Payment policies are potentially a strong driver of diffusion of

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1 Medical Devices Diffusion Of New Technology And Payment Policies: Coronary Stents The implementation of a higher payment rate for stenting did not drive the acceleration of the technology s diffusion, as has been claimed. by Chuck Shih and Elise Berliner ABSTRACT: Medicare payment is often cited as a major driver of medical technology diffusion. Stakeholders claimed that beneficiaries would be denied access to stents because Medicare payment did not initially cover the cost of stents. Nevertheless, stents diffused rapidly, including to untested indications. Outcomes with stents improved over time, primarily because of a fundamental property of technology diffusion termed reinvention, in which new technology is modified by users. The traditional system of regulatory approval and reimbursement does not account for this dynamic process. There has been no incentive for systematic collection of data to determine which modifications are most beneficial. [Health Affairs 27, no. 6 (2008): ; /hlthaff ] Payment policies are potentially a strong driver of diffusion of new technologies. The task of determining appropriate payment levels is often made more difficult by the limited information available. Despite limitations in evidence, there is often enthusiasm for new technologies based on potential benefits that have not yet been shown. In this paper we discuss how such issues came into play in the early use of baremetal coronary stenting. When stents were first approved for coronary indications, the predecessor agency (HCFA) of the Centers for Medicare and Medicaid Services (CMS) paid for all angioplasty procedures at the same rate, regardless of stent usage. At the time, it was criticized for withholding beneficial technology from Medicare beneficiaries. A stakeholder commented that as a result of delayed action, hospitals [would] not be able to provide stent therapy to Medicare beneficiaries, thereby depriving them of state-of-the-art technology and better outcomes. 1 Others asserted that stenting was a technology that Medicare patients wanted and needed. 2 Chuck Shih is a doctoral student in the Department of Health Policy and Management, Johns Hopkins Bloomberg School of Public Health, located in Baltimore, Maryland. Elise Berliner (elise.berliner@ahrq.hhs.gov) is director of the Technology Assessment Program, Center for Outcomes and Evidence, Agency for Healthcare Research and Quality, in Rockville November/December 2008 DOI /hlthaff Project HOPE The People-to-People Health Foundation, Inc.

2 Coronary Stents We examine two aspects of this policy issue. The first is the evidence on the balance of benefits and harms provided by the stents when they were first introduced. The second is whether the data on usage suggest that Medicare patients were denied stents prior to the payment rate increase. We then propose a model of technology diffusion and reinvention. Early Clinical History Of Stents In 2005 an estimated 429,000 Medicare beneficiaries were discharged from short-stay hospitals with a primary diagnosis of acute myocardial infarction (AMI). 3 In the same year, approximately 119,000 beneficiaries died from a heart attack. 4 Treatment options for coronary artery disease include medical therapy and revascularization procedures, includingcoronaryarterybypassgraft(cabg)surgery and percutaneous transluminal coronary angioplasty (PTCA), with or without stents. In 1977 the first PTCA was performed using a balloon catheter to expand the arterial diameter. As the use of PTCA expanded, however, complications associated with the procedure became apparent. Abrupt vessel closure occurred in approximately 3 5 percent of cases, often necessitating emergency bypass surgery or resulting in death. Restenosis (a renarrowing of an artery previously opened by angioplasty) had an incidence of percent during the six months after the procedures were performed. 5 Coronary stenting was developed with the goal of reducing restenosis rates. Although similar to PTCA, angioplasty with a stent involves leaving a scaffold inside the artery. Stent use in coronary arteries was first reported in In 1992, the Gianturco-Roubin stent became the first to receive approval for coronary procedures from the Food and Drug Administration (FDA); the specific indication was emergency management of coronary blood vessel closures during angiography. In August 1994 the Palmaz-Schatz stent received approval for elective coronary stenting. The package insert noted many concerns and warnings, including the fact that the stent was indicated only in a select group of patients, and that although the stent is a permanent implant, one-year and longer follow-up was not well characterized. Compliance with the recommended antiplatelet and anticoagulation regimen was highly recommended, but the protocol was based on empirical testing; no