Harms of Hepatocellular Carcinoma Surveillance

NCT03756051 | Completed

• 2 other identifiers: STU 102016-012R01CA212008
• Study Type: observational
• Target: 2,871
• Locations: 1 country
• Sites: 1

Brief Summary

This study leverage a multi-center randomized controlled trial assessing screening-related benefits (i.e. early tumor detection, treatment eligibility, and overall survival) among a racially and socioeconomically diverse population of patients with cirrhosis. However, the randomized controlled trial was not budgeted to assess hepatocellular carcinoma screening-related harms. The goal of this study is to quantify physical, financial, and psychosocial harms across three healthcare settings.

Conditions

Carcinoma, Hepatocellular

Keywords

Physical Harms; Financial Harms; Overdiagnosis; Psychosocial Harms

Outcome Measures

Primary Outcomes (4)

• Physical Harms

  Physical harms (contrast injury, radiation exposure, and biopsy complications) can result from screening or follow-up testing and extends beyond medical complications to include discomfort. A binary outcome (harm vs. no harm) will be defined for each person and each type of physical harm (contrast injury, radiation exposure, biopsy, and any physical harm). We will report the point estimate and 95% confidence interval for the proportion of patients with each type of harm in each arm, stratified by health system. Using an intention-to-treat principle, we will use Chi squared test to compare the proportion of patients with physical harms between the screening and usual care arms, with a secondary analysis stratified by health system. We will also perform a sensitivity analysis based on test intent, in which we will only include tests (and corresponding harms) performed as a direct result of hepatocellular carcinoma screening.

  4 Years

• Financial Harms

  Financial harms may include anticipated or real costs of hepatocellular carcinoma screening and diagnostic evaluation including, indirect costs such as missed work, and opportunity costs such as distraction from other health-related activities. Financial harms will be summarized for each arm using descriptive analyses as average and range of costs per person. Degree of financial harms will be compared between the hepatocellular carcinoma screening and usual care arms using Student T test, with a secondary analysis stratified by health system. In a secondary analysis, a mixed-effect model approach will be employed to identify patient-, provider- and system-level factors associated with financial harm.

  4 Years

• Overdiagnosis

  Defined as hepatocellular carcinoma diagnoses that are unlikely to have an effect on mortality, specifically among patients with: 1) significant comorbid conditions or 2) severe liver dysfunction, i.e. Child Pugh C cirrhosis, who are not candidates for liver transplantation, at hepatocellular carcinoma diagnosis. For the primary analysis, Chi squared test will be used to compare the proportion of patients with overdiagnosis between the screening arm and usual care arm, stratified by health system.

  4 Years

• Psychosocial Harms

  Patients will be divided into 4 categories: true positives, false positives, true negatives, and no screening. True positives will be defined as those who develop hepatocellular carcinoma within 6 months of the screening test; false positives as those who remain without hepatocellular carcinoma diagnosis during 6 months of follow-up; and true negatives as those with normal screening tests and without hepatocellular carcinoma diagnosis during 6 months of follow-up. Psychosocial harms (cancer-specific worry, situational anxiety, mood disturbances, and decisional regret) will be defined by change in survey scores from baseline and will be calculated at 1 month and 6 months for each patient.

  4 Years

Secondary Outcomes (3)

• Patient-, Provider-, and System-level Factors Associated with Physical Harms

  4 Years

• Patient-, Provider-, and System-level Factors Associated with Psychosocial Harms

  4 Years

• Physical Harms

  12 Months

Study Arms (1)

Cohort

This study will collect prospective longitudinal data to characterize rates and identify correlates of a) physical harms due to follow-up tests, b) financial harms, and c) inappropriate screening using electronic medical record data and manual chart review. The study will also use surveys and semi-structured interviews to characterize rates and identify correlates of screening-related psychological harms, e.g. cancer specific worry, situational anxiety, mood disturbances, and decisional regret. Lastly, investigators will create and disseminate a balance sheet of benefits and harms to inform patients, providers, healthcare organizations, payers, and policymakers about the role of hepatocellular carcinoma screening in patients with cirrhosis.

Other: Prospective Longitudinal Data; Other: Surveys and Semi-structured Interviews

Interventions

Prospective Longitudinal Data OTHER

We will prospectively follow the cohort using electronic medical record to document the hepatocellular carcinoma screening process and characterize physical and financial harms related to positive or indeterminate screening results and burden of inappropriate screening. Patients are anticipated to undergo hepatocellular carcinoma screening every 6-12 months, so each patient will have \~4-8 screening encounters over the study duration. We will use manual chart review to determine intent of ultrasound exams (screening vs. diagnostic) and test results. Receipt of follow-up tests after positive or indeterminate screening results will be identified through electronic medical record extraction using Current Procedural Terminology (CPT) codes for CT, MRI, and biopsy.

Cohort

Surveys and Semi-structured Interviews OTHER

We will use surveys and semi-structured interviews to characterize psychological harms after positive or indeterminate screening tests. Patient surveys will include patient-reported scales to measure psychosocial factors at three times points: baseline, 1 month after screening result, and 4 months after screening result. Semi-structured interviews will be conducted via telephone to explore patient attitudes toward risk perception, test follow-up, competing demands, and "downstream harms", particularly financial issues (e.g., out-of-pocket costs, access to insurance, and juggling hepatocellular carcinoma screening process completion with competing demands-work and family).

Cohort

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

All patients from the parent randomized controlled trial will be included in this study.

You may not qualify if:

• Adult patients (≥ 21 years old)
• Cirrhosis
• Outpatient visit in year prior to randomization
• English or Spanish speaking
• History of hepatocellular carcinoma
• History of liver transplantation
• Child Pugh C cirrhosis
• Significant comorbid conditions with life expectancy \< 1 year, (e.g., extrahepatic malignancy)

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead
• National Cancer Institute (NCI): collaborator
• Parkland Health and Hospital System: collaborator
• Baylor College of Medicine: collaborator
• Michael E. DeBakey VA Medical Center: collaborator
• Kaiser Permanente: collaborator

Study Sites (1)

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Related Publications (2)

• Singal AG, Daher D, Narasimman M, Yekkaluri S, Liu Y, Cerda V, Banala C, Khan A, Lee M, Seif El Dahan K, Murphy CC, Kramer JR, Hernaez R. Benefits and harms of hepatocellular carcinoma screening outreach in patients with cirrhosis: a multicenter randomized clinical trial. J Natl Cancer Inst. 2025 Feb 1;117(2):262-269. doi: 10.1093/jnci/djae228.

  PMID: 39288308 DERIVED

• Singal AG, Reddy S, Radadiya Aka Patel H, Villarreal D, Khan A, Liu Y, Cerda V, Rich NE, Murphy CC, Tiro JA, Kramer JR, Hernaez R. Multicenter Randomized Clinical Trial of a Mailed Outreach Strategy for Hepatocellular Carcinoma Surveillance. Clin Gastroenterol Hepatol. 2022 Dec;20(12):2818-2825.e1. doi: 10.1016/j.cgh.2021.12.014. Epub 2021 Dec 10.

  PMID: 34902568 DERIVED

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Surveys and Questionnaires

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Data Collection; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Study Officials

• Amit Singal, MD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: November 26, 2018
• First Posted: November 28, 2018
• Study Start: April 1, 2018
• Primary Completion: June 30, 2022
• Study Completion: June 30, 2022
• Last Updated: December 30, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)