Estimating vaccine efficacy over time after a randomized study is unblinded

Purpose: To compare the efficacy of two different suture types in levator plication for correction of congenital ptosis. Subjects and methods: Prospective comparative interventional randomized study involving 42 eyes of 42 patients aged more than 6 years with congenital ptosis and good levator action. The exclusion criteria were as follows: bilateral ptosis, history of previous surgery, fair or poor levator action, and associated other ocular diseases. Patients were randomized into group A, in which double-armed 5/0 polyester Ethibond were used, and group B, in which double-armed 5/0 Coated Vicryl® (polyglactin 910) suture material we used. Outcomes including eyelid height and stability of eyelid height over time were compared with follow-up data. The MRD was 4.05 ± 0.36 mm and 3.95 ± 0.34 after 1 week for both groups A and B, respectively. At the end of study follow up period (24 weeks), the MRD was 3.60 ± 0.42 mm in group A, and 2.52 ± 0.85 mm in group B. Conclusion: No difference in eyelid height between two groups in early postoperative period, but the postoperative eyelid height was more stable over time in the 5/0 polyester Ethibond group (group A) than in the 5/0 Coated Vicryl® (polyglactin 910) group (group B).

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The Impact of Serotype Cross-Protection on Vaccine Trials: DENVax as a Case Study

Vaccines ◽

10.3390/vaccines8040674 ◽

2020 ◽

Vol 8 (4) ◽

pp. 674

Author(s):

Maíra Aguiar ◽

Nico Stollenwerk

Keyword(s):

Vaccine Efficacy ◽

Careful Consideration ◽

Dengue Vaccine ◽

Serious Adverse Events ◽

Post Vaccination ◽

Vaccine Trials ◽

Long Time ◽

Health Need ◽

The Impact ◽

Over Time

There is a growing public health need for effective preventive interventions against dengue, and a safe, effective and affordable dengue vaccine against the four serotypes would be a significant achievement for disease prevention and control. Two tetravalent dengue vaccines, Dengvaxia (CYD-TDV—Sanofi Pasteur) and DENVax (TAK 003—Takeda Pharmaceutical Company), have now completed phase 3 clinical trials. Although Dengvaxia resulted in serious adverse events and had to be restricted to individuals with prior dengue infections, DENVax has shown, at first glance, some encouraging results. Using the available data for the TAK 003 trial, we estimate, via the Bayesian approach, vaccine efficacy (VE) of the post-vaccination surveillance periods of 12 and 18 months. Although better measurement over a long time was expected for the second part of the post-vaccination surveillance, variation in serotype-specific efficacy needs careful consideration. Besides observing that individual serostatus prior to vaccination is determinant of DENVax vaccine efficacy, such as for Dengvaxia, we also noted, after comparing the VE estimations for 12- and 18-month periods, that vaccine efficacy is decreasing over time. The comparison of efficacies over time is informative and very important, and brings up the discussion of the role of temporary cross-immunity in dengue vaccine trials and the impact of serostatus prior to vaccination in the context of dengue fever epidemiology.

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Initiating epoetin-alpha (EPO) 120,000 units (U) every three weeks (Q3W) in patients with chemotherapy (CT)-induced anemia (CIA) and a hemoglobin (Hb) of <11 g/dL

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.19589 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 19589-19589

Author(s):

F. E. Wilhelm ◽

V. Charu ◽

J. Glaspy ◽

V. Moyo ◽

M. Kamin

Keyword(s):

