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2.
JACC Heart Fail ; 9(1): 1-12, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33309582

RESUMO

The treatment of heart failure with reduced ejection fraction (HFrEF) has changed considerably over time, particularly with the sequential development of therapies aimed at antagonism of maladaptive biologic pathways, including inhibition of the sympathetic nervous system and the renin-angiotensin aldosterone system. The sequential nature of earlier HFrEF trials allowed the integration of new therapies tested against the background therapy of the time. More recently, multiple heart failure therapies are being evaluated simultaneously, and the number of therapeutic choices for treating HFrEF has grown considerably. In addition, implementation science has lagged behind discovery science in heart failure. Furthermore, given there are currently >200 ongoing clinical trials in heart failure, further complexities are anticipated. In an effort to provide a decision-making framework in the current era of expanding therapeutic options in HFrEF, the Heart Failure Collaboratory convened a multi-stakeholder group, including patients, clinicians, clinical investigators, the U.S. Food and Drug Administration, industry, and payers who met at the U.S. Food and Drug Administration campus on March 6, 2020. This paper summarizes the discussions and expert consensus recommendations.

3.
Clin Pharmacol Ther ; 2020 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-33278832

RESUMO

Chronic kidney disease (CKD) is a common comorbidity among patients taking direct-acting oral anticoagulants (DOACs). Herein, we evaluate the influence of kidney function on Stroke/SEE, hemorrhage and composite endpoints (Stroke/SEE/hemorrhage/death and Stroke/SEE/death) among patients on DOACs and warfarin. Baseline kidney function was categorized as GFR≥60 (reference), 45-59 and <45ml/min/1.73m2 for participants in the RE-LY (n=18,049), ARISTOTLE (n=18,187), and ENGAGE AF (n=20,798) trials. Incidence of events was compared across GFR categories. Hazard ratios for events was estimated using Cox regression using intention-to-treat analysis adjusting for known predictors. A large proportion of participants had GFR<60 (25-29% had GFR ≥45<60 and 9.5 to 12.6% with GFR <45). Compared to patients with GFR≥60, warfarin users across the trials with GFR≥45-59 and GFR<45 had a higher incidence of hemorrhage (p-values<0.0001) and warfarin users in the ARISTOTLE and ENGAGE trials had higher incidence of stroke/SEE (p-values ≤0.05). Compared to patients with GFR≥60, dabigatran users with GFR≥45-59 and GFR<45 had a higher incidence of stroke/SEE (p≤0.02), hemorrhage (p<0.001) and both composite endpoints (p<0.0001). Compared to patients with GFR≥60, apixaban and edoxaban users with GFR≥45-59 and GFR<45 had a higher incidence of hemorrhage (p-values≤0.05) and composite endpoints (p-values≤0.05). After adjustment, compared to patients with GFR≥60, warfarin users with GFR<60 in the ARISTOTLE and RELY trials had a higher risk of hemorrhage (p<0.05), as did dabigatran (p<0.001) and edoxaban (p≤0.005) users, while apixaban users did not exhibit an increased risk (p=0.08 GFR≥45-59; p=0.71 GFR<45). Kidney function significantly influences the safety and efficacy of oral anticoagulants.

4.
J Am Coll Cardiol ; 76(20): 2368-2378, 2020 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-33183511

RESUMO

The coronavirus disease-2019 (COVID-19) pandemic has profoundly changed clinical care and research, including the conduct of clinical trials, and the clinical research ecosystem will need to adapt to this transformed environment. The Heart Failure Academic Research Consortium is a partnership between the Heart Failure Collaboratory and the Academic Research Consortium, composed of academic investigators from the United States and Europe, patients, the U.S. Food and Drug Administration, the National Institutes of Health, and industry members. A series of meetings were convened to address the challenges caused by the COVID-19 pandemic, review options for maintaining or altering best practices, and establish key recommendations for the conduct and analysis of clinical trials for cardiovascular disease and heart failure. This paper summarizes the discussions and expert consensus recommendations.


