Adhering to Ethical Benchmarks in Neurology Clinical Trials Using iPSCs.
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ABSTRACT:
SUBMITTER: Akabayashi A
PROVIDER: S-EPMC7283412 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The proliferation of clinical trials in the last decade and the relatively limited number of experienced clinical trial sites in comparison has created in some sites an environment of clinical trial abundance. As clinical trial protocols typically restrict patients from concurrent clinical trial participation, and patients may be eligible for more than one trial at any given time, selecting the best trial for an individual patient requires evaluation of not only the merits of the individual trials but also patient preferences. This article highlights some potential ethical issues which should be considered when clinical trials are raised as a treatment option and when patients are eligible for more than one trial at the time of evaluation.
| S-EPMC6461579 | biostudies-literature
Project description:We examined the use of clinical trials registries in published systematic reviews and meta-analyses from clinical neurology. A review of publications between January 1, 2008 and December 31, 2014 from five neuroscience journals (Annals of Neurology, Brain, Lancet Neurology, Neurology, and The Neuroscientist) was performed to identify eligible systematic reviews. The systematic reviews comprising the final sample were independently appraised to determine if clinical trials registries had been included as part of the search process. Studies acknowledging the use of a trials registry were further examined to determine whether trial data had been incorporated into the analysis. The initial search yielded 194 studies, of which 78 systematic reviews met the selection criteria. Of those, five acknowledged the use of a specific clinical trials registry: four reviewed unpublished trial data and two incorporated unpublished trial data into their results. Based on our sample of systematic reviews, there was no increase in the use of trials registries in systematic review searches over time. Few systematic reviews published in clinical neurology journals included data from relevant clinical trials registries.
| S-EPMC4520588 | biostudies-literature
Project description:The selection of an appropriate outcome measure is crucial to the success of a clinical trial, in order to obtain accurate results, which, in turn, influence patient care and future research. Outcomes that can be directly measured are mortality/survival. More frequently, neurology clinical trials evaluate outcomes that cannot be directly measured, such as disability, cognitive function, or change in symptoms of the condition under study. These complex outcomes are abstract ideas or latent constructs and are measured using rating scales. Functional rating scales typically assess the ability of patients to perform tasks and roles for everyday life. Rating scales should be valid (measure what they are supposed to measure), reliable (provide similar results if administered under the same conditions), and responsive (able to detect clinically important changes over time). The clinical relevance of rating scales depends on their ability to detect a minimal clinically important difference, and should be distinguished from statistical significance. Most rating scales are ordinal scales and have limitations. Modern psychometric methods of Rasch analysis and item response theory, termed latent trait theory, are increasingly being utilized to convert ordinal data to interval measurements, both to validate existing scales and to develop new scales. Patient-reported outcomes are being increasingly used in clinical trials and have a role in clinical quality assessment. The PROMIS and NeuroQoL databases are excellent resources for rigorously developed and validated patient-reported outcomes.
| S-EPMC5233630 | biostudies-literature
Project description:ImportancePragmatic clinical trials that seek informed consent after randomization (ie, postrandomization consent) are increasingly used, but debate on ethics persists because control arm patients are not specifically informed about the trials and randomization occurs before consent for the trials. The public's attitude toward postrandomization consent trials is unknown, but the way the trials are described could bias people's views.ObjectivesTo assess the attitudes of the US general public toward postrandomization informed consent for pragmatic trials and to measure potential framing and other factors associated with those attitudes.Design, setting, and participantsAn online, 2 × 2 experimental survey (fielded between February 23 and April 3, 2018) portraying 4 scenarios of postrandomization informed consent (with prior broad consent for medical record use) was conducted. These scenarios included traditional randomized clinical trial language framing vs alternative framing in a high-stakes trial (ie, survival in leukemia) or low-stakes trial (ie, blood glucose level in diabetes). A total of 3793 individuals invited to participate were part of an existing panel representative of the US general public (GfK KnowledgePanel).Main outcomes and measuresThe proportion of participants who would recommend that an ethics review board approve a postrandomization consent pragmatic trial.ResultsA total of 2042 of 3739 invitees (54.6%) responded; after exclusion of 38 incomplete surveys, 2004 participants were included in the analysis. Of these, 997 (49.8%) were women, 1440 (71.9%) were white non-Hispanic, 199 (9.9%) were black non-Hispanic, and 233 (11.6%) were Hispanic. Mean (SD) age was 47.5 (17.4) years. Across scenarios, weighted data showed that 75.4% of the participants would recommend approval of the postrandomization consent pragmatic trial, 20.4% would probably not recommend approval, and 4.2% would definitely not recommend approval. Approval was not sensitive to framing language (traditional vs new framing in high-stakes scenario, 74.3% vs 76.8%, P = .40; in low-stakes scenario, 77.7% vs 72.9%, P = .10) or to the stakes (low vs high stakes in traditional framing, 77.7% vs 74.3%, P = .25; in new framing, 72.9% vs 76.8%, P = .18). Better understanding of the postrandomization consent design was associated with higher rate of approval (78.1% vs 65.0%, P = .002 for high-stakes scenario; 77.2% vs 64.9%, P = .004 for low-stakes scenario), especially among those with less education. However, opinions about personal involvement in the control arm were more cautious (range depending on scenario, 45.6%-59.7%) and sensitive to stakes but not to framing.Conclusions and relevanceThe public's generally high rate of approval of the ethics of postrandomization informed consent for pragmatic trial designs does not appear to be affected by whether postrandomization consent design is framed using traditional randomized clinical trial terminology, regardless of the stakes of the trial. Promoting better understanding of the design may increase its acceptance by the public.
