scholarly journals Rethinking Remdesivir for COVID-19: A Bayesian Reanalysis of Trial Findings

2020 ◽  
Author(s):  
Sarahanne Miranda Field ◽  
Joyce M. Hoek ◽  
Ymkje Anna de Vries ◽  
Maximilian Linde ◽  
Merle-Marie Pittelkow ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Mortality Rate ◽  
Clinical Improvement ◽  
Primary Outcome ◽  
Secondary Outcome ◽  
Moderate Evidence ◽  
The World ◽  
The Usa ◽  
Regulatory Bodies ◽  
Take All

Following testing in clinical trials, the use of remdesivir for treatment of COVID-19 has been authorized for use in parts of the world, including the USA and Europe. These early authorizations were largely based on results from two clinical trials. A third study published by Wang et al. was deemed inconclusive. We demonstrate the utility of Bayesian reanalyses in the context of non-significant results like the Wang et al. trial. Results of a reanalysis of the three trials show ambiguous evidence for the primary outcome of clinical improvement and moderate evidence against efficacy of remdesivir for the secondary outcome of mortality rate. We recommend that regulatory bodies take all available evidence into account for endorsement decisions.

scholarly journals Rethinking remdesivir for COVID-19: A Bayesian reanalysis of trial findings

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0255093
Author(s):  
Joyce M. Hoek ◽  
Sarahanne M. Field ◽  
Ymkje Anna de Vries ◽  
Maximilian Linde ◽  
Merle-Marie Pittelkow ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Primary Outcome ◽  
Secondary Outcome ◽  
Marketing Approval ◽  
Significant Finding ◽  
Efficacy Data ◽  
Bayesian Hypothesis Testing ◽  
The Usa ◽  
Regulatory Bodies ◽  
Take All

Background Following testing in clinical trials, the use of remdesivir for treatment of COVID-19 has been authorized for use in parts of the world, including the USA and Europe. Early authorizations were largely based on results from two clinical trials. A third study published by Wang et al. was underpowered and deemed inconclusive. Although regulators have shown an interest in interpreting the Wang et al. study, under a frequentist framework it is difficult to determine if the non-significant finding was caused by a lack of power or by the absence of an effect. Bayesian hypothesis testing does allow for quantification of evidence in favor of the absence of an effect. Findings Results of our Bayesian reanalysis of the three trials show ambiguous evidence for the primary outcome of clinical improvement and moderate evidence against the secondary outcome of decreased mortality rate. Additional analyses of three studies published after initial marketing approval support these findings. Conclusions We recommend that regulatory bodies take all available evidence into account for endorsement decisions. A Bayesian approach can be beneficial, in particular in case of statistically non-significant results. This is especially pressing when limited clinical efficacy data is available.

ACE-2-Receptors of the Epidermis, Dermal Vascular Walls and Sebaceous Gland Cells: The Way of COVID-19 Entry into the Body?

2020 ◽  
Author(s):  
Stefan Bittmann
Keyword(s):  
Clinical Trials ◽  
Viral Infection ◽  
Sebaceous Gland ◽  
The Body ◽  
Viral Agent ◽  
Therapy Options ◽  
Vascular Walls ◽  
Fish Market ◽  
The World ◽  
The Usa

Since the outbreak near a fish market in Wuhan, China, in December 2019, researchers have been searching for an effective therapy to control the spreading of the new coronavirus SARS-CoV-2 and inhibit COVID-19 infection. Many countries like Italy, Spain, and the USA were ambushed by this viral agent. To date, more than 2.5 million people were infected with SARS-CoV-2. There is no clear answer, why SARS-CoV-2 infects so many people so fast. To date of April 2020, no effective drug has been found to treat this new severe viral infection. There are many therapy options under review and clinical trials were initiated to get clearer information, what kind of drug can help in this devastating and serious situation. The world has no time.

