-
JAMA Jun 2023
Topics: Diagnostic Tests, Routine; Clinical Trials as Topic; Diagnostic Techniques and Procedures; Treatment Outcome
PubMed: 37338887
DOI: 10.1001/jama.2023.8972 -
Clinical Microbiology and Infection :... Jul 2019
Topics: Biostatistics; Clinical Trials as Topic; Diagnostic Tests, Routine; Humans; Sample Size
PubMed: 30986555
DOI: 10.1016/j.cmi.2019.04.011 -
The Lancet. Oncology May 2024The requirement of large-scale expensive cancer screening trials spanning decades creates considerable barriers to the development, commercialisation, and implementation... (Review)
Review
The requirement of large-scale expensive cancer screening trials spanning decades creates considerable barriers to the development, commercialisation, and implementation of novel screening tests. One way to address these problems is to use surrogate endpoints for the ultimate endpoint of interest, cancer mortality, at an earlier timepoint. This Review aims to highlight the issues underlying the choice and use of surrogate endpoints for cancer screening trials, to propose criteria for when and how we might use such endpoints, and to suggest possible candidates. We present the current landscape and challenges, and discuss lessons and shortcomings from the therapeutic trial setting. It is hugely challenging to validate a surrogate endpoint, even with carefully designed clinical studies. Nevertheless, we consider whether there are candidates that might satisfy the requirements defined by research and regulatory bodies.
Topics: Humans; Early Detection of Cancer; Neoplasms; Biomarkers, Tumor; Clinical Trials as Topic; Research Design; Biomarkers; Endpoint Determination
PubMed: 38697164
DOI: 10.1016/S1470-2045(24)00015-9 -
Seminars in Arthritis and Rheumatism Dec 2019In the last two decades drug trials in ankylosing spondylitis (AS) have been extremely successful and many effective new drugs have been approved for the treatment of... (Review)
Review
In the last two decades drug trials in ankylosing spondylitis (AS) have been extremely successful and many effective new drugs have been approved for the treatment of patients with AS. In 2009, new classification criteria for axial spondyloarthritis (axSpA) have been released that capture not only AS, but also patients with presumably earlier non-radiographic axSpA. These criteria have served as inclusion criteria for patients to be enrolled in drug trials for the indication of nr-axSpA. The theme to be discussed in this article pertains to changes in the design of clinical trials required to optimize the process of drug-testing and -approval in a changed environment. Additional treatment criteria (MRI-and CRP-positivity), better response measurement (ASDAS) and trial homogeneity will be addressed against the background of the expansion of the disease spectrum of axSpA which has been the consequence of the new classification criteria for axSpA.
Topics: Antirheumatic Agents; Clinical Trials as Topic; Diagnostic Imaging; Humans; Spondylarthritis
PubMed: 31779854
DOI: 10.1016/j.semarthrit.2019.09.016 -
Recenti Progressi in Medicina Nov 2019
Topics: Control Groups; Data Interpretation, Statistical; Databases, Factual; Equivalence Trials as Topic; Evidence-Based Medicine; Humans; Observational Studies as Topic; Pharmaceutical Preparations; Pragmatic Clinical Trials as Topic; Randomized Controlled Trials as Topic; Reproducibility of Results; Technology Assessment, Biomedical; Technology Transfer; Time Factors; Treatment Outcome
PubMed: 31808432
DOI: 10.1701/3265.32327 -
British Journal of Haematology Jan 2022Most patients with myelodysplastic syndromes (MDS) require therapeutic intervention. However, there are few approved treatments for MDS. To explore reasons, we searched... (Meta-Analysis)
Meta-Analysis Review
Most patients with myelodysplastic syndromes (MDS) require therapeutic intervention. However, there are few approved treatments for MDS. To explore reasons, we searched clinicaltrials.gov and clinicaltrialsregister.eu for MDS trials from 2000 to 2020. We assessed which agents were under investigation and analysed clinical trial characteristics and continuation rates from phase I to II to III to approval. As such, we identified 384 unique agents in 426 phase I, 430 phase II and 48 phase III trials. Success rates for phase III trials and agents were low, and MDS trials took markedly longer to complete than the average clinical trial. Although success rates were higher when MDS-specific phase I trials were conducted, 52% of the agents had not been evaluated in a phase I trial for MDS. MDS trials often failed to include quality of life, an especially important outcome for older MDS patients. Our work identifies factors potentially contributing to the paucity of available agents for MDS. We suggest a framework to improve clinical research in MDS that might ultimately augment the number of available agents.
