This was a cross-sectional study, with registry data covering the whole country. The data sources used were the Swedish Prescribed Drug Register  and the Swedish National Patient Register , both held by the National Board of Health and Welfare, and the national quality register InfCare Hepatitis, held by the Karolinska University Hospital, Stockholm. The Swedish Prescribed Drug Register is a mandatory national register with information about each individual and their prescription drug purchases (age, sex, Anatomical Therapeutic Chemical [ATC] codes, prescribing and dispensing dates, number of packages, and prescribed dose). The National Patient Register is also a mandatory national register, with individual level data on documented main and contributory diagnoses (ICD codes) and diagnostic and clinical measures taken. It contains data on all hospitalizations and consultations to specialists in ambulatory care, but not consultations in primary care. InfCare Hepatitis is a national database including clinical data from 87% of the infectious disease clinics in Sweden, and one of the gastroenterology clinics. It was started in 2009 and serves primarily as a clinical decision support and benchmarking tool, but can also be used for research . In this study, InfCare Hepatitis is considered a treatment-specific quality register, not disease specific, as the current number of untreated patients in the register is low .
Data from these sources were linked on an individual level, using the personal identification number (PIN) .
Patients who were dispensed or administered any of the following drugs in Sweden during 2014–2015 and who therefore are detected in either the Swedish Prescribed Drug Register and InfCare Hepatitis or in the Prescribed Drug Register only were included: sofosbuvir (ATC code J05AX15), simeprevir (ATC code J05AE14), daclatasvir (ATC code J05AX14), sofosbuvir/ledipasvir (ATC code J05AX65), dasabuvir (ATC code J05AX16), and ombitasvir/paritaprevir/ritonavir (ATC code J05AX67).
The analysis of treatment outcome was based on total treatment given, including potential add-on treatment given when the patient did not respond sufficiently to the initial treatment and re-treatment for patients with a relapse.
Adherence to drug recommendations was defined as initiation of treatment with the drug or drugs recommended for the genotype in question at the time of treatment initiation. This analysis includes all patients with genotype 1–4 starting treatment from November 7th 2014, when the introduction protocol was implemented. Time of treatment initiation is based on the date of first dispensing in the Prescribed Drug Register or the treatment start date in InfCare Hepatitis (for patients without data in the Prescribed Drug Register).
The treatment eligibility criteria before and after July 2nd, 2015 respectively, were based on stage of fibrosis, prevalence of cirrhosis, and/or previous transplantation (Table 2). Adherence to the treatment eligibility criteria was defined as initiation of treatment in a patient who, at the time of initiation, did fulfill at least one of the criteria.
Treatment outcome, i.e. cure rate, was measured as the proportion of patients per genotype who achieved a sustained viral response, i.e. undetectable levels of HCV-RNA in plasma 12 weeks after end of treatment (SVR12).
Adherence to the introduction protocol was measured as follows:
the proportion of patients who were treated with the drug or drugs recommended as first-line treatment for their specific genotype at the time of treatment initiation and
the proportion of patients who met the treatment eligibility criteria before and after July 2nd, 2015, at the time of treatment initiation.
Introduction rate was measured as the relative proportion of patients on treatment per region over time, and comparisons were made between the six healthcare regions: northern, middle, south-east, western and southern Sweden, and the region of Stockholm-Gotland, respectively. The general population distribution of the regions was based on population statistics dated June 30th 2015, from Statistics Sweden.
InfCare completeness was calculated as the number of patients with the specific characteristic in InfCare divided by the number of patients in the study cohort.
Descriptive statistics, such as numbers and proportions, were used to describe the study cohorts and the utilization patterns, with 95% confidence intervals (95% CI) where appropriate. Analyses were stratified by sex and age in the categories 0–20, 21-30, 31-40, 41-50, 51-60, 61-70, 71-80 and ≥ 81 years. Means were presented with standard deviations (SD). Data were analyzed in SAS Enterprise Guide 6.1. (SAS Institute, Cary, NC).
The study was reviewed and approved by the Regional Ethical Review Board in Stockholm, approval no. 2015/497-31/1.