Related Experiment Videos
Simultaneous screening for three correlated lipids in the VA HDL Intervention Trial
M K Iwane1, J Wittes, D E Collins
1Cooperative Studies Program, VAMC, West Haven, Connecticut, USA.
Insights
Developing an effective multistage lipid screen methodology is crucial for clinical trials. This approach successfully managed participant recruitment for a study on high-density lipoprotein (HDL) therapy.
Area of Science:
- Cardiovascular Medicine
- Clinical Trial Design
- Lipid Metabolism
Background:
- High-density lipoprotein (HDL) cholesterol plays a vital role in cardiovascular health.
- Low HDL-cholesterol is a risk factor for coronary events, especially in men with desirable LDL-cholesterol.
- Effective screening is essential for recruiting appropriate participants into secondary prevention trials.
Purpose of the Study:
- To develop and validate a multistage lipid screening methodology for a clinical trial.
- To determine optimal cutpoints for excluding participants based on lipid profiles (HDL-cholesterol, LDL-cholesterol, triglycerides).
- To assess the feasibility of recruiting participants for a trial investigating HDL-raising therapy.
Main Methods:
- Developed a multistage screening methodology using joint lipid distributions.
- Utilized estimates from previous studies to derive lipid parameter cutpoints.
- Performed simulations to optimize screening rules for participant exclusion.
- Conducted a randomized double-blind placebo-controlled trial with 2531 participants.
Main Results:
- The developed methodology effectively managed participant recruitment for the VA HDL Intervention Trial.
- Predicted recruitment lipid characteristics showed good agreement with actual study results.
- The screening process successfully identified participants with low HDL-cholesterol and desirable LDL-cholesterol.
- Demonstrated the complexity of simultaneously screening on correlated lipid parameters.
Conclusions:
- The multistage lipid screening methodology is effective for clinical trial recruitment.
- The approach balances the need for specific lipid profiles with recruitment efficiency.
- This methodology provides a framework for designing similar screening protocols in future cardiovascular trials.
Abstract:
We developed methodology to design the multistage lipid screen for the VA HDL Intervention Trial, a randomized double-blind placebo-controlled secondary prevention clinical trial of 2531 participants. The trial aimed to determine if HDL-raising therapy reduces coronary events in men with low HDL-cholesterol and desirable LDL-cholesterol. Joint lipid distributions for HDL-cholesterol, LDL-cholesterol, and triglycerides were derived on the basis of estimates from previous studies, and simulations were performed to determine the cutpoints for excluding screenees for the three lipid parameters to be used at each recruitment stage. Operating characteristics for different screening rules are presented. Comparisons between the predicted and actual study recruitment results show good agreement in lipid characteristics and underscore the complexity of simultaneously screening on correlated continuous physiologic parameters such as lipids.