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Proteomics. Clinical Applications Mar 2019The application of protein (or peptide) biomarkers in clinical studies is a dynamic, ever-growing field. The introduction of clinical proteomics/peptidomics, such as... (Review)
Review
The application of protein (or peptide) biomarkers in clinical studies is a dynamic, ever-growing field. The introduction of clinical proteomics/peptidomics, such as mass spectrometry-based assays and multiplexed antibody-based protein arrays, has reshaped the landscape of biomarker identification and validation, allowing the discovery of novel biomarkers at an unprecedented rate and reliability. To reflect the current status with respect to implementation of protein/peptide biomarkers, an investigation of the most recent (last 6 years) clinical studies from clinicaltrials.gov is presented. Forty-two clinical trials involving the direct use of protein or peptide biomarkers in patient stratification and/or disease diagnosis and prognosis are highlighted. Most of the clinical trials that include proteomics/protein assays are aiming toward implementation of non-invasive diagnostic tools for early detection, while many of the clinical trials are targeting to correlate the protein abundance with the risk of a disease event. Less in number are the studies in which the protein biomarkers are applied to stratify the patients for intervention. All the above areas of application are considered of great importance for improving disease management, in an era where implementation toward precision medicine is the desired outcome of proteomics biomarker research.
Topics: Biomarkers; Clinical Trials as Topic; Diagnosis; Humans; Proteomics
PubMed: 30702805
DOI: 10.1002/prca.201800198 -
Trials Jan 2018Once the excitement of trial design, grant-writing and award are behind us, the great open expanse of the next few years is filled almost exclusively by trial...
Once the excitement of trial design, grant-writing and award are behind us, the great open expanse of the next few years is filled almost exclusively by trial management, the nitty-gritty of getting stuff done - delivering the goal. The most important members of the trial team now are not the professors and investigators but the trial managers. These trial managers have limited published information to help them make informed decisions about how to handle the day-to-day challenges that trials present. This special series aims to highlight the fact that writing on trial management is important, publishable and that Trials would welcome more of it.
Topics: Access to Information; Attitude of Health Personnel; Clinical Decision-Making; Clinical Trials as Topic; Evidence-Based Medicine; Health Knowledge, Attitudes, Practice; Humans; Information Dissemination; Periodicals as Topic; Research Design; Research Personnel; Writing
PubMed: 29310691
DOI: 10.1186/s13063-017-2322-8 -
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 -
Clinical and Translational Science Mar 2021The rapidly advancing field of digital health technologies provides a great opportunity to radically transform the way clinical trials are conducted and to shift the... (Review)
Review
The rapidly advancing field of digital health technologies provides a great opportunity to radically transform the way clinical trials are conducted and to shift the clinical trial paradigm from a site-centric to a patient-centric model. Merck's (Kenilworth, NJ) digitally enabled clinical trial initiative is focused on introduction of digital technologies into the clinical trial paradigm to reduce patient burden, improve drug adherence, provide a means of more closely engaging with the patient, and enable higher quality, faster, and more frequent data collection. This paper will describe the following four key areas of focus from Merck's digitally enabled clinical trials initiative, along with corresponding enabling technologies: (i) use of technologies that can monitor and improve drug adherence (smart dosing), (ii) collection of pharmacokinetic (PK), pharmacodynamic (PD), and biomarker samples in an outpatient setting (patient-centric sampling), (iii) use of digital devices to collect and measure physiological and behavioral data (digital biomarkers), and (iv) use of data platforms that integrate digital data streams, visualize data in real-time, and provide a means of greater patient engagement during the trial (digital platform). Furthermore, this paper will discuss the synergistic power in implementation of these approaches jointly within a trial to enable better understanding of adherence, safety, efficacy, PK, PD, and corresponding exposure-response relationships of investigational therapies as well as reduced patient burden for clinical trial participation. Obstacle and challenges to adoption and full realization of the vision of patient-centric, digitally enabled trials will also be discussed.
