Study type

Study topic

Disease /health condition
Human medicinal product

Study type

Non-interventional study

Scope of the study

Assessment of risk minimisation measure implementation or effectiveness

Data collection methods

Secondary use of data
Non-interventional study

Non-interventional study design

Cohort
Study drug and medical condition

Name of medicine

DAKLINZA
EPCLUSA
EXVIERA
HARVONI
MAVIRET
SOVALDI
VIEKIRAX
VOSEVI
ZEPATIER

Medical condition to be studied

Chronic hepatitis C
Population studied

Short description of the study population

The analysis will be conducted among US veterans, aged 18 years or older, with chronic HCV who sought care at any of the medical centers and ambulatory care and community-based outpatient clinics that comprise the national VA healthcare system. This analysis will be restricted to HCV mono-infected (i.e., no hepatitis B virus or human immunodeficiency virus coinfection) patients with compensated liver cirrhosis.
Inclusion criteria:
1. Patients with chronic HCV defined as a positive test for HCV ribonucleic acid (RNA) in plasma by qualitative or quantitative assays or genotype test between January 01, 2005 and December 31, 2017.
2. For the first primary objective (DAA only treated and untreated patients): a clinical encounter (i.e., office visit, procedure, lab result, prescription, etc.) recorded in the 6 months preceding and including January 01, 2013 or between January 01, 2013 and December 31, 2017.
3. For the second primary objective: for IFN treated patients, the IFN based treatment was initiated after the above HCV diagnosis, but between January 01, 2005 and December 31, 2013. If DAA-only exposed, the DAA treatment was initiated after the above HCV diagnosis, but between January 01, 2014 and December 31, 2017.
4. Patients with data in VA sources to establish a diagnosis of compensated cirrhosis as follows: • At least 1 fibrosis-4 (FIB-4) > 3.25 within 24 months before or 6 months after the index date but before any HCV treatment (and with all measurements for FIB-4 calculation within 6 months of each other) or at least 1 ICD-9 (571.2, 571.5) or ICD-10 (K70.30, K70.31, K74.60, K74.69, K74.3, K74.4 and K74.5) code indicating cirrhosis, and • No diagnosis codes for hepatic decompensation defined as ascites, variceal bleeding, hepatic encephalopathy, spontaneous bacterial peritonitis, or hepatorenal syndrome based on inpatient or outpatient ICD-9 codes of 789.5, 456.0–2, 572.4, 572.2, 348.3×, 070.0, 070.2×, 070.4×, 070.6, 070.71, or corresponding ICD-10 codes d

Age groups

Adults (18 to < 46 years)
Adults (46 to < 65 years)
Adults (65 to < 75 years)
Adults (75 to < 85 years)
Adults (85 years and over)

Special population of interest

Hepatic impaired

Estimated number of subjects

16000
Study design details

Main study objective

This analysis examines the following research question: among compensated cirrhotic patients, does DAA therapy for chronic HCV infection increase the risk of incident HCC compared to no treatment or treatment with IFN-based regimens?

Outcomes

1. Estimate the risk of de novo HCC associated with DAA therapy exposure in cirrhotic HCV patients compared to no anti-HCV therapy exposure in cirrhotic HCV patients. 2. Estimate the risk of de novo HCC in cirrhotic HCV patients treated with DAA therapy compared to those treated with IFN-based therapy. To compare, in a subset of patients with available data recorded in the VA CCR, tumor characteristics (i.e. tumor size, tumor number, tumor stage, tumor type) of the de novo HCC cases observed following initiation of DAA therapy to those of de novo HCC cases observed (a) following initiation of IFN-containing regimens and (b) in untreated patients.

Data analysis plan

For the first primary objective, a multivariable Cox proportional hazards regression model will be used to examine the risk of HCC associated with DAA exposed time compared to untreated time using DAA exposure as a time-varying covariate and adjusting for values of potential confounders ascertained at index date or most recently prior to index date and updated at 12-month time intervals until DAA exposure start or through untreated person time if no DAA start. For the second primary objective, another multivariable proportional hazards model will be used to examine the risk of HCC in the DAA treated patients compared to the IFN-based therapy treated patients. For the secondary objective, in all patients with HCC recorded in the VA CCR, the first occurrence of de novo HCC during the observation period will be identified by any instance of primary site code C220 and histology codes 817XX through 818XX.
Documents
Study results
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