Publications

2010
Laura Mauri, Dean J Kereiakes, Sharon-Lise T Normand, Stephen D Wiviott, David J Cohen, David R Holmes, Sripal Bangalore, Donald E Cutlip, Michael Pencina, and Joseph M Massaro. 2010. “Rationale and design of the dual antiplatelet therapy study, a prospective, multicenter, randomized, double-blind trial to assess the effectiveness and safety of 12 versus 30 months of dual antiplatelet therapy in subjects undergoing percutaneous coronary.” Am Heart J, 160, 6, Pp. 1035-41, 1041.e1.Abstract
BACKGROUND: Dual antiplatelet therapy with aspirin and thienopyridines (clopidogrel or prasugrel) is required after placement of coronary stents to prevent thrombotic complications. Although current clinical practice guidelines recommend 12-month treatment after drug-eluting stent placement, even longer durations may prevent thrombotic events. STUDY DESIGN: The Dual Antiplatelet Therapy (DAPT) Study is comparing the benefits and risks of 12 versus 30 months of dual antiplatelet therapy in preventing stent thrombosis or major adverse cardiovascular and cerebrovascular events in subjects undergoing percutaneous coronary intervention (PCI) for the treatment of coronary artery obstructive lesions. The DAPT Study is a multicenter, international, randomized, double-blind, placebo-controlled trial that will enroll 15,245 subjects treated with drug-eluting stent (DES) and 5,400 subjects treated with bare-metal stents (BMS). All subjects will receive 12 months of open-label thienopyridine treatment in addition to aspirin. After 12 months, subjects who are free from death, myocardial infarction, or stroke (MACCE), repeat revascularization, and GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) moderate or severe bleeding events will be randomized to receive either 18 additional months of thienopyridine (clopidogrel or prasugrel) (30 month DAPT arm) or placebo (12 month DAPT arm) plus aspirin. Coprimary end points are MACCE and stent thrombosis. The primary safety end point is GUSTO moderate or severe bleeding. CONCLUSIONS: This randomized trial is designed to define the relative safety and effectiveness of 12 versus 30 months of dual antiplatelet therapy across the broad spectrum of patients receiving coronary stents.
Jersey Chen, Sharon-Lise T Normand, Yun Wang, Elizabeth E Drye, Geoffrey C Schreiner, and Harlan M Krumholz. 2010. “Recent declines in hospitalizations for acute myocardial infarction for Medicare fee-for-service beneficiaries: progress and continuing challenges.” Circulation, 121, 11, Pp. 1322-8.Abstract
BACKGROUND: Amid recent efforts to reduce cardiovascular risk, whether rates of acute myocardial infarction (AMI) in the United States have declined for elderly patients is unknown. METHODS AND RESULTS: Medicare fee-for-service patients hospitalized in the United States with a principal discharge diagnosis of AMI were identified through the use of data from the Centers for Medicare and Medicaid Services from 2002 to 2007, a time period selected to reduce changes arising from the new definition of AMI. The Medicare beneficiary denominator file was used to determine the population at risk. AMI hospitalization rates were calculated annually per 100,000 beneficiary-years with Poisson regression analysis and stratified according to age, sex, and race. The annual AMI hospitalization rate in the fee-for-service Medicare population fell from 1131 per 100,000 beneficiary-years in 2002 to 866 in 2007, a relative 23.4% decline. After adjustment for age, sex, and race, the AMI hospitalization rate declined by 5.8%/y. From 2002 to 2007, white men experienced a 24.4% decrease in AMI hospitalizations, whereas black men experienced a smaller decline (18.0%; P<0.001 for interaction). Black women had a smaller decline in AMI hospitalization rate compared with white women (18.4% versus 23.3%, respectively; P<0.001 for interaction). CONCLUSIONS: AMI hospitalization rates fell markedly in the Medicare fee-for-service population between 2002 and 2007. However, black men and women appeared to have had a slower rate of decline compared with their white counterparts.
