Original Article Priorities for Comparative Effectiveness Reviews in Cardiovascular Disease Zubin J. Eapen, MD; Amanda J. McBroom, PhD; Rebecca Gray, DPhil; Michael D. Musty, BA; Corey Hadley, MMCI; Adrian F. Hernandez, MD, MHS; Gillian D. Sanders, PhD Background—Comparative effectiveness reviews offer a systematic method to critically appraise existing research and to identify unaddressed clinical areas in cardiovascular disease where significant morbidity, mortality, and variation in the use of resources persist. To delineate and help select areas where comparative effectiveness reviews are needed, the Effective Health Care Program of the Agency for Healthcare Research and Quality involved stakeholders in prioritization of the research agenda. Methods and Results—We involved a diverse panel of stakeholders representing a broad range of clinical, policy, and patient perspectives. To assist in prioritization of topics for evidence synthesis, we created a framework evaluating 12 cardiovascular disease subcategories that reflect American College of Cardiology/American Heart Association disease-based guidelines. We performed an environmental scan for each disease subcategory to populate this framework with existing knowledge, levels of evidence, and degrees of public interest. Through a formalized process, 4 disease subcategories were prioritized: chronic coronary artery disease, ventricular arrhythmias, heart failure, and cerebrovascular disease. Within these subcategories, 11 topics that address the comparative safety and effectiveness of existing treatments and evaluate emerging treatments were nominated by the stakeholder panel to proceed for feasibility assessment before developing comparative effectiveness reviews. Conclusions—Using a systematic process deriving consensus from multiple stakeholders across cardiovascular disease states, we generated a prioritized list of evidence synthesis topics to inform decision makers. The topics vetted through this process seek to determine the comparative safety and effectiveness of a range of treatments, both established and emerging, and are immediately relevant for prevalent disease states. (Circ Cardiovasc Qual Outcomes. 2013;6:139-147.) Key Words: cardiovascular disease ◼ comparative effectiveness ◼ research prioritization ◼ systematic review
A
merican healthcare expenditures are the highest in the world and accounted for 15% of gross domestic product in 2008.1 As the leading cause of death in the United States, cardiovascular disease is responsible for 17% of national medical expenditures.2,3 Despite declines in mortality for various conditions, such as acute myocardial infarction,4 Americans now rank 49th in the world for life expectancy, significantly worse than 5th place in 1950.5 Given the significant morbidity and mortality associated with cardiovascular disease, there is a growing imperative to identify areas of uncertainty within this domain where new syntheses of evidence may improve the quality of care by reducing morbidity, mortality, and costs. Comparative effectiveness reviews offer a systematic method to critically appraise existing research and to identify areas of remaining clinical uncertainty. To delineate these areas of need and to help select topics for systematic review, the Effective Health Care (EHC) Program of the Agency for
Healthcare Research and Quality involves stakeholders in the prioritization of its research agenda through a topic identification process. The Duke Evidence-based Practice Center (EPC) conducted such a topic identification activity within the clinical area of cardiovascular disease. This clinical area is a priority within the EHC Program; it encompasses 21 of the top 100 prioritized topics in comparative effectiveness research as ranked by the Institute of Medicine,6 and as described above, it represents the leading cause of death within the United States and imposes a substantial economic burden. To inform the research agenda of the EHC Program, we worked with a group of stakeholders to develop and prioritize a list of comparative effectiveness review topics in the area of cardiovascular disease that have the potential to improve patient-centered outcomes and are eligible for further topic development and refinement within the EHC Program. This article outlines the methods we used for topic identification and the results of this process.
