Dataset Information

Limited Generalizability of Registration Trials in Hepatitis C: A Nationwide Cohort Study.

ABSTRACT:

Background

Approval of drugs in chronic hepatitis C is supported by registration trials. These trials might have limited generalizability through use of strict eligibility criteria. We compared effectiveness and safety of real world hepatitis C patients eligible and ineligible for registration trials.

Methods

We performed a nationwide, multicenter, retrospective cohort study of chronic hepatitis C patients treated in the real world. We applied a combined set of inclusion and exclusion criteria of registration trials to our cohort to determine eligibility. We compared effectiveness and safety in eligible vs. ineligible patients, and performed sensitivity analyses with strict criteria. Further, we used log binomial regression to assess relative risks of criteria on outcomes.

Results

In this cohort (n = 467) 47% of patients would have been ineligible for registration trials. Main exclusion criteria were related to hepatic decompensation and co-morbidity (cardiac disease, anemia, malignancy and neutropenia), and were associated with an increased risk for serious adverse events (RR 1.45-2.31). Ineligible patients developed significantly more serious adverse events than eligible patients (27% vs. 11%, p< 0.001). Effectiveness was decreased if strict criteria were used.

Conclusions

Nearly half of real world hepatitis C patients would have been excluded from registration trials, and these patients are at increased risk to develop serious adverse events. Hepatic decompensation and co-morbidity were important exclusion criteria, and were related to toxicity. Therefore, new drugs should also be studied in these patients, to genuinely assess benefits and risk of therapy in the real world population.

SUBMITTER: Berden FA

PROVIDER: S-EPMC5012685 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Publications

Limited Generalizability of Registration Trials in Hepatitis C: A Nationwide Cohort Study.

Berden Floor A C FA de Knegt Robert J RJ Blokzijl Hans H Kuiken Sjoerd D SD van Erpecum Karel J L KJ Willemse Sophie B SB den Hollander Jan J van Vonderen Marit G A MG Friederich Pieter P van Hoek Bart B van Nieuwkerk Carin M J CM Drenth Joost P H JP Kievit Wietske W

PloS one 20160906 9

<h4>Background</h4>Approval of drugs in chronic hepatitis C is supported by registration trials. These trials might have limited generalizability through use of strict eligibility criteria. We compared effectiveness and safety of real world hepatitis C patients eligible and ineligible for registration trials.<h4>Methods</h4>We performed a nationwide, multicenter, retrospective cohort study of chronic hepatitis C patients treated in the real world. We applied a combined set of inclusion and exclu ...[more]

PMID: 27598789

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Project description:BackgroundWhether infection with the hepatitis C virus (HCV) causes schizophrenia - and whether the associated risk reverses after anti-HCV therapy - is unknown; we aimed to investigate these topics.MethodsWe conducted a nationwide, population-based cohort study using the Taiwan National Health Insurance Research Database (TNHIRD). A diagnosis of schizophrenia was based on criteria from the International Classification of Diseases, 9th revision (295.xx).ResultsFrom 2003 to 2012, from a total population of 19 298 735, we enrolled 3 propensity-score-matched cohorts (1:2:2): HCV-treated (8931 HCV-infected patients who had received interferon-based therapy for ≥ 6 months); HCV-untreated (17 862); and HCV-uninfected (17 862) from the TNHIRD. Of the total sample (44 655), 82.81% (36 980) were 40 years of age or older. Of the 3 cohorts, the HCV-untreated group had the highest 9-year cumulative incidence of schizophrenia (0.870%, 95% confidence interval [CI] 0.556%-1.311%; p < 0.001); the HCV-treated (0.251%, 95% CI 0.091%-0.599%) and HCV-uninfected (0.118%, 95% CI 0.062%-0.213%) cohorts showed similar cumulative incidence of schizophrenia (p = 0.33). Multivariate Cox analyses showed that HCV positivity (hazard ratio [HR] 3.469, 95% CI 2.168-5.551) was independently associated with the development of schizophrenia. The HCV-untreated cohort also had the highest cumulative incidence of overall mortality (20.799%, 95% CI 18.739%-22.936%; p < 0.001); the HCV-treated (12.518%, 95% CI 8.707%-17.052%) and HCV uninfected (6.707%, 95% CI 5.533%-8.026%) cohorts showed similar cumulative incidence of mortality (p = 0.12).LimitationsWe were unable to determine the precise mechanism of the increased risk of schizophrenia in patients with HCV infection.ConclusionIn a population-based cohort (most aged ≥ 40 years), HCV positivity was a potential risk factor for the development of schizophrenia; the HCV-associated risk of schizophrenia might be reversed by interferon-based antiviral therapy.

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Dataset Information

Limited Generalizability of Registration Trials in Hepatitis C: A Nationwide Cohort Study.

Background

Methods

Results

Conclusions

Publications

Limited Generalizability of Registration Trials in Hepatitis C: A Nationwide Cohort Study.

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