Background

As the landscape of haematological malignancies dramatically changes due to diagnostic and therapeutic advances, it is important to evaluate trends in clinical trial designs. The objective of our study was to describe the design of clinical trials for five common haematological malignancies with respect to randomisation and end-points. We also aimed to assess trends over time and examine the relationships of funding source and country of origin to proportions of randomisation and utilisation of clinical end-points.

Methods

This systematic review identified haematological malignancy clinical trials starting in 2015-2020 registered at ClinicalTrials.gov as of 20th February 2021. Trial-related variables including randomisation status, type of primary end-point, and both projected and actual enrolment numbers were captured. Clinical end-points were defined as overall survival and quality of life, while surrogate end-points included all other end-points.

Results

Of 2609 relevant trials included in this analysis, only one-fifth were randomised (538, 21%), with a significant decrease in the proportion of randomised clinical trials from 26% of trials in 2015 to 19% in 2020 (p < 0.00001). Between the years 2015 and 2020, the proportion of randomised trials for all haematological malignancies using primary surrogate end-points remained relatively consistent, ranging from 84% in 2015 to 78% in 2020 (p = 0.352). Overall, only 15% of trials utilised primary end-points of overall survival or quality of life in a randomised design.

Conclusions

This systematic review of haematological malignancy trials found that the majority of trials are non-randomised and that there has been an increase in the ratio of non-randomised to randomised studies over time. The vast majority of randomised haematological malignancy trials use surrogate primary end-points.