Use of rt-PA is associated with long-term cost savings, but more high-quality, current cost-effectiveness research is needed for stroke centers, care networks, and telemedicine.
Objective: To conduct a systematic literature review analyzing cost-effectiveness or cost savings associated with use of recombinant tissue plasminogen activator (rt-PA), stroke centers, and telemedicine programs for acute ischemic stroke.
Methods: A literature search was conducted of the PubMed/MEDLINE and Ovid/EMBASE databases from January 1, 1995, to August 30, 2008, limited to English-language articles and using the search terms [stroke and cost and telemedicine] or [stroke and cost and alteplase] or [stroke and cost and tissue plasminogen activator] or [stroke and cost and rt-PA] or [stroke center and cost] or [stroke unit and cost]. Abstracts were reviewed, and inclusion/exclusion criteria were used to select studies. The analysis was limited to studies addressing costs or cost-effectiveness of the interventions in the United States.
Results: This search identified 748 abstracts, of which 24 were included. Among these 24 studies were 2 cost-effectiveness, 8 cost-savings, and 4 cost-benefit analyses. All discussed some aspect of practice economics. The primary cost-effectiveness data available for rt-PA use demonstrated increased hospitalization costs but long-term cost savings due to decreased nursing home and rehabilitation costs. No cost-effectiveness studies for stroke centers or telemedicine programs were identified, although stroke centers have been shown to reduce hospital length of stay and both stroke centers and telemedicine programs have demonstrated increased rates of rt-PA administration within 3 hours of the onset of stroke symptoms.
Conclusion: More high-quality, current cost-effectiveness research for stroke centers, care networks, and telemedicine is needed to inform treatment decisions and resource utilization.
(Am J Manag Care. 2010;16(7):537-544)
This systematic literature review highlights the need for more current health economic research on acute stroke care to inform treatment decisions and resource utilization.
New or recurrent stroke affects approximately 780,000 people in the United States each year, with ischemic stroke being the most common type, representing 87% of all strokes.1 The prevalence of stroke among adults aged 20 years or older was estimated at 5.8 million in 2005.2 The consequences of stroke can be devastating for patients and their families, and stroke treatment and long-term care impose an enormous economic burden on society. Stroke is the third leading cause of death in the United States, behind heart disease and cancer; stroke mortality reported in 2004 was more than 150,000.2 Stroke is also a leading cause of serious, long-term disability in the United States, with up to 30% of stroke survivors becoming permanently disabled and 20% requiring institutional care at 3 months after onset. The total direct and indirect costs of stroke for 2008 have been estimated at $65.5 billion.2
Currently, intravenous infusion of recombinant tissue plasminogen activator (rt-PA; alteplase [Activase]) is the only treatment approved by the US Food and Drug Administration for acute ischemic stroke.3 Approved since 1996, rt-PA is a thrombolytic agent indicated for the management of acute ischemic stroke in adults to improve neurologic recovery and reduce the incidence of disability.4 In the original National Institute of Neurological Disorders and Stroke (NINDS) rt-PA Stroke Study, a randomized, double-blind, 2-part trial of 624 patients treated with rt-PA or given a placebo within 3 hours of symptom onset, those given rt-PA were significantly more likely to have a favorable outcome at 3 months (odds ratio, 1.7; 95% confidence interval , 1.2-2.6) based on a global outcome score that combined 4 different stroke scales. Favorable outcome, defined as minimal or no disability at 3 months after stroke, was achieved in 31% to 50% of patients given rt-PA versus 20% to 38% of those given placebo.5 Symptomatic intracerebral hemorrhage within 36 hours of stroke onset was increased in the rt-PA group (6.4% vs 0.6% in the placebo group, P <.001), but mortality rates at 3 months were not different between groups (17% and 21% in the rt-PA and placebo groups, respectively).5
On the strength of this and subsequent efficacy data, the American Heart Association/American Stroke Association (AHA/ASA) guidelines for early management of adults with ischemic stroke recommended the use of rt-PA for carefully selected patients who can be treated within 3hours of the onset of ischemic stroke.3 However, the challenges involved with this therapy—including the timing of patient presentation after onset of symptoms and perceived risks of bleeding complications—have meant that only 2% to 3% of stroke patients receive treatment with rt-PA nationally.6 Recently, results of the European Cooperative Acute Stroke Study (ECASS III) were published, showing that alteplase given 3 to 4.5 hours after the onset of stroke symptomssignificantly improved clinical outcomes in patients with acuteischemic stroke compared with placebo.7 These results may enable more patients to receive rt-PA as treatment guidelines are updated to reflect this expanded time window.
