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International Psychogeriatrics May 2012The social and economic burden of Alzheimer's disease (AD) and its increasing prevalence has led to much work on new treatment strategies and clinical trials. The search... (Review)
Review
BACKGROUND
The social and economic burden of Alzheimer's disease (AD) and its increasing prevalence has led to much work on new treatment strategies and clinical trials. The search for surrogate markers of disease progression continues but traditional parallel group trial designs that use well-established, but often insensitive, clinical outcome measures predominate.
METHODS
We performed a systematic search across the Cochrane Library and PubMed abstracts published between January 2004 and August 2009. Information regarding the clinical trial methodology, outcome measures, intervention type and primary statistical analysis techniques was extracted and categorized, according to a standard protocol.
RESULTS
We identified 149 papers describing results from clinical trials in AD containing sufficient detail for our purposes. The largest proportion (38%) presented results of trials based on tests of cognition as the primary outcome measure. The primary analysis in most papers (85%) was a univariate significance test of a single primary outcome measure.
CONCLUSIONS
The majority of trials reported a comparison of baseline and end-point assessment over relatively short patient follow-up periods, using univariate statistical methods to compare differences between intervention and control groups in the primary analysis. There is considerable scope to introduce newer statistical methods and trial designs in treatment evaluations in AD.
Topics: Aged; Alzheimer Disease; Clinical Trials as Topic; Cognition; Data Interpretation, Statistical; Disease Progression; Humans; Statistics as Topic; Time Factors; Treatment Outcome
PubMed: 21910950
DOI: 10.1017/S1041610211001116 -
Clinical Pharmacology and Therapeutics Jul 2007Conclusions from clinical trial results that are derived from model-based analyses rely on the model adequately describing the underlying system. The traditionally used... (Review)
Review
Conclusions from clinical trial results that are derived from model-based analyses rely on the model adequately describing the underlying system. The traditionally used diagnostics intended to provide information about model adequacy have seldom discussed shortcomings. Without an understanding of the properties of these diagnostics, development and use of new diagnostics, and additional information pertaining to the diagnostics, there is risk that adequate models will be rejected and inadequate models accepted. Thus, a diagnosis of available diagnostics is desirable.
Topics: Clinical Trials as Topic; Computer Graphics; Computer Simulation; Data Interpretation, Statistical; Humans; Models, Biological; Models, Statistical; Nonlinear Dynamics; Regression Analysis; Reproducibility of Results; Research Design
PubMed: 17571070
DOI: 10.1038/sj.clpt.6100241 -
Investigative Radiology Apr 1986The underlying goal of all breast imaging procedures is the detection of cancer. X-ray mammography places greatest emphasis on the disclosure of early, nonpalpable,... (Clinical Trial)
Clinical Trial Review
The underlying goal of all breast imaging procedures is the detection of cancer. X-ray mammography places greatest emphasis on the disclosure of early, nonpalpable, curable cancer. Diagnostic ultrasonography stresses the differentiation of benign cysts from diagnostically indeterminate solid masses that require biopsy. Evolving experimental procedures such as transillumination light-scanning and magnetic resonance imaging currently are undergoing preliminary evaluation. An older procedure, thermography, seems to operate at a high level of effectiveness only for advanced cancer. Since x-ray mammography is the technique that has proven most successful in detecting early breast cancer, it is the standard to which all imaging alternatives must be compared.
Topics: Adult; Breast Neoplasms; Clinical Trials as Topic; Female; Humans; Magnetic Resonance Spectroscopy; Mammography; Mass Screening; Middle Aged; Thermography; Transillumination; Ultrasonography
PubMed: 3516919
DOI: No ID Found -
Digestive and Liver Disease : Official... May 2016Clinical guidelines are commonly based on inadequate evidence, suggesting deficiencies in the present portfolio of clinical research. (Review)
Review
BACKGROUND
Clinical guidelines are commonly based on inadequate evidence, suggesting deficiencies in the present portfolio of clinical research.
AIMS
To investigate characteristics of clinical trials examining gastrointestinal (GI) diseases registered in ClinicalTrials.gov.
METHODS
A cross-sectional analysis of 13,647 GI trials and 111,535 non-GI trials initiated between January 1997 and September 2013 was performed. Entries were sorted by operational status, purpose, interventions, trial design, and epochs to identify trends and interactions in trial properties.
RESULTS
The global production of GI trials has remained static in recent years and a majority of research efforts are focused on a few diseases. While GI trials are generally produced by highly populated US states and countries, they are also seldom larger than 500 patients. The likelihood of using data monitoring committees, randomization, and double blinding in GI trials has increased over time, though a substantial fraction of GI trials still do not employ rigorous trial designs. While levels of GI trials correlate with disease burden, the explained variance of GI trials by disease burden worldwide is poor.
CONCLUSION
GI trials are chiefly concentrated in few diseases and highly populated regions, exhibit heterogeneous trends and methodologies, and are sensitive to disease burdens, though more so within North America than worldwide.