Received June 30, 2012; accepted January 11, 2013. From the Duke Evidence-based Practice Center (Z.J.E., A.J.M., R.G., M.D.M., C.H., A.F.H., G.D.S.) and Department of Medicine (Z.J.E., A.F.H., G.D.S.), Duke Clinical Research Institute, Duke University, Durham, NC. This manuscript was handled independently by Alan S. Go, MD as Guest Editor. The editors had no role in the evaluation of the manuscript or the decision about its acceptance. The online-only Data Supplement is available at http://circoutcomes.ahajournals.org/lookup/suppl/doi:10.1161/CIRCOUTCOMES.111.000046/-/DC1. Correspondence to Gillian D. Sanders, PhD, Duke Clinical Research Institute, Duke Box 3485, 7020 N Pavilion Bldg, Durham, NC 27710. E-mail
[email protected] © 2013 American Heart Association, Inc. Circ Cardiovasc Qual Outcomes is available at http://circoutcomes.ahajournals.org
DOI: 10.1161/CIRCOUTCOMES.111.000046
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140 Circ Cardiovasc Qual Outcomes March 2013
WHAT IS KNOWN • Although cardiovascular disease is an area of active clinical trials and outcomes research, the current body of evidence for cardiovascular disease has not resulted in sufficient guidelines for the care of patients. • Comparative effectiveness reviews offer a systematic method to critically appraise existing research and to identify the areas of remaining clinical uncertainty.
WHAT THE STUDY ADDS • Through a systematic process deriving consensus from a diverse panel of stakeholders, the Duke Evidence-based Practice Center identified chronic coronary artery disease, ventricular arrhythmias, heart failure, and cerebrovascular disease as disease subcategories in the greatest need of comparative effectiveness reviews. • Stakeholders prioritized topics addressing the comparative safety and effectiveness of established treatments, such as clopidogrel for drug-eluting stents, and emerging treatments, such as transcatheter aortic valve replacement in high-risk subgroups. • This prioritization exercise will help identify areas in need of evidence synthesis as well as evidence gaps that warrant future clinical trials and outcomes research.
Methods Figure 1 depicts an overview of the topic identification process. To identify and prioritize topics for evidence synthesis, we (1) identified a group of stakeholders in cardiovascular disease; (2) developed and populated a framework incorporating quantitative data and stakeholder input to select subcategories within cardiovascular disease to focus on; (3) solicited candidate topics from our group of stakeholders; (4) provided additional data concerning these topics using our prioritization framework; and (5) engaged the stakeholders in a prioritization exercise to determine the top-ranked topics. These final top-ranked topics became our recommended research agenda for future systematic reviews within the cardiovascular domain.
Stakeholder Identification We recruited stakeholders from a diverse group of interested parties to ensure representation of a broad range of clinical, policy, and patient perspectives. The initial group of stakeholders approached were members of the Developing Evidence to Inform Decisions About Effectiveness Cardiovascular Consortium, representing a broad range of clinical and methodological expertise and perspectives. After reviewing the makeup of the group who expressed interest, additional individuals were approached to fill in gaps in representation of particular perspectives or potential priority areas within cardiovascular disease. These individuals were identified primarily through referrals from members of professional groups and experts in the field. The stakeholder panel included 18 individuals representing clinicians, healthcare industry professionals, US federal agencies, payers, researchers, and consumers/patients. Stakeholders represented clinical expertise in the domains of emergency medicine, internal medicine, general cardiology, cardiovascular surgery, neurology, electrophysiology, and heart failure. Although many of the stakeholders are active members of key professional organizations (American College of Emergency Physicians, American College of Physicians, American Heart Association [AHA], Society for Thoracic Surgeons,
Heart Failure Society of America, American College of Cardiology, American Society of Echocardiography, and the American Stroke Association), they represented their own personal opinions on the stakeholder panel and as such were not acting as official representatives of their respective societies or institutions. Conflict of interest disclosure forms and biosketch or curricula vitae information were collected and reviewed by the Duke EPC team and Agency for Healthcare Research and Quality to ensure both balance in representation and absence of significant conflicts of interest that, in the opinion of the EPC team and Agency for Healthcare Research and Quality, might negatively impact the process. Of the potential stakeholders recruited, none were disqualified on the basis of other interests.
Framework Development We began by developing a framework to evaluate 12 cardiovascular disease subcategories that reflect American College of Cardiology/ AHA disease-based guidelines published between 1984 and 2011 (Table 1). To assist in prioritization of candidate topics across these disease subcategories, we populated the framework with data from multiple sources, evaluating each disease subcategory according to criteria, such as burden of disease, interest from relevant parties, state of evidence, and potential impact. This framework was used first to determine which specific disease subcategories to target for further topic development and then to prioritize specific topics for systematic review within the chosen subcategories. After developing our framework, we conducted an environmental scan for each disease subcategory to evaluate the existing knowledge and level of evidence in the context of the level of public interest and the feasibility of conducting a comparative effectiveness review.
