-
Controlled Clinical Trials Jun 1984Concepts used in evaluating the results of diagnostic tests have been applied to clinical trials by several authors and each has reached the same conclusion: positive...
Concepts used in evaluating the results of diagnostic tests have been applied to clinical trials by several authors and each has reached the same conclusion: positive trials are more often falsely positive than would intuitively be expected. This conclusion is, however, based on assumptions that require close examination. First of all, it depends upon equating the power of a clinical trial with the sensitivity of a diagnostic test. Although it is possible to define circumstances in which the two are equivalent, decisions made on the basis of the results of clinical trials usually employ a broader definition of "true positive" than, it is shown, is implied by equating sensitivity with power. Secondly, it is assumed that one can speak meaningfully of the baseline "prevalence" of positive trials. The practical application of this concept can be shown to be extremely difficult. Thus, approaching clinical trials as if they were a type of diagnostic test is superficially appealing. However, this may result in misleading conclusions.
Topics: Clinical Trials as Topic; False Negative Reactions; False Positive Reactions; Humans; Random Allocation
PubMed: 6744884
DOI: 10.1016/0197-2456(84)90117-x -
Statistics in Medicine Jun 2011Adaptive designs or flexible designs in a broader sense have increasingly been considered in planning pivotal registration clinical trials. Sample size reassessment...
Adaptive designs or flexible designs in a broader sense have increasingly been considered in planning pivotal registration clinical trials. Sample size reassessment design and adaptive selection design are two of such designs that appear in regulatory applications. At the design stage, consideration of sample size reassessment at an interim time of the trial should lead to extensive discussion about how to appropriately size the trial. Additionally, careful attention needs to be paid to the issue of how the size of the trial is impacted by the requirement that the final p-value of the trial meets the specific threshold of a clinically meaningful effect. These issues are not straightforward and will be discussed in this work. In a trial design that allows selection between a pre-specified patient subgroup and the initially planned overall patient population based on the accumulating data, there is an issue of what the 'overall' population means. In addition, it is critically important to know how such selection influences the validity of statistical inferences on the potentially modified overall population. This work presents the biases that may incur under adaptive patient selection designs.
Topics: Antihypertensive Agents; Bias; Blood Pressure; Clinical Trials as Topic; Humans; Hypertension; Patient Selection; Sample Size; United States
PubMed: 21344470
DOI: 10.1002/sim.4021 -
Alzheimer's & Dementia : the Journal of... Jul 2015This article reviews the current status of the Clinical Core of the Alzheimer's Disease Neuroimaging Initiative (ADNI), and summarizes planning for the next stage of the... (Review)
Review
INTRODUCTION
This article reviews the current status of the Clinical Core of the Alzheimer's Disease Neuroimaging Initiative (ADNI), and summarizes planning for the next stage of the project.
METHODS
Clinical Core activities and plans were synthesized based on discussions among the Core leaders and external advisors.
RESULTS
The longitudinal data in ADNI-2 provide natural history data on a clinical trials population and continue to inform refinement and standardization of assessments, models of trajectories, and clinical trial methods that have been extended into sporadic preclinical Alzheimer's disease (AD).
DISCUSSION
Plans for the next phase of the ADNI project include maintaining longitudinal follow-up of the normal and mild cognitive impairment cohorts, augmenting specific clinical cohorts, and incorporating novel computerized cognitive assessments and patient-reported outcomes. A major hypothesis is that AD represents a gradually progressive disease that can be identified precisely in its long presymptomatic phase, during which intervention with potentially disease-modifying agents may be most useful.
Topics: Age Factors; Alzheimer Disease; Clinical Trials as Topic; Cognition Disorders; Computer Communication Networks; History, 20th Century; History, 21st Century; Humans; Longitudinal Studies; Neuroimaging
PubMed: 26194309
DOI: 10.1016/j.jalz.2015.05.005 -
Pharmaceutical Statistics 2014In this paper, we describe a method of comparing agreement between two diagnostic contingency tables after adjustment to more clinically relevant marginal distributions... (Comparative Study)
Comparative Study
In this paper, we describe a method of comparing agreement between two diagnostic contingency tables after adjustment to more clinically relevant marginal distributions using the iterative proportional fitting algorithm. When the categories of a contingency table represent mild, moderate, and severe outcomes, the majority of patients often are in the mild category. Because it is often of more interest to evaluate agreement when patients are uniformly distributed among categories, we present the primary results of two clinical trials with adjustment to this structure. We also describe the relationship between the sponsor's pre-specified agreement measure for the observed contingency table and kappa for the adjusted table; and by either criterion, we then show that the agreement of the new diagnostic tool with the standard diagnostic tool is comparably non-inferior to the agreement of the standard diagnostic tool with itself.
