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Clinical Trials (London, England) Oct 2021The COVID-19 pandemic has resulted in unprecedented challenges for healthcare systems worldwide. It has also stimulated research in a wide range of areas including rapid...
The COVID-19 pandemic has resulted in unprecedented challenges for healthcare systems worldwide. It has also stimulated research in a wide range of areas including rapid diagnostics, novel therapeutics, use of technology to track patients and vaccine development. Here, we describe our experience of rapidly setting up and delivering a novel COVID-19 vaccine trial, using clinical and research staff and facilities in three National Health Service Trusts in Cambridgeshire, United Kingdom. We encountered and overcame a number of challenges including differences in organisational structures, research facilities available, staff experience and skills, information technology and communications infrastructure, and research training and assessment procedures. We overcame these by setting up a project team that included key members from all three organisations that met at least daily by teleconference. This group together worked to identify the best practices and procedures and to harmonise and cascade these to the wider trial team. This enabled us to set up the trial within 25 days and to recruit and vaccinate the participants within a further 23 days. The lessons learned from our experiences could be used to inform the conduct of clinical trials during a future infectious disease pandemic or public health emergency.
Topics: COVID-19; COVID-19 Vaccines; Clinical Trials as Topic; Humans; Pandemics; State Medicine; United Kingdom
PubMed: 34154428
DOI: 10.1177/17407745211024764 -
Translational Neurodegeneration May 2024The use of biomarker-led clinical trial designs has been transformative for investigating amyloid-targeting therapies for Alzheimer's disease (AD). The designs have... (Review)
Review
The use of biomarker-led clinical trial designs has been transformative for investigating amyloid-targeting therapies for Alzheimer's disease (AD). The designs have ensured the correct selection of patients on these trials, supported target engagement and have been used to support claims of disease modification and clinical efficacy. Ultimately, this has recently led to approval of disease-modifying, amyloid-targeting therapies for AD; something that should be noted for clinical trials investigating tau-targeting therapies for AD. There is a clear overlap of the purpose of biomarker use at each stage of clinical development between amyloid-targeting and tau-targeting clinical trials. However, there are differences within the potential context of use and interpretation for some biomarkers in particular measurements of amyloid and utility of soluble, phosphorylated tau biomarkers. Given the complexities of tau in health and disease, it is paramount that therapies target disease-relevant tau and, in parallel, appropriate assays of target engagement are developed. Tau positron emission tomography, fluid biomarkers reflecting tau pathology and downstream measures of neurodegeneration will be important both for participant recruitment and for monitoring disease-modification in tau-targeting clinical trials. Bespoke design of biomarker strategies and interpretations for different modalities and tau-based targets should also be considered.
Topics: Alzheimer Disease; Humans; tau Proteins; Biomarkers; Clinical Trials as Topic
PubMed: 38773569
DOI: 10.1186/s40035-024-00417-w -
Endocrinology, Diabetes & Metabolism Apr 2021Developing a novel therapeutic product for the treatment of type 2 diabetes (T2D) is a long, resource-intensive process. Novel biomarkers could potentially aid clinical...
Developing a novel therapeutic product for the treatment of type 2 diabetes (T2D) is a long, resource-intensive process. Novel biomarkers could potentially aid clinical trial design by shortening clinical trials or enabling better prediction of at-risk populations and/or disease progression. Novel clinical trial designs could lead to reduced costs of development and less burden to patients, due to shorter trial duration, and/or less burdensome assessments.
Topics: Biomarkers; Clinical Trials as Topic; Cohort Studies; Cost Savings; Cost of Illness; Diabetes Mellitus, Type 2; Disease Progression; Humans; Monitoring, Physiologic; Patient Reported Outcome Measures; Prediabetic State; Research Design; Time Factors
PubMed: 33855210
DOI: 10.1002/edm2.207 -
BMJ Open Jul 2022Malaria is one of the major public health problems in sub-Saharan Africa. It contributes significantly to maternal and fetal morbidity and mortality in affected...
