scholarly journals Informing selection of drugs for COVID-19 treatment through adverse events analysis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wenjing Guo ◽  
Bohu Pan ◽  
Sugunadevi Sakkiah ◽  
Zuowei Ji ◽  
Gokhan Yavas ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Adverse Events ◽  
Safety Concern ◽  
Clinical Practices ◽  
Safety Concerns ◽  
Post Market ◽  
Z Scores ◽  
Favorable Safety ◽  
Effective Drugs ◽  
Selection Of

AbstractCoronavirus disease 2019 (COVID-19) is an ongoing pandemic and there is an urgent need for safe and effective drugs for COVID-19 treatment. Since developing a new drug is time consuming, many approved or investigational drugs have been repurposed for COVID-19 treatment in clinical trials. Therefore, selection of safe drugs for COVID-19 patients is vital for combating this pandemic. Our goal was to evaluate the safety concerns of drugs by analyzing adverse events reported in post-market surveillance. We collected 296 drugs that have been evaluated in clinical trials for COVID-19 and identified 28,597,464 associated adverse events at the system organ classes (SOCs) level in the FDA adverse events report systems (FAERS). We calculated Z-scores of SOCs that statistically quantify the relative frequency of adverse events of drugs in FAERS to quantitatively measure safety concerns for the drugs. Analyzing the Z-scores revealed that these drugs are associated with different significantly frequent adverse events. Our results suggest that this safety concern metric may serve as a tool to inform selection of drugs with favorable safety profiles for COVID-19 patients in clinical practices. Caution is advised when administering drugs with high Z-scores to patients who are vulnerable to associated adverse events.

scholarly journals Pharmacology and Adverse Events of Emergency-Use Authorized Medication in Moderate to Severe COVID-19

2021 ◽  
Vol 14 (10) ◽  
pp. 955
Author(s):  
Jen-Yu Hsu ◽  
Yan-Chiao Mao ◽  
Po-Yu Liu ◽  
Kuo-Lung Lai
Keyword(s):  
Adverse Events ◽  
Metabolic Pathways ◽  
Case Reports ◽  
Secondary Infection ◽  
Treatment Strategies ◽  
Serious Adverse Events ◽  
Small Molecule Drugs ◽  
Post Market ◽  
Inflammatory Processes ◽  
Effective Drugs

Some effective drugs have been approved or issued an Emergency Use Authorization for the treatment of COVID-19 in hospitalized patients, but post-market surveillance is warranted to monitor adverse events. We reviewed clinical trials and case reports in patients with moderate-to-severe COVID-19 infection who received remdesivir, baricitinib, tocilizumab, or sarilumab. The drug-specific pharmacokinetics, toxicity, and drug interactions are summarized in this study. Remdesivir and baricitinib are small-molecule drugs that are mainly metabolized by the kidneys, while tocilizumab and sarilumab are monoclonal antibody drugs with metabolic pathways that are currently not fully understood. The most common adverse events of these drugs are alterations in liver function, but serious adverse events have rarely been attributed to them. Only a few studies have reported that remdesivir might be cardiotoxic and that baricitinib might cause thromboembolism. Biological agents such as baricitinib, tocilizumab, and sarilumab could inhibit the pathway of inflammatory processes, leading to immune dysregulation, so the risk of secondary infection should be assessed before prescribing. Further recognition of the pathogenic mechanism and risk factors of adverse events is essential for optimizing treatment strategies.

scholarly journals P14.59 Post-Market Surveillance Data of the EMEA region indicate good tolerability of TTFields in WHO Grade III Glioma

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii80-iii81
Author(s):  
A F Keßler ◽  
R Ritz
Keyword(s):  
Clinical Trials ◽  
Adverse Event ◽  
Adverse Events ◽  
Skin Reaction ◽  
Surveillance Data ◽  
Phase Iii ◽  
Market Surveillance ◽  
Post Market Surveillance ◽  
Post Market ◽  
Grade Iii

