RESUMEN
Strategies to bring clinical trials closer to patients gained momentum during the COVID-19 pandemic, enabling more participants to receive treatment and/or testing in their local communities. Incorporation of decentralized trial elements presents both opportunities and challenges, spanning regulatory, technical, and operational aspects. This ASCO research statement includes timely consensus-driven recommendations and a call for engagement of all research stakeholders. ASCO held multistakeholder meetings with leaders in oncology research and concluded that research-related regulatory and administrative requirements and burdens present critical barriers to decentralizing trials. One example is sponsor and contract research organization (CRO) use of US Food and Drug Administration (FDA)'s Statement of Investigator (Form 1572), which was found to exceed FDA's stated intent and used in conservative ways disproportionate to potential risks to participants and scientific integrity. As a result, research sites experience an avalanche of downstream administrative and regulatory activities that consume considerable resources. This statement recommends four key solutions to address such barriers and recalibrate regulatory and administrative expectations for decentralizing trials: (1) FDA should engage the research community in a public-private partnership to modernize standards and enable local access to trials; (2) sponsors and CROs should develop standards and protocols that accommodate flexible approaches, enable local participation, provide clarity around roles and requirements, and promote consistency; (3) research centers, networks, and sites should update policies and procedures to implement decentralized trial elements; and (4) research community should develop a streamlined, uniform mechanism to simplify regulatory data collection and documentation and use it consistently across trials. We can and must prioritize a concerted commitment to simplify and streamline regulatory requirements and practices to broaden access to and participation in cancer clinical trials.
RESUMEN
PURPOSE: Community-based research programs face many barriers to participation in clinical trials. Although the majority of people with cancer are diagnosed and treated in the community setting, only roughly 3% are enrolled onto clinical trials. Research contract and budget negotiations have been consistently identified as time consuming and a barrier to participation in clinical trials. ASCO's Community Research Forum conducted a survey about specific challenges of research contract and budget negotiation processes in community-based research settings. The goal was to ultimately identify potential solutions to these barriers. METHODS: A survey was distributed to 780 community-based physician investigators and research staff. The survey included questions to provide insight into contract and budget negotiation processes and perceptions about related barriers. RESULTS: A total of 77% of the 150 respondents acknowledged barriers in the process. Respondents most frequently identified budget-related issues (n = 133), inefficiencies in the process (n = 80), or legal review and negotiation issues (n = 70). Of the respondents, 44.1% indicated that contract research organizations made the contract negotiations process harder for their research program, and only 5% believed contract research organizations made the process easier. The contract negotiations process is perceived to be impeded by sponsors through underestimation of costs, lack of flexibility with the contract language, and excessive delays. CONCLUSION: Improving clinical trial activation processes and reducing inefficiencies would be beneficial to all interested stakeholders, including patients who may ultimately stand to benefit from participation in clinical trials. The following key recommendations were made: standardization of contracts and negotiation processes to promulgate transparency and efficiencies, improve sponsor processes to minimize burden on sites, create and promote use of contract templates and best practices, and provide education and consultation.
Asunto(s)
Investigación Biomédica , Investigación Participativa Basada en la Comunidad , Contratos , Negociación , Investigación Biomédica/economía , Presupuestos , Investigación Participativa Basada en la Comunidad/economía , Humanos , NeoplasiasRESUMEN
Histological processing of the cochlea for immunochemistry is often a compromise between good anatomical resolution and preservation of antigenicity. Techniques able to preserve tissue architecture invariably demand elevated temperatures and harsh chemicals or a combination of both. The likely result is reduced antigenicity, enzyme activity and nucleic acid integrity. We have modified an existing embedding medium for use in the cochlea that operates at physiological temperature and avoids denaturing agents and organic solvents. Tissue antigenicity is maximised and anatomical detail preserved, normally two mutually exclusive goals. The method is attractive because of its simplicity, speed and transparency for easy cochlear orientation. It is also likely to be adaptable for the infiltration of other heterogeneous structures prone to distortion during frozen sectioning.
Asunto(s)
Cóclea/química , Gelatina , Canales de Potasio con Entrada de Voltaje , Adhesión del Tejido/métodos , Animales , Cobayas , Inmunohistoquímica/métodos , Indicadores y Reactivos , Canal de Potasio Kv.1.1 , Proteína Básica de Mielina/análisis , Proteína P0 de la Mielina/análisis , Proteínas Nucleares/análisis , Técnicas de Cultivo de Órganos , Canales de Potasio/análisis , Ratas , Tubulina (Proteína)/análisisRESUMEN
Loss of sensory hair cells within the cochlea results in a permanent sensorineural hearing loss and initiates the gradual degeneration of spiral ganglion neurons (SGNs) - the primary afferent neurons of the cochlea. While these neurons are normally myelinated via Schwann cells, loss of myelin occurs as a precursor to neural degeneration. However, the relationship between demyelination and the status of Schwann cells in deafness is not well understood. We used a marker of peripheral myelin (myelin protein zero; P0) and a marker of Schwann cells (S100) to determine the temporal sequence of myelin and Schwann cell loss as a function of duration of deafness. Rat pups were systemically deafened for periods ranging from 2 weeks to greater than 6 months by co-administration of frusemide and gentamicin. Cochleae were cryosectioned and quantitative immunohistochemistry used to determine the extent of P0 and S100 labelling within the peripheral processes, SGN soma and their central processes within the modiolus. SGN density was also determined for each cochlear turn. P0 labelling decreased throughout the cochlea with increasing duration of deafness. The reduction in P0 labelling occurred at a faster rate than the SGN loss. In contrast, S100 labelling was not significantly reduced compared with age-matched controls in any cochlear region until 6 months post-deafening. These results suggest that Schwann cells may revert to non-myelinating phenotypes in response to deafness and exhibit greater survival traits than SGNs. The potential clinical significance of these findings for cochlear implants is discussed.