Randomized Study ◽

Intervention Group ◽

Screening Methods ◽

Transfusion Rate ◽

Open Label ◽

Epoetin Alpha ◽

Changes Over Time ◽

To Receive ◽

Prescribing Information ◽

Over Time

19589 Background: Reported here are the final Hb results for the group of patients enrolled under an amendment to a larger study that was the first to compare early vs standard intervention with EPO 120,000 U Q3W in patients with CIA and Hb of 11 to 12 g/dL. The amendment allowed for treatment of patients who had a Hb value <11g/dL at screening. Methods: The larger study was a 16-week open-label randomized study that enrolled patients with non-myeloid malignancy, baseline (BL) Hb =11.0 and =12.0 g/dL, and CT planned for =9 weeks. Patients were randomized (1:1) to receive EPO 120,000 U subcutaneously Q3W immediately (early intervention group, EIG) or when their Hb fell to <11.0 g/dL (standard intervention group, SIG). If, at any dosing visit after the first EPO dose, Hb decreased to <10.0 g/dL, patients were switched to EPO 40,000 U weekly (QW). An amendment was added to the larger study to allow similar patients whose Hb was <11 g/dL at screening to be treated with EPO 120,000 U Q3W. EPO was withheld for Hb >13.0 g/dL at any dosing visit; dose was reduced for Hb >12.0 g/dL or Hb increase >1.5 g/dL in a 3-week period (current prescribing information recommends target Hb not to exceed 12 g/dL). Hb response was analyzed using an observed case approach and Hb data following switch to 40,000 U QW were censored. Results: Fifty patients were enrolled under the amendment. BL characteristics were: mean age, 62.0 years; 67% female; mean Hb 10.1 g/dL. Mean Hb changes over time from BL for patients receiving Q3W dosing are shown in the table . PRBC transfusion rate after 4 weeks on treatment was 24.5%. 18.0% of patients had at least one dose withheld and 22.0% had at least one dose reduction. Five deaths and 6 clinically relevant TVEs were reported. Conclusions: This study shows that EPO is effective in raising Hb when initiated in patients with CIA and a Hb of <11 g/dL at 120,000 U every 3 weeks. Further studies are warranted. No significant financial relationships to disclose. [Table: see text]

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RV144 Vaccine Imprinting Constrained HIV-1 Evolution Following Breakthrough Infection

Virus Evolution ◽

10.1093/ve/veab057 ◽

2021 ◽

Author(s):

Eric Lewitus ◽

Eric Sanders-Buell ◽

Meera Bose ◽

Anne Marie O’Sullivan ◽

Kultida Poltavee ◽

...

Keyword(s):

Placebo Group ◽

Vaccine Efficacy ◽

Vaccine Group ◽

Efficacy Trial ◽

Breakthrough Infection ◽

Diversifying Selection ◽

Hiv 1 ◽

Rv144 Vaccine ◽

Over Time ◽

Roll Out

Abstract The scale of the HIV-1 epidemic underscores the need for a vaccine. The multitude of circulating HIV-1 strains together with HIV-1’s high evolvability hint that HIV-1 could adapt to a future vaccine. Here we wanted to investigate the effect of vaccination on the evolution of the virus post-breakthrough infection. We analyzed 2,635 HIV-1 env sequences sampled up to a year post-diagnosis from 110 vaccine and placebo participants who became infected in the RV144 vaccine efficacy trial. We showed that the Env signatures sites that were previously identified to distinguish vaccine and placebo participants were maintained over time. In addition, fewer sites were under diversifying selection in the vaccine group than in the placebo group. These results indicate that HIV-1 would possibly adapt to a vaccine upon its roll out.

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Systemic Expression of Cytokine Production in Patients with Severe Pneumococcal Pneumonia: Effects of Treatment with a β-Lactam versus a Fluoroquinolone

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00658-07 ◽

2008 ◽

Vol 52 (7) ◽

pp. 2395-2402 ◽

Cited By ~ 22

Author(s):

Esther Calbo ◽

Montserrat Alsina ◽

Mónica Rodríguez-Carballeira ◽

Josep Lite ◽

Javier Garau

Keyword(s):

