scholarly journals Glaucoma Clinical Research: Trends in Treatment Strategies and Drug Development

2021 ◽  
Vol 8 ◽  
Author(s):  
Line Storgaard ◽  
Thuy Linh Tran ◽  
Josefine Clement Freiberg ◽  
Alexander S. Hauser ◽  
Miriam Kolko
Keyword(s):  
Clinical Trials ◽  
Medical Treatment ◽  
Treatment Strategies ◽  
Success Rates ◽  
Traditional Medicines ◽  
Clinical Trial Registries ◽  
Glaucoma Treatment ◽  
Phase Ii And Iii ◽  
New Compounds ◽  
All Diseases

Purpose: To investigate the trends and progresses in glaucoma research by searching two major clinical trial registries; clinicaltrials.gov, and Australianclinicaltrials.gov.au.Methods: All clinical trials with glaucoma covered by Clinicaltrials.gov, and Australianclinicaltrials.gov.au starting the study before 1 January 2021 were included. Trials evaluating glaucoma treatment were separated from non-treatment trials and divided into three major categories: “laser treatment,” “surgical treatment,” and “medical treatment.” In the category of “medical treatment,” new compounds and their individual targets were identified and subcategorized according to treatment strategy; intraocular pressure (IOP)-lowering, neuroprotective or vascular. The phase transition success rates were calculated.Results: One-thousand five hundred and thirty-seven trials were identified. Sixty-three percent (n = 971) evaluated glaucoma treatment, of which medical treatment accounted for the largest proportion (53%). The majority of medical trials evaluated IOP-lowering compounds, while trials with neuroprotective or vascular compounds accounted for only 5 and 3%, respectively. Eighty-eight new compounds were identified. Phase I, II, and III transition success rates were 63, 26, and 47%, respectively.Conclusion: The number of clinical trials in glaucoma research has increased significantly over the last 30 years. Among the most recently evaluated compounds, all three main treatment strategies were represented, but clinical trials in neuroprotection and vascular modalities are still sparse. In addition to traditional medicines, dietary supplements and growth factors are assessed for a potential anti-glaucomatous effect. Phase II and III success rates were below previously reported success rates for all diseases and ophthalmology in general. A stricter phenotyping of patients can improve the success rates in glaucoma and ophthalmological research and gain a better understanding of responders and non-responders.

scholarly journals Progression-free survival as a surrogate endpoint in advanced neuroendocrine neoplasms

2017 ◽  
Vol 24 (9) ◽  
pp. 475-483 ◽  
Author(s):  
Hiroshi Imaoka ◽  
Mitsuhito Sasaki ◽  
Hideaki Takahashi ◽  
Yusuke Hashimoto ◽  
Izumi Ohno ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Medical Treatment ◽  
Phase Ii ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Neuroendocrine Neoplasms ◽  
Cochrane Central Register ◽  
Free Survival ◽  
Phase Ii And Iii

In oncology clinical trials, overall survival (OS) is considered the gold standard outcome measure. In phase III trials for neuroendocrine neoplasms (NENs), however, progression-free survival (PFS) is more frequently used, as NENs are relatively rare and indolent neoplasms. But this surrogacy of PFS for OS has never been systematically validated. We, therefore, performed a literature-based analysis of phase II and III trials for NENs to evaluate the correlation between PFS and OS in NENs treated with medical treatment. We identified phase II and III clinical trials of medical treatment for advanced NENs based on a systematic electronic search using MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials. A total of 20 trials were identified, and 2530 patients and 30 treatment arms were included in the analysis. There was a statistically significant relationship between PFS and OS (rs, 0.587; 95% confidence interval, 0.249–0.925). Conversely, the objective response rate was not significantly correlated with OS. The results of subgroup analyses indicated that the correlation between PFS and OS was higher for study arms that prohibited concomitant therapy with somatostatin analogues than for those that permitted it. The results of the present analysis indicate that PFS is significantly correlated with OS, and suggest that PFS is an acceptable surrogate for OS in clinical trials for NENs.

scholarly journals Clinical trial registries as Scientometric data: A novel solution for linking and deduplicating clinical trials from multiple registries

2021 ◽  
Author(s):  
Christian Thiele ◽  
Gerrit Hirschfeld ◽  
Ruth von Brachel
Keyword(s):  
Clinical Trials ◽  
Random Forest ◽  
Random Forest Model ◽  
Scientometric Analysis ◽  
Data Set ◽  
The Public ◽  
Forest Model ◽  
Clinical Trial Registries ◽  
Multiple Primary ◽  
Clinical Trials Registry

