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1دورية أكاديمية
المؤلفون: Fleming, Thomas R., Garnett, Christine E., Conklin, Laurie S., Corriol-Rohou, Solange, Hariharan, Sudharshan, Hsu, Daphne, Mueller-Velten, Guenther, Mulugeta, Yeruk, Portman, Ronald, Rothmann, Mark D., Stockbridge, Norman L., Wandel, Simon, Zhang, Jialu, Yao, Lynne
المصدر: Therapeutic Innovation & Regulatory Science ; volume 57, issue 1, page 109-120 ; ISSN 2168-4790 2168-4804
مصطلحات موضوعية: Pharmacology (medical), Public Health, Environmental and Occupational Health, Pharmacology, Toxicology and Pharmaceutics (miscellaneous)
الوصف: Even with recent substantive improvements in health care in pediatric populations, considerable need remains for additional safe and effective interventions for the prevention and treatment of diseases in children. The approval of prescription drugs and biological products for use in pediatric settings, as in adults, requires demonstration of substantial evidence of effectiveness and favorable benefit-to-risk. For diseases primarily affecting children, such evidence predominantly would be obtained in the pediatric setting. However, for conditions affecting both adults and children, pediatric extrapolation uses scientific evidence in adults to enable more efficiently obtaining a reliable evaluation of an intervention’s effects in pediatric populations. Bridging biomarkers potentially have an integral role in pediatric extrapolation. In a setting where an intervention reliably has been established to be safe and effective in adults, and where there is substantive evidence that disease processes in pediatric and adult settings are biologically similar, a ‘bridging biomarker’ should satisfy three additional criteria: effects on the bridging biomarker should capture effects on the principal causal pathway through which the disease process meaningfully influences ‘feels, functions, survives’ measures; secondly, the experimental intervention should not have important unintended effects on ‘feels, functions, survives’ measures not captured by the bridging biomarker; and thirdly, in statistical analyses in adults, the intervention’s net effect on ‘feels, functions, survives’ measures should be consistent with what would be predicted by its level of effect on the bridging biomarker. A validated bridging biomarker has considerable potential utility, since an intervention’s efficacy could be extrapolated from adult to pediatric populations if evidence in children establishes the intervention not only to be safe but also to have substantive effects on that bridging biomarker. Proper use of bridging biomarkers could ...
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2دورية أكاديمية
المصدر: Biometrics; Dec2023, Vol. 79 Issue 4, p3792-3802, 11p
مصطلحات موضوعية: BAYESIAN field theory, CLINICAL trials, TREATMENT effectiveness, HEART failure
مستخلص: Recurrent events are often important endpoints in randomized clinical trials. For example, the number of recurrent disease‐related hospitalizations may be considered as a clinically meaningful endpoint in cardiovascular studies. In some settings, the recurrent event process may be terminated by an event such as death, which makes it more challenging to define and estimate a causal treatment effect on recurrent event endpoints. In this paper, we focus on the principal stratum estimand, where the treatment effect of interest on recurrent events is defined among subjects who would be alive regardless of the assigned treatment. For the estimation of the principal stratum effect in randomized clinical trials, we propose a Bayesian approach based on a joint model of the recurrent event and death processes with a frailty term accounting for within‐subject correlation. We also present Bayesian posterior predictive check procedures for assessing the model fit. The proposed approaches are demonstrated in the randomized Phase III chronic heart failure trial PARAGON‐HF (NCT01920711). [ABSTRACT FROM AUTHOR]
: Copyright of Biometrics is the property of Oxford University Press / USA and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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3دورية أكاديمية
المؤلفون: Simpson, Joanne, Jhund, Pardeep S., Lund, Lars H., Padmanabhan, Sandosh, Claggett, Brian L., Shen, Li, Petrie, Mark C., Abraham, William T., Desai, Akshay S., Dickstein, Kenneth, Køber, Lars, Packer, Milton, Rouleau, Jean L., Mueller-Velten, Guenther, Solomon, Scott D., Swedberg, Karl, Zile, Michael R., McMurray, John J.V.
