Search results “Cardiovascular disease primary efficacy endpoints”
Topic 2: Efficacy endpoints in clinical trials
- Endpoints that may correlate with cure and validation of biomarkers Geraint Davies, University of Liverpool - Industry/Developers Perspective Lawrence Geiter, Otsuka - Industry/Developers Perspective Robert Wallis, Aurum Institute - Discussion
Views: 464 emainfo
What is SURROGATE ENDPOINT? What does SURROGATE ENDPOINT mean? SURROGATE ENDPOINT meaning - SURROGATE ENDPOINT definition - SURROGATE ENDPOINT explanation. Source: Wikipedia.org article, adapted under https://creativecommons.org/licenses/by-sa/3.0/ license. SUBSCRIBE to our Google Earth flights channel - https://www.youtube.com/channel/UC6UuCPh7GrXznZi0Hz2YQnQ In clinical trials, a surrogate endpoint (or marker) is a measure of effect of a specific treatment that may correlate with a real clinical endpoint but does not necessarily have a guaranteed relationship. The National Institutes of Health (USA) defines surrogate endpoint as "a biomarker intended to substitute for a clinical endpoint". Surrogate markers are used when the primary endpoint is undesired (e.g., death), or when the number of events is very small, thus making it impractical to conduct a clinical trial to gather a statistically significant number of endpoints. The FDA and other regulatory agencies will often accept evidence from clinical trials that show a direct clinical benefit to surrogate markers. Surrogate endpoints can be obtained from different modalities, such as, behavioural or cognitive scores, or biomarkers from Electroencephalography (qEEG), MRI, PET, or biochemical biomarkers. A correlate does not make a surrogate. It is a common misconception that if an outcome is a correlate (that is, correlated with the true clinical outcome) it can be used as a valid surrogate end point (that is, a replacement for the true clinical outcome). However, proper justification for such replacement requires that the effect of the intervention on the surrogate end point predicts the effect on the clinical outcome—a much stronger condition than correlation. The term "surrogate" should not be used in describing end points. Instead, descriptions of results and interpretations should be formulated in terms that designate the specific nature and category of variable assessed. A surrogate endpoint of a clinical trial is a laboratory measurement or a physical sign used as a substitute for a clinically meaningful endpoint that measures directly how a patient feels, functions or survives. Changes induced by a therapy on a surrogate endpoint are expected to reflect changes in a clinically meaningful endpoint. A commonly used example is cholesterol. While elevated cholesterol levels increase the likelihood for heart disease, the relationship is not linear - many people with normal cholesterol develop heart disease, and many with high cholesterol do not. "Death from heart disease" is the endpoint of interest, but "cholesterol" is the surrogate marker. A clinical trial may show that a particular drug (for example, simvastatin (Zocor)) is effective in reducing cholesterol, without showing directly that simvastatin prevents death. Proof of Zocor's efficacy in reducing cardiovascular disease was only presented five years after its original introduction, and then only for secondary prevention. In another case, AstraZeneca has been accused of marketing rosuvastatin (Crestor) without providing hard endpoint data, relying instead on surrogate endpoints. The company counters that it had been tested on larger groups of patients than any other drug in the class, and that its effects should be comparable to the other statins. There have been a number of instances when studies using surrogate markers have been used to show benefit from a particular treatment, but later, a repeat study looking at endpoints has not shown a benefit, or has even shown a harm.
Views: 529 The Audiopedia
Clinical endpoint
In a clinical research trial, a clinical endpoint generally refers to occurrence of a disease, symptom, sign or laboratory abnormality that constitutes one of the target outcomes of the trial, but may also refer to any such disease or sign that strongly motivates the withdrawal of that individual or entity from the trial, then often termed humane endpoint. The primary endpoint of a clinical trial is the endpoint for which subjects are randomized and for which the trial is powered. Secondary endpoints are endpoints that are analyzed post hoc, for which the trial may not be powered nor randomized. This video is targeted to blind users. Attribution: Article text available under CC-BY-SA Creative Commons image source in video
Views: 2001 Audiopedia
DAPT--Primary Endpoint Results
Primary investigator Laura Mauri, MD, MSc, discusses the results of the DAPT trial on the risk and benefits of DAPT after drug-eluting coronary stents, presented at Scientific Sessions 2014 in Chicago.
Views: 1814 AHAScienceNews
BIOFLOW-V Clinical Study on Drug-Eluting Coronary Stents: Interview with Dr. Kandzari*
Dr. Kandzari, US Principal Investigator of the BIOFLOW-V clinical trial speaks about the late-breaking study results at ESC 2017 in Barcelona. BIOFLOW-V is an international, multi-center, prospective randomized control trial comparing Orsiro* and Xience** drug-eluting stents with 12-month Target Lesion Failure (TLF) as the primary endpoint. *CAUTION - Investigational device. Limited by United States law to investigational use. ** Xience is a registered trademark of Abbott Cardiovascular Inc.
Views: 887 BIOTRONIKmedia
Viabahn VBX, which can treat clogged arteries | Approved|
Viabahn VBX, which can treat clogged arteries, has been approved for medical use 100% restoration of lumen diameter 100% maintenance of stent length 100% stent delivery at target site with no stent dislodgement 96.9% primary patency The Gore Viabahn VBX balloon expandable endoprosthesis has received US Food & Drug Administration (FDA) approval for treatment of de novo or restenotic lesions found in iliac arteries, including lesions at the aortic bifurcation. This marks the availability of the only balloon expandable stent graft with an indication for the iliac artery. “The VBX stent graft demonstrated notable immediate and nine-month safety and efficacy in treating patients with iliac occlusive disease which can be attributed to the exceptional device design,” says Jean Bismuth, vascular surgeon at /Houston Methodist, Houston, USA. “Overall, there were multiple clinical benefits observed, including no median change in the device length upon deployment and a 100% technical success rate with no occurrences of stent dislodgement or significant residual stenosis. The study device performed well in disadvantaged lesions, including occlusions, which speaks to its trackability, radial strength, conformability, and stent retention.” Of the patients in the Gore VBX FLEX IDE clinical study (n=134), 32% presented with TASC II type C or D lesions, 18% required contralateral access to the lesion, and 42% involved kissing stents at the aortic bifurcation. Clinical data from the Gore VBX FLEX IDE clinical study conducted for FDA approval reflected that the design components of the VBX stent graft were resilient both during stenting procedures and over time: 100% success rate in device delivery and coverage of target lesions in all study subjects; 100%success rate in reducing the target lesion to less than or equal to 30 percent of the original stenosis; No change in median length of the device upon deployment; and 96.9% primary patency at nine-months, including a 95.3% primary patency rate in those patients with TASC II C or D type lesions. Further, there were no reported incidences of device dislodgement, failures in stent integrity, or device-related serious adverse events through the primary endpoint follow up, meaning no additional costs incurred for either endovascular or surgical stent removal. The VBX stent graft does not require pre-dilation, which is intended to reduce the number of balloons required, and the longer lengths available reduce the need to use multiple stents for extensive lesions, both of which also contribute to procedural cost savings.
Views: 1030 Science Director
Could you market a drug that matches Restasis' efficacy endpoints, but has a better safety profile?
The Inaugural Dry Eye Summit Section: Establishing Clinically Relevant Endpoints and General Criteria for Inclusion / Exclusion for Dry Eye Subgroups Topic: If a drug reaches the same efficacy endpoints as Restasis, but had a better safety profile, would it be enough to differentiate it in the marketplace?
Views: 508 DryEyeSummit
All about dronedarone, from ATHENA to PALLAS
http://www.theheart.org/editorial-program/1327907.do The study data, now detailed in the New England Journal of Medicine, show that the dronedarone-related CV events over a median follow-up of 3.5 months consisted largely of stroke, heart failure, CV death, and arrhythmic death. Those events contributed to significant increases, by a factor of about two, in the trial's pair of co--primary end points: stroke, MI, systemic embolism, or CV death; and death or unplanned CV hospitalization. The findings are in contrast to those of the ATHENA trial, which included somewhat lower-CV-risk patients with recent paroxysmal or intermittent AF and had a 24% drop in the primary end point of death or CV hospitalization over 21 months. ATHENA was the basis for the FDA approval of dronedarone in July 2009. Dr Melissa Walton-Shirley sits down with the Heart Rhythm Society's president-elect Dr Anne Gillis to talk about this new information and what it means for the future of dronedarone in the world of atrial fibrillation.