In recent years, more stroke centers and telemedicine programs have been developed to facilitate the use of rt-PA therapy in eligible patients and to improve overall care of stroke patients. A formal process for the certification of primary stroke centers (PSCs) was begun by The Joint Commission in February 2004, and by February 2006 this organization had certified approximately 200 US hospitals as PSCs. Since the publication of the AHA/ASA stroke guidelines, 7 states have implemented or were in the process of implementing guidelines to send stroke patients whose symptoms had begun within the past 3 hours directly to a stroke center.3 In rural or underserved areas, stroke centers have begun using telemedicine technology to provide expertise and expedite treatment at outlying hospitals.3
The AHA/ASA stroke guidelines recognized the clinical benefits of these approaches and strongly recommended the creation and certification of PSCs to provide specialized stroke service.3 For example, the use of rt-PA administration at 1 PSC in Bethesda, Maryland, increased from 1.5% to 10.5% of patients during the first 2 years of the center’s operation (P <.0001).8 Several urban and nonurban PSCs have since reported 10% to 20% of stroke patients receiving treatment with rt-PA.9 Recently, a study of 8 PSCs in Phoenix, Arizona, reported a mean of 18% of ischemic stroke patients receiving rt-PA, with half of the 8 matrix PSCs meeting or exceeding the 20% treatment target.10 Also, a prospective case-control study comparing telemedicine with traditional service delivery reported that telemedicine consultations shortened times to treatment from 33 minutes (control) to 17 minutes (telemedicine), and increased rt-PA administration from 5% to 24% at a remote hospital in Maryland.11 Similarly, a prospective study of a telemedicine program in Southern California reported that correct treatment decisions regarding the use of rt-PA were made in 98% of telemedicine consultations (compared with 82% with less expensive telephone consultations), with 28% of ischemic stroke patients receiving rt-PA administration.12
Given the enormous costs associated with treatment of acute ischemic stroke in the short term, as well as long-term costs required to deal with its consequences in severely affected patients, improved stroke systems of care have the potential to result in cost savings. However, establishing stroke centers and telemedicine programs can involve substantial initial costs, and administration of rt-PA—with its attendant increased diagnostic and patient-monitoring requirements—substantially increases hospital costs for stroke treatment. Indeed, to reflect these increased costs, Medicare reimbursement to hospitals was increased in 2005 by approximately $6000 per stroke patient when thrombolytic treatment was administered.13 As the use of rt-PA, stroke centers, and telemedicine programs becomes more widespread, it becomes important to better understand the economics of these treatment systems. Therefore, this article seeks to provide a systematic review of the available literature that analyzes cost-effectiveness or cost savings associated with each of these 3 components of acute stroke intervention.
This systematic review was intended to assess available cost information on rt-PA, stroke centers, and telemedicine, regardless of the type of cost analysis performed (Table 1). 14-31 The cost analyses identified in the literature search were categorized into 3 types: cost-effectiveness analysis, cost-benefit analysis, and practice economics.
Cost-effectiveness analysis is a systematic method of comparing 2 or more interventions by measuring their costs and consequences (health outcomes), where the consequences of each are measured in the same common units related to the clinical objective of the interventions (eg, life-years gained).14 The perspective for cost-effectiveness analysis is usually a societal one, as society incurs the costs associated with giving the intervention and realizes the consequences of the intervention (eg, the payer pays for a stroke treatment and its treated members gain an increase in quality-adjusted life-years [QALYs] from the treatment).
Cost-benefit analysis measures and compares the net costs of a healthcare intervention with the benefits that arise as a result of the intervention, where both net costs and benefits are expressed in monetary units.32 The perspective for cost-benefit analysis is the group or individual realizing the costs and benefits of the intervention, such as (1) a hospital investing in a stroke center, which results in cost savings because of decreased length of stay (LOS); or (2) a payer who pays for rt-PA administration, which saves on downstream rehabilitation costs because of decreased disability.