Assuntos
Ensaios Clínicos como Assunto , Infecções por Coronavirus , Pandemias , Pneumonia Viral , Determinação de Ponto Final , Humanos , Fatores Socioeconômicos , Estatística como Assunto
5.
Circulation ; 142(20): 1974-1988, 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33196311

RESUMO

Balancing benefits and risks is a complex task that poses a major challenge, both to the approval of new medicines and devices by regulatory authorities and in therapeutic decision-making in practice. Several analysis methods and visualization tools have been developed to help evaluate and communicate whether the benefit-risk profile is favorable or unfavorable. In this White Paper, we describe approaches to benefit-risk assessment using qualitative approaches such as the Benefit Risk Action Team framework developed by the Pharmaceutical Research and Manufacturers of America, and the Benefit-Risk Framework developed by the United States Food and Drug Administration; and quantitative approaches such as the numbers needed to treat for benefit and harm, the benefit-risk ratio, and Incremental Net Benefit. We give illustrative examples of benefit-risk evaluations using 4 treatment interventions including sodium glucose cotransporter 2 inhibitors in patients with type 2 diabetes; a direct antithrombin agent, dabigatran, for reducing stroke and systemic embolism in patients with nonvalvular atrial fibrillation; transcatheter aortic valve replacement in patients with symptomatic severe aortic valve stenosis; and antiplatelet agents vorapaxar and prasugrel for reducing cardiovascular events in patients at high cardiovascular risk. Regular applications of structured benefit-risk assessment, whether qualitative, quantitative, or both, enabled by easy-to-understand graphical presentations that capture uncertainties around the benefit-risk metric, may aid shared decision-making and enhance transparency of those decisions.

6.
JACC Heart Fail ; 8(12): 961-972, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33199251

RESUMO

The Heart Failure Academic Research Consortium is a partnership between the Heart Failure Collaboratory (HFC) and Academic Research Consortium (ARC), comprised of leading heart failure (HF) academic research investigators, patients, United States (US) Food and Drug Administration representatives, and industry members from the US and Europe. A series of meetings were convened to establish definitions and key concepts for the evaluation of HF therapies including optimal medical and device background therapy, clinical trial design elements and statistical concepts, and study endpoints. This manuscript summarizes the expert panel discussions as consensus recommendations focused on populations and endpoint definitions; it is not exhaustive or restrictive, but designed to stimulate HF clinical trial innovation.

7.
Eur J Heart Fail ; 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33017862

RESUMO

The Heart Failure Academic Research Consortium is a partnership between the Heart Failure Collaboratory (HFC) and Academic Research Consortium (ARC), comprised of leading heart failure (HF) academic research investigators, patients, United States (US) Food and Drug Administration representatives, and industry members from the US and Europe. A series of meetings were convened to establish definitions and key concepts for the evaluation of HF therapies including optimal medical and device background therapy, clinical trial design elements and statistical concepts, and study endpoints. This manuscript summarizes the expert panel discussions as consensus recommendations focused on populations and endpoint definitions; it is not exhaustive or restrictive, but designed to stimulate HF clinical trial innovation.

8.
Ther Innov Regul Sci ; 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32870460

RESUMO

BACKGROUND: Uncertain ascertainment of events in clinical trials has been noted for decades. To correct possible bias, Clinical Endpoint Committees (CECs) have been employed as a critical element of trials to ensure consistent and high-quality endpoint evaluation, especially for cardiovascular endpoints. However, the efficiency and usefulness of adjudication have been debated. METHODS: The multiple imputation (MI) method was proposed to incorporate endpoint event uncertainty. In a simulation conducted to explain this methodology, the dichotomous outcome was imputed each time with subject-specific event probabilities. As the final step, the desired analysis was conducted based on all imputed data. This proposed method was further applied to real trial data from PARADIGM-HF. RESULTS: Compared with the conventional Cox model with adjudicated events only, the Cox MI method had higher power, even with a small number of uncertain events. It yielded more robust inferences regarding treatment effects and required a smaller sample size to achieve the same power. CONCLUSIONS: Instead of using dichotomous endpoint data, the MI method enables incorporation of event uncertainty and eliminates the need for categorizing endpoint events. In future trials, assigning a probability of event occurrence for each event may be preferable to a CEC assigning a dichotomous outcome. Considerable resources could be saved if endpoint events can be identified more simply and in a manner that maintains study power.