Views: 796 theheartorg
A Vast Unmet Need: Challenges in Alzheimer’s Clinical Trials
Dementia is a growing global epidemic, affecting nearly 47 million people worldwide. That number is expected to approach 75 million by 2030, when the cost of patient care is forecast to reach $2 trillion. And the trend will only accelerate: By 2050, it’s estimated that 115 million will suffer from some form of dementia. Alzheimer’s disease is by far the most common of these afflictions occurring late in life, making it imperative that we develop new pharmacologic therapies. More than three decades ago, the cholinergic hypothesis proposed that degeneration of cholinergic neurons in the basal forebrain — and the associated loss of cholinergic neurotransmission in the cerebral cortex, hippocampus, and other areas — contributed significantly to cognitive deterioration in Alzheimer’s disease. That hypothesis led to development and FDA approval of the first Alzheimer’s drug, tacrine, in 1993. Despite clinical trials of numerous agents over a wide range of mechanisms that include neurotransmitter modulation and disease-modifying therapy targeting amyloid and tau, the last new Alzheimer’s medication, memantine, was approved in 2003. The only path to regulatory approval for treatments is well-conducted clinical trials, and trial failures may result from inadequate understanding of mechanisms of action and/or poor target engagement, inadequate study design, the stage of the disease along the continuum studied, inclusion of participants without Alzheimer’s pathology in clinical trials, and limited power of endpoint measures. There are currently 23 drugs in Phase II and III trials targeting amyloid protein buildup in the brain, while 28 drugs are targeting neurotransmitter activity. Twenty-seven Alzheimer’s drugs in Phase III clinical trials and eight drugs in Phase II trials may launch in the next five years, according to the Alzheimer’s pipeline analysis presented at the Alzheimer’s Association International Conference in July 2017. Preventing or delaying disease onset, slowing progression, and improving the symptoms of this disorder are critically important. Of 143 currently active Alzheimer’s trials, 71 percent are being conducted in the United States. While the U.S. has more trial sites than any other single country, the majority of sites are in other countries. Recruitment and site activation processes for Alzheimer’s clinical trials face a number of challenges, and consequently, 85 to 90 percent of U.S. trials experience delayed recruitment. The increasingly global nature of these trials emphasizes the importance of considering the ethnic and regional factors that may influence the outcome. Many Alzheimer’s trials rely on subjective endpoints as the primary measures of efficacy. Clinicians and trial sites vary widely in their experience administering assessment instruments, leading to unintentional variability of data. To overcome this challenge, many sponsors and CROs implement thorough training programs targeted to all raters and robust and ongoing rater monitoring and quality assurance programs. In addition, clinical assessments using scales to measure cognitive impairment, disability, quality of life, or global disease severity are affected by symptomatic effects of therapies and, in the short term, cannot differentiate this effect from disease modification. An alternative approach could be using surrogate outcome biomarkers that objectively measure characteristics of the disease. Unfortunately, there is no single accepted surrogate outcome biomarker for Alzheimer’s disease. Alzheimer’s drug development is costly, time-consuming, and inefficient. Site functions, trial design, and patient recruitment all require improvement. At 99.6 percent, the trial failure rate is the highest of any therapeutic area. Innovation is critical to shortening the development cycle of new therapies and identifying drugs that have limited or no therapeutic potential. This webinar will review the current global pipeline of Alzheimer’s trials and their geographic locations, describe innovations in trial design, and promote consideration of optimal clinical trial processes, including preclinical patient populations, clinical assessments sensitive to the earliest disease-related changes, and biomarkers as outcomes of clinical trials.
Views: 141 Premier Research
Epicor Cardiac Ablation LP (Low Profile) Thoracotomy Animation
The Epicor LP system has a lower profile (smaller relative to the first generation technology) as well as other features designed to facilitate easier device introduction and placement around and on patients' hearts. In addition, the Epicor LP System is equally suited for use in both closed-chest procedures performed through a single incision, and in open-chest procedures. In the December 2007 edition of The Annals of Thoracic Surgery, the results of an independent investigator clinical trial led by Mark Groh, M.D., showed that AF is effectively treated using the Epicor Cardiac Ablation System when used concomitantly to corrective heart surgery. The investigators reported that more than 83 percent of all patients, followed for at least six months after surgery, were free from AF. In addition, 86 percent of the patients followed for at least 18 months remained free from AF. The investigators reported that there were no device or ablative procedure-related adverse events and specifically noted an absence of esophageal, coronary or phrenic nerve damage. The 2007 results confirmed the findings of an earlier European multi-center trial published in the September 2005 Journal of Thoracic and Cardiovascular Surgery. The investigators in the European clinical trial reported an 85 percent freedom-from-AF rate at six months post-procedure - the study's primary efficacy end point - in patients concomitantly treated for AF with the Epicor Cardiac Ablation System.
Views: 30290 jrichmond4242
Dr Joao A Lima: CORE320 in Clinical Practice
The CORE320 International Multicenter study investigated the diagnostic accuracy of CT Angiography and CT Perfusion compared to the gold standard of SPECT and ICA. The primary results were presented at ESC 2012. These results show the incremental benefit of adding a CTP examination to CCTA. This presentation will discuss how CTP can be implemented into clinical practice. Using the results of CORE320 we will discuss which patients will benefit most from the addition of CTP and in which patients CCTA alone is able to accurately diagnose CAD. Where the combined CCTA/ CTP examination fits into the current diagnostic algorithm for CAD alongside other imaging techniques will also be discussed. Other insights from some of the CORE320 secondary endpoints will also be presented, including the comparative effectiveness of SPECT and CCTA for the diagnosis of CAD and the assessment of lesion severity by CCTA for detecting CAD associated with ischemia detected by SPECT. Find out more at http://toshiba-medical.eu
Edoxaban for Cancer-Associated Venous Thromboembolism
Daily injection with low-molecular-weight heparin is the recommended treatment for cancer-associated venous thromboembolism; the safety and efficacy of direct oral anticoagulants have not been established. New research findings are summarized in this short video. Full study: http://nej.md/2B733Bk Watch more Quick Take videos: http://nej.md/quick-take
Views: 2356 NEJMvideo
BIOFLOW-V Clinical Study on Drug-Eluting Stents: Presentation*
US Principal Investigator Dr David Kandzari presents the results of "BIOFLOW-V: A Prospective Randomized Multicenter Study to Assess the Safety and Effectiveness of the Orsiro* Sirolimus Eluting Coronary Stent System in the Treatment Of Subjects With up to Three De Novo or Restenotic Coronary Artery Lesions". BIOFLOW-V is an international, multi-center, prospective randomized control trial comparing Orsiro and Xience** drug-eluting stents with 12-month Target Lesion Failure (TLF) as the primary endpoint. The presentation was recorded at the ESC 2017 Congress in Barcelona. *CAUTION - Investigational device. Limited by United States law to investigational use. ** Xience is a registered trademark of Abbott Cardiovascular Inc.