Joseph S Ross, Jersey Chen, Zhenqiu Lin, Héctor Bueno, Jeptha P Curtis, Patricia S Keenan, Sharon-Lise T Normand, Geoffrey Schreiner, John A Spertus, Maria T Vidán, Yongfei Wang, Yun Wang, and Harlan M Krumholz. 2010. “Recent national trends in readmission rates after heart failure hospitalization.” Circ Heart Fail, 3, 1, Pp. 97-103.Abstract
BACKGROUND: In July 2009, Medicare began publicly reporting hospitals' risk-standardized 30-day all-cause readmission rates (RSRRs) among fee-for-service beneficiaries discharged after hospitalization for heart failure from all the US acute care nonfederal hospitals. No recent national trends in RSRRs have been reported, and it is not known whether hospital-specific performance is improving or variation in performance is decreasing. METHODS AND RESULTS: We used 2004-2006 Medicare administrative data to identify all fee-for-service beneficiaries admitted to a US acute care hospital for heart failure and discharged alive. We estimated mean annual RSRRs, a National Quality Forum-endorsed metric for quality, using 2-level hierarchical models that accounted for age, sex, and multiple comorbidities; variation in quality was estimated by the SD of the RSRRs. There were 570 996 distinct hospitalizations for heart failure in which the patient was discharged alive in 4728 hospitals in 2004, 544 550 in 4694 hospitals in 2005, and 501 234 in 4674 hospitals in 2006. Unadjusted 30-day all-cause readmission rates were virtually identical over this period: 23.0% in 2004, 23.3% in 2005, and 22.9% in 2006. The mean and SD of RSRRs were also similar: mean (SD) of 23.7% (1.3) in 2004, 23.9% (1.4) in 2005, and 23.8% (1.4) in 2006, suggesting similar hospital variation throughout the study period. CONCLUSIONS: National mean and RSRR distributions among Medicare beneficiaries discharged after hospitalization for heart failure have not changed in recent years, indicating that there was neither improvement in hospital readmission rates nor in hospital variations in rates over this time period.
Sharon-Lise Normand, Danica Marinac-Dabic, Art Sedrakyan, and Ronald Kaczmarek. 2010. “Rethinking analytical strategies for surveillance of medical devices: the case of hip arthroplasty.” Med Care, 48, 6 Suppl, Pp. S58-67.Abstract
BACKGROUND: Randomized trials that sometimes serve as the basis for device approval are small, short term, and generalizable to an increasingly smaller percentage of patients. Some of the most common and challenging devices are those used in hip replacement. Artificial hips are implanted in thousands to alleviate pain caused by noninflammatory joint disease and to restore patient mobility. During 2004 in the United States, although 68% of hospital stays for partial or total hip replacements were for those aged 65 years and older, younger patients will account for 52% by 2030. METHODS: Using hierarchical modeling, we propose a framework for combining information from premarket and postmarket settings. Our key assumption is that device performance characteristics and outcomes obtained from 1 cohort are related to device characteristics and outcomes of the same or similar devices observed in other cohorts. We illustrate methods by jointly modeling Harris Hip Scores (HHSs) and revision-success data from 1851 subjects who participated in 3 pivotal randomized or observational studies of artificial hips. RESULTS AND CONCLUSIONS: Subjects participating in randomized studies had better 2-year HHS than those in observational studies (posterior mean increase in HHS = 4.1, posterior standard deviation = 0.6). Patients implanted with ceramic-on-polyethylene hip used in 1 study had higher 2-year HHS than those implanted with a different ceramic-on-polyethylene hip in another study (mean difference = 4.2, standard deviation = 0.6). Our approach is feasible and will advance regulatory science using a transparent and dynamic new paradigm for knowledge management throughout the total product life cycle.
Khurram Nasir, Zhenqiu Lin, Hector Bueno, Sharon-Lise T Normand, Elizabeth E Drye, Patricia S Keenan, and Harlan M Krumholz. 2010. “Is same-hospital readmission rate a good surrogate for all-hospital readmission rate?” Med Care, 48, 5, Pp. 477-81.Abstract
BACKGROUND: The Centers for Medicare & Medicaid Services (CMS) readmission measure is based on all-cause readmissions to any hospital within 30 days of discharge. Whether a measure based on same-hospital readmission, an outcome that is easier for hospitals and some systems to track, could serve as a proxy for the all-hospital measure is not known. OBJECTIVES: Evaluate whether same-hospital readmission rate is a good surrogate for all-hospital readmission rate. RESEARCH DESIGN: The study population was derived from the Medicare inpatient, outpatient, and carrier (physician) Standard Analytic Files. Thirty-day risk-standardized readmission rates (RSRRs) for heart failure (HF) for both all-hospital readmission and same-hospital readmission were assessed by using hierarchical logistic regression models. SUBJECTS: The sample consisted of 501,234 hospitalizations in 4674 hospitals with at least 1 hospitalization. MEASURES: Thirty-day readmission was defined as occurrence of at least 1 hospitalization in any US acute care hospital for any cause within 30 days of discharge after an index hospitalization. Same-hospital readmission was considered if the patient was admitted to the hospital that produced the original discharge within 30 days. RESULTS: Overall, 80.9% of all HF readmissions occurred in the same- hospital, whereas 19.1% of readmissions occurred in a different hospital. The mean difference between all- versus same-hospital RSRR was 4.7 +/- 1.0%, ranging from 0.9% to 10.5% across these hospitals with 25th, 50th, and 75th percentiles of 4.1%, 4.7%, and 5.2%, respectively, and was variable across the range of average RSRR. CONCLUSION: Same-hospital readmission rate is an unreliable and biased indicator of all-hospital readmission rate with limited value as a benchmark for quality of care processes.