Burden of Disease We characterized the burden of disease for each of the 12 subcategories according to their incidence, prevalence, annual mortality, and annual costs using the AHA Heart Disease and Stroke Statistical Update as the primary data source.7 We supplemented this source with data from peer-reviewed literature when required. We primarily used incidence rates from the AHA Heart Disease and Stroke Statistical Update, which extrapolated rates from the epidemiological studies to the US population in 2008. We used prevalence rates reported by the National Center for Health Statistics. US mortality data are presented according to primary causes of death, rather than anymention mortality, which reports all causes of death reported on death certificates. Mortality and costs data are for 2007.
Level of Interest We assessed the level of public interest (patients and consumers) in each disease subcategory using Web-based interrogations of search engine data from Google Insights (http://www.google.com/insights/ search/#). Temporal trend data on the frequency of use of specific search terms relevant to each disease subcategory were acquired from January 1, 2004, to June 8, 2011. We used these data qualitatively to describe public interest as decreasing, stable, or increasing during this time period.
State of Evidence We evaluated both the strength of current evidence and the extent to which new evidence is being developed for each disease subcategory. The strength of current evidence was assessed by abstracting the predominant class of recommendation and level of evidence for each disease subcategory from an analysis of American College of Cardiology/AHA practice guidelines issued between 1984 and 2008 performed by Tricoci et al.8 To evaluate the extent to which new evidence is being produced for each disease subcategory, we searched ClinicalTrials.gov for ongoing interventional clinical trials. To evaluate the extent to which there is already sufficient evidence for each disease subcategory, we searched PubMed for relevant publications of randomized controlled trials from 1990 to 2011. The numbers of
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Eapen et al Comparative Effectiveness Review Priorities 141
Figure 1. Workflow schematic for topic identification within cardiovascular disease. CER indicates comparative effectiveness review.
randomized controlled trial publications from 1990 to 1994, 1995 to 1999, 2000 to 2004, and 2005 to 2010 were determined to evaluate trends within each disease subcategory. The same approach was used to assess the extent to which existing systematic reviews, meta-analyses, or guidelines were available for each disease subcategory. Details of all search strategies are provided in online-only Data Supplement Appendix A.
Potential Impact We evaluated the potential impact of future systematic reviews in each disease subcategory in terms of their ability to reduce clinical uncertainty, change clinical practice, reduce mortality, reduce morbidity, increase quality of life, or aid patient or provider decision making. We assessed the potential impact of future systematic reviews for each of these criteria through an online survey of our stakeholder group. For each criterion, stakeholders were asked to estimate the potential for positive impact (low, medium, high) of future systematic reviews in each of the subcategories of cardiovascular disease. They were also asked, for each criterion, to select the top 3 disease subcategories that, in their opinion, most urgently needed systematic reviews. We further characterized the potential impact of future systematic reviews by exploring the redundancy with the existing portfolio of research within the EHC Program (http://www.effectivehealthcare.ahrq. gov/index.cfm/search-for-guides-reviews-and-reports/), the Grants On-Line Database of the Agency for Healthcare Research and Quality (http://gold.ahrq.gov/projectsearch/), and the Duke EPC.
