Building a Fit for Purpose Clinical Trials Infrastructure to Accelerate the Assessment of Novel Hematopoietic Cell Transplantation Strategies and Cellular Immunotherapies.
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ABSTRACT:
SUBMITTER: Devine SM
PROVIDER: S-EPMC8443822 | biostudies-literature | 2021 Feb
REPOSITORIES: biostudies-literature
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Building a Fit for Purpose Clinical Trials Infrastructure to Accelerate the Assessment of Novel Hematopoietic Cell Transplantation Strategies and Cellular Immunotherapies.
Devine Steven M SM Horowitz Mary M MM
Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20210112 5
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Project description:Policy Points This analysis finds that government obesity policies in England have largely been proposed in a way that does not readily lead to implementation; that governments rarely commission evaluations of previous government strategies or learn from policy failures; that governments have tended to adopt less interventionist policy approaches; and that policies largely make high demands on individual agency, meaning they rely on individuals to make behavior changes rather than shaping external influences and are thus less likely to be effective or equitable. These findings may help explain why after 30 years of proposed government obesity policies, obesity prevalence and health inequities still have not been successfully reduced. If policymakers address the issues identified in this analysis, population obesity could be tackled more successfully, which has added urgency given the COVID-19 pandemic.ContextIn England, the majority of adults, and more than a quarter of children aged 2 to 15 years live with obesity or excess weight. From 1992 to 2020, even though the government published 14 obesity strategies in England, the prevalence of obesity has not been reduced. We aimed to determine whether such government strategies and policies have been fit for purpose regarding their strategic focus, nature, basis in theory and evidence, and implementation viability.MethodWe undertook a mixed-methods study, involving a document review and analysis of government strategies either wholly or partially dedicated to tackling obesity in England. We developed a theory-based analytical framework, using content analysis and applied thematic analysis (ATA) to code all policies. Our interpretation drew on quantitative findings and thematic analysis.FindingsWe identified and analyzed 14 government strategies published from 1992 to 2020 containing 689 wide-ranging policies. Policies were largely proposed in a way that would be unlikely to lead to implementation; the majority were not interventionist and made high demands on individual agency, meaning that they relied on individuals to make behavior changes rather than shaping external influences, and are thus less likely to be effective or to reduce health inequalities.ConclusionsThe government obesity strategies' failure to reduce the prevalence of obesity in England for almost 30 years may be due to weaknesses in the policies' design, leading to a lack of effectiveness, but they may also be due to failures of implementation and evaluation. These failures appear to have led to insufficient or no policy learning and governments proposing similar or identical policies repeatedly over many years. Governments should learn from their earlier policy failures. They should prioritize policies that make minimal demands on individuals and have the potential for population-wide reach so as to maximize their potential for equitable impacts. Policies should be proposed in ways that readily lead to implementation and evaluation.
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Project description:Hematopoietic cell transplantation (HCT) is a complex procedure that requires availability of adequate infrastructure, personnel, and resources at transplantation centers. We conducted a national survey of transplantation centers in the United States to obtain data on their personnel, infrastructure, and care delivery models. A 42-item web-based survey was administered to medical directors of transplantation centers in the United States that reported any allogeneic HCT to the Center for International Blood and Marrow Transplant Research in 2011. The response rate for the survey was 79% for adult programs (85 of 108 centers) and 82% for pediatric programs (54 of 66 centers). For describing results, we categorized centers into groups with similar volumes based on 2010 total HCT activity (adult centers, 9 categories; pediatric centers, 6 categories). We observed considerable variation in available resources, infrastructure, personnel, and care delivery models among adult and pediatric transplantation centers. Characteristics varied substantially among centers with comparable transplantation volumes. Transplantation centers may find these data helpful in assessing their present capacity and use them to evaluate potential resource needs for personnel, infrastructure, and care delivery and in planning for growth.
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Project description:This SuperSeries is composed of the SubSeries listed below.
