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EBioMedicine Dec 2019
Topics: Clinical Trials as Topic; Early Diagnosis; Humans; Precision Medicine; Rare Diseases; United Kingdom
PubMed: 31852592
DOI: 10.1016/j.ebiom.2019.12.001 -
Trials Aug 2023Arts therapies are widely but inconsistently provided in community mental health. Whilst they are appealing to patients, evidence for their effectiveness is mixed....
Effectiveness of group arts therapies (art therapy, dance movement therapy and music therapy) compared to group counselling for diagnostically heterogeneous psychiatric community patients: study protocol for a randomised controlled trial in mental health services (the ERA study).
BACKGROUND
Arts therapies are widely but inconsistently provided in community mental health. Whilst they are appealing to patients, evidence for their effectiveness is mixed. Trials to date have been limited to one art-form or diagnosis. Patients may hold strong preferences for or against an art-form whilst group therapies rely on heterogeneity to provide a range of learning experiences. This study will test whether manualised group arts therapies (art therapy, dance movement therapy and music therapy) are effective in reducing psychological distress for diagnostically heterogeneous patients in community mental health compared to active group counselling control.
METHODS
A pragmatic multi-centre 2-arm randomised controlled superiority trial with health economic evaluation and nested process evaluation. Adults aged ≥ 18, living in the community with a primary diagnosis of psychosis, mood, or anxiety disorder will be invited to participate and provide written informed consent. Participants are eligible if they score ≥ 1.65 on the Global Severity Index of the Brief Symptom Inventory. Those eligible will view videos of arts therapies and be asked for their preference. Participants are randomised to either their preferred type of group arts therapy or counselling. Groups will run twice per week in a community venue for 20 weeks. Our primary outcome is symptom distress at the end of intervention. Secondary outcomes include observer-rated symptoms, social situation and quality of life. Data will be collected at baseline, post-intervention and 6 and 12 months post-intervention. Outcome assessors and trial statisticians will be blinded. Analysis will be intention-to-treat. Economic evaluation will assess the cost-effectiveness of group arts therapies. A nested process evaluation will consist of treatment fidelity analysis, exploratory analysis of group process measures and qualitative interviews with participants and therapists.
DISCUSSION
This will be the first trial to account for patient preferences and diagnostic heterogeneity in group arts therapies. As with all group therapies, there are a number of logistical challenges to which we have had to further adapt due to the COVID-19 pandemic. Overall, the study will provide evidence as to whether there is an additive benefit or not to the use of the arts in group therapy in community mental health care.
TRIAL REGISTRATION
ISRCTN, ISRCTN88805048 . Registered on 12 September 2018.
Topics: Adult; Humans; Art Therapy; Counseling; COVID-19; Dance Therapy; Mental Health Services; Multicenter Studies as Topic; Music Therapy; Pandemics; Quality of Life; Randomized Controlled Trials as Topic; Adolescent; Pragmatic Clinical Trials as Topic; Equivalence Trials as Topic
PubMed: 37626418
DOI: 10.1186/s13063-023-07232-0 -
BMJ Open Oct 2022Whole-body MRI (WB-MRI) is recommended by the National Institute of Clinical Excellence as the first-line imaging tool for diagnosis of multiple myeloma. Reporting...
Development of machine learning support for reading whole body diffusion-weighted MRI (WB-MRI) in myeloma for the detection and quantification of the extent of disease before and after treatment (MALIMAR): protocol for a cross-sectional diagnostic test accuracy study.
INTRODUCTION
Whole-body MRI (WB-MRI) is recommended by the National Institute of Clinical Excellence as the first-line imaging tool for diagnosis of multiple myeloma. Reporting WB-MRI scans requires expertise to interpret and can be challenging for radiologists who need to meet rapid turn-around requirements. Automated computational tools based on machine learning (ML) could assist the radiologist in terms of sensitivity and reading speed and would facilitate improved accuracy, productivity and cost-effectiveness. The MALIMAR study aims to develop and validate a ML algorithm to increase the diagnostic accuracy and reading speed of radiological interpretation of WB-MRI compared with standard methods.
