A review of studies examining the relationship between progression ...

Table 2 summarises the methods used within the individual studies to analyse the relationshipbetween PFS/TTP and OS. The analyses conducted fall into three broad categories. Four studies usedaggregate data from multiple trials to examine the relationship between PFS and OS for individualtrial arms. The methods for these studies are summarised in Section 4.1 with results presented inSection 4.3. Seven studies use IPD to examine the relationship between PFS and OS for individualpatients. The methods for these studies are summarised in Section 4.2 and the results in Section 4.3.Thirteen studies examined the trial level relationship between treatment effect on PFS and treatmenteffect on OS with three using IPD and the remaining using aggregate data from multiple trials. Theseare summarised in Section 5. The majority of papers examining trial level association betweenoutcomes report either rank correlation coefficients or linear regressions. Landmark analysis, 29 whichassesses the prognostic impact on future survival of being alive and progression free at various timepoints, has been used by many of the more recent papers which use IPD to examine the associationbetween outcomes at the individual level.4. STUDIES EXAMINING THE RELATIONSHIP BETWEEN OUTCOMESFOR INDIVIDUALS OR SINGLE TREATMENT ARMS4.1. METHODS IN STUDIES USING AGGREGATE DATA FROM MULTIPLE TRIALSFour papers reported the relationship between median PFS or TTP and median OS using aggregatedata from multiple trials. 13,22,25,27 Due to inconsistency in the definition of TTP, Chirilia et al 13conducted separate analysis for PFS, TTP and a composite outcome including both PFS and TTP.One study also examined the relationship between OS and survival post-progression which wasdefined as the difference in median PFS and median OS. 25Three papers report spearman ρcorrelation coefficients 13,22,27 and two report linear regressions 22,25 with the more recent paperweighting the regression by trial size. Three papers included a variety of first-line treatments and oneincluded first, second and third-line treatments. 13 One paper 25 conducted subgroup analysis to assesswhether the relationship varied according to the following factors; treatment type (platinum-based,molecular-targeted agents, old chemotherapeutic agents), whether OS was the primary endpoint, theyear of trial initiation and whether the publication was full text or abstract only. The other threepapers did not conduct any analysis to assess whether factors such as treatment type had an effect onthe relationship between PFS/TTP and OS.21