Views: 931 BIOTRONIKmedia
Kelly Fabrega-Foster - Efficacy and Safety of Gadobutrol-Enhanced MRI of the Renal Arteries
JMRI, Volume 47, Issue 2, February 2018, Pages 572-581 TITLE: Efficacy and safety of gadobutrol‐enhanced MRA of the renal arteries: Results from GRAMS (Gadobutrol‐enhanced renal artery MRA study), a prospective, intraindividual multicenter phase 3 blinded study PURPOSE: To compare the performance of magnetic resonance angiography (MRA) with 1M gadobutrol, a high relaxivity macrocyclic contrast agent, to 2D time‐of‐flight MRA (ToF‐MRA) using computed tomographic angiography (CTA) as the standard of reference. Primary objectives were evaluation for superiority of structural delineation and noninferiority for detection and exclusion of clinically significant disease. MATERIALS AND METHODS: In all, 315 subjects underwent unenhanced and contrast‐enhanced MRA with 1M gadobutrol (CE‐MRA) and were scanned with 1.5T MRI equipped with an at least 6‐element body coil. Evaluations were based on both centralized blinded read (BR) performed by six readers as well as investigator site interpretations for the 292 subjects who completed the study. Quantitative evaluations including percent stenosis and normal vessel measurements were also performed. Secondary endpoints included identification of accessory renal arteries, diagnosis of fibromuscular dysplasia (FMD), diagnostic confidence, and need for additional imaging. RESULTS: A total of 292 patients suspected of renal artery disease completed the study. CE‐MRA demonstrated statistically significant improvement in assessability of vascular segments compared to ToF: 95.9% vs. 77.6% (P < 0.0001). In the BR, the sensitivity and specificity of CE‐MRA were noninferior to ToF‐MRA (53.4% vs. 46.6% and 95.1% vs. 85.7%, respectively). There was less error in the CE‐MRA stenosis measurements (0.15 mm gadobutrol vs. 0.41 mm ToF, P < 0.05). FMD was correctly diagnosed more frequently, 10% more accessory renal arteries were identified (P < 0.01), diagnostic confidence increased (P < 0.01), and fewer additional imaging studies were recommended (P < 0.01). CONCLUSION: Gadobutrol‐enhanced MRA of the renal arteries has superior visualization, more accurate vessel measurements, and may serve as a CTA alternative without any ionizing radiation. https://onlinelibrary.wiley.com/doi/abs/10.1002/jmri.25774/full
Views: 22 JMRI ISMRM
Clinical pharmacist interventions on mortality of cardiac patients – Video abstract [ID 98300]
Video abstract of an original research paper “Effectiveness of the clinical pharmacist in reducing mortality in hospitalized cardiac patients: a propensity score-matched analysis” published in the open access journal Therapeutics and Clinical Risk Management by Zhai XB, Gu ZC, Liu XY. Background: Pharmacist-led medication review services have been assessed in the meta-analyses in hospital. Of the 135 relevant articles located, 21 studies met the inclusion criteria; however, there was no statistically significant difference found between pharmacists’ interventions and usual care for mortality (odds ratio 1.50, 95% confidence interval 0.65, 3.46, P=0.34). These analyses may not have found a statistically significant effect because they did not adequately control the wide variation in the delivery of care and patient selection parameters. Additionally, the investigators did not conduct research on the cases of death specifically and did not identify all possible drug-related problems (DRPs) that could cause or contribute to mortality and then convince physicians to correct. So there will be a condition to use a more precise approach to evaluate the effect of clinical pharmacist interventions on the mortality rates of hospitalized cardiac patients. Objective: To evaluate the impact of the clinical pharmacist as a direct patient-care team member on the mortality of all patients admitted to the cardiology unit. Methods: A comparative study was conducted in a cardiology unit of a university-affiliated hospital. The clinical pharmacists did not perform any intervention associated with improper use of medications during Phase I (preintervention) and consulted with the physicians to address the DRPs during Phase II (postintervention). The two phases were compared to evaluate the outcome, and propensity score (PS) matching was applied to enhance the comparability. The primary endpoint of the study was the composite of all-cause mortality during Phase I and Phase II. Results: Pharmacists were consulted by the physicians to correct any drug-related issues that they suspected may cause or contribute to a fatal outcome in the cardiology ward. A total of 1,541 interventions were suggested by the clinical pharmacist in the study group; 1,416 (92.0%) of them were accepted by the cardiology team, and violation of incompatibilities had the highest percentage of acceptance by the cardiology team. All-cause mortality was 1.5% during Phase I (preintervention) and was reduced to 0.9% during Phase II (postintervention), and the difference was statistically significant (P=0.0005). After PS matching, all-cause mortality changed from 1.7% during Phase I down to 1.0% during Phase II, and the difference was also statistically significant (P=0.0074). Conclusion: DRPs that were suspected to cause or contribute to a possibly fatal outcome were determined by clinical pharmacist service in patients hospitalized in a cardiology ward. Correction of these DRPs by physicians after pharmacist’s advice caused a significant decrease in mortality as analyzed by PS matching. The significant reduction in the mortality rate in this patient population observed in this study is “hypothesis generating” for future randomized studies. Read the original research paper here: https://www.dovepress.com/effectiveness-of-the-clinical-pharmacist-in-reducing-mortality-in-hosp-peer-reviewed-article-TCRM
Views: 347 Dove Medical Press
Pharmacogenomics in Cardiac Drugs
Dr. Peter O’Donnell, from the University of Chicago’s Committee on Clinical Pharmacology and Pharmacogenomics, and Dr. Matthew Sorrentino, a Professor of Medicine in the Section of Cardiology at the University of Chicago, in Illinois, dialogue on their article appearing in the June 2015 issue of Mayo Clinic Proceedings, where they completed a rigorous examination of cardiac drugs using genetic markers and provide clinicians with clinical endpoints for enhanced patient care. Available at: http://tinyurl.com/ogkav72
Views: 1277 Mayo Proceedings
Dr. Patrick Wen Discusses the Clinical Trial Endpoints Initiative
Dr. Patrick Wen of Dana-Farber Cancer Institute discusses the National Brain Tumor Society's Clinical Trial Endpoints Initiative. See more here: http://tinyurl.com/l2owsmj
Dr. Michael Joner: Additional safety benefits of COMBO vs. DES
Dr. Joner discusses what makes the COMBO Stent unique to other drug-eluting stents. "I think most contemporary Drug Eluting Stents (DES) that are on the market are focused on the inhibition of the neointima and as primary efficacy endpoint, so we have coatings that also release antiproliferative drugs in high concentrations most often and they are focused on efficacy. What sets it apart is that the COMBO Dual Therapy Stent it also focuses on safety aspects. What we learned from the past that this is very important to have also long term success because efficacy also depends on long term safety and that is the funny thing here but this is certainly a very important point with the COMBO Stent."
Views: 76 orbusneichmedia
ESC: Cost, Safety, and Efficacy Guide Drug Choice
Prasugrel had no overall efficacy advantage over clopidogrel when treating patients with non--ST-elevation acute coronary syndrome in a prospective, randomized trial with more than 9,000 patients. Results from the Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndrome (TRILOGY ACS) did provide reassuring, new safety data for prasugrel compared with clopidogrel in the enrolled patient population. The study outcomes also supplied very suggestive evidence for certain efficacy advantages of prasugrel compared with clopidogrel in the study's target patients. But prasugrel's inability to beat clopidogrel for the study's primary efficacy end point produced an inescapable argument against springing for the more expensive prasugrel rather than the cheaper clopidogrel in most non--ST-elevation ACS patients who initially undergo medical management rather than revascularization therapy. For more, visit, http://www.ecardiologynews.com
Views: 260 MDedge
Edoxaban has similar efficacy, but better safety and net outcomes, compared with warfarin
Robert P. Giugliano, MD& SM from Harvard Medical School and Giulia Renda, MD & Associate Professor of Cardiology from d'Annunzio University of Chieti-Pescara discusses outcomes in 2824 patients with valvular heart disease treated with edoxaban or warfarin in the ENGAGE AF-TIMI 48 Trial at the American College of Cardiology 65th Annual Scientific Session & Expo (ACC.16). MDLinx Conference Coverage - American College of Cardiology 65th Annual Scientific Session & Expo (ACC.16): http://www.mdlinx.com/cardiology/conference-interview/american-college-of-cardiology-65th-annual-scientific-session-expo-acc-16-/231955 MDLinx: http://www.mdlinx.com/ Smartest Doc & Board Exam Prep: http://www.thesmartestdoc.com/ M3 USA: http://usa.m3.com/ Follow MDLinx: Facebook - https://www.facebook.com/MDLinx Twitter - https://twitter.com/MDLinx Google+ - https://plus.google.com/+Mdlinx/
Views: 849 MDLinx
The Great Debate: What is Enough … Women in Clinical Trials (complete recording)
This is the full recording of "The Great Debate: What is Enough ... Women in Clinical Trials?". The program was recorded on May 16th, 2018, and sponsored by the FDA Office of Women’s Health. It includes an introduction by Office of Women’s Health Director Marsha Henderson, a keynote address by FDA Commissioner Scott Gottlieb, and the complete debate. The Great Debate centered on the challenges and complexity of the question “What is enough?” when determining participation of women in cardiovascular disease clinical trials. The debate participants were two leading cardiovascular experts: Ellis F. Unger, M.D., FDA Center for Drug Evaluation and Research, and Rita Redberg, M.D., M.Sc., F.A.C.C., UCSF. It was a robust discussion centering on a complex question that has been debated among academia, federal, and non-government and consumer organizations for more than a quarter century. 0:00:00 – 0:04:02 Opening Remarks, Marsha Henderson 0:04:03 – 0:14:40 Keynote Address, FDA Commissioner Scott Gottlieb, M.D. 0:15:06 – 0:19:54 Introduction, Marjorie Jenkins, M.D. 0:20:20 – 1:21:40 Debate
Views: 44 USFoodandDrugAdmin
How to conduct a clinical trial - clinical end points
12 Hour MBA in Clinical Trials Master clinical trials at speed - big ideas and fundamentals for pharmaceutical companies, contract research organisations, banks, advisors and suppliers. The 12 Hour MBA in Clinical Trials is an introductory-level online training course designed to bridge knowledge gaps. It is most useful to new entrants, senior managers needing a big picture refresher and professional advisors and suppliers to the field. Explore real-world lessons they don't teach you on the job, from the comfort of your desk. In just 12 hours, you will: - Learn what the target product profile should include - Understand the different phases of the clinical development process - Discover the principles of clinical trial design - Find out how to design a protocol - Learn about good clinical practice and how to apply it - Discover how to collect, manage and analyse data in a clinical trial - Look at the ethical, legal and safety issues involved For more information: http://www.terrapinntraining.com/training/12-Hour-MBA-in-Clinical-Trials
Views: 328 TerrapinnTraining
Epicor Cardiac Ablation LP (Low Profile) Sternotomy Animation
The Epicor LP system has a lower profile (smaller relative to the first generation technology) as well as other features designed to facilitate easier device introduction and placement around and on patients' hearts. In addition, the Epicor LP System is equally suited for use in both closed-chest procedures performed through a single incision, and in open-chest procedures. In the December 2007 edition of The Annals of Thoracic Surgery, the results of an independent investigator clinical trial led by Mark Groh, M.D., showed that AF is effectively treated using the Epicor Cardiac Ablation System when used concomitantly to corrective heart surgery. The investigators reported that more than 83 percent of all patients, followed for at least six months after surgery, were free from AF. In addition, 86 percent of the patients followed for at least 18 months remained free from AF. The investigators reported that there were no device or ablative procedure-related adverse events and specifically noted an absence of esophageal, coronary or phrenic nerve damage. The 2007 results confirmed the findings of an earlier European multi-center trial published in the September 2005 Journal of Thoracic and Cardiovascular Surgery. The investigators in the European clinical trial reported an 85 percent freedom-from-AF rate at six months post-procedure - the study's primary efficacy end point - in patients concomitantly treated for AF with the Epicor Cardiac Ablation System.