METHODS AND ANALYSIS
This phase II/III imaging trial will perform retrospective analysis of previously obtained clinical radiology MRI scans and scans from healthy volunteers obtained prospectively to implement training and validation of an ML algorithm. The study will comprise three project phases using approximately 633 scans to (1) train the ML algorithm to identify active disease, (2) clinically validate the ML algorithm and (3) determine change in disease status following treatment via a quantification of burden of disease in patients with myeloma. Phase 1 will primarily train the ML algorithm to detect active myeloma against an expert assessment ('reference standard'). Phase 2 will use the ML output in the setting of radiology reader study to assess the difference in sensitivity when using ML-assisted reading or human-alone reading. Phase 3 will assess the agreement between experienced readers (with and without ML) and the reference standard in scoring both overall burden of disease before and after treatment, and response.
ETHICS AND DISSEMINATION
MALIMAR has ethical approval from South Central-Oxford C Research Ethics Committee (REC Reference: 17/SC/0630). IRAS Project ID: 233501. CPMS Portfolio adoption (CPMS ID: 36766). Participants gave informed consent to participate in the study before taking part. MALIMAR is funded by National Institute for Healthcare Research Efficacy and Mechanism Evaluation funding (NIHR EME Project ID: 16/68/34). Findings will be made available through peer-reviewed publications and conference dissemination.
TRIAL REGISTRATION NUMBER
NCT03574454.
Topics: Chlorobenzenes; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Cross-Sectional Studies; Diagnostic Tests, Routine; Humans; Machine Learning; Magnetic Resonance Imaging; Multiple Myeloma; Retrospective Studies; Sulfides; Whole Body Imaging
PubMed: 36198471
DOI: 10.1136/bmjopen-2022-067140 -
BMC Infectious Diseases Jul 2022Sepsis is still a major public health concern and a medical emergency due to its high morbidity and mortality. Accurate and timely etiology diagnosis is crucial for...
Evaluation of droplet digital PCR rapid detection method and precise diagnosis and treatment for suspected sepsis (PROGRESS): a study protocol for a multi-center pragmatic randomized controlled trial.
BACKGROUND
Sepsis is still a major public health concern and a medical emergency due to its high morbidity and mortality. Accurate and timely etiology diagnosis is crucial for sepsis management. As an emerging rapid and sensitive pathogen detection tool, digital droplet PCR (ddPCR) has shown promising potential in rapid identification of pathogens and antimicrobial resistance genes. However, the diagnostic value and clinical impact of ddPCR tests remains to be studied in patients with suspected sepsis. PROGRESS trial is aimed to evaluate the clinical effectiveness of a novel ddPCR assay compared with standard practice.
METHODS
PROGRESS is a multicenter, open-label, pragmatic randomized controlled trial (pRCT) set in ten hospitals, including departments of infectious disease and intensive care units. In this study, a total of 2292 patients with suspected sepsis will be randomly assigned to two arms: the ddPCR group and the control group with a ratio of 3:1. The primary outcome is the diagnostic efficacy, that is, the sensitivity and specificity of the ddPCR assay compared with the synchronous blood culture. Secondary outcomes include the mortality rates and the mean Sequential Organ Failure Assessment (SOFA) score at follow-up time points, the length of stay in the hospital, the time to directed antimicrobial therapy, duration of broad-spectrum antibiotic use, and the EQ-5D-5L score on day 90.
DISCUSSION
It is the first multicenter pragmatic RCT to explore the diagnostic efficacy and clinical impact of the ddPCR assay in patients with suspected sepsis, taking advantage of both RCT's ability to establish causality and the feasibility of pragmatic approaches in real-world studies (RWS). This trial will help us to get a comprehensive view of the assay's capacity for precise diagnosis and treatment of sepsis. It has the potential to monitor the pathogen load change and to guide the antimicrobial therapy, making a beneficial impact on the prognosis of sepsis patients.
TRIAL REGISTRATION
ClinicalTrial.gov, NCT05190861. Registered January 13, 2022-'Retrospectively registered', https://clinicaltrials.gov/ct2/show/NCT05190861 .
Topics: Humans; Multicenter Studies as Topic; Organ Dysfunction Scores; Polymerase Chain Reaction; Pragmatic Clinical Trials as Topic; Prognosis; Randomized Controlled Trials as Topic; Sepsis; Treatment Outcome
PubMed: 35854212
DOI: 10.1186/s12879-022-07557-2 -
Gut Jan 2020The optimal trial design for assessing novel therapies in paediatric IBD (PIBD) is a subject of intense ongoing global discussions and debate among the different...
