Answering Complex Hierarchy Questions in Network Meta-analysis

Background: Network meta-analysis estimates all relative effects between competing treatments and can produce a treatment hierarchy from the most to the least desirable option according to a health outcome. While about half of the published network meta-analyses present such a hierarchy, it is rarely the case that it is related to a clinically relevant decision question.

Methods: We first define treatment hierarchy and treatment ranking in a network meta-analysis and suggest a simulation method to estimate the probability of each possible hierarchy to occur. We then propose a stepwise approach to express clinically relevant decision questions as hierarchy questions and quantify the uncertainty of the criteria that constitute them. The steps of the approach are summarized as follows: a) a question of clinical relevance is defined, b) the hierarchies that satisfy the defined question are collected and c) the frequencies of the respective hierarchies are added; the resulted sum expresses the certainty of the defined set of criteria to hold. We then show how the frequencies of all possible hierarchies relate to common ranking metrics.

Results: We exemplify the method and its implementation using two networks. The first is a network of four treatments for chronic obstructive pulmonary disease where the most probable hierarchy has a frequency of 28%. The second is a network of 18 antidepressants, among which Vortioxetine, Bupropion and Escitalopram occupy the first three ranks with frequency 19%.

Conclusions: The developed method offers a generalised approach of producing treatment hierarchies in network meta-analysis, which moves towards attaching treatment ranking to a clear decision question, relevant to all or a subset of competing treatments.