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1.  Applying Process Improvement Methods to Clinical and Translational Research: Conceptual Framework and Case Examples 
There is growing appreciation that process improvement holds promise for improving the quality and efficiency across the translational research continuum but frameworks for such programs are not often described. The purpose of this paper is to present a framework and case examples of a Research Process Improvement Program implemented at Tufts CTSI. To promote research process improvement, we developed online training seminars, workshops, and in-person consultation models to describe core process improvement principles and methods, demonstrate the use of improvement tools, and illustrate the application of these methods in case examples. We implemented these methods, as well as relational coordination theory, with junior researchers, pilot funding awardees, our CTRC, and CTSI resource and service providers. The program focuses on capacity building to address common process problems and quality gaps that threaten the efficient, timely and successful completion of clinical and translational studies.
PMCID: PMC4703431  PMID: 26332869
3.  CTSA Consortium Consensus Scientific Review Committee (SRC) Working Group Report on the SRC Processes 
Human research projects must have a scientifically valid study design, analytic plan, and be operationally feasible in order to be successfully completed and thus to have translational impact. To ensure this, institutions that conduct clinical research should have a scientific review process prior to submission to the Institutional Review Committee (IRB). This paper reports the Clinical and Translational Science Award (CTSA) Consortium Scientific Review Committee (SRC) Consensus Working Group's proposed framework for a SRC process. Recommendations are provided for institutional support and roles of CTSAs, multisite research, criteria for selection of protocols that should be reviewed, roles of committee members, application process, and committee process. Additionally, to support the SCR process effectively, and to ensure efficiency, the Working Group recommends information technology infrastructures and evaluation metrics to determine outcomes are provided.
PMCID: PMC4703465  PMID: 26184433
translational research; clinical trials; outcomes research
4.  In-hospital measurement of left ventricular ejection fraction and one-year outcomes in acute coronary syndromes: results from the IMMEDIATE Trial 
In patients with acute coronary syndrome (ACS), reduced left ventricular ejection fraction (LVEF) is a known marker for increased mortality. However, the relationship between LVEF measured during index ACS hospitalization and mortality and heart failure (HF) within 1 year are less well-defined.
We performed a retrospective analysis of 445 participants in the IMMEDIATE Trial who had LVEF measured by left ventriculography or echocardiogram during hospitalization.
Adjusting for age and coronary artery disease (CAD) history, lower LVEF was significantly associated with 1-year mortality or hospitalization for HF. For every 5 % LVEF reduction, the hazard ratio [HR] was 1.26 (95 % CI 1.15, 1.38, P < 0.001). Participants with LVEF < 40 % had higher hazard of 1-year mortality or HF hospitalization than those with LVEF > 40 (HR 3.59; 95 % CI 2.05, 6.27, P < 0.001). The HRs for the association of LVEF with the study outcomes were similar whether measured by left ventriculography or by echocardiography, (respectively, HR 1.32; 95 % CI 1.15, 1.51 and 1.21; 95 % CI 1.106, 1.35, interaction P = 0.32) and whether done within 24 h or not within 24 h (respectively, HR 1.28; 95 % CI 1.10, 1.50 and 1.23; 95 % CI 1.10, 1.38, interaction P = 0.67).
Among patients with ACS, lower in-hospital LVEF is associated with increased 1-year mortality or hospitalization for HF, regardless of the method or timing of the LVEF assessment. This has prognostic implications for clinical practice and suggests the possibility of using various methods of LVEF determination in clinical research.
PMCID: PMC4973066  PMID: 27488569
Acute coronary syndromes; Glucose-insulin-potassium; Left ventricular ejection fraction; Death; Hospitalization from heart failure
5.  A predictive model to identify patients with suspected acute coronary syndromes at high risk of cardiac arrest or in-hospital mortality: An IMMEDIATE Trial sub-study☆,☆☆,☆☆☆,☆☆☆☆ 
The IMMEDIATE Trial of emergency medical service use of intravenous glucose–insulin–potassium (GIK) very early in acute coronary syndromes (ACS) showed benefit for the composite outcome of cardiac arrest or in-hospital mortality.