INTRODUCTION
The optimal trial design for assessing novel therapies in paediatric IBD (PIBD) is a subject of intense ongoing global discussions and debate among the different stakeholders. However, there is a consensus that the current situation in which most medications used in children with IBD are prescribed as off-label without sufficient paediatric data is unacceptable. Shortening the time lag between adult and paediatric approval of drugs is of the upmost importance. In this position paper we aimed to provide guidance from the global clinical research network (Pediatric Inflammatory Bowel Disease Network, PIBDnet) for designing clinical trials in PIBD in order to facilitate drug approval for children.
METHODS
A writing group has been established by PIBDnet and topics were assigned to different members. After an iterative process of revisions among the writing group and one face-to-face meeting, all statements have reached consensus of >80% as defined a priori. Next, all core members of PIBDnet voted on the statements, reaching consensus of >80% on all statements. Comments from the members were incorporated in the text.
RESULTS
The commentary includes 18 statements for guiding data extrapolation from adults, eligibility criteria to PIBD trials, use of placebo, dosing, endpoints and recommendations for feasible trials. Controversial issues have been highlighted in the text.
CONCLUSION
The viewpoints expressed in this paper could assist planning clinical trials in PIBD which are both of high quality and ethical, while remaining pragmatic.
Topics: Age Factors; Biological Products; Child; Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Approval; Gastrointestinal Agents; Humans; Inflammatory Bowel Diseases; Patient Selection; Research Design; Severity of Illness Index; Treatment Outcome
PubMed: 30979718
DOI: 10.1136/gutjnl-2018-317987 -
Journal of Clinical Oncology : Official... May 2022As prostate-specific membrane antigen (PSMA) positron emission tomography (PET) becomes increasingly available in the United States, the greater sensitivity of the...
Considerations on Integrating Prostate-Specific Membrane Antigen Positron Emission Tomography Imaging Into Clinical Prostate Cancer Trials by National Clinical Trials Network Cooperative Groups.
PURPOSE
As prostate-specific membrane antigen (PSMA) positron emission tomography (PET) becomes increasingly available in the United States, the greater sensitivity of the technology in comparison to conventional imaging poses challenges for clinical trials. The NCI Clinical Imaging Steering Committee (CISC) PSMA PET Working Group was convened to coordinate the identification of these challenges in various clinical scenarios and to develop consensus recommendations on how best to integrate PSMA PET into ongoing and upcoming National Clinical Trials Network (NCTN) trials.
METHODS
NCI CISC and NCI Genitourinary Steering Committee members and leadership nominated clinicians, biostatisticians, patient advocates, and other imaging experts for inclusion in the PSMA PET Working Group. From April to July 2021, the working group met independently and in conjunction with the CISC to frame challenges, including stage migration, response assessment, trial logistics, and statistical challenges, and to discuss proposed solutions. An anonymous, open-ended survey was distributed to members to collect feedback on challenges faced. Representatives from each NCTN group were invited to present an overview of affected trials. From these discussions, the consensus document was developed and circulated for the inclusion of multiple rounds of feedback from both the Working Group and CISC.
RESULTS
The current consensus document outlines the key challenges for clinical prostate cancer trials resulting from the increasing availability of PSMA PET. We discuss implications for patient selection and definition of end points and provide guidance and potential solutions for different clinical scenarios, particularly with regard to best practices in defining eligibility criteria and outcome measures.
RECOMMENDATIONS
This article provides guidance regarding clinical trial design and conduct, and the interpretation of trial results.
Topics: Clinical Trials as Topic; Humans; Male; Positron-Emission Tomography; Prostatic Neoplasms
PubMed: 35015566
DOI: 10.1200/JCO.21.02440 -
Trials Aug 2022Diabetic macular ischaemia (DMI) is a complication of diabetic retinopathy that leads to irreversible vision loss. DMI is characterised by reduced retinal vessel density...
HORNBILL: a phase I/IIa trial examining the safety, tolerability and early response of BI 764524 in patients with diabetic retinopathy and diabetic macular ischaemia-rationale, study design and protocol.