Subcategory Selection Our framework provided initial evidence for the disease subcategories according to the burden of disease, interest from relevant parties, state of evidence, and potential impact. Across all criteria, we then determined whether the specific criteria for a given disease subcategory indicated a need for future systematic review development, did not provide evidence for or against such a need, or demonstrated that further systematic reviews may not be needed at this time. Criteria for a given disease subcategory that indicated a need for future systematic review development were highlighted green (marked in Table 1 with a asterisk), those that did not provide evidence for or against such a need were highlighted yellow, and those that demonstrated that
such systematic reviews may not be needed at this time were highlighted red (marked in Table 1 with a dagger). When possible, these determinations were made looking across the disease subcategories and therefore represented the relative need under the specific criteria across the entire cardiovascular domain. For example, when looking at the criterion of whether there was new evidence available to review, we used data from http:/www.clinicaltrials.gov. Those subcategories that had a number of potentially relevant trials approximating the average across all 12 subcategories (186 trials) were highlighted yellow (ST-segment–elevation myocardial infarction, atrial fibrillation, peripheral artery disease), those with substantially more trials were highlighted green (chronic coronary artery disease, heart failure, cerebrovascular disease), and those with a reduced number were highlighted red (non–ST-segment–elevation myocardial infarction, valvular disease, ventricular arrhythmias, supraventricular arrhythmias, bradyarrhythmias, congenital disease). As another example, for those criteria that were estimated from our survey of stakeholders, we highlighted in green (indicating high priority) those categories that the survey responses indicated would be ranked in the top 3 subcategories. Note, however, that these top 3 rankings were not always consistent with the top ranking calculated when using the individual responder ratings. These additional categories were also highlighted in green as high priority. Those subcategories that received an average rank below 5 were considered low priority and highlighted in red.
Topic Solicitation and Prioritization Each stakeholder was asked to submit up to 5 potential comparative effectiveness review topics for each of the selected subcategories. These submitted topics were compiled into 1 list and redundancies removed. Stakeholders, who had an equal vote, were asked to prioritize the complete list of topics and then rank their top 10 topics across the selected disease subcategories. Topics that were in the top quartile of prioritization or were ranked in the top 10 by at least 2 stakeholders moved on to a final round of prioritization conducted through an online voting exercise. The top-tiered topics from this scoring process were selected as nominations for future systematic reviews.
Results Table 1 depicts the populated framework the EPC team used to determine subcategory selection. With these data, the EPC
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142 Circ Cardiovasc Qual Outcomes March 2013 Table 1. Cardiovascular Disease Subcategory Framework
Criteria
Data Source
Search Date
Chronic CAD
STEMI
NSTEMI
Burden of disease Incidence (annual)
AHA statistical update,7 unless otherwise noted
NA
Prevalence
AHA statistical update,7 unless otherwise noted
NA
Mortality (annual)
AHA statistical update,7 unless otherwise noted
NA
406 351*
132 968 (total MI)*
Cost (annual)
AHA statistical update,7 unless otherwise noted
NA
$177.5 billion*
$31 billion (total MI)
6/8/2011
Stable
Increasing*
Increasing*
NA
II/C*
I/C*
NA
935 000 (total MI)* 16 300 000*
7 900 000 (total MI)*
Interest Patient, consumers
Google Insights (2004–2011)
State of evidence Strength of evidence
Tricoci8 indicates the predominant class of recommendation and level of evidence‡
New evidence
http://www.clinicaltrials.gov
8/31/2011
721*
108
31†
Sufficient evidence
No. PubMed RCT publications during 1990–1994
9/1/2011
589*
62
117
No. PubMed RCT publications during 1995–1999
9/1/2011
