scholarly journals ENSAT registry-based randomized clinical trials for adrenocortical carcinoma

2021 ◽  
Vol 184 (2) ◽  
pp. R51-R59
Author(s):  
Joakim Crona ◽  
Eric Baudin ◽  
Massimo Terzolo ◽  
Alexandra Chrisoulidou ◽  
Anna Angelousi ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Adrenocortical Carcinoma ◽  
Randomized Clinical Trials ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Legal Aspects ◽  
Orphan Disease ◽  
Novel Approach ◽  
Ethical Approval ◽  
Significant Cost Reduction

Adrenocortical carcinoma (ACC) is an orphan disease lacking effective systemic treatment options. The low incidence of the disease and high cost of clinical trials are major obstacles in the search for improved treatment strategies. As a novel approach, registry-based clinical trials have been introduced in clinical research, so allowing for significant cost reduction, but without compromising scientific benefit. Herein, we describe how the European Network for the Study of Adrenal Tumours (ENSAT) could transform its current registry into one fit for a clinical trial infrastructure. The rationale to perform randomized registry-based trials in ACC is outlined including an analysis of relevant limitations and challenges. We summarize a survey on this concept among ENSAT members who expressed a strong interest in the concept and rated its scientific potential as high. Legal aspects, including ethical approval of registry-based randomization were identified as potential obstacles. Finally, we describe three potential randomized registry-based clinical trials in an adjuvant setting and for advanced disease with a high potential to be executed within the framework of an advanced ENSAT registry. Thus we, therefore, provide the basis for future registry-based trials for ACC patients. This could ultimately provide proof-of-principle of how to perform more effective randomized trials for an orphan disease.

scholarly journals Case Commentary: the Need for Cefiderocol Is Clear, but Are the Supporting Clinical Data?

2020 ◽  
Vol 64 (4) ◽  
Author(s):  
Ryan K. Shields
Keyword(s):  
Clinical Trials ◽  
Clinical Practice ◽  
Salvage Therapy ◽  
Randomized Clinical Trials ◽  
Treatment Options ◽  
Multidrug Resistant ◽  
Gram Negative Bacteria ◽  
Potential Utility ◽  
Gram Negative

ABSTRACT Cefiderocol is a newly approved siderophore cephalosporin that demonstrates expanded in vitro activity against multidrug-resistant Gram-negative bacteria. In two challenging cases reported here, cefiderocol shows potential utility as salvage therapy against difficult-to-treat pathogens with limited or no treatment options; however, two multicenter, randomized clinical trials have yielded mixed results among cefiderocol-treated patients. Taken together, clinicians must balance a clear need for cefiderocol in clinical practice with the uncertainties that have stemmed from the available data.

Modern Clinician-initiated Clinical Trials to Determine Optimal Therapy for Multidrug-resistant Gram-negative Infections

2019 ◽  
Vol 71 (2) ◽  
pp. 433-439
Author(s):  
Adam G Stewart ◽  
Patrick N A Harris ◽  
Mark Chatfield ◽  
Scott R Evans ◽  
David van Duin ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Multidrug Resistant ◽  
Small Sample ◽  
Consensus Approach ◽  
Gram Negative ◽  
Therapeutic Trials ◽  
Clinical Trial Designs ◽  
Small Sample Sizes

Abstract Treatment options for multidrug-resistant (MDR) gram-negative infection are growing. However, postregistration, pragmatic, and clinician-led clinical trials in this field are few, recruit small sample sizes, and experience deficiencies in design and operations. MDR gram-negative therapeutic trials are often inefficient, only evaluating a single antibiotic or strategy at a time. Novel clinical trial designs offer potential solutions by attempting to obtain clinically meaningful conclusions at the end or during a trial, for many treatment strategies, simultaneously. An integrated, consensus approach to MDR gram-negative infection trial design is crucial.

