Good Clinical Trials by removing defensive interpretation of Good Clinical Practice guidelines.
Ontology highlight
ABSTRACT:
SUBMITTER: den Heijer JM
PROVIDER: S-EPMC9292589 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundEarly Intervention in Psychosis (EIP) services have been implemented with the dual aims of preventing harmful outcomes associated with early-onset psychosis and improving prognosis. However, concerns have been raised regarding the ethical implications of involving young people in EIP services. One way to ensure high ethical standards and promote good practice in EIP delivery is through governance of clinical practice. This study aimed to investigate the normative dimensions of good practice in EIP through examination of clinical guideline documents published in England over the past 15 years.MethodsA total of 14 clinical guidelines and relevant policy documents for EIP were retrieved and analysed using a mixed inductive and deductive thematic approach. Themes were derived from the data itself, whereas the development of broader categories was performed through a constant comparison with the scientific literature describing ethical issues in EIP.ResultsEthical touchpoints of good practice in EIP included both procedural and substantive factors, which were seen to be interdependent and mutually constitutive. These ethical touchpoints were largely implicit in the documents analysed. Procedural requirements of EIP service delivery consisted of norms and rules pertaining to EIP service structure, adherence to codes of ethics, inclusivity, patient and family centredness and appropriate treatment provision. Substantive factors consisted of moral attributes that should be cultivated by healthcare professionals working in EIP: competency, empathy, sensitivity and trustworthiness.ConclusionsWe argue that, to ensure good practice in EIP, procedural and substantive ethical expectations embedded in EIP guideline documents should be made explicit in EIP service and care delivery. We suggest that the procedural and substantive factors highlighted in this paper contribute useful dimensions for the eventual evaluation of good practice in EIP services across England.
| S-EPMC6120554 | biostudies-literature
Project description:Randomized, clinical trials are commonly regarded as the highest level of evidence to support clinical decisions. Good Clinical Practice guidelines have been constructed to provide an ethical and scientific quality standard for trials that involve human subjects in a manner aligned with the Declaration of Helsinki. Originally designed to provide a unified standard of trial data to support submission to regulatory authorities, the principles may also be applied to other studies of human subjects. Although the application of Good Clinical Practice principles generally led to improvements in the quality and consistency of trial operations, these principles have also contributed to increasing trial complexity and costs. Alternatively, the growing availability of electronic health record data has facilitated the possibility for streamlined pragmatic clinical trials. The central tenets of Good Clinical Practice and pragmatic clinical trials represent potential tensions in trial design (stringent quality and highly efficient operations). In the present article, we highlight potential areas of discordance between Good Clinical Practice guidelines and the principles of pragmatic clinical trials and suggest strategies to streamline study conduct in an ethical manner to optimally perform clinical trials in the electronic age.
| S-EPMC4777975 | biostudies-literature
Project description:Bayesian analysis is firmly grounded in the science of probability and has been increasingly supplementing or replacing traditional approaches based on P values. In this review, we present gradually more complex examples, along with programming code and data sets, to show how Bayesian analysis takes evidence from randomized clinical trials to update what is already known about specific treatments in cardiovascular medicine. In the example of revascularization choices for diabetic patients who have multivessel coronary artery disease, we combine the results of the FREEDOM trial (Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multivessel Disease) with prior probability distributions to show how strongly we should believe in the new Class I recommendation ("should be done") for a preference of bypass surgery over percutaneous coronary intervention. In the debate about the duration of dual antiplatelet therapy after drug-eluting stent implantation, we avoid a common pitfall in traditional meta-analysis and create a network of randomized clinical trials to compare outcomes after specific treatment durations. Although we find no credible increase in mortality, we affirm the tradeoff between increased bleeding and reduced myocardial infarctions with prolonged dual antiplatelet therapy, findings that support the new Class IIb recommendation ("may be considered") to extend dual antiplatelet therapy after drug-eluting stent implantation. In the decision between culprit artery-only and multivessel percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction, we use hierarchical meta-analysis to analyze evidence from observational studies and randomized clinical trials and find that the probability of all-cause mortality at longest follow-up is similar after both strategies, a finding that challenges the older ban against noninfarct-artery intervention during primary percutaneous coronary intervention. These examples illustrate how Bayesian analysis integrates new trial information with existing knowledge to reduce uncertainty and change attitudes about treatments in cardiovascular medicine.