917*
98
258
No. PubMed RCT publications during 2000–2004
9/1/2011
1505*
231
370
No. PubMed RCT publications during 2005–2010
9/1/2011
2218*
603
387
Total PubMed RCT publications 1990–2011
9/1/2011
5367*
1041
1158
No. PubMed SR or guideline publications, 1990–1994
9/1/2011
90†
5*
17*
No. PubMed SR or guideline publications, 1995–1999
9/1/2011
205†
9*
39*
No. PubMed SR or guideline publications, 2000–2004
9/1/2011
448†
86*
134*
No. PubMed SR or guideline publications, 2005–2010
9/1/2011
1204†
320*
240*
Total PubMed SR or guideline publications, 1990–2011
9/1/2011
2064†
446*
449*
Impact on clinical practice
Stakeholder survey: average score (SD); 1=lowest and 10=highest ability to change practice
8/31/2011
5.56 (2.35)
4.75 (1.98)†
5.38 (2.77)
Impact on mortality
Stakeholder survey: average score (SD); 1=lowest and 10=highest impact on mortality
8/31/2011
6.22 (2.44)*§
6 (1.63)
5.67 (1.41)
Impact on morbidity
Stakeholder survey: average score (SD); 1=lowest and 10=highest impact on morbidity
8/31/2011
6.22 (3.11)
5.67 (2.24)
5.56 (1.94)
Impact on quality of life
Stakeholder survey: average score (SD); 1=lowest and 10= highest impact on quality of life
8/31/2011
6.5 (1.96)
4.86 (2.27)†
5 (2.08)
Impact on patient decision making
Stakeholder survey: average score (SD); 1=lowest and 10=highest impact on patient decision making
8/31/2011
7.2 (1.55)*
4.25 (2.76)†
4.75 (1.91)†
Impact on provider decision making
Stakeholder survey: average score (SD); 1=lowest 8/31/2011 and 10=highest impact on provider decision making
6.7 (2.36)*
5.29 (1.8)
5.5 (1.41)
Impact on uncertainty in clinical practice, diagnosis, or treatment
Stakeholder survey: average score (SD); 1=lowest and 10=highest impact on clinical uncertainty
6.33 (1.94)
4.11 (1.76)†
5.67 (2.29)
5 final/11 in progress†
0 final/7 in progress†
0 final/4 in progress
Noninvasive imaging technologies for the diagnosis of CAD in women; treatments for women with CAD
None*
Treatments for patients with unstable angina/ non–ST-segment– elevation myocardial infarction†
Existing guidance
Potential impact of future systematic reviews
AHRQ portfolio (combined) Ongoing EPC systematic reviews
Duke EPC Cardiovascular Portfolio
8/31/2011
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Eapen et al Comparative Effectiveness Review Priorities 143 Table 1. (Continued) Cardiovascular Disease Subcategory
Valvular
Ventricular Arrhythmias (Including SCA)
Supraventricular Arrhythmias Bradyarrhythmias
NA 180 000–450 000 18 7 035 500* (SCA; from Kong) * 23 313†
AF
Congenital
HF
PAD
CVD
NA
NA
75 000
36 000
670 000*
NA
795 000*
NA
NA
2 200 000
650 000– 1 300 000†
5 700 000*
85 000 000 (from Allison)19*
7 000 000*
140†
NA
14 490†
3547†
56 565
30 172
135 952*
NA
$2.2 billion†
NA
NA
$6.0–26.0 billion (from Kim)20
$1.4 billion†
$37.2 billion
$4.37 billion (from Hirsch)21†
$25.2 billion
Stable
Decreasing†
Stable
Stable
Stable
Stable
Decreasing†
Decreasing†
Stable
I/C†
I/C†
II/C*
NA
II/C*
NA
I/C†
I/B†
NA
96†
56†
8†
5†
143
86†
387*
195
405*
77†
106†
199
121†
128*
76†
647*
399*
376*
100†
158†
352
183†
287*
119†
885*
444*
634*
149†
177†
588
182†
498*
222†
1311*
375*
1100*
242†
247†
845
248†
755*
313†
2318*
535*
2037*
587†
700†
2032
739†
1711*
752†
5309*
1792*
4268*
25*
28*
38
10*
26
21
68†
73†
121†
39*
55*
92
9*
78
59
209†
111†
330†
83*
107*
213
59*
188
126
501†
231†
906†
242*
259*
492
83*
464
329
1394†
532†
1962†
404*
470*
921
166*
837
564
2329†
986†
3459†
5 (2.12)
6.8 (1.99)*
6.6 (2.5)*§
4.89 (2.52)†
7 (2.12)*§
5.9 (2.56)*§
6.4 (1.84)†
5.57 (2.51)
7.44 (2.19)*§
4.5 (2.07)†
5.11 (2.42)
6.33 (2.24)*§
4 (2.14)†
5.4 (1.9)
5.75 (2.49)
6.25 (2.96)
6.8 (2.62)*§
5.5 (2.93)
6.9 (1.85)*§
6.44 (1.88)*§
6.6 (1.9)*
6.13 (2.17)
5.5 (2.45)
6.9 (2.73)*§
5.86 (2.04)
7.5 (1.58)*§
6.89 (1.54)*§
6.9 (1.91)*§
6.3 (1.57)*
6 (2.96)*§
8 (1.05)*§
5.56 (0.88)
7.3 (1.64)*§
6.44 (1.13)*
5.9 (1.79)
6 (1.94)
6.88 (1.89)*§
7.3 (2.11)*§
5.14 (1.46)
7.11 (1.36)*§
6.2 (2.35)*§
6.38 (1.77)*
6 (1.76)
6.89 (1.36)*§
7.89 (1.05)*§
6 (2.29)
7.11 (1.27)*
6.63 (2.45)*§
7.29 (1.50)*
1 final/2 in progress
2 final/1 in progress
3 final/1 in 0 final/4 in progress progress None*
None*
0 final/0 in progress*
0 final/0 in progress*
1 final/2 in progress
1 final/0 in progress*
4 final/11 in progress†
None*
None*
Stroke prevention in patients with atrial fibrillation; treatment of atrial fibrillation†
