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.