AI-Assisted Anaerobic Threshold Interpretation in Cardiopulmonary Exercise Testing (PACE-Reader)

A Randomized Two-Period Crossover Reader Study of Artificial Intelligence-Assisted Anaerobic Threshold Interpretation in Cardiopulmonary Exercise Testing

This prospective randomized two-period crossover reader study will evaluate whether assistance from a frozen artificial intelligence model improves physicians' interpretation of the anaerobic threshold (AT) in cardiopulmonary exercise testing (CPET). Sixteen physicians, including 8 senior and 8 junior readers, will each interpret 150 de-identified CPET examinations once without AI assistance and once with AI assistance. The primary outcome is the within-physician difference in absolute AT localization error between the assisted and unassisted conditions. Secondary outcomes include signed timing error, agreement on whether AT is present, estimates within 15 and 30 seconds of the reference, inter-reader reliability, interpretation time, and whether the effect of AI assistance differs by physician seniority.

Study Overview

• Status: Not yet recruiting
• Conditions: Cardiopulmonary Exercise Test Interpretation
• Intervention / Treatment: Other: AI-Assisted Anaerobic Threshold Interpretation; Other: Unassisted Cardiopulmonary Exercise Test Interpretation

Detailed Description

The 150 de-identified CPET examinations will be divided into two non-overlapping case libraries, X and Y, with 75 examinations in each library. The libraries will be balanced, as far as feasible, by clinical severity and acquisition characteristics. None of the reader-study examinations will be used for model training, hyperparameter selection, or checkpoint selection.

Within each seniority stratum, physicians will be randomized in a 1:1 ratio to Sequence A or Sequence B. In period 1, Sequence A will interpret library X without AI assistance and library Y with AI assistance; Sequence B will receive the opposite conditions. Following a 14 ± 3 day washout, the assistance conditions will be reversed in period 2. Case order will be randomized within each period, and new blinded task identifiers will be assigned in period 2. Thus, every physician will interpret every examination once without AI assistance and once with AI assistance, yielding 4,800 interpretations.

In the assisted condition, the interface will display the frozen model's predicted AT time. In the unassisted condition, no model output will be shown. Readers will be masked to case source, routine-report and reference-standard labels, other readers' annotations, and their own annotations from the previous period. For each examination, the reader will classify AT as confirmed, not reached, or unable to confirm. When AT is confirmed, the reader will record the AT time and the interpretive method used. Interpretation time will also be recorded.

The reference standard will be prespecified from unassisted senior-physician annotations. AT will be considered present when at least 6 of 8 senior physicians confirm it, and the reference AT time will be the median of the confirming senior estimates. AT will be considered not reached when at least 6 of 8 senior physicians make that classification. Discordant cases will undergo adjudication by an additional senior physician who is masked to model output and reader identity. For analyses of senior readers, a leave-one-reader-out reference will be used.

The primary analysis will compare absolute AT localization error between assisted and unassisted interpretations using a crossed mixed-effects model. Fixed effects will include assistance condition, physician seniority, the assistance-by-seniority interaction, period, randomized sequence, and case library. Random intercepts will be included for physician and examination. Estimates will be reported with 95% confidence intervals. No simulated or pilot-result data will be included in the prospective study analysis.

• Study Type: Interventional
• Enrollment (Estimated): 16
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Cong Wang, MD, PhD; Phone Number: +86-21-64041990; Email: wang.cong1@zs-hospital.sh.cn

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200032
      • Zhongshan Hospital, Fudan University
      • Contact: Cong Wang, MD, PhD; Phone Number: +86-21-64041990; Email: wang.cong1@zs-hospital.sh.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18 years or older.
• Licensed physician or physician enrolled in a recognized postgraduate clinical training program at the study institution.
• Eligible for one of the two prespecified seniority strata: senior physicians are attending physicians or above with at least 5 years of independent CPET interpretation experience; junior physicians are residents or specialty trainees with less than 5 years of independent CPET interpretation experience.
• Able to interpret CPET examinations and use the study interface after standardized orientation.
• Willing and able to complete both study periods and the prespecified washout interval.
• Provides written informed consent.

