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Epilepsia 1997A number of clinical trials that test the efficacy and safety of the newer antiepileptic drugs (AEDs) have recently been concluded. Two dose-response trials in... (Comparative Study)
Comparative Study Review
A number of clinical trials that test the efficacy and safety of the newer antiepileptic drugs (AEDs) have recently been concluded. Two dose-response trials in inpatients with refractory partial seizures and outpatients with newly diagnosed partial epilepsy established the efficacy of gabapentin as monotherapy. Lamotrigine was found to have efficacy similar to that of phenytoin and carbamazepine (CBZ) and to be better tolerated than CBZ in patients with newly diagnosed epilepsy. It was also shown to have efficacy as monotherapy in partial seizures, based on the results of an active controlled trial, and in the treatment of absence seizures, based on the results of a responder-enriched study. Topiramate as monotherapy was found to be efficacious for treatment of partial-onset seizures, based on the results of a single-center dose-response trial. A dose-response trial that tested the efficacy of tiagabine monotherapy in patients with refractory partial epilepsy was uninformative. Oxcarbazepine was found to be safe and efficacious in four comparative trials in patients with newly diagnosed epilepsy as well as in one placebo-controlled inpatient trial in patients with refractory partial seizures.
Topics: Adolescent; Adult; Aged; Ambulatory Care; Anticonvulsants; Child; Child, Preschool; Clinical Trials as Topic; Double-Blind Method; Drug Administration Schedule; Drug Approval; Drug Therapy, Combination; Epilepsy; Female; Hospitalization; Humans; Middle Aged; Multicenter Studies as Topic; Placebos; Randomized Controlled Trials as Topic; Research Design; Treatment Outcome; United States; United States Food and Drug Administration
PubMed: 9578542
DOI: 10.1111/j.1528-1157.1997.tb05201.x -
BioMed Research International 2013The recent U.S. Food and Drug Administration (FDA) coapprovals of several therapeutic compounds and their companion diagnostic devices (FDA News Release, 2011, 2013) to... (Review)
Review
The recent U.S. Food and Drug Administration (FDA) coapprovals of several therapeutic compounds and their companion diagnostic devices (FDA News Release, 2011, 2013) to identify patients who would benefit from treatment have led to considerable interest in incorporating predictive biomarkers in clinical studies. Yet, the translation of predictive biomarkers poses unique technical, logistic, and regulatory challenges that need to be addressed by a multidisciplinary team including discovery scientists, clinicians, biomarker experts, regulatory personnel, and assay developers. These issues can be placed into four broad categories: sample collection, assay validation, sample analysis, and regulatory requirements. In this paper, we provide a primer for drug development teams who are eager to implement a predictive patient segmentation marker into an early clinical trial in a way that facilitates subsequent development of a companion diagnostic. Using examples of nucleic acid-based assays, we briefly review common issues encountered when translating a biomarker to the clinic but focus primarily on key practical issues that should be considered by clinical teams when planning to use a biomarker to balance arms of a study or to determine eligibility for a clinical study.
Topics: Biomarkers; Clinical Trials as Topic; Diagnostic Tests, Routine; Drug Discovery; High-Throughput Nucleotide Sequencing; Humans; Translational Research, Biomedical; United States; United States Food and Drug Administration
PubMed: 24236296
DOI: 10.1155/2013/891391 -
Trials Mar 2017Sharing interim data, results or result extrapolations is an important issue that can affect trial integrity. The different ways in which Data Safety Monitoring Boards... (Review)
Review
BACKGROUND
Sharing interim data, results or result extrapolations is an important issue that can affect trial integrity. The different ways in which Data Safety Monitoring Boards (DSMBs) share interim results with non-DSMB members and the acceptability of such practices are poorly understood. Our objective was to undertake a narrative review specifically on what kind of interim results, if any, should be shared by the DSMB with non-DSMB members and why.
METHODS
We conducted a narrative review using a systematic search strategy of several databases and major health research stakeholders. Literature was included if there was some discussion within the full text about sharing interim trial results with non-DSMB members.
RESULTS
About 79.6% (129/162) of included citations were based on author's views, 16.7% (27/162) on research guidelines and 3.7% (6/162) on surveys. The largest group of citations, 73/162 (45%), expresses the opinion or argument against sharing interim results with exceptions. Trailing closely, 71/162 (43.8%) of the included citations support the opinion or argument that interim results should not be shared and should remain confidential with the DSMB. Half of the six surveys support sharing in some capacity, while the other three do not. Eleven circumstances were found that potentially warrant interim result sharing by the DSMB; they relate to (1) usual practices by DSMBs, (2) trial completion threatened, (3) patient safety, (4) regulatory approval and (5) other circumstances. Dominant risks for sharing under these conditions are associated with introducing trial bias.