prospective randomized trial data were available at that time to assess the risk-benefit ratio of various anticoagulation regimens. FDA approval of the Palmaz-Schatz stent was based on two landmark randomized controlled trials (RCTs) the STRESS and Benestent studies both of which were published in Both studies found that stent use during PTCA improved coronary diameter among patients with new lesions in the main coronary arteries. The major clinical benefit for patients was a reduced need for revascularization: approximately 10 percent fewer patients with stents needed revascularization over the study follow-up period of seven to eight months. However, patients who received stents remained hospitalized significantly longer and expe- HEALTH AFFAIRS ~ Vo l u m e 2 7, N u m b e r

3 Medical Devices rienced higher rates of bleeding and vascular complications because of the intensive anticoagulation regimens used with the stents. No differences in mortality or myocardial infarction rates were observed in either study, which might have been underpowered to detect such differences. Because the landmark trials considered for FDA approval enrolled only patients with new coronary lesions in the main coronary arteries, important patient populations were not studied. Excluded were patients who had developed restenosis after balloon angioplasty or stenosis in bypass arteries following CABG. Patients were also excluded if they had large lesions or if the target lesion was located in a small coronary vessel. In regard to the issue of stenting after restenosis, no RCT data specific to this patient population were available until 1998 four years after initial FDA approval at which time the Restenosis Stent Study Group reported a major benefit of stenting for patients who experienced restenosis of a coronary vessel after balloon angioplasty. 8 On the eve of FDA approval, although coronary stenting had been shown to be effective on some outcome measures for a narrowly defined patient population, it is clear that data were lacking to inform many other aspects of clinical care. Soon thereafter, an observational study was published reporting use of intravascular ultrasound (IVUS) to image the coronary vessel after stenting. 9 This study suggested that there were often gaps between the vessel wall and the stent, which could lead to adverse events. Consequently, clinicians began to insert stents using a higher-pressure balloon. The 1996 American College of Cardiology (ACC) guidelines recommended high-pressure balloon inflation but noted that this recommendation was based on experience supported by only a small body of observational evidence and that more investigation was needed to assess long-term outcomes. 10 The 1998 guidelines recommended pressures somewhat lower than the 1996 recommendation and warned that excessively high pressure could cause adverse events. However, the guidelines noted that there was a lack of evidence and that the exact definition of high pressure inflation has yet to be determined. 11 The same observational study using IVUS suggested that intensive anticoagulation, which causes vascular complications, might not be necessary when the stents were optimally inserted. The 1996 ACC guidelines recommended a reduced anticoagulant regimen of aspirin/ticlopidine in certain patients, but they noted that this was considered off-label use and that results from RCTs in progress at the time were needed for ticlopidine, because of adverse events such as neutropenia (a blood disorder) in 2 3 percent of cases. At the time of the 1998 guidelines, key randomized trials were completed and found that the aspirin/ticlopidine regimen did lead to lower stent thrombosis and fewer vascular complications. 12 Patients in these studies received ticlopidine for four weeks. The 1998 guidelines noted that an increasing number of centers were using only two weeks of ticlopidine in attempts to lower the rate of neutropenia adverse events. Such changes in clinical practice reflect a typical pattern in innovation, in 1568 November/December 2008

4 Coronary Stents which practices change based on formal and informal sharing of physicians experiences. These changes occur more quickly than it takes for clinical trials to be completed. Therefore, clinical trials help answer some questions, but more questions often remain on the real-world effectiveness of new technology as it is used with evolving techniques and adjunctive therapies. The example of stents illustrates a fundamental property of innovation called reinvention, which Everett Rogers defines as the degree to which an invention is modified by a user in the process of adoption and implementation. 