Topics: Clinical Trials as Topic; Gastrointestinal Diseases; Humans; Registries; Research Design
PubMed: 26847963
DOI: 10.1016/j.dld.2016.01.003 -
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 -
Biomarkers in Medicine Dec 2012The current cost of developing a successful drug is typically over a billion dollars, with the registration trial(s) determining the success or failure of the entire... (Review)
Review
The current cost of developing a successful drug is typically over a billion dollars, with the registration trial(s) determining the success or failure of the entire development program. Often the primary endpoint of these trials is a subjective assessment. For registration trials with subjective endpoints, a regulatory agency may require a blinded independent central review (BICR) of the trial data. The BICR is a mechanism to reduce bias in open-labeled trials and to potentially increase accuracy and precision. A decision tree algorithm has been developed that can be used to determine when and what type of a BICR is needed. The US FDA draft Guidance Standard for Clinical Trial Imaging Endpoints can be used as an effective process map in exploring the value and use of BICRs in imaging, and in any hard to interpret variable subjective assessment in general.
Topics: Clinical Trials as Topic; Endpoint Determination; Humans; Molecular Imaging; Practice Guidelines as Topic; United States; United States Food and Drug Administration
PubMed: 23227850
DOI: 10.2217/bmm.12.74 -
Journal of the American College of... Jun 2014Management of patients with in-stent restenosis (ISR) remains an important clinical problem. Although drug-eluting stents (DES) have drastically reduced the incidence of... (Review)
Review
Management of patients with in-stent restenosis (ISR) remains an important clinical problem. Although drug-eluting stents (DES) have drastically reduced the incidence of ISR, treatment of DES-ISR is particularly challenging. ISR mainly results from aggressive neointimal proliferation, but recent data also suggest that neoatherosclerosis may play an important pathophysiological role. Intracoronary imaging provides unique insights to unravel the underlying substrate of ISR and may be used to guide repeated interventions. In this paper, we systematically reviewed clinical trial data with currently available therapeutic modalities, including DES and drug-coated balloons, in patients presenting with ISR within bare-metal stents or DES.
Topics: Animals; Clinical Trials as Topic; Coronary Restenosis; Drug-Eluting Stents; Humans; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 24632282
DOI: 10.1016/j.jacc.2014.02.545 -
Chinese Clinical Oncology Sep 2015High-throughput technologies enable the measurement of a large number of molecular characteristics from a small tissue specimen. High-dimensional molecular information... (Review)
Review
High-throughput technologies enable the measurement of a large number of molecular characteristics from a small tissue specimen. High-dimensional molecular information (referred to as omics data) offers the possibility of predicting the future outcome of a patient (prognosis) and predicting the likely response to a specific treatment (prediction). Embedded in the vast amount of data is the hope that there exists some signal that will enable practitioners to deliver therapy personalized to the molecular profile of a tumor, thereby improving health outcomes. The challenges are to determine that the omics assays are valid and reproducible in a clinical setting, to develop a valid and optimal omics-based test that algorithmically determines the optimal treatment regime, to evaluate that test in a powerful and unbiased manner, and finally to demonstrate clinical utility: that the test under study improves clinical outcome as compared to not using the test. We review the statistical considerations involved in each of these stages, specifically dealing with the challenges of high-dimensional, omics data.
Topics: Clinical Laboratory Techniques; Clinical Trials as Topic; Data Interpretation, Statistical; Genomics; High-Throughput Screening Assays; Humans; Models, Statistical; Neoplasms; Prognosis
PubMed: 26408296
DOI: 10.3978/j.issn.2304-3865.2015.01.02 -
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 -
Pain Physician 2009Diagnosis is a critical component of health care. The world of diagnostic tests is highly dynamic. New tests are developed at a fast pace and technology of existing... (Review)
Review
Diagnosis is a critical component of health care. The world of diagnostic tests is highly dynamic. New tests are developed at a fast pace and technology of existing tests is continuously being improved. However, clinicians, policy makers, and patients routinely face a range of questions regarding diagnostic tests. Well designed diagnostic test accuracy studies can help in making these decisions, provided that they transparently and fully report their participants, tests, methods, and results (as facilitated). For example, by the standards for the reporting of diagnostic accuracy studies (STARD) statement. Exaggerated and biased results from poorly designed and reported diagnostic test studies can trigger their premature dissemination and lead physicians into making incorrect treatment decisions. Thus, a diagnostic test is useful only to the extent that it distinguishes between conditions or disorders that might otherwise be confused. While almost any test can differentiate healthy persons from severely affected ones, appropriate diagnostic tests should differentiate mild and moderate forms of disease. Shortcomings in a study design and interpretation can affect estimates of diagnostic accuracy. Thus, quality diagnostic studies are essential in medicine in general and interventional pain management in particular. The STARD initiative was developed to improve the accuracy and completeness in the reporting of studies of diagnostic accuracy and provide guidance to assist in reducing the potential for bias in the study and to evaluate a study's generalizability. In the practice of interventional pain management, in addition to diagnostic tests which include laboratory tests, imaging tests, and physical examination, diagnostic interventional techniques are crucial. Interventional techniques as a diagnostic tool in painful conditions is important due to multiple challenging clinical situations, which include the purely subjective nature of pain and underdetermined and uncertain pathophysiology in most painful spinal conditions. Precision diagnostic blocks are used to clarify these challenging clinical situations in order to determine the pathophysiology of clinical pain, the site of nociception, and the pathway of afferent neural signals. Part 5 of evidence-based medicine (EBM) in interventional pain management describes the various aspects of diagnostic accuracy studies.
Topics: Clinical Protocols; Clinical Trials as Topic; Data Interpretation, Statistical; Diagnosis, Differential; Diagnostic Tests, Routine; Evidence-Based Medicine; Humans; Pain; Practice Guidelines as Topic; Predictive Value of Tests; Reproducibility of Results; Research Design
PubMed: 19461821
DOI: No ID Found