Related Experiment Video
Updated: Jul 1, 2026
02:47
Exercise Test for Evaluation of the Functional Efficacy of the Pig Cardiovascular System
Published on: May 12, 2023
Composite Endpoints in Contemporary Cardiovascular Trials: Trends in Phase 3 Trials and Key Issues in Regulatory
Hiromi Sugano1,2, Mamoru Narukawa1,2
1Department of Clinical Medicine (Pharmaceutical Medicine), Graduate School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
Clinical Pharmacology and Therapeutics
|June 30, 2026
Summary
Interpreting composite endpoints in cardiovascular drug development is challenging. Regulatory agencies consistently raise concerns about clinical importance and interpretability of composite results across regions.
Area of Science:
- Cardiovascular Medicine
- Clinical Trials
- Drug Development
Background:
- Composite endpoints in cardiovascular drug development present interpretation challenges.
- Previous reviews indicate potential masking of clinically significant component-level differences.
- Limited information exists on current usage and regulatory impact of composite endpoints.
Purpose of the Study:
- To review the use of composite endpoints in cardiovascular Phase III trials.
- To examine regulatory evaluations of composite endpoints in new drug applications.
- To understand how composite endpoint interpretation influences regulatory decision-making.
Main Methods:
- Descriptive review of cardiovascular Phase III trial publications and ClinicalTrials.gov registries (2015-2024).
- Analysis of regulatory evaluations for cardiovascular drug applications in Japan, the US, and the EU.
- Identification of 173 trials utilizing composite primary endpoints.
Main Results:
- Composite endpoints remain common in cardiovascular trials, with an increasing range of included events.
- Hard endpoints like death are still prevalent.
- Regulatory agencies consistently flagged concerns regarding component clinical importance and interpretability.
Conclusions:
- Regulatory agencies across Japan, the US, and EU express concerns about composite endpoint interpretability and component clinical importance.
- There is a need to consider component differences in clinical importance during trial design and evaluation.
- Careful interpretation of composite endpoint results alongside individual component outcomes is crucial.
Related Concept Videos
01:18Cardiovascular Drugs: Classification based on Therapeutic Indications
Cardiovascular diseases, encompassing a range of conditions, can significantly affect the heart's operations and the overall circulatory system. These conditions impair the heart's ability to pump blood, leading to a deficit in oxygen supply to crucial organs. Anomalies in the heart's electrical system, known as arrhythmias, can cause heartbeats to accelerate or slow down. Usually, heart rates increase during physical activity and decrease while resting or sleeping. However, frequent irregular...
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...
01:23Types 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...
01:26Drug Administration and Therapy Phases: Overview
Drugs, the chemical agents used in diagnosing, treating, or preventing diseases, undergo a four-phase process of development: pharmaceutic, pharmacokinetics, pharmacodynamics, and therapeutic.
The pharmaceutical phase focuses on leveraging the physicochemical properties of the drug to design and manufacture an effective product. Variants include orally administered tablets or capsules, topical creams or ointments, and parenteral-delivery solutions or emulsions.
The pharmacokinetic phase...
The pharmaceutical phase focuses on leveraging the physicochemical properties of the drug to design and manufacture an effective product. Variants include orally administered tablets or capsules, topical creams or ointments, and parenteral-delivery solutions or emulsions.
The pharmacokinetic phase...
01:15Impact of Pharmacokinetic–Pharmacodynamic Models: Regulatory Decisions
PK–PD modeling has significantly influenced FDA regulatory decisions, particularly drug approval, dosage optimization, and labeling. These models integrate pharmacokinetics (PK) and pharmacodynamics (PD) to predict drug behavior and effects, aiding in optimizing dosing regimens and enhancing the probability of clinical trial success.One notable example is Nesiritide (Natrecor®), a recombinant human brain natriuretic peptide for treating acute decompensated congestive heart failure (CHF).