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Surrogate endpoint

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https://www.readbyqxmd.com/read/28345017/proof-of-concept-demonstration-of-optimal-composite-mri-endpoints-for-clinical-trials
#1
Steven D Edland, M Colin Ard, Jaiashre Sridhar, Derin Cobia, Adam Martersteck, M Marsel Mesulam, Emily J Rogalski
BACKGROUND: Atrophy measures derived from structural MRI are promising outcome measures for early phase clinical trials, especially for rare diseases such as primary progressive aphasia (PPA), where the small available subject pool limits our ability to perform meaningfully powered trials with traditional cognitive and functional outcome measures. METHODS: We investigated a composite atrophy index in 26 PPA participants with longitudinal MRIs separated by two years...
September 2016: Alzheimer's & Dementia: Translational Research & Clinical Interventions
https://www.readbyqxmd.com/read/28341415/diuretic-strategies-in-acute-heart-failure-and-renal-dysfunction-conventional-vs-carbohydrate-antigen-125-guided-strategy-clinical-trial-design
#2
Sergio García-Blas, Clara Bonanad, Pau Llàcer, Silvia Ventura, José María Núñez, Ruth Sánchez, Carlos Chamorro, Lorenzo Fácila, Rafael de la Espriella, Juana María Vaquer, Alberto Cordero, Mercè Roqué, Víctor Ortiz, Paolo Racugno, Vicent Bodí, Ernesto Valero, Enrique Santas, María Del Carmen Moreno, Gema Miñana, Arturo Carratalá, Lourdes Bondanza, Ana Payá, Ingrid Cardells, Raquel Heredia, Mauricio Pellicer, Guillermo Valls, Patricia Palau, María José Bosch, Rafael Raso, Andrés Sánchez, Vicente Bertomeu-González, Vicente Bertomeu-Martínez, Vicente Montagud-Balaguer, Cristina Albiach-Montañana, Jezabel Pendás-Meneau, Goitzane Marcaida, Sonia Cervantes-García, Rodolfo San Antonio, Elisabet de Mingo, Francisco J Chorro, Juan Sanchis, Julio Núñez
INTRODUCTION AND OBJECTIVES: The optimal treatment of patients with acute heart failure (AHF) and cardiorenal syndrome type 1 (CRS-1) is far from being well-defined. Arterial hypoperfusion in concert with venous congestion plays a crucial role in the pathophysiology of CRS-I. Plasma carbohydrate antigen 125 (CA125) has emerged as a surrogate of fluid overload in AHF. The aim of this study was to evaluate the clinical usefulness of CA125 for tailoring the intensity of diuretic therapy in patients with CRS-1...
March 21, 2017: Revista Española de Cardiología
https://www.readbyqxmd.com/read/28337673/progression-free-survival-as-a-surrogate-for-overall-survival-in-clinical-trials-of-targeted-therapy-in-advanced-solid-tumors
#3
Stefan Michiels, Everardo D Saad, Marc Buyse
Over the past 15 years, targeted therapy has revolutionized the systemic treatment of cancer. In parallel, there has been a growing debate on the choice of end points in clinical trials in oncology. This debate basically hinges on the choice between overall survival (OS) and progression-free survival (PFS). PFS is advantageous because it is measured earlier than OS, requires a smaller sample size than OS to achieve the desired power, and is not influenced by cross-over. On the other hand, PFS is prone to measurement error and bias, and may not capture the entire treatment effect on the outcomes of most interest to patients with an incurable disease: a prolonged survival and improved quality of life...
March 23, 2017: Drugs
https://www.readbyqxmd.com/read/28336789/percutaneous-therapy-for-tricuspid-regurgitation-a-new-frontier-for-interventional-cardiology
#4
Samir R Kapadia, Amar Krishnaswamy, E Murat Tuzcu
Functional tricuspid regurgitation (FTR) is common, whether in association with mitral or aortic valve disease or presenting as an isolated valvular disease. Several studies have shown that TR is associated with poor patient outcomes, though a cause-and-effect relationship of TR to mortality has not been proven. Similarly the impact of surgical treatment of TR on outcomes needs well-controlled randomized trials that are under planning. The current professional society guidelines for treatment of TR are based on expert opinions with a level of evidence C for all indications...
