Journey across epidemiology’s third variables: an anesthesiologist’s guide for successfully navigating confounding, mediation, and effect modification

2021 ◽  
pp. rapm-2020-101984 ◽  
Author(s):  
Joshua Levy ◽  
Rebecca Lebeaux ◽  
Brock Christensen ◽  
Tor Tosteson ◽  
Yvon Bryan
Keyword(s):  
Clinical Trials ◽  
Clinical Study ◽  
Clinical Research ◽  
Patient Outcomes ◽  
Clinical Studies ◽  
Effect Modification ◽  
Medical Interventions ◽  
Patient Health ◽  
Independent Variable ◽  
The Relationship

Observational clinical research studies aim to assess which exposures (treatments or other factors; independent variable) affect patient outcomes (dependent variable). These exposures include medical interventions in situations where clinical trials are not possible or prior to their conduct and completion. However, the assessment of the relationship between exposures and outcomes is not straightforward, as other variables may need to be considered prior to reaching valid conclusions. Here, we present three hypothetical scenarios in regional anesthesia to review the epidemiological concepts of confounding, mediation, and effect modification. Understanding these concepts is critical for assessing the design, analysis, and interpretation of clinical studies. These terms may be confusing to anesthesiologists and researchers alike, where such confusion could affect the conclusions of a clinical study, mislead the target audience, and ultimately impact patient health.

scholarly journals Remdesivir: Critical Clinical Appraisal for COVID 19 Treatment

Drug Research ◽  
2020 ◽  
Author(s):  
Saptarshi Chatterjee
Keyword(s):  
Clinical Trials ◽  
Clinical Research ◽  
Clinical Studies ◽  
Promising Result ◽  
Drug Repurposing ◽  
In Vitro Studies ◽  
Therapeutic Molecules ◽  
Regulatory Aspect ◽  
Plausible Mechanism

AbstractRemdesivir is presently been considered as ‘molecule of hope’ to curb the menace of COVID19. Non-availability of any USFDA approved drug has led to several attempt of drug-repurposing and development of new therapeutic molecules. However, Remdesivir has been found to be effective against a broad range of virus including SARS, MERS and COVID 19 through in-vitro studies. Several clinical research attempt are presently being conducted showing promising result yet not conclusive. This review summarized all such clinical trials to critically appraise the usage of Remdesivir against COVID 19 along with the publications related to the results of the clinical studies. The present regulatory aspect i. e. Emergency Use Authorization (EYA) and information of molecule and plausible mechanism is also dealt.

Reviews in Medical Ethics

2008 ◽  
Vol 36 (2) ◽  
pp. 419-424
Author(s):  
Ana S. Iltis
Keyword(s):  
Clinical Trials ◽  
Medical Ethics ◽  
Clinical Research ◽  
Intended Audience ◽  
Institutional Review ◽  
Law And Ethics ◽  
Ethics Research ◽  
Depth Study ◽  
The Relationship ◽  
Shed Light

What the Doctor Didn’t Say, by Jerry Menikoff and Edward P. Richards, is a courageous and well-written volume that examines some of the fundamental debates pertaining to the ethics of clinical research. The volume deserves a careful reading by anyone with a potential role in clinical research: clinicians who might serve as investigators or refer patients to clinical trials; research staff; Institutional Review Board (IRB) members and administrators; sponsors who design clinical trials; and the book’s intended audience, namely, potential research participants and their families. A cursory reading of this volume might lead one to think that Menikoff and Richards have declared war on clinical research. They have not. Instead, they offer an in-depth study of the conduct and oversight of clinical research through the lens of law and ethics. They shed light on old issues and initiate discussion of new questions, challenging readers to think critically about the relationship between medical ethics, research ethics, the law, and the conduct of clinical research.

scholarly journals The role of a data manager at a clinical trial center: the experience of the Alessandria hospital, Italy

2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Fabio Giacchero ◽  
Carolina Pelazza ◽  
Serena Panpa ◽  
Marinella Bertolotti ◽  
Tatiana Bolgeo ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Clinical Research ◽  
Clinical Studies ◽  
Reference Period ◽  
Job Description ◽  
Data Manager

Objectives: To define the Data Manager (DM) job description within the Clinical Trial Center (CTC) of the Alessandria Hospital (AO AL). To identify the number of authorized clinical studies after the implementation of three DMs in the CTC of the AO AL. Methods: The activities of the DM within the CTC of the AO AL take place in the activation, management and conclusion of clinical trials. The activities were monitored through specific indicators from June 01st, 2019 to May 31st, 2020. Results: During the reference period, an increased authorized studies were observed. Conclusion: The implementation of DMs in the CTC of AO AL has been demonstrated the importance of the figure itself, which, although it has not professionally recognized yet, is found to be fundamental in clinical research.