| S-EPMC6421843 | biostudies-literature
Project description:Achondroplasia (ACH) is a skeletal dysplasia that presents with limb shortening, short stature, and characteristic facial configuration. ACH is caused by mutations of the FGFR3 gene, leading to constantly activated FGFR3 and activation of its downstream intracellular signaling pathway. This results in the suppression of chondrocyte differentiation and proliferation, which in turn impairs endochondral ossification and causes short-limb short stature. ACH also causes characteristic clinical symptoms, including foramen magnum narrowing, ventricular enlargement, sleep apnea, upper airway stenosis, otitis media, a narrow thorax, spinal canal stenosis, spinal kyphosis, and deformities of the lower extremities. Although outside Japan, papers on health supervision are available, they are based on reports and questionnaire survey results. Considering the scarcity of high levels of evidence and clinical guidelines for patients with ACH, clinical practical guidelines have been developed to assist both healthcare professionals and patients in making appropriate decisions in specific clinical situations. Eleven clinical questions were established and a systematic literature search was conducted using PubMed/MEDLINE. Evidence-based recommendations were developed, and the guidelines describe the recommendations related to the clinical management of ACH. We anticipate that these clinical practice guidelines for ACH will be useful for healthcare professionals and patients alike.
| S-EPMC6958518 | biostudies-literature
Project description:Background: Good Clinical Laboratory Practice (GCLP) is a standard that helps ensure the quality and reliability of research data through principles of Good Laboratory Practice (GLP) and Good Clinical Practice (GCP). The implementation of GCLP includes careful documentation of procedures, competencies and safety measures. Implementation of GCLP is influenced by existing resources and quality systems, thus laboratories in low- and middle-income countries may face additional challenges. Methods: This paper describes implementation of GCLP at the Kenya Medical Research Institute-Center for Microbiology Research (KEMRI-CMR) as part of a quality system to support medical research. This study employed assessment, twinning (institutional mentorship) model, conducting relevant training workshops and Kaizen 5S approaches to implement an effective quality management system using GCLP standard. This was achieved through a collaboration between the KEMRI/Wellcome Trust Research Programme (KWTRP) and KEMRI-CMR. The aim was compliance and continuous monitoring to meet international GCLP standards in a way that could be replicated in other research organizations. Results: Following a baseline assessment in March 2017, training, mentorship and a cycle of quality audit and corrective action using a Kaizen 5S approach (sorting, setting in order, shining, standardizing and sustaining) was established. Laboratory personnel were trained in writing standard operating procedures and analytical plans, microbiological techniques, and good documentation practice. Mid-term and exit assessments demonstrated significant declines in non-conformances across all GCLP elements. KEMRI-CMR achieved GCLP accreditation in May 2018 by Qualogy Ltd (UK). Conclusions: Involving all the laboratory personnel in implementation of quality management system processes is critical to success. An institutional mentorship (twinning) approach shows potential for future collaborations between accredited and non-accredited organizations to accelerate the implementation of high-quality management systems and continuous improvement.
| S-EPMC6305232 | biostudies-literature
Project description:Congenital hyperinsulinism is a rare condition, and following recent advances in diagnosis and treatment, it was considered necessary to formulate evidence-based clinical practice guidelines reflecting the most recent progress, to guide the practice of neonatologists, pediatric endocrinologists, general pediatricians, and pediatric surgeons. These guidelines cover a range of aspects, including general features of congenital hyperinsulinism, diagnostic criteria and tools for diagnosis, first- and second-line medical treatment, criteria for and details of surgical treatment, and future perspectives. These guidelines were generated as a collaborative effort between The Japanese Society for Pediatric Endocrinology and The Japanese Society of Pediatric Surgeons, and followed the official procedures of guideline generation to identify important clinical questions, perform a systematic literature review (April 2016), assess the evidence level of each paper, formulate the guidelines, and obtain public comments.
| S-EPMC5537210 | biostudies-other
Project description:BackgroundWhile patient and public involvement (PPI) in clinical trials is beneficial and mandated by some funders, formal guidance on how to implement PPI is limited and challenges have been reported. We aimed to investigate how PPI is approached within a UK Clinical Trials Unit (CTU)'s portfolio of randomised controlled trials, perceived barriers to/facilitators of its successful implementation, and perspectives on the CTU's role in PPI.MethodsA mixed-methods study design, involving (1) an online survey of 26 trial managers (TMs) and (2) Interviews with Trial Management Group members and public contributors from 8 case-study trials. Quantitative survey data were summarised using descriptive statistics and interview transcripts analysed thematically. Two public contributors advised throughout and are co-authors.Results(1) 21 TMs completed the survey; (2) 19 in-depth interviews were conducted with public contributors (n=8), TMs (n=5), chief investigators (n=3), PPI coordinators (n=2) and a researcher. 15/21 TMs surveyed reported that a public contributor was on the trial team, and 5 used another PPI method. 12/21 TMs reported that public contributors were paid (range £10-50/h). 5 TMs reported that training was provided for public contributors and few staff members had received any formal PPI training. The most commonly reported tasks undertaken by public contributors were the review of participant-facing materials/study documents and advising on recruitment/retention strategies. Public contributors wanted and valued feedback on changes made due to their input, but it was not always provided. Barriers to successful PPI included recruitment challenges, group dynamics, maintaining professional boundaries, negative attitudes to PPI amongst some researchers, a lack of continuity of trial staff, and the academic environment. Successful PPI required early and explicit planning, sharing of power and ownership of the trial with public contributors, building and maintaining relationships, and joint understanding and clarity about expectations/roles. CTUs have an important role to play in supporting recruitment, signposting and coordinating PPI.ConclusionsWhile highly valuable, PPI in trials is currently variable. PPI representatives are recruited informally, may not be provided with any training and are paid inconsistently across trials. Study findings can help optimise PPI in trials and ensure researchers and public contributors are adequately supported.
