptive innovation framework, at least in the short term. The performance dynamics of disruptive innovation in the clinical environment are worthy of additional evaluation, specifically due to the associated regulatory structure. The current regulatory structure for approval of medical devices in the United Sates creates significant hurdles for the introduction of technologies that offer a novel value proposition, as these new products are often held to the performance standards of existing marketed technologies.35,36 This dynamic may restrain the forces of innovation that have been so powerful in propelling the advancement of technology in other industries by limiting the introduction of technology that requires a trade-off between new and existing performance metrics. Nevertheless, both the Edwards LifeSciences Sapien Valve and the Medtronic CoreValve TAVI devices have been granted approval by the FDA for use in patients with severe AS who are at high mortality risk if they undergo traditional open-heart procedures. Although the long-term structural performance of transcatheter valves is unknown at this time, they may represent a performance dynamic more in line with the expected dynamics of disruptive innovations. TAVI will be done predominantly in elderly patients with AS, and, as previously demonstrated, bioprosthetic valves implanted in older patients have a better outcome than those in younger patients.37 Thus, long-term durability will be difficult to
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document. Moreover, if the durability of first-generation transcatheter valves in the long-term is poor, then iterative developments in design and potentially biomaterials will likely focus on enhancing durability. Commercial incentives for disruptive innovators As described previously, disruptive innovations generally represent economically unattractive initiatives for established market participants because they cannibalize existing high margin products with new low margin products. However, the incentives for commercialization essential for successful propagation of medical innovation are much greater for incumbent manufacturers of traditional surgical valves than the incentives described for incumbent manufacturers from other industries. As detailed above, the addition of a “new” patient population (i.e., previously inoperable patients) not at the expense of those undergoing traditional valve replacement is attractive. Moreover, the ability to offer a percutaneous procedure without the need for cardiopulmonary bypass will further expand (rather than segment) the pool of potential patients. Although the selling price of transcatheter valves is currently approximately six times the cost of a traditional biologic valve, it is reasonable to assume that the manufacturing cost of a transcatheter valve is not six times that of a traditional valve (exact costs of production are not available to these authors). This evaluation of margin and profitability is an important deviation from the classic analysis of disruptive innovation as it suggests that significant economic incentives exist for investment into, and commercialization of, transcatheter valves by incumbent device manufacturers, even when sales of the new product could lead to decreased sales of legacy surgical valves. Thus, even if sales of transcatheter valves were to be directly cannibalistic to surgically implanted valve sales, the transcatheter valve would continue to represent a significant commercial opportunity for incumbent device manufacturers. This feature stands in contrast to the stated characteristic that disruptive innovations “promise lower margins, not higher profits.” While specific pricing varies among institutions, and costs of production are both variable between manufacturers and closely guarded trade secrets, the average selling price of a transcatheter valve in the US has been estimated at $30,000 while the average selling price of a surgically implanted valve is approximately $5,000. If we consider most conservatively that the surgically implanted valve yields all profit, then we may deduce that a transcatheter valve sold at the average selling price of $30,000 and gross margin of at least 17% (i.e., $5,000/ $30,000) would be a more profitable product than a mechanical valve. While gross margins for specific products are not disclosed by manufacturers, the two largest transcatheter valve companies in the US, Medtronic and Edwards Lifesciences, are publicly traded entities and therefore report an aggregated gross margin that reflects their full product portfolio. For fiscal year 2013 both Edwards Lifesciences and Medtronic, the two companies with TAVI devices approved by the FDA in the US, reported gross profit margins of 75%.38 Thus, it is likely that transcatheter
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FIGURE 1. Evaluation of performance metrics with TAVI.
