Claims of subgroup effects
Characteristics of subgroup claims are listed in table 3. In 24 RCTs authors claim heterogeneity of treatment effect of at least one subject subgroup, 13 made a claim for a primary outcome, 2 for secondary outcomes and 9 for both primary and secondary outcomes. Six (25.00%) of these RCTS presented subgroup claims in the articles abstract and five (20.83%) were based on significant interaction tests, whereas the claims were based only on within-subgroup comparisons for most of trials (54.17%; n = 13). More than one subgroup claim was made in 54.17% (n = 13) of trials.
A total of 46 subgroup difference were claimed in these 24 trials (44 for primary outcomes and 2 for secondary outcomes). These claims were classified as 26 (59.10%) strong claims, two (4.54%) as claims of a likely effect and 18 (40.91%) as suggestion of a possible effect.
Respect to the 10 criteria to assess credibility of subgroups claims (table 4): Authors included subgroup variables for the primary outcome measured at baseline for 38 claims (86.36%), used subgroup variable as stratification factor at randomization for 14 (34.09%) claims, clearly prespecify their hypothesis for 11 (25.00%) claims, correctly prespecify direction for 5 (11.36%) claims, tested a small number of hypothesis for 17 (38.63%) claims, carried out a test of interaction that provide statistically significant for 18 (40.91%) claims, documented replication of a subgroup effect with previously related studies for 11 (25.00%) claims, identify consistency of a subgroup effect across related outcome for 10 (22.72%) claims, and provided a biological rationale for the effect for 8 (18.18%) claims. Of the 44 claims for the primary outcomes, 34 (77.27%) met 4 or fewer of the 10 criteria. For strong claims, 15 (60.00 %) met three or less criteria and only 6 (24.00%) met more than 5 criteria.
Risk of Bias Graphs Within Studies and across studies is available at supplemental material (Appendix D).