Topics: Clinical Decision-Making; Clinical Trials as Topic; Combined Modality Therapy; Disease Management; Disease Progression; Humans; Myelodysplastic Syndromes; Prognosis; Treatment Outcome
PubMed: 34632583
DOI: 10.1111/bjh.17892 -
Contemporary Clinical Trials Oct 2022Efficiency in clinical trial recruitment and enrollment remains a major challenge in many areas of clinical medicine. In particular, despite the prevalence of heart... (Review)
Review
Efficiency in clinical trial recruitment and enrollment remains a major challenge in many areas of clinical medicine. In particular, despite the prevalence of heart failure with preserved ejection fraction (HFpEF), identifying patients with HFpEF for clinical trials has proven to be especially challenging. In this manuscript, we review strategies for contemporary clinical trial recruitment and present insights from the results of the DELIVER Electronic Health Record (EHR) Screening Initiative. The DELIVER trial was designed to evaluate the effects of dapagliflozin on clinical outcomes in patients with HFpEF. Within this trial, the multicenter DELIVER EHR Screening Initiative utilized EHR-based techniques in order to improve recruitment at selected sites in the United States. For this initiative, we developed and deployed a computable phenotype from the trial's eligibility criteria along with additional EHR tools at interested sites. Sites were then surveyed at the end of the program regarding lessons learned. Six sites were recruited, trained, and supported to utilize the EHR methodology and computable phenotype. Sites found the initiative to be helpful in identifying eligible patients and cited the individualized expert technical support as a critical factor in utilizing the program effectively. We found that the major challenge of implementation was the process of converting traditional inclusion/exclusion criteria into a computable phenotype within an established and ongoing trial. Other significant challenges noted by sites were the following: impact of the COVID-19 pandemic, engagement/support by local institutions, and limited availability of internal EHR experts/resources to execute programming. The study represents a proof-of-concept in the ability to utilize EHR-based tools in clinical trial recruitment for patients with HFpEF and provides important lessons for future initiatives. ClinicalTrials.gov Identifier: NCT03619213.
Topics: COVID-19; Clinical Trials as Topic; Electronic Health Records; Heart Failure; Humans; Multicenter Studies as Topic; Pandemics; Stroke Volume
PubMed: 36100197
DOI: 10.1016/j.cct.2022.106924 -
Advances in Wound Care Jun 2022Nonhealing wounds are an ever-growing global pandemic, with mortality rates and management costs exceeding many common cancers. Although our understanding of the... (Review)
Review
Nonhealing wounds are an ever-growing global pandemic, with mortality rates and management costs exceeding many common cancers. Although our understanding of the molecular and cellular factors driving wound healing continues to grow, standards for diagnosing and evaluating wounds remain largely subjective and experiential, whereas therapeutic strategies fail to consistently achieve closure and clinicians are challenged to deliver individualized care protocols. There is a need to apply precision medicine practices to wound care by developing evidence-based approaches, which are predictive, prescriptive, and personalized. Recent developments in "advanced" wound diagnostics, namely biomarkers (proteases, acute phase reactants, volatile emissions, and more) and imaging systems (ultrasound, autofluorescence, spectral imaging, and optical coherence tomography), have begun to revolutionize our understanding of the molecular wound landscape and usher in a modern age of therapeutic strategies. Herein, biomarkers and imaging systems with the greatest evidence to support their potential clinical utility are reviewed. Although many potential biomarkers have been identified and several imaging systems have been or are being developed, more high-quality randomized controlled trials are necessary to elucidate the currently questionable role that these tools are playing in altering healing dynamics or predicting wound closure within the clinical setting. The literature supports the need for the development of effective point-of-care wound assessment tools, such as a platform diagnostic array that is capable of measuring multiple biomarkers at once. These, along with advances in telemedicine, synthetic biology, and "smart" wearables, will pave the way for the transformation of wound care into a precision medicine. Clinical Trial Registration number: NCT03148977.
Topics: Diagnostic Imaging; Precision Medicine; Randomized Controlled Trials as Topic; Wound Healing
PubMed: 34128387
DOI: 10.1089/wound.2020.1319 -
Journal of Biopharmaceutical Statistics Jul 2020Dose selection is one of the most difficult and crucial decisions to make during drug development. As a consequence, the dose-finding trial is a major milestone in the... (Review)
Review
Dose selection is one of the most difficult and crucial decisions to make during drug development. As a consequence, the dose-finding trial is a major milestone in the drug development plan and should be properly designed. This article will review the most recent methodologies for optimizing the design of dose-finding studies: all of them are based on the modeling of the dose-response curve, which is now the gold standard approach for analyzing dose-finding studies instead of the traditional ANOVA/multiple testing approach. We will address the optimization of both fixed and adaptive designs and briefly outline new methodologies currently under investigation, based on utility functions.
Topics: Adaptive Clinical Trials as Topic; Data Interpretation, Statistical; Dose-Response Relationship, Drug; Double-Blind Method; Drug Dosage Calculations; Humans; Models, Statistical; Randomized Controlled Trials as Topic; Research Design; Treatment Outcome
PubMed: 32183578
DOI: 10.1080/10543406.2020.1730874 -
Nature Reviews. Neurology Feb 2021Standardization is necessary to ensure the reliability of clinical data and to enable longitudinal and cross-sectional comparisons of data obtained in different centres... (Review)
Review
Standardization is necessary to ensure the reliability of clinical data and to enable longitudinal and cross-sectional comparisons of data obtained in different centres and countries. In patients with multiple sclerosis (MS), standardized clinical data are needed for monitoring of disability and for collecting real-world evidence for use in research. This Perspective describes attempts to improve the standardization and digitization of clinical data in MS, including digital electronic health recording systems and applications that attempt to offer a comprehensive assessment of patients' neurological deficits and their effects on daily life. Despite the challenges raised by regulatory, ethical and data-privacy considerations, the standardization and digitization of clinical data in MS is expected to generate new insights into the pathophysiology of the disease and to contribute to personalized patient care.
Topics: Clinical Trials as Topic; Cross-Sectional Studies; Data Analysis; Humans; Longitudinal Studies; Multiple Sclerosis; Reproducibility of Results
PubMed: 33452493
DOI: 10.1038/s41582-020-00448-7