Selection Of The Most Appropriate Epro Mode: Contributing To The Success Of Patient-Centered Clinical Trials

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.

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

Current Alzheimer Research ◽

10.2174/1567205014666171106150309 ◽

2018 ◽

Vol 15 (5) ◽

pp. 429-442 ◽

Cited By ~ 3

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.

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

European Radiology ◽

10.1007/s00330-020-07598-8 ◽

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

Scientific Reports ◽

10.1038/s41598-021-93500-5 ◽

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.

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Liver Biopsy for the Selection of Patients With Nonalcoholic Steatohepatitis for Clinical Trials

Gastroenterology ◽

10.1053/j.gastro.2014.09.047 ◽

2015 ◽

Vol 148 (1) ◽

pp. 262 ◽

Cited By ~ 1

Author(s):

Ian A. Rowe ◽

Richard Parker

Keyword(s):

Clinical Trials ◽

Liver Biopsy ◽

Nonalcoholic Steatohepatitis ◽

Selection Of Patients ◽

Selection Of

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Selection of composite binary endpoints in clinical trials

Biometrical Journal ◽

10.1002/bimj.201600229 ◽

2017 ◽

Vol 60 (2) ◽

pp. 246-261 ◽

Cited By ~ 1

Author(s):

Marta Bofill Roig ◽

Guadalupe Gómez Melis

Keyword(s):

Clinical Trials ◽

Selection Of

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The In Vitro Sensitivities of 70 Strains of Shigella

PEDIATRICS ◽

10.1542/peds.34.5.705 ◽

1964 ◽

Vol 34 (5) ◽

pp. 705-707

Author(s):

WILLIAM D. DONALD

Keyword(s):

Clinical Trials ◽

Gastrointestinal Tract ◽

Tetracycline Resistance ◽

The Other ◽

Drug Of Choice ◽

High Degree ◽

As Toxicity ◽

Selection Of

In vitro sensitivities of 70 shigella strains isolated over a recent 18-month period are reported. The high degree of sulfadiazine resistance casts some doubt on the selection of this agent as the drug of choice in the treatment of shigellosis, at least in this community. Some of the other agents, although inhibiting the growth of the organisms in vitro, have disadvantages such as toxicity or failure of absorption from the gastrointestinal tract. Tetracycline resistance was found in only 7% of the organisms tested, but from this and other reports we may anticipate the occurrence of more organisms resistant to this agent. The results of the sensitivities to ampicillin are encouraging and further studies including clinical trials of this agent are in order.

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Indicadores (Outcomes) Primários e Secundários em Ensaios Clínicos Oncológicos: Definição e Usos

Acta Médica Portuguesa ◽

10.20344/amp.5286 ◽

2014 ◽

Vol 27 (4) ◽

pp. 498

Author(s):

António Vaz-Carneiro ◽

Ricardo Da Luz ◽

Margarida Borges ◽

João Costa

Keyword(s):

Clinical Trials ◽

Methodological Issue ◽

Objective Response ◽

Disease Free Survival ◽

Progression Free Survival ◽

Free Survival ◽

Patient Reported ◽

Oncology Clinical Trials ◽

Alternative Drug ◽

Selection Of

Introduction: The proof of efficacy from a therapeutic intervention in oncology must be defined through well conducted clinical trials. One of the most important methodological issue is the outcome selection needed to calculate measures of association allowing definition of clinical efficacy. Material and Methods: We designed a narrative revision based on some of the international regulatory instructions from drug agencies, as well as consensus papers from scientific oncology societies, listing and critically assessing each outcome used in oncology clinical trials. Results: We identified as being the most important outcomes in oncology trials the overall survival, the progression free survival/ disease-free survival, the toxicity, the quality of life/patient- reported outcomes and the objective response rate. Discussion: The selection of the primary outcome must be based on therapeutic efficacy as well as toxicity, expected survival, alternative drug regimens and even disease prevalence. Conclusion: The selection of efficacy outcomes for clinical trials in oncology is very important and its selection must be well justified, and depends on the type of disease, the patients and the drug being studied. Keywords: Clinical Trials as Topic; Neoplasms; Medical Oncology; Treatment Outcome.

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Improving the External Validity of Clinical Trials: The Case of Multiple Chronic Conditions

Journal of Comorbidity ◽

10.15256/joc.2013.3.27 ◽

2013 ◽

Vol 3 (2) ◽

pp. 30-35 ◽

Cited By ~ 6

Author(s):

Fortin Martin ◽

Smith M. Susan

Keyword(s):

Clinical Trials ◽

External Validity ◽

Chronic Conditions ◽

Evidence Base ◽

Specific Reference ◽

Multiple Chronic Conditions ◽

Patient Centered ◽

Department Of Health ◽

Patient Groups ◽

Intervention Trials

The U.S. Department of Health and Human Services vision and strategic framework on multiple chronic conditions (MCCs) incorporates recommendations designed to facilitate research that will improve our knowledge about interventions and systems that will benefit individuals with MCCs (or multimorbidity). The evidence base supporting the management of patients with MCCs will be built through intervention trials specifically designed to address multimorbidity and identification of MCCs in participants across the clinical trial range. This article specifically focuses on issues relating to external validity with specific reference to trials involving patients with MCCs. The exclusion of such patients from clinical trials has been well documented. Randomized control trials (RCTs) are considered the “gold standard” of evidence, but may have drawbacks in relation to external validity, particularly in relation to multimorbidity. It may, therefore, be necessary to consider a broader range of research methods that can provide converging evidence on intervention effects to address MCCs. Approaches can also be taken to increase the usefulness of RCTs in general for providing evidence to inform multimorbidity management. Additional improvements to RCTs would include better reporting of inclusion and exclusion criteria and participant characteristics in relation to MCCs. New trials should be considered in terms of how they will add to the existing evidence base and should inform how interventions may work in different settings and patient groups. Research on treatments and interventions for patients with MCCs is badly needed. It is important that this research includes patient-centered measures and that generalizability issues be explicitly addressed.

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