Transcatheter mitral valve repair for functional mitral regurgitation: Evaluating the evidence.

OBJECTIVES: Two trials (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation Trial and Percutaneous Repair with the MitraClip Device for Severe Functional/Secondary Mitral Regurgitation Trial) were published in 2018 evaluating the effectiveness and safety of transcatheter repair for patients with heart failure with significant functional mitral regurgitation, which yielded different results. This article reviews the strength of the evidence, differences in trial designs, ethical and implementation implications, and delineates future research needs to help guide the appropriate dissemination of transcatheter repair for functional patients with mitral regurgitation. METHODS: The National Heart, Lung, and Blood Institute convened a workshop of interdisciplinary experts to address these objectives. RESULTS: Transcatheter repair of functional mitral regurgitation can provide significant benefits in terms of heart failure hospitalizations, survival, and quality of life when appropriate heart failure candidates with moderate to severe or severe mitral regurgitation while on optimal guideline-directed medical therapy can be identified. Key ingredients for success are preoperative evaluation and management and postoperative care by an interdisciplinary heart team. CONCLUSIONS: Given the discordance observed between trials, ongoing innovation in patient management, and potential expansion of indications for use, the evidence base must be expanded to optimize appropriate implementation of this complex therapy. This will require more complete capture of outcome data in real-world settings for all eligible candidates whether or not they receive this therapy. Inevitably, the indications for use of this therapy will expand, as will the devices and therapeutic approaches for this population, necessitating the study of comparative effectiveness through randomized trials or observational studies. Moreover, given the substantial variations in care delivery, conducting implementation research to delineate characteristics of the optimal care model would be of benefit.

Show Me the Money: Patients' Perspectives on a Decision Aid for Sacubitril/Valsartan Addressing Out-of-Pocket Cost.

BACKGROUND: Out-of-pocket medication costs for patients who have heart failure with reduced ejection fraction may be an important part of shared decision-making, but cost has generally been excluded from clinical discussions. This study reports patients' perspectives on a decision aid for sacubitril/valsartan that explicitly addresses out-of-pocket costs. METHODS: Structured, in-depth interviews were conducted with 20 patients with heart failure with reduced ejection fraction from 2 medical centers to elicit their views on a publicly available decision aid for sacubitril/valsartan that explicitly incorporates considerations related to out-of-pocket costs. Qualitative descriptive analysis was conducted. RESULTS: Key themes identified were general enthusiasm for decision aids for medication decisions, openness on the part of patients to incorporation of cost into decision-making and the decision aid, requests for greater specificity regarding patient-specific cost, and challenges communicating evidence of benefit in a way that allows patients to make cost-benefit analyses for themselves. Patients also raised questions regarding logistical challenges of incorporating a decision aid into the normal clinical and decision-making workflow. CONCLUSIONS: Patients were receptive to the inclusion of out-of-pocket cost as relevant in a decision aid for sacubitril/valsartan. Key challenges to effective integration of cost in these decisions include developing mechanisms for acquiring reliable patient-specific cost estimates and addressing patients' difficulties (and sometimes skepticism) applying trial evidence to their own situation. In addition, implementation strategies are important to develop to facilitate decision aid integration for routine medical decisions into clinic workflow.

Potential Unintended Consequences Of Recent Shared Decision Making Policy Initiatives.

Shared decision making (SDM)-when clinicians and patients make medical decisions together-is moving swiftly from an ethical ideal toward widespread clinical implementation affecting millions of patients through recent policy initiatives. We argue that policy initiatives to promote SDM implementation in clinical practice carry the risk of several unintended negative consequences if limitations in defining and measuring SDM are not addressed. We urge policy makers to include prespecified definitions of desired outcomes, offer guidance on the tools used to measure SDM in the multitude of contexts in which it occurs, evaluate the impact of SDM policy initiatives over time, review that impact at regular intervals, and revise SDM measurement tools as needed.

Ethical Acceptability of Postrandomization Consent in Pragmatic Clinical Trials.