9.
Artigo em Inglês | MEDLINE | ID: mdl-32937078

RESUMO

RATIONALE: Event-driven primary endpoints are increasingly used in pulmonary arterial hypertension clinical trials, substantially increasing required sample sizes and trial lengths. The U.S. Food and Drug Administration advocates the use of prognostic enrichment of clinical trials by preselecting a patient population with increased likelihood of experiencing the trial's primary endpoint. OBJECTIVE: This study compares validated clinical scales of risk (COMPERA, the French score, and REVEAL 2.0) to identify patients that are likely to experience a clinical worsening event for trial enrichment. METHODS: Baseline data from three pulmonary arterial hypertension clinical trials (AMBITION, SERAPHIN, and GRIPHON) were pooled and standardized. Receiver-operating curves were used to measure each algorithm's performance in predicting clinical worsening within the pooled placebo cohort. Power simulations were conducted to determine sample size and treatment time reductions for multiple enrichment strategies. A cost analysis was performed to illustrate potential financial savings by applying enrichment to GRIPHON. MEASUREMENTS AND RESULTS: All risk algorithms were compared using area under the receiver-operating curve and substantially outperformed prediction per New York Heart Association Functional Class. REVEAL 2.0's risk grouping provided the greatest time and sample size savings in AMBITION and GRIPHON for all enrichment strategies but lacked appropriate inputs (i.e., N-terminal-proB-type natriuretic peptide) to perform as well in SERAPHIN. Cost analysis applied to GRIPHON demonstrated the greatest financial benefit by enrolling patients with a REVEAL score ≥8. CONCLUSION: This preliminary study demonstrates the feasibility of risk algorithms for pulmonary arterial hypertension trial enrichment and a need for further investigation.

10.
J Am Coll Cardiol ; 76(12): 1468-1483, 2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32943165

RESUMO

Investigating the balance of risk for thrombotic and bleeding events after percutaneous coronary intervention (PCI) is especially relevant for patients at high bleeding risk (HBR). The Academic Research Consortium for HBR recently proposed a consensus definition in an effort to standardize the patient population included in HBR trials. The aim of this consensus-based document, the second initiative from the Academic Research Consortium for HBR, is to propose recommendations to guide the design of clinical trials of devices and drugs in HBR patients undergoing PCI. The authors discuss the designs of trials in HBR patients undergoing PCI and various aspects of trial design specific to HBR patients, including target populations, intervention and control groups, primary and secondary outcomes, and timing of endpoint reporting.

11.
JACC Heart Fail ; 8(6): 429-440, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32278679

RESUMO

Heart failure (HF) patients experience a high burden of symptoms and functional limitations, and morbidity and mortality remain high despite successful therapies. The majority of HF drugs in the United States are approved for reducing hospitalization and mortality, while only a few have indications for improving quality of life, physical function, or symptoms. Patient-reported outcomes that directly measure patient's perception of health status (symptoms, physical function, or quality of life) are potentially approvable endpoints in drug development. This paper summarizes the history of endpoints used for HF drug approvals in the United States and reviews endpoints that measure symptoms, physical function, or quality of life in HF patients.

