Related Experiment Video

Updated: Jan 23, 2026

In Silico Clinical Trials for Cardiovascular Disease
09:09

In Silico Clinical Trials for Cardiovascular Disease

Published on: May 27, 2022

2.2K

Factors Affecting Combination Trial Success (FACTS): Investigator Survey Results on Early-Phase Combination Trials

Channing J Paller1, Erich P Huang2, Thomas Luechtefeld3

  • 1Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, United States.

Frontiers in Medicine
|June 20, 2019
PubMed

Insights

Most experimental cancer drug combinations fail early trials. However, investigator-perceived "clinical promise" in phase 1 trials significantly boosts advancement toward regulatory approval, suggesting subjective assessment aids drug development.

Area of Science:

  • Oncology
  • Clinical Trials
  • Drug Development

Background:

  • Experimental cancer therapeutics are often combined to overcome tumor resistance.
  • However, most combination trials show insufficient safety and efficacy for advancement.
  • Early-phase combination trials face significant hurdles in demonstrating clinical benefit.

Purpose of the Study:

  • To evaluate the trial design and regulatory progression of early-phase oncology combination therapy trials.
  • To identify factors associated with successful advancement of combination agents through clinical development.
  • To assess concordance of trial designs with Clinical Trial Design Task Force (CTD-TF) recommendations.

Main Methods:

  • Survey data collected from Principal Investigators (PIs) of phase 1 combination therapy trials (2003-2017).
  • Analysis of trial progression rates to phase 2, phase 3, and regulatory approval.
  • Assessment of study design concordance with CTD-TF recommendations and impact of 'clinical promise' on outcomes.

Main Results:

  • Only 24.9% of phase 1 combination trials progressed to phase 2 or further; 18.7% reached phase 3 or regulatory approval.
  • Investigator-defined "clinical promise" was strongly associated with higher advancement rates (cumulative OR = 11.9; p = 0.0002).
  • Phase 1 trial designs showed high concordance (79.6%) with CTD-TF Recommendations, with most deviations in trials lacking expected PK/PD interactions.

Conclusions:

  • Investigator assessment of "clinical promise" in early-phase combination trials is a significant predictor of successful progression.
  • While trial designs generally align with recommendations, awareness may be needed for optimizing designs when pharmacokinetic or pharmacodynamic interactions are not anticipated.
  • Improving early-phase combination trial strategies could enhance the translation of novel therapeutics to approved cancer treatments.
Keywords:
clinical trialscombination therapydrug combinationsearly phasephase 1 trialsregulatory approvaltrial design

More Related Videos

Small-Cage Laboratory Trials of Genetically-Engineered Anopheline Mosquitoes07:45

Small-Cage Laboratory Trials of Genetically-Engineered Anopheline Mosquitoes

Published on: May 1, 2021

3.1K
Enumeration of Major Peripheral Blood Leukocyte Populations for Multicenter Clinical Trials Using a Whole Blood Phenotyping Assay14:45

Enumeration of Major Peripheral Blood Leukocyte Populations for Multicenter Clinical Trials Using a Whole Blood Phenotyping Assay

Published on: September 16, 2012

15.5K

Related Concept Videos

Clinical Trials01:16

Clinical 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...
10.2K
Clinical Trials: Overview01:11

Clinical 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...
4.7K
Trial and Error and Algorithm01:12

Trial and Error and Algorithm

A problem-solving strategy is a plan of action used to find a solution. Different strategies have distinct action plans. Trial and error involves trying different solutions until one works. For instance, to fix a broken printer, you might check ink levels, ensure the paper tray isn't jammed, and verify the printer's connection to your laptop. This method can be time-consuming but is commonly used. Thomas Edison, for example, used trial and error to find a suitable filament for the light...
403
Surveys02:16

Surveys

Often, psychologists develop surveys as a means of gathering data. Surveys are lists of questions to be answered by research participants, and can be delivered as paper-and-pencil questionnaires, administered electronically, or conducted verbally. Generally, the survey itself can be completed in a short time, and the ease of administering a survey makes it easy to collect data from a large number of people.
16.7K
Statistical Software for Data Analysis and Clinical Trials01:12

Statistical Software for Data Analysis and Clinical Trials

Statistical software is pivotal in data analysis and clinical trials by providing tools to analyze data, draw conclusions, and make predictions. These software packages range from simple data management applications to complex analytical platforms, supporting various statistical tests, models, and simulation techniques. Their significance lies in their ability to handle vast amounts of data with precision and efficiency, enabling researchers to validate hypotheses, identify trends, and make...
1.4K
Impedance Combination01:21

Impedance Combination

Consider a string of christmas lights, each bulb symbolizing an impedance element. In this series configuration, the flow of electric current remains uniform across every component. This behavior aligns with Kirchhoff's Voltage Law (KVL), which asserts that the total impedance in such a setup equals the sum of individual impedances—akin to resistors in series. It follows that the voltage from the power source is distributed proportionally among these components, adhering to the voltage...
735