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  1. Article ; Online: The Correlated Beta Dose Optimisation Approach

    John Benest / Sophie Rhodes / Thomas G. Evans / Richard G. White

    Vaccines, Vol 10, Iss 1838, p

    Optimal Vaccine Dosing Using Mathematical Modelling and Adaptive Trial Design

    2022  Volume 1838

    Abstract: Mathematical modelling methods and adaptive trial design are likely to be effective for optimising vaccine dose but are not yet commonly used. This may be due to uncertainty with regard to the correct choice of parametric model for dose-efficacy or dose- ... ...

    Abstract Mathematical modelling methods and adaptive trial design are likely to be effective for optimising vaccine dose but are not yet commonly used. This may be due to uncertainty with regard to the correct choice of parametric model for dose-efficacy or dose-toxicity. Non-parametric models have previously been suggested to be potentially useful in this situation. We propose a novel approach for locating optimal vaccine dose based on the non-parametric Continuous Correlated Beta Process model and adaptive trial design. We call this the ‘Correlated Beta’ or ‘CoBe’ dose optimisation approach. We evaluated the CoBe dose optimisation approach compared to other vaccine dose optimisation approaches using a simulation study. Despite using simpler assumptions than other modelling-based methods, we found that the CoBe dose optimisation approach was able to effectively locate the maximum efficacy dose for both single and prime/boost administration vaccines. The CoBe dose optimisation approach was also effective in finding a dose that maximises vaccine efficacy and minimises vaccine-related toxicity. Further, we found that these modelling methods can benefit from the inclusion of expert knowledge, which has been difficult for previous parametric modelling methods. This work further shows that using mathematical modelling and adaptive trial design is likely to be beneficial to locating optimal vaccine dose, ensuring maximum vaccine benefit and disease burden reduction, ultimately saving lives
    Keywords adaptive design ; clinical trials ; continual modelling ; dose response ; dosing ; modelling ; Medicine ; R
    Subject code 621
    Language English
    Publishing date 2022-10-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Mathematical Modelling for Optimal Vaccine Dose Finding

    John Benest / Sophie Rhodes / Thomas G. Evans / Richard G. White

    Vaccines, Vol 10, Iss 756, p

    Maximising Efficacy and Minimising Toxicity

    2022  Volume 756

    Abstract: Vaccination is a key tool to reduce global disease burden. Vaccine dose can affect vaccine efficacy and toxicity. Given the expense of developing vaccines, optimising vaccine dose is essential. Mathematical modelling has been suggested as an approach for ...

    Abstract Vaccination is a key tool to reduce global disease burden. Vaccine dose can affect vaccine efficacy and toxicity. Given the expense of developing vaccines, optimising vaccine dose is essential. Mathematical modelling has been suggested as an approach for optimising vaccine dose by quantitatively establishing the relationships between dose and efficacy/toxicity. In this work, we performed simulation studies to assess the performance of modelling approaches in determining optimal dose. We found that the ability of modelling approaches to determine optimal dose improved with trial size, particularly for studies with at least 30 trial participants, and that, generally, using a peaking or a weighted model-averaging-based dose–efficacy relationship was most effective in finding optimal dose. Most methods of trial dose selection were similarly effective for the purpose of determining optimal dose; however, including modelling to adapt doses during a trial may lead to more trial participants receiving a more optimal dose. Clinical trial dosing around the predicted optimal dose, rather than only at the predicted optimal dose, may improve final dose selection. This work suggests modelling can be used effectively for vaccine dose finding, prompting potential practical applications of these methods in accelerating effective vaccine development and saving lives.
    Keywords dosing ; dose response ; modelling ; clinical trials ; adaptive design ; continual modelling ; Medicine ; R
    Subject code 610
    Language English
    Publishing date 2022-05-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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    Inter-library loan at ZB MED

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  3. Article ; Online: Response Type and Host Species may be Sufficient to Predict Dose-Response Curve Shape for Adenoviral Vector Vaccines

    John Benest / Sophie Rhodes / Sara Afrough / Thomas Evans / Richard White

    Vaccines, Vol 8, Iss 155, p

    2020  Volume 155

    Abstract: Vaccine dose-response curves can follow both saturating and peaking shapes. Dose-response curves for adenoviral vector vaccines have not been systematically described. In this paper, we explore the dose-response shape of published adenoviral animal and ... ...

