Seamless trials in oncology: A cross-sectional analysis of characteristics and reporting

Katarzyna Klas; Karolina Strzebonska; Paola Buedo; Alicja Włodarczyk; Samuel Gordon; Paulina Kaszuba; Maciej Polak; Marcin Waligora

doi:10.1371/journal.pone.0312797

Seamless trials in oncology: A cross-sectional analysis of characteristics and reporting

PLoS One. 2024 Dec 3;19(12):e0312797. doi: 10.1371/journal.pone.0312797. eCollection 2024.

Authors

Katarzyna Klas^{1

2}, Karolina Strzebonska¹, Paola Buedo¹, Alicja Włodarczyk¹, Samuel Gordon¹, Paulina Kaszuba¹, Maciej Polak^{1

3}, Marcin Waligora¹

Affiliations

¹ Faculty of Health Sciences, Research Ethics in Medicine Study Group (REMEDY), Jagiellonian University Medical College, Krakow, Poland.
² Doctoral School of Medical and Health Sciences, Jagiellonian University Medical College, Krakow, Poland.
³ Faculty of Health Sciences, Department of Epidemiology and Population Studies, Institute of Public Health, Jagiellonian University Medical College, Krakow, Poland.

Abstract

Objectives: Seamless clinical trials have received much attention as a possible way to expedite drug development. The growing importance of seamless design can be seen in oncology research, especially in the early stages of drug development. Our objective is to examine the basic characteristics of seamless early-phase oncology trials registered on the ClinicalTrials.gov database and to determine their results reporting rates. We also aim to identify factors associated with results reporting.

Methods: Cross-sectional study. We defined seamless early-phase trials as either those registered as Phase 1/2 or Phase 1 with planned expansion cohort(s). Using the ClinicalTrials.gov registry, we searched for interventional cancer clinical trials with primary completion date (PCD) 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. We used logistic regression to search for predictors of results reporting. Protocol: https://osf.io/m346x/.

Results: We included 1051 seamless early-phase oncology trials reported as completed (PCD) between 2016 and 2020. We provided descriptive statistics including the number of patients enrolled, study start date, primary completion date, funding, type of intervention, cancer type, design details, type of endpoints, recruitment regions, and number of trial sites. Overall, only 34.7% trials reported results on ClinicalTrials.gov. The results reporting rates for 24 months was 24.0%. The overall reporting rate for Phase 1/2 studies was over three times higher than for seamless Phase 1.

Conclusions: Our study provides cross-sectional data on seamless early-phase oncology trials registered on ClinicalTrials.gov. We highlight the challenges of the evolving clinical trial design landscape and the problem of missing results in the seamless design context, which raises serious ethical concerns. Efforts should be made to adapt the functionality of the ClinicalTrials.gov database to emerging clinical trial models.

Copyright: © 2024 Klas et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

MeSH terms

Clinical Trials as Topic
Clinical Trials, Phase I as Topic
Clinical Trials, Phase II as Topic / methods
Cross-Sectional Studies
Databases, Factual
Humans
Medical Oncology* / methods
Neoplasms* / drug therapy
Neoplasms* / therapy
Registries
Research Design

Grants and funding

This study was funded by the National Science Center, Poland, UMO-2021/41/B/HS1/01123 (www.ncn.gov.pl). Authors received the funding: MW, KK, KS, MP. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors received funding for the Open Access fee from the Strategic Programme Excellence Initiative of the Jagiellonian University.