Placebo Orthodoxy in Clinical Research II: Ethical, Legal, and Regulatory Myths

1996 ◽  
Vol 24 (3) ◽  
pp. 252-259 ◽  
Author(s):  
Benjamin Freedman ◽  
Kathleen Cranley Glass ◽  
Charles Weijer
Keyword(s):  
Clinical Trials ◽  
Clinical Research ◽  
The United States ◽  
Human Experimentation ◽  
Medical Interventions ◽  
Placebo Controls ◽  
United States Food ◽  
Considerable Controversy ◽  
States Food ◽  
Continued Use

Placebo-controlled trials are held by many, including regulators at agencies like the United States Food and Drug Administration (FDA), to be the gold standard in the assessment of new medical interventions. Yet the use of placebo controls in clinical trials has been the focus of considerable controversy. In this two-part article, we challenge a number of common beliefs concerning the value of placebo controls. Part I critiques statistical and other scientific justifications for the use of placebo controls in clinical research. The continued use of placebo controls in clinical trials on diseases for which accepted treatment exists raises equally important ethical, legal, and regulatory issues for which various justifications have been given. Defense of this practice relies on normative as well as empirical myths.In their attack on the prevailing use of placebo controls, Kenneth Rothman and Karin Michels emphasize that this practice stands in violation of the World Medical Association's guidelines on the ethics of human experimentation, most commonly known as the Helsinki Declaration.

scholarly journals The Current Status and Future Direction of Clinical Research in Japan From a Regulatory Perspective

2022 ◽  
Vol 8 ◽  
Author(s):  
Hideki Maeda
Keyword(s):  
Clinical Trials ◽  
Clinical Study ◽  
Clinical Research ◽  
Personal Information ◽  
Human Subjects ◽  
Legal Framework ◽  
Current Status ◽  
Biological Research ◽  
Marketing Approval ◽  
Ethical Guidelines

In Japan, a law called the Clinical Trials Act went into being effective on April 1, 2018, and clinical research on human subjects conducted in Japan has been undergone major changes. Those other than clinical trials for marketing approval of drugs or medical devices are broadly classified into “specific clinical trials” and others, and regulations have been tightened for each. As a result, clinical interventional study was drastically reduced, and observational clinical study increased. For the observational clinical study, the two previous ethical guidelines were merged into the “Ethical Guidelines for Medical and Biological Research Involving Human Subjects,” which was enacted in March 2021. The observational clinical study is now subjected to these ethical guidelines. In addition, changes are planned for the Act on the Protection of Personal Information, which greatly affects data collection in clinical research. Clinical research in Japan must be conducted appropriately while adapting to these various changes in the external environment and legal framework. Adapting to these changes is not an easy task, as it requires increased financial and human resources for all stakeholders.

scholarly journals Clinical trials in the pandemic age: What is fit for purpose?

2020 ◽  
Vol 4 ◽  
pp. 58 ◽  
Author(s):  
Dan Hartman ◽  
Penny Heaton ◽  
Nick Cammack ◽  
Ian Hudson ◽  
Shawn Dolley ◽  
...  
Keyword(s):  
Public Health ◽  
Clinical Trials ◽  
Clinical Study ◽  
Clinical Research ◽  
Vulnerable Groups ◽  
Equitable Access ◽  
Fit For Purpose ◽  
Gates Foundation ◽  
And Migration ◽  
Scientific Questions

It is critical to ensure that COVID-19 studies provide clear and timely answers to the scientific questions that will guide us to scalable solutions for all global regions. Significant challenges in operationalizing trials include public policies for managing the pandemic, public health and clinical capacity, travel and migration, and availability of tests and infrastructure. These factors lead to spikes and troughs in patient count by location, disrupting the ability to predict when or if a trial will reach recruitment goals. The focus must also be on understanding how to provide equitable access to these interventions ensuring that interventions reach those who need them the most, be it patients in low resource settings or vulnerable groups.  We introduce a website to be used by The Bill & Melinda Gates Foundation, Wellcome Trust, and other funders of the COVID Therapeutics Accelerator that accept proposals for future clinical research. The portal enables evaluations of clinical study applications that focus on study qualities most likely to lead to informative outcomes and completed studies.

scholarly journals Adapt to Translate

2021 ◽  
Vol 17 (2) ◽  
pp. 5-24
Author(s):  
Daria Jadreškić
Keyword(s):  
Clinical Trials ◽  
Clinical Practice ◽  
Clinical Research ◽  
Pharmaceutical Research ◽  
Lessons Learned ◽  
Operational Conditions ◽  
Medical Interventions ◽  
Adaptive Trials ◽  
Adaptive Clinical Trials ◽  
Normative Argument