المصدر: Simpson , J , Jhund , P S , Lund , L H , Padmanabhan , S , Claggett , B L , Shen , L , Petrie , M C , Abraham , W T , Desai , A S , Dickstein , K , Køber , L , Packer , M , Rouleau , J L , Mueller-Velten , G , Solomon , S D , Swedberg , K , Zile , M R & McMurray , J J V 2020 , ' Prognostic Models Derived in PARADIGM-HF and Validated in ATMOSPHERE and the Swedish Heart Failure ....
الوصف: Importance: Accurate prediction of risk of death or hospitalizations in patients with heart failure (HF) may allow physicians to explore how more accurate decisions regarding appropriateness and timing of disease-modifying treatments, advanced therapies, or the need for end-of-life care can be made. Objective: To develop and validate a prognostic model for patients with HF. Design, Setting, and Participants: Multivariable analyses were performed in a stepwise fashion. Harrell C statistic was used to assess the discriminative ability. The derivation cohort was Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure trial (PARADIGM-HF) participants. The models were validated using the Aliskiren Trial to Minimize Outcomes in Patients with Heart Failure Trial (ATMOSPHERE) study and in the Swedish Heart Failure Registry (SwedeHF). A total of 8399 participants enrolled in PARADIGM-HF. Data were analyzed between June 2016 and June 2018. Main Outcomes and Measures: Cardiovascular death, all-cause mortality, and the composite of cardiovascular death or HF hospitalization at both 1 and 2 years. Results: Complete baseline clinical data were available for 8011 patients in PARADIGM-HF. The mean (SD) age of participants was 64 (11.4) years, 78.2% were men (n = 6567 of 8399), and 70.6% were New York Heart Association class II (n = 5919 of 8399). During a mean follow-up of 27 months, 1546 patients died, and 2031 had a cardiovascular death or HF hospitalization. The common variables were: male sex, race/ethnicity (black or Asian), region (Central Europe or Latin America), HF duration of more than 5 years, New York Heart Association class III/ IV, left ventricular ejection fraction, diabetes mellitus, β-blocker use at baseline, and allocation to sacubitril/valsartan. Ranked by χ 2 , N-terminal pro brain natriuretic peptide was the single most powerful independent predictor of each outcome. The C statistic at 1 and 2 years was 0.74 (95% CI, 0.71-0.76) and 0.71 (95% CI, ...
الإتاحة: https://doi.org/10.1001/jamacardio.2019.5850Test
https://curis.ku.dk/portal/da/publications/prognostic-models-derived-in-paradigmhf-and-validated-in-atmosphere-and-the-swedish-heart-failure-registry-to-predict-mortality-and-morbidity-in-chronic-heart-failureTest(3e1dc660-0e70-4113-bb65-f2f2b3d692a9).html
http://www.scopus.com/inward/record.url?scp=85078944579&partnerID=8YFLogxKTest
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6990745Test/ -
4دورية أكاديمية
المؤلفون: Mogensen, Ulrik M., Gong, Jianjian, Jhund, Pardeep S., Shen, Li, Køber, Lars, Desai, Akshay S., Lefkowitz, Martin P., Packer, Milton, Rouleau, Jean L., Solomon, Scott D., Claggett, Brian L., Swedberg, Karl, Zile, Michael R., Mueller-Velten, Guenther, McMurray, John J.V.
الوصف: Aims: Recurrent hospitalizations are a major part of the disease burden in heart failure (HF), but conventional analyses consider only the first event. We compared the effect of sacubitril/valsartan vs. enalapril on recurrent events, incorporating all HF hospitalizations and cardiovascular (CV) deaths in PARADIGM-HF, using a variety of statistical approaches advocated for this type of analysis. Methods and results: In PARADIGM-HF, a total of 8399 patients were randomized and followed for a median of 27 months. We applied various recurrent event analyses, including a negative binomial model, the Wei, Lin and Weissfeld (WLW), and Lin, Wei, Ying and Yang (LWYY) methods, and a joint frailty model, all adjusted for treatment and region. Among a total of 3181 primary endpoint events (including 1251 CV deaths) during the trial, only 2031 (63.8%) were first events (836 CV deaths). Among a total of 1195 patients with at least one HF hospitalization, 410 (34%) had at least one further HF hospitalization. Sacubitril/valsartan compared with enalapril reduced the risk of recurrent HF hospitalization using the negative binomial model [rate ratio (RR) 0.77, 95% confidence interval (CI) 0.67–0.89], the WLW method [hazard ratio (HR) 0.79, 95% CI 0.71–0.89], the LWYY method (RR 0.78, 95% CI 0.68–0.90), and the joint frailty model (HR 0.75, 95% CI 0.66–0.86) (all P < 0.001). The effect of sacubitril/valsartan vs. enalapril on recurrent HF hospitalizations/CV death was similar. Conclusions: In PARADIGM-HF, approximately one third of patients with a primary endpoint (time-to-first) experienced a further event. Compared with enalapril, sacubitril/valsartan reduced both first and recurrent events. The treatment effect size was similar, regardless of the statistical approach applied.