Melatonin reduces the mortality of severely-infected COVID-19 patients

2021 ◽  
Vol 4 (4) ◽  
pp. 613-616
Author(s):  
Dun-Xian Tan ◽  
Russel J Reiter
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Mortality Rate ◽  
Randomized Clinical Trial ◽  
Control Group ◽  
Mortality Reduction ◽  
Single Center ◽  
Open Label ◽  
Melatonin Treatment ◽  
The World

SARS-CoV-2 has ravaged the population of the world for two years. Scientists have not yet identified an effective therapy to reduce the mortality of severe COVID-19 patients. In a single-center, open-label, randomized clinical trial, it was observed that melatonin treatment lowered the mortality rate by 93% in severely-infected COVID-19 patients compared with the control group (see below). This is seemingly the first report to show such a huge mortality reduction in severe COVID-19 infected individuals with a simple treatment. If this observation is confirmed by more rigorous clinical trials, melatonin could become an important weapon to combat this pandemic.

Indian Pharmaceuticals Industry in Global Scenario: An Appraisal

2020 ◽  
Vol 22 (3) ◽  
pp. 424-429
Author(s):  
Prabal Chakraborty
Keyword(s):  
Clinical Trials ◽  
Cost Effectiveness ◽  
Intellectual Property Rights ◽  
Strategic Alliances ◽  
Direct Investment ◽  
Multinational Companies ◽  
Fdi Inflows ◽  
The World ◽  
The Usa ◽  
Offshore Plants

Today, the Indian pharmaceuticals industry is recognised the world over due to the quality and cost-effectiveness of its products. At present, globally it is one of the fastest-growing industries and contributes 2.4 per cent value wise and 10 per cent volume wise globally. India alone accounts for 20 per cent of global exports in generics. In 2016, the Indian pharma industry exported USD16.89 billion and is expected to touch USD40 billion by 2020. The present generics market has immense potentiality for foreign direct investment (FDI) inflows, and worth USD14.53 billion of FDI inflows came in between April 2000 and December 2016. We have witnessed that Indian pharma companies go for joint ventures with multinational companies, make strategic alliances and co-promotions, contract research and manufacturing services, export, acquisitions and mergers, focus on new markets other than the USA and Europe, buy offshore plants and increase stakes in other companies. India is also becoming an attractive investment for the clinical trials market. The objective of this paper is to analyse the Indian pharmaceuticals industry—opportunity and threats, strategies of the Indian companies particularly after trade-related aspects of intellectual property rights (TRIPS).

scholarly journals COVID-19: Evolving from Myths and Trials to a Potentially Treatable Disease

BioMedica ◽  
2020 ◽  
Vol 36 (2S) ◽  
pp. 130-136
Author(s):  
Afshan Mehvish Naz ◽  
Samina Kausar ◽  
Mansoor Ghani ◽  
Saima Kousar
Keyword(s):  
Clinical Trials ◽  
Immune System ◽  
High Risk ◽  
Mortality Rate ◽  
Randomized Trials ◽  
Fatal Outcome ◽  
The World ◽  
Morbid Conditions

<p>Since the COVID-19 outbreak has emerged, every nation and every government are trying its best to combat the disease and develop strategies for better prevention, diagnosis, treatment and management of this lethal virus. Though the mortality rate is far less than any other pandemic the world has experienced, still patients with co-morbid conditions and immune system disorders are at high risk of fatal outcome. There are no approved treatments for COVID-19; thus, people with COVID-19 should be referred to clinical trials. Several agents have been touted as treatments for COVID-19, but at this point, the data are insufficient to inform a recommendation for or against the use of these agents outside of clinical trials; well-conducted randomized trials will be critical in determining how COVID-19 should be treated.</p>

Outcome domains and measures for pain in psoriasis used in registered trials: analysis of studies on ClinicalTrials.gov

2021 ◽  
Author(s):  
Ana Sanader Vucemilovic ◽  
Livia Puljak
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Primary Outcome ◽  
Secondary Outcome ◽  
Future Studies ◽  
Psoriasis Treatment ◽  
Trial Protocols ◽  
Secondary Outcomes ◽  
Study Designs

Aim: Psoriasis includes unpleasant symptoms such as pain. This study aimed to investigate whether clinical trials have domains related to pain in their study designs. Materials and methods: We analyzed all clinical trials about interventions for psoriasis treatment registered on ClinicalTrials.gov and the frequency of pain-related outcomes. Results: Our analysis included 1033 registered clinical trials. They had 1329 primary outcomes and 5457 secondary outcomes. The pain was used in six (0.6%) protocols as a primary outcome and 68 (6.5%) protocols as a secondary outcome. Conclusion: Pain as an outcome was used in few registered clinical trial protocols for the treatment of psoriatic conditions. Future studies should investigate why the trialists do not include pain among primary or secondary outcomes.