13 In the case of stents, users modified the procedure of insertion and adjunctive therapy from the protocol used at the time of FDA approval. These modifications led to outcomes that were improved over those observed in the pivotal clinical trials. Reimbursement For And Use Of Stents In October 1994, a new International Classification of Diseases, Ninth Revision (ICD-9) code (36.06) was created by HCFA for the insertion of a stent into a coronary vessel. As was standard practice, the new code was placed into the same diagnosis-related group (DRG) category as its predecessor technology balloon angioplasty or PTCA (DRG 112). This decision was made despite the manufacturer s having provided the agency with data indicating higher costs in procedures with stenting compared to angioplasty procedures without stenting. 14 HCFA s own analysis of the data, however, found wide variation in reported costs, ranging from $9,000 to more than $45,000 per hospitalization. From the clinical data described above, the variation in costmighthavebeenattributabletothelonger hospitalization and to bleeding and vascular complications. Because of this variability as well as a lack of Medicare cost data, HCFA did not propose any immediate DRG changes for coronary stenting procedures. Nevertheless, as with all new technologies, a reconsideration of DRG assignment would be possible after collection and analysis of Medicare cost data, which can result in up to a two-year lag before a decision on final DRG assignment is reached. For fiscal year 1998 (beginning in October 1997), procedures involving the insertion of a coronary stent (36.06) were reassigned into a different DRG category (DRG 116) with a reimbursement rate $2,120 greater per stenting procedure. 15 Claims were made after this coding change that the new payment rate would increase Medicare beneficiaries access to the coronary stent. 16 If large numbers of hospitals were restricting patients from receiving a first stent prior to the increase in reimbursement, a sharp increase in use would be expected in Exhibit 1 shows the rate of year-to-year increase in the number of patients receiving at least one stent; the acceleration in this rate appears to decrease after This suggests that the increased payment did not drive an increase in use. Because these figures are an unadjusted count of all Medicare beneficiaries receiving a stent, care must be taken in interpreting their meaning. Changes in patient factors and severity of disease, for example, might have influenced stent use over time. Nonetheless, HEALTH AFFAIRS ~ Vo l u m e 2 7, N u m b e r

5 Medical Devices EXHIBIT 1 Total And Inpatient Coronary Stenting Procedures Among Medicare Beneficiaries, Thousands of procedures Total procedures Inpatient procedures SOURCE: Medicare beneficiaries use of coronary stenting was determined from an analysis of Medicare s Physician/Supplier Procedure Summary (PSPS) Master Files. The PSPS is a 100 percent summary of all Part B and Durable Medical Equipment Regional Carrier (DMERC) claims processed through the Common Working File and stored in the National Claims History Repository at the Centers for Medicare and Medicaid Services (CMS). The PSPS provides data on total services provided to beneficiaries during each respective calendar year. Procedures are identified using the Healthcare Common Procedure Coding System (HCPCS). The HCPCS code for single vessel stenting (92980) was created in For this analysis, this code was used to determine annual use of procedures that included insertion of one or more coronary stents. NOTES: The higher diagnosis-related group (DRG) payment for stenting was introduced in The gray shaded line indicates the approximate expected use if year-to-year growth had continued along the trend set in these findings are consistent with those of previously published studies that did adjust for patient differences among other factors. In one analysis of stent usage at the Mayo Clinic, the use of stents increased from 6.2 percent of procedures in 1993 to 46.3 percent in The authors noted that this was despite the lack of a specific DRG for stent implantation. By the end of the study, 59.4 percent of procedures used an unapproved device or unapproved indication. Another study analyzed data from twelve U.S. hospitals using the National Cardiovascular Network s Coronary Interventional Database during This analysis found that stent use as a percentage of PTCA procedures increased from 5.4 percent in 1994 to 69 percent in This study did not report the fraction of Medicare patients in the study population but found, after adjusting for race and sex, that age was not a predictor of stent use. Stent use was strongly influenced by the patient s coronary anatomy and procedural indication and also varied among different hospitals even after patient characteristics were adjusted for. These findings suggest that more than just clinical or payment factors influenced the use of stents. The analysis of the twelve hospitals also showed that outcomes were improved over time, with a significant decrease in urgent repeat revascularization, vascular complications, andlengthofhospitalstayforpatients receiving stents in 1997 compared to those in It cannot be determined from this analysis whether diffusion of stents might have followed a different course if payment policies had been different. Many factors might have affected the diffusion of coronary stenting technology, including separate payment to physicians and hospitals, the shift to outpatient settings for 1570 November/December 2008