وصف الملف: text
العلاقة: http://eprints.gla.ac.uk/154307/1/154307.pdfTest; Mogensen, U. M. et al. (2018) Effect of sacubitril/valsartan on recurrent events in the prospective comparison of ARNI with ACEI to determine impact on global mortality and morbidity in heart failure trial (PARADIGM-HF). European Journal of Heart Failure , 20(4), pp. 760-768. (doi:10.1002/ejhf.1139 ) (PMID:29431251)
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5دورية أكاديمية
المؤلفون: Mogensen, Ulrik M, Gong, Jianjian, Jhund, Pardeep S, Shen, Li, Køber, Lars, Desai, Akshay S, Lefkowitz, Martin P, Packer, Milton, Rouleau, Jean L, Solomon, Scott D, Claggett, Brian L, Swedberg, Karl, Zile, Michael R, Mueller-Velten, Guenther, McMurray, John J V
المصدر: Mogensen , U M , Gong , J , Jhund , P S , Shen , L , Køber , L , Desai , A S , Lefkowitz , M P , Packer , M , Rouleau , J L , Solomon , S D , Claggett , B L , Swedberg , K , Zile , M R , Mueller-Velten , G & McMurray , J J V 2018 , ' Effect of sacubitril/valsartan on recurrent events in the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM-HF) ....
مصطلحات موضوعية: Aged, Aminobutyrates/administration & dosage, Angiotensin Receptor Antagonists/administration & dosage, Angiotensin-Converting Enzyme Inhibitors/administration & dosage, Dose-Response Relationship, Drug, Enalapril/administration & dosage, Europe/epidemiology, Female, Heart Failure/drug therapy, Humans, Male, Middle Aged, Morbidity/trends, Prospective Studies, Recurrence, Stroke Volume/physiology, Survival Rate/trends, Tetrazoles/administration & dosage, United States/epidemiology
الوصف: AIMS: Recurrent hospitalizations are a major part of the disease burden in heart failure (HF), but conventional analyses consider only the first event. We compared the effect of sacubitril/valsartan vs. enalapril on recurrent events, incorporating all HF hospitalizations and cardiovascular (CV) deaths in PARADIGM-HF, using a variety of statistical approaches advocated for this type of analysis. METHODS AND RESULTS: In PARADIGM-HF, a total of 8399 patients were randomized and followed for a median of 27 months. We applied various recurrent event analyses, including a negative binomial model, the Wei, Lin and Weissfeld (WLW), and Lin, Wei, Ying and Yang (LWYY) methods, and a joint frailty model, all adjusted for treatment and region. Among a total of 3181 primary endpoint events (including 1251 CV deaths) during the trial, only 2031 (63.8%) were first events (836 CV deaths). Among a total of 1195 patients with at least one HF hospitalization, 410 (34%) had at least one further HF hospitalization. Sacubitril/valsartan compared with enalapril reduced the risk of recurrent HF hospitalization using the negative binomial model [rate ratio (RR) 0.77, 95% confidence interval (CI) 0.67-0.89], the WLW method [hazard ratio (HR) 0.79, 95% CI 0.71-0.89], the LWYY method (RR 0.78, 95% CI 0.68-0.90), and the joint frailty model (HR 0.75, 95% CI 0.66-0.86) (all P < 0.001). The effect of sacubitril/valsartan vs. enalapril on recurrent HF hospitalizations/CV death was similar. CONCLUSIONS: In PARADIGM-HF, approximately one third of patients with a primary endpoint (time-to-first) experienced a further event. Compared with enalapril, sacubitril/valsartan reduced both first and recurrent events. The treatment effect size was similar, regardless of the statistical approach applied.