March 23, 2017: Circulation
https://www.readbyqxmd.com/read/28332083/phase-iii-soft-tissue-sarcoma-trials-success-or-failure
#5
REVIEW
Alexander T J Lee, Seth M Pollack, Paul Huang, Robin L Jones
Two recently reported phase III randomised control trials (RCTs) have resulted in the registration of two new systemic therapies for advanced soft tissue sarcoma. Both of these trials' designs were informed by phase II data that guided the selection of sensitive STS diagnoses, enabling the demonstration of benefit in certain subtypes. A number of other phase III trials reported in the last 18 months have seemingly fit into a recurrent pattern of failure-promising efficacy signals in earlier phase studies being lost in the survival follow-up of large, highly heterogeneous cohorts...
March 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28331925/biological-effects-of-ticagrelor-over-clopidogrel-in-patients-with-stable-coronary-artery-disease-and-chronic-obstructive-pulmonary-disease
#6
Gianluca Campo, Francesco Vieceli Dalla Sega, Rita Pavasini, Giorgio Aquila, Francesco Gallo, Francesca Fortini, Elisabetta Tonet, Paolo Cimaglia, Annamaria Del Franco, Gabriele Pestelli, Alessandro Pecoraro, Marco Contoli, Cristina Balla, Simone Biscaglia, Paola Rizzo, Roberto Ferrari
Patients with SCAD and concomitant COPD are at high risk of cardiovascular adverse events, due to chronic inflammation, responsible of endothelial dysfunction, oxidative stress and heightened platelet reactivity (PR). The objective of this randomised clinical trial was to test if ticagrelor is superior to clopidogrel in improving endothelial function in patients with stable coronary artery disease (SCAD) and concomitant chronic obstructive pulmonary disease (COPD). Forty-six patients with SCAD and COPD undergoing percutaneous coronary intervention (PCI) were randomly assigned to receive clopidogrel (n=23) or ticagrelor (n=23) on top of standard therapy with aspirin...
March 23, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28325713/two-decades-of-cardiovascular-trials-with-primary-surrogate-endpoints-1990-2011
#7
Behnood Bikdeli, Natdanai Punnanithinont, Yasir Akram, Ike Lee, Nihar R Desai, Joseph S Ross, Harlan M Krumholz
BACKGROUND: Surrogate endpoint trials test strategies more efficiently but are accompanied by uncertainty about the relationship between changes in surrogate markers and clinical outcomes. METHODS AND RESULTS: We identified cardiovascular trials with primary surrogate endpoints published in the New England Journal of Medicine, Lancet, and JAMA: Journal of the American Medical Association from 1990 to 2011 and determined the trends in publication of surrogate endpoint trials and the success of the trials in meeting their primary endpoints...
March 21, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28325150/managing-expectations-in-the-transition-to-proof-of-concept-studies
#8
Thomas Kieber-Emmons, Issam Makhoul, Angela Pennisi, Eric R Siegel, Peter D Emanuel, Bejotaloh Monzavi-Karbassi, Zenon Steplewski, J Thaddeus Beck, Laura F Hutchins
BACKGROUND: As we are moving away from the traditional chemotherapy era to targeted therapy, the validity of old assessment paradigms associated with therapeutics are being raised in the context of immunotherapy. The old paradigm required elaborate assessment of toxicity with no expectation of efficacy in early phase trials. Safety data from Phase 1 and 2 studies with many immunotherapeutics show that they display limited toxicities and draw attention to the need to demonstrate efficacy in the early evaluation of new agents...
March 21, 2017: Reviews on Recent Clinical Trials
https://www.readbyqxmd.com/read/28319455/joint-model-imputation-to-estimate-the-treatment-effect-on-long-term-survival-using-auxiliary-events
#9
Audrey Mauguen, Stefan Michiels, Virginie Rondeau
Clinical trial duration may be a concern in clinical research, especially in cancer trials where the endpoint is overall survival. A surrogate endpoint can be used as an auxiliary variable to analyze the treatment effect earlier. At an early time point, the high number of censored observations can be compensated by the imputation of the unobserved deaths times. We propose to use predictions of the risk of death from a joint model for a recurrent event and a terminal event, which account for disease relapse information...
February 16, 2017: Journal of Biopharmaceutical Statistics
https://www.readbyqxmd.com/read/28315171/the-dilemma-of-adolescent-varicoceles-do-they-really-have-to-be-repaired
#10
REVIEW
Bryan S Sack, Mattias Schäfer, Michael P Kurtz
The primary indication for varicocele repair in adults, that of failed paternity, must be substituted in the adolescent population with surrogate parameters of testicular size differential and semen analysis. Making recommendations based on these two parameters is incredibly difficult because studies often have contradictory findings, different patient populations, and lack of long-term follow up of the key endpoint, paternity. Therefore, it is not a surprise that recommendations for adolescent varicocele repair are general (with some exceptions) and necessarily so because of limitations in quality of evidence...