Topics: Ambulatory Care; Clinical Trials as Topic; Drug Development; Humans; Monitoring, Ambulatory; Patient Participation; Patient-Centered Care; Telemedicine; Wearable Electronic Devices
PubMed: 33048475
DOI: 10.1111/cts.12910 -
Seminars in Oncology Nursing Apr 2020To describe the increasing complexity and scope of clinical trials research, convergent research, and the clinical nurse roles and responsibilities to ensure safe... (Review)
Review
OBJECTIVES
To describe the increasing complexity and scope of clinical trials research, convergent research, and the clinical nurse roles and responsibilities to ensure safe patient care and study data integrity.
DATA SOURCES
Textbooks, journal publications, federal regulations, US Food and Drug Administration documents, clinical practice guidelines.
CONCLUSION
The immune system, genetics, and molecular pathology are not new in the context of oncology treatments. The reliability and clinical validation of in vitro diagnostic medical devices is, however, becoming increasingly more important in the development of marker driven targeted therapies, immunotherapy, and adoptive T-cell transfer. Protecting patients and preserving the integrity of clinical trials is of utmost importance.
IMPLICATIONS FOR NURSING PRACTICE
The role and scope of oncology and research nurses will intersect and shift as clinical care continues to involve high-acuity patients who participate in complex in vitro diagnostic and therapeutics clinical trials. The expertise of oncology nurses may vary in skills and knowledge domain; however, all scopes of practice are underpinned by the nursing code of ethics to ensure accountability for all aspects of patient care.
Topics: Biomedical Research; Clinical Trials as Topic; Ethics, Nursing; Genetic Testing; Humans; Neoplasms; Oncology Nursing; Research Personnel
PubMed: 32265167
DOI: 10.1016/j.soncn.2020.151002 -
The Journal of Molecular Diagnostics :... Nov 2016Molecular diagnostic tests with application to clinical diagnostics involve studies in infectious diseases, inherited diseases, oncology, predisposition to disease, or... (Review)
Review
Molecular diagnostic tests with application to clinical diagnostics involve studies in infectious diseases, inherited diseases, oncology, predisposition to disease, or the description of polymorphisms linked to disease states. General considerations in the design of evaluation of diagnostic test trials and statistical principles for reporting the results are discussed. A brief overview of the general statistical considerations related to the intent of use, test development versus validation, different types of biases, and issues with missing data are provided. Furthermore, issues related to commonly used but not necessarily correct methods to characterize the performance in the presence and absence of a clinical reference standard are discussed. These issues are broadly applicable to any molecular diagnostic test with a dichotomous result. This overview may help the clinical molecular diagnostic community to evaluate tests that provide a dichotomous result.
Topics: Clinical Trials as Topic; Humans; Molecular Diagnostic Techniques; Reproducibility of Results; Research Design; Sensitivity and Specificity
PubMed: 27639547
DOI: 10.1016/j.jmoldx.2016.06.008 -
Leukemia Research May 2018Treatment regimens for acute myeloid leukemia (AML) have remained largely unchanged until recently. Molecular advances have opened the door to targeted therapies, many... (Review)
Review
Treatment regimens for acute myeloid leukemia (AML) have remained largely unchanged until recently. Molecular advances have opened the door to targeted therapies, many of which are in late-phase clinical trials. As new therapeutic opportunities arise, it is appropriate to review key aspects of clinical trial design, statistical interpretation of outcomes, and methods of data reporting. Complete remission and overall survival (OS) are common primary endpoints in early-phase AML clinical trials. OS and event-free survival are frequent primary endpoints in phase 3 trials. Clinical trials are designed to address the primary endpoint using prespecified α and power levels. Interpretation of additional endpoints (eg, secondary endpoints and subgroup analyses) must be viewed in light of a trial's statistical design. Furthermore, variations in reporting of endpoints must be considered in order to understand trial outcomes. Time-to-event endpoints are typically reported using Kaplan-Meier curves, which are visually informative. Statistical data derived from these curves can be complex, and a variety of factors may impact interpretation. The purpose of this review is to discuss the nuances of common AML trial endpoints and their data presentation to better inform evaluation and understanding of clinical trial data.