وصف الملف: application/pdf
الإتاحة: https://doi.org/10.1002/ejhf.1139Test
https://curis.ku.dk/portal/da/publications/effect-of-sacubitrilvalsartan-on-recurrent-events-in-the-prospective-comparison-of-arni-with-acei-to-determine-impact-on-global-mortality-and-morbidity-in-heart-failure-trial-paradigmhfTest(54665c94-aa68-46eb-b0fd-6afedafb27a5).html
https://curis.ku.dk/ws/files/218469358/Mogensen_et_al_2018_European_Journal_of_Heart_Failure.pdfTest -
6دورية أكاديمية
المؤلفون: Filippatos, Gerasimos S., de Graeff, Pieter, Bax, Jeroen J., Borg, John-Joseph, Cleland, John G. F., Dargie, Henry J., Flather, Marcus, Ford, Ian, Friede, Tim, Greenberg, Barry, Henon-Goburdhun, Cecile, Holcomb, Richard, Horst, Bradley, Lekakis, John, Mueller-Velten, Guenther, Papavassiliou, Athanasios G., Prasad, Krishna, Rosano, Giuseppe M. C., Severin, Thomas, Sherman, Warren, Stough, Wendy Gattis, Swedberg, Karl, Tavazzi, Luigi, Tousoulis, Dimitris, Vardas, Panagiotis, Ruschitzka, Frank, Anker, Stefan D.
المصدر: Filippatos , G S , de Graeff , P , Bax , J J , Borg , J-J , Cleland , J G F , Dargie , H J , Flather , M , Ford , I , Friede , T , Greenberg , B , Henon-Goburdhun , C , Holcomb , R , Horst , B , Lekakis , J , Mueller-Velten , G , Papavassiliou , A G , Prasad , K , Rosano , G M C , Severin , T , Sherman , W , Stough , W G , Swedberg , K , Tavazzi ....
مصطلحات موضوعية: Clinical trials, Data Monitoring Committees, Data safety monitoring board, Clinical trials as topic, Cardiovascular diseases, DATA SAFETY, RANDOMIZED-TRIALS, BOARDS, EXPERIENCE, BENEFIT, CHALLENGES, FUTURE, STOP, DSMB
الوصف: Data Monitoring Committees (DMCs) play a crucial role in the conducting of clinical trials to ensure the safety of study participants and to maintain a trial's scientific integrity. Generally accepted standards exist for DMC composition and operational conduct. However, some relevant issues are not specifically addressed in current guidance documents, resulting in uncertainties regarding optimal approaches for communication between the DMC, steering committee, and sponsors, release of information, and liability protection for DMC members. The Heart Failure Association (HFA) of the European Society of Cardiology (ESC), in collaboration with the Clinical Trials Unit of the European Heart Agency (EHA) of the ESC convened a meeting of international experts in DMCs for cardiovascular and cardiometabolic clinical trials to identify specific issues and develop steps to resolve challenges faced by DMCs. The main recommendations from the meeting relate to methodological consistency, independence, managing conflicts of interest, liability protection, and training of future DMC members. This paper summarizes the key outcomes from this expert meeting, and describes the core set of activities that might be further developed and ultimately implemented by the ESC, HFA, and other interested ESC constituent bodies. The HFA will continue to work with stakeholders in cardiovascular and cardiometabolic clinical research to promote these goals.