Time interval between final protocol approval (FPA) and inclusion of the first patient into randomized clinical trials (RCTs) performed by the Central European Cooperative Oncology Group (CECOG): A 10-year experience

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 6546-6546
Author(s):  
T. Brodowicz ◽  
I. Steiner ◽  
S. Beslija ◽  
T. E. Ciuleanu ◽  
M. Inbar ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Time Interval ◽  
Southeastern Europe ◽  
The Czech Republic ◽  
Multicenter Trials ◽  
Whole Process ◽  
Final Study ◽  
Ethical Approval ◽  
Central And Southeastern Europe

6546 Background: CECOG has been formed in 1999 to unite centers of clinical oncology from Central and Southeastern Europe and Israel in order to conduct and coordinate multicenter oncology RCTs. Based on the European legislation passed in 2001 (Directive 2001/20/EC), clinical trials must get ethical approval and approval from the competent authorities (CA). However, the duration of these regulatory procedures to initiate a clinical trial is a factor determining the competitive position in clinical research. Methods: Within the last 10 years, CECOG conducted trials in breast, colorectal, esophago-gastric, NSCLC, pancreatic, prostate cancer and GIST. We analyzed the dates of FPA, the approvals by Ethics Review Boards (ERB) and CAs, the letters of agreement between sponsor and site (LoA), the site initiation and the inclusion of the first patient in a total of 6 multicenter trials in 25 CECOG study centers in Austria, Bosnia, Bulgaria, Croatia, the Czech Republic, Hungary, Israel, Poland, Romania, Serbia, and Slovakia. Results: The average time interval from FPA to the inclusion of the first patient was 18.4 ± 9.4 months. Most of this time has been spent for regulatory procedures, i.e. the approval by ERBs (9.6 ± 7.2 months) and CAs (10.0 ± 6.6 months). The LoA were signed 11.5 ± 9.4 months after FPA. The time interval from approval by the CAs to site initiation was 3.3 ± 3.7 months and the interval between site initiation and the inclusion of the first patient was 4.2 ± 4.5 months. Conclusions: The ‘paper to patient process‘ - the time interval between the approval of the final study protocol and the inclusion of the first patient - required 18.4 months on average in 6 multicenter trials conducted by CECOG. As the regulatory procedures used up more than 50% of duration of the whole process, optimization is necessary and realistic in order to make novel therapies available to patients more quickly. No significant financial relationships to disclose.

Measuring clinical practice: science and methods

2013 ◽  
Vol 34 (1) ◽  
pp. E3 ◽  
Author(s):  
Peter D. Angevine ◽  
Paul C. McCormick
Keyword(s):  
Clinical Trials ◽  
Clinical Data ◽  
Observational Studies ◽  
Randomized Clinical Trials ◽  
Treatment Options ◽  
Routine Practice ◽  
Clinical Settings ◽  
Clinical Registries ◽  
Basic Understanding

The routine practice of neurosurgery generates a large amount of clinical data. The structured, systematic capture of this information using clinical registries or other rigorously designed observational studies can yield useful evidence to help improve the care of patients. Registries in particular can be designed to measure outcomes in real-world clinical settings and to study differences in outcomes between subgroups. This information can help clinicians to advise patients regarding their treatment options. To provide valid, generalizable evidence, however, registries and other observational studies must be designed and conducted with a rigor similar to that of randomized clinical trials. Neurosurgeons with a basic understanding of the potential advantages and pitfalls of nonrandomized trials and the methods of statistical analysis will be able to assess the quality of clinical data and to incorporate the findings appropriately into their patients' care.

scholarly journals Professional Vital Bleaching Using a Thin and Concentrated Peroxide Gel on Whitening Strips: An Integrated Clinical Summary

2004 ◽  
Vol 5 (1) ◽  
pp. 1-17 ◽  
Author(s):  
Robert W. Gerlach ◽  
Matthew L. Barker
Keyword(s):  
Hydrogen Peroxide ◽  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Treatment Options ◽  
New Paradigm ◽  
Tooth Color ◽  
Number Of Treatment ◽  
Advanced System ◽  
Better Than ◽  
Positive Controls

Abstract Rapid innovation in vital bleaching continues to expand the number of treatment options available to patients, particularly in the area of at-home whitening. The development of bleaching strips represented a new paradigm in the delivery of peroxide. The efficacy and safety of bleaching strip systems delivering up to 6.5% hydrogen peroxide has been established in numerous randomized clinical trials. In 2003, a novel bleaching strip with 14% hydrogen peroxide (Crest® Whitestrips® Supreme) was introduced. This advanced system carries a thinner but more concentrated gel on each strip, resulting in a relatively similar total amount of peroxide as compared to other strip systems. This 2-variable change, higher concentration gel with lowered gel volume translates to improved whitening without adversely affecting oral soft tissue tolerability and irritation. This paper provides an integrated review of 9 comparative clinical trials evaluating the whitening response (six trials) and safety (nine trials) of this novel vital bleaching system. Efficacy results for the 14% hydrogen peroxide strips were significantly (p<0.05) better than the placebo or pooled positive controls evaluated in the clinical trials assessing tooth color or shade. Adverse events were similar in type to the other vital bleaching systems. Overall, the research of 408 patients showed generally better efficacy and similar to or better tolerability for the 14% hydrogen peroxide strips compared to a selected group of marketed positive bleaching controls. Citation Gerlach RW, Barker ML. Professional Vital Bleaching Using a Thin and Concentrated Peroxide Gel on Whitening Strips: An Integrated Clinical Summary. J Contemp Dent Pract 2004 February;(5)1:001-017.

