Subgroup analysis in Haematologic Malignancies Phase III Clinical
Trials: A systematic review
Abstract
Aims: To assess the appropriateness of the use and interpretation of
subgroup analysis in haematology randomized clinical trials (RCT).
Method: A systematic review of Medline including Haematology phase III
RCT published between January 2013 and October 2019 was carried to
identify subgroup analysis reported. Information related to trials
characteristics, subgroup analysis reported and claims of subgroup
difference were collected. Results: A total of 98 studies reporting
subgroup analyses were identified. Of those, 24 RCT reported 46 claims
of subgroup difference. Among them, 44 were claims for the primary
outcome, of which 25 were considered strong claims and 17 were
considered suggestions of a possible effect. Authors included subgroup
variables for the primary outcome measured at baseline for 38 claims (n
= 86.36%), used subgroup variable as stratification factor at
randomization for 15 (34.09%), clearly prespecify their hypothesis for
11 (25%), the subgroup effect was one of a small number of hypothesised
effects tested for 17 (38.36%), carried out a test of interaction that
provide statistically significant for 18 (40.91%), documented
replication of a subgroup effect with previously related studies for 11
(25%), identify consistency of a subgroup effect across related outcome
for 10 (22.72%), and provided a biological rationale for the effect for
8 (18.18%). Of the 44 claims for the primary outcome, 34 (77.27%) met
4 or fewer of the 10 credibility criteria. Conclusion: Credibility of
subgroup claims reported in haematology RCT lack of credibility, even
when claims are strong. Information about subgroup difference should be
interpreted ca