وصف الملف: application/pdf
الإتاحة: https://doi.org/10.1002/ejhf.761Test
https://hdl.handle.net/11370/3dcc0ce2-e767-4d46-b913-de821a29dcf1Test
https://research.rug.nl/en/publications/3dcc0ce2-e767-4d46-b913-de821a29dcf1Test
https://pure.rug.nl/ws/files/46755699/Filippatos_et_al_2017_European_Journal_of_Heart_Failure.pdfTest -
7دورية أكاديمية
المؤلفون: Fleming, Thomas R., Garnett, Christine E., Conklin, Laurie S., Corriol-Rohou, Solange, Hariharan, Sudharshan, Hsu, Daphne, Mueller-Velten, Guenther, Mulugeta, Yeruk, Portman, Ronald, Rothmann, Mark D., Stockbridge, Norman L., Wandel, Simon, Zhang, Jialu, Yao, Lynne
المصدر: Therapeutic Innovation & Regulatory Science; Jan2023, Vol. 57 Issue 1, p109-120, 12p
مصطلحات موضوعية: BIOMARKERS, DRUG efficacy, PEDIATRICS, MEDICAL care, TREATMENT effectiveness, DRUGS, DRUG development, STATISTICAL models, DIFFUSION of innovations, PATIENT safety, EVALUATION, CHILDREN
مستخلص: Even with recent substantive improvements in health care in pediatric populations, considerable need remains for additional safe and effective interventions for the prevention and treatment of diseases in children. The approval of prescription drugs and biological products for use in pediatric settings, as in adults, requires demonstration of substantial evidence of effectiveness and favorable benefit-to-risk. For diseases primarily affecting children, such evidence predominantly would be obtained in the pediatric setting. However, for conditions affecting both adults and children, pediatric extrapolation uses scientific evidence in adults to enable more efficiently obtaining a reliable evaluation of an intervention's effects in pediatric populations. Bridging biomarkers potentially have an integral role in pediatric extrapolation. In a setting where an intervention reliably has been established to be safe and effective in adults, and where there is substantive evidence that disease processes in pediatric and adult settings are biologically similar, a 'bridging biomarker' should satisfy three additional criteria: effects on the bridging biomarker should capture effects on the principal causal pathway through which the disease process meaningfully influences 'feels, functions, survives' measures; secondly, the experimental intervention should not have important unintended effects on 'feels, functions, survives' measures not captured by the bridging biomarker; and thirdly, in statistical analyses in adults, the intervention's net effect on 'feels, functions, survives' measures should be consistent with what would be predicted by its level of effect on the bridging biomarker. A validated bridging biomarker has considerable potential utility, since an intervention's efficacy could be extrapolated from adult to pediatric populations if evidence in children establishes the intervention not only to be safe but also to have substantive effects on that bridging biomarker. Proper use of bridging biomarkers could increase availability of reliably evaluated therapies approved for use in pediatric settings, enabling children and their caregivers to make informed choices about health care. [ABSTRACT FROM AUTHOR]
: Copyright of Therapeutic Innovation & Regulatory Science is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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8دورية أكاديمية
المؤلفون: Akacha, Mouna, Binkowitz, Bruce, Claggett, Brian, Hung, H. M. James, Mueller-Velten, Guenther, Stockbridge, Norman
المصدر: Therapeutic Innovation & Regulatory Science ; volume 53, issue 3, page 387-397 ; ISSN 2168-4790 2168-4804
مصطلحات موضوعية: Pharmacology (medical), Public Health, Environmental and Occupational Health, Pharmacology, Toxicology and Pharmaceutics (miscellaneous)
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9دورية أكاديمية
المؤلفون: Taylor, Lloyd M, Mueller-Velten, Guenther, Koslow, Allen, Hunter, Glenn, Naslund, Thomas, Kline, Ronald
المصدر: Journal of Vascular Surgery ; volume 38, issue 4, page 766-771 ; ISSN 0741-5214
مصطلحات موضوعية: Cardiology and Cardiovascular Medicine, Surgery
الإتاحة: https://doi.org/10.1016/s0741-5214Test(03)00474-9
https://api.elsevier.com/content/article/PII:S0741521403004749?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S0741521403004749?httpAccept=text/plainTest -
10
المؤلفون: Filippatos, Gerasimos S, et al, Ruschitzka, Frank, Mueller-Velten, Guenther, Severin, Thomas
المساهمون: University of Zurich
مصطلحات موضوعية: 10209 Clinic for Cardiology, 610 Medicine & health, 2705 Cardiology and Cardiovascular Medicine
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=od_______885::d39bba567654f32b2d852720f5c07236Test
https://www.zora.uzh.ch/id/eprint/150140Test/
