scholarly journals An Introduction to Pathology in Biomedical Research: A Mission-Critical Specialty for Reproducibility and Rigor in Translational Research

ILAR Journal ◽  
2018 ◽  
Vol 59 (1) ◽  
pp. 1-3 ◽  
Author(s):  
Cory F Brayton ◽  
Kelli L Boyd ◽  
Jeffrey L Everitt ◽  
David K Meyerholz ◽  
Piper M Treuting ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Translational Research ◽  
Study Design ◽  
Biomedical Research ◽  
Digital Pathology ◽  
Molecular Techniques ◽  
Device Development ◽  
Nonhuman Animals ◽  
Academic Settings ◽  
Mission Critical

Abstract This issue of ILAR Journal focusses on pathology and pathologists in biomedical research, more specifically in preclinical translational research involving (nonhuman) animals, emphasizing academic settings. Considerations in study design and planning to maximize benefit from pathologists and pathology resources are reviewed. Adjunctive technologies including molecular techniques, digital pathology, and imaging are highlighted. Additional considerations regarding safety and regulatory concerns, and veterinary clinical trials are reviewed as well. Pathology has been fundamental to understanding clinical disease, remains fundamental to diagnosing disease, and is required in drug and device development. Broader integration of pathology expertise and well-designed pathology investigations have much to offer research rigor and reproducibility, and successful translation from biomedical research.

The results of fundamental and translational research carried out In the Department of Biomedical Research and Technology of the SBRAS INC in 2012-2016

2017 ◽  
Author(s):  
Константин Апарцин ◽  
Konstantin Apartsin
Keyword(s):  
Clinical Trials ◽  
Myocardial Ischemia ◽  
Translational Research ◽  
Progenitor Cells ◽  
Biomedical Research ◽  
Target Cells ◽  
Logit Analysis ◽  
Scientific Center ◽  
Surgical Methods

The results of basic and translational research of the Department of Biomedical Research and Technology of Irkutsk Scientific Center of the Siberian Branch of the Russian Academy of Sciences in 2012–2016 The paper presents the results of interdisciplinary research carried out in 2012–2016. The review includes the study of molecular mechanisms of pathogenesis of reparative regeneration, experimental substantiation of methods of diagnosis and prognosis of systemic disturbances of regeneration process, carrying out clinical trials of medicinal products and the formation of observational studies in the field of personalized medicine, the preparation of practical recommendations on the testing of previously developed surgical methods of prevention or correction of postoperative recovery disorders. New data are obtained on the role of the MAP-kinase cascade in the process of regeneration of muscle tissue. It has been established, that with a significant increase of VEGF concentration at the site of the repair of ischemic myocardium, progenitor cells with the CD34+CD45+ phenotype appear, which opens up prospects for the development of biotechnology to restore the damaged myocardium with its own pool of progenitor cells. The new data on the role of growth factors in the post-infarction remodeling are found. It has been revealed, that in local increase of selenium concentration low intensity of mineralization of forming callus in the area of the damage is observed and the formation of bone regeneration slows down. Prospects for the use of nanocomposites of elemental selenium for modulation of reparative response are marked. The dynamics of the level of free circulating mitochondrial DNA (mtDNA) of blood in the early stages of experimental dyslipidemia has been studied. Atherogenic blood factors do not have a significant effect on the release of the mtDNA from dyslipidemia target cells. On the model of acute small-focal myocardial ischemia, we revealed the increase in the mtDNA levels. Prospects of broadcast of diagnostic mtDNA monitoring technology in myocardial ischemia have been marked. The mtDNA monitoring was first tested as a molecular risk pattern in acute coronary syndrome. In survived patients, the concentration of freely circulating mtDNA in blood plasma was 164 times lower. The probability of death of the patient with a high level of mtDNA (over 4000 copies/mL) was 50 % (logit analysis). Methodological level of translational research in the ISC SB RAS has increased due to effective participation in international multi-center clinical trials of drugs, mainly direct anticoagulants: fondaparinux, edoksabana, betriksabana. “Feedback broadcast” of the results of clinical trials of p38-kinase inhibitor, was carried out in the process of changing the model (initially – neuropathic pain) for coronary atherosclerosis. Technologies of pharmacogenetic testing and personalized treatment of diseases in the employees of the Irkutsk Scientific Center were applied. Step T2. Previously developed at the Irkutsk State Medical University and the Irkutsk Scientific Center of Surgery and Traumatologies approaches to surgical prevention and medicinal correction of postoperative hyposplenism were translated into practical health care. Thus, these results obtained in different areas of translational medicine will determine scientific topics of the department in future research cycle.