Topics: Clinical Trials as Topic; Data Interpretation, Statistical; Endpoint Determination; Humans; Kaplan-Meier Estimate; Leukemia, Myeloid, Acute; Remission Induction; Treatment Outcome
PubMed: 29524739
DOI: 10.1016/j.leukres.2018.02.002 -
Contemporary Clinical Trials Mar 2021This paper describes the need to prepare for the development of antiviral therapeutics for the next pandemic. Preparation would consist of a stockpiling of best...
This paper describes the need to prepare for the development of antiviral therapeutics for the next pandemic. Preparation would consist of a stockpiling of best practices for clinical trial design, analysis and operations during the current SARS-CoV-2 pandemic as well as continuous development of treatments and methodology between pandemics. This development would be facilitated by a global clinical trial pandemic reserve similar to the military reserves consisting of medical and quantitative methods professionals who would remain engaged between pandemics. Continuous identification of potential antiviral drugs and diagnostic methods would also be needed. Specific methodology addressed includes the importance of large simple trials, follow up time, efficacy endpoint, appropriate estimands, non-inferiority trials, more sophisticated patient accrual models and procedures for data sharing between clinical trials.
Topics: Antiviral Agents; COVID-19; Clinical Trials as Topic; Diagnostic Techniques, Cardiovascular; Drug Development; Humans; Pandemics; Research Design; SARS-CoV-2; Time Factors; COVID-19 Drug Treatment
PubMed: 33515783
DOI: 10.1016/j.cct.2021.106292 -
Journal of Nuclear Medicine : Official... Jun 2021This article explores basic statistical concepts of clinical trial design and diagnostic testing, or how one starts with a question, formulates it into a hypothesis on... (Review)
Review
This article explores basic statistical concepts of clinical trial design and diagnostic testing, or how one starts with a question, formulates it into a hypothesis on which a clinical trial is then built, and integrates it with statistics and probability, such as determining the probability of rejecting the null hypothesis when it is actually true (type I error) and the probability of failing to reject the null hypothesis when it is false (type II error). There are a variety of tests for different types of data, and the appropriate test must be chosen for which the sample data meet the assumptions. Correcting type I error in the presence of multiple testing is needed to control the error's inflation. Within diagnostic testing, identifying false-positive and false-negative results is critical to understanding the performance of a test. These are used to determine the sensitivity and specificity of a test along with the test's negative predictive value and positive predictive value. These quantities, specifically sensitivity and specificity, are used to determine the accuracy of a diagnostic test using receiver-operating-characteristic curves. These concepts are briefly introduced to provide a basic understanding of clinical trial design and analysis, with references to allow the reader to explore various concepts at a more detailed level if desired.
Topics: Clinical Trials as Topic; Diagnostic Techniques and Procedures; Humans; Predictive Value of Tests; ROC Curve; Sensitivity and Specificity; Statistics as Topic
PubMed: 33608427
DOI: 10.2967/jnumed.120.245654 -
British Journal of Cancer Oct 2019International collaboration in oncology trials has the potential to enhance clinical trial activity by expediting the recruitment of large patient populations, testing... (Review)
Review
International collaboration in oncology trials has the potential to enhance clinical trial activity by expediting the recruitment of large patient populations, testing treatments in diverse populations and facilitating the study of rare tumours or specific molecular subtypes. However, a number of challenges continue to hinder the efficient and productive conduct of both commercial and non-commercial international clinical trials. These challenges include complex and burdensome regulatory requirements, the high cost of conducting trials, and logistical challenges associated with ethics review, drug supply and biospecimen collection and management. We propose solutions to promote oncology trial collaboration, such as regulatory reform, harmonisation of trial initiation and management processes and greater recognition and funding of academic (non-commercial) clinical trials. It is only through coordinated effort and leadership from researchers, regulators and those responsible for health systems that the full potential of international trial collaboration can be realised.
Topics: Antineoplastic Agents; Clinical Trials as Topic; Government Regulation; Humans; Information Dissemination; International Cooperation; Medical Oncology; Multicenter Studies as Topic; Neoplasms; Research Support as Topic; Specimen Handling
PubMed: 31378784
DOI: 10.1038/s41416-019-0532-4