INTRODUCTION
Malaria is one of the major public health problems in sub-Saharan Africa. It contributes significantly to maternal and fetal morbidity and mortality in affected countries. This study aims to evaluate the impact of enhanced case detection using molecular testing called loop-mediated isothermal amplification (LAMP) on birth outcomes in a prospective study design.
METHODS AND ANALYSIS
A pragmatic randomised diagnostic outcomes trial will be conducted in several health institutes in different Ethiopian regions. Women (n=2583) in their first and second trimesters of pregnancy will be included in the study and individually randomised to the standard of care or enhanced case detection arms, and followed until delivery. Enrolment will encompass the malaria peak transmission seasons. In the standard of care arm, a venous blood sample will be collected for malaria diagnosis only in symptomatic patients. In contrast, in the intervention arm, mothers will be tested by a commercially available Conformité Européene (CE)-approved LAMP malaria test, microscopy and rapid diagnostic test for malaria regardless of their symptoms at each antenatal care visit. The primary outcome of the study is to measure birth weight.
ETHICS AND DISSEMINATION
The study was approved by the following ethical research boards: Armauer Hansen Research Institute/ALERT Ethics Review Committee (FORM AF-10-015.1, Protocol number PO/05/20), the Ethiopia Ministry of Science and Higher Education National Research Ethics Review Committee (approval SRA/11.7/7115/20), the Ethiopia Food and Drug Administration (approval 02/25/33/I), UCalgary Conjoint Health Research Ethics Board (REB21-0234). The study results will be shared with the institutions and stakeholders such as the Ethiopia Ministry of Health, the Foundation for Innovative Diagnostics, WHO's Multilateral initiative on Malaria - Tropical Diseases Research (TDR-MIM), Roll Back Malaria and the Malaria in Pregnancy Consortium. The study results will also be published in peer-reviewed journals and presented at international conferences.
TRIAL REGISTRATION NUMBER
NCT03754322.
Topics: Female; Humans; Malaria; Mass Screening; Molecular Diagnostic Techniques; Nucleic Acid Amplification Techniques; Pragmatic Clinical Trials as Topic; Pregnancy; Pregnancy Complications, Parasitic; Prospective Studies; Randomized Controlled Trials as Topic; Technology
PubMed: 35851027
DOI: 10.1136/bmjopen-2021-058397 -
Cardiovascular Drugs and Therapy Feb 2021Theranostics, the practice of systematically integrating diagnostics with treatment, has evolved as a field of medicine. In the context of ultrasound based theranostics,... (Review)
Review
Theranostics, the practice of systematically integrating diagnostics with treatment, has evolved as a field of medicine. In the context of ultrasound based theranostics, both traditional microbubbles and inorganic nanoparticles have emerged as technologies of clinical interest. Ultrasound induced microbubble cavitation has demonstrated efficacy in a variety of applications, including thrombolysis, tumor ablation, targeted microvascular flow enhancement, and targeted drug and gene delivery. This commentary summarizes the mechanisms and applications of ultrasound-based theranostics in cardiovascular medicine, including its impact in pediatric cardiology. It also provides an overview of ongoing clinical trials for theranostics in cardiovascular medicine.
Topics: Adult; Cardiovascular Diseases; Child; Clinical Trials as Topic; Gene Transfer Techniques; Humans; Microbubbles; Nanoparticles; Precision Medicine; Ultrasonography
PubMed: 32495071
DOI: 10.1007/s10557-020-07016-7 -
Expert Opinion on Biological Therapy Nov 2020Biologic agents have revolutionized the therapeutic management of ulcerative colitis. Anti-tumor necrosis factor agents were the first biologic drugs used to induce and... (Review)
Review
INTRODUCTION
Biologic agents have revolutionized the therapeutic management of ulcerative colitis. Anti-tumor necrosis factor agents were the first biologic drugs used to induce and maintain remission in this inflammatory bowel disease. Recently, another biologic option, ustekinumab, has become available for the treatment of moderate-to-severe ulcerative colitis.