AbstractRegistries of clinical trials are a potential source for scientometric analysis of medical research and serve important functions for the research community and the public at large. Clinical trials that recruit patients in Germany are usually registered in the German Clinical Trials Register (DRKS) or in international registries such as ClinicalTrials.gov. Furthermore, the International Clinical Trials Registry Platform (ICTRP) aggregates trials from multiple primary registries. We queried the DRKS, ClinicalTrials.gov, and the ICTRP for trials with a recruiting location in Germany. Trials that were registered in multiple registries were linked using the primary and secondary identifiers and a Random Forest model based on various similarity metrics. We identified 35,912 trials that were conducted in Germany. The majority of the trials was registered in multiple databases. 32,106 trials were linked using primary IDs, 26 were linked using a Random Forest model, and 10,537 internal duplicates on ICTRP were identified using the Random Forest model after finding pairs with matching primary or secondary IDs. In cross-validation, the Random Forest increased the F1-score from 96.4% to 97.1% compared to a linkage based solely on secondary IDs on a manually labelled data set. 28% of all trials were registered in the German DRKS. 54% of the trials on ClinicalTrials.gov, 43% of the trials on the DRKS and 56% of the trials on the ICTRP were pre-registered. The ratio of pre-registered studies and the ratio of studies that are registered in the DRKS increased over time.

scholarly journals Reporting of harms in oncological clinical study reports submitted to the European Medicines Agency compared to trial registries and publications—a methodological review

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Asger S. Paludan-Müller ◽  
Perrine Créquit ◽  
Isabelle Boutron
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Clinical Study ◽  
Primary Source ◽  
European Medicines Agency ◽  
Clinical Trial Registries ◽  
Number Of Patients ◽  
Journal Publications ◽  
Clinical Study Reports ◽  
Completeness Of Reporting

Abstract Background An accurate and comprehensive assessment of harms is a fundamental part of an accurate weighing of benefits and harms of an intervention when making treatment decisions; however, harms are known to be underreported in journal publications. Therefore, we sought to compare the completeness of reporting of harm data, discrepancies in harm data reported, and the delay to access results of oncological clinical trials between three sources: clinical study reports (CSRs), clinical trial registries and journal publications. Methods We used the EMA clinical data website to identify all trials submitted to the EMA between 2015 and 2018. We retrieved all CSRs and included all phase II, II/III or III randomised controlled trials (RCTs) assessing targeted therapy and immunotherapy for cancer. We then identified related records in clinical trial registries and journals. We extracted harms data for eight pre-specified variables and determined the completeness of reporting of harm data in each of the three sources. Results We identified 42 RCTs evaluating 13 different drugs. Results were available on the EMA website in CSRs for 37 (88%) RCTs, ClinicalTrials.gov for 36 (86%), the European Clinical Trials Register (EUCTR) for 20 (48%) and in journal publications for 32 (76%). Harms reporting was more complete in CSRs than other sources. We identified marked discrepancies in harms data between sources, e.g. the number of patients discontinuing due to adverse events differed in CSRs and clinical trial registers for 88% of trials with data in both sources. For CSRs and publications, the corresponding number was 90%. The median (interquartile range) delay between the primary trial completion date and access to results was 4.34 (3.09–7.22) years for CSRs, 2.94 (1.16–4.52) years for ClinicalTrials.gov, 5.39 (4.18–7.33) years for EUCTR and 2.15 (0.64–5.04) years for publications. Conclusions Harms of recently approved oncological drugs were reported more frequently and in more detail in CSRs than in trial registries and journal publications. Systematic reviews seeking to address harms of oncological treatments should ideally use CSRs as the primary source of data; however, due to problems with access, this is currently not feasible.

scholarly journals Ixabepilone-associated peripheral neuropathy: data from across the phase II and III clinical trials

2012 ◽  
Vol 20 (11) ◽  
pp. 2661-2668 ◽  
Author(s):  
Linda T. Vahdat ◽  
Eva S. Thomas ◽  
Henri H. Roché ◽  
Gabriel N. Hortobagyi ◽  
Joseph A. Sparano ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Peripheral Neuropathy ◽  
Phase Ii ◽  
Phase Ii And Iii

scholarly journals Immunocompetent Mouse Models in the Search for Effective Immunotherapy in Glioblastoma

Cancers ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 19
Author(s):  
Roxanne Wouters ◽  
Sien Bevers ◽  
Matteo Riva ◽  
Frederik De Smet ◽  
An Coosemans
Keyword(s):  
Immune Response ◽  
Clinical Trials ◽  
Mouse Models ◽  
Standard Of Care ◽  
Preclinical Studies ◽  
Success Rates ◽  
Immunocompetent Mouse ◽  
Full Spectrum ◽  
Effective Immune Response ◽  
Radio Chemotherapy