This analysis of IMMEDIATE Trial data sought to develop a predictive model to help clinicians identify patients at highest risk for this outcome and most likely to benefit from GIK.
Multivariable logistic regression was used to develop a predictive model for the composite endpoint cardiac arrest or in-hospital mortality using the 460 participants in the placebo arm of the IMMEDIATE Trial.
The final model had four variables: advanced age, low systolic blood pressure, ST elevation in the presenting electrocardiogram, and duration of time since ischemic symptom onset. Predictive performance was good, with a C statistic of 0.75, as was its calibration. Stratifying patients into three risk categories based on the model's predictions, there was an absolute risk reduction of 8.6% with GIK in the high-risk tertile, corresponding to 12 patients needed to treat to prevent one bad outcome. The corresponding values for the low-risk tertile were 0.8% and 125, respectively.
The multivariable predictive model developed identified patients with very early ACS at high risk of cardiac arrest or death. Using this model could assist treating those with greatest potential benefit from GIK.
PMCID: PMC4762054  PMID: 26913292
Acute coronary syndrome; Glucose–insulin–potassium (GIK); Predictive model; Cardiac arrest; Mortality; Emergency medical service
6.  C-Reactive protein reactions to glucose-insulin-potassium infusion and relations to infarct size in patients with acute coronary syndromes 
Some benefits of glucose-insulin-potassium (GIK) in patients with acute coronary syndromes (ACS) may be from an anti-inflammatory effect. The primary aim of this study was to assess the impact of GIK administration early in the course of ACS on inflammatory marker C-reactive protein (CRP) levels. A secondary aim was to investigate the association between CRP and 30-day infarct size.
Methods and Results
Retrospective analysis of participants with ACS randomly assigned to GIK or placebo for at least 8 h in the IMMEDIATE Trial biological mechanism cohort (n = 143). High sensitivity CRP (hs-CRP) was measured at emergency department presentation, and 6 and 12 h into infusion. Logarithmically transformed hs-CRP values at 12-hours were lower with GIK vs. placebo (mean =0.65 mg/L in GIK, 0.84 mg/L in placebo), with a marginal trend toward significance (P = 0.053). Furthermore, using mixed models of hs-CRP, time, and study group, there was a significant increase in hs-CRP levels over time, but the rate of change did not differ between treatment arms (P = 0.3). Multivariable analysis showed that an elevation in hs-CRP, measured at 12 h, was an independent predictor of 30-day infarct size (β coefficient, 6.80; P = 0.04) using sestamibi SPECT imaging.
The results of this study show no significant effect of GIK on hs-CRP. In addition our results show that in patients with ACS, hs-CRP measured as early as 12 h can predict 30-day infarct size.
Electronic supplementary material
The online version of this article (doi:10.1186/s12872-015-0153-7) contains supplementary material, which is available to authorized users.
PMCID: PMC4668670  PMID: 26631004
Acute coronary syndromes; Glucose-insulin-potassium (GIK); Inflammation; C-reactive protein; Metabolic therapy
7.  One-Year Outcomes of Out-of-Hospital Administration of Intravenous Glucose, Insulin, and Potassium (GIK) in Patients with Suspected Acute Coronary Syndromes (from the IMMEDIATE [Immediate Myocardial Metabolic Enhancement During Initial Assessment and Treatment in Emergency care] Trial) 
The American journal of cardiology  2014;113(10):1599-1605.
