Integrating trials into a whole-population cohort of children and parents: statement of intent (trials) for the Generation Victoria (GenV) cohort

Melissa Wake, Yanhong Jessika Hu, Hayley Warren, Margie Danchin, Michael Fahey, Francesca Orsini, Maurizio Pacilli, Kirsten P Perrett, Richard Saffery, Andrew Davidson, Melissa Wake, Yanhong Jessika Hu, Hayley Warren, Margie Danchin, Michael Fahey, Francesca Orsini, Maurizio Pacilli, Kirsten P Perrett, Richard Saffery, Andrew Davidson

Abstract

Background: Very large cohorts that span an entire population raise new prospects for the conduct of multiple trials that speed up advances in prevention or treatment while reducing participant, financial and regulatory burden. However, a review of literature reveals no blueprint to guide this systematically in practice. This Statement of Intent proposes how diverse trials may be integrated within or alongside Generation Victoria (GenV), a whole-of-state Australian birth cohort in planning, and delineates potential processes and opportunities.

Methods: Parents of all newborns (estimated 160,000) in the state of Victoria, Australia, will be approached for two full years from 2021. The cohort design comprises four elements: (1) consent soon after birth to follow the child and parent/s until study end or withdrawal; retrospective and prospective (2) linkage to clinical and administrative datasets and (3) banking of universal and clinical biosamples; and (4) GenV-collected biosamples and data. GenV-collected data will focus on overarching outcome and phenotypic measures using low-burden, universal-capable electronic interfaces, with funding-dependent face-to-face assessments tailored to universal settings during the early childhood, school and/or adult years.

Results: For population or registry-type trials within GenV, GenV will provide all outcomes data and consent via traditional, waiver, or Trials Within Cohorts models. Trials alongside GenV consent their own participants born within the GenV window; GenV may help identify potential participants via opt-in or opt-out expression of interest. Data sharing enriches trials with outcomes, prior data, and/or access to linked data contingent on custodian's agreements, and supports modeling of causal effects to the population and between-trials comparisons of costs, benefits and utility. Data access will operate under the Findability, Accessibility, Interoperability, and Reusability (FAIR) and Care and Five Safes Principles. We consider governance, ethical and shared trial oversight, and expectations that trials will adhere to the best practice of the day.

Conclusions: Children and younger adults can access fewer trials than older adults. Integrating trials into mega-cohorts should improve health and well-being by generating faster, larger-scale evidence on a longer and/or broader horizon than previously possible. GenV will explore the limits and details of this approach over the coming years.

Keywords: Children; Clinical trial as topic; Generation Victoria (GenV); Intervention; Multiple baseline randomized trials; Population studies; Randomization; Registry trials; Research methodology; Trials within cohorts.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Relationship of the main cohort to trials within and alongside GenV
Fig. 2
Fig. 2
a GenV Principles. b Principles for Trials Within and Alongside GenV
Fig. 3
Fig. 3
Statement of intent: process flowchart for trials within and alongside GenV
Fig. 4
Fig. 4
Schematic diagram showing life course accrual of parent and child data
Fig. 5
Fig. 5
GenV’s outcomes hierarchy
Fig. 6
Fig. 6
Benefits of trials sharing data with GenV and of GenV sharing data with trials
Fig. 7
Fig. 7
Age of children by calendar year to 2027 to assist with planning trials

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