Topics: Algorithms; Clinical Trials as Topic; Diagnostic Techniques and Procedures; Humans; Reproducibility of Results; Research Design
PubMed: 24715653
DOI: 10.1002/pst.1614 -
Anaesthesia Jul 2018
Topics: Clinical Decision-Making; Humans; Perioperative Care; Pragmatic Clinical Trials as Topic; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 29577228
DOI: 10.1111/anae.14238 -
Journal of the American College of... Apr 2021The momentum of cardiovascular drug development has slowed dramatically. Use of validated cardiac biomarkers in clinical trials could accelerate development of... (Review)
Review
The momentum of cardiovascular drug development has slowed dramatically. Use of validated cardiac biomarkers in clinical trials could accelerate development of much-needed therapies, but biomarkers have been used less for cardiovascular drug development than in therapeutic areas such as oncology. Moreover, there are inconsistences in biomarker use in clinical trials, such as sample type, collection times, analytical methods, and storage for future research. With these needs in mind, participants in a Cardiac Safety Research Consortium Think Tank proposed the development of international guidance in this area, together with improved quality assurance and analytical methods, to determine what biomarkers can reliably show. Participants recommended the development of systematic methods for sample collection, and the archiving of samples in all cardiovascular clinical trials (including creation of a biobank or repository). The academic and regulatory communities also agreed to work together to ensure that published information is fully and clearly expressed.
Topics: Biomarkers; Cardiovascular Diseases; Clinical Trials as Topic; Drug Discovery; Humans; Precision Medicine; Prognosis; Treatment Outcome
PubMed: 33858628
DOI: 10.1016/j.jacc.2021.02.040 -
AJR. American Journal of Roentgenology Apr 2021The purpose of this article is to provide radiologists with a guide to the fundamental principles of oncology clinical trials. The review summarizes the evolution and... (Review)
Review
The purpose of this article is to provide radiologists with a guide to the fundamental principles of oncology clinical trials. The review summarizes the evolution and structure of modern clinical trials with an emphasis on the relevance of clinical trials in the field of oncologic imaging. Understanding the structure and clinical relevance of modern clinical trials is beneficial for radiologists in the field of oncologic imaging.
Topics: Biomarkers, Tumor; Clinical Trials as Topic; Drug Development; Humans; Neoplasms; Radiologists; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 33594911
DOI: 10.2214/AJR.20.22852 -
Clinical Pharmacology and Therapeutics Apr 2020Our goal was to assess the enrichment utility of hippocampal volume (HV) as an enrichment biomarker in amnestic mild cognitive impairment (aMCI) clinical trials, and,...
Our goal was to assess the enrichment utility of hippocampal volume (HV) as an enrichment biomarker in amnestic mild cognitive impairment (aMCI) clinical trials, and, hence, develop an HV neuroimaging-informed clinical trial enrichment tool. Modeling of integrated longitudinal patient-level data came from open-access natural history studies in patients diagnosed with aMCI-the Alzheimer's Disease Neuroimaging Initiative (ADNI)-1 and ADNI-2-and indicated that a decrease of 1 cm with respect to the analysis dataset median baseline intracranial volume-adjusted HV (ICV-HV; ~ 5 cm ) is associated with > 50% increase in disease progression rate as measured by the Clinical Dementia Rating Scale-Sum of Boxes. Clinical trial simulations showed that the inclusion of aMCI subjects with baseline ICV-HV below the 84th or 50th percentile allowed an approximate reduction in trial size of at least 26% and 55%, respectively. This clinical trial enrichment tool can help design more efficient and informative clinical trials.
Topics: Aged; Aged, 80 and over; Clinical Trials as Topic; Cognitive Dysfunction; Data Interpretation, Statistical; Databases, Factual; Female; Hippocampus; Humans; Longitudinal Studies; Male; Middle Aged; Monte Carlo Method; Neuroimaging
PubMed: 31899810
DOI: 10.1002/cpt.1766 -
Fertility and Sterility May 2014Clinical trials in infertility choose from a variety of outcomes including change in some surrogate marker of gamete quality to healthy live birth. Incomplete reporting...
Clinical trials in infertility choose from a variety of outcomes including change in some surrogate marker of gamete quality to healthy live birth. Incomplete reporting of outcomes makes it difficult to compare studies and to determine the clinical impact of infertility treatments. In this Views and Reviews, we explore the merits of collecting various outcomes of interest in infertility trials from the vantage point of infertility specialists, an obstetrician, and a pediatrician. These articles support more complete reporting of maternal, paternal, fetal, and infant outcomes from infertility trials to improve patient care and ultimately public health.
Topics: Choice Behavior; Clinical Trials as Topic; Female; Fertilization in Vitro; Humans; Infant, Newborn; Infertility; Male; Physician's Role; Pregnancy; Reproductive Techniques, Assisted; Treatment Outcome
PubMed: 24786738
DOI: 10.1016/j.fertnstert.2014.03.051 -
Circulation Jun 2012
Topics: Aortic Valve; Cardiac Catheterization; Clinical Trials as Topic; Heart Valve Prosthesis Implantation; Humans
PubMed: 22916357
DOI: 10.1161/circulationaha.112.121251