Roger E Meyer, Carl Salzman, Eric A Youngstrom, Paula J Clayton, Frederick K Goodwin, John J Mann, Larry D Alphs, Karl Broich, Wayne K Goodman, John F Greden, Herbert Y Meltzer, Sharon-Lise T Normand, Kelly Posner, David Shaffer, Maria A Oquendo, Barbara Stanley, Madhukar H Trivedi, Gustavo Turecki, Charles M Beasley, Annette L Beautrais, Jeffrey A Bridge, Gregory K Brown, Dennis A Revicki, Neal D Ryan, and David V Sheehan. 2010. “Suicidality and risk of suicide--definition, drug safety concerns, and a necessary target for drug development: a brief report.” J Clin Psychiatry, 71, 8, Pp. 1040-6.Abstract
OBJECTIVE: To address issues concerning potential treatment-emergent "suicidality," a consensus conference was convened March 23-24, 2009. PARTICIPANTS: This gathering of participants from academia, government, and industry brought together experts in suicide prevention, clinical trial design, psychometrics, pharmacoepidemiology, and genetics, as well as research psychiatrists involved in studies in studies of psychiatric disorders associated with elevated suicide risk across the life cycle. The process involved reviews of the relevant literature, and a series of 6 breakout sessions focused on specific questions of interest. EVIDENCE: Each of the participants at the meeting received references relevant to the formal presentations (as well as the slides for the presentations) for their review prior to the meeting. In addition, the assessment instruments of suicidal ideation/behavior were reviewed in relationship to standard measures of validity, reliability, and clinical utility, and these findings were discussed at length in relevant breakout groups, in the final plenary session, and in the preparation of the article. Consensus and dissenting views were noted. CONSENSUS PROCESS: Discussion and questions followed each formal presentation during the plenary sessions. Approximately 6 questions per breakout group were prepared in advance by members of the Steering Committee and each breakout group chair. Consensus in the breakout groups was achieved by nominal group process. Consensus recommendations and any dissent were reviewed for each breakout group at the final plenary session. All plenary sessions were recorded and transcribed by a court stenographer. Following the transcript, with input by each of the authors, the final paper went through 14 drafts. The output of the meeting was organized into this brief report and the accompanying full article from which it is distilled. The full article was developed by the authors with feedback from all participants at the meeting and represents a consensus view. Any areas of disagreement at the conference have been noted in the text. CONCLUSIONS: The term suicidality is not as clinically useful as more specific terminology (ideation, behavior, attempts, and suicide). Most participants applauded the FDA's encouragement of standard definitions and definable expectations for investigators and industry sponsors. Further research of available assessment instruments is needed to verify their utility, reliability, and validity in identifying suicide-associated treatment-emergent adverse effects and/or a signal of efficacy in suicide prevention trials. The FDA needs to systematically monitor postmarketing events by encouraging the development of a validated instrument for postmarketing surveillance of suicidal ideation, behavior, and risk. Over time, the FDA, industry, and clinical researchers should evaluate the impact of the requirement that all central nervous system clinical drug trials must include a Columbia Classification Algorithm of Suicide Assessment (C-CASA)-compatible screening instrument for assessing and documenting the occurrence of treatment-emergent suicidal ideation and behavior. Finally, patients at high risk for suicide can safely be included in clinical trials, if proper precautions are followed.