6 Coronary Stents which there is a different payment system, increasing competition from new stents entering the marketplace, and changes in prevalence of disease. Hideki Hashimoto and colleagues have attributed differences in stenting technology diffusion between teaching hospitals in the United States and Japan to differences in hospital reimbursement policies as well as to differences in practice norms, physician reimbursement, and patient characteristics. 19 Ahigherinitialpaymentmighthavecreatedadditionaldemandanddriveneven more rapid diffusion, which, from a clinical perspective, would probably not have been desirable. Even without higher payment, stents were rapidly adopted for unapproved indications without evidence. Further, the number of adverse events in the first patients was high; the balance of benefits and harms might not have been beneficial for many patients. Outcomes improved as techniques and adjunctive therapies evolved. Drug-Eluting Stents In 2004 the CMS faced a similar situation with drug-eluting stents. Studies of these stents showed lower rates of restenosis and reprocedure compared to bare metal stents but no differences in mortality or myocardial infarction rates. Late stent thrombosis was identified as a potentially important adverse event. Early studies did not show a difference in thrombosis rates or other adverse events between study groups but had limited power and lacked the follow-up necessary to detect any such differences. To account for the higher cost of the stent, the CMS assigned the procedure to a new DRG (with a reimbursement of about $1,500 greater than the DRG used for bare metal stents) at the same time as FDA approval, explaining that they were concerned that the predicted rapid diffusion of drug-eluting stents would lead to astrainonhospitals financialresources. 20 Drug-eluting stents did diffuse more rapidly than bare metal stents, with a majority of procedures using a drug-eluting stent eighteen months after approval. 21 This quick diffusion occurred even though the additional reimbursement amount was not expected to cover the cost of the stents. 22 Further, the adoption of drug-eluting stents was expected to decrease the overall profitability of hospitals because of a reduced need for procedures to treat restenosis and a shift to stents from bypass surgeries, both of which are profit centers for hospitals. 23 Hospital economics are complex, and the specific reimbursement level for a single new technology is only one factor in determining overall use. One potential factor in the faster diffusion of drug-eluting stents over bare metal stents was that bare metal stents represented a larger change in clinical practice compared to drug-eluting stents. There was also good evidence that drug-eluting stents reduced the problem of restenosis widely observed with bare metal stents. Therefore, drug-eluting stents were compatible with both practice patterns and perceived clinical needs. 24 In September 2006 the FDA issued a statement that data suggested a small but HEALTH AFFAIRS ~ Vo l u m e 2 7, N u m b e r

7 Medical Devices significant increase in the rate of death and myocardial infarction, possibly as a result of stent thrombosis, in patients treated with drug-eluting stents. Researchers are attempting to confirm this and understand which patients might be at increased risk and the appropriate use of drug-eluting versus bare metal stents. Nevertheless, it is clear that drug-eluting stents, like bare metal stents, diffused rapidly to off-label indications and that there was a lack of careful documentation of patient characteristics and outcomes across a broad population that could help resolve uncertainties. Discussion And Policy Implications In this model of technology diffusion (Exhibit 2), clinical studies establish safety and effectiveness in limited populations under carefully controlled conditions. These clinical studies become the basis for FDA approval and dictate labeling indications and specific instructions for future clinical use. Technology then diffuses into clinical practice and is reinvented in different patient populations with different protocols of use. Based on this paradigm, evaluation of the safety and effectiveness of new technology as it is used in clinical practice should not rely solely on clinical studies, but should involve the continued evaluation of the new technology. In the case of coronary stents, reinvention led to improvements in outcomes over time. However, because of the lack of systematic data collection, many questions remained unanswered years after FDA