Glioblastoma (GBM) is the most aggressive intrinsic brain tumor in adults. Despite maximal therapy consisting of surgery and radio/chemotherapy, GBM remains largely incurable with a median survival of less than 15 months. GBM has a strong immunosuppressive nature with a multitude of tumor and microenvironment (TME) derived factors that prohibit an effective immune response. To date, all clinical trials failed to provide lasting clinical efficacy, despite the relatively high success rates of preclinical studies to show effectivity of immunotherapy. Various factors may explain this discrepancy, including the inability of a single mouse model to fully recapitulate the complexity and heterogeneity of GBM. It is therefore critical to understand the features and limitations of each model, which should probably be combined to grab the full spectrum of the disease. In this review, we summarize the available knowledge concerning immune composition, stem cell characteristics and response to standard-of-care and immunotherapeutics for the most commonly available immunocompetent mouse models of GBM.

scholarly journals Influence of EPs 7630 on Antipyretic Comedication and Recovery from Acute Tonsillopharyngitis in Children: A Meta-analysis of Randomized, Placebo-Controlled, Clinical Trials

2021 ◽  
Author(s):  
Georg Seifert ◽  
Petra Funk ◽  
Thorsten Reineke ◽  
Walter Lehmacher
Keyword(s):  
Clinical Trials ◽  
Medical Literature ◽  
Meta Analysis ◽  
Controlled Clinical Trials ◽  
Viral Origin ◽  
Treatment Risk ◽  
Pelargonium Sidoides ◽  
Clinical Trial Registries ◽  
End Of Treatment ◽  
Seasonal Infection

Abstract Objective Acute tonsillopharyngitis (ATP) is a common, seasonal infection of predominantly viral origin. Management is aimed at shortening the course of the disease and restoring the comfort of the patient. We performed a meta-analysis to investigate whether treatment with the Pelargonium sidoides extract EPs 7630 reduces the use of antipyretic comedication (i.e., acetaminophen) in children suffering from ATP. Methods Studies were identified from clinical trial registries and medical literature. Randomized, placebo-controlled, clinical trials investigating EPs 7630 in children with ATP and reporting the coadministration of paracetamol were eligible. Based on the raw data of eligible trials, we analyzed cumulative paracetamol use, as well as the ability to attend school at the end of treatment. Three trials including a total of 345 children aged 6 to 10 years and suffering from non-β-hemolytic streptococcal ATP were identified and eligible. Children were administered EPs 7630 or placebo for 6 days. Results Compared with placebo, EPs 7630 reduced the cumulative paracetamol dose by an average of 449 mg (95% confidence interval [CI]: 252–646 mg; p < 0.001). A total of 19.1% (EPs 7630) and 71.5% (placebo) of children were still unable to attend school at the end of the treatment (risk ratio = 0.28; 95% CI: 0.16–0.48; p < 0.001). Conclusion Our meta-analysis demonstrates that EPs 7630 reduced the use of antipyretic comedication and accelerated recovery.

scholarly journals Targeting Cytokines as Evolving Treatment Strategies in Chronic Inflammatory Airway Diseases

2018 ◽  
Vol 19 (11) ◽  
pp. 3402 ◽  
Author(s):  
Jaleesa Garth ◽  
Jarrod Barnes ◽  
Stefanie Krick
Keyword(s):  
Clinical Trials ◽  
Allergic Asthma ◽  
Inflammatory Marker ◽  
Interleukin 1 ◽  
Treatment Strategies ◽  
Bronchial Epithelium ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Airway Diseases ◽  
Novel Treatment Strategies

Cytokines are key players in the initiation and propagation of inflammation in chronic inflammatory airway diseases such as chronic obstructive pulmonary disease (COPD), bronchiectasis and allergic asthma. This makes them attractive targets for specific novel anti-inflammatory treatment strategies. Recently, both interleukin-1 (IL-1) and IL-6 have been associated with negative health outcomes, mortality and a pro-inflammatory phenotype in COPD. IL-6 in COPD was shown to correlate negatively with lung function, and IL-1beta was induced by cigarette smoke in the bronchial epithelium, causing airway inflammation. Furthermore, IL-8 has been shown to be a pro-inflammatory marker in bronchiectasis, COPD and allergic asthma. Clinical trials using specific cytokine blockade therapies are currently emerging and have contributed to reduce exacerbations and steroid use in COPD. Here, we present a review of the current understanding of the roles of cytokines in the pathophysiology of chronic inflammatory airway diseases. Furthermore, outcomes of clinical trials in cytokine blockade as novel treatment strategies for selected patient populations with those diseases will be discussed.

Biomarker-Based Phase II and III Clinical Trials in Oncology

2019 ◽  
pp. 261-284
Author(s):  
Shigeyuki Matsui ◽  
Masataka Igeta ◽  
Kiichiro Toyoizumi
Keyword(s):  
Clinical Trials ◽  
Phase Ii ◽  
Phase Ii And Iii
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