Roger E Meyer, Carl Salzman, Eric A Youngstrom, Paula J Clayton, Frederick K Goodwin, John J Mann, Larry D Alphs, Karl Broich, Wayne K Goodman, John F Greden, Herbert Y Meltzer, Sharon-Lise T Normand, Kelly Posner, David Shaffer, Maria A Oquendo, Barbara Stanley, Madhukar H Trivedi, Gustavo Turecki, Charles M Beasley, Annette L Beautrais, Jeffrey A Bridge, Gregory K Brown, Dennis A Revicki, Neal D Ryan, and David V Sheehan. 2010. “Suicidality and risk of suicide--definition, drug safety concerns, and a necessary target for drug development: a consensus statement.” J Clin Psychiatry, 71, 8, Pp. e1-e21.Abstract
OBJECTIVE: To address issues concerning potential treatment-emergent "suicidality," a consensus conference was convened March 23-24, 2009. PARTICIPANTS: This gathering of participants from academia, government, and industry brought together experts in suicide prevention, clinical trial design, psychometrics, pharmacoepidemiology, and genetics, as well as research psychiatrists involved in studies of major depression, bipolar disorder, schizophrenia, substance abuse/dependence, and other psychiatric disorders associated with elevated suicide risk across the life cycle. The process involved reviews of the relevant literature, and a series of 6 breakout sessions focused on specific questions of interest. EVIDENCE: Each of the participants at the meeting received references relevant to the formal presentations (as well as the slides for the presentations) for their review prior to the meeting. In addition, the assessment instruments of suicidal ideation/behavior were reviewed in relationship to standard measures of validity, reliability, and clinical utility, and these findings were discussed at length in relevant breakout groups, in the final plenary session, and in the preparation of the article. Consensus and dissenting views were noted. CONSENSUS PROCESS: Discussion and questions followed each formal presentation during the plenary sessions. Approximately 6 questions per breakout group were prepared in advance by members of the Steering Committee and each breakout group chair. Consensus in the breakout groups was achieved by nominal group process. Consensus recommendations and any dissent were reviewed for each breakout group at the final plenary session. All plenary sessions were recorded and transcribed by a court stenographer. Following the transcript, with input by each of the authors, the final paper went through 14 drafts. The output of the meeting was organized into this scholarly article, which has been developed by the authors with feedback from all participants at the meeting and represents a consensus view. Any areas of disagreement have been noted. CONCLUSIONS: The term suicidality is not as clinically useful as more specific terminology (ideation, behavior, attempts, and suicide). Most participants applauded the FDA's effort to promote standard definitions and definable expectations for investigators and industry sponsors by endorsing the terminology in the Columbia Classification Algorithm of Suicide Assessment (C-CASA). Further research of available assessment instruments is needed to verify their utility, reliability, and validity in identifying suicide-associated treatment-emergent adverse effects and/or a signal of efficacy in suicide prevention trials. The FDA needs to build upon its new authority to systematically monitor postmarketing events by encouraging the development of a validated instrument for postmarketing surveillance of suicidal ideation, behavior, and risk within informative large health care-related databases in the United States and abroad. Over time, the FDA, industry, and clinical researchers should evaluate the impact of the current Agency requirement that all CNS clinical drug trials must include a C-CASA-compatible screening instrument for assessing and documenting the occurrence of treatment-emergent suicidal ideation and behavior. Finally, patients at high risk for suicide can safely be included in clinical trials, if proper precautions are followed, and they need to be included to enable premarket assessments of the risks and benefits of medications related to suicidal ideation, suicidal behavior, and suicide in such patients.
Anas Allam, Jean-Bernard Behr, Laurent Dupont, Véronique Nardello-Rataj, and Richard Plantier-Royon. 2010. “Synthesis, physico-chemical properties and complexing abilities of new amphiphilic ligands from D-galacturonic acid.” Carbohydr Res, 345, 6, Pp. 731-9.Abstract
This paper describes a convenient and efficient synthesis of new complexing surfactants from d-galacturonic acid and n-octanol as renewable raw materials in a two-step sequence. In the first step, simultaneous O-glycosidation-esterification under Fischer conditions was achieved. The anomeric ratio of the products was studied based on the main experimental parameters and the activation mode (thermal or microwave). In the second step, aminolysis of the n-octyl ester was achieved with various functionalized primary amines under standard thermal or microwave activation. The physico-chemical properties of these new amphiphilic ligands were measured and these compounds were found to exhibit interesting surface properties. Complexing abilities of one uronamide ligand functionalized with a pyridine moiety toward Cu(II) ions was investigated in solution by EPR titrations. A solid compound was also synthesized and characterized, its relative structure was deduced from spectroscopic data.