The IMMEDIATE Trial of very early intravenous glucose-insulin-potassium (GIK) for acute coronary syndromes (ACS) in out-of-hospital emergency medical service (EMS) settings showed 80% reduction in infarct size at 30 days, suggesting potential longer-term benefit. Here we report 1-year outcomes. Pre-specified 1-year endpoints of this randomized, placebo-controlled, double-blind, effectiveness trial included all-cause mortality, and composites including cardiac arrest, mortality, or hospitalization for heart failure (HF). Among 871 participants randomized to GIK vs. placebo, respectively, death occurred within 1 year in 11.6% vs. 13.5% (unadjusted hazard ratio [HR] 0.83; 95% CI 0.57, 1.23, P=0.36). The composite of cardiac arrest or 1-year mortality was 12.8% vs. 17.0% (HR 0.71; 95% CI 0.50, 1.02, P=0.06). The composite of hospitalization for HF or mortality within 1 year was 17.2% vs. 17.2% (HR 0.98; 95% CI 0.70, 1.37, P=0.92). The composite of mortality, cardiac arrest, or HF hospitalization within 1 year was 18.1% vs. 20.4% (HR 0.85; 95% CI 0.62, 1.16, P=0.30). Among patients presenting with suspected ST elevation myocardial infarction (STEMI), hazard ratios for 1-year mortality and the 3 composites were, respectively, 0.65 (95% CI 0.33, 1.27, P=0.21); 0.52 (95% CI 0.30, 0.92, P=0.03); 0.63 (95% CI 0.35, 1.16, P=0.14); and 0.51 (95% CI 0.30, 0.87, P=0.01). Among patients with suspected ACS, serious endpoints generally were lower with GIK than placebo, but the differences were not statistically significant. However, among those with STEMI, the composites of cardiac arrest or 1-year mortality, and of cardiac arrest, mortality, or HF hospitalization within 1 year, were significantly reduced.
PMCID: PMC4043184  PMID: 24792735
acute myocardial infarction; acute coronary syndromes; emergency medical services; glucose-insulin-potassium; ACS; GIK
9.  A Community Consultation Survey to Evaluate Support for and Success of the IMMEDIATE Trial 
Clinical trials (London, England)  2014;11(2):178-186.
The IMMEDIATE (Immediate Myocardial Metabolic Enhancement During Initial Assessment and Treatment in Emergency care) Trial, a randomized controlled double-blind clinical effectiveness trial of glucose-insulin-potassium (GIK) administered in ambulances in the out-of-hospital setting, used the Exception from Informed Consent Requirements (EFIC) for Emergency Research under Title 21 of the Code of Federal Regulations. EFIC requirements include community consultation that typically involves using a variety of communication methods and venues to inform the public of the research and to receive their feedback. Although not the primary purpose of the community consultation process, a common concern to research sponsors, staff, and institutional review boards (IRBs) is whether there will be a sufficient number of participants to justify mounting a study in their community. Information from community consultation regarding the community acceptance might inform this question. .
We evaluated the utility of telephone survey data done as part of the EFIC process as a way to project the ultimate rate of trial participant enrollment.
A telephone survey community consultation process was undertaken in nine communities planning to be IMMEDIATE Trial sites using a representative sampling of the target population in the areas covered by participating emergency medical service (EMS) agencies. Survey respondents were read a description of the planned study and its informed consent approach that included the option for patients to decline participation in the trial while being transported for acute care in an ambulance. Survey respondents were then asked whether they would object to participating in the study. At the conclusion of actual trial enrollment, the Coordinating Center compared the survey results with the actual rates of enrollment at each site.
Approximately 200 (range 200 - 271) respondents completed the survey in each of the study communities. Of 2,079 survey respondents, 68% (range 61% - 75%) said that they would not object to participating in the trial if experiencing a heart attack, and 85% (range 79% - 89%) that they would allow the study to be done in their community. During actual trial enrollment in the communities, 79% (range 63% - 91%) of the 828 potential participants agreed in the ambulance to have the study drug started and provided informed consent at the hospital, an average of 13 percentage-points higher than projected by the survey (95% confidence interval [CI] 9%, 17%), 19% higher on a relative scale (CI 14%, 25%).
