Individual participant data meta-analysis of prognostic factor studies: state of the art?

Abstract

Background: Prognostic factors are associated with the risk of a subsequent outcome in people with a given disease or health condition. Meta-analysis using individual participant data (IPD), where the raw data are synthesised from multiple studies, has been championed as the gold-standard for synthesising prognostic factor studies. We assessed the feasibility and conduct of this approach.

Methods: A systematic review to identify published IPD meta-analyses of prognostic factors studies, followed by detailed assessment of a random sample of 20 articles published from 2006. Six of these 20 articles were from the IMPACT (International Mission for Prognosis and Analysis of Clinical Trials in traumatic brain injury) collaboration, for which additional information was also used from simultaneously published companion papers.

Results: Forty-eight published IPD meta-analyses of prognostic factors were identified up to March 2009. Only three were published before 2000 but thereafter a median of four articles exist per year, with traumatic brain injury the most active research field. Availability of IPD offered many advantages, such as checking modelling assumptions; analysing variables on their continuous scale with the possibility of assessing for non-linear relationships; and obtaining results adjusted for other variables. However, researchers also faced many challenges, such as large cost and time required to obtain and clean IPD; unavailable IPD for some studies; different sets of prognostic factors in each study; and variability in study methods of measurement. The IMPACT initiative is a leading example, and had generally strong design, methodological and statistical standards. Elsewhere, standards are not always as high and improvements in the conduct of IPD meta-analyses of prognostic factor studies are often needed; in particular, continuous variables are often categorised without reason; publication bias and availability bias are rarely examined; and important methodological details and summary results are often inadequately reported.

Conclusions: IPD meta-analyses of prognostic factors are achievable and offer many advantages, as displayed most expertly by the IMPACT initiative. However such projects face numerous logistical and methodological obstacles, and their conduct and reporting can often be substantially improved.

Figure 1

An IPD meta-analysis of whether microvessel density is a prognostic factor for death in patients with non-metastatic surgically treated non-small-cell lung carcinoma, as undertaken by Trivella et al.[14]. The forest plot shows the individual study hazard ratio estimates (with confidence intervals), which indicate the association between risk of death and an increase of ten microvessel counts, as assessed by measurement of all vessels. A random-effects meta-analysis was used to combine estimates (I² = 73.7%), and the overall hazard ratio shown is thus the estimated average of all the underlying hazard ratios across studies.

Figure 2

Details of the search and classification of IMPF articles.

Figure 3

Number of published IMPF articles over time (NB no articles were identified in 2009 up to the start of March, when our review was conducted); the spike in 2007 is due to eight articles[28-35]from the IMPACT collaboration being published simultaneously within the Journal of Neurotrauma.

Figure 4

The number of studies for which IPD was requested and obtained in each of the nine IMPF articles using a literature review to identify relevant studies.