May 2017: Current Urology Reports
https://www.readbyqxmd.com/read/28302142/maximum-inspiratory-pressure-as-a-clinically-meaningful-trial-endpoint-for-neuromuscular-diseases-a-comprehensive-review-of-the-literature
#11
REVIEW
Benedikt Schoser, Edward Fong, Tarekegn Geberhiwot, Derralynn Hughes, John T Kissel, Shyam C Madathil, David Orlikowski, Michael I Polkey, Mark Roberts, Harm A W M Tiddens, Peter Young
Respiratory muscle strength is a proven predictor of long-term outcome of neuromuscular disease (NMD), including amyotrophic lateral sclerosis, Duchenne muscular dystrophy, and spinal muscular atrophy. Maximal inspiratory pressure (MIP), a sensitive measure of respiratory muscle strength, one of several useful tests of respiratory muscle strength, is gaining interest as a therapeutic clinical trial endpoint for NMD. In this comprehensive review we investigate the use of MIP as a measure of respiratory muscle strength in clinical trials of therapeutics targeting respiratory muscle, examine the correlation of MIP with survival, quality of life, and other measures of pulmonary function, and outline the role of MIP as a clinically significantly meaningful outcome measure...
March 16, 2017: Orphanet Journal of Rare Diseases
https://www.readbyqxmd.com/read/28299202/the-role-for-infarct-volume-as-a-surrogate-measure-of-functional-outcome-following-ischemic-stroke
#12
Ryan C Turner, Kenneth DiPasquale, Aric F Logsdon, Zhenjun Tan, Zachary J Naser, Jason D Huber, Charles L Rosen, Brandon P Lucke-Wold
The failed translation of proposed therapeutic agents for ischemic stroke from preclinical to clinical studies has led to increased scrutiny of preclinical studies, namely the model and outcome measures utilized. Preclinical studies routinely use infarct volume as an experimental endpoint or measure in studies employing young-adult, healthy male animals despite the fact that clinically, ischemic stroke is a disease of the elderly and improvements in functional outcome from pre- to post-intervention remains the most widely utilized assessment...
December 2016: Journal of Systems and Integrative Neuroscience
https://www.readbyqxmd.com/read/28292317/the-association-of-funding-source-on-effect-size-in-randomized-controlled-trials-2013-2015-a-cross-sectional-survey-and-meta-analysis
#13
Alberto Falk Delgado, Anna Falk Delgado
BACKGROUND: Trials financed by for-profit organizations have been associated with favorable outcomes of new treatments, although the effect size of funding source impact on outcome is unknown. The aim of this study was to estimate the effect size for a favorable outcome in randomized controlled trials (RCTs), stratified by funding source, that have been published in general medical journals. METHODS: Parallel-group RCTs published in The Lancet, New England Journal of Medicine, and JAMA between 2013 and 2015 were identified...
March 14, 2017: Trials
https://www.readbyqxmd.com/read/28289525/cardiovascular-magnetic-resonance-imaging-assessment-of-outcomes-in-acute-myocardial-infarction
#14
REVIEW
Jamal N Khan, Gerry P McCann
Cardiovascular magnetic resonance (CMR) imaging uniquely characterizes myocardial and microvascular injury in acute myocardial infarction (AMI), providing powerful surrogate markers of outcomes. The last 10 years have seen an exponential increase in AMI studies utilizing CMR based endpoints. This article provides a contemporary, comprehensive review of the powerful role of CMR imaging in the assessment of outcomes in AMI. The theory, assessment techniques, chronology, importance in predicting left ventricular function and remodelling, and prognostic value of each CMR surrogate marker is described in detail...
February 26, 2017: World Journal of Cardiology
https://www.readbyqxmd.com/read/28280607/pathologic-complete-response-and-disease-free-survival-are-not-surrogate-endpoints-for-5-year-survival-in-rectal-cancer-an-analysis-of-22-randomized-trials
#15
Fausto Petrelli, Karen Borgonovo, Mary Cabiddu, Mara Ghilardi, Veronica Lonati, Sandro Barni
BACKGROUND: We performed a literature-based analysis of randomized clinical trials to assess the pathologic complete response (pCR) (ypT0N0 after neoadjuvant therapy) and 3-year disease-free survival (DFS) as potential surrogate endpoints for 5-year overall survival (OS) in rectal cancer treated with neoadjuvant (chemo)radiotherapy (CT)RT. METHODS: A systematic literature search of PubMed, EMBASE, the Web of Science, SCOPUS, CINAHL, and the Cochrane Library was performed...