The survey-based approach to community consultation proved to be an efficient way to obtain representative input from potential clinical trial participants. The survey data generated a relatively good and conservative estimate of the ultimate rate of trial enrollment. This information could be useful to investigators and IRBs in projecting enrollment for clinical trials using EFIC.
PMCID: PMC4025913  PMID: 24686107
IMMEDIATE Trial; Exception from Informed Consent (EFIC); 50.24; Emergency Research; Acute Coronary Syndromes (ACS); Emergency Medical Service (EMS)
10.  Quantity Over Quality: How the Rise in Quality Measures is Not Producing Quality Results 
Journal of General Internal Medicine  2015;30(8):1204-1207.
Over the past decade, quality measures (QMs) have been implemented nationally in order to establish standards aimed at improving the quality of care. With the expansion of their role in the Affordable Care Act and pay-for-performance, QMs have had an increasingly significant impact on clinical practice. However, adverse patient outcomes have resulted from adherence to some previously promulgated performance measures. Several of these QMs with unintended consequences, including the initiation of perioperative beta-blockers in noncardiac surgery and intensive insulin therapy for critically ill patients, were instituted as QMs years before large randomized trials ultimately refuted their use. The future of quality care should emphasize the importance of evidence-based, peer-reviewed measures.
PMCID: PMC4510222  PMID: 25801695
quality improvement; performance measurement; medical errors; patient safety; Medicaid
11.  Factors associated with longer time to treatment for patients with suspected acute coronary syndromes: a cohort study 
Rapid treatment of acute coronary syndromes (ACS) is important; causes of delay in emergency medical services (EMS) care of ACS are poorly understood.
Methods and results
Analysis of data from the IMMEDIATE randomized controlled trial of EMS treatment of people with symptoms suggesting ACS, using hierarchical multiple regression of elapsed time. Out-of-hospital electrocardiograms were performed on 54,230 adults calling 9-1-1; 871 had presumed ACS, 303 of whom had ST-segment elevation myocardial infarction and underwent percutaneous coronary intervention. Compared to their counterparts, women, participants with diabetes, and participants without prior cardiovascular disease waited longer to call 9-1-1(by 28, p <0.01; 10, p 0.03; and 6 minutes, p 0.02, respectively). EMS arrival to electrocardiogram was longer for women (1.5 minutes, p <0.01), older individuals (1.3 minutes, p <0.01), and those without a primary complaint of chest pain (3.5 minutes, p <0.01). On-scene times were longer for women (2 minutes, p < 0.01) and older individuals (2 minutes, p <0.01). Older individuals and participants presenting on weekends and nights had longer door-to-balloon times (by 10, 14 and 11 minutes respectively, p < 0.01). Women and older individuals had longer total times (medical contact to balloon inflation 16, p 0.01, and 9 minutes, p <0.01, respectively; symptom onset to balloon inflation 31.5 minutes for women, p 0.02).
We found delays throughout ACS care, resulting in substantial differences in total times for women and older individuals. These delays may impact outcomes; a comprehensive approach to reduce delay is needed.
PMCID: PMC3985420  PMID: 24425697
acute coronary syndrome; emergency medical services; women
12.  Out-of-Hospital Administration of Intravenous Glucose-Insulin-Potassium in Patients With Suspected Acute Coronary Syndromes 
JAMA  2012;307(18):1925-1933.
Laboratory studies suggest that in the setting of cardiac ischemia, immediate intravenous glucose-insulin-potassium (GIK) reduces ischemia-related arrhythmias and myocardial injury. Clinical trials have not consistently shown these benefits, possibly due to delayed administration.
To test out-of hospital emergency medical service (EMS) administration of GIK in the first hours of suspected acute coronary syndromes (ACS).