scholarly journals Analytical validation of a real-time hydrolysis probe PCR assay for quantifying Plasmodium falciparum parasites in experimentally infected human adults

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Claire Y. T. Wang ◽  
Emma L. Ballard ◽  
Zuleima Pava ◽  
Louise Marquart ◽  
Jane Gaydon ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Plasmodium Falciparum ◽  
18S Rrna ◽  
Drug Efficacy ◽  
18S Rrna Gene ◽  
Molecular Techniques ◽  
Qpcr Assay ◽  
Rrna Gene ◽  
Analytical Sensitivity ◽  
Blood Samples

Abstract Background Volunteer infection studies have become a standard model for evaluating drug efficacy against Plasmodium infections. Molecular techniques such as qPCR are used in these studies due to their ability to provide robust and accurate estimates of parasitaemia at increased sensitivity compared to microscopy. The validity and reliability of assays need to be ensured when used to evaluate the efficacy of candidate drugs in clinical trials. Methods A previously described 18S rRNA gene qPCR assay for quantifying Plasmodium falciparum in blood samples was evaluated. Assay performance characteristics including analytical sensitivity, reportable range, precision, accuracy and specificity were assessed using experimental data and data compiled from phase 1 volunteer infection studies conducted between 2013 and 2019. Guidelines for validation of laboratory-developed molecular assays were followed. Results The reportable range was 1.50 to 6.50 log10 parasites/mL with a limit of detection of 2.045 log10 parasites/mL of whole blood based on a parasite diluted standard series over this range. The assay was highly reproducible with minimal intra-assay (SD = 0.456 quantification cycle (Cq) units [0.137 log10 parasites/mL] over 21 replicates) and inter-assay (SD = 0.604 Cq units [0.182 log10 parasites/mL] over 786 qPCR runs) variability. Through an external quality assurance program, the QIMR assay was shown to generate accurate results (quantitative bias + 0.019 log10 parasites/mL against nominal values). Specificity was 100% after assessing 164 parasite-free human blood samples. Conclusions The 18S rRNA gene qPCR assay is specific and highly reproducible and can provide reliable and accurate parasite quantification. The assay is considered fit for use in evaluating drug efficacy in malaria clinical trials.

scholarly journals Canadian Recommendations for Clinical Trials of Pharmacologic Interventions in Rheumatoid Arthritis: Inclusion Criteria and Study Design: Table 1.

2011 ◽  
Vol 38 (10) ◽  
pp. 2095-2104 ◽  
Author(s):  
JACOB KARSH ◽  
EDWARD C. KEYSTONE ◽  
BOULOS HARAOUI ◽  
J. CARTER THORNE ◽  
JANET E. POPE ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Trial ◽  
Clinical Trials ◽  
Disease Activity ◽  
Study Design ◽  
New Drugs ◽  
Nominal Group ◽  
Consensus Method ◽  
Inclusion Criteria ◽  
Design Features

Objective.Current clinical trial designs for pharmacologic interventions in rheumatoid arthritis (RA) do not reflect the innovations in RA diagnosis, treatment, and care in countries where new drugs are most often used. The objective of this project was to recommend revised entry criteria and other study design features for RA clinical trials.Methods.Recommendations were developed using a modified nominal group consensus method. Canadian Rheumatology Research Consortium (CRRC) members were polled to rank the greatest challenges to clinical trial recruitment in their practices. Initial recommendations were developed by an expert panel of rheumatology trialists and other experts. A scoping study methodology was then used to examine the evidence available to support or refute each initial recommendation. The potential influence of CRRC recommendations on primary outcomes in future trials was examined. Recommendations were finalized using a consensus process.Results.Recommendations for clinical trial inclusion criteria addressed measures of disease activity [Disease Activity Score 28 using erythrocyte sedimentation rate (DAS28-ESR) > 3.2 PLUS ≥ 3 tender joints using 28-joint count (TJC28) PLUS ≥ 3 swollen joint (SJC28) OR C-reactive protein (CRP) or ESR > upper limit of normal PLUS ≥ 3 TJC28 PLUS ≥ 3 SJC28], functional classification, disease classification and duration, and concomitant RA treatments. Additional recommendations regarding study design addressed rescue strategies and longterm extension.Conclusion.There is an urgent need to modify clinical trial inclusion criteria and other study design features to better reflect the current characteristics of people living with RA in the countries where the new drugs will be used.