valves represent a more profitable commercial opportunity, on a marginal basis, than surgically implanted valves. These results imply that the TAVI technology represents a profitable business opportunity for incumbent manufacturers due to improved gross margins, higher selling prices, and increased volume. The higher selling prices are related to a manufacturer’s ability to capture value created in disrupting ancillary procedural expenses and, as with most medical devices, are not driven by the costs of production. It is interesting to speculate how market dynamics may change, should the long-term performance (particularly durability and freedom from stroke or paravalvar leak) of transcatheter valves improve and ultimately approach that of surgical valves. If this occurs, the indications for the use of transcatheter valve implantation technology may expand to include lower risk patients who would potentially be surgical AVR candidates.39 This dynamic is already emerging in Germany whereas long ago as 2004, 20% of aortic valve procedures were already being performed using transcatheter techniques.40 This expansion of utilization is consistent with the characteristics of disruptive innovation, which repeatedly identifies technologies that start in a niche market and, through sustaining technological improvements, steadily march into the mainstream. Impact on providers and health care costs Examination of TAVI from the perspective of the physician provider is also particularly interesting in the contemporary
era of changing health care economics. Particularly important will be the accumulating data that examines TAVI in the context of the overall impact of a particular patient’s care on the total accumulated cost of care to the hospital and to insurers. The analysis described above suggests that the cost of TAVI for one patient is presently comparable to the cost of open AVR. However, since the patient population receiving TAVI tends to be older and have a higher incidence of frailty, avoidance of a major invasive procedure (obviating sternotomy and cardiopulmonary bypass) has the potential to reduce stays in hospital, and in long-term care facilities and potentially hospital readmissions. Though unproven, it is possible that these downstream effects could potentially offset some of the cost of the procedure. An interesting potential consequence of the use of TAVI in highrisk patients is the decrease in mortality and adverse postoperative events in the lower risk patients now selected for surgical valve replacement.41 Moreover, the treatment environment, technology, and procedure associated with TAVI are dramatically different from traditional surgical AVR such that leading customers for surgically implanted prosthetic valves will generally not be capable of using transcatheter technology without specific supplemental training.42 Therefore, the required skill set for TAVI is distinct from the skill set historically utilized by cardiothoracic surgeons. Thus, while certain forms of transcatheter technology exist amenable to use by cardiac surgeons, specifically transapical (rather than peripheral)
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implantation, the main developmental focus for transcatheter valve manufacturers is transfemoral implantation devices, which are most typically used by interventional cardiologists, or cardiothoracic surgeons with specific crosstraining in the techniques of implantation. These specialists (i.e., cardiac surgeons and interventional cardionalists) have traditionally competed with one another. Therefore, to date, implementation of TAVI, especially in the United States, has centered around integrated “heart teams” comprised of both interventional cardiologists and surgeons, primarily at large academic medical centers. This is due to the fact that initial rollout of this technology was to clinical investigation sites, all of which had large and active valve programs prior to TAVI. After the devices were approved by FDA for limited commercial use, the Medicare National Coverage Decision mandated that TAVI must be performed conjointly by interventional cardiology and cardiac surgery and only be available at centers that meet volume metrics for heart valve surgery and interventional cardiology. This has limited implementation to centers which can achieve these metrics. However, the quality and cost advantages of TAVI may extend beyond large academic medical centers. As the procedure becomes more routine and, importantly, if these constraints change, it is possible that the technology will migrate to smaller, non-academic centers and potentially to underserved areas. Indeed, a recent study in Germany suggested that performing TAVI in highly selected patients at hospitals without cardiac surgical capabilities is feasible.43 Additionally, a recent analysis from South Africa suggested that TAVI as an alternative to conventional surgery in highrisk patients was feasible and cost-effective at a group of eight private cardiac hospitals.44 Thus, the model of implementation may ultimately reflect that of existing advanced heart failure/transplant centers, with regional referral “Centers of Excellence” for TAVI. Another potential disruptive effect is in developing countries where access to cardiac surgery and other resources are more limited. Though AS tends to represent a smaller disease burden in the developing world, this less-invasive technology could potentially offer therapy to patients otherwise untreatable.
