Stakeholder Reflections on Implementing the National Institutes of Health's Policy on Single Institutional Review Boards.

The National Institutes of Health (NIH) requires use of a single institutional review board (sIRB) for multisite, nonexempt, NIH-funded research with human participants. The Clinical Trials Transformation Initiative (CTTI) conducted in-depth interviews with 34 stakeholders at two universities and in research administration leadership positions at multiple institutions about their experiences implementing the sIRB model, focusing on the NIH policy's goals soon after the policy was enacted. While some stakeholders suggested that using an sIRB has streamlined and reduced inefficiencies associated with the local IRB model, more stakeholders indicated that the sIRB model has not simplified the ethics review process and instead created new inefficiencies due to unclear roles and responsibilities for staff and institutions; a lack of systems and processes for implementing the sIRB model, including communication systems; and increased workloads. CTTI used these findings to propose a new framework for evaluating the NIH sIRB policy.

Enhancing Diversity and Inclusion in Clinical Trials.

Women and people from most racial and ethnic groups in the United States have historically been under-represented in clinical trials of investigational medical products. Inadequate representation of these groups may lead to an incomplete understanding of the safety and efficacy of new drugs, devices, biologics, and vaccines, and limit the generalizability of trial findings. As a result, new medical products may not be beneficial to all people who need them, and existing inequities in outcomes among various population groups may remain unchanged or worsen, or new disparities may arise. Although much work has focused on study-level strategies, research organizations must make systemic changes to how clinical trials are envisioned and implemented to achieve sustainable support for diversity and inclusion in clinical trials. The Clinical Trials Transformation Initiative (CTTI) conducted interviews with leaders at institutions that conduct clinical trials to explore perspectives on organizational-level practices that promote diversity and inclusion in clinical trials. Leaders described motivations, such as an ethical and moral imperative; organizational practices, such as staff investment and resource allocation; perceived return on investments, such as better science; and deterrents, such as cost and time. The CTTI also convened an expert meeting to discuss the interview findings and provide guidance. We present the interview findings and expert guidance in a framework that describes four key areas-commitment, partnerships, accountability, and resources-on sustaining organizational-level approaches for improving diversity and inclusion in clinical trials, with the ultimate goal of advancing health equity. Institutions who conduct and support clinical trials should implement organizational-level approaches to improve equitable access and diverse patient participation in clinical trials.

Lipid-lowering treatment among older patients with atherosclerotic cardiovascular disease.

BACKGROUND: The contemporary uptake of lipid-lowering therapies (LLT), including more intensive treatment with high-intensity statins and non-statin LLT, among U.S. older adults (≥75 years old) with ASCVD is unknown. METHODS: In this multicenter retrospective cohort study of a large geographically diverse sample of commercially insured U.S. older adults with ASCVD, we assessed treatment with LLT. Secondary measures included LDL-C above target ≥70 mg/dl, persistence and adherence to therapy. RESULTS: Treatment with statins, high-intensity statins, ezetimibe, and PCSK9 inhibitors was assessed in 194,503 older adults (49.9% female) with known ASCVD on January 31st, 2019. 49.3% of older adults with ASCVD were on any statin, with 16.6% receiving a high-intensity statin and 32.7% on low-or moderate-intensity statins. Treatment with ezetimibe (2.4%) or PCSK9 inhibitors (0.24%) was rare and 62.6% of the overall cohort had an LDL-C above target at ≥70 mg/dl. Patients on high-intensity statins were more frequently male, had a diagnosis of coronary artery disease, and were more frequently seen by a cardiologist compared with those on low-or moderate-intensity statins and untreated individuals (p < 0.0001). The majority of older adults on high-intensity statins remained on therapy at 12 months (91.9%) and 85.7% had ≥75% adherence to treatment. CONCLUSIONS: Less than half of eligible older adults with ASCVD are on statins and only a minority of patients are receiving more intensive lipid-lowering to improve outcomes.

PROPHETIC EU: Prospective Identification of Pneumonia in Hospitalized Patients in the Intensive Care Unit in European and United States Cohorts.