scholarly journals Effect of bromhexine in hospitalized patients with COVID-19

2021 ◽  
pp. jim-2020-001747
Author(s):  
Ramin Tolouian ◽  
Zuber D Mulla ◽  
Hamidreza Jamaati ◽  
Abdolreza Babamahmoodi ◽  
Majid Marjani ◽  
...  
Keyword(s):  
Hospital Discharge ◽  
Clinical Improvement ◽  
Primary Outcome ◽  
Adverse Drug Events ◽  
Antiviral Effect ◽  
Hospitalized Patients ◽  
Secondary Outcome ◽  
Risk Of Death ◽  
Significant Difference ◽  
Transmembrane Serine Protease

BackgroundBromhexine is a potent inhibitor of transmembrane serine protease 2 and appears to have an antiviral effect in controlling influenza and parainfluenza infection; however, its efficacy in COVID-19 is controversial.MethodsA group of hospitalized patients with confirmed COVID-19 pneumonia were randomized using 1:1 allocation to either standard treatment lopinavir/ritonavir and interferon beta-1a or bromhexine 8 mg four times a day in addition to standard therapy. The primary outcome was clinical improvement within 28 days, and the secondary outcome measures were time to hospital discharge, all-cause mortality, duration of mechanical ventilation, the temporal trend in 2019-nCoV reverse transcription-polymerase chain reaction positivity and the frequency of adverse drug events within 28 days from the start of medication.ResultsA total of 111 patients were enrolled in this randomized clinical trial and data from 100 patients (48 patients in the treatment arm and 52 patients in the control arm) were analyzed. There was no significant difference in the primary outcome of this study, which was clinical improvement. There was no significant difference in the average time to hospital discharge between the two arms. There were also no differences observed in the mean intensive care unit stay, frequency of intermittent mandatory ventilation, duration of supplemental oxygenation or risk of death by day 28 noted between the two arms.ConclusionBromhexine is not an effective treatment for hospitalized patients with COVID-19. The potential prevention benefits of bromhexine in asymptomatic postexposure or with mild infection managed in the community remain to be determined.

scholarly journals Safety and efficacy of the European Society of Cardiology 0/1-hour algorithm for diagnosis of myocardial infarction: systematic review and meta-analysis

Heart ◽  
2020 ◽  
Vol 106 (13) ◽  
pp. 985-991 ◽  
Author(s):  
Cho-Han Chiang ◽  
Cho-Hung Chiang ◽  
Gin Hoong Lee ◽  
Weng-Tein Gi ◽  
Yuan-Kun Wu ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Mortality Rate ◽  
European Society ◽  
Primary Outcome ◽  
Meta Analysis ◽  
High Sensitivity ◽  
Secondary Outcome ◽  
Cochrane Central Register ◽  
Registration Number ◽  
European Society Of Cardiology

ObjectiveThe European Society of Cardiology (ESC) 0/1 hour algorithm has been primarily validated in Europe, America and Australasia with less knowledge of its performance outside of these settings. We aim to evaluate the performance of the ESC 0/1 hour algorithm across different contexts.MethodsWe searched PubMed, Embase, Scopus, Web of Science and the Cochrane Central Register of Controlled Trials for relevant studies published between 1 January 2008 and 31 May 2019. The primary outcome was index myocardial infarction and the secondary outcome was major adverse cardiac event or mortality. A bivariate random-effects meta-analysis was used to derive the pooled estimate of each outcome.ResultsA total of 11 014 patients from 10 cohorts were analysed for the primary outcome. The algorithm based on high-sensitivity cardiac troponin (hs-cTn)T (Roche), hs-cTnI (Abbott) and hs-cTnI (Siemens) had pooled sensitivity of 98.4% (95% CI=95.1% to 99.5%), 98.1% (95% CI=94.6% to 99.3%) and 98.7% (95% CI=97.3% to 99.3%), respectively. The algorithm based on hs-cTnT (Roche) and hs-cTnI (Siemens) had pooled specificity of 91.2% (95% CI=86.0% to 94.6%) and 95.9% (95% CI=94.1% to 97.2%), respectively. Among patients in the rule-out category, the pooled mortality rate at 30 days and at 1 year was 0.1% (95% CI=0.0% to 0.4%) and 0.8% (95% CI=0.5% to 1.2%), respectively. Among patients in the observation zone, the pooled mortality rate was 0.7% (95% CI=0.3% to 1.2%) at 30 days but increased to 8.1% (95% CI=6.1% to 10.4%) at 1 year, comparable to the mortality rate in the rule-in group.ConclusionThe ESC 0/1 hour algorithm has high diagnostic accuracy but may not be sufficiently safe if the 1% miss-rate for myocardial infarction is desired.PROSPERO registration numberCRD42019142280.