The category of practice economics was defined as involving the study of costs, revenues, operational efficiency, and/or profitability related to administering an intervention. The perspective for practice economics is a provider (hospital, system, or practice) that operates a practice that administers the intervention and realizes both costs and revenues related to its use (eg, a hospital that invests in a telestroke system and gains revenue from increased neurosurgery referrals). Although many articles discussed practice economics, cost-benefit or cost-effectiveness analyses of these stroke systems of care were relatively rare.
The literature search was performed using PubMed/MEDLINE and Ovid/EMBASE databases, limited to English-language articles of studies performed in the United States and published between January 1, 1995, and August 30, 2008 (ure). Restriction to the United States was because of significant differences in the healthcare systems of other countries. Specific search terms included [stroke and cost and telemedicine] or [stroke and cost and alteplase] or [stroke and cost and tissue plasminogen activator] or [stroke and cost and rt-PA] or [stroke center and cost] or [stroke unit and cost]. After a brief review of abstracts from the initial search, potentially relevant publications were read in full to determine suitability for inclusion in this analysis, and further studies were identified in some cases from the publications’ references.
Economic Outcomes Analyses
As shown in the Figure, the search terms yielded 748 abstracts, of which 24 articles were ultimately considered appropriate for inclusion in this analysis. Table 1 lists the types of cost analyses performed in each of these articles by intervention (rt-PA, stroke center, and/or telemedicine). Among the 24 articles selected for inclusion, there were 2 true cost-effectiveness analyses (excluding reviews), 8 cost-savings analyses, and 4 cost-benefit analyses. All 24 discussed some aspect of practice economics.
Recombinant Tissue Plasminogen Activator
Articles specifically addressing costs associated with rt-PA use are described in more detail in Table 2.The primary cost-effectiveness data available for rt-PA use are from the study published by Fagan and colleagues in 1998.26 The authors used data from the NINDS rt-PA Stroke Study5 and the medical literature to estimate health and economic outcomes associated with rt-PA use in patients with acute ischemic stroke, and then developed a Markov model to estimate costs per 1000 patients eligible for treatment with rt-PA versus costs per 1000 untreated patients.26 The estimated impact of rt-PA use on long-term health outcomes was a savings of 564 QALYs over 30 years of the model per 1000 patients.26 rt-PA was associated with increased hospitalization costs of $1.7 million, or $1700 for each patient treated, and an increased hospitalization cost of $15,000 per additional patient discharged home. However, rt-PA also was associated with decreased nursing home and rehabilitation costs, resulting in a net predicted cost savings of approximately $600,000 at 1 year for 1000 treated patients. Cost-effectiveness calculations showed that rt-PA treatment resulted in an incremental cost savings of $8000 per QALY gained.26 Using Fagan and colleagues’ basic cost-savings result, at $600 per rt-PA—treated patient, Demaerschalk and colleagues estimated in 2005 that every 2% increase in the proportion of ischemic stroke patients receiving rt-PA would result in $7 million of annual savings in healthcare costs to the United States.9
Taking a different approach, Stahl and colleagues evaluated the cost-effectiveness of implementing a process of compliance with NINDS recommendations for care of patients presenting with signs and symptoms of acute ischemic stroke.20 They reported that the QALY value for a patient treated with rt-PA was 3.99 versus 3.62 for a patient not treated in time to receive rt-PA. The cost savings were from reduced hospital costs and reduced rehabilitation and nursing home costs.20 Finally, Demaerschalk and colleagues looked at costs to the hospital of administering rt-PA relative to Medicare reimbursement rates for the treatment of acute stroke (the cost/reimbursement ratio). In this analysis, the cost/reimbursement ratio for patients treated with rt-PA from 2001 through 2004 was 1.41, meaning that the hospital was absorbing the excess costs of patients treated with rt-PA. After the new reimbursement rate took effect, the cost/reimbursement ratio was estimated to be 0.82 (ie, the administration of rt-PA became more cost-effective to the institution providing stroke care).13
Three articles from the mid to late 1990s reported specific data on hospitalization costs for treatment of acute stroke before and after adoption of some type of stroke-center program at a given institution (Table 3).27,30,31 In each case, the implementation of a specialized stroke program was associated with a decline in the average cost of treating stroke patients and with a lower average LOS. For example, development of a comprehensive program for stroke patients, including a dedicated stroke unit, at a hospital in Kansas City, Missouri, resulted in a decreased average cost per patient (from $7451 in 1993 to $6667 in 1997, not adjusted for inflation), and a reduction in average LOS from 7.5 to 6.0 days.27 However, as all 3 analyses were conducted in the mid-1990s before the approval of rt-PA for stroke, costs for thrombolytic treatment may not have been incorporated.
