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Postgraduate Medicine Sep 2011The recent focus of federal funding on comparative effectiveness research underscores the importance of clinical trials in the practice of evidence-based medicine and... (Review)
Review
The recent focus of federal funding on comparative effectiveness research underscores the importance of clinical trials in the practice of evidence-based medicine and health care reform. The impact of clinical trials not only extends to the individual patient by establishing a broader selection of effective therapies, but also to society as a whole by enhancing the value of health care provided. However, clinical trials also have the potential to pose unknown risks to their participants, and biased knowledge extracted from flawed clinical trials may lead to the inadvertent harm of patients. Although conducting a well-designed clinical trial may appear straightforward, it is founded on rigorous methodology and oversight governed by key ethical principles. In this review, we provide an overview of the ethical foundations of trial design, trial oversight, and the process of obtaining approval of a therapeutic, from its pre-clinical phase to post-marketing surveillance. This narrative review is based on a course in clinical trials developed by one of the authors (DJM), and is supplemented by a PubMed search predating January 2011 using the keywords "randomized controlled trial," "patient/clinical research," "ethics," "phase IV," "data and safety monitoring board," and "surrogate endpoint." With an understanding of the key principles in designing and implementing clinical trials, health care providers can partner with the pharmaceutical industry and regulatory bodies to effectively compare medical therapies and thereby meet one of the essential goals of health care reform.
Topics: Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Clinical Trials, Phase IV as Topic; Drug Evaluation; Humans; Randomized Controlled Trials as Topic; United States
PubMed: 21904102
DOI: 10.3810/pgm.2011.09.2475 -
British Journal of Clinical Pharmacology Mar 2015Safety and efficacy data on many medicines used in children are surprisingly scarce. As a result children are sometimes given ineffective medicines or medicines with... (Review)
Review
Safety and efficacy data on many medicines used in children are surprisingly scarce. As a result children are sometimes given ineffective medicines or medicines with unknown harmful side effects. Better and more relevant clinical trials in children are needed to increase our knowledge of the effects of medicines and to prevent the delayed or non-use of beneficial therapies. Clinical trials provide reliable evidence of treatment effects by rigorous controlled testing of interventions on human subjects. Paediatric trials are more challenging to conduct than trials in adults because of the paucity of funding, uniqueness of children and particular ethical concerns. Although current regulations and initiatives are improving the scope, quantity and quality of trials in children, there are still deficiencies that need to be addressed to accelerate radically equitable access to evidence-based therapies in children.
Topics: Child; Clinical Trials as Topic; Drug Evaluation; Drugs, Investigational; Ethics, Medical; Humans; Pediatrics; Research Design
PubMed: 24325152
DOI: 10.1111/bcp.12305 -
Annals of Internal Medicine Feb 2013The protocol of a clinical trial serves as the foundation for study planning, conduct, reporting, and appraisal. However, trial protocols and existing protocol...
The protocol of a clinical trial serves as the foundation for study planning, conduct, reporting, and appraisal. However, trial protocols and existing protocol guidelines vary greatly in content and quality. This article describes the systematic development and scope of SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013, a guideline for the minimum content of a clinical trial protocol.The 33-item SPIRIT checklist applies to protocols for all clinical trials and focuses on content rather than format. The checklist recommends a full description of what is planned; it does not prescribe how to design or conduct a trial. By providing guidance for key content, the SPIRIT recommendations aim to facilitate the drafting of high-quality protocols. Adherence to SPIRIT would also enhance the transparency and completeness of trial protocols for the benefit of investigators, trial participants, patients, sponsors, funders, research ethics committees or institutional review boards, peer reviewers, journals, trial registries, policymakers, regulators, and other key stakeholders.