scholarly journals An overview of treatment options for COVID-19

2020 ◽  
Vol 9 (11) ◽  
pp. 1770
Author(s):  
Madhusmita Mohanty Mohapatra ◽  
Manju Rajaram ◽  
Dharm Prakash Dwivedi ◽  
Vishnukant Govindraj ◽  
Pratap Upadhya
Keyword(s):  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Treatment Options ◽  
Unknown Origin ◽  
The Novel ◽  
Clinical Trial Registry ◽  
Repurposed Drugs ◽  
Novel Coronavirus ◽  
Meta Analyses ◽  
Effective Drugs

Severe acute respiratory syndrome- coronavirus-2 (SARS-CoV-2) which emerged in Wuhan initially as pneumonia of unknown origin in December 2019, later spread to whole world and became pandemic on 11th March, 2020. Many drugs have been proposed but are backed without clinical evidence. Scientific bodies are in the row to discover a reliable vaccine and effective drugs against the novel coronavirus. Many antiviral and anti-parasitic drugs which were thought to have some effect on Coronavirus disease 2019 (COVID-19) have been tried during the crisis but none have shown concrete evidence of action. Randomized clinical trials on the repurposed drugs are now registered under clinical trial registry to look at the safety profile and efficacy of the drugs to be used against SARS-CoV-2. Many meta-analyses are being conducted worldwide to frame evidence for the fight against this novel coronavirus. We are providing below a review of various drugs that have been tried for treatment of COVID-19 as well as different clinical trials which are underway.

scholarly journals The Prospects of tumor necrosis factor α inhibitors use in patients with COVID-19

2021 ◽  
Vol 15 (2) ◽  
pp. 89-93
Author(s):  
E. S. Aronova ◽  
B. S. Belov
Keyword(s):  
Clinical Trials ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Randomized Clinical Trials ◽  
Treatment Strategies ◽  
Current Data ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

The review highlights the problem of finding new effective treatment strategies for COVID-19. Tumor necrosis factor α (TNF-α) is considered as a therapeutic target. The theoretical basis for the successful use of TNF-α inhibitors (ITNFα) for the treatment of COVID-19 is presented, as well as data on existing practical developments, including ongoing clinical trials. Two drugs from the group of ITNFα – infliximab and adalimumab – are currently being considered as possible options. The safety issues of ITNFα treatment in patients with immunophaling rheumatic diseases and COVID-19 are discussed. The review also provides current data on vaccination against COVID-19, in particular on the vaccines currently available in Russia, which are at different stages of clinical trials. We conclude that randomized clinical trials of the effectiveness and safety of ITNF-α in patients with the new coronavirus infection are needed. Such trials will promote transition from theoretical speculations to real clinical practice.

scholarly journals Repurposed pharmacological agents for the potential treatment of COVID-19: a literature review

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Alina Kröker ◽  
Madara Tirzīte
Keyword(s):  
Clinical Trials ◽  
Literature Review ◽  
Pharmacological Treatment ◽  
Drug Targets ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Supplemental Oxygen ◽  
Potential Treatment ◽  
Pharmacological Agents ◽  
The World

