Methods for network meta-analysis of continuous outcomes using individual patient data: a case study in acupuncture for chronic pain

Pedro Saramago, Beth Woods, Helen Weatherly, Andrea Manca, Mark Sculpher, Kamran Khan, Andrew J Vickers, Hugh MacPherson, Pedro Saramago, Beth Woods, Helen Weatherly, Andrea Manca, Mark Sculpher, Kamran Khan, Andrew J Vickers, Hugh MacPherson

Abstract

Background: Network meta-analysis methods, which are an extension of the standard pair-wise synthesis framework, allow for the simultaneous comparison of multiple interventions and consideration of the entire body of evidence in a single statistical model. There are well-established advantages to using individual patient data to perform network meta-analysis and methods for network meta-analysis of individual patient data have already been developed for dichotomous and time-to-event data. This paper describes appropriate methods for the network meta-analysis of individual patient data on continuous outcomes.

Methods: This paper introduces and describes network meta-analysis of individual patient data models for continuous outcomes using the analysis of covariance framework. Comparisons are made between this approach and change score and final score only approaches, which are frequently used and have been proposed in the methodological literature. A motivating example on the effectiveness of acupuncture for chronic pain is used to demonstrate the methods. Individual patient data on 28 randomised controlled trials were synthesised. Consistency of endpoints across the evidence base was obtained through standardisation and mapping exercises.

Results: Individual patient data availability avoided the use of non-baseline-adjusted models, allowing instead for analysis of covariance models to be applied and thus improving the precision of treatment effect estimates while adjusting for baseline imbalance.

Conclusions: The network meta-analysis of individual patient data using the analysis of covariance approach is advocated to be the most appropriate modelling approach for network meta-analysis of continuous outcomes, particularly in the presence of baseline imbalance. Further methods developments are required to address the challenge of analysing aggregate level data in the presence of baseline imbalance.

Keywords: Analysis of covariance; Continuous outcome; Evidence synthesis; Heterogeneity; Individual-patient data; Mixed treatment comparisons; Network meta-analysis.

Figures

Fig. 1
Fig. 1
Network of RCTs. Legend: In the network, a unique treatment category is indicated by a circle. Arrows between circles indicate that these treatments have been compared in a trial (trials are identified using ‘[]’, numbered according to column ‘ID’ in Table 1. (Pain groups: H – Headache/migraine; MSK – Musculoskeletal; OAK – Osteoarthritis of the knee)
Fig. 2
Fig. 2
Forest plot showing network meta-analysis results for standardised pain and EQ-5D outcomes

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