Views: 5826 jrichmond4242
NovaBay Highlights Data from Phase 2 Urinary Catheter Blockage and Encrustation Study
http://NovaBay.com NovaBay Pharmaceuticals Announces Positive Results from Phase 2 Clinical Study of Auriclosene to Reduce Urinary Catheter Blockage and Encrustation Primary Endpoints Achieved Showing Statistically Significant and Clinically Meaningful Benefits for Patients with Long-Term Indwelling Catheters Results Pave the Way for Phase 3 Pivotal Studies EMERYVILLE, CA - September 16, 2013 NovaBay Pharmaceuticals, Inc., an advanced clinical-stage biopharmaceutical company developing anti-microbial products, today announced positive top-line results from its recently completed Phase 2 clinical study CL1001 for auriclosene (NVC-422) to prevent urinary catheter blockage and encrustation (UCBE) of indwelling urinary catheters. The results of the study show that NovaBay's auriclosene-based irrigation solution has demonstrated the ability to mitigate an important medical problem, cut healthcare costs, and improve the quality of life for tens of thousands of patients in the U.S. alone. Full Press Release Here: http://novabay.com/pressrelease/novabay-pharmaceuticals-announces-positive-results-phase-2-clinical-study-auriclosene-reduce-urinary-catheter-blockage-encrustation
Views: 5784 Stock-Sector
The NACIAM Trial: N-Acetylcysteine reduces infarct size - Prof John Beltrame - ESC2016
Prof John Beltrame from the University of Adelaide, Australia, speaks to Cardio Debate & Radcliffe Cardiology about the NACIAM Trial, during the ESC2016 Congress held in Rome, Italy. For more interviews like this please visit www.cardio-debate.com *TRANSCRIPT* Could you explain the rationale and design behind the NACIAM trial? The NACIAM trial, which stands for the N-acetylcysteine in Acute Myocardial Infarction trial, is a study investigating the potential benefits of N-acetylcysteine in both reperfusion injury as well as perfusion in patients with ST-elevation myocardial infarction. The rational behind this is, as we all know ST-elevated myocardial infarction is associated with an acute coronary occlusion, for which we undertake reperfusion therapy. As a result of the promptness of the reperfusion therapy will result in an infarct size. But the dependent variables for the infarct size are the duration of ischaemia as well as reperfusion injury. So the duration of ischemia results in ischaemic injury due to free radical generation, as does the reperfusion injury. The rational behind using N-acetylcysteine is that it is a free radical scavenger, and therefore reduces oxidative stress and also reperfusion injury. It also has a secondary effect in that it potentiates the effect of glyceryl trinitrate, or GTN. And GTN has beneficial properties both in vasodilation, anti-platelet effects as well as reducing inflammation. So these benefits are enhanced with the use of N-acetylcysteine. The purpose of the NACIEM study was to assess the efficacy of adding high-dose intravenous N-acetylcysteine to low-dose intravenous GNT in acute ST-elevation myocardial infarction patients undergoing primary percutaneous coronary interventions. It was a randomised double-blind placebo-controlled multi-centre trial, and it involved patients who had a first time ST-elevation myocardial infarction within 12 hours of being randomized to either N-acetylcysteine or placebo with background GTN therapy. It was a high-dose of NACIAN given in the first hour, and then continued at a low dose for the next 47 hours. An MRI was performed was performed at about five days, the primary end point being the myocardial infarct size on MRI. The secondary end point was myocardial salvage. The key findings from this study was that there was a 5.5 per cent reduction in infarct size with the use of N-acetylcysteine compared with placebo. This is despite the fact that there was not any difference between the groups in terms of size of infarction. Consequently, there was a significant improvement in myocardial salvage. The plot you can see [see video] looking at myocardial salvage demonstrates that the shorter ischaemic time results in a greater beneficial effect of the N-acetylcysteine. To summarise, the main findings from the study is that the addition of N-acetylcysteine to low-dose intravenous GTN reduces infarct size, increases myocardial salvage and there is a larger effect with a shorter duration of ischaemia. The implications of this study is that with a reduction in infarct size of about 5.5 per cent could potentially translate in a 20 per cent reduction in mortality based on previous studies. From here the next point to move on to, is to undertake a study where we’re looking at clinical end points, rather than the surrogate end point of myocardial infarct size.
Views: 102 Cardio Debate
Charité Clinical Journal Club by Fred Luft - 26.09.2017
The N Engl J Med image of the week shows a head-and-neck CT of a 35 year-old man with neck pain and swallowing difficulties for over a year. You are offered cervical spondyloarthropathy, fish-bone foreign body, temporomandibular joint dysfunction, Ernest syndrome, and Eagle’s syndrome. Knowledge of head-and-neck anatomy is helpful here. Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Investigators conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. Canakinumab induced more sepsis deaths, which is not surprising. However, cancer deaths were reduced, which surprised me. Effects on cardiovascular outcomes was significant but at $200,000 per year hardly practicable. Heparin is used as the anticoagulant for percutaneous coronary interventions in Europe, while bivalirudin is favored in the USA. Swedish investigators enrolled patients with either ST-segment elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI) who were undergoing PCI and receiving treatment with a potent P2Y12 inhibitor (ticagrelor, prasugrel, or cangrelor) without the planned use of glycoprotein IIb/IIIa inhibitors. The trialists found no significant difference between treatment with bivalirudin and treatment with heparin with respect to the rate of death, repeat myocardial infarction, or major bleeding events during 180 days of follow-up. US surgeons report 12-year outcomes for Roux-en-Y gastric bypass surgery for obesity. There are two control groups, namely the uninsured and the unwilling. Weight loss comprised about 30% of body mass in the operated, while the control groups lost no weight. Type-2 diabetes regressed, at least if the patients were not yet insulin-dependent and new cases of diabetes were decreased. A salubrious effect on blood pressure is also reported. We next inspect a genome-wide association study on gestational duration and preterm birth. Five genes were found with astoundingly low p values. However, the practicable magnitude of the effects was not given. There are excellent reviews on food allergy and the point of performing molecular diagnostic screening (thrombophilia testing) after venous thromboembolism. The case of the week involves a 59 year-old woman with a two week history of an asymmetrical polyarthropathy with acutely inflamed affected joints. Duchenne muscular dystrophy (DMD) is a severe, progressive, and rare neuromuscular, X-linked recessive disease. Dystrophin deficiency is the underlying cause of disease; therefore, mutation-specific therapies aimed at restoring dystrophin protein production are being explored. Investigators aimed to assess the efficacy and safety of ataluren in ambulatory boys with nonsense mutation DMD. Ataluren is a small molecule designed to cause stop codons to be skipped over during translation. I found the results disappointing and modest. Cabotegravir and rilpivirine are antiretroviral drugs in development as long-acting injectable formulations. The LATTE-2 study evaluated long-acting cabotegravir plus rilpivirine for maintenance of HIV-1 viral suppression through 96 weeks. The injectable strategy was effective. mRNA vaccines combine desirable immunological properties with an outstanding safety profile and the unmet flexibility of genetic vaccines. Based on in situ protein expression, mRNA vaccines are capable of inducing a balanced immune response comprising both cellular and humoral immunity while not subject to MHC haplotype restriction. We inspect a German mRNA vaccine in humans directed against rabies. Japan has entered the era of super-ageing and advanced health transition, which is increasingly putting pressure on the sustainability of its health system. The level and pace of this health transition might vary across regions within Japan and concern is growing about increasing regional variations in disease burden. If the poor Japanese would just stop smoking and embrace healthier life styles, their Global Burden of aging could get even worse. We inspect reviews on cholera and on hypothyroidism. We close the session with a patient who has mycosis fungoides. How is this T-cell lymphoma best treated?
