Overcoming challenges to data quality in the ASPREE clinical trial

© 2019 The Author(s). Background: Large-scale studies risk generating inaccurate and missing data due to the complexity of data collection. Technology has the potential to improve data quality by providing operational support to data collectors. However, this potential is under-explored in community-based trials. The Aspirin in reducing events in the elderly (ASPREE) trial developed a data suite that was specifically designed to support data collectors: the ASPREE Web Accessible Relational Database (AWARD). This paper describes AWARD and the impact of system design on data quality. Methods: AWARD's operational requirements, conceptual design, key challenges and design solutions for data quality are presented. Impact of design features is assessed through comparison of baseline data collected prior to implementation of key functionality (n = 1000) with data collected post implementation (n = 18,114). Overall data quality is assessed according to data category. Results: At baseline, implementation of user-driven functionality reduced staff error (from 0.3% to 0.01%), out-of-range data entry (from 0.14% to 0.04%) and protocol deviations (from 0.4% to 0.08%). In the longitudinal data set, which contained more than 39 million data values collected within AWARD, 96.6% of data values were entered within specified query range or found to be accurate upon querying. The remaining data were missing (3.4%). Participant non-attendance at scheduled study activity was the most common cause of missing data. Costs associated with cleaning data in ASPREE were lower than expected compared with reports from other trials. Conclusions: Clinical trials undertake complex operational activity in order to collect data, but technology rarely provides sufficient support. We find the AWARD suite provides proof of principle that designing technology to support data collectors can mitigate known causes of poor data quality and produce higher-quality data. Health information technology (IT) products that support the conduct of scheduled activity in addition to traditional data entry will enhance community-based clinical trials. A standardised framework for reporting data quality would aid comparisons across clinical trials

Bean Golden Mosaic: Research Advances

El frijol (Phaseolus vulgaris L.) es una de las fuentes de proteina (15-35%) y calorías (ca. 340 caI./100 gr) más importantes en la América Latina. En esta región, centro de origen de esta especie, se producen más de cuatro millones de toneladas de frijol al año, lo cual equivale al 88% de la semilla de frijol producida en las regiones tropicales del mundo. Brasil, el mayor productor de frijol del mundo, posee un consumo per capita de cerca de 20 kg/año. En America Central, el frijol es igualmente importante, siendo consumido en la mayoría de los países centroamericanos hasta tres veces por día. Proporcionalmente, en la America Central se cultiva el doble del área que en Brasil, relativo a sus extensiones territoriales. El frijol es también producido en islas del Caribe, tales como Cuba (ca. 26.000 TM), Haití (56.000 TM) y República Dominicana (55.000 TM) según datos de 1990 (CIAT). México, el segundo productor de frijol en la America Latina, consume aproximadamente 1.2 millones de toneladas métricas de frijol al año. A pesar de que México cultiva cerca de 1.800.000 hectáreas de frijol, la demanda interna no es satisfecha en algunos años dado la baja productividad del cultivo. Esta baja productividad relativa del frijol, no solo en México sino también en el resto de la América Latina (700 kg/ha vs. 1.600 kg/ha en los Estados Unidos), es una consecuencia de los múltiples problemas bióticos y abióticos que inciden en el cultivo, en el trópico Americano. Es precisamente en las regiones productoras de frijol situadas en climas cálidos, de altitud baja a intermedia (0-1200 m.s.n.m), donde el mosaico dorado del frijol alcanza su mayor incidencia.The common bean (Phaseolus vulgaris L.) is an important source of protein and calories in Latin America. In this region, the center of origin of this legume species, over 4 million tons of dry beans are produced per year. Nevertheless, many Latin American countries, including two of the largest producers of beans in the world, Brazil and Mexico, have to import beans to meet internal demand. This shortage of beans is related to the low productivity of this crop in Latin America (700 kg /ha vs. 1,600 kg/ ha average in the USA). The low productivity in the main bean production regions of tropical America is associated to the incidence of several biotic and abiotic constraints. Among the biotic constraints, bean golden mosaic virus is undoubtedly the main bean production problem in the lowland tropics, particularly, during the dry seasons of the year.Programa Cooperativo Regional de Frijol para Centroamérica, México y el Caribe (PROFRIJOL)Cooperación Suiza para el Desarrollo (COSUDE)Centro Internacional de Agricultura Tropical (CIAT)UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Agroalimentarias::Estación Experimental Agrícola Fabio Baudrit Moreno (EEAFBM

Designing a broad-spectrum integrative approach for cancer prevention and treatment

Targeted therapies and the consequent adoption of "personalized" oncology have achieved notablesuccesses in some cancers; however, significant problems remain with this approach. Many targetedtherapies are highly toxic, costs are extremely high, and most patients experience relapse after a fewdisease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistantimmortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are notreliant upon the same mechanisms as those which have been targeted). To address these limitations, aninternational task force of 180 scientists was assembled to explore the concept of a low-toxicity "broad-spectrum" therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspectsof relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a widerange of high-priority targets (74 in total) that could be modified to improve patient outcomes. For thesetargets, corresponding low-toxicity therapeutic approaches were then suggested, many of which werephytochemicals. Proposed actions on each target and all of the approaches were further reviewed forknown effects on other hallmark areas and the tumor microenvironment. Potential contrary or procar-cinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixedevidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of therelationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. Thisnovel approach has potential to be relatively inexpensive, it should help us address stages and types ofcancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for futureresearch is offered

Prediction of disability-free survival in healthy older people

Prolonging survival in good health is a fundamental societal goal. However, the leading determinants of disability-free survival in healthy older people have not been well established. Data from ASPREE, a bi-national placebo-controlled trial of aspirin with 4.7 years median follow-up, was analysed. At enrolment, participants were healthy and without prior cardiovascular events, dementia or persistent physical disability. Disability-free survival outcome was defined as absence of dementia, persistent disability or death. Selection of potential predictors from amongst 25 biomedical, psychosocial and lifestyle variables including recognized geriatric risk factors, utilizing a machine-learning approach. Separate models were developed for men and women. The selected predictors were evaluated in a multivariable Cox proportional hazards model and validated internally by bootstrapping. We included 19,114 Australian and US participants aged ≥65 years (median 74 years, IQR 71.6–77.7). Common predictors of a worse prognosis in both sexes included higher age, lower Modified Mini-Mental State Examination score, lower gait speed, lower grip strength and abnormal (low or elevated) body mass index. Additional risk factors for men included current smoking, and abnormal eGFR. In women, diabetes and depression were additional predictors. The biased-corrected areas under the receiver operating characteristic curves for the final prognostic models at 5 years were 0.72 for men and 0.75 for women. Final models showed good calibration between the observed and predicted risks. We developed a prediction model in which age, cognitive function and gait speed were the strongest predictors of disability-free survival in healthy older people. Trial registration Clinicaltrials.gov (NCT01038583)