Assessing Treatment Effects That Capture Disease Burden in Serious Chronic Diseases

Area of Science:

• Clinical trials methodology
• Cardiovascular disease research
• Health outcomes research

Background:

• Serious and chronic health conditions, including cardiovascular diseases (CVDs), present significant challenges to healthcare systems.
• Clinical trials increasingly utilize composite endpoints combining mortality and morbidity events to assess treatments.
• The traditional time-to-first event analysis, while common, overlooks subsequent events in chronic disease progression.

Purpose of the Study:

• To explore the limitations of the traditional time-to-first event analysis in chronic disease clinical trials.
• To discuss the value of incorporating recurrent event information into composite endpoints.
• To advocate for endpoint measures that better reflect overall disease burden and treatment effects.

Main Methods:

• Review and critique of the time-to-first event analysis approach.
• Exploration of alternative endpoint measures that capture recurrent events.
• Discussion of the implications for interpreting treatment effects in chronic diseases.

Main Results:

• The time-to-first event approach can lead to substantial loss of information, particularly in chronic conditions like heart failure (HF).
• Ignoring subsequent events, such as deaths following hospitalizations, provides an incomplete assessment of treatment efficacy.
• Endpoints incorporating recurrent events offer more interpretable measures of treatment effect and disease burden.

Conclusions:

• Alternative endpoint measures that utilize all available event data beyond the first event are valuable.
• These recurrent event endpoints can provide a more comprehensive understanding of treatment benefits in chronic diseases.
• Raising awareness among trialists, regulators, payers, and physicians is crucial for adopting more informative endpoint measures.