Dataset Information

Statistical analysis plan for the OPTIMUM study: optimising immunisation using mixed schedules, an adaptive randomised controlled trial of a mixed whole-cell/acellular pertussis vaccine schedule.

ABSTRACT:

Objective

The purpose of this double-blind, randomised, controlled trial is to compare allergic outcomes in children following vaccination with acellular pertussis (aP) antigen (standard of care in Australia) given at 2 months of age versus whole cell pertussis (wP) in the infant vaccine schedule.

Participants

Up to 3000 Australian infants 6 to <12 weeks of age born ≥32 weeks gestation.

Interventions

The intervention is a wP containing vaccine as the first scheduled pertussis vaccine dose instead of an aP containing vaccine.

Outcomes

The primary outcome is a binary indicator of history of IgE-mediated food allergy at the age of 12 months confirmed, where necessary, with an oral food challenge before 18 months of age. Secondary outcomes include (1) history of parent-reported clinician-diagnosed new onset of atopic dermatitis by 6 or 12 months of age with a positive skin prick test to any allergen before 12 months of age, (2) geometric mean concentration in pertussis toxin-specific IgG before and 21 to 35 days after a booster dose of aP at 18 months of age, and (3) sensitisation to at least one allergen by 12 months of age.

Results

Operating characteristics of trial decision rules were evaluated by trial simulation. The selected rules for success and futility approximately maintain type I error of 0.05 and achieved power 0.85 for a reduction in the primary outcome from 10% in the control group to 7% in the intervention group.

Discussion

A detailed, prospective statistical analysis plan (SAP) is presented for this Bayesian adaptive design. The plan was written by the trial statistician and details the study design, pre-specified adaptive elements, decision thresholds, statistical methods, and the simulations used to evaluate the operating characteristics of the trial. Application of this SAP will minimise bias and supports transparent and reproducible research.

Trial registration

Australia & New Zealand Clinical Trials Registry, ACTRN12617000065392 . Registered on 12 January 2017 STUDY PROTOCOL: https://doi.org/10.1136/bmjopen-2020-042838.

SUBMITTER: Totterdell JA

PROVIDER: S-EPMC8819850 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Statistical analysis plan for the OPTIMUM study: optimising immunisation using mixed schedules, an adaptive randomised controlled trial of a mixed whole-cell/acellular pertussis vaccine schedule.

Totterdell James A JA Chacon Gladymar Perez GP Estcourt Marie J MJ Jones Mark M Richmond Peter P Snelling Thomas L TL Marsh Julie A JA

Trials 20220207 1

<h4>Objective</h4>The purpose of this double-blind, randomised, controlled trial is to compare allergic outcomes in children following vaccination with acellular pertussis (aP) antigen (standard of care in Australia) given at 2 months of age versus whole cell pertussis (wP) in the infant vaccine schedule.<h4>Participants</h4>Up to 3000 Australian infants 6 to <12 weeks of age born ≥32 weeks gestation.<h4>Interventions</h4>The intervention is a wP containing vaccine as the first scheduled pertuss ...[more]

PMID: 35130946

Similar Datasets

Project description:IntroductionCombination vaccines containing whole-cell pertussis antigens were phased out from the Australian national immunisation programme between 1997 and 1999 and replaced by the less reactogenic acellular pertussis (aP) antigens. In a large case-control study of Australian children born during the transition period, those with allergist diagnosed IgE-mediated food allergy were less likely to have received whole-cell vaccine in early infancy than matched population controls (OR: 0.77 (95% CI, 0.62 to 0.95)). We hypothesise that a single dose of whole-cell vaccine in early infancy is protective against IgE-mediated food allergy.Methods and analysisThis adaptive double-blind randomised controlled trial is investigating whether a mixed whole-cell/aP vaccine schedule prevents allergic disease in the first year of life. The primary outcome is IgE-mediated food allergy by 12 months of age. Secondary outcomes include new onset of atopic dermatitis by 6 or 12 months of age; sensitisation to at least one allergen by 12 months of age; seroconversion in anti-pertussis toxin IgG titres after vaccination with aP booster at 18 months of age; and solicited systemic and local adverse events following immunisation with pertussis-containing vaccines. Analyses will be performed using a Bayesian group sequential design.Ethics and disseminationThis study has been approved by the Child and Adolescent Health Service Human Research Ethics Committee, Perth, Western Australia (RGS 00019). The investigators will ensure that this trial is conducted in accordance with the principles of the Declaration of Helsinki and with the International Conference on Harmonisation Guidelines for Good Clinical Practice. Individual consent will be requested. Parents will be reimbursed reasonable travel and parking costs to attend the study visits. The dissemination of these research findings will follow the National Health and Medical Research Council of Australia Open Access Policy.Trial registration numberACTRN12617000065392p.

Dataset Information

Statistical analysis plan for the OPTIMUM study: optimising immunisation using mixed schedules, an adaptive randomised controlled trial of a mixed whole-cell/acellular pertussis vaccine schedule.

Objective

Participants

Interventions

Outcomes

Results

Discussion

Trial registration

Publications

Statistical analysis plan for the OPTIMUM study: optimising immunisation using mixed schedules, an adaptive randomised controlled trial of a mixed whole-cell/acellular pertussis vaccine schedule.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets