RANDOMIZATION IS AN INFREQUENTLY USED METHOD IN INTERVENTIONAL PHASE II CLINICAL TRIALS OF ADULT PATIENTS WITH LYMPHOMA

Abstract

Introduction: Clinical trials are important to inform decision making and to improve outcomes for patients with lymphoma. Phase II trials are designed to determine if a new treatment has enough promising efficacy and safety to warrant further investigation in a phase III trial. Randomized controlled trials have historically received the greatest consideration in providing reliable evidence of a drug's safety and efficacy. However, Single Arm Non-Randomized Studies (SANRS) have been considered as a valid option by regulators. It has been reported that 66% (49/74) of approvals granted between 1999 and 2014 from the European Medicines Agency (EMA) and U.S. Food and Drug Administration (FDA) were based on nonrandomized experiments in oncology including hematological malignancies, and lymphoma is one of the most common cancer types that has single arm FDA drug approval. The aim of this report is to evaluate the proportion and evolution in time of the use of randomization in interventional phase II clinical trials in adult patients with lymphoma, using a sample of the ClinicalTrials.govdatabase. Methods: We conducted a predefined search in the United States National Library of Medicine clinical trials database (ClinicalTrials.gov) in the field “condition or disease” for the term "lymphoma" with filters for "interventional studies", "phase 2 studies” and “adults = >18–64 years old” plus “older adults = 65 years and older”. We examined all clinical trials that met the inclusion criteria from January 1st, 2012, through December 31st, 2022. We excluded trials with overlapping terminology that did not enroll patients with mature lymphoid neoplasms, such as precursor b-lymphoblastic lymphoma/leukaemia, anaplastic lymphoma kinase (ALK) non-small-cell lung cancer and trials involving very broad disease categories such as “advanced cancer”, “hematological malignancies” or “high risk populations” with the exception when a significant proportion of patients with lymphoma was expected to be enrolled. Difficult cases were discussed and decided at the discretion of the authors. Results: Our search returned 2085 clinical trials, of those we included 1376 in the analysis according to our inclusion/exclusion criteria. We found that between 2012 and 2022 randomization was performed in 12.8% (177/1376) of interventional phase II clinical trials of adult patients with lymphoma. The histogram (Figure 1) shows that the number of trials increased during the analysis period, but the number of randomized clinical trials remained proportionally low. Keywords: therapeutics and clinical trials in lymphoma, other No conflicts of interests pertinent to the abstract.