Related Experiment Video
Updated: May 25, 2026
05:10
Drug Repurposing Hypothesis Generation Using the "RE:fine Drugs" System
Published on: December 11, 2016
Resampling phase III data to assess phase II trial designs and endpoints
Manish R Sharma1, Theodore G Karrison, Yuyan Jin
1Departments of Medicine and Health Studies, University of Chicago, Chicago, Illinois, USA.
Summary
For growth inhibitory agents in metastatic renal cancer, a randomized phase II trial using the log ratio of tumor sizes is more powerful than single-arm designs or those using progression-free survival to predict phase III outcomes.
Area of Science:
- Oncology
- Clinical Trial Design
- Biostatistics
Background:
- The optimal phase II clinical trial design and endpoint for evaluating growth inhibitory agents remain debated.
- Predicting phase III outcomes from phase II trials is crucial for drug development efficiency.
Purpose of the Study:
- To compare the predictive power of various phase II trial designs and endpoints for growth inhibitory agents.
- To evaluate the ability of different designs to predict known phase III results in metastatic renal cancer.
Main Methods:
- Simulated 5,000 phase II trials by resampling patients from positive (sorafenib) and negative (AE941) phase III trials in metastatic renal cancer.
- Assessed single-arm and randomized designs using endpoints such as response rate (RR) by RECIST, mean log ratio of tumor sizes, and progression-free survival (PFS) at 90 days (PFS-90) and overall PFS.
Main Results:
- Single-arm trials showed a 55% positive prediction rate for sorafenib and 1% for AE941 using RR by RECIST.
- Randomized trials (20 patients/arm) demonstrated higher positive prediction rates: RR by RECIST (55% vs 7%), log ratio (88% vs 25%), PFS-90 (64% vs 15%), and overall PFS (69% vs 9%) for sorafenib vs AE941, respectively.
Conclusions:
- The randomized phase II design with the log ratio endpoint offers superior power to predict positive phase III results (sorafenib).
- This design also exhibits a higher false positive rate for negative phase III results (AE941) compared to single-arm designs or those using overall PFS.
Related Concept Videos
01:11Clinical Trials: Overview
Clinical development focuses on how the drug will interact with the human body and encompasses four key phases of clinical trials, each serving a specific purpose in assessing the safety and effectiveness of new drugs. These phases overlap and build upon one another. Phase I involves a small group of healthy volunteers (typically 20-80 individuals) or, in cases where significant toxicity is expected, patients with the targeted disease, such as cancer or AIDS. The volunteers are tested for...
01:16Clinical Trials
Clinical trials are prospective experimental studies conducted on humans to determine the safety and efficacy of treatments, drugs, diet methods, and medical devices. Using statistics in clinical trials enables researchers to derive reasonable and accurate conclusions from the collected data, allowing them to make wise decisions in uncertain situations. In medical research, statistical methods are crucial for preventing errors and bias.
There are four phases in a clinical trial. A phase one...
There are four phases in a clinical trial. A phase one...
01:15Bioequivalence Experimental Study Designs: Repeated Measures, Cross-Over, Carry-Over, and Latin Square Designs
Bioequivalence experimental study designs play a pivotal role in testing the effectiveness of various treatments. Key among these are the repeated measures, cross-over, carry-over, and Latin square designs. In the repeated measures design, each subject receives all treatments, allowing for temporal comparisons. This type of design is useful in reducing variability but requires careful planning to avoid bias.The cross-over design, an economical method, involves sequential administration of...
01:23Types of Biopharmaceutical Studies: Controlled and Non-Controlled Approaches
Biopharmaceutical studies constitute a vital field aiming to enhance drug delivery methods and refine therapeutic approaches, drawing upon diverse interdisciplinary knowledge. In research methodologies, the choice between controlled and non-controlled studies significantly influences the study's reliability and accuracy.
Non-controlled studies, commonly employed for initial exploration, lack a control group, rendering them susceptible to biases and external influences. In contrast, controlled...
Non-controlled studies, commonly employed for initial exploration, lack a control group, rendering them susceptible to biases and external influences. In contrast, controlled...
01:28Preclinical Development: Overview
Preclinical development consists of a series of tests that ensure the safety and efficacy of a new therapeutic compound before it is tested in humans. There are four main phases to this process. First, safety pharmacology tests are conducted to ensure the drug does not produce any acutely harmful effects. These tests examine parameters such as bronchoconstriction, cardiac dysrhythmias, blood pressure changes, and ataxia. Next, preliminary toxicological testing is performed to determine the...
01:20Bioequivalence Experimental Study Designs: Completely Randomized and Randomized Block Designs
Bioequivalence experimental study designs are crucial methodologies used in evaluating and comparing the bioavailability of different drug products. These designs are categorized into various types: completely randomized, randomized block, repeated measures, cross and carry-over, and Latin square designs.Completely randomized designs involve randomly allocating treatments to all subjects participating in the experiment. This allocation is achieved by assigning unique random numbers to subjects...