Abstract Background The COVID-19 pandemic has affected the world extraordinarily. This disease has a potential to cause a significantly severe course of disease leading to respiratory complications, multiple organ failure and possibly death. In the fight against this pandemic-causing disease, medical professionals around the world are searching for pharmacological agents that could treat and prevent disease progression and mortality. To speed the search of promising treatment options, already existing pharmacological agents are repurposed for the potential treatment of COVID-19 and tested in clinical trials. The aim of this literature review is to investigate the efficacy and safety of repurposed pharmacological agents for the treatment of COVID-19 at different pathophysiologic stages of the disease. For this literature review, online-databases PubMed and Google Scholar were utilised. Keywords “COVID-19”, “SARS-CoV-2”, “pathogenesis”, “drug targets”, “pharmacological treatment”, “cytokine storm”, “coagulopathy” and individual drug names were used. Scientific articles, including reviews, clinical trials, and observational cohorts, were collected and analysed. Furthermore, these articles were examined for references to find more clinical trials testing for the potential treatment of COVID-19. In total, 97 references were used to conduct this research paper. Results The most beneficial pharmacological agent for the treatment of COVID-19 are corticosteroids, especially dexamethasone, for the treatment of mechanically ventilated COVID-19 patients. Other promising agents are remdesivir for the treatment of patients with COVID-19 pneumonia requiring minimal supplemental oxygen therapy, and IL-6 receptor antagonist monoclonal antibodies in severe COVID-19. Lopinavir/ritonavir, as well as chloroquine or hydroxychloroquine with or without azithromycin demonstrate the least efficacy in the treatment of COVID-19. The clinical benefits of the treatment of a COVID-19-specific coagulopathy with increased dosing of anticoagulation need further research and confirmation of randomised controlled trials. Conclusion The search for pharmacological treatment of COVID-19 has elicited great controversy. Whereas drugs like chloroquine, hydroxychloroquine, and lopinavir/ritonavir have not shown proven benefit, the agents remdesivir and dexamethasone are recommended for clinical use for the treatment of COVID-19. Further randomised trials for other pharmacological treatment strategies are awaited.

scholarly journals Primum non nocere – Are chloroquine and hydroxychloroquine safe prophylactic/treatment options for SARS-CoV-2 (covid-19)?

2020 ◽  
Vol 54 ◽  
pp. 68 ◽  
Author(s):  
Claudia Biguetti ◽  
Mauro Toledo Marrelli ◽  
Marco Brotto
Keyword(s):  
Clinical Trials ◽  
Side Effects ◽  
Animal Studies ◽  
Prophylactic Treatment ◽  
Randomized Clinical Trials ◽  
Treatment Options ◽  
Vulnerable Groups ◽  
Drug Effectiveness ◽  
Risk Balance

ABSTRACT Chloroquine (CQ) and its analog hydroxychloroquine (HCQ) were recently included in several clinical trials as potential prophylactic and therapeutic options for SARS-CoV-2 infection/covid-19. However, drug effectiveness in preventing, treating, or slowing the progression of the disease is still unknown. Despite some initial promising in vitro results, rigorous pre-clinical animal studies and randomized clinical trials have not been performed yet. On the other hand, while the potential effectiveness of CQ/HCQ is, at best, hypothetical, their side effects are factual and most worrisome, particularly when considering vulnerable groups of patients being treated with these drugs. In this comment, we briefly explain the possible mechanisms of action of CQ/HCQ for treating other diseases, possible actions against covid-19, and their potent side effects, in order to reinforce the necessity of evaluating the benefit-risk balance when widely prescribing these drugs for SARS-CoV-2 infection/covid-19. We conclude by strongly recommending against their indiscriminate use. DESCRIPTORS: Coronavirus Infections. Chloroquine, toxicity. Hydroxychloroquine, toxicity. Contraindications, Drug.

scholarly journals Therapy of Mucormycosis

2018 ◽  
Vol 4 (3) ◽  
pp. 90 ◽  
Author(s):  
Nikolaos V. Sipsas ◽  
Maria N. Gamaletsou ◽  
Amalia Anastasopoulou ◽  
Dimitrios P. Kontoyiannis
Keyword(s):  
Clinical Trials ◽  
Amphotericin B ◽  
Opportunistic Infection ◽  
Randomized Clinical Trials ◽  
Treatment Options ◽  
Management Plan ◽  
Current Status ◽  
Pharmacological Properties ◽  
Different Types ◽  
Individualized Management

Despite the recent introduction of mold-active agents (posaconazole and isavuconazole), in addition to amphotericin B products, to our armamentarium against mucormycosis, many uncertainties remain for the management of this uncommon opportunistic infection, as there are no data from prospective randomized clinical trials to guide therapy. In this mini-review, we present the current status of treatment options. In view of the heterogeneity of the disease (different types of affected hosts, sites of infection, and infecting Mucorales), mucormycosis management requires an individualized management plan that takes into account the net state of immunosuppression of the host, including comorbidities, certainty of diagnosis, site of infection, and antifungal pharmacological properties.

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