July 2, 2026

Navigating Complexity in Pulmonary Trials: Enrichment Strategies & Targeting the Right Patients

This is article three in our series on smarter trial designs for complex pulmonary diseases. To view the full series as a PDF, download our Navigating Complexity in Pulmonary Trials whitepaper here.

Welcome back to our series on smarter trial designs for complex pulmonary diseases. If you’ve worked on trials in Idiopathic Pulmonary Fibrosis (IPF), Acute Respiratory Distress Syndrome (ARDS), or Cystic Fibrosis (CF), you know how unpredictable these diseases can be. Patients progress at different rates, respond differently to therapies, and often face burdensome endpoints. That variability can make it tough to detect a treatment effect, unless you’re targeting the right patients from the start.

That’s where enrichment strategies come in.

What Are Enrichment Strategies?

Enrichment strategies are all about selectively including participants who are more likely to benefit from or respond to the investigational therapy. By narrowing the focus, you can increase statistical power, reduce variability, improve feasibility, and accelerate timelines.

There are three main types:

Prognostic enrichment

Patients more likely to experience the event of interest (e.g., IPF patients with rapid Forced Vital Capacity (FVC) decline)

Predictive enrichment

Patients more likely to respond to the therapy (e.g., CF patients with specific cystic fibrosis transmembrane conductance regulator (CFTR) genetic mutations)

Strategies to Decrease Variability

Patients reflect a more narrow characterization of the disease (e.g., ARDS patients without multi-organ failure)

Operationalizing Enrichment Strategies: A High-Level Look at Tools and Challenges

Especially in rare or high-risk diseases, enrichment strategies can mean the difference between a trial that succeeds and one that stalls.

Sponsors can use a variety of tools to operationalize enrichment including:

Biomarker screening (blood, imaging, genetic);
Run-in periods to identify stable or responsive patients; and
Historical data modeling to simulate enrichment impact.

It is important to note that enrichment isn’t without trade-offs. This includes generalizability, as highly enriched populations may not reflect broader clinical practice, as well as challenges with recruitment and slow enrollment due to narrow eligibility criteria. Enriched trials also require an increased focus on regulatory alignment, as strategies must be justified and clearly documented.

Examples of Pulmonary Studies Using Enrichment Strategies

Predictive Enrichment in CF – Vertex’s CFTR Modulator Trials

Vertex Pharmaceuticals has led the way in predictive enrichment by enrolling only CF patients with specific CFTR mutations (like F508del homozygous). This approach delivered strong efficacy signals with smaller sample sizes, streamlined recruitment, and accelerated regulatory approval.

Takeaway: If your therapy targets a specific mutation or pathway, predictive enrichment can help you demonstrate efficacy faster and more convincingly.

Prognostic Enrichment in IPF – The ASCEND Trial

In the ASCEND trial for pirfenidone, researchers focused on IPF patients with measurable FVC decline. By enriching for patients likely to progress, they increased the likelihood of detecting a treatment effect, reduced noise in endpoint data, and improved trial efficiency.

Takeaway: Prognostic enrichment helps ensure your endpoints are meaningful and measurable, especially in diseases with variable progression.

Decreased Variability in ARDS – The ART Trial

The ART trial evaluated high vs. low Positive End Expiratory Pressure (PEEP) strategies in ARDS. To improve feasibility and endpoint clarity, the trial excluded patients with multi-organ failure who were unlikely to survive long enough for meaningful assessment.

Takeaway : Selecting patients who can complete the protocol improves data quality and retention.

Conclusion

Complex pulmonary trials – including trials within indications like IPF, ARDS, and CF – may leverage enrichment strategies that can accelerate trial timelines and support precision medicine. For more information on how we can support your upcoming pulmonary trial, reach out to our team.