None*
None*
Treatment of Stroke prevention in patients with patients with atrial peripheral artery fibrillation disease† (Continued )
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144 Circ Cardiovasc Qual Outcomes March 2013 Table 1. (Continued) AF indicates atrial fibrillation; AHA, American Heart Association; AHRQ, Agency for Healthcare Research and Quality; CAD, coronary artery disease; CVD, cerebrovascular disease; EPC, Evidence-based Practice Center; HF, heart failure; MI, myocardial infarction; NA, not applicable; NSTEMI, non–ST-segment–elevation myocardial infarction; PAD, peripheral artery disease; RCT, randomized controlled trial; SCA, sudden cardiac arrest; SR, systematic review; and STEMI, ST-segment– elevation myocardial infarction. Class of recommendations and levels of evidence were defined as follows: Class of recommendations: • Class I: conditions for which there is evidence or general agreement that a given procedure or treatment is useful and effective • Class II: conditions for which there is conflicting evidence or a divergence of opinion about the usefulness/efficacy of a procedure or treatment • Class IIa: weight of evidence/opinion is in favor of usefulness/efficacy • Class IIb: usefulness/efficacy is less well established by evidence/opinion • Class III: conditions for which there is evidence or general agreement that the procedure/treatment is not useful/effective and in some cases may be harmful. Levels of evidence: • Level of evidence A: recommendation based on evidence from multiple randomized trials or meta-analyses • Level of evidence B: recommendation based on evidence from a single randomized trial or nonrandomized studies • Level of evidence C: recommendation based on expert opinion, case studies, or standards of care. Criteria for a given disease subcategory that indicated a need for future systematic review development are indicated with an asterisk (*); those criteria that demonstrated that such systematic reviews may not be needed at this time are indicated with a dagger (†). Other cells not marked with either of these symbols represent those criteria that did not provide evidence for or against such a need. Within each row, the § indicates the disease categories most frequently selected by stakeholders as among the top 3 that, in their opinion, most needed systematic reviews to have an impact on the specified criterion (clinical uncertainty, clinical practice, mortality, and so on).
team determined that 4 subcategories—chronic coronary artery disease, ventricular arrhythmias (including sudden cardiac arrest), heart failure, and cerebrovascular disease—were identified as having a strong need for future systematic reviews. Nomination of 5 topics by each stakeholder in each of these 4 subcategories resulted in 112 topics for potential systematic review (online-only Data Supplement Appendix II). Those that were in the top quartile of prioritization or were ranked in top 10 by at least 2 stakeholders moved on in our process; these included 31 topics. Stakeholders were provided with data to
help with a final round of selection, including the number of trials completed or ongoing in each topic (Figure 2) and the number of guidelines and systematic reviews for each topic (Figure 3). Stakeholders were also provided the opportunity to generate feedback on the wording of these topics to make improvements and enhance clarity. After a restructuring of the topics in response to this feedback, which included combining 2 topics, 30 topics remained for the final prioritization (online-only Data Supplement Appendix III). From these, stakeholders finalized a list of 11 topics (Table 2) to proceed to
Figure 2. Sufficient evidence: ongoing or completed randomized controlled trials (RCTs) relating to topics nominated for systematic review by stakeholders. CABG indicates coronary artery bypass grafting; CEA, carotid endarterectomy; CRT, cardiac resynchronization therapy; HF, heart failure; ICD, implantable cardioverter-defibrillator; IHD, ischemic heart disease; LDL, low-density lipoprotein; LVAD, left ventricular assist device; MI, myocardial infarction; PCI, percutaneous coronary intervention; PEF, preserved ejection fraction; PFO, patent foramen ovale; and SCA, sudden cardiac arrest.
