Correction to: Population Pharmacokinetics, Efficacy Exposure-response Analysis, and Model-based Meta-analysis of Fenebrutinib in Subjects with Rheumatoid Arthritis.

The article was published with an incomplete title. The complete title is "Population Pharmacokinetics, Efficacy Exposure-response Analysis, and Model-based Meta-analysis of Fenebrutinib in Subjects with Rheumatoid Arthritis" The original article has been corrected.

Population Pharmacokinetics, Efficacy Exposure-response Analysis, and Model-based Meta-analysis of Fenebrutinib in Subjects with Rheumatoid Arthritis [corrected].

PURPOSE: Fenebrutinib (GDC-0853), a Bruton's tyrosine kinase (BTK) inhibitor was investigated in a Phase 2 clinical trial in patients with rheumatoid arthritis (RA). Our aim was to apply a model-informed drug development (MIDD) approach to examine the totality of available clinical efficacy data. METHODS: Population pharmacokinetics (popPK) modeling, exposure-response (E-R) analysis, and model-based meta-analysis (MBMA) of fenebrutinib were performed based on the Phase 2 data. RESULTS: PopPK of fenebrutinib after oral administration was described using a 3-compartment model with linear elimination and a flexible absorption transit compartment model. Healthy subjects had a 52% higher apparent clearance than patients. E-R analyses based on longitudinal ACR20, ACR50, and ACR70 and DAS28 (CRP) data modeled fenebrutinib effect with an Emax function, and an efficacy plateau was achieved within the exposure range obtained in the Phase 2 clinical trial. Based on literature data, a summary-level clinical efficacy database was constructed, and MBMA determined ACR20, ACR50, and ACR70 responder rates in the placebo and adalimumab arms of the Phase 2 clinical trial were found to be consistent with historical data for these treatments. CONCLUSIONS: Our multi-pronged approach applied MIDD to maximize knowledge extraction of efficacy data and enabled robust interpretation from a Phase 2 clinical trial.

What Factors Influence Non-Participation Most in Colorectal Cancer Screening? A Discrete Choice Experiment.

BACKGROUND AND OBJECTIVE: Non-participation in colorectal cancer (CRC) screening needs to be decreased to achieve its full potential as a public health strategy. To facilitate successful implementation of CRC screening towards unscreened individuals, this study aimed to quantify the impact of screening and individual characteristics on non-participation in CRC screening. METHODS: An online discrete choice experiment partly based on qualitative research was used among 406 representatives of the Dutch general population aged 55-75 years. In the discrete choice experiment, respondents were offered a series of choices between CRC screening scenarios that differed on five characteristics: effectiveness of the faecal immunochemical screening test, risk of a false-negative outcome, test frequency, waiting time for faecal immunochemical screening test results and waiting time for a colonoscopy follow-up test. The discrete choice experiment data were analysed in a systematic manner using random-utility-maximisation choice processes with scale and/or preference heterogeneity (based on 15 individual characteristics) and/or random intercepts. RESULTS: Screening characteristics proved to influence non-participation in CRC screening (21.7-28.0% non-participation rate), but an individual's characteristics had an even higher impact on CRC screening non-participation (8.4-75.5% non-participation rate); particularly the individual's attitude towards CRC screening followed by whether the individual had participated in a cancer screening programme before, the decision style of the individual and the educational level of the individual. Our findings provided a high degree of confidence in the internal-external validity. CONCLUSIONS: This study showed that although screening characteristics proved to influence non-participation in CRC screening, a respondent's characteristics had a much higher impact on CRC screening non-participation. Policy makers and physicians can use our study insights to improve and tailor their communication plans regarding (CRC) screening for unscreened individuals.

The impact of vaccination and patient characteristics on influenza vaccination uptake of elderly people: A discrete choice experiment.

OBJECTIVES: To improve information for patients and to facilitate a vaccination coverage that is in line with the EU and World Health Organization goals, we aimed to quantify how vaccination and patient characteristics impact on influenza vaccination uptake of elderly people. METHODS: An online discrete choice experiment (DCE) was conducted among 1261 representatives of the Dutch general population aged 60 years or older. In the DCE, we used influenza vaccination scenarios based on five vaccination characteristics: effectiveness, risk of severe side effects, risk of mild side effects, protection duration, and absorption time. A heteroscedastic multinomial logit model was used, taking scale and preference heterogeneity (based on 19 patient characteristics) into account. RESULTS: Vaccination and patient characteristics both contributed to explain influenza vaccination uptake. Assuming a base case respondent and a realistic vaccination scenario, the predicted uptake was 58%. One-way changes in vaccination characteristics and patient characteristics changed this uptake from 46% up to 61% and from 37% up to 95%, respectively. The strongest impact on vaccination uptake was whether the patient had been vaccinated last year, whether s/he had experienced vaccination side effects, and the patient's general attitude towards vaccination. CONCLUSIONS: Although vaccination characteristics proved to influence influenza vaccination uptake, certain patient characteristics had an even higher impact on influenza vaccination uptake. Policy makers and general practitioners can use these insights to improve their communication plans and information regarding influenza vaccination for individuals aged 60 years or older. For instance, physicians should focus more on patients who had experienced side effects due to vaccination in the past, and policy makers should tailor the standard information folder to patients who had been vaccinated last year and to patient who had not.