Choice and Trade-offs: Parent Decision Making for Neurotechnologies for Pediatric Drug-Resistant Epilepsy.

This qualitative study investigated factors that guide caregiver decision making and ethical trade-offs for advanced neurotechnologies used to treat children with drug-resistant epilepsy. Caregivers with affected children were recruited to semi-structured focus groups or interviews at one of 4 major epilepsy centers in Eastern and Western Canada and the USA (n = 22). Discussions were transcribed and qualitative analytic methods applied to examine values and priorities (eg, risks, benefits, adherence, invasiveness, reversibility) of caregivers pertaining to novel technologies to treat drug-resistant epilepsy. Discussions revealed 3 major thematic branches for decision making: (1) features of the intervention-risks and benefits, with an emphasis on an aversion to perceived invasiveness; (2) decision drivers-trust in the clinical team, treatment costs; and (3) quality of available information about neurotechnological options. Overall, caregivers' definition of treatment success is more expansive than seizure freedom. The full involvement of their values and priorities must be considered in the decision-making process.

Novel Neurotechnological Interventions for Pediatric Drug-Resistant Epilepsy: Physician Perspectives.

This qualitative study investigated factors that guide physicians' choices for minimally invasive and neuromodulatory interventions as alternatives to conventional surgery or medical management for pediatric drug-resistant epilepsy. North American physicians were recruited to one of 4 focus groups at national conferences. Discussions were analyzed using qualitative content analysis. A pragmatic neuroethics framework was applied to interpret results. Discussions revealed 2 major thematic branches: (1) clinical decision making and (2) ethical considerations. Under clinical decision making, physicians emphasized scientific evidence and patient candidacy when assessing neurotechnologies for patients. Ongoing seizures without intervention was important for safety and neurodevelopment. Under ethical considerations, resource allocation, among other financial considerations for technology adoption, were considerable sources of pressure on decision making. Access to neurotechnology was a salient theme differentiating Canadian and American contexts. When assessing novel neurotechnological interventions for pediatric drug-resistant epilepsy, physicians balance clinical and ethical factors to guide decision making and best practice.

Multivariate meta-analysis of mixed outcomes: a Bayesian approach.

Multivariate random effects meta-analysis (MRMA) is an appropriate way for synthesizing data from studies reporting multiple correlated outcomes. In a Bayesian framework, it has great potential for integrating evidence from a variety of sources. In this paper, we propose a Bayesian model for MRMA of mixed outcomes, which extends previously developed bivariate models to the trivariate case and also allows for combination of multiple outcomes that are both continuous and binary. We have constructed informative prior distributions for the correlations by using external evidence. Prior distributions for the within-study correlations were constructed by employing external individual patent data and using a double bootstrap method to obtain the correlations between mixed outcomes. The between-study model of MRMA was parameterized in the form of a product of a series of univariate conditional normal distributions. This allowed us to place explicit prior distributions on the between-study correlations, which were constructed using external summary data. Traditionally, independent 'vague' prior distributions are placed on all parameters of the model. In contrast to this approach, we constructed prior distributions for the between-study model parameters in a way that takes into account the inter-relationship between them. This is a flexible method that can be extended to incorporate mixed outcomes other than continuous and binary and beyond the trivariate case. We have applied this model to a motivating example in rheumatoid arthritis with the aim of incorporating all available evidence in the synthesis and potentially reducing uncertainty around the estimate of interest.

Construct and criterion validity of the short form-6D utility measure in patients with systemic lupus erythematosus.

OBJECTIVE: Preference-based measures, such as the Short Form-6D (SF-6D), allow quality-adjusted life-years, used in cost-utility evaluations, to be calculated. We investigated the construct and criterion validity of the SF-6D in patients with systemic lupus erythematosus (SLE). METHODS: Female patients with SLE were recruited from outpatient clinics at 2 timepoints, 5 years apart. Cross-sectional correlation of the SF-6D with domains of the disease-specific LupusQol health-related quality of life (HRQOL) measure, the Systemic Lupus International Collaborating Clinics Damage Index (SDI; for damage) and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI; for activity) measures, and patient characteristics was tested. The ability to discriminate between groups defined by smoking status, presence/absence of carotid plaque, depression, and fatigue was tested using the t-test. RESULTS: In total 181 patients were recruited at baseline. The SF-6D correlated moderately to strongly with all domains of the LupusQoL (0.6-0.8) apart from intimate relationships (0.42) and body image (0.34). Correlations of the SF-6D with the demographic and disease-specific measures at baseline were small for the SDI score (-0.23) and age (-0.19) and in the expected direction. The SF-6D did not correlate with disease activity (SLEDAI -0.08). The SF-6D could distinguish those who smoked, had carotid plaque, had depression, and reported fatigue from those who did not, with the largest effect size being for depression (0.75). CONCLUSION: The SF-6D displays construct and criterion validity for use in patients with SLE, but the low correlation with aspects of intimate relationships and body image represents a concern and reinforces the need to collect disease-specific measures of HRQOL alongside generic preference-based instruments.

The relationship between social deprivation, disease outcome measures, and response to treatment in patients with stable, long-standing rheumatoid arthritis.

OBJECTIVE: Patients with rheumatoid arthritis (RA) with lower socioeconomic status (SES) are known to have more severe disease, more comorbidity, and higher mortality. It is not known whether SES influences response to treatment in RA. We examined the relationship between area of residence (as a surrogate for SES) and baseline outcome measures and response to treatment, using data from the British Rheumatoid Outcome Study Group randomized controlled trial of aggressive versus symptomatic treatment of long-standing, stable RA. METHODS: A total of 466 patients from 5 centers were recruited to the trial. Baseline data included age, sex, smoking status, and comorbidity. Patients were assigned a Townsend score (a measure of social deprivation) according to their area of residence. Outcome measures including the Disease Activity Score (DAS28), Health Assessment Questionnaire, Medical Outcomes Study Short Form-36, and EuroQol (EQ5D) were recorded at the beginning and end of the 3 year trial. The baseline, 3 year values, and change data were examined by Townsend quintile adjusting for each treatment arm. RESULTS: Significant relationships between increasing social deprivation by area of residence and higher disease activity, higher pain, poorer physical function, poorer emotional aspects of mental health, and lower quality of life were found at baseline (adjusted for age, sex, disease duration, current smoking, treatment center, and treatment group). During the 3 year trial period, patients from the most deprived areas showed greater improvement, with statistically significant greater improvement on DAS28 (p = 0.041) and 28 tender joint count (p = 0.015). CONCLUSION: Area of residence is related to the severity of RA at recruitment and is a predictor of response in a clinical trial situation. The results suggest that measures of SES should be recorded for patients enrolled in clinical trials, longitudinal observational studies, and in the clinical setting.