The article presents the advantages and limitations of adaptive clinical trials for assessing the effectiveness of medical interventions and specifies the conditions that contributed to their development and implementation in clinical practice. I advance two arguments by discussing different cases of adaptive trials. The normative argument is that responsible adaptation should be taken seriously as a new way of doing clinical research insofar as a valid justification, sufficient understanding, and adequate operational conditions are provided. The second argument is historical. The development of adaptive trials can be related to lessons learned from research in cases of urgency and to the decades-long efforts to end the productivity crisis of pharmaceutical research, which led to the emergence of translational, personalized, and, recently, precision medicine movements.

scholarly journals The Critical Role of the Clinical Research Coordinator for Clinical Trials: A Survey in Oncology

2017 ◽  
Vol 1 ◽  
pp. maapoc.0000015 ◽  
Author(s):  
Margherita Cinefra ◽  
Celeste Cagnazzo ◽  
Laura McMahon ◽  
Francesca Arizio ◽  
Sara Campora ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Clinical Research ◽  
Clinical Studies ◽  
Research Team ◽  
Critical Role ◽  
Strong Support ◽  
Web Survey ◽  
Clinical Research Coordinator ◽  
Research Activities ◽  
Research Coordinator

Introduction Access to innovative medicine requires proper evidence from clinical trials with the growing demand of qualified and experienced personnel. The clinical research coordinator (CRC) plays an important role in the conduction of research activities and provides a strong support to the research team. In Italy, this role is not recognized at any institutional level and its professional outline is still indefinite. Several national associations (Associazione Italiana di Oncologia Medica, Collegio Italiano dei Primari Oncologi Medici Ospedalieri, Gruppo Italiano Data Manager) are committed to promoting the enhancement and recognition of the professional status of CRCs, underlining their role as fundamental. Methods A web survey, proposed by the AIOM CRC Working Group, was submitted to 319 Italian oncology sites with items focusing on the organization of sites, the research activities, the staff composition, and the presence of coordinators and the multidisciplinary team. Results A total of 115 sites (35.9%) responded to the web survey. Clinical studies were carried out at 88.7% of the investigated sites, and coordinators were on staff at 75.5% of the active investigational sites. Interestingly, there was a direct association between the number of clinical studies and the number of coordinators, whose contribution to the research activities is believed to be essential for trial conduct in 82.4% of cases. Most sites retain that the quality of clinical research has absolutely improved (83.3%) after the implementation of a coordinator as member of the team. Conclusions Given the constant growth of the number of clinical trials performed at Italian oncology sites, the CRC proves to be an essential component of the research team. However, there is an urgent need to institute the professional role alongside the need to standardize the training of coordinators to establish the minimum requirements enhanced by qualifying courses.

Sex differences in experimental studies of depression: How can clinical research benefit?

2017 ◽  
Vol 41 (S1) ◽  
pp. s905-s905
Author(s):  
N. Kokras ◽  
C. Dalla
Keyword(s):  
Clinical Trials ◽  
Sex Differences ◽  
Clinical Research ◽  
Clinical Studies ◽  
Rating Scales ◽  
Experimental Studies ◽  
Preclinical Studies ◽  
Antidepressant Response ◽  
Preclinical Research ◽  
Behavioral Indices

IntroductionSex differences in depression and antidepressant response in humans are modestly studied and results are controversial. Experimental studies using animal models may provide insights that could be useful in clinical trials.ObjectivesThe objective is to summarize findings from preclinical studies on sex differences and suggest how such preclinical research might be of use in clinical research.AimsSpecifically it is aimed to summarize evidence for both sexes in relation to the phenotype of depression, its endophenotype and the antidepressant response.MethodsA selection of experimental studies on sex differences in stress and antidepressant response was performed and their findings were linked to potential confounders or methodological issues that might obscure the results of clinical trials.ResultsIn preclinical studies, behavioral indices and models are adjusted for both sexes, in order to properly identify sex differences in primary outcomes. This is not routinely happening in clinical studies when using depression rating scales, which is the analogue of behavioral indices. Moreover, preclinical studies show sex differences at the baseline behavioral response and underlying mechanisms that often converge following antidepressant treatment. This is also a neglected issue in human studies. Finally, preclinical research suggests that when researching on potential biomarkers for depression and antidepressant response sex should be an important factor to consider.ConclusionsCautious exploitation of findings on sex differences from preclinical research could improve the design and quality of clinical studies for disease biomarkers and novel antidepressants and facilitate the drug development in a gender aware manner.Disclosure of interestNK has received honoraria and travel support from Janssen-Cilag, Lundbeck, Sanofi-Aventis, Medochemie Generics and Elpen S.A. CD has received honoraria from Janssen-Cilag and travel support from Boehringer Ingelheim. None of those is relevant to this study.

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