12.
Toxicol Sci ; 174(2): 254-265, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32040191

RESUMO

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) hold great potential for personalized cardiac safety prediction, particularly for that of drug-induced proarrhythmia. However, hiPSC-CMs fire spontaneously and the variable beat rates of cardiomyocytes can be a confounding factor that interferes with data interpretation. Controlling beat rates with pacing may reduce batch and assay variations, enable evaluation of rate-dependent drug effects, and facilitate the comparison of results obtained from hiPSC-CMs with those from adult human cardiomyocytes. As electrical stimulation (E-pacing) of hiPSC-CMs has not been validated with high-throughput assays, herein, we compared the responses of hiPSC-CMs exposed with classic cardiac ion channel blockers under spontaneous beating and E-pacing conditions utilizing microelectrode array technology. We found that compared with spontaneously beating hiPSC-CMs, E-pacing: (1) reduced overall assay variabilities, (2) showed limited changes of field potential duration to pacemaker channel block, (3) revealed reverse rate dependence of multiple ion channel blockers on field potential duration, and (4) eliminated the effects of sodium channel block on depolarization spike amplitude and spike slope due to a software error in acquiring depolarization spike at cardiac pacing mode. Microelectrode array optogenetic pacing and current clamp recordings at various stimulation frequencies demonstrated rate-dependent block of sodium channels in hiPSC-CMs as reported in adult cardiomyocytes. In conclusion, pacing enabled more accurate rate- and concentration-dependent drug effect evaluations. Analyzing responses of hiPSC-CMs under both spontaneously beating and rate-controlled conditions may help better assess the effects of test compounds on cardiac electrophysiology and evaluate the value of the hiPSC-CM model.

13.
Am Heart J ; 219: 1-8, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31707323
14.
Clin Pharmacol Ther ; 107(1): 102-111, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31709525

RESUMO

This white paper presents principles for validating proarrhythmia risk prediction models for regulatory use as discussed at the In Silico Breakout Session of a Cardiac Safety Research Consortium/Health and Environmental Sciences Institute/US Food and Drug Administration-sponsored Think Tank Meeting on May 22, 2018. The meeting was convened to evaluate the progress in the development of a new cardiac safety paradigm, the Comprehensive in Vitro Proarrhythmia Assay (CiPA). The opinions regarding these principles reflect the collective views of those who participated in the discussion of this topic both at and after the breakout session. Although primarily discussed in the context of in silico models, these principles describe the interface between experimental input and model-based interpretation and are intended to be general enough to be applied to other types of nonclinical models for proarrhythmia assessment. This document was developed with the intention of providing a foundation for more consistency and harmonization in developing and validating different models for proarrhythmia risk prediction using the example of the CiPA paradigm.


Assuntos
Arritmias Cardíacas/induzido quimicamente , Simulação por Computador , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Medição de Risco/métodos , Arritmias Cardíacas/prevenção & controle , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Humanos , Modelos Teóricos , Estudos de Validação como Assunto
15.
Circulation ; 140(25): 2108-2118, 2019 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-31841369

RESUMO

Following regulatory guidance set forth in 2008 by the US Food and Drug Administration for new drugs for type 2 diabetes mellitus, many large randomized, controlled trials have been conducted with the primary goal of assessing the safety of antihyperglycemic medications on the primary end point of major adverse cardiovascular events, defined as cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Heart failure (HF) was not specifically mentioned in the US Food and Drug Administration guidance and therefore it was not a focus of these studies when planned. Several trials subsequently showed the impact of antihyperglycemic drugs on HF outcomes, which were not originally specified as the primary end point of the trials. The most impressive finding has been the substantial and consistent risk reduction in HF hospitalization seen across 4 trials of sodium glucose cotransporter 2 inhibitors. However, to date, these results have not led to regulatory approval of any of these drugs for a HF indication or a recommendation for use by US HF guidelines. It is therefore important to explore to what extent persuasive treatment effects on nonprimary end points can be used to support regulatory claims and guideline recommendations. This topic was discussed by researchers, clinicians, industry sponsors, regulators, and representatives from professional societies, who convened on the US Food and Drug Administration campus on March 6, 2019. This report summarizes these discussions and the key takeaway messages from this meeting.