    Abstract Vaccine dose-response curves can follow both saturating and peaking shapes. Dose-response curves for adenoviral vector vaccines have not been systematically described. In this paper, we explore the dose-response shape of published adenoviral animal and human studies. Where data were informative, dose-response was approximately five times more likely to be peaking than saturating. There was evidence that host species and response type may be sufficient for prediction of dose-response curve shape. Dose-response curve shape prediction could decrease clinical trial costs, accelerating the development of life-saving vaccines.
    Keywords dosing ; dose-response ; adenovirus-vectored vaccines ; dose dynamics ; Medicine ; R
    Language English
    Publishing date 2020-03-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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    Inter-library loan at ZB MED

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  4. Article ; Online: Immunologic Dose-Response to Adenovirus-Vectored Vaccines in Animals and Humans

    Sara Afrough / Sophie Rhodes / Thomas Evans / Richard White / John Benest

    Vaccines, Vol 8, Iss 1, p

    A Systematic Review of Dose-Response Studies of Replication Incompetent Adenoviral Vaccine Vectors when Given via an Intramuscular or Subcutaneous Route

    2020  Volume 131

    Abstract: Optimal vaccine dosing is important to ensure the greatest protection and safety. Analysis of dose-response data, from previous studies, may inform future studies to determine the optimal dose. Implementing more quantitative modelling approaches in ... ...

    Abstract Optimal vaccine dosing is important to ensure the greatest protection and safety. Analysis of dose-response data, from previous studies, may inform future studies to determine the optimal dose. Implementing more quantitative modelling approaches in vaccine dose finding have been recently suggested to accelerate vaccine development. Adenoviral vectored vaccines are in advanced stage of development for a variety of prophylactic and therapeutic indications, however dose-response has not yet been systematically determined. To further inform adenoviral vectored vaccines dose identification, historical dose-response data should be systematically reviewed. A systematic literature review was conducted to collate and describe the available dose-response studies for adenovirus vectored vaccines. Of 2787 papers identified by Medline search strategy, 35 were found to conform to pre-defined criteria. The majority of studies were in mice or humans and studied adenovirus serotype 5. Dose-response data were available for 12 different immunological responses. The majority of papers evaluated three dose levels, only two evaluated more than five dose levels. The most common dosing range was 10 7 −10 10 viral particles in mouse studies and 10 8 −10 11 viral particles in human studies. Data were available on adenovirus vaccine dose-response, primarily on adenovirus serotype 5 backbones and in mice and humans. These data could be used for quantitative adenoviral vectored vaccine dose optimisation analysis.
    Keywords dosing ; dose-response ; adenovirus-vectored vaccines ; immunogenicity ; clinical ; pre-clinical ; Medicine ; R
    Language English
    Publishing date 2020-03-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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    Inter-library loan at ZB MED

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  5. Article ; Online: Optimising Vaccine Dose in Inoculation against SARS-CoV-2, a Multi-Factor Optimisation Modelling Study to Maximise Vaccine Safety and Efficacy

    John Benest / Sophie Rhodes / Matthew Quaife / Thomas G. Evans / Richard G. White

    Vaccines, Vol 9, Iss 2, p

    2021  Volume 78

    Abstract: Developing a vaccine against the global pandemic SARS-CoV-2 is a critical area of active research. Modelling can be used to identify optimal vaccine dosing; maximising vaccine efficacy and safety and minimising cost. We calibrated statistical models to ... ...

    Abstract Developing a vaccine against the global pandemic SARS-CoV-2 is a critical area of active research. Modelling can be used to identify optimal vaccine dosing; maximising vaccine efficacy and safety and minimising cost. We calibrated statistical models to published dose-dependent seroconversion and adverse event data of a recombinant adenovirus type-5 (Ad5) SARS-CoV-2 vaccine given at doses 5.0 × 10 10 , 1.0 × 10 11 and 1.5 × 10 11 viral particles. We estimated the optimal dose for three objectives, finding: (A) the minimum dose that may induce herd immunity, (B) the dose that maximises immunogenicity and safety and (C) the dose that maximises immunogenicity and safety whilst minimising cost. Results suggest optimal dose [95% confidence interval] in viral particles per person was (A) 1.3 × 10 11 [0.8–7.9 × 10 11 ], (B) 1.5 × 10 11 [0.3–5.0 × 10 11 ] and (C) 1.1 × 10 11 [0.2–1.5 × 10 11 ]. Optimal dose exceeded 5.0 × 10 10 viral particles only if the cost of delivery exceeded £0.65 or cost per 10 11 viral particles was less than £6.23. Optimal dose may differ depending on the objectives of developers and policy-makers, but further research is required to improve the accuracy of optimal-dose estimates.
    Keywords dosing ; dose-response ; adenovirus-vectored vaccines ; dose dynamics ; COVID-19 ; Medicine ; R
    Subject code 333
    Language English
    Publishing date 2021-01-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

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