Background: The prospective identification of patients at high risk for hospital-acquired/ventilator-associated bacterial pneumonia may improve clinical trial feasibility and foster antibacterial development. In a prior study conducted in the United States, clinical criteria were used to prospectively identify these patients; however, these criteria have not been applied in a European population. Methods: Adults considered high risk for pneumonia (treatment with ventilation or high levels of supplemental oxygen) in the intensive care units of 7 European hospitals were prospectively enrolled from June 12 to December 27, 2017. We estimated the proportion of high-risk patients developing pneumonia according to US Food and Drug Administration guidance and a subset potentially eligible for antibacterial trial enrollment. We compared patient characteristics, treatment exposures, and pneumonia incidence in a European cohort and a previously described US cohort. Results: Of 888 high-risk patients, 211/888 (24%) were treated for possible pneumonia, and 150/888 (17%) met the Food and Drug Administration definition for hospital-acquired/ventilator-associated bacterial pneumonia. A higher proportion of European patients treated for possible pneumonia met the pneumonia definition (150/211 [71%] vs 537/1464 [37%]; P < .001). Among patients developing pneumonia, a higher proportion of European patients met antibacterial trial eligibility criteria (124/150 [83%] vs 371/537 [69%]; P < .001). Conclusions: Clinical criteria prospectively identified high-risk patients with high rates of pneumonia in the European cohort. Despite higher rates of established risk factors and incident pneumonia, European patients were significantly less likely to receive antibiotics for possible pneumonia than US patients. Different treatment practices may contribute to lower rates of antibacterial trial enrollment in the United States.

Effect of Mailing Educational Material to Patients With Atrial Fibrillation and Their Clinicians on Use of Oral Anticoagulants: A Randomized Clinical Trial.

Importance: Only about half of patients with atrial fibrillation (AF) who are at increased risk for stroke are treated with an oral anticoagulant (OAC), despite guideline recommendations for their use. Educating patients with AF about prevention of stroke with OACs may enable them as agents of change to initiate OAC treatment. Objective: To determine whether an educational intervention directed to patients and their clinicians stimulates the use of OACs in patients with AF who are not receiving OACs. Design, Setting, and Participants: The Implementation of a Randomized Controlled Trial to Improve Treatment With Oral Anticoagulants in Patients With Atrial Fibrillation (IMPACT-AFib) trial was a prospective, multicenter, open-label, pragmatic randomized clinical trial conducted from September 25, 2017, to May 1, 2019, embedded in health plans that participate in the US Food and Drug Administration's Sentinel System. It used the distributed database comprising health plan members to identify eligible patients, their clinicians, and outcomes. IMPACT-AFib enrolled patients with AF, a CHA2DS2-VASc (cardiac failure or dysfunction, hypertension, age 65-74 [1 point] or ≥75 years [2 points], diabetes, and stroke, transient ischemic attack or thromboembolism [2 points]-vascular disease, and sex category [female]) score of 2 or more, no evidence of OAC prescription dispensing in the preceding 12 months, and no hospitalization-related bleeding event within the prior 6 months. Interventions: Randomization to a single mailing of patient and/or clinician educational materials vs control. Main Outcomes and Measures: Analysis was performed on a modified intention-to-treat basis. The primary end point was the proportion of patients with at least 1 OAC prescription dispensed or at least 4 international normalized ratio test results within 1 year of the intervention. Results: Among 47 333 patients, there were 24 909 men (52.6%), the mean (SD) age was 77.9 (9.7) years, mean (SD) CHA2DS2-VASc score was 4.5 (1.7), 22 404 patients (47.3%) had an ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation) bleeding risk score of 5 or more, and 8890 patients (18.8%) had a history of hospitalization for bleeding. There were 2328 of 23 546 patients (9.9%) in the intervention group with initiation of OAC at 1 year compared with 2330 of 23 787 patients (9.8%) in the control group (adjusted OR, 1.01 [95% CI, 0.95-1.07]; P = .79). Conclusions and Relevance: Among a large population with AF with a guideline indication for OACs for stroke prevention who were randomized to a mailed educational intervention or to usual care, there was no clinically meaningful, numerical, or statistically significant difference in rates of OAC initiation. More-intensive interventions are needed to try and address the public health issue of underuse of anticoagulation for stroke prevention among patients with AF. Trial Registration: ClinicalTrials.gov Identifier: NCT03259373.

High-Intensity Statin Use Among Patients With Atherosclerosis in the U.S.

