Placebo use in vaccine trials: recommendations of a WHO expert panel.
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SUBMITTER: Rid A
PROVIDER: S-EPMC4157320 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:About half of survivors with stroke experience severe and significant long-term disability. The purpose of this article is to review the state of the science and to make recommendations for measuring patient-centric outcomes in interventions for motor improvement in the chronic stroke phase.A 9-member expert panel reviewed evidence to identify measures of upper and lower extremity function used to date as outcomes in trials with patients who experienced a stroke ?6 months before assessment. Outcome measures were screened using StrokEDGE consensus panel recommendations, and evaluated for availability of a published minimal clinically important difference. Measures meeting these criteria were further evaluated with regard to their level of measurement, psychometric properties, and ability of minimal clinically important difference to capture gains associated with improved function and clinical relevance to patients, to arrive at recommendations. A systematic literature review yielded 115 clinical trials of upper and lower extremity function in chronic stroke that used a total of 34 outcome measures. Seven of these had published minimal clinically important differences and were recommended or highly recommended by StrokEDGE. Those are the Fugl-Meyer Upper Extremity and Lower Extremity scales, Wolf Motor Function Test, Action Research Arm Test, Ten-Meter and Six-Minute Walk Tests, and the Stroke Impact Scale. All had evidence for their psychometric performance, although the strength of evidence for validity varied, especially in populations with chronic stroke Fugl-Meyer Upper and Lower Extremity scales showing the strongest evidence for validity.The panel recommends that the Fugl-Meyer Upper and Lower Extremity scales be used as primary outcomes in intervention trials targeting motor function in populations with chronic stroke. The other 6 measures are recommended as secondary outcomes.
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Project description: Not available
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Project description:ObjectivesTo provide recommendations for the selection of comparators for randomized controlled trials of health-related behavioral interventions.Study design and settingThe National Institutes of Health Office of Behavioral and Social Science Research convened an expert panel to critically review the literature on control or comparison groups for behavioral trials and to develop strategies for improving comparator choices and for resolving controversies and disagreements about comparators.ResultsThe panel developed a Pragmatic Model for Comparator Selection in Health-Related Behavioral Trials. The model indicates that the optimal comparator is the one that best serves the primary purpose of the trial but that the optimal comparator's limitations and barriers to its use must also be taken into account.ConclusionWe developed best practice recommendations for the selection of comparators for health-related behavioral trials. Use of the Pragmatic Model for Comparator Selection in Health-Related Behavioral Trials can improve the comparator selection process and help resolve disagreements about comparator choices.
| S-EPMC6543841 | biostudies-literature
Project description:Vestibular migraine (VM) is an increasingly recognized pathology yet remains as an underdiagnosed cause of vestibular disorders. While current diagnostic criteria are codified in the 2012 Barany Society document and included in the third edition of the international classification of headache disorders, the pathophysiology of this disorder is still elusive. The Association for Migraine Disorders hosted a multidisciplinary, international expert workshop in October 2020 and identified seven current care gaps that the scientific community needs to resolve, including a better understanding of the range of symptoms and phenotypes of VM, the lack of a diagnostic marker, a better understanding of pathophysiologic mechanisms, as well as the lack of clear recommendations for interventions (nonpharmacologic and pharmacologic) and finally, the need for specific outcome measures that will guide clinicians as well as research into the efficacy of interventions. The expert group issued several recommendations to address those areas including establishing a global VM registry, creating an improved diagnostic algorithm using available vestibular tests as well as others that are in development, conducting appropriate trials of high quality to validate current clinically available treatment and fostering collaborative efforts to elucidate the pathophysiologic mechanisms underlying VM, specifically the role of the trigemino-vascular pathways.