scholarly journals Heterogeneity of Recent Phase 3 Complicated Urinary Tract Infection Clinical Trials

2021 ◽  
Vol 8 (3) ◽  
Author(s):  
Simon Portsmouth ◽  
Almasa Bass ◽  
Roger Echols ◽  
Glenn Tillotson
Keyword(s):  
Clinical Trials ◽  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Study Design ◽  
Patient Population ◽  
Complicated Urinary Tract Infection ◽  
Gram Negative ◽  
Regulatory Guidelines ◽  
New Antibiotics

Abstract Background For new antibiotics developed to treat antibiotic-resistant Gram-negative infections, the US Food and Drug Administration (FDA) regulatory pathway includes complicated urinary tract infection (cUTI) clinical trials in which the clinical isolates are susceptible to the active control. This allows for inferential testing in a noninferiority study design. Although complying with regulatory guidelines, individual clinical trials may differ substantially in design and patient population. To determine variables that impacted patient selection and outcome parameters, 6 recent cUTI trials that were pivotal to an new drug application (NDA) submission were reviewed. Methods This selective descriptive analysis utilized cUTI trial data, obtained from publicly disclosed information including FDA documents and peer-reviewed publications, from 6 new antibiotics developed to treat multidrug-resistant Gram-negative infections: ceftolozane-tazobactam, ceftazidime-avibactam, meropenem-vaborbactam, cefiderocol, plazomicin, and fosfomycin. Eravacycline was not approved for cUTI and is not included. Results Microbiologic modified intent-to-treat sample size, age, proportions of female patients, acute pyelonephritis (AP), Escherichia coli and other pathogens at baseline, protocol-specified switch to oral antibiotic, and the noninferiority margin were compared. Outcome data included clinical response, microbiologic eradication, and composite outcomes, including a subset of patients with AP. Conclusions A study design can follow regulatory guidelines but still have variable populations. The proportion of AP within a study varied greatly and influenced population demographics (age, gender) and baseline microbiology. A smaller proportion of AP resulted in an older patient population, fewer females, less E coli, and lower proportions of patients achieving success. Fluoroquinolones and piperacillin/tazobactam should be reconsidered as active comparators given the high rates of resistance to these antibiotics.

Cell Block in Cytological Diagnostics: Review of Preparatory Techniques

2018 ◽  
Vol 62 (4) ◽  
pp. 237-243 ◽  
Author(s):  
Leena Krogerus ◽  
Ivana Kholová
Keyword(s):  
Targeted Therapy ◽  
Study Design ◽  
Molecular Techniques ◽  
Cell Block ◽  
Wide Range ◽  
Blood Clots ◽  
The Future ◽  
Golden Standard ◽  
Agar Method ◽  
Cytological Diagnostics

Objective: The cell block (CB) technique refers to the processing of sediments, blood clots, or grossly visible tissue fragments from cytological specimens into paraffin blocks that can be cut and stained by the same methods used for histopathology. The technique brings additional tissue architectural information. CB can be used for ancillary techniques such as immunocytochemistry and molecular techniques. Study Design: We reviewed the literature on the various preparatory techniques of CBs. Results: There is a wide range of preparatory techniques for CBs and no golden standard for CBs exists: tens of methods are used in various institutions. The majority of the methods are modified in house techniques with a few commercially available kits. The techniques most commonly used are the plasma/thrombin method, the agar method, and commercially available Histogel- and Cellient CB-methods. Dissatisfaction with the cellular yield of the CBs is common. Conclusions: In the CBs, the cytological material is preserved for future use, which is a tremendous advantage in the era of targeted therapy and biobanking. The CB is thus central to the future of cytology: more can be done with less material and with less invasiveness to the patient.