Design, Setting, and Participants
Randomized, placebo-controlled, double-blind effectiveness trial in 13 US cities (36 EMS agencies), from December 2006 through July 31, 2011, in which paramedics, aided by electrocardiograph (ECG)-based decision support, randomized 911 (871 enrolled) patients (mean age, 63.6 years; 71.0% men) with high probability of ACS.
Intravenous GIK solution (n=411) or identical-appearing 5% glucose placebo (n=460) administered by paramedics in the out-of-hospital setting and continued for 12 hours.
Main Outcome Measures
The prespecified primary end point was progression of ACS to myocardial infarction (MI) within 24 hours, as assessed by biomarkers and ECG evidence. Prespecified secondary end points included survival at 30 days and a composite of prehospital or in-hospital cardiac arrest or in-hospital mortality, analyzed by intent-to-treat and by presentation with ST-segment elevation.
There was no significant difference in the rate of progression to MI among patients who received GIK (n=200; 48.7%) vs those who received placebo (n=242; 52.6%) (odds ratio [OR], 0.88; 95% CI, 0.66–1.13; P=.28). Thirty-day mortality was 4.4% with GIK vs 6.1% with placebo (hazard ratio [HR], 0.72; 95% CI, 0.40–1.29; P=.27). The composite of cardiac arrest or in-hospital mortality occurred in 4.4% with GIK vs 8.7% with placebo (OR, 0.48; 95% CI, 0.27–0.85; P=.01). Among patients with ST-segment elevation (163 with GIK and 194 with placebo), progression to MI was 85.3% with GIK vs 88.7% with placebo (OR, 0.74; 95% CI, 0.40–1.38; P=.34); 30-day mortality was 4.9% with GIK vs 7.7% with placebo (HR, 0.63; 95% CI, 0.27–1.49; P=.29). The composite outcome of cardiac arrest or in-hospital mortality was 6.1% with GIK vs 14.4% with placebo (OR, 0.39; 95% CI, 0.18–0.82; P=.01). Serious adverse events occurred in 6.8% (n=28) with GIK vs 8.9% (n=41) with placebo (P=.26).
Among patients with suspected ACS, out-of-hospital administration of intravenous GIK, compared with glucose placebo, did not reduce progression to MI. Compared with placebo, GIK administration was not associated with improvement in 30-day survival but was associated with lower rates of the composite outcome of cardiac arrest or in-hospital mortality.
Trial Registration Identifier: NCT00091507
PMCID: PMC4167391  PMID: 22452807
13.  White Paper on CTSA Consortium Role in Facilitating Comparative Effectiveness Research 
PMCID: PMC4130456  PMID: 20443951
research infrastructure; clinical research; health policy; comparative effectiveness research; clinical and translational science
14.  Emergency Medical Service Predictive Instrument Aided Diagnosis and Treatment of Acute Coronary Syndromes and ST Elevation Myocardial Infarction in the IMMEDIATE Trial 
Achallenge for emergency medical service (EMS) is accurate identification of acute coronary syndromes (ACS) and ST elevation myocardial infarction (STEMI) for immediate treatment and transport. The electrocardiograph-based acute cardiac ischemia time-insensitive predictive instrument (ACI-TIPI) and the thrombolytic predictive instrument (TPI) have been shown to improve diagnosis and treatment in emergency departments (EDs), but their use by paramedics in the community has been less studied.
Ambulances in study municipalities were outfitted with electrocardiographs with ACI-TIPI and TPI software. Using a before-after quasi-experimental design, in Phase 1, for seven months, paramedics were provided with the ACI-TIPI/TPI continuous 0–100% predictions automatically printed on electrocardiogram (ECG) text headers to supplement their identification of ACS; in Phase 2, for 11 months, paramedics were told to identify ACS based on an ACI-TIPI cutoff probability of ACS ≥ 75% and/or TPI detection of STEMI. In Phase 3, this cutoff approach was used in seven additional municipalities. Confirmed diagnoses of ACS, acute myocardial infarction (AMI), and STEMI were made by blinded physician review for 100% of patients.
