Related Experiment Video
Updated: Jun 7, 2026
Enumeration of Major Peripheral Blood Leukocyte Populations for Multicenter Clinical Trials Using a Whole Blood Phenotyping Assay
Published on: September 16, 2012
Trends in design of FDA registrational randomized clinical trials in hematology and oncology: a 20-year cohort study
Charles J Milrod1, Aidan Petrovich2, Wayne Liang3
1Department of Medicine, Division of Hematology and Oncology, Brown University Health, Providence, Rhode Island.
Introduction:
Registrational trials are clinical trials which are used to justify regulatory approval of a new medication by the FDA. However, clinical trials may not be designed around patient-centered outcomes, like overall survival or quality of life. This disconnect raises concerns about whether current trial designs are truly aligned with the long-term needs and priorities of patients. A comprehensive analysis of trial designs and endpoints is necessary to ensure that future oncologic therapies deliver meaningful clinical improvements. Our objective was to describe types of clinical trial design and primary endpoints used for registrational trials, and their trends over time.
Research Design And Methods:
In this cohort study, the HemOnc database was used to identify registrational trials supporting cancer drug approval from 2004 through 2023.Clinical trial design (escalation, de-escalation, in-class switch, out-of-class switch) and primary endpoint (overall survival; time-to-event including progression free survival; response-based endpoint).
Results:
Escalation trial designs were more common than in-class switches or out-of-class switches. De-escalation and mixed designs were exceedingly rare. The most common primary endpoint was a composite time-to-event endpoint.
Conclusion:
Most clinical trials leading to FDA approval for cancer-directed therapies employ escalation designs with composite time-to-event endpoints. Designs reflecting paradigm shifts in therapy (in-class switches and out-of-class switches) are sparsely used. This approach raises the concern that trials may increase therapeutic toxicity without delivering meaningful improvements in overall survival or quality of life.
Insights
Most cancer drug approval trials use escalation designs and time-to-event endpoints, potentially increasing toxicity without guaranteed patient benefit. Patient-centered outcomes need better integration into clinical trial design for meaningful improvements.
Area of Science:
- Oncology
- Clinical Trial Design
- Regulatory Science
Background:
- Registrational trials support FDA approval for new cancer medications.
- Current trial designs may not prioritize patient-centered outcomes like survival or quality of life.
- Ensuring alignment between trial designs and patient needs is crucial for meaningful therapeutic advancements.
Purpose of the Study:
- To analyze clinical trial designs and primary endpoints in cancer drug approvals.
- To identify trends in these designs and endpoints over time.
- To assess the alignment of trial methodologies with patient-centered goals.
Main Methods:
- A cohort study analyzing registrational trials from the HemOnc database (2004-2023).
- Categorization of trial designs (escalation, de-escalation, in-class switch, out-of-class switch).
- Classification of primary endpoints (overall survival, time-to-event including progression-free survival, response-based).
Main Results:
- Escalation designs were most prevalent, while de-escalation and mixed designs were rare.
- Composite time-to-event endpoints were the most frequently used primary endpoint.
- In-class and out-of-class switch designs, representing therapeutic shifts, were sparsely utilized.
Conclusions:
- The majority of cancer therapy registrational trials utilize escalation designs with composite time-to-event endpoints.
- Limited use of designs reflecting therapeutic paradigm shifts raises concerns.
- Current trial structures may risk increased toxicity without guaranteed improvements in overall survival or quality of life.
More Related Videos
04:53A Clinical Trial Assessing the Safety, Efficacy, and Delivery of Olive-Oil-Based Three-Chamber Bags for Parenteral Nutrition
Published on: September 20, 2019
07:40Preparation of Peripheral Blood Mononuclear Cell Pellets and Plasma from a Single Blood Draw at Clinical Trial Sites for Biomarker Analysis
Published on: March 20, 2021
Related Concept Videos
02:20Longitudinal Research
01:16Clinical Trials
There are four phases in a clinical trial. A phase one...
01:11Clinical Trials: Overview
01:15Bioavailability Study Design: Healthy Subjects Versus Patients
01:28Dosage Regimens: Designs and Approaches
01:20Study Designs in Epidemiology
Observational studies are those where the researcher does not intervene but rather observes natural variations. They include cross-sectional, cohort, and case-control studies.