Extending methods for investigating the relationship between treatment effect and baseline risk from pairwise meta-analysis to network meta-analysis.

Baseline risk is a proxy for unmeasured but important patient-level characteristics, which may be modifiers of treatment effect, and is a potential source of heterogeneity in meta-analysis. Models adjusting for baseline risk have been developed for pairwise meta-analysis using the observed event rate in the placebo arm and taking into account the measurement error in the covariate to ensure that an unbiased estimate of the relationship is obtained. Our objective is to extend these methods to network meta-analysis where it is of interest to adjust for baseline imbalances in the non-intervention group event rate to reduce both heterogeneity and possibly inconsistency. This objective is complicated in network meta-analysis by this covariate being sometimes missing, because of the fact that not all studies in a network may have a non-active intervention arm. A random-effects meta-regression model allowing for inclusion of multi-arm trials and trials without a 'non-intervention' arm is developed. Analyses are conducted within a Bayesian framework using the WinBUGS software. The method is illustrated using two examples: (i) interventions to promote functional smoke alarm ownership by households with children and (ii) analgesics to reduce post-operative morphine consumption following a major surgery. The results showed no evidence of baseline effect in the smoke alarm example, but the analgesics example shows that the adjustment can greatly reduce heterogeneity and improve overall model fit.

The use and reporting of WOMAC in the assessment of the benefit of physical therapies for the pain of osteoarthritis of the knee: findings from a systematic review of clinical trials.

OBJECTIVE: For the purposes of meta-analysis and network meta-analysis, the use of standard outcome measures is ideal. In OA research, the WOMAC was developed as an OA-specific measure of disability. It includes a pain subscale. In 1994 a consensus meeting recommended the use of WOMAC as a primary measure of efficacy in OA. In the context of a review of the efficacy of physical interventions for the relief of the pain of OA of the knee, we investigated the use of WOMAC. METHODS: A systematic review (December 2009-January 2010) identified trials that used the WOMAC outcome. These were investigated for correct use and clear reporting of the WOMAC pain subscale and the WOMAC index. RESULTS: The WOMAC pain subscale was used in 45% of the 134 trials. Reporting of the exact method of administering the WOMAC pain subscale was poor in many cases: in 53% of trials the reporting of the type of WOMAC scale used was inadequate; the score range was reported ambiguously in 38% of trials, with a further 10% being completely unclear. Similar less than optimal reporting of the WOMAC index was found. CONCLUSION: Poor reporting of both the WOMAC pain subscale and the WOMAC index resulted in significant uncertainty in the interpretation of the results of individual trials and limited their contribution to evidence synthesis. Improved adherence with the standard use of the WOMAC scoring system, with clear reporting of it in trials of OA of the knee should be encouraged.

Economic evaluation of enhanced staff contact for the promotion of breastfeeding for low birth weight infants.

OBJECTIVES: There is evidence that breastmilk feeding reduces mortality and short and long-term morbidity among infants born too soon or too small. The aim of this study was to evaluate the cost-effectiveness of enhanced staff contact for mothers with infants in a neonatal unit with a birth weight of 500-2,500 g from the perspective of the UK National Health Service. METHODS: A decision-tree model linked clinical outcomes with long-term health outcomes. The study population was divided into three weight bands: 500-999 g, 1000-1,749 g, and 1,750-2,500 g. Clinical and resource use data were obtained from literature reviews. The measure of benefit was quality-adjusted life-years. Uncertainty was evaluated using cost-effectiveness acceptability curves and sensitivity analyses. RESULTS: The intervention was less costly and more effective than the comparator in the base-case analysis for each birth weight group. The results were quite robust to the sensitivity analyses performed. CONCLUSIONS: This is the first economic evaluation in this complex field and offers a model to be developed in future research. The results provide preliminary indications that enhanced staff contact may be cost-effective. However, the limited evidence available, and the limited UK data in particular, suggest that further research is required to provide results with confidence.