In Phase 1, paramedics identified 107 patients as having ACS; in Phase 2, 104. In Phase 1, 45.8% (49) of patients so-identified had ACS confirmed, which increased to 76.0% (79) in Phase 2 (p < 0.001). Of those with ACS, in Phase 1 59.2% (29) had AMI versus 84.8% (67) with AMI in Phase 2 (p <0.01), and, STEMI was confirmed, respectively, in 40.8% (20), versus 68.4% (54) (p <0.01). In Phase 3, of 226 patients identified by paramedics as having ACS, 74.3% (168) had ACS confirmed, of whom 81.0% (136) had AMI and 65.5% (110) had STEMI.
In a wide range of EMS systems, use of electrocardiographs with ACI-TIPI and TPI decision support using a 75% ACI-TIPI cutoff improves paramedic diagnostic performance for ACS, AMI, and STEMI.
PMCID: PMC4104416  PMID: 21366431
acute coronary syndromes; acute myocardial infarction; electrocardiology; emergency medical service; clinical decision support
15.  Academic General Internal Medicine: A Mission for the Future 
After five decades of growth that has included advances in medical education and health care delivery, value cohesion, and integration of diversity, we propose an overarching mission for academic general internal medicine to lead excellence, change, and innovation in clinical care, education, and research. General internal medicine aims to achieve health care delivery that is comprehensive, technologically advanced and individualized; instills trust within a culture of respect; is efficient in the use of time, people, and resources; is organized and financed to achieve optimal health outcomes; maximizes equity; and continually learns and adapts. This mission of health care transformation has implications for the clinical, educational, and research activities of divisions of general internal medicine over the next several decades.
PMCID: PMC3663942  PMID: 23321931
16.  Study Design for the IMMEDIATE (Immediate Myocardial Metabolic Enhancement During Initial Assessment and Treatment in Emergency Care) Trial: A Double-blind Randomized Controlled Trial of Intravenous Glucose, Insulin, and Potassium (GIK) for Acute Coronary Syndromes in Emergency Medical Services 
American heart journal  2012;163(3):315-322.
Experimental studies suggest that metabolic myocardial support by intravenous (IV) glucose, insulin, and potassium (GIK) reduces ischemia-induced arrhythmias, cardiac arrest, mortality, progression from unstable angina pectoris (UAP) to acute myocardial infarction (AMI), and MI size. However, trials of hospital administration of IV GIK to patients with ST elevation MI (STEMI) have generally not shown favorable effects, possibly due to the GIK intervention taking place many hours after ischemic symptom onset. A trial of GIK used in the very first hours of ischemia has been needed, consistent with the timing of benefit seen in experimental studies.
The Immediate Myocardial Metabolic Enhancement During Initial Assessment and Treatment in Emergency care (IMMEDIATE) Trial tested whether, if given very early, GIK could have the impact seen in experimental studies. Accordingly, distinct from prior trials, IMMEDIATE tested the impact of GIK 1) in patients with acute coronary syndromes (ACS), rather than only AMI or STEMI, and 2) administered in prehospital emergency medical service (EMS) settings, rather than later, in hospitals, following emergency department evaluation.
IMMEDIATE was an EMS-based randomized placebo-controlled clinical effectiveness trial conducted in 13 cities across the US which enrolled 911 participants. Eligible were patients age 30 or older for whom a paramedic performed a 12-lead electrocardiogram (ECG)to evaluate chest pain or other symptoms suggestive of ACS for whom electrocardiograph-based ACI-TIPI (acute cardiac ischemia time-insensitive predictive instrument) indicated a > 75% probability of ACS, and/or the TPI (thrombolytic predictive instrument) indicated presence of a STEMI, or if local criteria for STEMI notification of receiving hospitals were met. Prehospital IV GIK or placebo was started immediately.