CONCLUSIONS
Our discussion shows that TAVI exemplifies some but not all characteristics of classical disruptive innovation, as formulated by Christensen. In particular, transcatheter valves are not cheaper than surgical valves, TAVI is generally not considered lower performing than surgical valve replacement (in the short-term), and the development and commercialization of transcatheter valves can represent an attractive commercial opportunity for the incumbent medical device manufacturer. However, the technology is not directly applicable to the traditional customer for surgically implanted valves and is first being commercialized in an expanded market for surgical valve manufacturers, particularly patients with a contraindication to surgical intervention. Clearly, additional research, development, and analysis of the impact of TAVI are warranted. Questions remain
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regarding the impact of medical device regulation upon the characteristics of disruptive innovation in this industry and the conclusions reached regarding cost and performance may also differ if evaluated from a long-term and comprehensive health care economics perspective. DISCLOSURES
Mr. Berlin is currently an employee of Covidien. This paper is based upon research completed while he was a student in the Harvard-MIT Division of Health Sciences and Technology, prior to and independent from his current employment. This paper is the work of the attributed author, and does not necessarily represent the views of, and should not be attributed to, Covidien. Dr. Davidson is a paid consultant to Edwards LifeSciences, and Sorin. Dr. Schoen is a paid consultant to Boston Scientific, CardiAQ, Direct Flow Medical, Edwards LifeSciences, Medtronic, Sorin, St Jude Medical, and Symetis. REFERENCES 1. Kramer DB, Xu S, Kesselheim AS. Regulation of medical devices in the United States and European Union. N Engl J Med 2012;366: 848–855. 2. Chatterjee A, King J, Kubendran S, DeVol R. Healthy savings: Medical technology and the economic burden of disease. Milken Institute Report; Santa Monica, CA, July 2014. 3. Porter EM, Lee TH. The strategy that will fix health care. Harvard Business Review October, 2013. pp 50–70. 4. Christensen CM. The Innovator’s Dilemma: When New Technologies Cause Great Firms to Fail. Boston, MA: Harvard Business School Press; 1997. 5. Christensen CM, Grossman JH, Hwang J. The Innovator’s Prescription: A Disruptive Solution for Health Care. New York: McGraw-Hill; 2009. 6. Mohr FW, Morice M-C, Kappetein AP, Feldman TE, Stahle E, Colombo A, Mack MJ, Holmes JR DR, Morel M-a, van Dyck N, Houle VM, Dawkins KD, Serruys PW. Coronary artery bypass graft surgery versus percutaneous coronary intervention in patients with three-vessel disease and left main coronary disease: 5-year follow-up of the randomised, clinical SYNTAX trial. Lancet 2013; 381:629–638. 7. Cohen DJ, Osnabrugge RL, Magnuson EA, et al. Cost-effectiveness of percutaneous coronary intervention with drug-eluting stents vs. bypass surgery for patients with 3-vessel or left main coronary artery disease. Final results from the SYNTAX trial. Circulation 2014;130:1146–1157. 8. Dangas G, O’Connor D, Firwana B, et al. Open versus endovascular stent graft repair of abdominal aortic aneurysms. J Am Coll Cardiol Interv 2012;5:1071–1080. 9. Stroupe KT, Lederle FA, Matsumura JS, Kyriakides TC, Jonk YC, Ge L, Freischlag JA. Cost-effectiveness of open versus endovascular repair of abdominal aortic aneurysm in the OVER trial. J Vasc Surg 2012;56:901–910. 10. Carabello BA, Paulus WJ. Aortic stenosis. Lancet 2009;373:956– 966. 11. Rajamannan NM, Evans FJ, Aikawa E, Grande-Allen KJ, Demer LL, Heistad DD, Simmons CA, Masters KS, Mathieu P, O’Brien KD, Schoen FJ, Towler DA, Yoganathan AP, Otto CM. Calcific aortic valve disease: Not simply a degenerative process. A Review and Agenda for Research from the National Heart and Lung and Blood Institute Aortic Stenosis Working Group. Circulation 2011;124: 1783–1791. 12. Chiang YP, Chikwe J, Moskowitz AJ, Itagaki S, Adams DH, Egorova NN. Survival and long-term outcomes following bioprosthetic vs mechanical aortic valve replacement in patients aged 50–69 years. JAMA 2014;312:1323–1329. 13. Rahimtoola SH. The next generation of prosthetic heart valves needs a proven track record of patient outcomes at > or =15 to 20 years. J Am Coll Cardiol 2003;42:1720–1721.