BACKGROUND
Diabetic macular ischaemia (DMI) is a complication of diabetic retinopathy that leads to irreversible vision loss. DMI is characterised by reduced retinal vessel density and enlargement of the foveal avascular zone (FAZ). Despite its clinical burden, there is no formal consensus on the definition of DMI, and no approved treatment. Semaphorin 3A (Sema3A) is an axonal guidance molecule that blocks revascularisation of the ischaemic retina. Sema3A modulation is therefore a promising mechanism of action for the treatment of ischaemic eye diseases. BI 764524 is an intravitreal anti-Sema3A ischaemia modulator agent.
METHODS
HORNBILL (NCT04424290) is a phase I/IIa trial comprising a non-randomised, open-label, single rising dose (SRD) part and a randomised, masked, sham-controlled multiple dose (MD) part to investigate the safety, tolerability and early biological response of ischaemia modulator BI 764524 in adults (≥18 years) with DMI. DMI will be defined using optical coherence tomography angiography (OCTA) as either any degree of disruption in the retinal vascularity (SRD) or a FAZ of ≥0.5 mm (MD). Subjects in the SRD part will receive 0.5, 1.0 or 2.5 mg of BI 764524; the maximum tolerated dose will then be used in the MD part. A minimum of 12 subjects will be enrolled into the SRD part; planned enrollment is 30 for the MD part. The primary endpoint of the SRD part is the number of subjects with dose-limiting adverse events (AEs) until day 8. The primary endpoint of the MD part is the number of subjects with drug-related AEs from baseline to end of study, and secondary endpoints include change from baseline in the size of the FAZ, best-corrected visual acuity and central retinal thickness.
DISCUSSION
DMI is a poorly defined condition with no treatment options. HORNBILL is the first clinical trial to assess a treatment for DMI and to use OCTA as a means to define and examine DMI. The OCTA data generated in this trial could form the basis of formal diagnostic criteria for DMI. Furthermore, the novel mechanism of action (Sema3A modulation) explored in this trial has the potential to revolutionise the treatment landscape for patients with DMI.
TRIAL REGISTRATION
ClinicalTrials.gov NCT04424290 ; EudraCT 2019-004432-28. Registered on 9 June 2020.
Topics: Adult; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Diabetes Mellitus; Diabetic Retinopathy; Fluorescein Angiography; Humans; Ischemia; Macula Lutea; Randomized Controlled Trials as Topic; Tomography, Optical Coherence; Visual Acuity
PubMed: 35978329
DOI: 10.1186/s13063-022-06527-y -
BMC Medical Research Methodology Mar 2024Clinical trials are of high importance for medical progress. This study conducted a systematic review to identify the applications of EHRs in supporting and enhancing...
BACKGROUND AND OBJECTIVE
Clinical trials are of high importance for medical progress. This study conducted a systematic review to identify the applications of EHRs in supporting and enhancing clinical trials.
MATERIALS AND METHODS
A systematic search of PubMed was conducted on 12/3/2023 to identify relevant studies on the use of EHRs in clinical trials. Studies were included if they (1) were full-text journal articles, (2) were written in English, (3) examined applications of EHR data to support clinical trial processes (e.g. recruitment, screening, data collection). A standardized form was used by two reviewers to extract data on: study design, EHR-enabled process(es), related outcomes, and limitations.
RESULTS
Following full-text review, 19 studies met the predefined eligibility criteria and were included. Overall, included studies consistently demonstrated that EHR data integration improves clinical trial feasibility and efficiency in recruitment, screening, data collection, and trial design.
CONCLUSIONS
According to the results of the present study, the use of Electronic Health Records in conducting clinical trials is very helpful. Therefore, it is better for researchers to use EHR in their studies for easy access to more accurate and comprehensive data. EHRs collects all individual data, including demographic, clinical, diagnostic, and therapeutic data. Moreover, all data is available seamlessly in EHR. In future studies, it is better to consider the cost-effectiveness of using EHR in clinical trials.
Topics: Humans; Data Collection; Electronic Health Records; PubMed; Research Design; Clinical Trials as Topic
PubMed: 38494497
DOI: 10.1186/s12874-024-02177-7 -
JCO Oncology Practice Jan 2020Patients with advanced cancer and oncologists deliberate about early-phase (EP) trials as they consider whether to pursue EP trial enrollment. We have limited...
