HCR 566 Module 11 Final Capstone Paper Example

One in Four Still Capped: Maximum-Age Rules in Late-Phase Heart Failure Trials Started 2015 to 2024

Student Name

MS in Clinical Research Management, Arizona State University

HCR 566: Clinical Research Management Capstone

Instructor Name

Month Day, Year

One in Four Still Capped: Maximum-Age Rules in Late-Phase Heart Failure Trials Started 2015 to 2024

Abstract

Background: Older adults are underrepresented in heart failure trials, partly because of upper age limits. Objective: To measure how often recent Phase 3 heart failure trials set upper age limits. Methods: Cross-sectional analysis of ClinicalTrials.gov records for interventional Phase 3 trials with heart failure in the condition list and start dates from 2015 through 2024, accessed October 10, 2026. Results: Of 175 trials, 46 (26.3%; 95% CI, 20.3% to 33.3%) listed a maximum age of 85 years or younger. Limits were more common in industry-led trials (37.5%) than others (21.0%; p = .021) and did not differ between 2015 to 2019 (25.0%) and 2020 to 2024 (27.4%; p = .72). Conclusion: Upper age limits remain common in Phase 3 heart failure trials and have not declined.

Introduction

Heart failure is concentrated in older adults, yet trial participants have averaged about 65 years of age while patients in epidemiologic studies average 69 to 73 (Tahhan et al., 2018). In 2008, a quarter of ongoing heart failure trials excluded patients by an arbitrary upper age limit (Cherubini et al., 2011). In the years that followed, the NIH has required inclusion across the lifespan in funded research (Bernard et al., 2018), and the FDA has told sponsors to justify or drop restrictive entry rules (U.S. Food and Drug Administration, 2020). This study asks whether recent late-phase heart failure trials still restrict enrollment by maximum age, whether limits differ by sponsor and period and how much enrollment such trials represent.

Methods

Design and Data Source

Cross-sectional study of public records from ClinicalTrials.gov, retrieved through the registry's application programming interface on October 10, 2026. No human participants were involved.

Eligibility

The search returned 225 records for condition "heart failure," interventional study type, Phase 3 (including combined Phase 2/3) and start dates from January 1, 2015, to December 31, 2024. Records were included if the trial's own condition list named heart failure or cardiac failure; 44 records whose conditions did not, such as trials in cancer patients or of anesthesia techniques, were excluded. Six trials limited to children were also excluded, leaving 175.

Variables and Definitions

The main outcome was whether the record listed a maximum eligible age no higher than 85 years. Ceilings above 85, for example 99 or 130 years, were read as default entries, not true restrictions. Other variables were start year, lead sponsor class (industry or other) and enrollment.

Analysis and Validation

Proportions are reported with Wilson 95% confidence intervals and compared with chi-square tests. A random sample of 20 records was checked against the full registry entries; the extracted maximum age matched in all 20, and the check led to the condition-list rule above after it revealed off-topic records.

Results

Of 175 trials, 46 (26.3%; 95% CI, 20.3% to 33.3%) listed a maximum age no higher than 85, and 22 (12.6%) set a limit of 75 or younger.

Trials with limits were smaller, with median enrollment of 128.5 against 182 for trials without, and accounted for 19,970 of 142,352 enrolled or planned participants (14.0%).

Discussion

About one Phase 3 heart failure trial in four still caps enrollment by age, almost exactly the share found in 2008 (Cherubini et al., 2011), and the proportion did not fall after 2020, when FDA guidance on broadening eligibility was issued. The persistence suggests that guidance has not yet changed this criterion in heart failure trials.

The sponsor finding reverses the earlier pattern. In 2008, publicly sponsored drug trials were more likely than privately sponsored trials to set age limits; in this sample, industry-led trials were more likely to do so. Possible explanations include safety concerns in early registration trials of new mechanisms and a focus on enrolling patients with fewer competing risks so that treatment effects are easier to detect. These explanations are hypotheses; the registry does not record why limits were set.

Because trials with limits were smaller, they account for a modest share of enrollment. The largest outcome trials, which shape guidelines, more often have no upper limit. The concern is therefore concentrated in mid-sized trials, which may still contribute to dosing and approval decisions.

Limitations

The study measures only explicit upper age limits; indirect exclusions, such as kidney function thresholds, were not captured and are common (Zulman et al., 2011). Registry fields depend on sponsor entry, and some listed maximums may be data entry choices rather than true criteria. The search depends on how sponsors describe conditions. Comparisons are unadjusted and the sample is modest, so the sponsor difference should be confirmed in a larger or longer sample.

Recommendations

Conclusion

Upper age limits remain common in Phase 3 heart failure trials, have not declined since 2015 and are more frequent in industry-led trials. For a disease of older age, dropping age ceilings without a safety reason is an easy step toward evidence that fits the patients who need it.

References

Bernard, M. A., Clayton, J. A., & Lauer, M. S. (2018). Inclusion across the lifespan: NIH policy for clinical research. JAMA, 320(15), 1535-1536. https://doi.org/10.1001/jama.2018.12368

Cherubini, A., Oristrell, J., Pla, X., Ruggiero, C., Ferretti, R., Diestre, G., Clarfield, A. M., Crome, P., Hertogh, C., Lesauskaite, V., Prada, G.-I., Szczerbinska, K., Topinkova, E., Sinclair-Cohen, J., Edbrooke, D., & Mills, G. H. (2011). The persistent exclusion of older patients from ongoing clinical trials regarding heart failure. Archives of Internal Medicine, 171(6), 550-556. https://doi.org/10.1001/archinternmed.2011.31

Tahhan, A. S., Vaduganathan, M., Greene, S. J., Fonarow, G. C., Fiuzat, M., Jessup, M., Lindenfeld, J., O'Connor, C. M., & Butler, J. (2018). Enrollment of older patients, women, and racial and ethnic minorities in contemporary heart failure clinical trials: A systematic review. JAMA Cardiology, 3(10), 1011-1019. https://doi.org/10.1001/jamacardio.2018.2559

U.S. Food and Drug Administration. (2020). Enhancing the diversity of clinical trial populations: Eligibility criteria, enrollment practices, and trial designs [Guidance for industry]. https://www.fda.gov/media/127712/download

Zulman, D. M., Sussman, J. B., Chen, X., Cigolle, C. T., Blaum, C. S., & Hayward, R. A. (2011). Examining the evidence: A systematic review of the inclusion and analysis of older adults in randomized controlled trials. Journal of General Internal Medicine, 26(7), 783-790. https://doi.org/10.1007/s11606-010-1629-x