Introduction
Subgroup analysis are important elements in the report of results of
randomized clinical trials (RCTs)1 -2. Clinical
practice guidelines (GPC) recommendations in haematology are guided by
phase III RCTs results. Usually only average results are reported in
RCTs and trial participants are frequently recruited from a
heterogeneous population. Subgroup analysis are born with the aim to
detect subgroup effects, in other words they have the aim of predicting
which patients will benefit more from therapies2-4.
Interpretation of subgroup
analysis is potentially important for treatment decisions in medical
practice. Subgroup analysis can provide clinicians with a better
perspective on the individualized treatment of patients, which is
particularly interesting in the field of haematology due to the lower
therapeutic index and higher toxicity of
used-drugs5-6. However, subgroup analysis can
introduce analytical challenges leading to misleading and exaggerated
results, which may result in denial of a beneficial treatment or even
receiving a potentially harmful or ineffective
treatment7-9.
Subgroups analysis have the potential to generate hypotheses for further
prospective investigation10, their exploratory nature
requires results to be confirmed in a new study to ensure their findings
with statistical reliability. However, confirmatory studies are
generally never carried out and decisions in clinical practice are made
with this lack of information. On the other hand, the option of
completely discarding subgroups analysis finding is also a decision that
has its consequences, and is especially controversial in situations with
very high risks or costs that are difficult to assume, which are not
uncommon in clinical practice11.
Concerns about the correct interpretation of subgroup analysis has
recently grown. With the intention of reducing the problems related to
subgroup analysis misinterpretation, several tools have been developed
to assess the credibility of the effects of subgroups reported in
RCTs12-17.
With the results of this study we will be able to determine if subgroup
analysis claims of phase III RCTs in haematology malignancies are
carried out correctly.
The main objective of this study is to assess the appropriateness of the
use and interpretation of subgroup analysis in recently published
haematologic malignancies RCTs. To achieve our objective the following
aspects will be evaluated:
1- To describe subgroups analysis and claims of subgroup effects.
2- To assess study characteristics of subgroup analyses.
3- To examine the analysis and interpretation of subgroup effects for
primary outcomes and to assess the credibility of subgroup claims using
“the 10 criteria for assessing the credibility of a subgroup claim” by
Sun et al 201217.