Data extraction
For data extraction additional sources referenced in the included study
(i.e., trial register, published protocol and online supplements) were
used. Data were extracted and entered in a structured Microsoft Excel
(Redmond, WA, USA) database.
Eligible RCTs were evaluated to determine whether a subgroup analysis
was reported. A subgroup analysis was defined as a statistical analysis
that explores whether effects of the intervention differ according to
status of a subgroup variable. A subgroup effect was defined as a
difference in the magnitude of a treatment effect across a group of a
study population16. For each RCT reporting subgroup
analysis and subgroup claims the following information was collected:
- Trial characteristics: information on funding source, year and
journal of publication, journal impact factor (<10 o
>10), haematological malignancy type, disease status
(naive/untreated or refractory/relapse), type of intervention
(chemotherapy, immunotherapy or haematopoietic transplant),centre
(multicentric or unicentric), trial design (parallel, cross-over or
factorial), trial type (superiority, non-inferiority or equivalence),
allocation concealment, blinding of patients, number of patients
recruited and randomized for the trial and number of treatment arms.
The primary endpoint was categorized according to whether results were
statistically significant and the type of outcome variable
(time-to-event, binary, continuous or count).
- Reporting of subgroup analysis : number of subgroup factors,
type of subgroup factors (clinical factors or biomarkers), number of
subgroup analysis and outcomes for subgroup analysis reported, forest
plots used, prespecify or post hoc subgroup, statistical method used
to assess heterogeneity of the treatment effect (descriptive only,
subgroup P values and confidence interval or interaction test).
A subgroup factor was defined as each of the subgroup analysed in the
RCT (i.e. sex, age, presence of a mutation).
Claims of subgroup effects: Subgroup claims mode of
presentation (abstract or text only), number of subgroup claims,
subgroup variable (primary or secondary outcome) and number of
outcomes for subgroup claims were recorded. A subgroup effect was
considered claimed when the authors states in the abstract or
discussion that the effect of intervention differs between the
categories of the subgroup variable. Claims of subgroup effect were
classified according to the strength of the claim into 3 categories:
Strong claim, claim of a likely effect or suggestion of a possible
effect based on Sun et al 2009 clasification16(Appendix B). To evaluate the credibility of subgroup claims for
primary outcomes “the 10 criteria for assessing the credibility of a
subgroup claim” by Sun et al 201217 were applied
(Appendix C). These criteria have been widely
used13-15,17 and are recommended for assessing how
much confidence to place in subgroup analyses19. If
the subgroup claim met less than half of criteria, the credibility of
this claim was considered low.