BACKGROUND: Preventive therapy among patients with established atherosclerotic cardiovascular disease (ASCVD) is generally underused. Whether new guideline recommendations and a focus on implementation have improved the use of high-intensity statins is unknown. OBJECTIVES: This study sought to evaluate the patterns and predictors of statin use among patients with ASCVD. METHODS: In this retrospective cohort study, pharmacy and medical claims data from a commercial health plan were queried for patients with established ASCVD between January 31, 2018, and January 31, 2019. Statin use on an index date of January 31, 2019, was evaluated, as was 12-month adherence and discontinuation. Multivariable logistic regression was used to determine independent associations with statin use of varying intensities. RESULTS: Of the 601,934 patients with established ASCVD, 41.7% were female, and the mean age was 67.5 ± 13.3 years. Overall, 22.5% of the cohort were on a high-intensity statin, 27.6% were on a low- or moderate-intensity statin, and 49.9% were not on any statin. In multivariable analysis, younger patients, female patients, and those with higher Charlson comorbidity score were less likely to be prescribed any statin. Among statin users, female patients, older patients, and those with peripheral artery disease were less likely to be on a high-intensity formulation, whereas a cardiology encounter in the prior year increased the odds. The majority of high-intensity stain users achieved high levels of adherence. CONCLUSIONS: Substantial underuse of statins persists in a large, insured, and contemporary cohort of patients with ASCVD from the United States. In particular, concerning gaps in appropriate statin use remain among younger patients, women, and those with noncoronary ASCVD.

Stakeholder Experiences with the Single IRB Review Process and Recommendations for Food and Drug Administration Guidance.

The revised Common Rule requires using a single institutional review board (sIRB) for U.S.-based, multisite, nonexempt, federally conducted or supported research with human participants. The 21st Century Cures Act directs the Department of Health and Human Services (HHS) to harmonize differences between HHS and the U.S. Food and Drug Administration (FDA) regulations governing research with humans. Anticipating that the FDA may update its 2006 centralized IRB guidance, we conducted interviews with 34 stakeholders engaged in FDA-regulated clinical research to identify benefits and challenges of using sIRBs and to gather recommendations for revising the FDA's guidance. The main benefits were consistency and standardization, speed and efficiency, and streamlining and simplification. The main challenges were uncertainty at local institutions, including addressing local context; decreased timeliness of the research review process; variable processes; and insufficient communication. Several recommendations for FDA guidance focused on the local context and communication plans. Findings suggest that the sIRB review process may be gaining efficiency although challenges remain.

Determining the Suitability of Registries for Embedding Clinical Trials in the United States: A Project of the Clinical Trials Transformation Initiative.

BACKGROUND: Patient registries are organized systems that use observational methods to collect uniform data on specified outcomes in a population defined by a particular disease, condition, or exposure. Data collected in registries often coincide with data that could support clinical trials. Integrating clinical trials within registries to create registry-embedded clinical trials offers opportunities to reduce duplicative data collection, identify and recruit patients more efficiently, decrease time to database lock, accelerate time to regulatory decision-making, and reduce clinical trial costs. This article describes a project of the Clinical Trials Transformation Initiative (CTTI) intended to help clinical trials researchers determine when a registry could potentially serve as the platform for the conduct of a clinical trial. METHODS: Through a review of registry-embedded clinical trials and commentaries, semi-structured interviews with experts, and a multi-stakeholder expert meeting, the project team addressed how to identify and describe essential registry characteristics, practices, and processes required to for conducting embedded clinical trials intended for regulatory submissions in the United States. RESULTS: Recommendations, suggested practices, and decision trees that facilitate the assessment of whether a registry is suitable for embedding clinical trials were developed, as well as considerations for the design of new registries. Essential registry characteristics include relevancy, robustness, reliability, and assurance of patient protections. CONCLUSIONS: The project identifies a clear role for registries in creating a sustainable and reusable infrastructure to conduct clinical trials. Adoption of these recommendations will facilitate the ability to perform high-quality and efficient prospective registry-based clinical trials.

PROPHETIC: Prospective Identification of Pneumonia in Hospitalized Patients in the ICU.