Cooperative group and pharmaceutical sponsored clinical trials: Perceptions of U.S. community oncologists.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e13571-e13571
Author(s):  
Richard Scott Swain ◽  
Marjorie E. Zettler ◽  
Yolaine Jeune-Smith ◽  
Bruce A. Feinberg ◽  
Ajeet Gajra
Keyword(s):  
Clinical Trials ◽  
Clinical Research ◽  
Healthcare Providers ◽  
Loved One ◽  
Academic Affiliation ◽  
Development Teams ◽  
Hypothetical Scenario ◽  
Academic Settings ◽  
Survey Responses ◽  
Patient Advocacy Groups

e13571 Background: Many community-based oncologists in the US participate in clinical trials. These trials largely fall into two categories: trials run by cooperative (co-op) groups, funded and supported by the National Cancer Institute and trials developed, and supported by the pharmaceutical (pharma) industry. This study aimed to assess participation in, and perceptions regarding, co-op versus pharma trials among US community oncologists. Methods: We invited healthcare providers (HCP) across the continental US to attend 4 virtual meetings held between September and November 2020. Participants submitted their demographic information and responses to targeted questions regarding their opinions about co-op- and pharma-sponsored trials via a web-based pre-meeting survey. We evaluated participant HCP practice demographics and survey responses using descriptive statistics. Results: Of 259 surveyed participants, HCPs specialized in hematology-oncology (57%) and medical oncology (40%) with mean (median) 19 (18) years’ clinical experience. Most HCPs (178; 69%) reported participating in clinical research, and of these, 137 (77%) participated in co-op-led and 156 (88%) participated in pharma-led clinical research. HCPs preferred participating in both pharma and co-op (49%), pharma only (22%), and co-op only (11%) trials, while 18% preferred not to participate. Co-op trials were considered more prestigious to lead (86%), less likely to imply a conflict of interest (59%), and to address more pertinent questions (58%), while pharma trials had perceived advantages of better compensation (61%) and superior efficiency (48%). Co-op trials were perceived as not being financially sustainable (69%) and slower to accrue patients (85%) than pharma-led trials. Relatedly, in a hypothetical scenario of competing trials with identical design, the majority (60%) of HCPs preferred enrolling a loved one in a co-op trial. HCPs practicing in facilities with academic affiliation (34%) and in non-academic (66%) settings reported similar perceptions about co-op- and pharma-led trials; though, HCPs in academic settings were more likely to participate in clinical research compared to those in non-academic settings (82% vs. 62% [ P=0.001], respectively). Conclusions: In our survey of experienced HCPs, co-op-led clinical trials were perceived generally more favorably than pharma-led trials, even with concerns regarding cost, feasibility, and slower recruitment. However, despite their preference for co-op trials, HCPs were more likely to participate in pharma-led trials. Almost a third of surveyed HCPs are not participating in clinical trials and a fifth do not wish to. These findings can inform stakeholders (co-op trial leadership, pharma drug development teams, and patient advocacy groups) regarding appropriate education, design, and messaging regarding future clinical trials in oncology.

Digital Pathology and Virtual Microscopy Integration in E-Health Records

2010 ◽  
pp. 457-484 ◽  
Author(s):  
Marcial García Rojo ◽  
Christel Daniel
Keyword(s):  
Biomedical Research ◽  
Digital Pathology ◽  
Virtual Microscopy ◽  
Limiting Factors ◽  
Snomed Ct ◽  
Health Records ◽  
Anatomic Pathology ◽  
Healthcare Enterprise ◽  
Information Management Systems ◽  
Research And Education

In anatomic pathology, digital pathology integrates information management systems to manage both digital images and text-based information. Digital pathology allows information sharing for diagnosis, biomedical research and education. Virtual microscopy resulting in digital slides is an outreaching technology in anatomic pathology. Limiting factors in the expansion of virtual microscopy are formidable storage dimension, scanning speed, quality of image and cultural change. Anatomic pathology data and images should be an important part of the patient electronic health records as well as of clinical datawarehouses, epidemiological or biomedical research databases, and platforms dedicated to translational medicine. Integrating anatomic pathology to the “healthcare enterprise” can only be achieved using existing and emerging medical informatics standards like Digital Imaging and Communications in Medicine (DICOM®1), Health Level Seven (HL7®), and Systematized Nomenclature of Medicine-Clinical Terms (SNOMED CT®), following the recommendations of Integrating the Healthcare Enterprise (IHE®).

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