Exclusion Criteria:

• Direct involvement in development, training, hyperparameter selection, or checkpoint selection of the PACE-Former model.
• Prior access to the study case libraries, reference-standard annotations, or model outputs for the study examinations.
• Unable to complete the required interpretation tasks or the 14 ± 3 day washout interval.
• Withdrawal of consent before completion of study procedures.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sequence A; Period 1: library X interpreted without AI assistance and library Y interpreted with AI assistance. Period 2, after a 14 ± 3 day washout: library X interpreted with AI assistance and library Y interpreted without AI assistance.	Other: AI-Assisted Anaerobic Threshold Interpretation; A frozen PACE-Former model provides a predicted anaerobic threshold time within the CPET review interface. Physicians retain responsibility for the final classification and AT time annotation. No other model output or reference label is displayed.; Other: Unassisted Cardiopulmonary Exercise Test Interpretation; The physician reviews the same de-identified CPET data using the study interface without display of any model prediction or AI-generated suggestion and independently classifies AT status and records the AT time when confirmed.
Experimental: Sequence B; Period 1: library X interpreted with AI assistance and library Y interpreted without AI assistance. Period 2, after a 14 ± 3 day washout: library X interpreted without AI assistance and library Y interpreted with AI assistance.	Other: AI-Assisted Anaerobic Threshold Interpretation; A frozen PACE-Former model provides a predicted anaerobic threshold time within the CPET review interface. Physicians retain responsibility for the final classification and AT time annotation. No other model output or reference label is displayed.; Other: Unassisted Cardiopulmonary Exercise Test Interpretation; The physician reviews the same de-identified CPET data using the study interface without display of any model prediction or AI-generated suggestion and independently classifies AT status and records the AT time when confirmed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in Absolute Anaerobic Threshold Localization Error	Absolute difference, in seconds, between the physician-selected AT time and the prespecified expert reference AT time. The primary estimand is the within-physician difference between AI-assisted and unassisted interpretations, analyzed across the same examinations using a crossed mixed-effects model.	Recorded immediately after each case interpretation and analyzed after completion of both study periods, up to 2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Signed Anaerobic Threshold Localization Error	Signed difference, in seconds, between the physician-selected AT time and the prespecified expert reference AT time. Negative values indicate earlier placement and positive values indicate later placement relative to the reference.	Recorded immediately after each case interpretation and analyzed after completion of both study periods, up to 2 months
Proportion of Anaerobic Threshold Estimates Within 15 Seconds of the Reference	Proportion of interpretable examinations for which the physician-selected AT time is within 15 seconds, in either direction, of the prespecified expert reference AT time.	Recorded immediately after each case interpretation and analyzed after completion of both study periods, up to 2 months
Proportion of Anaerobic Threshold Estimates Within 30 Seconds of the Reference	Proportion of interpretable examinations for which the physician-selected AT time is within 30 seconds, in either direction, of the prespecified expert reference AT time.	Recorded immediately after each case interpretation and analyzed after completion of both study periods, up to 2 months
Agreement With the Reference Anaerobic Threshold Status	Agreement between the physician classification (AT confirmed, AT not reached, or unable to confirm) and the prespecified expert reference classification. Results will be summarized as overall agreement and condition-specific classification performance.	Recorded immediately after each case interpretation and analyzed after completion of both study periods, up to 2 months
Inter-Reader Reliability	Reliability among physicians for AT timing and AT-status classification under AI-assisted and unassisted conditions, summarized using appropriate intraclass correlation and chance-corrected agreement statistics with 95% confidence intervals.	Recorded immediately after each case interpretation and analyzed after completion of both study periods, up to 2 months
Interpretation Time per Examination	Elapsed time, in seconds, from opening the blinded CPET task to submission of the physician's AT classification and, when applicable, the selected AT time.	Recorded immediately after each case interpretation and analyzed after completion of both study periods, up to 2 months
Interaction Between AI Assistance and Physician Seniority	Difference in the effect of AI assistance between senior and junior physicians, estimated from the prespecified assistance-by-seniority interaction term in the crossed mixed-effects model for absolute AT localization error.	Recorded immediately after each case interpretation and analyzed after completion of both study periods, up to 2 months

Collaborators and Investigators

• Sponsor: Shanghai Zhongshan Hospital
• Investigators: Principal Investigator: Cong Wang, MD, PhD, Fudan University

Study record dates

Study Major Dates

• Study Start (Estimated): September 25, 2026
• Primary Completion (Estimated): November 25, 2026
• Study Completion (Estimated): November 25, 2026

Study Registration Dates

• First Submitted: September 16, 2026
• First Submitted That Met QC Criteria: September 16, 2026
• First Posted (Actual): September 22, 2026

Study Record Updates

• Last Update Posted (Actual): September 22, 2026
• Last Update Submitted That Met QC Criteria: September 16, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: Clinical Decision Support; Artificial Intelligence; Reader Study; Cardiopulmonary Exercise Testing; Human-AI Collaboration; Anaerobic Threshold
• Other Study ID Numbers: PACE-AT-READER-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No