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

作者：Berden Floor A C; de Knegt Robert J; Blokzijl Hans; Kuiken Sjoerd D; van Erpecum Karel J L; Willemse Sophie B; den Hollander Jan; van Vonderen Marit G A; Friederich Pieter; van Hoek Bart; van Nieuwkerk Carin M J; Drenth Joost P H^*; Kievit Wietske

来源：PLos One, 2016, 11(9): e0161821.

DOI：10.1371/journal.pone.0161821

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.

• 出版日期2016-9-6