Topics: Checklist; Clinical Protocols; Clinical Trials as Topic; Humans
PubMed: 23295957
DOI: 10.7326/0003-4819-158-3-201302050-00583 -
Frontiers in Public Health 2022Decentralized clinical trials (DCTs) are studies in which the need for patients to physically access hospital-based trial sites is reduced or eliminated. The CoViD-19... (Review)
Review
Decentralized clinical trials (DCTs) are studies in which the need for patients to physically access hospital-based trial sites is reduced or eliminated. The CoViD-19 pandemic has caused a significant increase in DCT: a survey shows that 76% of pharmaceutical companies, device manufacturers, and Contract Research Organizations adopted decentralized techniques during the early phase of the pandemic. The implementation of DCTs relies on the use of digital tools such as e-consent, apps, wearable devices, Electronic Patient-Reported Outcomes (ePRO), telemedicine, as well as on moving trial activities to the patient's home (e.g., drug delivery) or to local healthcare settings (i.e., community-based diagnosis and care facilities). DCTs adapt to patients' routines, allow patients to participate regardless of where they live by removing logistical barriers, offer better access to the study and the investigational product, and permit the inclusion of more diverse and more representative populations. The feasibility and quality of DCTs depends on several requirements including dedicated infrastructures and staff, an adequate regulatory framework, and partnerships between research sites, patients and sponsors. The evaluation of Ethics Committees (ECs) is crucial to the process of innovating and digitalizing clinical trials: adequate assessment tools and a suitable regulatory framework are needed for evaluation by ECs. DCTs also raise issues, many of which are of considerable ethical significance. These include the implications for the relationship between patients and healthcare staff, for the social dimension of the patient, for data integrity (at the source, during transmission, in the analysis phase), for personal data protection, and for the possible risks to health and safety. Despite their considerable growth, DCTs have only received little attention from bioethicists. This paper offers a review on some ethical implications and requirements of DCTs in order to encourage further ethical reflection on this rapidly emerging field.
Topics: Humans; COVID-19; Delivery of Health Care; Pandemics; Telemedicine; Clinical Trials as Topic
PubMed: 36590004
DOI: 10.3389/fpubh.2022.1081150 -
The New England Journal of Medicine Jul 2016
Review
Topics: Biomarkers; Clinical Trials as Topic; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Government Regulation; Humans; Research Design; Sample Size
PubMed: 27406349
DOI: 10.1056/NEJMra1510061 -
Pharmaceutical Statistics 2016A sample size justification is a vital part of any trial design. However, estimating the number of participants required to give a meaningful result is not always...
A sample size justification is a vital part of any trial design. However, estimating the number of participants required to give a meaningful result is not always straightforward. A number of components are required to facilitate a suitable sample size calculation. In this paper, the steps for conducting sample size calculations for non-inferiority and equivalence trials are summarised. Practical advice and examples are provided that illustrate how to carry out the calculations by hand and using the app SampSize.
Topics: Clinical Trials as Topic; Humans; Sample Size; Therapeutic Equivalency
PubMed: 26604186
DOI: 10.1002/pst.1716 -
British Journal of Anaesthesia Jul 2021
Topics: Clinical Trials as Topic; Data Interpretation, Statistical; Humans; Meta-Analysis as Topic
PubMed: 33992396
DOI: 10.1016/j.bja.2021.04.007 -
Trials Jul 2010Managing clinical trials, of whatever size and complexity, requires efficient trial management. Trials fail because tried and tested systems handed down through... (Review)
Review
Managing clinical trials, of whatever size and complexity, requires efficient trial management. Trials fail because tried and tested systems handed down through apprenticeships have not been documented, evaluated or published to guide new trialists starting out in this important field. For the past three decades, trialists have invented and reinvented the trial management wheel. We suggest that to improve the successful, timely delivery of important clinical trials for patient benefit, it is time to produce standard trial management guidelines and develop robust methods of evaluation.
Topics: Clinical Trials as Topic; Communication; Cooperative Behavior; Efficiency, Organizational; Guideline Adherence; Humans; Publishing
PubMed: 20626885
DOI: 10.1186/1745-6215-11-78 -
Journal of Surgical Oncology Jul 2020
Topics: Clinical Trials as Topic; Cooperative Behavior; Curriculum; Education, Medical, Graduate; Fellowships and Scholarships; Humans; Interprofessional Relations; Research Design; Surgical Oncology; Texas
PubMed: 32149390
DOI: 10.1002/jso.25889 -
Chinese Clinical Oncology Sep 2015Treatment of brain tumors is increasingly informed by biomarkers. One use is to appropriately group tumors with similar genetic/genomic characteristics and to design... (Review)
Review
Treatment of brain tumors is increasingly informed by biomarkers. One use is to appropriately group tumors with similar genetic/genomic characteristics and to design trials separately for the individual groups. The biomarker's use is to predict patient response so that the most effective treatment can be selected for patients based on their tumor characteristics. Trial designs that recruit unselected patients are poorly suited for identifying treatments effective only in subsets of patients given the relatively small numbers of patients available for trials. Investigators are beginning to use different designs that better account for tumor heterogeneity. In this article, an overview of the role of biomarkers in brain tumor trials is presented in the context of existing clinical trials as well as trials that may be launched within the next several years.
Topics: Biomarkers, Tumor; Brain Neoplasms; Clinical Trials as Topic; History, 20th Century; History, 21st Century; Humans; Research Design
PubMed: 26408305
DOI: 10.3978/j.issn.2304-3865.2015.09.04