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Project description:An overview of proceedings, findings, and recommendations from the workshop on "Advancing Symptom Science Through Symptom Cluster Research" sponsored by the National Institute of Nursing Research (NINR) and the Office of Rare Diseases Research, National Center for Advancing Translational Sciences, is presented. This workshop engaged an expert panel in an evidenced-based discussion regarding the state of the science of symptom clusters in chronic conditions including cancer and other rare diseases. An interdisciplinary working group from the extramural research community representing nursing, medicine, oncology, psychology, and bioinformatics was convened at the National Institutes of Health. Based on expertise, members were divided into teams to address key areas: defining characteristics of symptom clusters, priority symptom clusters and underlying mechanisms, measurement issues, targeted interventions, and new analytic strategies. For each area, the evidence was synthesized, limitations and gaps identified, and recommendations for future research delineated. The majority of findings in each area were from studies of oncology patients. However, increasing evidence suggests that symptom clusters occur in patients with other chronic conditions (eg, pulmonary, cardiac, and end-stage renal disease). Nonetheless, symptom cluster research is extremely limited and scientists are just beginning to understand how to investigate symptom clusters by developing frameworks and new methods and approaches. With a focus on personalized care, an understanding of individual susceptibility to symptoms and whether a "driving" symptom exists that triggers other symptoms in the cluster is needed. Also, research aimed at identifying the mechanisms that underlie symptom clusters is essential to developing targeted interventions.
| S-EPMC5939621 | biostudies-literature
Project description:Standardized variant curation is essential for clinical care recommendations for patients with inherited disorders. Clinical Genome Resource (ClinGen) variant curation expert panels are developing disease-associated gene specifications using the 2015 American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP) guidelines to reduce curation discrepancies. The ClinGen Myeloid Malignancy Variant Curation Expert Panel (MM-VCEP) was created collaboratively between the American Society of Hematology and ClinGen to perform gene- and disease-specific modifications for inherited myeloid malignancies. The MM-VCEP began optimizing ACMG/AMP rules for RUNX1 because many germline variants have been described in patients with familial platelet disorder with a predisposition to acute myeloid leukemia, characterized by thrombocytopenia, platelet functional/ultrastructural defects, and a predisposition to hematologic malignancies. The 28 ACMG/AMP codes were tailored for RUNX1 variants by modifying gene/disease specifications, incorporating strength adjustments of existing rules, or both. Key specifications included calculation of minor allele frequency thresholds, formulating a semi-quantitative approach to counting multiple independent variant occurrences, identifying functional domains and mutational hotspots, establishing functional assay thresholds, and characterizing phenotype-specific guidelines. Preliminary rules were tested by using a pilot set of 52 variants; among these, 50 were previously classified as benign/likely benign, pathogenic/likely pathogenic, variant of unknown significance (VUS), or conflicting interpretations (CONF) in ClinVar. The application of RUNX1-specific criteria resulted in a reduction in CONF and VUS variants by 33%, emphasizing the benefit of gene-specific criteria and sharing internal laboratory data.
| S-EPMC6849945 | biostudies-literature
Project description:OBJECTIVES:This paper describes recommendations from a panel of UK retina experts on aflibercept in diabetic macular oedema (DMO). METHODS:A roundtable meeting was held in London, UK in March 2018. The meeting was sponsored by Bayer. RESULTS:Recommendations are based on clinical experience and level 1 evidence. Clinical experience supports the evidence base, reinforcing that aflibercept should be initiated with intensive proactive dosing at 2?mg every 4 weeks. Most panel members use six initial 4-weekly doses as in Protocol T, rather than five initial monthly doses as recommended in the Summary of product characteristics (SmPC). After intensive proactive dosing, patients with a good response (meet Protocol T 'improvement' criteria ?5-letter improvement in visual acuity [VA] and/or ?10% improvement in central subfield thickness [CST] from baseline) but who are not yet stable should continue with 4-weekly aflibercept until stability is reached. Patients with a good response and stability should initiate monitor-and-extend (not in line with SmPC). Those with a sub-optimal response (meet 'improvement' criteria but with additional concerns e.g. fluid worsening on macular volume map) should continue with 4-weekly aflibercept but additional treatments should be considered (aflibercept is not licensed for combination treatment). For patients with no response (no change, or meeting Protocol T 'worsening' criteria [?5-letter decrease in VA and/or???10% increase in CST] from baseline), switching to a non-anti-vascular endothelial growth factor treatment should be considered. CONCLUSIONS:Clinical experience reinforces that, when using aflibercept in DMO, the licensed posology or Protocol T regimens achieve the best outcomes.