Scott L Hummel, Natalie P Pauli, Harlan M Krumholz, Yun Wang, Jersey Chen, Sharon-Lise T Normand, and Brahmajee K Nallamothu. 2010. “Thirty-day outcomes in Medicare patients with heart failure at heart transplant centers.” Circ Heart Fail, 3, 2, Pp. 244-52.Abstract
BACKGROUND: Heart transplant centers are generally considered "centers of excellence" for heart failure care. However, their overall performance has not previously been evaluated in a broad population of elderly patients with heart failure, many of whom are not transplant candidates. METHODS AND RESULTS: We identified >1 million elderly Medicare beneficiaries who were hospitalized for heart failure between 2004 and 2006 at >4500 hospitals. We calculated 30-day risk-standardized mortality rates and standardized mortality ratios as well as 30-day risk-standardized readmission rates and standardized readmission ratios at heart transplant centers and non-heart transplant hospitals using risk-standardization models that the Centers for Medicare & Medicaid Services uses for public reporting. The 30-day risk-standardized mortality rates were lower at heart transplant centers than non-heart transplant hospitals nationally (10.6% versus 11.5%, P<0.001) but were similar at peer institutions offering coronary artery bypass grafting within the same geographical region (10.6% versus 10.6%, P=0.96). The mean standardized mortality ratio for heart transplant centers was 0.9 (SD, 0.1; range, 0.7 to 1.3). No differences were noted in 30-day risk-standardized readmission rates between heart transplant centers and non-heart transplant hospitals nationally (23.6% versus 23.8%, P=0.55). The mean standardized readmission ratio for heart transplant centers was 1.0 (SD, 0.1; range, 0.8 to 1.2). CONCLUSIONS: In elderly Medicare patients with heart failure, heart transplant centers have lower 30-day risk-standardized mortality rates than non-heart transplant hospitals nationally; however, this difference is not present in comparison with peer institutions or for 30-day risk-standardized readmission rates.
Héctor Bueno, Joseph S Ross, Yun Wang, Jersey Chen, María T Vidán, Sharon-Lise T Normand, Jeptha P Curtis, Elizabeth E Drye, Judith H Lichtman, Patricia S Keenan, Mikhail Kosiborod, and Harlan M Krumholz. 2010. “Trends in length of stay and short-term outcomes among Medicare patients hospitalized for heart failure, 1993-2006.” JAMA, 303, 21, Pp. 2141-7.Abstract
CONTEXT: Whether decreases in the length of stay during the past decade for patients with heart failure (HF) may be associated with changes in outcomes is unknown. OBJECTIVE: To describe the temporal changes in length of stay, discharge disposition, and short-term outcomes among older patients hospitalized for HF. DESIGN, SETTING, AND PARTICIPANTS: An observational study of 6,955,461 Medicare fee-for-service hospitalizations for HF between 1993 and 2006, with a 30-day follow-up. MAIN OUTCOME MEASURES: Length of hospital stay, in-patient and 30-day mortality, and 30-day readmission rates. RESULTS: Between 1993 and 2006, mean length of stay decreased from 8.81 days (95% confidence interval [CI], 8.79-8.83 days) to 6.33 days (95% CI, 6.32-6.34 days). In-hospital mortality decreased from 8.5% (95% CI, 8.4%-8.6%) in 1993 to 4.3% (95% CI, 4.2%-4.4%) in 2006, whereas 30-day mortality decreased from 12.8% (95% CI, 12.8%-12.9%) to 10.7% (95% CI, 10.7%-10.8%). Discharges to home or under home care service decreased from 74.0% to 66.9% and discharges to skilled nursing facilities increased from 13.0% to 19.9%. Thirty-day readmission rates increased from 17.2% (95% CI, 17.1%-17.3%) to 20.1% (95% CI, 20.0%-20.2%; all P < .001). Consistent with the unadjusted analyses, the 2005-2006 risk-adjusted 30-day mortality risk ratio was 0.92 (95% CI, 0.91-0.93) compared with 1993-1994, and the 30-day readmission risk ratio was 1.11 (95% CI, 1.10-1.11). CONCLUSION: For patients admitted with HF during the past 14 years, reductions in length of stay and in-hospital mortality, less marked reductions in 30-day mortality, and changes in discharge disposition accompanied by increases in 30-day readmission rates were observed.
