Towards application of rule learning to the meta-analysis of clinical data: An example of the metabolic syndrome

Abstract 

Purpose

Systematic reviews and meta-analysis of published clinical datasets are important part of medical research. By combining results of multiple studies, meta-analysis is able to increase confidence in its conclusions, validate particular study results, and sometimes lead to new findings. Extensive theory has been built on how to aggregate results from multiple studies and arrive to the statistically valid conclusions. Surprisingly, very little has been done to adopt advanced machine learning methods to support meta-analysis.

Methods

In this paper we describe a novel machine learning methodology that is capable of inducing accurate and easy to understand attributional rules from aggregated data. Thus, the methodology can be used to support traditional meta-analysis in systematic reviews. Most machine learning applications give primary attention to predictive accuracy of the learned knowledge, and lesser attention to its understandability. Here we employed attributional rules, the special form of rules that are relatively easy to interpret for medical experts who are not necessarily trained in statistics and meta-analysis.

Results

The methodology has been implemented and initially tested on a set of publicly available clinical data describing patients with metabolic syndrome (MS). The objective of this application was to determine rules describing combinations of clinical parameters used for metabolic syndrome diagnosis, and to develop rules for predicting whether particular patients are likely to develop secondary complications of MS. The aggregated clinical data was retrieved from 20 separate hospital cohorts that included 12 groups of patients with present liver disease symptoms and 8 control groups of healthy subjects. The total of 152 attributes were used, most of which were measured, however, in different studies. Twenty most common attributes were selected for the rule learning process. By applying the developed rule learning methodology we arrived at several different possible rulesets that can be used to predict three considered complications of MS, namely nonalcoholic fatty liver disease (NAFLD), simple steatosis (SS), and nonalcoholic steatohepatitis (NASH).

Keywords: Machine learning, Knowledge representation, Meta-analysis, Metabolic syndrome, Adipokines, Clinical data