AREAS COVERED
In this article, the authors review the literature on the efficacy and safety of ustekinumab in the context of current biologic agents used for the management of this disease. The potential role of ustekinumab in the treatment paradigm of the disease is also discussed. : The UNIFI trial has demonstrated the efficacy and safety of ustekinumab in induction and maintenance phases of treatment for ulcerative colitis. Ustekinumab may provide clinical benefit in a range of settings in patients with ulcerative colitis, even for those with multiple treatment failures, which are relatively common in daily clinical practice. Future clinical trials should compare the efficacy of ustekinumab with existing biologic agents in the management of ulcerative colitis.
Topics: Clinical Trials as Topic; Colitis, Ulcerative; Expert Testimony; Humans; Salvage Therapy; Treatment Outcome; Tumor Necrosis Factor-alpha; Ustekinumab
PubMed: 32662683
DOI: 10.1080/14712598.2020.1792882 -
Journal of the National Cancer Institute Mar 2020Historically, the gold standard for evaluation of cancer therapeutics, including medical devices, has been the randomized clinical trial. Although high-quality clinical... (Review)
Review
Historically, the gold standard for evaluation of cancer therapeutics, including medical devices, has been the randomized clinical trial. Although high-quality clinical data are essential for safe and judicious use of therapeutic oncology devices, class II devices require only preclinical data for US Food and Drug Administration approval and are often not rigorously evaluated prior to widespread uptake. Herein, we review master protocol design in medical oncology and its application to therapeutic oncology devices, using examples from radiation oncology. Unique challenges of clinical testing of radiation oncology devices (RODs) include patient and treatment heterogeneity, lack of funding for trials by industry and health-care payers, and operator dependence. To address these challenges, we propose the use of master protocols to optimize regulatory, financial, administrative, quality assurance, and statistical efficiency of trials evaluating RODs. These device-specific master protocols can be extrapolated to other devices and encompass multiple substudies with the same design, statistical considerations, logistics, and infrastructure. As a practical example, we outline our phase I and II master protocol trial of stereotactic magnetic resonance imaging-guided adaptive radiotherapy, which to the best of our knowledge is the first master protocol trial to test a ROD. Development of more efficient clinical trials is needed to promote thorough evaluation of therapeutic oncology devices, including RODs, in a resource-limited environment, allowing more practical and rapid identification of the most valuable advances in our field.
Topics: Clinical Trials as Topic; Equipment and Supplies; Humans; Magnetic Resonance Imaging; Neoplasms; Radiation Oncology; Radiotherapy, Image-Guided; Randomized Controlled Trials as Topic; Stereotaxic Techniques; United States; United States Food and Drug Administration
PubMed: 31504680
DOI: 10.1093/jnci/djz167 -
The British Journal of Surgery Sep 2021Primary and incisional ventral hernia trials collect unstandardized inconsistent data, limiting data interpretation and comparison. This study aimed to create two...
BACKGROUND
Primary and incisional ventral hernia trials collect unstandardized inconsistent data, limiting data interpretation and comparison. This study aimed to create two minimum data sets for primary and incisional ventral hernia interventional trials to standardize data collection and improve trial comparison. To support these data sets, standardized patient-reported outcome measures and trial methodology criteria were created.
METHODS
To construct these data sets, nominal group technique methodology was employed, involving 15 internationally recognized abdominal wall surgeons and two patient representatives. Initially a maximum data set was created from previous systematic and panellist reviews. Thereafter, three stages of voting took place: stage 1, selection of the number of variables for data set inclusion; stage 2, selection of variables to be included; and stage 3, selection of variable definitions and detection methods. A steering committee interpreted and analysed the data.
RESULTS
The maximum data set contained 245 variables. The three stages of voting commenced in October 2019 and had been completed by July 2020. The final primary ventral hernia data set included 32 variables, the incisional ventral hernia data set included 40 variables, the patient-reported outcome measures tool contained 25 questions, and 40 methodological criteria were chosen. The best known variable definitions were selected for accurate variable description. CT was selected as the optimal preoperative descriptor of hernia morphology. Standardized follow-up at 30 days, 1 year, and 5 years was selected.