Assuntos
Ensaios Clínicos como Assunto/métodos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Insuficiência Cardíaca/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Determinação de Ponto Final , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/epidemiologia , Humanos , Relatório de Pesquisa/normas , Transportador 2 de Glucose-Sódio/sangue , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Resultado do Tratamento
16.
Sci Rep ; 9(1): 15060, 2019 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-31636317

RESUMO

Drug-induced changes of the J to T peak (JTp) and J to the median of area under the T wave (JT50) were reported to differentiate QT prolonging drugs that are predominant blockers of the delayed potassium rectifier current from those with multiple ion channel effects. Studies of drug-induced JTp/JT50 interval changes might therefore facilitate cardiac safety evaluation of new pharmaceuticals. It is not known whether formulas for QT heart rate correction are applicable to JTp and JT50 intervals. QT/RR, JTp/RR, and JT50/RR profiles were studied in 523 healthy subjects aged 33.5 ± 8.4 years (254 females). In individual subjects, 1,256 ± 220 electrocardiographic measurements of QT, JTp, and JT50 intervals were available including a 5-minute history of RR intervals preceding each measurement. Curvilinear, linear and log-linear regression models were used to characterize individual QT/RR, JTp/RR, and JT50/RR profiles both without and with correction for heart rate hysteresis. JTp/RR and JT50/RR hysteresis correction needs to be included but the generic universal correction for QT/RR hysteresis is also applicable to JTp/RR and JT50/RR profiles. Once this is incorporated, median regression coefficients of the investigated population suggest linear correction formulas JTpc = JTp + 0.150(1-RR) and JT50c = JT50 + 0.117(1-RR) where RR intervals of the underlying heart rate are hysteresis-corrected, and all measurements expressed in seconds. The established correction formulas can be proposed for future clinical pharmacology studies that show drug-induced heart rate changes of up to approximately 10 beats per minute.

17.
Circulation ; 140(17): 1426-1436, 2019 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-31634011

RESUMO

The complexity and costs associated with traditional randomized, controlled trials have increased exponentially over time, and now threaten to stifle the development of new drugs and devices. Nevertheless, the growing use of electronic health records, mobile applications, and wearable devices offers significant promise for transforming clinical trials, making them more pragmatic and efficient. However, many challenges must be overcome before these innovations can be implemented routinely in randomized, controlled trial operations. In October of 2018, a diverse stakeholder group convened in Washington, DC, to examine how electronic health record, mobile, and wearable technologies could be applied to clinical trials. The group specifically examined how these technologies might streamline the execution of clinical trial components, delineated innovative trial designs facilitated by technological developments, identified barriers to implementation, and determined the optimal frameworks needed for regulatory oversight. The group concluded that the application of novel technologies to clinical trials provided enormous potential, yet these changes needed to be iterative and facilitated by continuous learning and pilot studies.


Assuntos
Ensaios Clínicos como Assunto , Registros Eletrônicos de Saúde , Aplicativos Móveis , Dispositivos Eletrônicos Vestíveis , Humanos , Projetos de Pesquisa
18.
Circ Res ; 125(9): 855-867, 2019 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-31600125

RESUMO

Given that cardiovascular safety concerns remain the leading cause of drug attrition at the preclinical drug development stage, the National Center for Toxicological Research of the US Food and Drug Administration hosted a workshop to discuss current gaps and challenges in translating preclinical cardiovascular safety data to humans. This white paper summarizes the topics presented by speakers from academia, industry, and government intended to address the theme of improving cardiotoxicity assessment in drug development. The main conclusion is that to reduce cardiovascular safety liabilities of new therapeutic agents, there is an urgent need to integrate human-relevant platforms/approaches into drug development. Potential regulatory applications of human-derived cardiomyocytes and future directions in employing human-relevant platforms to fill the gaps and overcome barriers and challenges in preclinical cardiovascular safety assessment were discussed. This paper is intended to serve as an initial step in a public-private collaborative development program for human-relevant cardiotoxicity tools, particularly for cardiotoxicities characterized by contractile dysfunction or structural injury.