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14. Chaikof EL. The development of prosthetic heart valves—Lessons in form and function. N Engl J Med 2007;357:1368–1371. 15. Iung B, Cachier A, Baron G, Messika-Zeitoun D, Delahave F, Tornos P, Gohlke-Barwolf C, Boersma E, Ravaud P, Vahanian A. Decision-making in elderly patients with severe aortic stenosis: why are so many denied surgery? Eur Heart J 2005;26:2714–2720. 16. Charlson E, Legedza AT, Hamel MB. Decision-making and outcomes in severe symptomatic aortic stenosis. J Heart Valve Dis 2006;15:312–321. s-Cabau J. Transcatheter aortic valve implantation: current 17. Rode and future approaches. Nat Rev Cardiol 2012;9:15–29. ne reux P, Head SJ, Wood DA, Kodali SK, Williams MR, Paradis 18. Ge JM, Spaziano M, Kappetein AP, Webb JG, Cribier A, Leon MB. Transcatheter aortic valve implantation 10-year anniversary: review of current evidence and clinical implications. Eur Heart J 2012;33:2399–2402. 19. Giordana F, D’Ascenzo F, Nijhoff F, Moretti C, D’Amico M, Biondi Zoccai G, Simming JM, Nickenig G, Van Mieghem NM, Chieffo A, Dumonteil N, Tchetche D, Barbash IM, Waksman R, D’Onofrio A, Lefevre T, Pilgrim T, Amabile N, Cogner P, Kornowski R, Yong ZY, Baan J, Colombo A, Latib A, Salizzoni S, Omede P, Conrotto F, La Torre M, Marra S, Rinaldi M, Gaita F. Meta-analysis of predictors of all-cause mortality after transcatheter aortic valve implantation. Am J Cardiol 2014;114:1447–1455. 20. Kodali SK, Williams MR, Smith CR, Svensson LG, Webb JG, Makkar RR, Fontana GP, Dewey TM, Thourani VH, Pichard AD, Fischbein M, Szeto WY, Lim S, Greason KL, Teirstein PS, Malaisrie SC, Douglas PS, Hahn RT, Whisenant B, Zajarias A, Wang D, Akin JJ, Anderson WN, Leon MB; PARTNER Trial Investigators. Two-year outcomes after transcatheter or surgical aorticvalve replacement. N Engl J Med 2012;366:1686–1695. 21. Tice JA, Sellke FW, Schaff HV. Transcatheter aortic valve replacement in patients with severe aortic stenosis who are at high risk for surgical complications: Summary assessment of the California Technology Assessment Forum. J Thorac Cardiovasc Surg 2014;148:482–491. 22. Fassa AA, Himbert D, Vahanian A. Mechanisms and management of TAVR-related complications. Nat Rev Cardiol 2013;10:685–695. 23. Ielasi A, Latib A, Tespili M. Current and new-generation transcatheter aortic valve devices: An update on emerging technologies. Expert Rev Cardiovasc Ther 2013;11:1393–1405. 24. Schoen F, Levy RJ. Tissue heart valves: Current challenges and future research perspectives. J Biomed Mater Res 1999;47:439– 465. 25. Svensson LG. Evolution and results of aortic valve surgery, and a ‘disruptive’ technology. Cleve Clin J Med 2008;75:802–804. 26. Gilad R, Somogyi R. Percutaneous heart valves: the emergence of a disruptive technology. Univ Toronto Med J 2005;82:199–201. 27. Berlin DB. Characteristics of disruptive innovation within the medical device industry. Masters Dissertation, Massachusetts Institute of Technology, 2011. 28. Lim WL, Hang CC, Neo KB. Discontinuous innovations framework: A review of automatic external defibrillators in the healthcare industry. In: 4th IEEE International Conference on Management of Innovation and Technology, 2008. ICMIT 2008. 29. Vahanian, A, Alfieri O, Al-Attar N, Antunes M, Bax J, Cormier B, Cribier A, De Jaegere P, Fournial G, Kappetein AP, Kovac J, Ludgate S, Maisano F, Moat N, Mohr F, Nataf P, Pierard L, Pomar JL, Schofer J, Tornos P, Tuzcu M, van Hout B, Von Segesser LK, Walther T; European Association of Cardio-Thoracic Surgery; European Society of Cardiology; European Association of Percutaneous Cardiovascular Interventions. Transcatheter valve implantation for patients with aortic stenosis: A position statement from the European Association of Cardio-Thoracic Surgery (EACTS) and the European Society of Cardiology (ESC), in collaboration
30.