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Eapen et al Comparative Effectiveness Review Priorities 145
Figure 3. Existing guidance: systematic reviews and guidelines relating to topics nominated for systematic review by stakeholders. CABG indicates coronary artery bypass grafting; CEA, carotid endarterectomy; CRT, cardiac resynchronization therapy; HF, heart failure; ICD, implantable cardioverter-defibrillator; IHD, ischemic heart disease; LDL, low-density lipoprotein; LVAD, left ventricular assist device; MI, myocardial infarction; PCI, percutaneous coronary intervention; PEF, preserved ejection fraction; PFO, patent foramen ovale; and SCA, sudden cardiac arrest.
systematic reviews. Among the various disease subcategories, the final list of 11 topics includes 4 from chronic coronary artery disease, 1 from ventricular arrhythmias, 4 from heart failure, and 2 from cerebrovascular disease. Within these 4 disease subcategories, topics address the comparative safety and effectiveness of existing treatments, such as clopidogrel for drug-eluting stents and implantable cardioverter-defibrillators
for sudden cardiac arrest. Other topics seek to evaluate emerging treatments, such as transcatheter aortic valve replacement and the polypill.
Discussion Unlike investigator-initiated research, comparative effectiveness reviews start from questions that are generated by
Table 2. Final 11 Topics Recommended for Systematic Review by Stakeholders Disease Subcategory Chronic CAD
Topics Recommended for Systematic Review 1. What are the comparative diagnostic accuracy, diagnostic thinking, therapeutic, and patient outcome efficacy of noninvasive tests for the risk stratification of patients with chronic CAD? 2. Should clopidogrel be prescribed indefinitely in patients who have received drug-eluting stents for the treatment of chronic CAD? 3. Does the polypill improve adherence and the treatment of risk factors for chronic CAD? 4. What are the comparative safety and effectiveness of noninvasive and invasive strategies in the management of patients with chronic stable angina?
Ventricular arrhythmias (including SCA)
5. Are there safe and effective methods of identifying patients in need of implantable cardioverter-defibrillators for the primary prevention of SCA?
Heart failure
6. What are predictors of therapeutic benefit with cardiac resynchronization therapy? 7. Which interventions are effective in decreasing heart failure readmissions? 8. What are the comparative safety and effectiveness of left ventricular assist devices for patients with heart failure? 9. How do we determine the comparative safety and effectiveness of transcatheter aortic valve replacement in patients with heart failure and within specific high-risk subgroups of interest?
CVD
10. What is the role of patent foramen ovale identification and closure in the setting of stroke? 11. Are there data supporting the discontinuance of warfarin after catheter ablation for atrial fibrillation? What is the prevalence of symptomatic and asymptomatic atrial fibrillation after catheter ablation?
CAD indicates coronary artery disease; CVD, cerebrovascular disease; and SCA, sudden cardiac arrest.