Abstract BACKGROUND Despite considerable progress in molecular characterization and evidence for certain regimens, treatment of grade III gliomas is still ambiguous and, with surgery, radiotherapy and chemotherapy, in analogy to grade IV glioma treatment. Tumor treating fields (TTFields) therapy proved to be effective as an additional anti-mitotic treatment in glioblastoma and is available in several countries. While TTFields in grade III glioma are being investigated in several clinical trials, we report an analysis of surveillance safety data in patients with grade III glioma already treated with TTFields in the EMEA region. METHODS We reviewed post-marketing surveillance data of the EMEA region. Using the MedDRA body system with system organ class and preferred terms, adverse events reported in the subgroup of patients with grade III glioma treated with TTFields were systematically analysed. Patients with diagnosis of anaplastic astrocytoma and anaplastic oligodendroglioma were included. RESULTS This analysis includes 142 patients with grade III glioma treated with TTFields in the EMEA region. Median age was 47 years (range 5–78 years). 64% of the patients reported at least one adverse event. With an incidence of 35%, skin reaction was the most common reported adverse event, none of them were severe. 29 % of the patients reported general disorders, including general health deterioration (15%) and fatigue/malaise (6%). Adverse events related to the nervous system were reported in 26% of patients; seizures were noted in 9% and headache in 7% of patients. CONCLUSION The retrospective analysis of available post-market surveillance data of EMEA patients with grade III glioma showed no occurrence of serious adverse events that were associated with TTFields. Skin reaction, as the most commonly reported adverse event, but also other reported adverse events had comparable incidences to the rates observed in the phase III trials for patients with recurrent (EF-11) and newly diagnosed GBM (EF-14). In summary, this analysis identifies no additional safety signals on the use of TTFields in the treatment of patients with grade III glioma. Future results of clinical trials in these indications will give further insight into safety and efficacy in this subgroup.

1% Tirbanibulin Ointment for the Treatment of Actinic Keratoses

2021 ◽  
pp. 106002802110313
Author(s):  
Diem-Phuong D. Dao ◽  
Vikram Nath Sahni ◽  
Dev Ram Sahni ◽  
Esther A. Balogh ◽  
Ayman Grada ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Adverse Events ◽  
Safety Profile ◽  
Application Site ◽  
Phase 2 ◽  
Phase 3 ◽  
Local Skin ◽  
Actinic Keratoses ◽  
Favorable Safety Profile ◽  
Favorable Safety

Objective Actinic keratoses (AKs) are cutaneous lesions that arise in sun-damaged skin. AKs may transform into squamous cell carcinoma in situ. Tirbanibulin 1% ointment is a new topical treatment for AKs, recently approved by the Food and Drug Administration. Data Sources The PubMed database was searched for articles published from 1960 to March 31, 2021, using the keywords tirbanibulin and Klisyri. Data Extraction Phase 2 and phase 3 clinical trials were reviewed. Data Synthesis In phase 2 clinical trials, 43% of patients treated with tirbanibulin experienced complete clearance by day 57 (43% [95% CI = 32, 54]). Across two phase 3 clinical trials (pooled data), complete (100%) clearance occurred in 49% of patients in tirbanibulin groups and in only 9% of the vehicle groups (difference, 41% points; 95% CI = 35 to 47; P < 0.001). Although no comparative studies are available, tirbanibulin is applied for a shorter duration (5 days) compared with diclofenac 3% gel, fluorouracil 5% cream, and imiquimod 3.75% cream. Adverse events were mild and included pruritus, application site pain, and local skin reactions. Systemic adverse events such as necrosis and angioedema, observed with other AK treatments such as fluorouracil and imiquimod, were not observed with tirbanibulin, thus giving tirbanibulin a favorable safety profile. Relevance to Patient Care and Clinical Practice Tirbanibulin effectively reduces AK burden and recurrence and has a favorable safety profile with mild adverse events. In comparison, imiquimod, 5-flourouracil, and diclofenac can result in necrosis, angioedema, and arthralgias. Conclusion With a favorable safety profile and short regimen, tirbanibulin is an efficacious treatment for clinicians to utilize in their treatment toolbox when treating AKs on the face and scalp.

Safety of Efalizumab in Patients with Moderate to Severe Chronic Plaque Psoriasis: Review of Clinical Data. Part II

2005 ◽  
Vol 9 (6) ◽  
pp. 313-323 ◽  
Author(s):  
Kim A. Papp ◽  
Charles Camisa ◽  
Stephen P. Stone ◽  
Ivor Caro ◽  
Xiaolin Wang ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Adverse Events ◽  
Safety Profile ◽  
Controlled Trials ◽  
Efficacy And Safety ◽  
Chronic Plaque Psoriasis ◽  
Serious Adverse Events ◽  
The Third ◽  
Increased Risk ◽  
Favorable Safety