BACKGROUND: Pneumonia is the leading infection-related cause of death. The use of simple clinical criteria and contemporary epidemiology to identify patients at high risk of nosocomial pneumonia should enhance prevention efforts and facilitate development of new treatments in clinical trials. RESEARCH QUESTION: What are the clinical criteria and contemporary epidemiology trends that are helpful in the identification of patients at high risk of nosocomial pneumonia? STUDY DESIGN AND METHODS: Within the ICUs of 28 US hospitals, we conducted a prospective cohort study among adults who had been hospitalized >48 hours and were considered high risk for pneumonia (defined as treatment with invasive or noninvasive ventilatory support or high levels of supplemental oxygen). We estimated the proportion of high-risk patients who experienced the development of nosocomial pneumonia. Using multivariable logistic regression, we identified patient characteristics and treatment exposures that are associated with increased risk of pneumonia development during the ICU admission. RESULTS: Between February 6, 2016, and October 7, 2016, 4,613 high-risk patients were enrolled. Among 1,464 high-risk patients (32%) who were treated for possible nosocomial pneumonia, 537 (37%) met the study pneumonia definition. Among high-risk patients, a multivariable logistic model was developed to identify key patient characteristics and treatment exposures that are associated with increased risk of nosocomial pneumonia development (c-statistic, 0.709; 95% CI, 0.686-0.731). Key factors associated with increased odds of nosocomial pneumonia included an admission diagnosis of trauma or cerebrovascular accident, receipt of enteral nutrition, documented aspiration risk, and receipt of systemic antibacterials within the preceding 90 days. INTERPRETATION: Treatment for nosocomial pneumonia is common among patients in the ICU who are receiving high levels of respiratory support, yet more than one-half of patients who are treated do not fulfill standard diagnostic criteria for pneumonia. Application of simple clinical criteria may improve the feasibility of clinical trials of pneumonia prevention and treatment by facilitating prospective identification of patients at highest risk.

Consensus on Language for Advance Informed Consent in Health Care-Associated Pneumonia Clinical Trials Using a Delphi Process.

Importance: Information to be included in advance informed consent forms for health care-associated pneumonia treatment trials remains to be determined. Objective: To identify and determine how to describe information to be included in an advance informed consent form for an early-enrollment noninferiority hospital-acquired and/or ventilator-associated bacterial pneumonia (HABP/VABP) clinical trial. Design, Setting, and Participants: A Delphi consensus process with stakeholders in HABP/VABP clinical trials was conducted using qualitative semistructured telephone interviews from June to August 2016, followed by 2 online surveys, the first from April to May 2017, and the second from September to October 2017. All stakeholders who participated in the interview were invited to participate in the first survey. Stakeholders who participated in the first survey were invited to participate in the second survey. Stakeholders were patients at risk of pneumonia, caregivers, representatives of institutional review boards, investigators, and study coordinators. Main Outcomes and Measures: Description and consensus of information to be included in advance informed consent forms for early enrollment in noninferiority HABP/VABP clinical trials. Results: Suggestions from 52 stakeholders about what key informed consent concepts to include and how to explain them were used to create 3 categories to be included in an advance consent form: (1) reassurances on patient health and treatment, (2) rationale for advance consent and early enrollment, and (3) an explanation of noninferiority. At the end of the Delphi process, at least 80% consensus was reached among the 40 stakeholders who participated in the second online survey on each of the statements to include in the proposed consent text. Throughout the process, however, describing and reaching consensus on statements about noninferiority was more problematic than the other categories. Conclusions and Relevance: The stakeholders endorsed consent language to be used in combination with a strategy for enrolling patients at highest risk for pneumonia before infection onset. Data-driven consent language may help potential participants make informed decisions about their involvement in clinical research and improve enrollment rates, which are necessary to evaluate new treatments and improve patient care. The proposed consent language may be adapted for other trials using an early enrollment strategy and for noninferiority trials.

Evidence-based pregnancy testing in clinical trials: Recommendations from a multi-stakeholder development process.

Most clinical trials exclude pregnant women in order to avoid the possibility of adverse embryonic and/or fetal effects. Currently, there are no evidence-based guidelines regarding appropriate methods for identifying early pregnancy among research subjects. This lack of guidance results in wide variation in pregnancy testing plans, leading to the potential for inadequate protection against embryonic or fetal exposure in some cases and unnecessary burdens on research participants in others, as well as inefficiencies caused by disagreements among sponsors, investigators, and regulators. To address this issue, the Clinical Trials Transformation Initiative convened content experts and stakeholders to develop recommendations for pregnancy testing in clinical research based on currently available evidence. Recommendations included: 1) the study protocol should clearly state the rationale for pregnancy testing and the plan for handling positive and indeterminate tests; 2) protocols should include an assessment of the pregnancy testing plan advantages (reduced risk of embryo/fetal exposure) versus the burdens (participant burden, study team workload, costs); 3) protocols should assess the participant burdens regarding the likelihood of false negative and false positive results; 4) participant administered home pregnancy testing should be avoided in clinical trials; and 5) the consent process should describe the extent of knowledge about the study intervention's potential risk to the embryo/fetus and the limitations and consequences of pregnancy testing. CTTI has also developed an online tool to help implement these recommendations.