approval, even though several of these questions had been identified as important to understand. Indeed, reinvention and innovation are a natural consequence of physicians using their judgment and experience together with evidence to tailor therapies to the specific characteristics of patients and their conditions. However, reinvention EXHIBIT 2 Model Of Technology Diffusion And Reinvention Clinical studies Establish safety and effectiveness in limited populations under carefully controlled conditions FDA approval: specific labeled indications and instructions for use Diffusion to clinical settings REINVENTION: Different patient populations Different protocols of use Rate of diffusion, population, setting, provider, and so on may all be affected by reimbursement policy NEEDED INFORMATION Surveillance for adverse events Measurement of net benefit compared to alternative treatments in different clinical populations SOURCE: Authors analysis November/December 2008

8 Coronary Stents then leads to off-label uses for which there is often limited evidence on effectiveness and safety. The ways in which technology will be reinvented are difficult to anticipate because of the complexity of medical devices and unique characteristics of each patient. The extent to which reinvention is considered research is a gray area. Interviews with researchers and ethics boards found much disagreement on whether the introduction of a new diagnostic test into clinical practice was considered research. 25 Compliance with ethical and regulatory requirements of research such as informed consent could be burdensome and could delay patient care and access to new treatments. Conversely, rapid adoption of new technologies outside of research studies may result in patients not being adequately informed of their risks and benefits. The Society of University Surgeons has published a position paper recommending more than routine informed consent and oversight for some innovations, such as when the surgeon seeks to assess a hunch, hypothesis or theory (eg., that the innovation is an improvement of technique) even outside of formal studies. 26 In addition to protecting patients, formal studies provide the opportunity to collect data that can improve future patient care. Agrowingrecognitionoftheneedfordatacollectionhasledtolegislationto strengthen the FDA s postmarket authority. The Prescription Drug User Fee Act (PDUFA) and the Medical Device User Fee and Modernization Act (MDUFMA) both provide the FDA with resources to review the safety and effectiveness of drugs and medical devices, respectively, before and after FDA approval. More recently, the FDA Amendments Act (FDAAA) of 2007, in addition to reauthorizing and strengthening PDUFA and MDUFMA, gives the FDA the authority to require and enforce postmarket activities. The FDAAA also mandates public registration of results of applicable clinical trials of drugs, biologics, and devices online at The CMS, like the FDA, also has a need to review evidence on medical technology. The CMS has recognized that existing evidence sometimes suggests that new technologies are beneficial but that more information is needed on the specific clinical populations and settings in which they should be used. Coverage with evidence development (CED) allows payment for new technologies while data are collected and analyzed through clinical trials or patient registries. A benefit of using CED to generate evidence is the ability to collect clinical data with which to evaluate how a new technology is being used and subsequently reinvented. The current FDA regulatory process and the CED policy at the CMS are designed to meet each agency s respective needs; however, it is important to note that their roles are complementary, as are the data collected and analyzed at the two agencies. There have been proposals in the past to have the FDA and the CMS work in partnership. For example, in 1987, the FDA and HCFA jointly issued a rule to establish a national cardiac pacemaker registry as required by the Deficit Reduction Act of The final rule allowed HCFA to deny Medicare payment if HEALTH AFFAIRS ~ Vo l u m e 2 7, N u m b e r

9 Medical Devices the required information was not submitted to the FDA. This registry was a positive example of how HCFA and the FDA could reinforce each other s responsibilities and also was a model for future collaboration. 28 The requirement was subsequently revoked after Congress passed An Act to Repeal an Unnecessary Medical Device Reporting Requirement in 1996 to eliminate what it considered duplicative reporting. 29 Although some of the information in the registry would have been duplicative, the registry also would have been an important source of information not available elsewhere. The same year as the congressional repeal, there was a consensus recommendation for a North American Device/Lead Database, which was never implemented in the United States. 