CONCLUSION
These minimum data sets, patient-reported outcome measures, and methodological criteria have allowed creation of a manual for investigators aiming to undertake primary ventral hernia or incisional ventral hernia interventional trials. Adopting these data sets will improve trial methods and comparisons.
Topics: Abdominal Wall; Clinical Trials as Topic; Female; Hernia, Ventral; Herniorrhaphy; Humans; Incisional Hernia; Laparoscopy; Male; Practice Guidelines as Topic; Recurrence; Surgical Mesh; Treatment Outcome
PubMed: 34286842
DOI: 10.1093/bjs/znab157 -
The British Journal of Ophthalmology Sep 2020Ongoing and recent clinical trials for geographic atrophy (GA) have used different outcomes. The goal of this study was to identify a core outcome set (COS) important...
BACKGROUND/AIMS
Ongoing and recent clinical trials for geographic atrophy (GA) have used different outcomes. The goal of this study was to identify a core outcome set (COS) important for patients, clinicians and researchers, and to propose the use of COS in the design of future GA trials.
METHODS
Five-component project including: Delphi method with patients and experts, focus groups and interviews with patients, relatives and workers supporting patients. Three hundred and one patients (301) with age-related macular degeneration participated in round 1 of a Delphi exercise. Most subjects had GA; 183 patients (61%) were females and the median (range) age was 77 (50-99) years. In round 2, of the 301 of the first round, 100 participants were randomly selected of whom 76 agreed to take part. In a parallel Delphi exercise, panellists comprised a mix of non-clinical scientists and clinicians (43 in the initial and 21 in the final round). In addition, interviews and focus groups consisting of patients (n=20), family members (n=4) and support workers (n=5) were undertaken.
RESULTS
Core outcomes identified as important for age-related macular degeneration trials were the health of the outer retina, multimodal estimation of lesion size, reading speed, best corrected distance and near acuity, low luminance visual acuity, patient reported visual performance and safety.
CONCLUSION
This study identified a set of core outcomes that should be used in GA trials. The COS include patient-reported outcome measures, near visual acuity, reading speed and assessment of the outer retina.
Topics: Aged; Aged, 80 and over; Clinical Trials as Topic; Consensus; Delphi Technique; Endpoint Determination; Female; Geographic Atrophy; Humans; Male; Middle Aged; Patient Outcome Assessment; Reading; Retina; Surveys and Questionnaires; Treatment Outcome; Visual Acuity
PubMed: 31848211
DOI: 10.1136/bjophthalmol-2019-314949 -
Archives of Disease in Childhood Apr 2021There is a well-known knowledge gap regarding the efficacy and safety of medicines in children of all ages and children are often treated with medicines off-label.... (Review)
Review
There is a well-known knowledge gap regarding the efficacy and safety of medicines in children of all ages and children are often treated with medicines off-label. Children are thus deprived of treatment based on the same quality of information that guides treatment in adults. The knowledge gap regarding efficacy and safety of medicines in children has been acknowledged by authorities and is reflected in legislation both in North America and in the European Union. Recent reports on the effects of legislation indicates that paediatric clinical trials remain a challenge.Paediatric clinical trials are needed in the entire developmental age spectrum and are especially needed in certain therapy areas. Paediatric clinical trials have special features compared with trials in adults, and these need to be taken into account. These special features include scientific issues related to small samples and heterogeneity, the consent/assent procedure, the need for age-appropriate study information, specific outcomes and safety issues related to development and maturation. Competence in paediatric clinical trials is required in both designing, planning, co-ordinating and organising paediatric clinical trials, as well as research infrastructure and networks to increase power and disseminate information and expert advice. Strengthening of paediatric clinical research is essential to facilitate generating the data that will let children enjoy new medical advances in a similar manner as adults.
Topics: Adolescent; Adult; Child; Clinical Trials as Topic; European Union; Evidence-Based Medicine; Female; Humans; Legislation, Drug; North America; Pharmacology; Safety; Treatment Outcome; Young Adult
PubMed: 33077422
DOI: 10.1136/archdischild-2019-318676