Mortality Benefit of Ultrasound for Thyroid Nodules Identified With PET Imaging: Non-Inferiority Emulated Target Trial

NCT07255482 | Active Not Recruiting

• 2 other identifiers: 2024P002073-1R18HS029839
• Study Type: observational
• Target: 5,000
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators hypothesize that all-cause mortality in patients with an incidental thyroid nodule on PET-CT who did not have thyroid ultrasound (the exposure) within 3 months of the PET-CT is non-inferior within a 5% margin to those who have thyroid ultrasound at 7-years. That is, among patients with an incidental thyroid nodule on PET-CT, mortality is no more than 5% larger (in absolute difference) for those who do not have thyroid ultrasound compared to those who do. The investigators will also report mortality differences at landmark timeframes of 1-year, 3-years, 5-years, and 10-years. To estimate group differences in mortality, the investigators will conduct a non-inferiority emulated target trial utilizing clone-censor weighting to address potential immortal time bias introduced by the 3-month grace period. The investigators will adjust for demographic, potential confounder, and mortality risk adjustor factors. The investigators will stratify analyses based on baseline disease severity (estimated 5-year relative survival risk) and disease status (progression, lymph node involvement, other sites of metastases). All subjects will be accrued from the Mass General Brigham healthcare system, which includes two academic medical centers, a specialty head and neck hospital, and multiple community hospitals and numerous community clinics.

Conditions

Thyroid Nodule (Benign); Thyroid Cancer; Thyroid Nodule (Diagnosis)

Outcome Measures

Primary Outcomes (1)

• All-Cause Mortality

  7 Years

Secondary Outcomes (4)

• Number of Thyroid Cancer Diagnoses

  7 Years

• Number of Thyroid Ultrasound Examinations

  7 Years

• Number of Thyroid Biopsies

  7 Years

• Number of Thyroid Surgeries

  7 Years

Other Outcomes (1)

• Types of Thyroid Cancers

  7 Years

Study Arms (1)

Patients with thyroid nodule on PET

Diagnostic Test: Thyroid Ultrasound

Interventions

Thyroid Ultrasound DIAGNOSTIC_TEST

Thyroid ultrasound performed within 3 months of PET to characterize a thyroid nodule identified on the PET

Patients with thyroid nodule on PET

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients who had a PET-CT at Mass General Brigham 1/1/2015 to 12/31/2021

You may qualify if:

• Age \>=18
• Thyroid nodule on PET-CT performed 1/1/2015 to 12/31/2021
• At least one clinical note in the EHR from the 36-month window prior to the PET

You may not qualify if:

• Thyroid ultrasound listed in the medical record in the prior 3 years
• Documented history of prior thyroid cancer diagnosis

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• Harvard School of Public Health (HSPH): collaborator
• Agency for Healthcare Research and Quality (AHRQ): collaborator

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Thyroid Nodule; Disease; Thyroid Neoplasms

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Endocrine System Diseases; Thyroid Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Radiology

Study Record Dates

• First Submitted: November 20, 2025
• First Posted: December 1, 2025
• Study Start: October 15, 2025
• Primary Completion: November 30, 2025
• Study Completion (Estimated): June 30, 2026
• Last Updated: April 21, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: Study protocol with study analysis plan submitted at time of clinicaltrials.gov registration. IPD and analytic code will be shared upon manuscript publication.
• Access Criteria: General public via the Harvard Dataverse repository.

Locations

US (1)