Joseph S Ross, Charles Maynard, Harlan M Krumholz, Haili Sun, John S Rumsfeld, Sharon-Lise T Normand, Yun Wang, and Stephan D Fihn. 2010. “Use of administrative claims models to assess 30-day mortality among Veterans Health Administration hospitals.” Med Care, 48, 7, Pp. 652-8.Abstract
BACKGROUND: The Centers for Medicare and Medicaid Services (CMS) publicly reports hospital-specific risk-standardized, 30-day, all-cause, mortality rates (RSMRs) for all hospitalizations among fee-for-service Medicare beneficiaries for acute myocardial infarction (AMI), heart failure (HF), and pneumonia at non-Federal hospitals. OBJECTIVE: To examine the performance of the statistical models used by CMS among veterans at least 65 years of age hospitalized for AMI, HF, and pneumonia in Veterans Health Administration (VHA) hospitals. RESEARCH DESIGN: Cross-sectional analysis of VHA administrative claims data between October 1, 2006 and September 30, 2009. SUBJECTS: Thirteen thousand forty-six veterans hospitalized for AMI among 123 VHA hospitals; 26,379 veterans hospitalized for HF among 124 VHA hospitals; and 31,126 veterans hospitalized for pneumonia among 124 VHA hospitals. MEASURES: Hospital-specific RSMR for AMI, HF, and pneumonia hospitalizations calculated using hierarchical generalized linear models. RESULTS: Median number of AMI hospitalizations per VHA hospital was 87. Average AMI RSMR was 14.3% [95% confidence interval (CI), 13.9%-14.6%] with modest heterogeneity among VHA hospitals (RSMR range: 8.4%-20.3%). The c-statistic for the AMI RSMR statistical model was 0.79. Median number of HF hospitalizations was 188. Average HF RSMR was 10.1% (95% CI, 9.9%-10.4%) with modest heterogeneity (RSMR range: 6.1%-14.9%). The c-statistic for the HF RSMR statistical model was 0.73. Median number of pneumonia hospitalizations was 221.5. Average pneumonia RSMR was 13.0% (95% CI, 12.7%-13.3%) with modest heterogeneity (RSMR range: 9.0%-18.4%). The c-statistic for the pneumonia RSMR statistical model was 0.72. CONCLUSIONS: The statistical models used by CMS to estimate RSMRs for AMI, HF, and pneumonia hospitalizations at non-Federal hospitals demonstrate similar discrimination when applied to VHA hospitals.
David M Shahian, Robert E Wolf, Lisa I Iezzoni, Leslie Kirle, and Sharon-Lise T Normand. 2010. “Variability in the measurement of hospital-wide mortality rates.” N Engl J Med, 363, 26, Pp. 2530-9.Abstract
BACKGROUND: Several countries use hospital-wide mortality rates to evaluate the quality of hospital care, although the usefulness of this metric has been questioned. Massachusetts policymakers recently requested an assessment of methods to calculate this aggregate mortality metric for use as a measure of hospital quality. METHODS: The Massachusetts Division of Health Care Finance and Policy provided four vendors with identical information on 2,528,624 discharges from Massachusetts acute care hospitals from October 1, 2004, through September 30, 2007. Vendors applied their risk-adjustment algorithms and provided predicted probabilities of in-hospital death for each discharge and for hospital-level observed and expected mortality rates. We compared the numbers and characteristics of discharges and hospitals included by each of the four methods. We also compared hospitals' standardized mortality ratios and classification of hospitals with mortality rates that were higher or lower than expected, according to each method. RESULTS: The proportions of discharges that were included by each method ranged from 28% to 95%, and the severity of patients' diagnoses varied widely. Because of their discharge-selection criteria, two methods calculated in-hospital mortality rates (4.0% and 5.9%) that were twice the state average (2.1%). Pairwise associations (Pearson correlation coefficients) of discharge-level predicted mortality probabilities ranged from 0.46 to 0.70. Hospital-performance categorizations varied substantially and were sometimes completely discordant. In 2006, a total of 12 of 28 hospitals that had higher-than-expected hospital-wide mortality when classified by one method had lower-than-expected mortality when classified by one or more of the other methods. CONCLUSIONS: Four common methods for calculating hospital-wide mortality produced substantially different results. This may have resulted from a lack of standardized national eligibility and exclusion criteria, different statistical methods, or fundamental flaws in the hypothesized association between hospital-wide mortality and quality of care. (Funded by the Massachusetts Division of Health Care Finance and Policy.).