Background: The efficacy and safety of efalizumab have been evaluated in multiple clinical trials. ObjectiveThe purpose of this review is to provide an overview of the safety profile of efalizumab during the clinical trials. Methods: Twelve-week data from four placebo-controlled trials were pooled and analyzed. Data from patients receiving 13—60 weeks of efalizumab therapy were pooled to evaluate longer-term safety. Results: The most common adverse events were mild to moderate, self-limiting, flulike symptoms that were most frequent following the first two efalizumab doses; by the third dose the incidence was comparable to placebo. Serious adverse events were observed in 2.2% and 1.7% of efalizumab- and placebo-treated patients, respectively. Nonserious adverse events leading to withdrawal were infrequent and similar to placebo (2.8% vs 1.8%). There does not appear to be increased risk of end-organ toxicity, infection, or malignancy in efalizumab-treated patients. Conclusion: Efalizumab was well tolerated, with a favorable safety profile.

PILONIDAL DISEASE: CHANGES IN UNDERSTANDING OF ETIOLOGY, PATHOGENESIS AND APPROACH TO TREATMENT

2019 ◽  
Vol 72 (8) ◽  
pp. 1559-1565
Author(s):  
Viktor Konoplitskyi ◽  
Ruslan Shavliuk ◽  
Dmytro Dmytriiev ◽  
Kostiantyn Dmytriiev ◽  
Oleksii Kyrychenko ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Pilonidal Sinus ◽  
Randomized Clinical Trials ◽  
Web Of Science ◽  
Surgical Intervention ◽  
Pilonidal Disease ◽  
Treatment Methods ◽  
Principles Of Treatment ◽  
Selection Of

Data from Web of Science, SCOPUS, Pub Med, Medline, E-library, and other sources was used in writing this article. The main focus was directed towards literature written in English. The selection of literature was based on such concepts as: etiopathogenesis, historical principles of treatment, methods of surgical and non-surgical intervention. Data from metanalysis publications and randomized clinical trials pertaining to the treatment of the pilonidal sinus at various stages of its formation was used, as well.

A Biomarker Combining Imaging and Neuropsychological Assessment for Tracking Early Alzheimer's Disease in Clinical Trials

2018 ◽  
Vol 15 (5) ◽  
pp. 429-442 ◽  
Author(s):  
Nishant Verma ◽  
S. Natasha Beretvas ◽  
Belen Pascual ◽  
Joseph C. Masdeu ◽  
Mia K. Markey ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Cognitive Impairment ◽  
Latent Variable ◽  
Brain Regions ◽  
Disease Assessment ◽  
Latent Variable Analysis ◽  
The Relationship ◽  
Selection Of

Background: Combining optimized cognitive (Alzheimer's Disease Assessment Scale- Cognitive subscale, ADAS-Cog) and atrophy markers of Alzheimer's disease for tracking progression in clinical trials may provide greater sensitivity than currently used methods, which have yielded negative results in multiple recent trials. Furthermore, it is critical to clarify the relationship among the subcomponents yielded by cognitive and imaging testing, to address the symptomatic and anatomical variability of Alzheimer's disease. Method: Using latent variable analysis, we thoroughly investigated the relationship between cognitive impairment, as assessed on the ADAS-Cog, and cerebral atrophy. A biomarker was developed for Alzheimer's clinical trials that combines cognitive and atrophy markers. Results: Atrophy within specific brain regions was found to be closely related with impairment in cognitive domains of memory, language, and praxis. The proposed biomarker showed significantly better sensitivity in tracking progression of cognitive impairment than the ADAS-Cog in simulated trials and a real world problem. The biomarker also improved the selection of MCI patients (78.8±4.9% specificity at 80% sensitivity) that will evolve to Alzheimer's disease for clinical trials. Conclusion: The proposed biomarker provides a boost to the efficacy of clinical trials focused in the mild cognitive impairment (MCI) stage by significantly improving the sensitivity to detect treatment effects and improving the selection of MCI patients that will evolve to Alzheimer’s disease.

Crizotinib Versus Chemotherapy on ALK-positive NSCLC: A Systematic Review of Efficacy and Safety

2018 ◽  
Vol 19 (1) ◽  
pp. 41-49 ◽  
Author(s):  
Mingxia Wang ◽  
Guanqi Wang ◽  
Haiyan Ma ◽  
Baoen Shan
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Adverse Events ◽  
Objective Response Rate ◽  
Retrospective Studies ◽  
Response Rate ◽  
Objective Response ◽  
Treated Group ◽  
Efficacy And Safety ◽  
Alk Positive