United Therapeutics Advances to Second Cohort in Phase I Trial of PSTI's PLX-PAD Cells
HAIFA, Israel, Sept. 8, 2014 (GLOBE NEWSWIRE) -- Pluristem Therapeutics Inc. (PSTI) (TASE:PLTR), a leading developer of placenta-based cell therapy products, announced today that its licensee, United Therapeutics Corporation, has completed the dosing of the first cohort of patients in its Phase I study using Pluristem's PLacental eXpanded (PLX-PAD) cells in patients diagnosed with pulmonary arterial hypertension (PAH). PAH, with a global market estimated at approximately $3 billion, is characterized by abnormally high blood pressure in the arteries of the lungs; it can disrupt lung and heart function, leading to debilitating conditions such as heart failure. The Phase I study, being conducted in Australia, is an open-label, dose-escalation study designed to enroll 9 patients diagnosed with PAH. The first cohort of 3 patients has received 0.5 million PLX cells per kilogram body weight. An independent Data Safety Monitoring Board recommended advancement to the second cohort. The second cohort will receive 1 million cells per kilogram, while the third cohort is planned to be administered 2 million cells per kilogram. The primary endpoint of the study is the safety of PLX-PAD cells, which will be evaluated at 12 weeks and one year after dosing. Secondary efficacy endpoints are to be measured at six weeks post-treatment in order to assess changes in the ability to exercise, disease severity and cardio-respiratory function; measures include six-minute walk distance and cardio-pulmonary hemodynamic parameters evaluated via right heart catheterization and echocardiogram. "We look forward to preliminary results for this trial in 2015, after completion of dosing in all three cohorts," stated Pluristem Chairman and CEO Zami Aberman. "This Phase I study is important to the development of our PAH program in conjunction with United Therapeutics, and we are delighted to work with United Therapeutics in advancing the promise of cell therapy to treat pulmonary diseases." The Phase I study is being conducted as part of a 2011 licensing agreement between United Therapeutics and Pluristem. Pursuant to the agreement, United Therapeutics will develop, market and sell Pluristem's PLX-PAD cells for PAH. Pluristem is eligible to receive up to $55 million based on successful achievement of clinical milestones and commercialization, and reimbursement of certain R&D costs. Following commercialization, United Therapeutics will purchase commercial supplies of PLX-PAD cells from Pluristem at a specified margin over Pluristem's cost, and will pay royalties at a percentage of its gross profits.
Views: 115 CorporateProfile
Can-Fite Completes Development of Commercial Biomarker Test
PETACH TIKVA, Israel, March 18, 2015 /PRNewswire/ -- Can-Fite BioPharma Ltd. (NYSE MKT: CANF) (CFBI.TA), a biotechnology company with a pipeline of proprietary small molecule drugs that are being developed to treat inflammatory diseases, cancer and sexual dysfunction, announced today it has completed the development of a commercial predictive biomarker blood test kit for the A3 adenosine receptor (A3AR). The biomarker test can be used at any molecular biology lab, where a small blood sample from a prospective patient would be tested and within just a few hours, results indicate if the patient would benefit from treatment with Can-Fite's drugs, which are currently in clinical trials for rheumatoid arthritis, psoriasis, and liver cancer. A3AR is present in high concentrations in inflammatory cells and cancer cells. Can-Fite's proprietary drugs target and bind to A3AR, causing cancer and inflammatory cell apoptosis (programmed cell death). This creates a targeted anti-cancer and anti-inflammatory effect, while leaving normal cells unharmed. Identifying patients with elevated A3AR levels would indicate which patients would benefit most from Can-Fite's drugs, thereby offering personalized medicine. "The completion of the development of our commercial A3AR biomarker test kit comes at a very important time since we plan to use the test kit in our upcoming advanced clinical studies. We believe the test kit will create efficiencies in our trials in patient enrollment and monitoring. As we progress into late-stage clinical trials for CF101 in auto-immune diseases, our A3AR biomarker test kit is ready for wide-scale use to help doctors and their patients identify who will be most responsive to Can-Fite's drugs. We believe these patients can significantly benefit from personalized medicine due to the high degree of clinical heterogeneity," stated Can-Fite CEO Dr. Pnina Fishman. The U.S. Patent and Trademark Office issued Can-Fite a patent for the utilization of A3AR as a biomarker to predict patient response to its drug CF101 in autoimmune inflammatory indications. In December 2013, Can Fite reported favorable results from its Phase IIb rheumatoid arthritis clinical trial for CF101, an A3AR agonist. Only patients with elevated baseline expression levels of the biomarker A3AR were enrolled in the study. CF101 met all primary efficacy endpoints, showing statistically significant superiority over placebo in reducing signs and symptoms of rheumatoid arthritis. About Can-Fite BioPharma Ltd. Can-Fite BioPharma Ltd. (NYSE MKT: CANF) (CFBI.TA) is an advanced clinical stage drug development Company with a platform technology that is designed to address multi-billion dollar markets in the treatment of cancer, inflammatory disease and sexual dysfunction. The Company's CF101 is in Phase II/III trials for the treatment of psoriasis and the Company is preparing for a Phase III CF101 trial for rheumatoid arthritis. Can-Fite's liver cancer drug CF102 is in Phase II trials and has been granted Orphan Drug Designation by the U.S. Food and Drug Administration. CF102 has also shown proof of concept to potentially treat other cancers including colon, prostate, and melanoma. The Company's CF602 has shown efficacy in the treatment of erectile dysfunction. Can-Fite has initiated a full pre-clinical program for CF602 in preparation for filing an IND with the U.S. FDA in this indication. These drugs have an excellent safety profile with experience in over 1,200 patients in clinical studies to date. For more information please visit: www.can-fite.com
Views: 74 CorporateProfile
Is the Trial Negative or Indeterminate: Hot to Tell and More.
Get more medical news analysis at http://www.medpagetoday.com or http://www.methodsman.com Today we’re talking about negative clinical trials. This discussion / rant is inspired by this article, appearing in the New England Journal of Medicine: The article, which you should read, by the way, is much more in depth than I can be in the time I have here, but I will give you the gist and my own take on the issue. So, here’s the deal. We often say that a clinical trial “failed”, meaning the drug that was being tested did not perform statistically better than placebo. We also call that a “negative” trial. A “positive trial” is a good thing – one of the few places in medicine, aside from the letter from Donald Trump’s doctor, where a “positive finding” is something you want to get. Now, we label a trial as positive or negative based upon, generally, one test – a test of statistical significance of the primary outcome. And we set a threshold for statistical significance at a p-value of 0.05. Sound good? It’s not. For many reasons. For a detailed description why, check out the link below this video. But quickly, here are the biggies: First, as the authors of the NEJM paper note, describing a trial as “negative” is often misleading. The literature is rife with underpowered studies that didn’t enroll enough people to ensure that a clinically meaningful effect of the drug was ruled out. Better to describe such studies as “uninformative”. How do you tell the difference? Decide what the smallest difference in effect size would be to be clinically important. If the 95% confidence interval includes that number, you’re underpowered. If it doesn’t the study is negative. We should also note the arbitrariness of the 0.05 threshold for the p-value. The authors note, correctly that “P-values should be interpreted as a continuum wherein the smaller the P value, the greater the strength of the evidence for a real treatment effect”. Using a bit of Bayes theorem can highlight this issue to an even greater extent. If you had 50% confidence in the efficacy of a drug before the study, and the p-value in the trial was 0.04, you should be 74% confident in the drug efficacy after the trial. If the p-value was 0.01, you’d be 89% confident. The equation to figure this out appears below, but take my word for it. In other words, we should take the degree of statistical significance and allow that to inform our future confidence in the drug. Taking a binary positive/negative approach misses this point entirely. Finally, a word on secondary outcomes. The primacy of the primary outcome is due in large part to concerns about multiple comparisons. Without a pre-specified primary outcome, a researcher could check multiple outcomes and just report on whichever one happens to give the best results. All-cause mortality doesn’t work? How about cardiovascular mortality? No? How about myocardial infarction? We often tell our students that if you check 20 outcomes, statistically speaking, at least one is likely to be a false positive. Here’s a little graph that shows, over 10,000 simulated studies, the number of false positive outcomes you’d get if you checked 20 total. This is true, but only if the secondary outcomes are completely independent of each other. Think of it this way – if we wanted to compare hand size between the current presidential candidates, and measured in both inches and centimeters, we wouldn’t really penalize ourselves for multiple comparisons – inches and centimeters are 100% correlated. This matters because often secondary outcomes are highly correlated. So, in certain circumstances, when the primary outcome is negative we should look to those secondary outcomes – if they seem to be telling a coherent biologically-plausible story, we might not want to dismiss that new drug out of hand. Hopefully this wasn’t too depressing a glimpse into the world of clinical trial outcomes. If it was, well, try to stay positive.