DISCUSSION/CONCLUSION
There was no majority view in the literature. However, the largest group of citations included express the idea that interim results should remain confidential with the DSMB but also acknowledge circumstances when they could be shared with non-DSMB members. Limitations of this review are that (1) the included literature predominately provides personal perspectives, not evidence, and (2) surveys found globally focus on trial monitoring practices lacking detailed information on what specifically to share, with whom and why. More research is needed with the use of a detailed survey of the clinical trial community focused on DSMB sharing interim results, to better understand and guide DSMB interim result sharing practices.
Topics: Access to Information; Attitude of Health Personnel; Clinical Trials Data Monitoring Committees; Clinical Trials as Topic; Humans; Information Dissemination; Patient Safety; Research Design; Research Personnel; Risk Factors; Stakeholder Participation; Time Factors; Treatment Outcome
PubMed: 28279205
DOI: 10.1186/s13063-017-1858-y -
Cold Spring Harbor Perspectives in... Nov 2014For over the last three decades, extensive testing of antifungal compounds in clinical trials has been essential to the development of treatment guidelines for the most... (Review)
Review
For over the last three decades, extensive testing of antifungal compounds in clinical trials has been essential to the development of treatment guidelines for the most common invasive fungal infections, including cryptococcosis, candidiasis, aspergillosis, and the endemic fungi. These guidelines have greatly helped guide clinicians in the management of these complicated diseases. The data on which most of these guidelines are based are among the most widely recognized and cited clinical trials comparing antimicrobial agents. Unfortunately, there are many unanswered questions with respect to the diagnosis and treatment of these emerging disorders. Regarding treatment, there is a need for more clinically effective and less toxic agents. The current armamentarium of antifungal agents represents important progress over gold standard agents such as amphotericin B, but there is much progress to be made. With respect to diagnostics, mycology has generally lagged behind other disciplines in microbiology, as there are very few rapid, sensitive, specific, and point-of-care diagnostics. The ability to implement therapies for at-risk patients based on positive early diagnostic signals would greatly enhance the ability to intervene with appropriate antifungal therapy in a more targeted and specific manner. This article will review some of the major advances, as well as significant challenges that remain in the management of invasive mycoses.
Topics: Antifungal Agents; Aspergillosis; Candidiasis; Clinical Trials as Topic; Cryptococcosis; Humans; Mycoses; Practice Guidelines as Topic
PubMed: 25368017
DOI: 10.1101/cshperspect.a019745 -
Pediatrics Jun 2014Survival rates for children with cancer have significantly increased over the past 35 years. However, adolescents with cancer aged 15 to 19 years have had less progress... (Review)
Review
BACKGROUND
Survival rates for children with cancer have significantly increased over the past 35 years. However, adolescents with cancer aged 15 to 19 years have had less progress in survival prolongation compared with younger children, which may be due to lower clinical trial enrollment among adolescents with cancer. To help address this issue, the Centers for Disease Control and Prevention (CDC) convened a series of webinars to identify salient issues and measures to address this problem. This supplement is intended to raise awareness about the unique challenges of clinical trial enrollment among adolescents with cancer.
METHODS
The CDC convened a workgroup of researchers and health care providers in the field of adolescent and young adult oncology and cancer survivorship to examine the barriers and challenges limiting the participation of adolescents in clinical trials and to define ways to improve on these concerns.
RESULTS
The workgroup identified 3 distinct issues affecting clinical trial enrollment among adolescents with cancer: (1) many adolescents with cancer are not referred to institutions where clinical trials are offered, (2) there are limited numbers of clinical trials for adolescents with cancer, and (3) psychosocial barriers impede adolescents with cancer from enrolling in clinical trials.
CONCLUSIONS
Adolescents with cancer have the smallest proportion and least number of patients enrolled in clinical trials in pediatric oncology. Successfully addressing this challenge requires improving referral to existing clinical trials, addressing regulatory barriers to clinical trial enrollment, increasing the number of clinical trials for adolescents, and addressing unique psychosocial barriers to clinical trial enrollment.
Topics: Adolescent; Clinical Trials as Topic; Education; Humans; Neoplasms; Patient Selection; Survival Rate
PubMed: 24918212
DOI: 10.1542/peds.2014-0122B -
JACC. Cardiovascular Imaging Mar 2017Cardiovascular imaging is an integral component of many clinical trials beyond those for which the primary goal is to evaluate or validate imaging technologies. The... (Review)
Review
Cardiovascular imaging is an integral component of many clinical trials beyond those for which the primary goal is to evaluate or validate imaging technologies. The scope of such trials is broad, ranging from those in which a medical, surgical, or interventional cardiovascular device or drug is being evaluated to those in which there is concern about cardiovascular adverse events complicating treatment for noncardiac conditions. This paper discusses study design as itĀ pertains to the incorporation of imaging elements, the important role played by imaging core laboratories, the rationale for and approaches to involvement of imagers in clinical trials, and guidance by the U.S. Food and Drug Administration onĀ imaging endpoints in clinical trials.