Importance: Pragmatic clinical trials that seek informed consent after randomization (ie, postrandomization consent) are increasingly used, but debate on ethics persists because control arm patients are not specifically informed about the trials and randomization occurs before consent for the trials. The public's attitude toward postrandomization consent trials is unknown, but the way the trials are described could bias people's views. Objectives: To assess the attitudes of the US general public toward postrandomization informed consent for pragmatic trials and to measure potential framing and other factors associated with those attitudes. Design, Setting, and Participants: An online, 2 × 2 experimental survey (fielded between February 23 and April 3, 2018) portraying 4 scenarios of postrandomization informed consent (with prior broad consent for medical record use) was conducted. These scenarios included traditional randomized clinical trial language framing vs alternative framing in a high-stakes trial (ie, survival in leukemia) or low-stakes trial (ie, blood glucose level in diabetes). A total of 3793 individuals invited to participate were part of an existing panel representative of the US general public (GfK KnowledgePanel). Main Outcomes and Measures: The proportion of participants who would recommend that an ethics review board approve a postrandomization consent pragmatic trial. Results: A total of 2042 of 3739 invitees (54.6%) responded; after exclusion of 38 incomplete surveys, 2004 participants were included in the analysis. Of these, 997 (49.8%) were women, 1440 (71.9%) were white non-Hispanic, 199 (9.9%) were black non-Hispanic, and 233 (11.6%) were Hispanic. Mean (SD) age was 47.5 (17.4) years. Across scenarios, weighted data showed that 75.4% of the participants would recommend approval of the postrandomization consent pragmatic trial, 20.4% would probably not recommend approval, and 4.2% would definitely not recommend approval. Approval was not sensitive to framing language (traditional vs new framing in high-stakes scenario, 74.3% vs 76.8%, P = .40; in low-stakes scenario, 77.7% vs 72.9%, P = .10) or to the stakes (low vs high stakes in traditional framing, 77.7% vs 74.3%, P = .25; in new framing, 72.9% vs 76.8%, P = .18). Better understanding of the postrandomization consent design was associated with higher rate of approval (78.1% vs 65.0%, P = .002 for high-stakes scenario; 77.2% vs 64.9%, P = .004 for low-stakes scenario), especially among those with less education. However, opinions about personal involvement in the control arm were more cautious (range depending on scenario, 45.6%-59.7%) and sensitive to stakes but not to framing. Conclusions and Relevance: The public's generally high rate of approval of the ethics of postrandomization informed consent for pragmatic trial designs does not appear to be affected by whether postrandomization consent design is framed using traditional randomized clinical trial terminology, regardless of the stakes of the trial. Promoting better understanding of the design may increase its acceptance by the public.

Does experience matter? Implications for community consultation for research in emergency settings.

BACKGROUND: Community consultation (CC) is required for research in emergency settings using an exception from informed consent (EFIC) in the United States, but uncertainty persists regarding best CC practices. There is ongoing debate about whom to include in CC, specifically, whether to prioritize geographically defined communities or individuals with connections to the condition. Understanding the impact of personal disease experience on views of EFIC research is important for designing CC and interpreting its results. METHODS: This study was a secondary analysis of surveys administered to 2612 participants at 12 sites in CC events conducted for ProTECT III: Progesterone for Traumatic Brain Injury, a Phase III, randomized trial conducted using EFIC. Key survey domains included personal traumatic brain injury (TBI) experience, demographic information, and acceptance of both hypothetical personal enrollment under EFIC and the use of EFIC in general in ProTECT III. Descriptive statistics and multivariable regression models were used to explore relationships between key domains. RESULTS: TBI patients, those with family members/loved ones with TBI, and those who knew someone else with TBI were slightly more accepting of hypothetical personal enrollment under EFIC (adjusted odds ratio [OR] 1.14 [0.78-1.67], 1.54 [1.17-2.02], and 1.51 [1.19-1.92], respectively) and use of EFIC in general (adjusted OR 1.17 [0.83-1.64], 1.39 [1.08-1.77], and 1.06 [0.86-1.31], respectively) than those without this. In a subgroup analysis based on race, white participants with any disease experience had higher levels of acceptance of EFIC, as expected. However, there was numerically lower acceptance of personal and general EFIC enrollment among black participants with closer TBI connections. CONCLUSIONS: Personal TBI experience was associated with increased acceptance of EFIC research for that condition, except among black participants. Heterogeneity of the effect of personal disease experience on EFIC views further supports inclusion of individuals with relevant disease experience in CC and highlights the importance of engaging minority participants.

Impact of individual clinical outcomes on trial participants' perspectives on enrollment in emergency research without consent.