February 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28279371/carotid-plaque-lipid-content-and-fibrous-cap-status-predict-systemic-cv-outcomes-the-mri-substudy-in-aim-high
#16
Jie Sun, Xue-Qiao Zhao, Niranjan Balu, Moni B Neradilek, Daniel A Isquith, Kiyofumi Yamada, Gádor Cantón, John R Crouse, Todd J Anderson, John Huston, Kevin O'Brien, Daniel S Hippe, Nayak L Polissar, Chun Yuan, Thomas S Hatsukami
OBJECTIVES: The aim of this study was to investigate whether and what carotid plaque characteristics predict systemic cardiovascular outcomes in patients with clinically established atherosclerotic disease. BACKGROUND: Advancements in atherosclerosis imaging have allowed assessment of various plaque characteristics, some of which are more directly linked to the pathogenesis of acute cardiovascular events compared to plaque burden. METHODS: As part of the event-driven clinical trial AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health Outcomes), subjects with clinically established atherosclerotic disease underwent multicontrast carotid magnetic resonance imaging (MRI) to detect plaque tissue composition and high-risk features...
March 2017: JACC. Cardiovascular Imaging
https://www.readbyqxmd.com/read/28277807/magnetic-resonance-imaging-and-transient-elastography-in-the-management-of-nonalcoholic-fatty-liver-disease-nafld
#17
Ma Ai Thanda Han, Rola Saouaf, Walid Ayoub, Tsuyoshi Todo, Edward Mena, Mazen Noureddin
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease and cirrhosis worldwide and the second most common cause of liver transplantation in major medical centers. Because liver steatosis and fibrosis severity are related to disease morbidity and mortality, the extent of disease, and disease progression, they need to be assessed and monitored. In addition, innovation with new drug developments requires disease staging and monitoring in both phase 2 and 3 clinical trials. Currently, disease assessment in both clinical practice and research is mostly performed by liver biopsy, an invasive, procedure with risks...
April 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28276870/renal-sympathetic-denervation-for-treatment-of-patients-with-heart-failure-summary-of-the-available-evidence
#18
Wail Nammas, Juhani Koistinen, Tuomas Paana, Pasi P Karjalainen
Heart failure syndrome results from compensatory mechanisms that operate to restore - back to normal - the systemic perfusion pressure. Sympathetic overactivity plays a pivotal role in heart failure; norepinephrine contributes to maintenance of the systemic blood pressure and increasing preload. Cardiac norepinephrine spillover increases in patients with heart failure; norepinephrine exerts direct toxicity on cardiac myocytes resulting in a decrease of synthetic activity and/or viability. Importantly, cardiac norepinephrine spillover is a powerful predictor of mortality in patients with moderate to severe HF...
February 10, 2017: Annals of Medicine
https://www.readbyqxmd.com/read/28276821/current-and-future-treatment-options-in-non-alcoholic-steatohepatitis-nash
#19
Nikos Lazaridis, Emmanuel Tsochatzis
Non-alcoholic steatohepatitis (NASH) is a chronic liver disease that can progress to cirrhosis and hepatocellular carcinoma. Diagnosis of NASH requires a liver biopsy and is defined as presence of hepatic steatosis, ballooning and lobular inflammation with or without fibrosis. Although NASH is the most common cause of liver disease in the west world and among the top three indications for liver transplantation, there are no universally accepted pharmacological therapies and therapeutic advances have been slow...
April 2017: Expert Review of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28261960/neurofilament-light-chain-in-cerebrospinal-fluid-and-prediction-of-disease-activity-in-clinically-isolated-syndrome-and-relapsing-remitting-multiple-sclerosis
#20
I Håkansson, A Tisell, P Cassel, K Blennow, H Zetterberg, P Lundberg, C Dahle, M Vrethem, J Ernerudh
BACKGROUND AND PURPOSE: Improved biomarkers are needed to facilitate clinical decision-making and as surrogate endpoints in clinical trials in multiple sclerosis (MS). We assessed whether neurodegenerative and neuroinflammatory markers in cerebrospinal fluid (CSF) at initial sampling could predict disease activity during 2 years of follow-up in patients with clinically isolated syndrome (CIS) and relapsing-remitting MS. METHODS: Using multiplex bead array and enzyme-linked immunosorbent assay, CXCL1, CXCL8, CXCL10, CXCL13, CCL20, CCL22, neurofilament light chain (NFL), neurofilament heavy chain, glial fibrillary acidic protein, chitinase-3-like-1, matrix metalloproteinase-9 and osteopontin were analysed in CSF from 41 patients with CIS or relapsing-remitting MS and 22 healthy controls...
March 6, 2017: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
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