30 This recommendation was made after it became clear that there was no systematic or complete registry with which to analyze the causes of reported device failures or identify possible fixes to the failing devices. An analysis of pacemaker malfunctions in 2006 also found the same limitations in the existing small and voluntary registries. 31 Although ten years had passed, these limitations had not been addressed. The payment system is a theoretically important driver of technology diffusion and innovation. The Medicare inpatient prospective payment system (PPS) is intended to reimburse hospitals for reasonably efficient, high-quality care; those with lower costs are rewarded, while those with higher costs are penalized. 32 This payment system may provide an undesirable disincentive to the diffusion of beneficial technologies that also increase costs. However, in the stent example, the implementation of a higher payment rate did not drive the acceleration of the diffusion of the technology, as has been claimed. Because of a belief that lack of payment would restrict access to new procedures and devices, the Benefits Improvement and Protection Act (BIPA) of 2000 provided an add-on payment under the Medicare hospital PPS to new technologies meeting specified criteria. One of the first technologies to receive an add-on payment was the sepsis drug Xigris. The 2008 Surviving Sepsis Campaign guidelines produced by a consortium of physician specialty societies states that the evidence for the use of Xigris is only moderate because of inconsistencies in the results of two RCTs and that the European Medicines Agency (EMeA) is currently requiring a placebo-controlled trial. 33 The drug is potentially lifesaving but also has a high risk of bleeding and other adverse events; the overall risk versus benefit is still not known six years after FDA approval and five years after implementation of the Medicare add-on payment. The primary concern in allowing the add-on payment was access to the technology, but the need for continuing data collection was not addressed. The current regulatory and payment system is mismatched to the fundamentally dynamic process of innovation. The example of stents shows that even when there are high-quality clinical trials available, continuing data collection is needed to adequately assess the net benefit of new technology as it is reinvented in clinical practice, particularly as patient populations and adjunctive technologies evolve November/December 2008

10 Coronary Stents There is a lack of incentives for data collection in the current system, which has led to a lack of clinically important information not only for the original coronary stents, but also for drug-eluting stents, pacemakers, Xigris, and many other innovations. Payment systems that encourage the data collection such as CED and increased collaboration between the FDA and the CMS may provide the needed incentive for additional data collection. To developtheevidencebase for evaluating new technologies, systems must be created that build upon existing initiatives at the CMS and the FDA. There is no single solution for addressing all evidentiary needs for all technologies for which coverage and regulatory decisions are made. The continued evaluation of stents, for example, is likely to require a different model of evaluation than that necessary to study the use of Xigris. A commonality in all technology evaluation, however, is that its diffusion and reinvention necessitate continued data collection and evaluation. The FDA and the CMS should work with each other, other government agencies, industry, and physician groups to determine the balance of benefits and harms of new technologies as used in clinical practice. Such a collaborative effort will ensure that patients have access to novel, potentially lifesaving technology; that harms are identified quickly; and that data are available to determine the best treatments. The opinions expressed herein are those of the authors alone and do not represent the official positions or policies of the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services. The authors thank Margaret Coopey for extensive feedback and help; Lisa Dubay, David Matchar, and Jean Slutsky for helpful comments on the manuscript; and Angela Smith and Hesha Duggirala for finding original stent product labels at the Food and Drug Administration. This paper is dedicated to the memory of Louis Berliner, who always demanded to know, How will this treatment benefit me? NOTES 1. Centers for Medicare and Medicaid Services, Medicare Program; Changes to the Hospital Inpatient Prospective Payment Systems and Fiscal Year 1997 Rates; Final Rule, Federal Register 61, no. 170 (1996): B.G. Firth, The Disconnect between HCFA and the FDA, Journal of Invasive Cardiology 13, no. 2 (2001): H.C. Kung et al., Deaths: Final Data for 2005, National Vital Statistics Reports 56, no. 10 (2008). 