2025-04-27 | GSE165881 | GEO
Project description:The organization and function of the institutional animal care and use committee (IACUC) is the key component of government regulation and oversight of necessary scientific research using live animals and of AAALAC - International accreditation of animal care and use programs in the United States. The regulations, roles, and responsibilities of IACUCs have evolved since their inception 35 years ago from a limited focus on animal welfare and specific animal procedures to embracing scientific quality, data reproducibility and translation, and animal welfare as inextricably interdependent and critical components of generation of new scientific knowledge and medical treatments. A current challenge for IACUCs is in evaluating whether benefits to be derived (eg, new knowledge or treatments) justify any unavoidable pain, stress, or injury associated with proposed research protocols, because the former are long-term and at best speculative outcomes, whereas the latter are immediate and tangible for the study animals. Scientific consensus is that research most likely to generate significant new knowledge and medical treatments is that conducted to high scientific, technical, and quality standards and reported with full transparency to facilitate reproducibility. As an alternative to current benefits evaluations included in risk benefit and harm benefit constructs, the authors propose that IACUCs assess the proposed research for scientific quality and alignment of study elements with the study purpose (e.g., Fit for Purpose [FfP]), including justifications for study design components, selection of primary endpoints and technologies, rationale for data and statistical analyses, and research communication plans. Fit for Purpose endpoints are objective, immediate, and impactful as are the potential risks for study animals, and at the same time they are the best predictors for achievement of longer-term benefits. We propose that IACUCs and any revision of The ILAR Guide consider FfP concepts in place of traditional benefits assessment to accelerate the generation of new knowledge and treatments benefiting medical and veterinary patients and the environment through better science and animal welfare rather than to continue to rely on speculative future outcomes.
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Project description:Purpose of reviewCytomegalovirus (CMV) remains a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (Allo-HSCT). New strategies and methods for prevention and management of CMV infection are urgently needed. We aim to review the new developments in diagnostics, prevention, and management strategies of CMV infection in Allo-HSCT recipients.Recent findingsThe approval of the novel anti-CMV drug letermovir in 2017 has led to an increase in the use of antiviral prophylaxis as a preferred approach for prevention in many centers. Real-world studies have shown efficacy similar to the clinical trial. CMV-specific T cell-mediated immunity assays identify patients with immune reconstitution and predict disease progression. Phase 2 trials of maribavir have shown its efficacy as preemptive therapy and treatment of resistant and refractory CMV infections. Adoptive T cell therapy is an emerging option for treatment of refractory and resistant CMV. Of the different CMV vaccine trials, PepVax has shown promising results in a phase 1 trial.SummaryCMV cell-mediated immunity assays have potential to be used as an adjunctive test to develop individualized management plan by identifying the patients who develop immune reconstitution; however, further prospective interventional studies are needed. Maribavir and adoptive T cell therapy are promising new therapies for treatment of CMV infections. CMV vaccine trials for prevention are also under way.
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Project description:As our understanding of the impact of specific molecular properties on applications in discovery-based disciplines improves, the extent to which published synthetic methods meet (or do not meet) desirable criteria is ever clearer. Herein, we show how the application of simple (and in many cases freely available) computational tools can be used to develop a semiquantitative understanding of the potential of new methods to support molecular discovery. This analysis can, among other things, inform the design of improved substrate scoping studies; direct the prioritization of specific exemplar structures for synthesis; and substantiate claims of potential future applications for new methods.
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Project description:Rationale, aims and objectivesThe field of implementation science is critical for embedding research evidence into healthcare practice, benefiting individuals, organizations, governments, and the broader community. Implementation science is messy and complex, underpinned by many theories and frameworks. Efficacious interventions for older people with multiple comorbidities exist, yet many lack effectiveness evaluation relevant to pragmatic implementation within aged care practice. This article outlines the conceptualization and development of an Implementation Framework for Aged Care (IFAC), fit-for-purpose for an aged care organization, Bolton Clarke, intent on embedding evidence into practice.MethodA four-stage process was adopted to (1) explore context and relevant literature to conceptualize the IFAC; (2) identify key elements for a draft IFAC; (3) expand elements and refine the draft in consultation with experts and (4) apply the IFAC to three existing projects, identifying key learnings. A checklist to operationalize the IFAC was then developed.ResultsThe IFAC is grounded in codesign principles and encapsulated by the implementation context, from a social, cultural and political perspective. The IFAC addresses the questions of (1) why do we need to change?; (2) what do we know?; (3) who will benefit?; (4) who will make the change?; (5) what strategies will be used?; and (6) what difference are we making? Three pilot projects: early adoption of a Wellness and Reablement approach; a care worker and virtual physiotherapist-led program to prevent falls; and a therapeutic horticulture program for residential communities, highlight learnings of applying the IFAC in practice.ConclusionThis fit-for-purpose IFAC was developed for a proactive and responsive aged care provider. The simplicity of the six-question IFAC is underpinned by substantial theoretical perspectives for its elements and their connections. This complexity is then consolidated into an 18-question checklist to operationalize the IFAC, necessary to advance the translation of evidence into clinical practice.
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Project description:Tracing the hematopoietic regeneration of HSC clones by coupling single HSC transplantation and single-cell RNA sequencing (scRNA-seq) of clone-derived cells from 1 to 12 months after transplantation.
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