Views: 105 F. Perry Wilson
Turmeric and arthritis | Why Turmeric is useful in managing Arthritis
Turmeric and Arthritis | Why Turmeric is useful in managing Arthritis Visit http://goo.gl/j1NJgw to know more about Arthritis pain management "Turmeric, Curcumin, And Rheumatoid Arthritis" According to the World Health Organization, 80% of the Earth's inhabitants rely upon traditional medicines for their primary health-care needs, in part due to the high cost of Western pharmaceuticals.Medicines derived from plants have played a pivotal role in the health care of both ancient and modern cultures. One of the prime sources of plant-derived medicines is spices. Turmeric is one such spice known around the world by different names. Turmeric is the dried powdered root stalks of the turmeric plant, a member of the ginger family, from which the orange-yellow pigment curcumin can be extracted. The spice turmeric is what makes curry powder yellow, and curcumin is what makes turmeric yellow. Rheumatoid arthritis is a chronic is a systemic inflammatory disorder that causes progressive destruction of the cartilage and bone of joints. The long-term prognosis of RA is poor with as much as 80% of patients affected becoming disabled with a reduction of years in life expectancy. There's lots of drugs one can take, but unfortunately they're often associated with severe side effects including blood loss, and bone loss, and bone marrow suppression, and toxicity to the liver and eyes. There's got to be a better way. Well, efficacy of curcumin was first demonstrated over 30 years ago. Forty-five patients diagnosed with rheumatoid arthritis were randomized into three groups: curcumin, the standard of care drug, or both. The primary endpoint was a reduction in disease activity, as well as a reduction in joint tenderness and swelling.All three groups got better, but interestingly the curcumin groups showed the highest percentage of improvement, significantly better than those in the drug group. The findings are significant, demonstrating that curcumin alone was not only safe and effective, but surprisingly more effective in alleviating any pain compared to the leading drug of choice, all without any apparent adverse side effects. In fact curcumin appeared protective, given that there were more adverse reactions in the drug group than the combined drug and curcumin group. In contrast to the non-steroidal anti-inflammatory drugs, curcumin has no gastrointestinal side effects and may even protect the lining of the stomach. ======================================================= Related videos Why Arthritis Causes Pain https://youtu.be/ooDzTErR3iI How to Choose A Pair of Compression Gloves https://youtu.be/cydMzegFTOg 7 foods to avoid in arthritis https://youtu.be/j1kP6I-YWqA Arthritis Pain Relief In 9 Simple Ways | Arthritis Treatment Natural Way https://youtu.be/x7Q9n8JLZRw Arthritis facts | Seven Facts About Arthritis | Rheumatoid Arthritis Facts https://www.youtube.com/watch?v=HriWKghw81k ======================================================= Read interesting articles on Best Compression Gloves What is Arthritis: http://bestcompressiongloves.com/what-is-arthritis/ Why Compression Gloves Are Really Helpful in Treatment For Arthritis? http://bestcompressiongloves.com/why-compression-gloves-are-really-helpful-in-treatment-for-arthritis/ 5 Simple Things You Can Do to Help in Treatment For Arthritis: http://bestcompressiongloves.com/5-things-you-can-do-to-help-treatment-for-arthritis/ Visit http://bestcompressiongloves.com for more arthritis related news. Join us on Facebook https://www.facebook.com/copressiongloves123 Follow us on Twitter http://twitter.com/cure_arthritis
PIs Christopher P. Cannon, MD and Robert P. Giugliano, MD discuss the results of the IMPROVE-IT trial, which were presented at the American Heart Association Scientific Sessions 2014 in Chicago. Read the text from section 6.3.2. of the Guidelines “Nonstatins Added to Statins or in Statin-Intolerant Individuals. 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults http://circ.ahajournals.org/content/129/25_suppl_2/S1
Views: 1944 AHAScienceNews
Randomized comparison of ticagrelor versus prasugrel in ST elevation myocardial infarction
Additional effective antiplatelet agents in your armamentarium for treating patients with STEMI are always welcome. Before the Prague 18 trial, two of these – prasugrel and ticagrelor – had each been compared separately to clopidogrel, but had never been compared directly to each other. Join Dejan Milasinovic (Serbia) as he reports from ESC Congress 2016 the details of this illuminating trial: What were the primary and secondary endpoints? How did each of these agents perform? What is the importance of the so-called “neutral” results? Learn why the results of Prague 18 offer additional choices for DAPT today… For more on this subject, please visit https://www.pcronline.com/
Views: 860 PCR
ESC 2014 Hotline I Cardiovascular Disease Novel Therapies
Elliott Antman, MD, FAHA, Mariell Jessup, MD, FAHA, and Mark Creager MD, FAHA discuss the science that was presented during Hotline I Cardiovascular Disease Novel Therapies at ESC 2014 in Barcelona, including PARADIGM HF, CONFIRM, MORE-CRT, COPPS-2.
Views: 541 AHAScienceNews
Demystifying Medicine 2016: Progress in Understanding Congenital Heart Disease
Demystifying Medicine 2016: Progress in Understanding Congenital Heart Disease (the #1 killer in birth defects): mechanisms and new technologies Air date: Tuesday, March 22, 2016, 4:00:00 PM Category: Demystifying Medicine Runtime: 01:36:07 Description: Demystifying Medicine is an annual course from January to May designed to help bridge the gap between advances in biology and their application to major human diseases. The course includes presentation of patients, pathology, diagnosis, and therapy in the context of major disease problems and current research, primarily directed toward Ph.D. students, fellows, and staff. All are invited. For more information go to https://demystifyingmedicine.od.nih.gov/ Author: Gail Pearson, MD, ScD, NHLBI, NIH and Robert Lederman, MD, NHLBI, NIH Permanent link: http://videocast.nih.gov/launch.asp?19567
Views: 768 nihvcast
Charité Clinical Journal Club by Fred Luft - 28.1.2015
The N Engl J Med image of the week is an abdominal transverse CT. We observe a stomach filled with dark matter. You are offered gastrointestinal stromal tumor, obstipation, pancreatic phlegmon, subphrenic abscess, and trichobezoar. We discuss all these conditions. How hypertension during pregnancy should be managed is unclear. Thus, hypertensive pregnant women were randomly assigned to less-tight control (target diastolic blood pressure, 100 mm Hg) or tight control (target diastolic blood pressure, 85 mm Hg). The composite primary outcome was pregnancy loss or high-level neonatal care for more than 48 hours during the first 28 postnatal days. The study showed that tight control of hypertension conferred no apparent benefits to the fetus and only a moderate benefit (a lower rate of progression to severe hypertension) for the mother. Angioedema induced by treatment with angiotensin-converting–enzyme (ACE) inhibitors accounts for one third of angioedema cases in the emergency room. Icantibant blocks the bradykinin B2 receptor and could help the condition. Investigators assigned patients who had ACE-inhibitor–induced angioedema of the upper aerodigestive tract to treatment with 30 mg of subcutaneous icatibant or to the current off-label standard therapy consisting of intravenous prednisolone (500 mg) plus clemastine (2 mg). The primary efficacy end point was the median time to complete resolution of edema. Icantibant may have helped. Ruxolitinib, a Janus kinase (JAK) 1 and 2 inhibitor, was shown to have a clinical benefit in patients with polycythemia vera in a phase 2 study. Thus, investigators conducted a phase 3 open-label study to evaluate the efficacy and safety of ruxolitinib versus standard therapy in patients with polycythemia vera who had an inadequate response to or had unacceptable side effects from hydroxyurea. Ruxolitinib was effective in controlling the hematocrit, reducing spleen size, and improving symptoms in patients with polycythemia vera who had an inadequate response to or had unacceptable side effects from hydroxyurea. The next investigators randomly assigned 3066 premenopausal women with breast cancer, stratified according to prior receipt or nonreceipt of chemotherapy, to receive 5 years of tamoxifen, tamoxifen plus ovarian suppression, or exemestane plus ovarian suppression. Exemestane was not convincing in my view. On the basis of the 2014 guidelines for hypertension therapy in the United States, many eligible adults remain untreated. Epidemiologists projected the cost-effectiveness of treating hypertension in U.S. adults according to the 2014 guidelines. If you like crystal ball gazing you will love this paper. The N Engl J Med reviews allergic rhinitis. We learn that combining a nasal antihistamine with an intranasal glucocorticoid could offer additive effects. In cases in which pharmacotherapy is ineffective or not acceptable to the patient, allergen-specific immunotherapy could be used. The case of the week concerns a 49 year-old person with a broad anion gap metabolic acidosis and envelope-like structures in his urine. Lancet investigators randomly assigned 490 adults with rheumatoid arthritis who had pain and dysfunction of the hands and had been on a stable drug regimen for at least 3 months, to either usual care or usual care plus a tailored strengthening and stretching hand exercise program. The exercises seemed to help. Trend data for causes of child death are crucial to inform priorities for improving child survival by and beyond 2015. The next group reports child mortality by cause estimates in 2000–13, and cause-specific mortality scenarios to 2030 and 2035. Despite the importance of ST-segment elevation myocardial infarction (STEMI) in China, no nationally representative studies have characterized the clinical profiles, management, and outcomes of this cardiac event during the past decade. The Chinese STEMI patients resemble STEMI patients elsewhere. Dengue viruses have spread rapidly within countries and across regions in the past few decades, resulting in an increased frequency of epidemics and severe dengue disease, hyperendemicity of multiple dengue virus serotypes in many tropical countries, and autochthonous transmission in Europe and the USA. If you know what autochthonous means, you are better than me. We review the topic. The patient of the week is a 71-year-old man with a 1-week history of lethargy, worsening confusion, and cough. He has eosinophilia, acute cerebral infarcts, and lung lesions.