Lattimore and colleagues, in contrast, reported an increase in rt-PA use in ischemic stroke patients from 1.5% in the year prior to creation of a PSC in 1999-2000 to 10.5% in the 2-year period following its initiation.8 Using an extrapolation of the Fagan et al 1998 data on rt-PA cost-effectiveness,26 these authors estimated that a 5% increase in rt-PA use nationwide would result in approximately 30,000 more patients each year receiving this treatment, with approximately 4000 of those patients avoiding long-term disability and conferring a net cost savings to the healthcare system of more than $100 million annually.8
The published literature on the economic impact of stroke telemedicine programs is even more limited, with no actual cost-effectiveness studies for telemedicine identified in this systematic review. Articles discussing the economics of telemedicine primarily addressed the costs of implementing and/or operating this type of system, rather than its impact on overall costs of stroke treatment. A 2003 editorial published by David Wang, University of Illinois, in reaction to a report of a German telemedicine program, opined that “the cost of $8000 for a stroke network center and $500 for each network site is very affordable,” referring to the setup costs of the needed technology.21
Cho and colleagues discussed the business aspects of a telemedicine program (REACH) set up in 2003 to treat stroke patients at local hospitals in rural Georgia.14 This program evaluated more than 400 patients at 9 rural hospitals in its first 3 years of operation, and 65 of these patients (16%) were treated with rt-PA—approximately half of them in less than 2 hours. The system did not produce direct revenue from the neurology consultations for the hub hospital, because it did not provide 2-way interactive video (a requirement for reimbursement), but the system was eventually profitable for the hub hospital because most of the stroke patients evaluated were subsequently referred to the hub center. The rural hospitals, however, experienced financial losses because of insufficient Medicare/Medicaid reimbursement for rt-PA administration (prior to the increased reimbursement rates implemented in 2005).
Several authors have commented on initial funding sources and reimbursement policies being the current barriers to more widespread use of telemedicine programs.11,16 Nevertheless, an analysis of business models for telemedicine applied to poststroke rehabilitation at outpatient clinics in Oklahoma reported that 340 telemedicine visits would generate positive net cash flow each year, and the project is expected to recoup its initial investment by the 4th year of operation.17 Regarding acute stroke care, there also are implied long-term cost savings to the healthcare system associated with increased rt-PA usage facilitated by access to telemedicine consultations.11,19 Unfortunately, there were no published, formal cost-effectiveness studies analyzing and quantifying the actual costs and benefits of acute stroke treatment provided through telemedicine programs in the United States.
Results of this systemic literature review indicate that there is published evidence for rt-PA as a cost-effective treatment that improves stroke outcomes and reduces costs of care in the long term. However, the cost-effectiveness data are becoming outdated—the key study cited in subsequent discussions of stroke care economics was published in 1998—and more current health economics research of acute stroke care is warranted. The past decade has seen widespread growth in the development of PSCs33 and telemedicine programs34-36 to facilitate improved delivery of acute stroke care. The use of both PSCs and telemedicine has been shown to increase rates of rt-PA administration, which may, by extension, reduce long-term costs of stroke care, but the true cost-effectiveness of these programs in the United States has yet to be studied in a rigorous fashion.37 Implementation of dedicated stroke teams and units in a stroke-center model has demonstrated decreased average per-patient costs of treating stroke and average hospital LOS, but much of these data were based on costs prior to the introduction of rt-PA.
An International Classification of Diseases, Ninth Revision V-code (V45.88) became effective in October 2008 by the Centers for Medicare & Medicaid Services to track “drip and ship” patients.38 The Centers for Medicare & Medicaid Services is interested in data collection on cost of care for patients who receive rt-PA for acute stroke at outside emergency departments and then are transferred to a stroke center. The purpose is to determine whether such patients require increased hospital reimbursement. Currently, when ischemic stroke patients receive thrombolysis at one facility’s emergency department and are transferred to another facility for admission, neither of the facilities is eligible for the higher diagnosis-related group reimbursement related to thrombolysis administration. The lack of increased reimbursement in the drip and ship model may limit further development of sustainable telestroke networks. The Centers for Medicare & Medicaid Services may recommend changes dependent upon review of the V45.88 data.