Introduction: Crizotinib was approved to treat anaplastic lymphoma kinase (ALK)- positive non-small cell lung cancer (NSCLC) by the Food and Drug Administration in 2011.We conducted a systematic review of clinical trials and retrospective studies to compare the efficacy and safety of crizotinib with chemotherapy. </P><P> Methods: We searched electronic databases from inception to Dec. 2016. Clinical trials and retrospective studies regarding crizotinib and crizotinib versus chemotherapy in treatment of NSCLC were eligible. The primary outcomes were the objective response rate (ORR) and disease control rate (DCR). Results: Nine studies (five clinical trials and four retrospective studies) including 729 patients met the inclusion criteria. Crizotinib treatment revealed 1-year OS of 77.1% and PFS of 9.17 months. And crizotinib had a better performance than chemotherapy in ORR (OR: 4.97, 95%CI: 3.16 to 7.83, P<0.00001, I2=35%). DCR revealed superiority with crizotinib than chemotherapy (OR: 3.42, 95% CI: 2.33 to 5.01, P<0.00001, I2=0%). PR (partial response) were significant superior to that of chemotherapy through direct systematic review. No statistically significant difference in CR (complete response) was found between crizotinib-treated group and chemotherapy-treated group. Regarding SD (stable disease), chemotherapy-treated group had a better performance than crizotinib-treated group. Common adverse events associated with crizotinib were visual disorder, gastrointestinal side effects, and elevated liver aminotransferase levels, whereas common adverse events with chemotherapy were fatigue, nausea, and hematologic toxicity. This systematic review revealed improved objective response rate and increased disease control rate in crizotinib group comparing with chemotherapy group. Crizotinib treatment would be a favorable treatment option for patients with ALK-positive NSCLC. ALK inhibitors may have future potential applications in other cancers driven by ALK or c-MET gene mutations.

The Detection of Adverse Events in Randomized Clinical Trials: Can we Really Say New Medicines are Safe?

2013 ◽  
Vol 8 (2) ◽  
pp. 104-113 ◽  
Author(s):  
Izyan Wahab ◽  
Nicole Pratt ◽  
Lisa Kalisch ◽  
Elizabeth Roughead
Keyword(s):  
Clinical Trials ◽  
Adverse Events ◽  
Randomized Clinical Trials

scholarly journals Incorporating radiomics into clinical trials: expert consensus on considerations for data-driven compared to biologically driven quantitative biomarkers

2021 ◽  
Author(s):  
Laure Fournier ◽  
Lena Costaridou ◽  
Luc Bidaut ◽  
Nicolas Michoux ◽  
Frederic E. Lecouvet ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Quantitative Imaging ◽  
A Priori ◽  
External Validation ◽  
Data Driven ◽  
Imaging Biomarkers ◽  
Clinical Validation ◽  
Biological Processes ◽  
Imaging Data ◽  
Selection Of

Abstract Existing quantitative imaging biomarkers (QIBs) are associated with known biological tissue characteristics and follow a well-understood path of technical, biological and clinical validation before incorporation into clinical trials. In radiomics, novel data-driven processes extract numerous visually imperceptible statistical features from the imaging data with no a priori assumptions on their correlation with biological processes. The selection of relevant features (radiomic signature) and incorporation into clinical trials therefore requires additional considerations to ensure meaningful imaging endpoints. Also, the number of radiomic features tested means that power calculations would result in sample sizes impossible to achieve within clinical trials. This article examines how the process of standardising and validating data-driven imaging biomarkers differs from those based on biological associations. Radiomic signatures are best developed initially on datasets that represent diversity of acquisition protocols as well as diversity of disease and of normal findings, rather than within clinical trials with standardised and optimised protocols as this would risk the selection of radiomic features being linked to the imaging process rather than the pathology. Normalisation through discretisation and feature harmonisation are essential pre-processing steps. Biological correlation may be performed after the technical and clinical validity of a radiomic signature is established, but is not mandatory. Feature selection may be part of discovery within a radiomics-specific trial or represent exploratory endpoints within an established trial; a previously validated radiomic signature may even be used as a primary/secondary endpoint, particularly if associations are demonstrated with specific biological processes and pathways being targeted within clinical trials. Key Points • Data-driven processes like radiomics risk false discoveries due to high-dimensionality of the dataset compared to sample size, making adequate diversity of the data, cross-validation and external validation essential to mitigate the risks of spurious associations and overfitting. • Use of radiomic signatures within clinical trials requires multistep standardisation of image acquisition, image analysis and data mining processes. • Biological correlation may be established after clinical validation but is not mandatory.

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