The Clinical Trials Transformation Initiative: Methodology supporting the mission.

The mission of the Clinical Trials Transformation Initiative, a public-private partnership co-founded by the U.S. Food and Drug Administration and Duke University, is to develop and drive adoption of practices that will increase the quality and efficiency of clinical trials. The Clinical Trials Transformation Initiative works collaboratively with key stakeholders, implements "fit-for-purpose" evidence-gathering projects, and develops actionable recommendations and tools to address the challenges faced by the clinical trials enterprise. In pursuit of its mission, The Clinical Trials Transformation Initiative follows an innovative and collaborative, five-step methodology: (1) state the problem and identify impediments to research, (2) gather evidence to identify gaps and barriers, (3) explore results by analyzing and interpreting findings, (4) finalize solutions by developing recommendations and tools, and (5) drive adoption through disseminating and implementing recommendations and tools. This article describes each step of the Clinical Trials Transformation Initiative's methodology, with a specific focus on describing the evidence-gathering activities.

Assessment of the Perceived Acceptability of an Early Enrollment Strategy Using Advance Consent in Health Care-Associated Pneumonia.

Importance: Better treatment options are needed in life-threatening infections, including health care-associated pneumonia. Enrolling patients in antibacterial clinical trials before diagnosis may circumvent existing time-to-enrollment constraints. However, the acceptability of an early enrollment strategy using advance consent is unknown. Objective: To assess the perceived acceptability of an early enrollment strategy for enrolling patients in an antibacterial clinical trial before a pneumonia diagnosis. Design, Setting, and Participants: This qualitative, descriptive study used semistructured telephone interviews. Framed within a planned noninferiority pneumonia antibiotic trial, an early enrollment strategy was described and perceptions were assessed. Using this strategy, patients give consent to enroll before developing pneumonia, to be monitored by study staff, and to be randomly assigned a study antibiotic if pneumonia develops. All interviews were audiorecorded, transcribed verbatim, and analyzed using applied thematic analysis. Fifty-two key stakeholders from across the United States, including 18 patients at risk of pneumonia, 12 caregivers, 10 representatives of institutional review boards, 7 investigators, and 5 study coordinators, were interviewed from June 20 to August 19, 2016. Main Outcomes and Measures: Perceived acceptability of the early enrollment strategy. Results: Among the 52 stakeholders interviewed (ages 29-75 years; 14 women), patients and caregivers expressed no concerns about patients being approached about participation before developing pneumonia; however, some patients may experience anxiety on learning about their risk for pneumonia. No concerns with study staff accessing patients' medical records were expressed. The clarity of consent information was important for understanding the study rather than having the condition under investigation. Among patients, caregivers, and institutional review board representatives, preferences varied regarding opt-out and precedent autonomy procedures. Nearly all patients would be willing to join a trial using the early enrollment strategy and caregivers would be willing to provide proxy consent. Institutional review board representatives were supportive of the strategy and made recommendations for the study protocol, primarily around informed consent. Investigators and study coordinators believed the strategy would not be burdensome and offered suggestions to ensure its feasibility. Conclusion and Relevance: Results of the study suggest that the early enrollment strategy is acceptable. Future research should evaluate whether the strategy improves enrollment rates in registrational pneumonia trials and in trials of other acute infection syndromes with narrow enrollment windows and/or patients with transient decisional incapacity.

Cost Drivers of a Hospital-Acquired Bacterial Pneumonia and Ventilator-Associated Bacterial Pneumonia Phase 3 Clinical Trial.

Background: Studies indicate that the prevalence of multidrug-resistant infections, including hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP), has been rising. There are many challenges associated with these disease conditions and the ability to develop new treatments. Additionally, HABP/VABP clinical trials are very costly to conduct given their complex protocol designs and the difficulty in recruiting and retaining patients. Methods: With input from clinicians, representatives from industry, and the US Food and Drug Administration, we conducted a study to (1) evaluate the drivers of HABP/VABP phase 3 direct and indirect clinical trial costs; (2) to identify opportunities to lower these costs; and (3) to compare (1) and (2) to endocrine and oncology clinical trials. Benchmark data were gathered from proprietary and commercial databases and used to create a model that calculates the fully loaded (direct and indirect) cost of typical phase 3 HABP/VABP endocrine and oncology clinical trials. Results: Results indicate that the cost per patient for a 200-site, 1000-patient phase 3 HABP/VABP study is $89600 per patient. The cost of screen failures and screen failure rates are the main cost drivers. Conclusions: Results indicate that biopharmaceutical companies and regulatory agencies should consider strategies to improve screening and recruitment to decrease HABP/VABP clinical trial costs.