4. National Center for Health Statistics, Health: United States, 2007, with Chartbook on Trends in the Health of Americans (Hyattsville, Md.: NCHS, 2007). 5. E.D. Grech, ABC of Interventional Cardiology: Percutaneous Coronary Intervention, I: History and Development, British Medical Journal 326, no (2003): U. Sigwart et al., Intravascular Stents to Prevent Occlusion and Restenosis after Transluminal Angioplasty, New England Journal of Medicine 315, no. 12 (1987): P.W. Serruys et al., A Comparison of Balloon-Expandable-Stent Implantation with Balloon Angioplasty in Patients with Coronary Artery Disease, New England Journal of Medicine 331, no. 8 (1994): ; and D.L. Fischman et al., A Randomized Comparison of Coronary-Stent Placement and Balloon Angioplasty in the Treatment of Coronary Artery Disease, New England Journal of Medicine 331, no. 8 (1994): R. Erbel et al., Coronary-Artery Stenting Compared with Balloon Angioplasty for Restenosis after Initial Balloon Angioplasty, New England Journal of Medicine 339, no. 23 (1998): HEALTH AFFAIRS ~ Vo l u m e 2 7, N u m b e r

11 Medical Devices 9. A. Colombo et al., Intracoronary Stenting without Anticoagulation Accomplished with Intravascular Ultrasound Guidance, Circulation 91, no. 6 (1995): C.J. Pepine and D.R. Holmes Jr., Coronary Artery Stents, Journal of the American College of Cardiology 28, no. 3 (1996): D.R. Holmes Jr. et al., ACC Expert Consensus Document on Coronary Artery Stents: Document of the American College of Cardiology, Journal of the American College of Cardiology 32, no. 5 (1998): A. Schömig et al., Coronary Stent Placement in Patients with Acute Myocardial Infarction: Comparison of Clinical and Angiographic Outcome after Randomization to Antiplatelet or Anticoagulant Therapy, Journal of the American College of Cardiology 29, no. 1 (1997): 28 34; and M.B. Leon et al., Clinical and Angiographic Results from the Stent Anticoagulation Regime Study STARS (Abstract), Circulation 94 (1996): 4002A. 13. E.M. Rogers, Diffusion of Innovations, 5th ed. (New York: Free Press, 2003). 14. CMS, Medicare Program: Changes to the Hospital Inpatient Prospective Payment Systems and Fiscal Year 1997 Rates: Final Rule, Federal Register 61, no. 412 (1997): P.T. Vaitkus, Economic Impact on Physicians and Hospitals of Proposed Changes in Medicare Reimbursement for Coronary Interventions, American Heart Journal 137, no. 2 (1999): Firth, The Disconnect 17. D.R. Holmes Jr. et al., Interventional Cardiology and Intracoronary Stents A Changing Practice: Approved versus Nonapproved Indications, Catheterization and Cardiovascular Diagnosis 40, no. 2 (1997): E.D. Peterson, A.J. Lansky, and K.J. Anstrom, Evolving Trends in Interventional Device Use and Outcomes: Results from the National Cardiovascular Network Database, American Heart Journal 139, no. 2, Part 1(2000): H. Hashimoto et al., The Diffusion of Medical Technology, Local Conditions, and Technology Re-Invention: A Comparative Case Study on Coronary Stenting, Health Policy 79, nos. 2 3 (2006): CMS, Medicare Program; Changes to the Hospital Inpatient Prospective Payment Systems and Fiscal Year 2003 Rates; Final Rule, Federal Register 67, no. 148 (2002): S.V. Rao et al., Patterns and Outcomes of Drug-Eluting Coronary Stent Use in Clinical Practice, American Heart Journal 152, no. 2 (2006): New Stents May Block Income, Modern Healthcare 33, no. 31 (2003): C. Becker, Stuck in the Middle, Modern Healthcare 32, no. 42 (2002): Rogers, Diffusion of Innovations. 25. J. Patenaude et al., Evaluation of Clinical Innovation: A Gray Zone in the Ethics of Modern Clinical Practice? Journal of General Internal Medicine 23, no. 1 Supp. (2007): W.L. Biffl et al., Responsible Development and Application of Surgical Innovations: A Position Statement of the Society of University Surgeons, Journal of the American College of Surgery 206, no. 3 (2008): Food and Drug Administration and Health Care Financing Administration, Cardiac Pacemaker Registry, Federal Register 52, no. 141 (1987): S.B. Foote, Managing the Medical Arms Race: Innovation and Public Policy in the Medical Device Industry (Berkeley: University of California Press, 1992). 29. Food and Drug Administration, Medical Devices: Revocation of Cardiac Pacemaker Registry, Federal Register 64, no. 226 (1999): W.H. Maisel et al., Recalls and Safety Alerts Involving Pacemakers and Implantable Cardioverter- Defibrillator Generators, Journal of the American Medical Association 286, no. 7 (2001): W.H. Maisel et al., Pacemaker and ICD Generator Malfunctions: Analysis of Food and Drug Administration Annual Reports, Journal of the American Medical Association 295, no. 16 (2006): Medicare Payment Advisory Commission, Payment Basics: Hospital Acute Inpatient Services Payment System (Washington: MedPAC, September 2006). 33. R.P. Dellinger et al., Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock: 2008, Journal of Intensive Care Medicine 34, no. 1 (2008): November/December 2008

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