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146 Circ Cardiovasc Qual Outcomes March 2013 decision makers. Because comparative effectiveness reviews are intended to synthesize evidence for decision makers, identification and prioritization of topics must take into account the end users’ needs, the timing of the reviews in relation to guideline development initiatives, and the feasibility and value of the review to help inform healthcare decisions. Through a systematic process deriving consensus from multiple stakeholders across disease states within cardiovascular disease, we generated a list of topics prioritized for evidence synthesis to inform decision makers. The topics vetted through this process seek to determine the comparative safety and effectiveness of a range of treatments, both established and emerging, and are immediately relevant for prevalent disease states. To ensure that these topics meet the needs of users in both clinical practice and clinical research, these topics proceed to the EHC Program for Topic Triage, a process whereby the nominated topics are assessed for feasibility. Approved topics are vetted with stakeholders again before proceeding to the comparative effectiveness review stage to ensure that these reviews are useful to as many potential stakeholders as possible. These comparative effectiveness reviews can help stakeholders and decision makers better match funding and resources to remaining areas of clinical uncertainty. Although cardiovascular disease is an area of active clinical trials and outcomes research, the current body of evidence for cardiovascular disease has not resulted in sufficient guidelines for the care of patients. In 2009, only 11% of recommendations made in the joint cardiovascular practice guidelines of the American College of Cardiology and the AHA were classified as Level of Evidence A.8 Instead of a solid evidentiary base of randomized controlled trials, most recommendations are based on expert opinion or case studies. With a proliferation of treatments and little evidence to determine the standard of care, the management of patients with cardiovascular diseases has been characterized by considerable variation and disparities in care.9–14 Identifying appropriate, high-impact questions that are relevant to decision makers is a challenging task. Topics or questions submitted by patients or clinicians may be in areas where reviews have already been done but without adequate dissemination to the public or where the available evidence is sparse. In some cases, conversion of clinical questions to researchable questions results in changes to the focus of a systematic review. The goal of providing timely information to decision makers and the length of time for conducting a review once identified require that areas in need of evidence synthesis are identified well before they are a clinical or policy issue for healthcare decision makers. To help overcome some of these challenges, the Duke EPC considered other sources of information in addition to directly asking decision makers to identify topics that maintain an end user focus. Data sources that provide insight into patients’ concerns, information sought by patients, unmet information needs, topics that attract readers’ interest, burden of disease, and what experts believe patients need or want to know were used to inform decisions in this process. Additionally, engaging a diverse set of stakeholders was integral to enabling this topic identification process to identify those topics that are most relevant to end user needs and capable of improving the usefulness, impact, and dissemination of the resulting research products.15
Although we did not use value-of-information analyses in this process, recent work by our group16,17 has emphasized the benefits (and limitations) of such value-of-information analyses in research prioritization, and future work in how to best integrate these analyses into a prioritization process with stakeholders is both timely and needed. To create a robust comparative effectiveness research enterprise, as recommended by the Institute of Medicine, research priorities must be appraised in a continuous and dynamic manner. As new diseases and treatments emerge, comparative effectiveness reviews must adapt to the evolving landscape of each disease state. This requires the development of “robust, consistent topic briefs providing background information, current practice, and research status of the condition and its interventions.”6 The topics for comparative effectiveness reviews generated through this exercise will help identify areas in need of evidence synthesis by subsequent reviews as well as future areas in need of evidence generation. Using this systematic approach to identifying future priorities of the comparative effectiveness research enterprise in cardiovascular disease can ultimately reduce morbidity, mortality, and costs and improve quality of care.
Acknowledgments The authors thank Megan von Isenburg, MLS, for help with literature search and retrieval and gratefully acknowledge the contributions of members of the stakeholder panel, which included Larry Allen, MD, MHS; Javed Butler, MD, MPH; Daniel Caños; Larry Clark, MD; Lesley Curtis, PhD; Hesha Duggirala, PhD; Fred Edwards, MD; Peter Groeneveld, MD; Neil Jensen, MHA, MBA; Tom Maddox, MD, MSc; Dan Mark, MD, MPH; Alice Mascette, MD; Pam Peterson, MD, MSPH; Veronica Sansing, PhD; Lawrence Sadwin; Lee Schwamm, MD; Jeff Tabas, MD; and Paul Varosy, MD.
Sources of Funding This project was funded under contract No. 290-2007-10066-I from the Agency for Healthcare Research and Quality, US Department of Health and Human Services. The authors of this report are responsible for its contents. Statements in the report should not be construed as endorsements by the Agency for Healthcare Research and Quality or the US Department of Health and Human Services.
Disclosures Dr Hernandez reports receiving research funding from Amylin and Johnson & Johnson, and honoraria from Corthera and Daiichi Sankyo. The other authors report no conflicts.
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