31.
32.
33.
34. 35.
36.
37. 38. 39.
40. 41.
42.
43.
44.
with the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J 2008;29:1463–1470. King SB III, Smith SC Jr, Hirshfeld JW Jr, Jacobs AK, Morrison DA, Williams DO. 2007 focused update of the ACC/AHA/SCAI 2005 guideline update for percutaneous coronary intervention: A report of the American College of Cardiology/American Heart Association task force on practice guidelines: 2007 writing group to review new evidence and update the ACC/AHA/SCAI 2005 guideline update for percutaneous coronary intervention, writing on behalf of the 2005 writing committee. Circulation 2008;117: 261– 295. Leon MB, Smith CR, Mack M, Miller DC, Moses JW, Svensson LG, Tuzcu EM, Webb JG, Fontana GP, Makkar RR, Brown DL, Block PC, Guyton RA, Pichard AD, Bavaria JE, Herrmann HC, Douglas PS, Petersen JL, Akin JJ, Anderson WN, Wang D, Pocock S; PARTNER Trial Investigators. Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery. N Engl J Med 2010;363:1597–1607. Dvir D, Barbanti M, Tan J, Webb JG. Transcatheter aortic valvein-valve implantation for patients with degenerative surgical bioprosthetic valves. Curr Probl Cardiol 2014;39:7–27. Reynolds MR, Magnuson EA, Wang K, Lei Y, Vilain K, Walczak J, Kodali SK, Lasala JM, O’Neill WW, Davidson CJ, Smith CR, Leon MB, Cohen DJ; PARTNER Investigators. Cost-effectiveness of transcatheter aortic valve replacement compared with standard care among inoperable patients with severe aortic stenosis Clinical Perspective Results From the Placement of Aortic Transcatheter Valves (PARTNER) Trial (Cohort B). Circulation 2012;125:1102–1109. Harken DE. Heart valves: Ten commandments and still counting. Ann Thorac Surg 1989;48 (3 Suppl):S18–S19. US Food and Drug Administration. Heart Valves—Investigational Device Exemption (IDE) and Premarket Approval (PMA) Applications, Draft Guidance. January 20, 2010. US Food and Drug Administration [Internet]. Device Classification. [Last reviewed April 27, 2009]. Available from: http://www.fda. gov/MedicalDevices/DeviceRegulationandGuidance/Overview/ClassifyYourDevice/default.htm. Last accessed December 19, 2014. Rahimtoola SH. Choice of prosthetic heart valve for adult patients. J Am Coll Cardiol 2003;41:893–904. http://ycharts.com/companies/MDT/gross_profit_margin and http:// ycharts.com/companies/EW/gross_profit_margin Mack MJ. Does transcatheter aortic valve implantation mean the end of surgical aortic valve replacement? Texas Heart Inst J 2010; 37:658–659. Fish RD. Percutaneous heart valve replacement: Enthusiasm tempered. Circulation 2004;110:1876–1878. Rozen G, Fefer P, Shinfeld A, Sternik L, Guetta V, Malachy A, Levin S, Feinberg M, Raanani E, Segev A. The changing characteristics and outcomes of patients undergoing surgical aortic valve replacement in the transcatheter aortic valve implantation era. J Cardiovasc Med. Forthcoming. Walther T, Simon P, Dewey T, Wimmer-Greinecker G, Falk V, Kasimir MT, Doss M, Borger MA, Schuler G, Glogar D, Fehske W, Wolner E, Mohn FW, Mack M. Transapical minimally invasive aortic valve implantation multicenter experience. Circulation 2007; 116 (Suppl):I240–I245. Eggebrecht H, Mehta RH, Haude M, Sack S, Mudra H, Hein R, Brachmann J, Gerckens U, Kuck KH, Zahn R, Sechtem U, Richardt G, Schneider S, Senges J. Transcatheter aortic valve implantation (TAVI) by centres with and without an on-site cardiac surgery programme: preliminary experience from the German TAVI registry. EuroIntervention 2014;10:602–608. Mabin TA, Candolfi P. An analysis of real-world cost-effectiveness of TAVI in South Africa. Cardiovasc J Afr 2014;25:21–26.
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