Elizabeth H Bradley, Jeph Herrin, Leslie Curry, Emily J Cherlin, Yongfei Wang, Tashonna R Webster, Elizabeth E Drye, Sharon-Lise T Normand, and Harlan M Krumholz. 2010. “Variation in hospital mortality rates for patients with acute myocardial infarction.” Am J Cardiol, 106, 8, Pp. 1108-12.Abstract
Hospitals vary by twofold in their hospital-specific 30-day risk-stratified mortality rates (RSMRs) for Medicare beneficiaries with acute myocardial infarction (AMI). However, we lack a comprehensive investigation of hospital characteristics associated with 30-day RSMRs and the degree to which the variation in 30-day RSMRs is accounted for by these characteristics, including the socioeconomic status (SES) profile of hospital patient populations. We conducted a cross-sectional national study of hospitals with ≥15 AMI discharges from July 1, 2005 to June 20, 2008. We estimated a multivariable weighted regression using Medicare claims data for hospital-specific 30-day RSMRs, American Hospital Association Survey of Hospitals for hospital characteristics, and the United States Census data reported by Neilsen Claritas, Inc., for zip-code level estimates of SES status. Analysis included 2,908 hospitals with 513,202 AMI discharges. Mean hospital 30-day RSMR was 16.5% (SD 1.7 percentage points). Our multivariable model explained 17.1% of the variation in hospital-specific 30-day RSMRs. Teaching status, number of hospital beds, AMI volume, cardiac facilities available, urban/rural location, geographic region, ownership type, and SES profile of patients were significantly (p < 0.05) associated with 30-day RSMRs. In conclusion, substantial variation in hospital outcomes for patients with AMI remains unexplained by measurements of hospital characteristics including SES patient profile.
Sharon-Lise T Normand and Barbara J McNeil. 2010. “What is evidence?” Stat Med, 29, 19, Pp. 1985-8; discussion 1996-7.Abstract
The assumption that comparative effectiveness research will provide timely, relevant evidence rests on changing the current framework for assembling evidence. In this commentary, we provide the background of how coverage decisions for new medical technologies are currently made in the United States. We focus on the statistical issues regarding how to use the ensemble of information for inferring comparative effectiveness. It is clear a paradigm shift in how clinical information is integrated in real-world settings to establish effectiveness is required.
Robert L Wears and Sharon-Lise Normand. 2010. “When less is more: using shrinkage to increase accuracy.” Ann Emerg Med, 55, 6, Pp. 553-5.
2009
Haiden A Huskamp, Alisa B Busch, Marisa E Domino, and Sharon-Lise T Normand. 2009. “Antidepressant reformulations: who uses them, and what are the benefits?” Health Aff (Millwood), 28, 3, Pp. 734-45.Abstract
The Hatch-Waxman Act of 1984 provides pharmaceutical manufacturers with an incentive to introduce reformulations of existing products that are about to lose patent protection, to extend marketing exclusivity and maintain high prices. Antidepressant reformulations are particularly common. To determine whether the use of reformulations confers benefits, we examined who uses them and whether they affect the duration of medication use. We found some evidence of benefit for subgroups of antidepressant users, although benefits varied across reformulations.
