scholarly journals The role of data and safety monitoring boards in implementation trials: When are they justified?

2020 ◽  
Vol 4 (3) ◽  
pp. 229-232
Author(s):  
Kevin Fiscella ◽  
Mechelle Sanders ◽  
Tameir Holder ◽  
Jennifer K. Carroll ◽  
Amneris Luque ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Safety Monitoring ◽  
National Institutes Of Health ◽  
Phase Iii ◽  
Blood Institute ◽  
Phase Iii Clinical Trials ◽  
National Heart Lung ◽  
Cooperative Agreements ◽  
Monitor Data

AbstractThe National Institutes of Health requires data and safety monitoring boards (DSMBs) for all phase III clinical trials. The National Heart, Lung and Blood Institute requires DSMBs for all clinical trials involving more than one site and those involving cooperative agreements and contracts. These policies have resulted in the establishment of DSMBs for many implementation trials, with little consideration regarding the appropriateness of DSMBs and/or key adaptations needed by DSMBs to monitor data quality and participant safety. In this perspective, we review the unique features of implementation trials and reflect on key questions regarding the justification for DSMBs and their potential role and monitoring targets within implementation trials.

scholarly journals Anti-inflammatory Treatment and Cardiovascular Outcomes: Results of Clinical Trials

2021 ◽  
Vol 16 ◽  
Author(s):  
Alberto J Lorenzatti
Keyword(s):  
Clinical Trials ◽  
Arterial Wall ◽  
Plaque Formation ◽  
Phase Iii ◽  
Inflammatory Disorder ◽  
Chronic Inflammatory Disorder ◽  
Phase Iii Clinical Trials ◽  
Cytokines And Chemokines ◽  
Pro Inflammatory Cytokines

Atherosclerosis is a chronic inflammatory disorder of the vasculature where cholesterol accumulates in the arterial wall stimulating infiltration of immune cells. This plays an important role in plaque formation, as well as complications caused by its build up. Pro-inflammatory cytokines and chemokines are implicated throughout the progression of the disease and different therapies that aim to resolve this chronic inflammation, reduce cardiovascular (CV) events and improve clinical outcomes have been tested. The results from the pivotal CANTOS trial show that targeting the pro-inflammatory cytokine IL-1β successfully reduces the incidence of secondary CV events. This review briefly assesses the role of inflammation in atherosclerosis, providing a picture of the multiple players involved in the process and offering a perspective on targeting inflammation to prevent atherosclerotic CV events, as well as focusing on the results of the latest Phase III clinical trials.

scholarly journals Ustekinumab in psoriatic arthritis and related phenotypes

2018 ◽  
Vol 9 (10) ◽  
pp. 191-198 ◽  
Author(s):  
Isobel Dobbin-Sears ◽  
Janet Roberts ◽  
Darren D. O’Rielly ◽  
Proton Rahman
Keyword(s):  
Clinical Trials ◽  
Psoriatic Arthritis ◽  
Clinical Efficacy ◽  
Phase Iii ◽  
Two Phase ◽  
Phase Iii Clinical Trials ◽  
Th 17 ◽  
Inflammatory Bowel ◽  
Inflammatory Drugs

Psoriatic arthritis (PsA) is an inflammatory arthritis that commonly occurs with psoriasis and is attributed to genetic, immunologic and environmental factors. The T-helper (Th)-17 pathway and the interleukin (IL)-23/IL-17 axis have become prominent players in PsA and considerably increased our understanding of disease pathogenesis. In this review article, we will focus on the emerging role of IL-12/23 and its blockade, in the pathogenesis and management of PsA as well as of psoriasis and inflammatory bowel disease. Ustekinumab, is a fully human monoclonal immunoglobulin (Ig)G1 antibody that binds specifically to the p40 subunit of IL-12 and IL-23, primarily inhibiting downstream Th-17 signalling pathways. Ustekinumab produced consistent and sustained clinical efficacy in two phase III clinical trials in PsA, PSUMMIT-1 and PSUMMIT-2, with data out to 52 weeks, and no new safety signals. PSUMMIT-1 included patients with active PsA despite conventional therapy who were all naïve to anti-tumour necrosis factor (TNF) agents, whereas PSUMMIT-2 also included anti-TNF experienced patients. Similarly, ustekinumab produced consistent clinical efficacy in two phase III clinical trials in psoriasis, PHOENIX-1 and PHOENIX-2, and in both induction and maintenance of moderate-to-severe Crohn’s disease, UNITI-1, UNITI-2 and IM-UNITI, without an increased safety signal. Currently, ustekinumab is used in the treatment of PsA following the failure of nonsteroidal anti-inflammatory drugs (NSAIDs) and conventional disease-modifying antirheumatic drugs (DMARDs), and as an alternative to, or after failure of an anti-TNF agent.

