RESUMEN
OBJECTIVE: Accurate and consistent outcome assessment is essential to randomized clinical trials. We aimed to explore observer variation in the assessment of outcome in a recently completed trial of dexanabinol in head injury and to consider steps to reduce such variation. METHODS: Eight hundred sixty-one patients with severe traumatic brain injury who were admitted to 86 centers were included in a multicenter, placebo-controlled, Phase III trial. Outcome was assessed at 3 and 6 months postinjury using the extended Glasgow Outcome Scale; standardized assessment was facilitated by the use of a structured interview. Before initiation of trial centers, outcome ratings were obtained for sample cases to establish initial levels of agreement. Training sessions in outcome assessment were held, and problems in assigning outcome were investigated. During the trial, a process of central review was established to monitor performance. Interobserver variation was analyzed using the kappa statistic. RESULTS: Substantial observer variation was found in the rating of sample cases (weighted kappa, 0.72; confidence interval, 0.68-0.75) and in assigning outcome based on completed structured interviews (weighted kappa, 0.61; confidence interval, 0.57-0.64). In the early stages of the trial, a relatively large number of discrepancies (29-37%) were identified on central review. This number declined as the trial progressed and coincided with investigator training and feedback from central review. Centers with higher enrollment rates showed better performance. CONCLUSION: Observer variation in outcome assessment is a significant problem for head injury trials. Consistency can be improved by standardizing procedures, training assessors, and monitoring the quality of assessments and providing feedback to interviewers.
Asunto(s)
Lesiones Encefálicas/diagnóstico , Lesiones Encefálicas/epidemiología , Evaluación de Resultado en la Atención de Salud/métodos , Evaluación de Resultado en la Atención de Salud/estadística & datos numéricos , Medición de Riesgo/métodos , Adolescente , Adulto , Anciano , Lesiones Encefálicas/terapia , Femenino , Humanos , Internacionalidad , Masculino , Persona de Mediana Edad , Pronóstico , Reproducibilidad de los Resultados , Factores de Riesgo , Sensibilidad y Especificidad , Resultado del TratamientoRESUMEN
Outcome following traumatic brain injury (TBI) is not only dependent on the nature and severity of injury and subsequent treatment, but also on constituent characteristics of injured individuals. We aimed to describe and quantify the relationship between demographic characteristics and six month outcome assessed by the Glasgow Outcome Scale (GOS) after TBI. Individual patient data on age (n = 8719), gender (n = 8720), race (n = 5320), and education (n = 2201) were extracted from eight therapeutic Phase III randomized clinical trials and three surveys in moderate or severe TBI, contained in the IMPACT database. The strength of prognostic effects was analyzed with binary and proportional odds regression analysis and expressed as an odds ratio. Age was analyzed as a continuous variable with spline functions, and the odds ratio calculated over the difference between the 75 th and 25 th percentiles. Associations with other predictors were explored. Increasing age was strongly related to poorer outcome (OR 2.14; 95% CI 2.00-2.28) in a continuous fashion that could be approximated by a linear function. No gender differences in outcome were found (OR: 1.01; CI 0.92-1.11), and exploratory analysis failed to show any gender/age interaction. The studies included predominantly Caucasians (83%); outcome in black patients was poorer relative to this group (OR 1.30; CI 1.09-1.56). This relationship was sustained on adjusted analyses, and requires further study into mediating factors. Higher levels of education were weakly related to a better outcome (OR: 0.70; CI 0.52-0.94). On multivariable analysis adjusting for age, motor score, and pupils, the prognostic effect of race and education were sustained. We conclude that outcome following TBI is dependent on age, race, to a lesser extent on education, but not on gender.