| S-EPMC7182551 | biostudies-literature
Project description:Insulin degludec/insulin aspart (IDegAsp) is a fixed-ratio co-formulation of insulin degludec (IDeg), which provides long-lasting basal insulin coverage, and insulin aspart (IAsp), which targets post-prandial glucose. This expert panel aimed to provide a practical and implementable guidance document to assist clinicians in prescribing IDegAsp in the diabetes management with respect to different patient populations including children and adults with type 1 diabetes (T1D) or type 2 diabetes (T2D) as well as pregnant, elderly and hospitalized patients and varying practice patterns (insulin-naive, insulin-treated, switching from basal, basal bolus and premix regimens). The experts recommended that IDegAsp can be used in insulin-naive T2D patients with poor glycemic control (HbA1c >8.5%) despite optimal oral antidiabetic drugs (OADs) as well as in insulin-treated T2D patients by switching from basal insulin, basal-bolus therapy or premixed insulins in relation to lower risk of nocturnal hypoglycemia, fewer injections and lower intraday glycemic variability, respectively. The experts considered the use of IDegAsp in children with T2D as a basal bolus alternative rather than as an alternative to basal insulin after metformin failure, use of IDegAsp in adult T1D patients as a simplified basal bolus regimen with lesser nocturnal hypoglycemia, fewer injections and better fasting plasma glucose control and in children with T1D as an alternative insulin regimen with fewer injection to increase treatment adherence. The proposed expert opinion provides practical information on use of IDegAsp in different patient populations and practice patterns to assist clinicians, which seems to compensate the need for easily implementable guidance on this novel insulin regimen.
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Project description:Septic arthritis is a serious condition with significant morbidity and mortality, routinely diagnosed using culture. The FDA has recently approved the rapid molecular BioFire® Joint Infection Panel (BJIP) for synovial fluid. We aimed to evaluate the BJIP compared to culture and its potential use in patient management. A multicentre retrospective evaluation of BJIP was conducted in the UK and Ireland. Positive percent agreement (PPA) and negative percent agreement (NPA) were calculated between the BJIP and routine culture. A multidisciplinary team (MDT) discussion addressing the optimal or potential case use of the assay practice was facilitated. Three hundred ninety-nine surplus synovial fluid samples (~ 70% from native joints) from eight centres were processed using BJIP in addition to routine culture. An increased yield of positive results was detected using BJIP compared to routine culture (98 vs 83), giving an overall PPA of 91.6% and overall NPA of 93% for the BJIP compared to culture results. The BJIP detected resistant markers and additional organisms that could influence antibiotic choices including Neisseria gonorrhoeae and Kingella kingae. The MDT agreed that the assay could be used, in addition to standard methods, in adult and children patients with specialist advice use based on local needs. Rapid results from BJIP were assessed as having potential clinical impact on patient management. Organisms not included in the panel may be clinically significant and may limit the value of this test for PJI.
| S-EPMC9836977 | biostudies-literature
Project description:PurposeAs a ClinGen Expert Panel (EP) we set out to adapt the American College of Medical Genetics and Genomics (ACMG)/Association for Molecular Pathology (AMP) pathogenicity criteria for classification of RYR1 variants as related to autosomal dominantly inherited malignant hyperthermia (MH).MethodsWe specified ACMG/AMP criteria for variant classification for RYR1 and MH. Proposed rules were piloted on 84 variants. We applied quantitative evidence calibration for several criteria using likelihood ratios based on the Bayesian framework.ResultsSeven ACMG/AMP criteria were adopted without changes, nine were adopted with RYR1-specific modifications, and ten were dropped. The in silico (PP3 and BP4) and hotspot criteria (PM1) were evaluated quantitatively. REVEL gave an odds ratio (OR) of 23:1 for PP3 and 14:1 for BP4 using trichotomized cutoffs of ≥0.85 (pathogenic) and ≤0.5 (benign). The PM1 hotspot criterion had an OR of 24:1. PP3 and PM1 were implemented at moderate strength. Applying the revised ACMG/AMP criteria to 44 recognized MH variants, 29 were classified as pathogenic, 13 as likely pathogenic, and 2 as variants of uncertain significance.ConclusionCuration of these variants will facilitate classification of RYR1/MH genomic testing results, which is especially important for secondary findings analyses. Our approach to quantitatively calibrating criteria is generalizable to other variant curation expert panels.
| S-EPMC8263483 | biostudies-literature