Assuntos
Cardiotoxicidade/epidemiologia , Cardiotoxinas/toxicidade , Educação/normas , Relatório de Pesquisa/normas , United States Food and Drug Administration/normas , Animais , Cardiotoxicidade/prevenção & controle , Avaliação Pré-Clínica de Medicamentos/métodos , Avaliação Pré-Clínica de Medicamentos/normas , Avaliação Pré-Clínica de Medicamentos/tendências , Educação/tendências , Humanos , Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos , Células-Tronco Pluripotentes Induzidas/patologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Relatório de Pesquisa/tendências , Estados Unidos/epidemiologia , United States Food and Drug Administration/tendências
19.
Front Physiol ; 10: 934, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31402872

RESUMO

Electrocardiogram (ECG) studies of drug-induced prolongation of the interval between the J point and the peak of the T wave (JTp interval) distinguished QT prolonging drugs that predominantly block the delayed potassium rectifier current from those affecting multiple cardiac repolarisation ion channel currents. Since the peak of the T wave depends on ECG lead, a "global" T peak requires to combine ECG leads into one-dimensional signal in which the T wave peak can be measured. This study aimed at finding the optimum one-dimensional representation of 12-lead ECGs for the most stable JTp measurements. Seven different one-dimensional representations were investigated including the vector magnitude of the orthogonal XYZ transformation, root mean square of all 12 ECG leads, and the vector magnitude of the 3 dominant orthogonal leads derived by singular value decomposition. All representations were applied to the median waveforms of 660,657 separate 10-s 12-lead ECGs taken from repeated day-time Holter recordings in 523 healthy subjects aged 33.5 ± 8.4 years (254 women). The JTp measurements were compared with the QT intervals and with the intervals between the J point and the median point of the area under the T wave one-dimensional representation (JT50 intervals) by means of calculating the residuals of the subject-specific curvilinear regression models relating the measured interval to the hysteresis-corrected RR interval of the underlying heart rate. The residuals of the regression models (equal to the intra-subject standard deviations of individually heart rate corrected intervals) expressed intra-subject stability of interval measurements. For both the JTp intervals and the JT50 intervals, the curvilinear regression residuals of measurements derived from the orthogonal XYZ representation were marginally but statistically significantly lower compared to the other representations. Using the XYZ representation, the residuals of the QT/RR, JTp/RR and JT50/RR regressions were 5.6 ± 1.1 ms, 7.2 ± 2.2 ms, and 4.9 ± 1.2 ms, respectively (all statistically significantly different; p < 0.0001). The study concludes that the orthogonal XYZ ECG representation might be proposed for future investigations of JTp and JT50 intervals. If the ability of classifying QT prolonging drugs is further confirmed for the JT50 interval, it might be appropriate to replace the JTp interval since with JT50 it appears more stable.

20.
JACC Heart Fail ; 7(11): 913-921, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31401097

RESUMO

The development of treatments for heart failure (HF) is challenged by burdensome clinical trials. Reducing the need for extensive data collection and increasing opportunities for data compatibility between trials may improve efficiency and reduce resource burden. The Heart Failure Collaboratory (HFC) multi-stakeholder consortium sought to create a lean case report form (CRF) for use in HF clinical trials evaluating cardiac devices. The HFC convened patients, clinicians, clinical researchers, the U.S. Food and Drug Administration (FDA), payers, industry partners, and statisticians to create a consensus core CRF. Eight recent clinical trial CRFs for the treatment of HF from 6 industry partners were analyzed. All CRF elements were systematically reviewed. Those elements deemed critical for data collection in HF clinical trials were used to construct the final, harmonized CRF. The original CRFs included 176 distinct data items covering demographics, vital signs, physical examination, medical history, laboratory and imaging testing, device therapy, medications, functional and quality of life assessment, and outcome events. The resulting, minimally inclusive CRF device contains 75 baseline data items and 6 events, with separate modular additions that can be used depending on the additional detail required for a particular intervention. The consensus electronic form is now freely available for use in clinical trials. Creation of a core CRF is important to improve clinical trial efficiency in HF device development in the United States. This living document intends to reduce clinical trial administrative burden, increase evidence integrity, and improve comparability of clinical data between trials.


Assuntos
Formulários como Assunto , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Registros Médicos , Humanos
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