| S-EPMC8542312 | biostudies-literature
Project description:Mesenchymal stem/stromal cells (MSCs) are widely studied by both academia and industry for a broad array of clinical indications. The collective body of data provides compelling evidence of the clinical safety of MSC therapy. However, generally accepted proof of therapeutic efficacy has not yet been reported. In an effort to generate a more effective therapeutic cell product, investigators are focused on modifying MSC processing protocols to enhance the intrinsic biologic activity. Here, we report a Good Manufacturing Practice-compliant two-step MSC manufacturing protocol to generate MSCs or interferon γ (IFNγ) primed MSCs which allows freshly expanded cells to be infused in patients on a predetermined schedule. This protocol eliminates the need to infuse cryopreserved, just thawed cells which may reduce the immune modulatory activity. Moreover, using (IFNγ) as a prototypic cytokine, we demonstrate the feasibility of priming the cells with any biologic agent. We then characterized MSCs and IFNγ primed MSCs prepared with our protocol, by karyotype, in vitro potential for malignant transformation, biodistribution, effect on engraftment of transplanted hematopoietic cells, and in vivo toxicity in immune deficient mice including a complete post-mortem examination. We found no evidence of toxicity attributable to the MSC or IFNγ primed MSCs. Our data suggest that the clinical risk of infusing MSCs or IFNγ primed MSCs produced by our two-step protocol is not greater than MSCs currently in practice. While actual proof of safety requires phase I clinical trials, our data support the use of either cell product in new clinical studies. Stem Cells Translational Medicine 2017;6:1868-1879.
| S-EPMC6430053 | biostudies-literature
Project description:BackgroundThere is a lack of a comprehensive evaluation for pediatric clinical practice guidelines (CPGs) published in recent years. Here, we assessed the quality of pediatric CPGs, considering factors that might affect their quality. The aim of the study is to promote a more coherent development and application of CPGs.MethodsPediatric CPGs published in PubMed, MedLive, Guidelines International Network, National Institute for Health and Care Excellence, and World Health Organization between 2017 and 2019 were searched and collected. Paired researchers conducted screening, data extraction, and quality assessment using the Appraisal of Guidelines for Research and Evaluation II (AGREE II). Linear regression analysis determined the factors affecting CPGs' quality.ResultsThe study included a total of 216 CPGs, which achieved a mean score of 4.26 out of 7 points (60.86%) in the AGREE II assessment. Only 6.48% of the CPGs reached the "recommend" level. The remaining 69.91% should have been modified before recommendation, while the other 23.61% did not reach the recommended level at all. The overall quality of recent pediatric CPGs was higher than previously, and the proportion of CPGs with low-quality decreased over time. However, there were still too few CPGs that reached a high-quality level. The "applicability" and "rigor of development" domains had generally low scores. CPGs formulated by developing countries or regions, those that are not under an organizations or groups responsibility, and those that used non-evidence-based methods were found to be associated with poorer quality in different domains as independent or combinational factors.ConclusionsThe quality of pediatric CPGs still needs to be improved. Specifically, a quality control before applying new CPGs should be essential to ensure their quality and applicability.
| S-EPMC8103635 | biostudies-literature
Project description:A Good Clinical Practices (GCPs) course, based on the combination of theoretical modules with a practical training in real-life conditions, was held in 2010 in Burkina Faso. It was attended by 15 trainees from nine African, Asian, and Latin American countries. There were some discrepancies between the average good results at the end of the theoretical phase and the GCP application during the first days of the practical phase, underlying the difficulties of translating theoretical knowledge into good practices. Most of the findings were not unexpected and reflected the challenges commonly faced by clinical investigators in resource-poor contexts (i.e., the high workload at peripheral health facilities, the need to conciliate routine clinical activities with clinical research, and the risk of creating a double standard among patients attending the same health facility [free care for recruited patients versus user fees for non-recruited patients with the same medical condition]). Even if limited in number and time, these observations suggest that a theoretical training alone may not be sufficient to prepare trainees for the challenges of medical research in real-life settings. Conversely, when a practical phase immediately follows a theoretical one, trainees can immediately experience what the research methodology implicates in terms of work organization and relationship with recruited and non-recruited patients. This initial experience shows the complexity of translating GCP into practice and suggests the need to rethink the current conception of GCP training.
| S-EPMC3617841 | biostudies-literature