Topics: Cardiac Imaging Techniques; Cardiovascular Diseases; Clinical Trials as Topic; Endpoint Determination; Humans; Observer Variation; Predictive Value of Tests; Reproducibility of Results; Research Design; United States; United States Food and Drug Administration
PubMed: 28279377
DOI: 10.1016/j.jcmg.2016.12.003 -
Journal of Vascular and Interventional... Aug 2013A sophisticated understanding of the rapidly changing field of oncology, including a broad knowledge of oncologic disease and the therapies available to treat them, is... (Review)
Review
A sophisticated understanding of the rapidly changing field of oncology, including a broad knowledge of oncologic disease and the therapies available to treat them, is fundamental to the interventional radiologist providing oncologic therapies, and is necessary to affirm interventional oncology as one of the four pillars of cancer care alongside medical, surgical, and radiation oncology. The first part of this review intends to provide a concise overview of the fundamentals of oncologic clinical trials, including trial design, methods to assess therapeutic response, common statistical analyses, and the levels of evidence provided by clinical trials.
Topics: Clinical Trials as Topic; Confidence Intervals; Data Interpretation, Statistical; Disease Progression; Disease-Free Survival; Endpoint Determination; Evidence-Based Medicine; Humans; Kaplan-Meier Estimate; Medical Oncology; Neoplasms; Radiography, Interventional; Research Design; Time Factors; Treatment Outcome
PubMed: 23809510
DOI: 10.1016/j.jvir.2013.04.024 -
Gut Feb 2021Central reading, that is, independent, off-site, blinded review or reading of imaging endpoints, has been identified as a crucial component in the conduct and analysis... (Review)
Review
Central reading, that is, independent, off-site, blinded review or reading of imaging endpoints, has been identified as a crucial component in the conduct and analysis of inflammatory bowel disease clinical trials. Central reading is the final step in a workflow that has many parts, all of which can be improved. Furthermore, the best reading algorithm and the most intensive central reader training cannot make up for deficiencies in the acquisition stage (clinical trial endoscopy) or improve on the limitations of the underlying score (outcome instrument). In this review, academic and industry experts review scoring systems, and propose a theoretical framework for central reading that predicts when improvements in statistical power, affecting trial size and chances of success, can be expected: Multireader models can be conceptualised as statistical or non-statistical (social). Important organisational and operational factors, such as training and retraining of readers, optimal bowel preparation for colonoscopy, video quality, optimal or at least acceptable read duration times and other quality control matters, are addressed as well. The theory and practice of central reading and the conduct of endoscopy in clinical trials are interdisciplinary topics that should be of interest to many, regulators, clinical trial experts, gastroenterology societies and those in the academic community who endeavour to develop new scoring systems using traditional and machine learning approaches.
Topics: Algorithms; Clinical Trials as Topic; Colonoscopy; Endpoint Determination; Forecasting; Humans; Inflammatory Bowel Diseases; Observer Variation
PubMed: 32699100
DOI: 10.1136/gutjnl-2020-320690 -
BMJ Open Feb 2019Patients, families and clinicians rely on published research to help inform treatment decisions. Without complete reporting of the outcomes studied, evidence-based...
INTRODUCTION
Patients, families and clinicians rely on published research to help inform treatment decisions. Without complete reporting of the outcomes studied, evidence-based clinical and policy decisions are limited and researchers cannot synthesise, replicate or build on existing research findings. To facilitate harmonised reporting of outcomes in published trial protocols and reports, the Instrument for reporting Planned Endpoints in Clinical Trials (InsPECT) is under development. As one of the initial steps in the development of InsPECT, a scoping review will identify and synthesise existing guidance on the reporting of trial outcomes.
METHODS AND ANALYSIS
We will apply methods based on the Joanna Briggs Institute scoping review methods manual. Documents that provide explicit guidance on trial outcome reporting will be searched for using: (1) an electronic bibliographic database search; (2) a grey literature search; and (3) solicitation of colleagues for guidance documents using a snowballing approach. Reference list screening will be performed for included documents. Search results will be divided between two trained reviewers who will complete title and abstract screening, full-text screening and data charting. Captured trial outcome reporting guidance will be compared with candidate InsPECT items to support, refute or refine InsPECT content and to assess the need for the development of additional items. Data analysis will explore common features of guidance and use quantitative measures (eg, frequencies) to characterise guidance and its sources.
ETHICS AND DISSEMINATION
A paper describing the review findings will be published in a peer-reviewed journal. The results will be used to inform the InsPECT development process, helping to ensure that InsPECT provides an evidence-based tool for standardising trial outcome reporting.
Topics: Clinical Trials as Topic; Consensus; Consensus Development Conferences as Topic; Endpoint Determination; Humans; Information Dissemination; Research Design; Review Literature as Topic; Treatment Outcome
PubMed: 30782872
DOI: 10.1136/bmjopen-2018-023001 -
Tidsskrift For Den Norske Laegeforening... Sep 2001
Topics: Clinical Trials as Topic; Female; Humans; Mammography
PubMed: 11668767
DOI: No ID Found