Charité Clinical Journal Club by Fred Luft - 08.02.2017
The N Engl J Med image of the week shows an an eye with remnant pieces of iris crossing the pupil. You are offered juvenile xanthogranuloma, persistent hyperplastic primary vitreous, protruding iris collarette, iris duplication, and persistent pupillary membranes. Even a non-opthalmologist should be able to figure this one out. Salvage radiation therapy is often necessary in men who have undergone radical prostatectomy and have evidence of prostate-cancer recurrence signaled by a persistently or recurrently elevated prostate-specific antigen (PSA) level. Whether antiandrogen therapy with radiation therapy will further improve cancer control and prolong overall survival is unknown. We inspect a randomized trial of irradiation with or without concomitant antiandrogen therapy. The addition of 24 months of antiandrogen therapy with daily bicalutamide to salvage radiation therapy resulted in significantly higher rates of long-term overall survival and lower incidences of metastatic prostate cancer and death from prostate cancer than radiation therapy plus placebo. In sickle-cell anemia, the sickled cells stick to endothelium via the adhesion molecule P-selectin. The up-regulation of P-selectin in endothelial cells and platelets contributes to the cell–cell interactions that are involved in the pathogenesis of vaso-occlusion and sickle cell–related pain crises. The safety and efficacy of crizanlizumab, an antibody against the adhesion molecule P-selectin, were evaluated in patients with sickle cell disease. It looks like crizanlizumab will join hydroxyurea as the second effective therapy for sickle cell disease. Continuous-flow left ventricular assist device (LVAD) systems increase the rate of survival among patients with advanced heart failure but are associated with the development of pump thrombosis. Heart surgeons investigated the effects of a new magnetically levitated centrifugal continuous-flow pump that was engineered to avert thrombosis. They randomly assigned patients with advanced heart failure to receive either the new centrifugal continuous-flow pump or a commercially available axial continuous-flow pump. The primary end point was a composite of survival free of disabling stroke (with disabling stroke. It looks like the new pump may be better than the older model. The next investigators compared a newer LVAD design (a small intrapericardial centrifugal-flow device) against existing technology (a commercially available axial-flow device) in patients with advanced heart failure who were ineligible for heart transplantation. The centrifugal-flow device was found to be noninferior to the axial-flow device with respect to survival free from disabling stroke or need for device replacement. The N Engl J Med review is on long-acting reversible contraception. The patient of the week is a man with BMI above 40 who undergoes Roux-en-Y surgery and develops severe diarrhea 8 years later. These episodes were most voluminous after meals and often had visible particulate matter that was consistent with what he had recently eaten. In the Lancet, we inspect the efficacy and effectiveness of an rVSV-vectored vaccine in preventing Ebola virus disease; the final results from the Guinea ring vaccination, open-label, cluster-randomised trial. When the investigators compared randomly assigned contacts and contacts of contacts vaccinated in immediate clusters (day 0) versus all eligible in delayed clusters, vaccine efficacy was 100%. The next investigators aimed to study whether the addition of bortezomib to lenalidomide and dexamethasone would improve progression-free survival and provide better response rates in patients with previously untreated multiple myeloma who were not planned for immediate autologous stem-cell transplant. It did. Methotrexate is one of the most commonly used systemic drugs for the treatment of moderate to severe psoriasis; however, high-quality evidence for its use is sparse and limited to use of oral dosing. We now have the evidence. We then learn that in-utero MRI improves the diagnosis of cerebral abnormalities in infants as compared to ultrasound. The Lancet review is about medical care in slums. A slum is defined by UN Habitat as “a group of individuals that live under the same roof that lack one or more of the following conditions: access to improved water, access to improved sanitation, sufficient living space, durability of housing and secure tenure”. We close with a pregnant woman who develops fever, widespread pruritic rash, and sore throat, which were followed by myalgias and joint pain 2 days later. The patient had not yet initiated routine prenatal care. Both the patient and her partner reported no travel outside the United States for the past 2 years. The case is from South Florida, enough said.
Charité Clinical Journal Club by Fred Luft - 18.04.2018
The N Engl J Med image of the week shows a 70-year-old man who presented to the ophthalmology clinic with a 1-year history of progressive bluish discoloration of the sclerae of both eyes. He reported no ocular discomfort or blurry vision. He had previously received a diagnosis of an inflammatory arthritis for which he had been taking minocycline for more than 15 years. Examination was notable for bluish discoloration of the sclera of both eyes and pinnae of both ears. Ophthalmologic examination was otherwise normal. What is the diagnosis? Osteogenesis imperfecta, Minocycline, Ehler’s Danlos syndrome, Primary, and acquired melanosis, and Conjunctival melanoma. We review all of these conditions. Zika virus (ZIKV) is an emerging mosquito-borne flavivirus that has been linked to adverse birth outcomes. Earlier, we discussed the fact that person-to-person transmission can occur by means of sexual contact. Investigators conducted a prospective study involving men with symptomatic ZIKV infection to determine the frequency and duration of ZIKV shedding in semen and urine and to identify risk factors for prolonged shedding in these fluids. Specimens were obtained twice per month for 6 months after illness onset and were tested by real-time reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assay for ZIKV RNA and by Vero cell culture and plaque assay for infectious ZIKV. The results showed that ZIKV RNA was commonly present in the semen of men with symptomatic ZIKV infection and persisted in some men for more than 6 months. In contrast, shedding of infectious ZIKV appeared to be much less common and was limited to the first few weeks after illness onset. In addition, we review a brief case of a pregnant woman infected with ZIKV through intercourse. Thus, spread of ZIKV through intercourse appears to be a risk. In an early analysis of this next randomized-trial study, use of a magnetically levitated centrifugal continuous-flow circulatory pump was found to improve clinical outcomes, as compared with a mechanical-bearing axial continuous-flow pump, at 6 months in patients with advanced heart failure. In a randomized noninferiority and superiority trial, investigators compared the centrifugal-flow pump with the axial-flow pump in patients with advanced heart failure, irrespective of the intended goal of support (bridge to transplantation or destination therapy). The composite primary end point was survival at 2 years free of disabling stroke. Both devices are manufactured by Abbott. The investigators found that implantation of the HeartMate 3 fully magnetically levitated continuous-flow centrifugal pump prolonged survival free of disabling stroke or reoperation to replace or remove a malfunctioning device, as compared with the HeartMate II continuous-flow axial mechanical-bearing pump, at 2 years among patients with advanced heart failure. In this trial, the centrifugal-flow pump also resulted in a lower risk of stroke than the axial-flow pump, while averting pump thrombosis–related device malfunction. Diffuse large B-cell lymphomas (DLBCLs) are phenotypically and genetically heterogeneous. Gene-expression profiling has identified subgroups of DLBCL (activated B-cell–like [ABC], germinal-center B-cell–like [GCB], and unclassified) according to cell of origin that are associated with a differential response to chemotherapy and targeted agents. The next investigators sought to extend these findings by identifying genetic subtypes of DLBCL based on shared genomic abnormalities and to uncover therapeutic vulnerabilities based on tumor genetics. They studied 574 DLBCL biopsy samples using exome and transcriptome sequencing, array-based DNA copy-number analysis, and targeted amplicon resequencing of 372 genes to identify genes with recurrent aberrations. They next developed and implemented an algorithm to discover genetic subtypes based on the co-occurrence of genetic alterations. The investigators identified four prominent genetic subtypes in DLBCL, termed MCD (based on the co-occurrence of MYD88L265P and CD79B mutations), BN2 (based on BCL6 fusions and NOTCH2 mutations), N1 (based on NOTCH1 mutations), and EZB (based on EZH2 mutations and BCL2 translocations). The results could foster precision medicine treatments for DLBCLs. Apalutamide, a competitive inhibitor of the androgen receptor, is under development for the treatment of prostate cancer. They evaluated the efficacy of apalutamide in men with nonmetastatic castration-resistant prostate cancer who were at high risk for the development of metastasis. Investigators conducted a double-blind, placebo-controlled, phase 3 trial involving men with nonmetastatic castration-resistant prostate cancer and a prostate-specific antigen doubling time of 10 months or less. The testosterone-receptor targeted strategy resulted in impressive improvements...