Paediatric heart failure research: role of the National Heart, Lung, and Blood Institute

2015 ◽  
Vol 25 (S2) ◽  
pp. 167-171 ◽  
Author(s):  
Kristin M. Burns
Keyword(s):  
Heart Failure ◽  
Technology Development ◽  
National Institutes Of Health ◽  
Circulatory Support ◽  
Blood Institute ◽  
Research Technology ◽  
National Heart ◽  
National Heart Lung ◽  
Pediatric Circulatory Support

AbstractThe National Heart, Lung, and Blood Institute, of the National Institutes of Health, is committed to supporting research in paediatric heart failure. The Institute’s support of paediatric heart failure research includes both investigator-initiated grants and Institute initiatives. There were 107 funded grants in paediatric heart failure over the past 20 years in basic, translational and clinical research, technology development, and support of registries. Such research includes a broad diversity of scientific topics and approaches. The Institute also supports several initiatives for paediatric heart failure, including the Pediatric Circulatory Support Program, the Pumps for Kids, Infants, and Neonates (PumpKIN) Program, PediMACS, and the Pediatric Heart Network. This review article describes the National Heart, Lung, and Blood Institute’s past, present, and future efforts to promote a better understanding of paediatric heart failure, with the ultimate goal of improving outcomes.

scholarly journals An Update on the Leading COVID-19 Vaccines

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Ahmed Eladely ◽  
Keyword(s):  
Clinical Trials ◽  
Vaccine Efficacy ◽  
Vaccine Development ◽  
Vaccine Safety ◽  
Clinical Development ◽  
Phase Iii ◽  
Phase Iii Clinical Trials

We reviewed the COVID-19 vaccines that reached phase III of clinical development. For each of the 10 vaccines identified, we described the technology used for vaccine development, the available data from phase III clinical trials, data on vaccine safety, and the role of new SARS-CoV-2 variants on vaccine efficacy.

scholarly journals B-cell–targeted therapies in relapsing forms of MS

2017 ◽  
Vol 4 (6) ◽  
pp. e405 ◽  
Author(s):  
Divyanshu Dubey ◽  
Thomas Forsthuber ◽  
Eoin P. Flanagan ◽  
Sean J. Pittock ◽  
Olaf Stüve
Keyword(s):  
Clinical Trials ◽  
B Cells ◽  
B Cell ◽  
Therapeutic Strategies ◽  
Phase Iii ◽  
B Cell Depletion ◽  
Pathogenic Role ◽  
Phase Iii Clinical Trials ◽  
Anti Cd20

In recent years, there has been a significant increase in the therapeutic options available for the management of relapsing forms of MS. Therapies primarily targeting B cells, including therapeutic anti-CD20 monoclonal antibodies, have been evaluated in phase I, phase II, and phase III clinical trials. Results of these trials have shown their efficacy and relatively tolerable adverse effect profiles, suggesting a favorable benefit-to-risk ratio. In this review, we discuss the pathogenic role of B cells in MS and the rationale behind the utilization of B-cell depletion as a therapeutic cellular option. We also discuss the data of clinical trials for anti-CD20 antibodies in relapsing forms of MS and existing evidence for other B-cell–directed therapeutic strategies.

Monitoring Participant Safety in Phase I and II Interventional Trials: Options and Controversies

2004 ◽  
Vol 52 (7) ◽  
pp. 446-452 ◽  
Author(s):  
Patricia L. Hibberd ◽  
Debra L. Weiner
Keyword(s):  
Clinical Trials ◽  
Phase I ◽  
Safety Monitoring ◽  
National Institutes Of Health ◽  
Phase Iii ◽  
Roles And Responsibilities ◽  
Versus Phase ◽  
The Us ◽  
Unbiased Manner ◽  
Phase I And Ii

BackgroundThe need for phase I and II clinical trials to have a data and safety monitoring plan (DSMP) is widely accepted; however, whether and/or when these trials should also have oversight by a data and safety monitoring board (DSMB) is controversial. Monitoring requirements also depend on whether the study is funded by the National Institutes of Health, funded and/or monitored by the US Food and Drug Administration (FDA), or funded by industry. However, there is little guidance about when and how to constitute a DSMB for phase I and II clinical trials.ObjectivesThe objectives of this article are to suggest guidelines for when and how to constitute a DSMB for phase I and II studies and to highlight the similarities and differences between DSMBs monitoring phase I and II versus phase III clinical studies. We highlight the utility of these guidelines in the safety monitoring of a mechanism of disease-based study of inhaled nitric oxide for acute vaso-occlusive crisis in pediatric patients with sickle cell disease that was funded and regulated by the FDA.ConclusionThe goal of DSMPs regardless of the phase of the clinical trial is to protect participant safety and ensure the integrity and validity of the data. A DSMB can ensure that risks and data are evaluated in a timely, efficient, and unbiased manner. We describe “risk-based” guidelines to determine situations in which a DSMB may be an appropriate addition to a DSMP for phase I and II clinical trials. We also address the roles and responsibilities of the DSMB for these studies.

Rome I versus Rome II; Overlap in patients enrolled in tegaserod phase III clinical trials for irritable bowel syndrome (IBS)

2001 ◽  
Vol 120 (5) ◽  
pp. A284-A284
Author(s):  
B NAULT ◽  
S SUE ◽  
J HEGGLAND ◽  
S GOHARI ◽  
G LIGOZIO ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Irritable Bowel Syndrome ◽  
Phase Iii ◽  
Phase Iii Clinical Trials ◽  
Irritable Bowel ◽  
Rome I

Neovastat, a naturally occurring multifunctional antiangiogenic drug, in phase III clinical trials

2001 ◽  
Vol 28 (6) ◽  
pp. 620-625 ◽  
Author(s):  
Pierre Falardeau ◽  
Pierre Champagne ◽  
Patrick Poyet ◽  
Claude Hariton ◽  
[Eacute]ric Dupont
Keyword(s):  
Clinical Trials ◽  
Phase Iii ◽  
Phase Iii Clinical Trials ◽  
Naturally Occurring ◽  
Antiangiogenic Drug
Sign in / Sign up

Export Citation Format

Share Document