BACKGROUND: Evidence suggests that patients are generally accepting of their enrollment in trials for emergency care conducted under exception from informed consent. It is unknown whether individuals with more severe initial injuries or worse clinical outcomes have different perspectives. Determining whether these differences exist may help to structure post-enrollment interactions. METHODS: Primary clinical data from the Progesterone for the Treatment of Traumatic Brain Injury trial were matched to interview data from the Patients' Experiences in Emergency Research-Progesterone for the Treatment of Traumatic Brain Injury study. Answers to three key questions from Patients' Experiences in Emergency Research-Progesterone for the Treatment of Traumatic Brain Injury study were analyzed in the context of enrolled patients' initial injury severity (initial Glasgow Coma Scale and Injury Severity Score) and principal clinical outcomes (Extended Glasgow Outcome Scale and Extended Glasgow Outcome Scale relative to initial injury severity). The three key questions from Patients' Experiences in Emergency Research-Progesterone for the Treatment of Traumatic Brain Injury study addressed participants' general attitude toward inclusion in the Progesterone for the Treatment of Traumatic Brain Injury trial (general trial inclusion), their specific attitude toward being included in Progesterone for the Treatment of Traumatic Brain Injury trial under the exception from informed consent (personal exception from informed consent enrollment), and their attitude toward the use of exception from informed consent in the Progesterone for the Treatment of Traumatic Brain Injury trial in general (general exception from informed consent enrollment). Qualitative analysis of interview transcripts was performed to provide contextualization and to determine the extent to which respondents framed their attitudes in terms of clinical experience. RESULTS: Clinical data from Progesterone for the Treatment of Traumatic Brain Injury trial were available for all 74 patients represented in the Patients' Experiences in Emergency Research-Progesterone for the Treatment of Traumatic Brain Injury study (including 46 patients for whom the surrogate was interviewed due to the patient's cognitive status or death). No significant difference was observed regarding acceptance of general trial inclusion or acceptance of general exception from informed consent enrollment between participants with favorable neurological outcomes and those with unfavorable outcomes relative to initial injury. Agreement with personal enrollment in Progesterone for the Treatment of Traumatic Brain Injury trial under exception from informed consent, however, was significantly higher among participants with favorable outcomes compared to those with unfavorable outcomes (89% vs 59%, p = 0.003). There was also a statistically significant relationship between more severe initial injury and increased acceptance of personal exception from informed consent enrollment ( p = 0.040) or general exception from informed consent use ( p = 0.034) in Progesterone for the Treatment of Traumatic Brain Injury trial. Many individuals referenced personal experience as a basis for their attitudes, but these references were not used to support negative views. CONCLUSION: Patients and surrogates of patients with unfavorable clinical outcomes were somewhat less accepting of their own inclusion in the Progesterone for the Treatment of Traumatic Brain Injury trial under exception from informed consent than were patients or surrogates of patients with favorable clinical outcomes. These findings suggest a need to identify optimal strategies for communicating with patients and their surrogates regarding exception from informed consent enrollment when clinical outcomes are poor.

Patients' perspectives of enrollment in research without consent: the patients' experiences in emergency research-progesterone for the treatment of traumatic brain injury study.

OBJECTIVE: Research in acute illness often requires an exception from informed consent. Few studies have assessed the views of patients enrolled in exception from informed consent trials. This study was designed to assess the views of patients and their surrogates of exception from informed consent enrollment within the context of a randomized, placebo-controlled trial of an investigational agent for traumatic brain injury. DESIGN: Interactive interview study. SETTING: Nested within the Progesterone for the Treatment of Traumatic Brain Injury trial, a Phase III randomized controlled trial in acute traumatic brain injury. SUBJECTS: Patients and surrogates (for patients incapable of being interviewed) enrolled in Progesterone for the Treatment of Traumatic Brain Injury under exception from informed consent at 12 sites. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Interviews focused on respondents' acceptance of exception from informed consent enrollment in Progesterone for the Treatment of Traumatic Brain Injury, use of placebo and randomization, understanding of major study elements, and views regarding regulatory protections. Descriptive statistical analysis was performed; textual data were analyzed thematically. Eighty-five individuals were interviewed. Eighty-four percent had positive attitudes toward Progesterone for the Treatment of Traumatic Brain Injury inclusion. Seventy-eight percent found their inclusion under exception from informed consent acceptable, and 72% found use of exception from informed consent in Progesterone for the Treatment of Traumatic Brain Injury acceptable in general. Only two respondents clearly disagreed with both personal and general exception from informed consent enrollment. The most common concerns (26%) related to absence of consent. Eighty percent and 92% were accepting of placebo use and randomization, respectively. Although there were few black respondents (n = 11), they were less accepting of personal exception from informed consent enrollment than white respondents (55% vs 83%; p = 0.0494). CONCLUSIONS: Acceptance of exception from informed consent in this placebo-controlled trial of an investigational agent was high and exceeded acceptance among community consultation participants. Exception from informed consent enrollment appears generally consistent with patients' preferences.

Patient-centered imaging: shared decision making for cardiac imaging procedures with exposure to ionizing radiation.

The current paper details the recommendations arising from an NIH-NHLBI/NCI-sponsored symposium held in November 2012, aiming to identify key components of a radiation accountability framework fostering patient-centered imaging and shared decision-making in cardiac imaging. Symposium participants, working in 3 tracks, identified key components of a framework to target critical radiation safety issues for the patient, the laboratory, and the larger population of patients with known or suspected cardiovascular disease. The use of ionizing radiation during an imaging procedure should be disclosed to all patients by the ordering provider at the time of ordering, and reinforced by the performing provider team. An imaging protocol with effective dose ≤3 mSv is considered very low risk, not warranting extensive discussion or written informed consent. However, a protocol effective dose >20 mSv was proposed as a level requiring particular attention in terms of shared decision-making and either formal discussion or written informed consent. Laboratory reporting of radiation dosimetry is a critical component of creating a quality laboratory fostering a patient-centered environment with transparent procedural methodology. Efforts should be directed to avoiding testing involving radiation, in patients with inappropriate indications. Standardized reporting and diagnostic reference levels for computed tomography and nuclear cardiology are important for the goal of public reporting of laboratory radiation dose levels in conjunction with diagnostic performance. The development of cardiac imaging technologies revolutionized cardiology practice by allowing routine, noninvasive assessment of myocardial perfusion and anatomy. It is now incumbent upon the imaging community to create an accountability framework to safely drive appropriate imaging utilization.