Association between patient beliefs and medication adherence following hospitalization for acute coronary syndrome.

BACKGROUND: Patient adherence to medications is crucial for reducing risks following acute coronary syndrome (ACS). We assessed the degree to which medication beliefs were associated with patient adherence to ß-blockers, angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB), and lipid-lowering medications (LL) 3 months following ACS hospitalization. METHODS: We enrolled eligible ACS patients from 41 hospitals to participate in a telephone survey. The Beliefs in Medication Questionnaire-Specific was administered to assess perceived necessity for and concerns about heart medications. Three cohorts were identified for analysis: ß-blockers, ACEI/ARBs, and LL. Patients discharged on or starting the medication class after discharge were included in the cohort. The primary outcome was self-reported nonadherence to the medication class 3 months following hospitalization. Factors associated with nonadherence to each medication class were determined using logistic regression analysis. RESULTS: Overall, 973 patients were surveyed. Of these, 882 were in the ß-blocker cohort, 702 in the ACEI/ARB cohort, and 873 in the LL cohort. Nonadherence rates at 3 months were 23%, 26%, and 23%, respectively. In adjusted analyses, greater perceived necessity for heart medications was significantly associated with lower likelihood of nonadherence in all cohorts (ß-blocker: odds ratio 0.94, 95% CI 0.91-0.98; ACEI/ARB: OR 0.94, 95% CI 0.90-0.98; LL: OR 0.96, 95% CI 0.92-1.00). A greater perceived concern was significantly associated with a higher likelihood of nonadherence in all cohorts (ß-blocker: OR 1.08, 95% CI 1.04-1.13; ACEI/ARB: OR 1.07, 95% CI 1.02-1.11; LL: OR 1.09, 95% CI 1.05-1.14). CONCLUSIONS: Patients' perceived necessity for and concerns about heart medication were independently associated with adherence to 3 medication classes. Assessment of patient beliefs may be useful in clinical practice to identify those at greatest risk for nonadherence and to stimulate development of individualized interventions to change beliefs and improve adherence.

Changes in beliefs about medications during long-term care for ischemic heart disease.

BACKGROUND: Beliefs such as self-reported low necessity for medications and high concerns about medications are associated with nonadherence. Changes in these beliefs during long-term care have not previously been studied and were evaluated for purposes of this analysis. METHODS: From January 2006 through September 2007, patients at 41 hospitals who met entry criteria for the CRUSADE Quality Improvement Initiative were consented for participation in a longitudinal follow-up survey study called MAINTAIN. The patients completed The Beliefs about Medicines Questionnaire at 3 and 12 months postdischarge to assess necessity and concerns related to heart medications. Internal reliability and construct validity of the survey were evaluated at both time points. Changes in necessity and concern scores from 3 to 12 months were determined, and factors associated with negative changes were explored. RESULTS: A total of 812 patients completed both surveys. Internal reliability and construct validity were good. From 3 to 12 months, only 9.2% of patients shifted from a high to low necessity score; however, 20.7% of patients shifted from a low to high concern score. Factors found to be statistically significantly and independently associated with increased concern were the perception that the provider did not listen carefully to the patient (odds ratio [OR] 2.63, 95% CI 1.49-4.76), depression at 12 months (OR 2.95, 95% CI 1.57-5.55), hospital discharge with > or =7 medications (OR 1.71, 95% CI 1.07-2.74), and not receiving a medication list/instructions at hospital discharge (OR 1.69, 95% CI 1.05, 2.78). Factors associated with decreased necessity included not having a cardiologist (OR 2.26, 95% CI 1.34-3.83) and nonpersistence at 12 months with lipid-lowering medication (OR 1.85, 95% CI 1.01-3.45). CONCLUSIONS: One third of the patients reported a negative change in their beliefs about heart medications. Although some changes were observed in perceived necessity, negative changes in concerns occurred in 1 of every 5 patients. Interventions that address these concerns may be useful in improving adherence and clinical outcomes.