Health Technology Assessments (HTAs) and guidelines often meta-analyze non-binary outcomes, such as continuous and time-to-event outcomes, in order to elucidate the observed effect of a health intervention. However, these types of outcomes may require more sophisticated analysis and modeling techniques, making it more difficult to be synthesized by authors with limited statistical knowledge or resources.
A newly published review by Freeman and colleagues aimed to describe the use and presentation of these outcomes, and in doing so, identify potential challenges and facilitators to improving their application in future publications. The study analyzed a total of 25 technology appraisals and 15 guidelines from the UK’s National Institute for Health Care Excellence (NICE) and 7 HTA reports from the National Institute of Health Research (NIHR) for a total of 47 documents using meta-analyses (MA), network meta-analyses (NMA), or a combination of the two.
About half (51%) of the items reported at least one continuous outcome, while just over half (55%) reported at least one time-to-event outcome. Continuous outcomes were most commonly presented as a mean difference (MD). The most commonly used time-to-event outcomes were overall and progression-free survival, presented as a hazard ratio. Notably, no articles reported the methods used to handle multiplicity of either continuous or time-to-event outcomes. The existence of multiple time-points was largely handled by presenting multiple separate meta-analyses analyzing the appropriate time-points against one another.
Although most of the analyzed documents provided a decision model based on continuous or time-to-event outcomes, but many of them were based on the results of a single trial only, despite the fact that meta-analyses were undertaken.
|Reporting of Decision Models Across Publications Using Continuous Outcomes. Click to enlarge.|
|Reporting of Decision Models Across Publications Using Time-to-Event Outcomes. Click to enlarge.|
The authors present a list of the key challenges faced by authors of meta-analyses using these outcomes, such as the use of continuous outcomes that are reported with different scales, the multiplicity of related outcomes from the same study or various time-points in time-to-event outcomes, and nonproportional hazards (hazards that change over the course of time) in time-to-event outcomes. They present the following suggestions for better managing these issues:
- Increased availability of statistical expertise on MA and NMA teams
- Development of user-friendly software that allows users to approach more complex statistical techniques – for instance, those that allow for multiple outcomes from the same study to be analyzed simultaneously – with the same ease and accessibility as a point-and-click software such as RevMan.
- Increased reporting of outcomes within individual trials, as well as the reporting of individual patient data by trial authors.
Freeman, S.C., Sutton, A.J., & Cooper, N.J. Update of methodological advances for synthesis of continuous and time-to-event outcomes would maximize use of evidence base. J Clin Epidemiol, 2020; 124: 94-105.
Manuscript available from publisher's website here.