Alisa B Busch, Richard G Frank, Gary Sachs, and Sharon-Lise T Normand. 2009. “Bipolar-I patient characteristics associated with differences in antimanic medication prescribing.” Psychopharmacol Bull, 42, 1, Pp. 35-49.Abstract
OBJECTIVE: Second-generation antipsychotics offer more choice in antimanic pharmacologic treatment. Unclear though is whether they are expanding antimanic treatment, replacing mood stabilizers, or if/which patient characteristics influence prescribing choices. We studied the association between patient characteristics and patient-reported antimanic medication use upon entry in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). EXPERIMENTAL DESIGN: Observational study using STEP-BD baseline data from bipolar-I patients (N = 1,943) during years 2000-2004. Two logistic regression models (binomial and multinomial) were estimated to examine associations between patient characteristics and patient-reported drug use: 1) any antimanic medication (antipsychotic or mood stabilizer), and 2) mood stabilizer, antipsychotic monotherapy, or neither. PRINCIPAL OBSERVATIONS: At study entry over 80% of participants reported receiving at least one antimanic medication; 73% a mood stabilizer specifically. In general, there was no association between study year and the odds of entering on antimanic medication. Measures of psychiatric severity or complexity were more likely to be associated with differences in the drugs used; co-occurring medical conditions were not. Depressed states were associated with similar odds of antipsychotic monotherapy as elevated or mixed states. Compared to whites, blacks had greater odds of entering on antipsychotic monotherapy relative to a mood stabilizer. CONCLUSIONS: Despite increasing pharmacotherapy options, we found no evidence that over time more patients received antimanic medication. Not all prescribing differences were consistent with the medical literature. Also, blacks were more likely to receive antipsychotic monotherapy, even after adjusting for clinical characteristics. Future research examining provider characteristics that influence prescribing is needed.
Jose A Suaya, William B Stason, Philip A Ades, Sharon-Lise T Normand, and Donald S Shepard. 2009. “Cardiac rehabilitation and survival in older coronary patients.” J Am Coll Cardiol, 54, 1, Pp. 25-33.Abstract
OBJECTIVES: This study assessed the effects of cardiac rehabilitation (CR) on survival in a large cohort of older coronary patients. BACKGROUND: Randomized controlled trials and meta-analyses have shown that CR improves survival. However, trial participants have been predominantly middle-aged, low- or moderate-risk, white men. METHODS: The population consisted of 601,099 U.S. Medicare beneficiaries who were hospitalized for coronary conditions or cardiac revascularization procedures. One- to 5-year mortality rates were examined in CR users and nonusers using Medicare claims and 3 analytic techniques: propensity-based matching, regression modeling, and instrumental variables. The first method used 70,040 matched pairs, and the other 2 techniques used the entire cohort. RESULTS: Only 12.2% of the cohort used CR, and those users averaged 24 sessions. Each technique showed significantly lower (p < 0.001) 1- to 5-year mortality rates in CR users than nonusers. Five-year mortality relative reductions were 34% in propensity-based matching, 26% from regression modeling, and 21% with instrumental variables. Mortality reductions extended to all demographic and clinical subgroups including patients with acute myocardial infarctions, those receiving revascularization procedures, and those with congestive heart failure. The CR users with 25 or more sessions were 19% relatively less likely to die over 5 years than matched CR users with 24 or fewer sessions (p < 0.001). CONCLUSIONS: Mortality rates were 21% to 34% lower in CR users than nonusers in this socioeconomically and clinically diverse, older population after extensive analyses to control for potential confounding. These results are of similar magnitude to those observed in published randomized controlled trials and meta-analyses in younger, more selected populations.
Armando Teixeira-Pinto and Sharon-Lise T Normand. 2009. “Comments on 'The BUGS project: Evolution, critique, and future directions'.” Stat Med, 28, 25, Pp. 3075-8.
Justin W Timbie, David M Shahian, Joseph P Newhouse, Meredith B Rosenthal, and Sharon-Lise T Normand. 2009. “Composite measures for hospital quality using quality-adjusted life years.” Stat Med, 28, 8, Pp. 1238-54.Abstract
Developing clinically meaningful summary measures of health-care quality is key to inferring quality of care. Current summary measures use a number of different approaches to weight their individual measures but rarely use weights based on clinical 'importance'. Such an approach would help to focus quality improvement efforts on areas likely to have the largest impact on health outcomes. Using coronary artery bypass graft (CABG) surgery as a case study, we weight and combine 11 process, complication, and survival measures to summarize differences in quality-adjusted life expectancy 1 year following surgery for a sample of hospitals. We use a fully Bayesian analysis to estimate 1-year survival outcomes using a hierarchical exponential survival model. We then estimate the expected utility of the year following surgery for each patient using complication probabilities fitted from hierarchical models and utility values from the literature. We estimate quality-adjusted life years (QALYs) for each hospital as the utility-weighted average 1-year survival probability and then estimate 'incremental QALYs' by taking the difference in QALYs for each hospital relative to a comparison group that reflects the average performance of all hospitals in the state. We illustrate our framework by estimating incremental QALYs for 14 hospitals performing CABG surgery in Massachusetts in 2003 and find that a composite measure based on QALYs can change the classification of quality outliers relative to conventional mortality measures.

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