I-Feng Lin

Background In observational studies, how the magnitude of potential selection bias in a sensitivity analysis can be quantified is rarely discussed. The purpose of this study was to develop a sensitivity analysis strategy by using the bias-correction index (BCI) approach for quantifying the influence and direction of selection bias. Methods We used a BCI, a function of selection probabilities conditional on outcome and covariates, with different selection bias scenarios in a logistic regression setting. A bias-correction sensitivity plot was illustrated to analyze the associations between proctoscopy examination and sociodemographic variables obtained using the data from the Taiwan National Health Interview Survey (NHIS) and of a subset of individuals who consented to having their health insurance data further linked. Results We included 15,247 people aged ≥20 years, and 87.74% of whom signed the informed consent. When the entire sample was considered, smokers were less likely to undergo proctoscopic examination (odds ratio (OR): 0.69, 95% CI [0.57–0.84]), than nonsmokers were. When the data of only the people who provided consent were considered, the OR was 0.76 (95% CI [0.62–0.94]). The bias-correction sensitivity plot indicated varying ORs under different degrees of selection bias. Conclusions When data are only available in a subsample of a population, a bias-correction sensitivity plot can be used to easily visualize varying ORs under different selection bias scenarios. The similar strategy can be applied to models other than logistic regression if an appropriate BCI is derived.

This study investigated the relative effectiveness of a mix-and-match vaccination strategy, primarily comprising ChAdOx1 nCOV-19, mRNA-1273, BNT162b2, and a protein-based vaccine, MVC-COV1901, against COVID-19 in a healthcare worker (HCW) cohort in Taiwan during a period when the Omicron variant was predominant. The analysis included a total of 21,729 HCWs and recorded 3,672 infections with no severe disease nor death. Two main findings were observed from the study. Firstly, for those with ChAdOx1 nCOV-19 as primary series, a booster dose with BNT162b2 was associated with a small decrease in the risk of acquiring infection compared to those with mRNA-1273 as a booster (Adjust hazard ratio [Adj HR] 0.864; 95% confidence interval [CI] 0.761‒0.981, P = .024). Secondly, for HCWs receiving an mRNA-1273 booster, compared to those receiving ChAdOx1 nCOV-19 as the primary series, mixed primary series and homologous mRNA-1273 primary series were associated with a higher (Adj HR 1.144; 95% CI 1.021‒1.282, P = .021) and lower risk (Adj HR 0.735; 95% CI 0.671‒0.805, P < .001) of acquiring infection, respectively. Our study demonstrated that mix-and-match vaccination strategy may be associated with different level of risk reduction in acquiring infection, and sizable, prospective studies are encouraged to further elucidate our observation.

Rapid development and deployment of vaccines is crucial to control the continuously evolving COVID-19 pandemic. The placebo-controlled phase 3 efficacy trial is still the standard for authorizing vaccines in the majority of the world. However, due to a lack of eligible participants in parts of the world, this has not always been feasible. Recently, the Taiwan Food and Drug Administration, following the consensus of the International Coalition of Medicines Regulatory Authorities (ICMRA), adopted the use of immunobridging studies as acceptable for authorizing COVID-19 vaccines in lieu of efficacy data. Here, we describe a study in which our candidate vaccine, MVC-COV1901, an adjuvanted protein subunit vaccine, has been granted emergency use authorization (EUA) in Taiwan based on a noninferiority immunobridging study. Immunogenicity results from the per protocol immunogenicity (PPI) subset (n = 903) from the MVC-COV1901 phase 2 trial were compared with results from 200 subjects who had received an adenovirus vector vaccine, AstraZeneca ChAdOx nCOV-19 (AZD1222), in a separate study. The lower bound of the 95% confidence interval (CI) of the geometric mean titer (GMT) ratio comparing MVC-COV1901 to AZD1222 was 3.4. The lower bound of the 95% CI of the sero-response rate was 95.5%. Both the GMT ratio and sero-response rate exceeded the criteria established by the Taiwan regulatory authority, leading to EUA approval of MVC-COV1901 in Taiwan.

Background Rapid development and deployment of vaccine is crucial to control the continuously evolving COVID-19 pandemic. Placebo-controlled phase 3 efficacy trial is still standard for authorizing vaccines in majority of the world. However, due to lack of cases or participants in parts of the world, this has not always been feasible. An alternative to efficacy trial is immunobridging, in which the immune response or correlates of protection of a vaccine candidate is compared against an approved vaccine. Here we describe a case study where our candidate vaccine, MVC-COV1901, has been granted for emergency use authorization (EUA) locally based on the non-inferiority immunobridging process. Methods The per protocol immunogenicity (PPI) subset from the MVC-COV1901 phase 2 trial was used for this study and consisted of 903 subjects who have received two doses of MVC-COV1901 as scheduled in the clinical trial. The comparator set of population consisted of 200 subjects of ≥ 20 years of age who were generally healthy and have received two doses of AstraZeneca ChAdOx nCOV-19 (AZD1222) recruited from Taoyuan General Hospital, Ministry of Health and Welfare. Results MVC-COV1901 was shown to have a geometric mean titer (GMT) ratio lower bound 95% confidence interval (CI) of 3.4 against the comparator vaccine and a seroconversion rate of 95.5% at the 95% CI lower bound, which both exceeded the criteria set by the Taiwan regulatory authority for EUA approval. These results supported the EUA approval of MVC-COV1901 by the Taiwanese regulatory authority in July 2021. Following the consensus of the International Coalition of Medicines Regulatory Authorities (ICMRA), countries from the Access Consortium has recently adopted the use of immunobridging studies as acceptable for authorizing COVID-19 vaccines in lieu of efficacy data. Conclusion The data presented in the study showed that it is reasonably likely that the vaccine efficacy of MVC-COV1901 is similar or superior to that of AZ. Data could be used in support of further vaccine development and regulatory approval.

Infection with hepatitis C virus (HCV) does not induce protective immunity, and re-exposure to HCV can reinfect the population engaging in high-risk behavior. An increasing incidence of acute hepatitis C infection in people living with HIV (PLWH) has been described in recent years. This retrospective cohort study was conducted in PLWH who completed HCV therapy between June 2009 and June 2020 at an HIV care hospital, to analyze their basic characteristics and risky behavior. Of 2419 patients, 639 were diagnosed with HCV infection and 516 completed the HCV therapy with a sustained virologic response. In total, 59 patients (11.4%) were reinfected with acute hepatitis C, and the median time to reinfection was 85.3 weeks (IQR: 57–150). The incidence of reinfection was 6.7 cases/100 person-years. The factors associated with reinfection were being male (AHR, 8.02; 95% CI 1.08–59.49), DAA (direct-acting antiviral) treatment (AHR, 2.23; 95% CI 1.04–4.79), liver cirrhosis (AHR, 3.94; 95% CI 1.09–14.22), heroin dependency (AHR: 7.41; 95% CI 3.37–14.3), and HIV viral loads <50 copies/mL at the follow-up (AHR: 0.47, 95% CI 0.24–0.93) in the subgroup of people who inject drugs (PWID). Amphetamine abuse (AHR: 20.17; 95% CI 2.36–172.52) was the dominant factor in the subgroup of men who have sex with men (MSM). Our study suggests that education and behavioral interventions are needed in this population to prevent reinfection.