Characteristics and Reporting of Seamless Early-Phase Trials in Oncology - A Cross-Sectional Analysis of Trials Registered on ClinicalTrials.gov

Article type
Authors
Klas K1, Strzebonska K1, Buedo P1, Wlodarczyk A1, Gordon S1, Kaszuba P2, Polak M3, Waligora M1
1Research Ethics in Medicine Study Group (REMEDY), Faculty of Health Sciences, Jagiellonian University Medical College, Krakow, Poland
2Research Ethics in Medicine Study Group (REMEDY), Faculty of Health Sciences, Jagiellonian University Medical College
3Research Ethics in Medicine Study Group (REMEDY), Faculty of Health Sciences, Jagiellonian University Medical College, Krakow, Poland; Department of Epidemiology and Population Studies, Institute of Public Health, Faculty of Health Sciences, Jagiellonian University Medical College, Krakow, Poland
Abstract
Background: The seamless clinical trial has received much attention as a possible way to accelerate drug development. A seamless clinical trial typically combines two different stages of the drug development process to address multiple objectives that are traditionally addressed in separate trials. The growing importance of seamless design can be seen in oncology research, especially in the early stages of drug development.

Objectives: Our objective is to examine the basic characteristics of seamless early-phase oncology trials that are registered on the ClinicalTrials.gov database. We also aim to determine their results reporting rates and identify factors associated with faster results reporting.

Methods: This cross-sectional meta-research study follows a pre-specified protocol available on the Open Science Framework website (https://osf.io/m346x/). We defined seamless early-phase trials as phase 1/2 trials or phase 1 trials with planned expansion cohort(s). Using the ClinicalTrials.gov registry, we searched for interventional cancer clinical trials completed between 2016 and 2020. After trial selection, we performed manual data extraction based on the trial record description and the results posted in the trial registry.

Results: We included 1051 seamless early-phase oncology trials that were completed between 2016 and 2020, including 562 (53,5%) phase 1 trials with planned expansion cohort(s) and 489 (46,5%) trials registered as phase 1/2. We provided descriptive statistics including the number of patients enrolled, study start date, primary completion date, funding, type of intervention and tumor type, design details and type of endpoints, recruitment regions, and number of trial sites. We found that only 365 of 1051 trials (34,7%) reported results on the ClinicalTrials.gov. The reporting rates were 9,6% for 12 months and 69,0% for 24 months after the primary completion date. The median (IQR) follow-up of results reporting was 518 (389) days.

Conclusions: Our study provides cross-sectional data on seamless early-phase oncology trials registered on the ClinicalTrials.gov registry. We highlight the challenges of the evolving clinical trial design landscape and the problem of missing results.