Introduction to Clinical Pharmacology and Therapeutics - Module 1, Session 1
Introduction to Clinical Pharmacology and Therapeutics - Module 1, Session 1 with Dr. Juan J. L. Lertora This is Module 1, Session 1, of the NIH Clinical Center's "2017-2018 Principles of Clinical Pharmacology" course. The course is a lecture series covering the fundamentals of clinical pharmacology as a translational scientific discipline focused on rational drug development and utilization in therapeutics. If you have any questions or need additional information regarding the Principles of Clinical Pharmacology course, please email the course coordinator at: cc-od_clinp@mail.nih.gov.
Views: 5944 NIH Clinical Center
What does the FDA look for from Dry Eye Phase II study results?
The Inaugural Dry Eye Summit 2010 Section: Establishing Clinically Relevant Endpoints and General Criteria for Inclusion / Exclusion for Dry Eye Subgroups Topic: What does the FDA look for from Dry Eye Phase II study results?
Views: 143 DryEyeSummit
Rick Doblin, Ph.D.: "Psychedelics..." | Talks at Google
Rick Doblin - "Psychedelics: Mystical Experiences, Cultural Evolution, Non-Profit MDMA/PTSD Research, and Burning Man" Rick Doblin, the co-founder and CEO of the Multidisciplinary Association for Psychedelic Studies (MAPS, www.maps.org) discusses: - The FDA-approved research into the use of MDMA-assisted psychotherapy for Post-traumatic Stress Disorder (PTSD) in veterans and survivors of sexual abuse, rape, accidents and other traumas - What role psychedelics can play in generating mystical experiences and the political implications of those experiences for cultural evolution - How MAPS will market MDMA as a prescription medicine (projected to start in 2021), train therapists/psychiatrists, establish a network of psychedelic clinics, and provide psychedelic harm reduction services at Burning Man and festivals and venues around the world
Views: 28604 Talks at Google
Dr. Chang Discusses Combining HER2 Targeted Therapies
Jenny C. Chang, MD, director, Methodist Cancer Center, The Methodist Hospital, Professor of Medicine, Weill Cornell Medical College of Cornell University, discusses the efficacy of combining multiple targeted agents to fully block the HER2 signaling pathway in patients with breast cancer. Chang alludes to research presented at the 2011 ASCO meeting that clarified the advantages of fully blocking the HER2 receptor. These studies explored the combination of trastuzumab, a monoclonal antibody targeting HER2, and lapatinib, a dual inhibitor of HER2 and EGFR, in HER2-positive breast cancer. These agents were provided to patients without chemotherapy with pathologic complete response (pCR) as a primary endpoint. Patients that were both HER2-positive and estrogen receptor (ER)-positive were given the estrogen deprivation therapy letrozole, plus goserelin if premenopausal. The overall pCR rate for all groups was approximately 30%. Participants that were HER2-positive and ER-negative demonstrated nearly a 40% increase in pCR. The high rates of response without chemotherapy suggest that some tumors can be controlled using a combination of targeted therapies alone. Omitting chemotherapy from the treatment process would avoid many of the adverse events associated with the treatment.
Views: 586 OncLiveTV
TRACO 2017 - Clinical trials and Precision Medicine
TRACO 2017 - Clinical trials and Precision Medicine Air date: Monday, September 11, 2017, 4:00:00 PM Category: TRACO Runtime: 02:00:08 Description: Translational Research in Clinical Oncology (TRACO) Recent advances in understanding cancer biology are beginning to be translated into improvements in diagnosis and treatment of cancer. In the post-genome era, we increasingly rely on strong collaboration between basic and clinical scientists to develop novel approaches for treatment of human disease. The NCI Center for Cancer Research (CCR) is one of the largest cancer research organizations in the world, with more than 200 principal investigators, and has played a major role in developing and implementing many new technologies, such as nanotechnology, next generation sequencing, genomics and proteomics. For more information go to http://ccr.cancer.gov/trainee-resources-courses-workshops-traco Author: Jill Smith, MD, Georgetown University and Curtis C. Harris, M.D., NCI, NIH Permanent link: https://videocast.nih.gov/launch.asp?23453
Views: 789 nihvcast
The Great Debate: What is Enough … Women in Clinical Trials (debate portion only)
This is the debate portion of the program "The Great Debate: What is Enough ... Women in Clinical Trials?". Recorded on May 16th, 2018, and sponsored by the FDA Office of Women’s Health. See the Keynote remarks for The Great Debate at: https://youtu.be/zBMMOOTgHdg The Great Debate centered on the challenges and complexity of the question “What is enough?” when determining participation of women in cardiovascular disease clinical trials. The debate participants were two leading cardiovascular experts: Ellis F. Unger, M.D., FDA Center for Drug Evaluation and Research, and Rita Redberg, M.D., M.Sc., F.A.C.C., UCSF. It was a robust discussion centering on a complex question that has been debated among academia, federal, and non-government and consumer organizations for more than a quarter century.
Views: 205 USFoodandDrugAdmin
Stanford Health Policy Forum: Controlling the Cost of Healthcare
The United States health care system is a $3 trillion enterprise, the largest in the developed world. Yet Americans often experience more severe access and quality problems, and spend much more for the same procedures and medications, than patients in other countries. Projections of the future cost of health care are unsustainable, yet many well-intended cost-control efforts have been ineffective. This forum features two renowned experts who will discuss the causes of and potential solutions to the extraordinary cost of American health care. Physician, journalist and Stanford alum Elisabeth Rosenthal has drawn national attention to the issue through her widely praised “Paying Till It Hurts” series in the New York Times. She will be joined by Professor Doug Owens, the director of Stanford’s Center for Health Policy and an expert in health care cost-effectiveness research. Speakers: Doug Owens, Elisabeth Rosenthal, Paul Costello http://med.stanford.edu/healthpolicyforum.html
Views: 6864 Stanford
Surgeon and interventionalist: Teaming up to tackle new technologies
From PARTNER to EVEREST II, technology-oriented clinical trials are presenting new treatment options and new challenges. Dr Bob Harrington sits down with Drs Laura Mauri and Neil Moat to talk about the importance of the heart team in the success of these trials and how to ensure this multidisciplinary approach in applying trial results in clinical practice.
Views: 81 theheartorg
Transcatheter Aortic-Valve Replacement
In patients with severe, symptomatic aortic stenosis, transcatheter aortic-valve replacement has become the preferred therapy for those at high surgical risk; efficacy and safety in lower-risk patients are unclear. New research findings are summarized in this short video. Full study: http://nej.md/2msIEei Watch more Quick Take videos: http://nej.md/quick-take
Views: 1793 NEJMvideo