| S-EPMC6324565 | biostudies-literature
Project description:ObjectiveTo understand how often 'breakthroughs,' that is, treatments that significantly improve health outcomes, can be developed.DesignWe applied weighted adaptive kernel density estimation to construct the probability density function for observed treatment effects from five publicly funded cohorts and one privately funded group.Data sources820 trials involving 1064 comparisons and enrolling 331,004 patients were conducted by five publicly funded cooperative groups. 40 cancer trials involving 50 comparisons and enrolling a total of 19,889 patients were conducted by GlaxoSmithKline.ResultsWe calculated that the probability of detecting treatment with large effects is 10% (5-25%), and that the probability of detecting treatment with very large treatment effects is 2% (0.3-10%). Researchers themselves judged that they discovered a new, breakthrough intervention in 16% of trials.ConclusionsWe propose these figures as the benchmarks against which future development of 'breakthrough' treatments should be measured.
| S-EPMC4208055 | biostudies-literature
Project description:In 2004 and 2005, the first clinical trials were launched to investigate the use of tenofovir for HIV prevention in Cambodia,Cameroon, Nigeria and Thailand. Controversies erupted over the ethical integrity of the research protocol. We reflect on the events that ledto the controversies and identified that scientific and ethical concerns raised by members of local communities at each of these sites wereerased by trialists, causing crisis that led to premature shut down the early PrEP trials. In the aftermath of these trials, the World HealthOrganisation, UNAIDS, and AVAC developed ethics guidelines intended to recognize the concerns as authentic, and developed guidelines toimprove researchers' engagement of communities in biomedical HIV prevention trial design and implementation. Our findings suggest thatthe ethics guidelines are limited in its ability to address power inequalities that leads to voice erasures and non-recognition of localcompetencies. Rather the ethical documents enabled trialists to gain a new sense of authority through the interpretations of ethical researchconduct enabling trialists regain power that can further entrench inequality and voice erasures. To address concerns with what seems anintractable problem, we suggested models of engagement for off-shored research may be the option.
| S-EPMC7448920 | biostudies-literature
Project description:Drug repurposing is a strategy of identifying new potential uses for already existing drugs. Many researchers adopted this method to identify treatment or prevention during the COVID-19 pandemic. However, despite the considerable number of repurposed drugs that were evaluated, only some of them were labeled for new indications. In this article, we present the case of amantadine, a drug commonly used in neurology that attracted new attention during the COVID-19 outbreak. This example illustrates some of the ethical challenges associated with the launch of clinical trials to evaluate already approved drugs. In our discussion, we follow the ethics framework for prioritization of COVID-19 clinical trials proposed by Michelle N Meyer and colleagues (2021). We focus on four criteria: social value, scientific validity, feasibility, and consolidation/collaboration. We claim that launching amantadine trials was ethically justified. Although the scientific value was anticipated to be low, unusually, the social value was expected to be high. This was because of significant social interest in the drug. In our view, this strongly supports the need for evidence to justify why the drug should not be prescribed or privately accessed by interested parties. Otherwise, a lack of evidence-based argument could enhance its uncontrolled use. With this paper, we join the discussion on the lessons learned from the pandemic. Our findings will help to improve future efforts to decide on the launch of clinical trials on approved drugs when dealing with the widespread off-label use of the drug.
| S-EPMC9989564 | biostudies-literature
Project description:ObjectivesThis study examines factors affecting reliability, or consistency of assessment scores, from an objective structured clinical examination (OSCE) in neurology through generalizability theory (G theory).MethodsData include assessments from a multistation OSCE taken by 194 medical students at the completion of a neurology clerkship. Facets evaluated in this study include cases, domains, and items. Domains refer to areas of skill (or constructs) that the OSCE measures. G theory is used to estimate variance components associated with each facet, derive reliability, and project the number of cases required to obtain a reliable (consistent, precise) score.ResultsReliability using G theory is moderate (Φ coefficient = 0.61, G coefficient = 0.64). Performance is similar across cases but differs by the particular domain, such that the majority of variance is attributed to the domain. Projections in reliability estimates reveal that students need to participate in 3 OSCE cases in order to increase reliability beyond the 0.70 threshold.ConclusionsThis novel use of G theory in evaluating an OSCE in neurology provides meaningful measurement characteristics of the assessment. Differing from prior work in other medical specialties, the cases students were randomly assigned did not influence their OSCE score; rather, scores varied in expected fashion by domain assessed.
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Project description:Scientifically rigorous clinical trials are needed to test continuous positive airway pressure's (CPAP) effect on important clinical endpoints known to be associated with obstructive sleep apnea, such as myocardial infarction, cardiac arrhythmias, stroke, mortality, seizures, and cognitive function. In this "Special Article," we review the regulatory and ethical issues that surround the design and conduct of CPAP trials, including selection of the appropriate control condition, exclusion criteria, and follow-up duration.
| S-EPMC3041615 | biostudies-other
Project description:Pragmatic clinical trials are increasingly used to generate knowledge about real-world clinical interventions. However, they involve some distinctive ethical and regulatory challenges. In this article, we examine a set of issues related to incentives and other payments to patients in pragmatic clinical trials. Although many of the ethical concerns related to incentives and payments in explanatory trials pertain to pragmatic clinical trials, the pragmatic features may introduce additional challenges. These include those related to the risk of incentives and payments undermining the scientific validity and social value of pragmatic clinical trials, the sources of data used in pragmatic clinical trials, and when the pragmatic clinical trials are conducted under waivers of consent. Based on our examination of these matters, we offer some preliminary recommendations regarding incentives and payments in pragmatic clinical trials, recognizing that additional data and experiences are needed to refine them.
| S-EPMC8597901 | biostudies-literature