scholarly journals A Normalized Mortality Rate Showed the Diverse Severity of COVID-19 in the World

2020 ◽  
Author(s):  
Santosh Kumar ◽  
P.R. Renjith ◽  
C. Priscilla ◽  
Selva Kumar Ganesan
Keyword(s):  
Cardiovascular Diseases ◽  
Mortality Rate ◽  
Respiratory Diseases ◽  
Kidney Diseases ◽  
The United States ◽  
World Health ◽  
The World ◽  
The Usa ◽  
Respiratory Infectious Diseases ◽  
Health Organization

Covid-19 has given a halt to all the activities in the world. Europe was most affected followed by the United States of America. In this study we have assessed the severity of Covid-19 by analyzing the mortality rate in Covid-19 and other diseases. The Covid-19 data and &ldquo;death rate&rdquo; data caused by other diseases (cardiovascular diseases, cancer, non-communicable respiratory diseases, respiratory infectious diseases, diabetes mellitus, and kidney diseases) were downloaded from the world health organization (WHO) website. A normalized period based method was used to see the mortality rate of Covid-19 in comparison to other diseases. The deaths occurred by cardiovascular diseases, cancer, and respiratory diseases were more in number than the Covid-19 caused deaths in the 45 days period where most of the Covid-19 deaths had taken place. The mortality rate of Covid-19 was highest in France followed by Belgium and the lowest in Russia while the share of Covid-19 caused deaths in total deaths by all causes was the highest in Belgium followed by Spain and the lowest in Japan. The severity of Covid-19 in the USA was moderate. The severity of Covid-19 in Asian countries was found to be moderate to low. The severity of Covid-19 was diverse in the world. Europe showed the highest diversity in the mortality rate of Covid-19. Cardiovascular diseases, cancer, and non-communicable diseases were still more lethal and caused more deaths than Covid-19.

scholarly journals Ongoing Clinical and Immunization Trials for Novel Zoonotic Covid -19 Pandemic

2021 ◽  
pp. 85-93
Author(s):  
Ramya Kumari B. S.
Keyword(s):  
Clinical Trials ◽  
Mortality Rate ◽  
Infectious Diseases ◽  
Phase I ◽  
Viral Infection ◽  
Host Cell ◽  
Phase Iii ◽  
Specific Level ◽  
Contagious Diseases ◽  
The World

Some of the contagious diseases have created history and also remains with us today. So it becomes utmost important to understand such infectious diseases and exploring their remedies. One such disease which has created havoc across the globe is COVID-19, caused by an agent SARS CoV-2 virus. The current threat of coronavirus is the human health and economy, which can be overcome by the development of a target vaccine at a specific level by blocking the entry of virus inside the host cell. This step not only will reduce the morbidity and mortality rate associated with this viral infection but will also improve upon the prevailing economy crisis. Hence, this review chapter aims at the ongoing clinical and immunization trials for novel zoonotic COVID-19 pandemic. Currently the clinical trials are happening throughout the world and all the trials are to be registered in publicly available domain which is recommended by ICMJE. Different phase of trials in various parts of the globe, includes Phase-I to Phase-III and insights of vaccine developers involved in the development of COVID vaccines are the focused areas in this review chapter.

Sign in / Sign up

Export Citation Format

Share Document