PURPOSE
Patients with advanced cancer and oncologists deliberate about early-phase (EP) trials as they consider whether to pursue EP trial enrollment. We have limited information about those deliberations and how they may facilitate or impede trial initiation. This study describes these deliberations and their relationship to trial initiation.
PATIENTS AND METHODS
We collected longitudinal, ethnographic data on deliberations of patients with advanced cancer at two academic medical centers. We used constant comparative and framework analyses to characterize the deliberative process and its relationship to trial initiation.
RESULTS
Of 96 patients with advanced cancer, 26% initiated EP enrollment and 19% joined a trial. Constant comparative analysis revealed two foci of deliberation. Setting the stage focused on patient and physician support for EP trial involvement, including patients' interest in research and oncologists' awareness of trials and assessment of patient fit. Securing a seat focused on eligibility for and entrance to a specific trial and involved trial availability, treatment history, disease progression, and enrollment timing. Patients enrolled in a trial only when both stages could be successfully navigated.
CONCLUSION
Ethnographic data revealed two foci of deliberation about EP trial enrollment among patients with advanced cancer. Physician support played a consequential role in both stages, but enrollment also reflected factors beyond the control of any specific individual. Insights from this study, combined with other recent studies of trial enrollment, advance our understanding of the complex process of EP trial accrual and may help identify strategies to improve rates of participation.
Topics: Clinical Trials as Topic; Eligibility Determination; Female; Humans; Informed Consent; Male; Middle Aged; Neoplasms; Qualitative Research
PubMed: 31603726
DOI: 10.1200/JOP.19.00256 -
Circulation Jul 2019Heart failure with preserved ejection fraction (HFpEF) is common, yet there is currently no consensus on how to define HFpEF according to various society and clinical...
BACKGROUND
Heart failure with preserved ejection fraction (HFpEF) is common, yet there is currently no consensus on how to define HFpEF according to various society and clinical trial criteria. How clinical and hemodynamic profiles of patients vary across definitions is unclear. We sought to determine clinical characteristics, as well as physiologic and prognostic implications of applying various criteria to define HFpEF.
METHODS
We examined consecutive patients with chronic exertional dyspnea (New York Heart Association class II to IV) and ejection fraction ≥50% referred for comprehensive cardiopulmonary exercise testing with invasive hemodynamic monitoring. We applied societal and clinical trial HFpEF definitions and compared clinical profiles, exercise responses, and cardiovascular outcomes.
RESULTS
Of 461 patients (age 58±15 years, 62% women), 416 met American College of Cardiology/American Heart Association (ACC/AHA), 205 met European Society of Cardiology (ESC), and 55 met Heart Failure Society of America (HFSA) criteria for HFpEF. Clinical profiles and exercise capacity varied across definitions, with peak oxygen uptake of 16.2±5.2 (ACC/AHA), 14.1±4.2 (ESC), and 12.7±3.1 mL·kg·min (HFSA). A total of 243 patients had hemodynamic evidence of HFpEF (abnormal rest or exercise filling pressures), of whom 222 met ACC/AHA, 161 met ESC, and 41 met HFSA criteria. Over a mean follow-up of 3.8 years, the incidence of cardiovascular outcomes ranged from 75 (ACC/AHA) to 298 events per 1000 person-years (HFSA). Application of clinical trial definitions of HFpEF similarly resulted in distinct patient classification and prognostication.
CONCLUSIONS
Use of different HFpEF classifications variably enriches for future cardiovascular events, but at the expense of not including up to 85% of individuals with physiologic evidence of HFpEF. Comprehensive phenotyping of patients with suspected heart failure highlights the limitations and heterogeneity of current HFpEF definitions and may help to refine HFpEF subgrouping to test therapeutic interventions.
Topics: Adult; Aged; Clinical Trials as Topic; Cohort Studies; Dyspnea; Exercise Test; Exercise Tolerance; Female; Heart Failure; Humans; Male; Middle Aged; Stroke Volume; Treatment Outcome
PubMed: 31132875
DOI: 10.1161/CIRCULATIONAHA.118.039136