Recently, a cost-effectiveness study was published examining the national use of rt-PA for acute ischemic stroke via telemedicine in Denmark.39 This analysis estimated that the administration of rt-PA for acute ischemic stroke via telemedicine was associated with additional costs to the hospitals totaling $3 million per year in a model of 5 centers and 5 satellite clinics. In the short term (1 year), the incremental cost-effectiveness ratio via telemedicine was approximately $50,000 per QALY, and, by the second year, it was a dominant (both cheaper and more effective) strategy due to savings in care and rehabilitation costs.39
Health economics research is still needed in the United States to examine the cost-effectiveness of acute stroke—care systems and treatments based on US healthcare costs and reimbursement structures. Currently, a period of rapid growth in the establishment of PSCs and the development of telemedicine programs essential to healthcare reform is under way.40 This is likely to have a positive clinical impact for stroke patients in many areas of the country previously lacking access to high-quality acute-care services and timely evaluation for appropriate therapies.
However, the net economic impact of these programs merits further study, such as through the collection of health economics outcome data alongside clinical outcomes data in prospective trials of stroke programs, stroke centers, stroke-care systems, stroke telemedicine networks, and treatments.
In conclusion, this systematic review of the published literature has found evidence regarding the ability of stroke centers and telemedicine programs to provide timely acute stroke care and to increase access to rt-PA therapy for eligible patients, but few data are available on the cost-effectiveness of these programs per se. More high-quality, current cost-effectiveness research on stroke interventions is needed to inform treatment decisions and resource utilization.
The authors gratefully acknowledge Marci Mikesell, PhD, Embryon, for assistance with the revisions and further development of the manuscript based on critical comments and direction from all authors; Susan Hogan, PhD, Embryon, for reviewing the manuscript for scientific accuracy; and Vicki Blasberg, Embryon, for managing the coordination of manuscript development and submission.
Author Affiliations: From the Department of Neurology (BMD), Mayo Clinic Hospital, Phoenix, AZ; and Genentech, Inc (HMH, GL), South San Francisco, CA.
Funding Source: Genentech, Inc, South San Francisco, CA, provided funding for editorial assistance to Embryon for editing, proofreading, and reference verification.
Author Disclosure: Dr Demaerschalk is the principal investigator (PI) for STRokE DOC AZ TIME (Arizona Department of Health Service [ADHS]) and Stroke Telemedicine for Arizona Rural Residents (ADHS); the site PI for Interventional Management of Stroke III (IMS III; National Institutes of Health [NIH]), Stenting and Aggressive Medical Management for Preventing Recurrent Stroke (SAMMPRIS; NIH), Secondary Pre-vention of Small Subcortical Strokes (SPS3; NIH), Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST; NIH), Randomized Evaluation of Recurrent Stroke Comparing PFO Closure to Established Current Standard of Care Treatment (RESPECT; AGA Medical Corpora-tion), V10153 Acute Stroke Thrombolysis Trial (VASTT; Vernalis), Ancrod Stroke Program (ASP, Neurobiological Technology), and MP-124-A07 Trial (Mitsubishi Pharma); a co-investigator for ALbumin In Acute Stroke (ALIAS; NIH), CHOICE (Abbott), and ACT I (Abbott); a steering commit-tee member for SPS3, ASP, and VASTT; a Data Safety Monitoring Board member for IN-STEP (Vernalis); medical monitor for Neuralieve; and an event adjudicator for Axio Research. He reports no other consultancies, honoraria, speaker bureau memberships, employment relationships, or stocks. Ms Leung is an employee of Genentech, the company that funded this work. Dr Hwang was an employee of Genentech at the time this study was developed. She is now with the University of California San Francisco, San Francisco, CA. The opinions expressed in the current article are those of the authors. The authors received no honoraria or other form of financial support related to the development of this manuscript.
Authorship Information: Concept and design (BMD, HMH, GL); acquisition of data (BMD, HMH, GL); analysis and interpretation of data (BMD, HMH, GL); drafting of the manuscript (BMD, GL); and critical revision of the manuscript for important intellectual content (BMD, HMH, GL).
Address correspondence to: Bart M. Demaerschalk, MD, MSc, FRCP(C), Department of Neurology, Mayo Clinic Hospital, 5777 E Mayo Blvd, Phoenix, AZ 85054. E-mail: firstname.lastname@example.org.
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