Pre-specified were the primary endpoint of progression of ACS to infarction, and as major secondary endpoints, the composite of cardiac arrest or in-hospital mortality; 30-day mortality; and the composite of cardiac arrest, 30-day mortality or hospitalization for heart failure (HF). Analyses were planned on an intent-to-treat basis, on a modified intent-to-treat group who were confirmed in emergency departments to have ACS, and for participants presenting with STEMI.
The IMMEDIATE Trial tested whether GIK, when administered as early as possible in the course of ACS by paramedics using ACI-TIPI and TPI decision support, would reduce progression to AMI, mortality, cardiac arrest, and HF. It also tested whether it would provide clinical and pathophysiological information on GIK’s biological mechanisms.
PMCID: PMC4009621  PMID: 22424000
17.  Gun Violence Is a Health Crisis: Physicians’ Responsibilities 
PMCID: PMC3631057  PMID: 23558774
18.  Preliminary Competencies for Comparative Effectiveness Research 
The Clinical and Translational Science Award (CTSA) Workgroup for Comparative Effectiveness Research (CER) Education, Training, and Workforce Development identified a need to delineate the competencies that practitioners and users of CER for patient centered outcomes research, should acquire. With input from CTSA representatives and collaborators, we began by describing the workforce. We recognize the workforce that conduct CER and the end users who use CER to improve the health of individuals and communities. We generated a preliminary set of competencies and solicited feedback from the CER representatives at each member site of the CTSA consortium. We distinguished applied competencies (i.e., skills needed by individuals who conduct CER) from foundational competencies that are needed by the entire CER workforce, including end users of CER. Key competency categories of relevance to both practitioners and users of CER were: 1) Asking relevant research questions; 2) Recognizing or designing ideal CER studies; 3) Executing or using CER studies; 4) Using appropriate statistical analyses for CER; and 5) Communicating and disseminating CER study results to improve health. While CER is particularly broad concept, we anticipate that these preliminary, relatively generic competencies will be used in tailoring curricula to individual learners from a variety of programmatic perspectives.
PMCID: PMC3533240  PMID: 23253670
19.  Comparative Effectiveness Research in Lung Diseases and Sleep Disorders 
The Division of Lung Diseases of the National Heart, Lung, and Blood Institute (NHLBI) held a workshop to develop recommendations on topics, methodologies, and resources for comparative effectiveness research (CER) that will guide clinical decision making about available treatment options for lung diseases and sleep disorders. A multidisciplinary group of experts with experience in efficacy, effectiveness, implementation, and economic research identified (a) what types of studies the domain of CER in lung diseases and sleep disorders should include, (b) the criteria and process for setting priorities, and (c) current resources for and barriers to CER in lung diseases. Key recommendations were to (1) increase efforts to engage stakeholders in developing CER questions and study designs; (2) invest in further development of databases and other infrastructure, including efficient methods for data sharing; (3) make full use of a broad range of study designs; (4) increase the appropriate use of observational designs and the support of methodologic research; (5) ensure that committees that review CER grant applications include persons with appropriate perspective and expertise; and (6) further develop the workforce for CER by supporting training opportunities that focus on the methodologic and practical skills needed.
PMCID: PMC3265273  PMID: 21965016
randomized controlled trials; observational studies; implementation; study designs; methodology
21.  Random Treatment Assignment Using Mathematical Equipoise for Comparative Effectiveness Trials 
In controlled clinical trials, random assignment of treatment is appropriate only when there is equipoise, i.e., no clear preference among treatment options. However, even when equipoise appears absent because prior trials show, on average, one treatment yields superior outcomes, random assignment still may be appropriate for some patients and circumstances. In such cases, enrollment into trials may be assisted by real-time patient-specific predictions of treatment outcomes, to determine whether there is equipoise to justify randomization.
