Publication of FAME Methodology

Our framework for prospective, adaptive meta-analysis (FAME), has helped produce more timely, thorough, and reliable evaluations of the effects of therapies for metastatic prostate cancer. A detailed description of the methods has now been published in PloS Medicine, which are illustrated using our STOPCAP meta-analyses.

The vast majority of systematic reviews are planned retrospectively, once most eligible trials have completed and reported, and are based on aggregate data that can be extracted from publications. Prior knowledge of trial results can introduce bias into both review and meta-analysis methods, and the omission of unpublished data can lead to reporting biases.

We demonstrate how FAME can produce evaluations of treatment effects that are less prone to bias than conventional retrospective approaches, and produce potentially definitive meta-analysis results months or years ahead of all trial results being available.

Additionally, we describe how working with trial investigators means that we gain access to better quality aggregate data, allowing more consistent, reliable, and thorough analyses than are usually possible. It also allows us to coordinate publication of meta-analysis and trials results potentially increasing the visibility and impact of each.

Jayne Tierney, who led the development of FAME commented “Less bias, better data and more timely results. I really believe that a collaborative and prospective approach should be the standard for aggregate data meta-analysis. I wish we had started doing it a long time ago!”.

To our knowledge, FAME represents the first prospective and collaborative approach to aggregate data meta-analysis. Now, similar prospective meta-analyses are being used to balance speed with rigour in the evaluation of COVID-19 therapies.

Indeed on the 7th July 2021, the World Health Organisation Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group published a collaborative prospective meta-analysis showing the benefits of the IL-6 antagonists, tocilizumab and sarilumab, for patients with severe COVID-19.

Claire Vale, Peter Godolphin, David Fisher and Jayne Tierney of the STOPCAP Programme Management Group were key members of The REACT Working Group.  Claire Vale commented “I think we have moved into a new era.  We can no longer wait for trial results to be reported before we think about starting a systematic review….I don’t believe we should ever again start a new systematic review at arm’s length from those who know the disease, the trials and the broader implications.” Read more from Claire in her Blog reflecting on the process.