Pneumococcal Pneumonia ◽

Cytokine Production ◽

Inflammatory Responses ◽

Randomized Study ◽

Venous Blood ◽

Severe Pneumonia ◽

Necrosis Factor Alpha ◽

Tnf Α ◽

Severity Scores ◽

Over Time

ABSTRACT Bacterial alveolar invasion is followed by an inflammatory response. A systemic extension of the compartmentalized immune response has been described in patients with severe pneumonia. The data suggest that some antimicrobials may induce a differential release of cytokines. We conducted a prospective, randomized study in adult patients with severe pneumococcal pneumonia to measure the effects of ceftriaxone and levofloxacin in the systemic cytokine expression over time. Demographic, clinical characteristics, and severity scores were recorded. The serum concentrations of tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), IL-6, IL-8, IL-10, and IL-1 receptor agonist were measured at 0, 24, 72, and 120 h. A total of 32 patients were included in the study. Both groups were homogeneous in terms of age, comorbidities, severity of disease, and corticosteroid or statin use. With the single exception of IL-1β, all cytokines were detected in venous blood. All of the cytokines studied showed a similar pattern of progressive decrease over time. No significant differences in the concentrations of any of the cytokines studied were found, with the exception of TNF-α, for which lower concentrations were obtained at 120 h in the levofloxacin group (P = 0.014). Basal oxygen saturation (P = 0.034) and heart rate (P = 0.029) returned to normal values earlier in the levofloxacin arm. We demonstrated that in patients with severe pneumococcal pneumonia pro- and anti-inflammatory responses could be detected in venous blood, representing a systemic extension of the compartmentalized response. Treatment with a β-lactam agent or a fluoroquinolone has different effects on cytokine production and its systemic expression, impacting the clinical course of the disease.

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Reduced neutralisation of the Delta (B.1.617.2) SARS-CoV-2 variant of concern following vaccination

PLoS Pathogens ◽

10.1371/journal.ppat.1010022 ◽

2021 ◽

Vol 17 (12) ◽

pp. e1010022

Author(s):

Chris Davis ◽

Nicola Logan ◽

Grace Tyson ◽

Richard Orton ◽

William T. Harvey ◽

...

Keyword(s):

South African ◽

Vaccine Efficacy ◽

Antigenic Drift ◽

Productive Infection ◽

Subsequent Reduction ◽

Fold Reduction ◽

Antibody Titres ◽

Efficacy Assessment ◽

Induced Immunity ◽

Over Time

Vaccines are proving to be highly effective in controlling hospitalisation and deaths associated with SARS-CoV-2 infection but the emergence of viral variants with novel antigenic profiles threatens to diminish their efficacy. Assessment of the ability of sera from vaccine recipients to neutralise SARS-CoV-2 variants will inform the success of strategies for minimising COVID19 cases and the design of effective antigenic formulations. Here, we examine the sensitivity of variants of concern (VOCs) representative of the B.1.617.1 and B.1.617.2 (first associated with infections in India) and B.1.351 (first associated with infection in South Africa) lineages of SARS-CoV-2 to neutralisation by sera from individuals vaccinated with the BNT162b2 (Pfizer/BioNTech) and ChAdOx1 (Oxford/AstraZeneca) vaccines. Across all vaccinated individuals, the spike glycoproteins from B.1.617.1 and B.1.617.2 conferred reductions in neutralisation of 4.31 and 5.11-fold respectively. The reduction seen with the B.1.617.2 lineage approached that conferred by the glycoprotein from B.1.351 (South African) variant (6.29-fold reduction) that is known to be associated with reduced vaccine efficacy. Neutralising antibody titres elicited by vaccination with two doses of BNT162b2 were significantly higher than those elicited by vaccination with two doses of ChAdOx1. Fold decreases in the magnitude of neutralisation titre following two doses of BNT162b2, conferred reductions in titre of 7.77, 11.30 and 9.56-fold respectively to B.1.617.1, B.1.617.2 and B.1.351 pseudoviruses, the reduction in neutralisation of the delta variant B.1.617.2 surpassing that of B.1.351. Fold changes in those vaccinated with two doses of ChAdOx1 were 0.69, 4.01 and 1.48 respectively. The accumulation of mutations in these VOCs, and others, demonstrate the quantifiable risk of antigenic drift and subsequent reduction in vaccine efficacy. Accordingly, booster vaccines based on updated variants are likely to be required over time to prevent productive infection. This study also suggests that two dose regimes of vaccine are required for maximal BNT162b2 and ChAdOx1-induced immunity.

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