The Percutaneous Coronary Intervention Thrombolytic Predictive Instrument (PCI-TPI) computes probabilities of 30-day mortality for patients having ST elevation myocardial infarction (STEMI), if treated with thrombolytic therapy, and if treated with PCI. We estimated uncertainty around differences in their respective predicted benefits using the estimated uncertainty of the model coefficients. Using the 2,781-patient PCI-TPI development dataset, we evaluated the distribution of predicted benefits for each patient. For three typical clinical situations, randomization was potentially warranted for 70%, 93%, and 80% of patients.
Predictive models may allow real-time patient-specific determination of whether there is equipoise that justifies trial enrollment for a given patient. This approach may have utility for comparative effectiveness trials and for application of trial results to clinical practice.
PMCID: PMC3076795  PMID: 21348950
23.  Improving Use of Prehospital 12-Lead Electrocardiography for Early Identification and Treatment of Acute Coronary Syndrome and ST-Elevation Myocardial Infarction 
Performance of Prehospital electrocardiograms (PH-ECGs) expedites identification of ST-elevation myocardial infarction (STEMI) and reduces door-to-balloon (D2B) times for patients receiving reperfusion therapy. To fully realize this benefit, emergency medical service (EMS) performance must be measured and used in feedback reporting and quality improvement (QI).
Methods and Results
This quasi-experimental design trial tested an approach to improving EMS PH-ECG using feedback reporting and QI interventions in two cities' EMS agencies and receiving hospitals. All patients ≥ 30 years, calling 9-1-1 with possible acute coronary syndrome (ACS) were included. In total 6,994 patients were included: 1,589 patients in the baseline period without feedback and 5,405 in the intervention period when there were feedback reports and QI interventions. Mean age (SD) was 66 (±17) and women represented 51%. Feedback and QI increased PH-ECG performance for patients with ACS from 76% to 93% (p=<.0001) and for patients with STEMI from 77% to 99% (p= <.0001). Aspirin administration increased from 75% to 82% (p=0.001) but the median total EMS run time remained the same at 22 minutes. The proportion of patients with D2B times of ≤90 minutes increased from 27% to 67% (p=0.006).
Feedback reports and QI improved PH-ECG performance for patients with ACS and STEMI and increased aspirin administration, without prehospital transport delays. Improvements in D2B times were also seen.
PMCID: PMC3103142  PMID: 20484201
electrocardiography; myocardial infarction; reperfusion; computers
25.  Comparative Effectiveness of STEMI Regionalization Strategies 
Primary percutaneous coronary intervention (PCI) is more effective on average than fibrinolytic therapy (FT) in the treatment of ST-segment elevation myocardial infarction (STEMI). Yet most U.S. hospitals are not equipped for PCI and FT is still widely used. This study evaluated the comparative effectiveness of STEMI regionalization strategies to increase the use of PCI against standard emergency transport and care.
We estimated incremental treatment costs and quality-adjusted life expectancies of 2,000 patients with STEMI who received PCI or FT in simulations of emergency care in a regional hospital system. To increase access to PCI across the system, we compared a base case strategy to 12 hospital-based strategies of building new PCI labs or extending the hours of existing labs, and one emergency medical services (EMS)-based strategy of transporting all patients with STEMI to existing PCI-capable hospitals. The base case resulted in 609 (569, 647) patients getting PCI. Hospital-based strategies increased the number of patients receiving PCI, the costs of care, and quality-adjusted life years (QALYs) saved, and were cost effective under a variety of conditions. An EMS-based strategy of transporting every patient to an existing PCI facility was less costly and more effective than all hospital expansion options.
Our results suggest that new construction and staffing of PCI labs may not be warranted if an EMS strategy is both available and feasible.
PMCID: PMC2967250  PMID: 20664025
cost-benefit analysis; fibrinolysis; Percutaneous coronary intervention; ST-segment elevation myocardial infarction; thrombolysis

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