The International Childhood Cancer Cohort Consortium (I4C)
Policies and procedures
Article
|Published
Find everything you need to collaborate with I4C or become a member here! This manual guides the governance of I4C and the execution of its projects.
Background
Understanding the primary causes and the main mechanisms in the development of cancer is crucial. The etiologies of cancers that occur in childhood, adolescence or early adulthood are poorly understood. The early debut points to causal factors that may have their influence as early as fetal life. Large population-based cohorts that include pregnancy information are needed to test out etiological hypotheses. Each cancer type is relatively rare, making it difficult to achieve sufficient sample sizes in one setting. In addition, replications of findings across populations will strengthen inference. To prevent initiation or progression of cancer, it is important to find environmental factors that have an impact on early development. In addition, deeper understanding of mechanisms in subtypes of cancers will support better treatment. The aim of I4C is to contribute to the prevention and treatment of early cancers by performing specific projects using data and biological samples from large international birth cohorts.
The first workshop that led to the formation of I4C was held in Rockville, MD, USA on September 28-29, 2005. Since then, I4C has developed into a consortium of cohorts that has managed to perform a series of collaborative projects (1,2). An important component for the collaboration was the creation of a data coordinating center in Murdoch Children’s Research Institute (MRCI) in Melbourne, Australia under the direction of Professor Terry Dwyer, who played a central role in initiating and leading I4C. Restrictions on the ability to share data from many cohorts into one location have, however, changed the strategy for conducting research.
The management of I4C and execution of specific projects is guided by a policies and procedures manual. Although many facets of I4C are unchanged, recent developments require an update. The Steering group of I4C decided on this revised manual, replacing the previous (3). Several historical and scientific issues will be presented in detail in a cohort update paper, to be published in an international journal (4).
Cohort members
Birth cohorts with sufficient data to contribute to I4C projects are eligible for membership. There are no specific criteria for membership. Each cohort will be evaluated based on population background, sample size, exposure data content and quality and cancer outcomes. The steering committee will decide on membership.
As of 2025, the following cohorts are members of I4C:
- Tasmanian Infant Health Study (THIS)
- Danish National Birth Cohort (DNBC)
- Jerusalem Perinatal Study (JPS)
- Norwegian Mother, Father, and Child Cohort Study (MoBa)
- Avon Longitudinal Study of Parents and Children (ALSPAC)
- Collaborative Perinatal Project (CPP)
- Campinas Infant Health Survey
- Japan National Children’s Study (JECS)
- Italian NINFEA (Nascita e INFanzia: gli Effetti dell'Ambiente) cohort
- The Korean Children’s Environmental Health Study (Ko-CHENS)
- The Born in Guangzhou Cohort Study (BIGCS)
- Generation Victoria (GenV)
Steering committee
The steering committee is composed of representatives from the participating cohorts. In addition, a representative from the International Agency on Research in Cancer (IARC), World Health Organization and a representative from the National Institute of Cancer (NCI) in the USA are members. The steering group has regular meetings. An important task is to stimulate researchers to come up with proposals for new projects and then to accept and monitor projects. The committee also decides on the inclusion of new cohorts and lays out strategies for achieving scientific aims.
Coordination center
During 2024, the coordination center has moved from MRCI in Australia to the Norwegian Institute of Public Health (NIPH) in Oslo, Norway. This center is responsible for preparing and arranging regular meetings for the steering group, maintaining a website, and for receiving and handling proposals for research projects. In addition, NIPH will write and archive minutes of meetings.
Annual meeting
Each year participants in I4C together with invited scientists meet for discussions of ongoing and new research projects, for informing each other of recent developments in the cohorts, and for presentations of new cohorts for potential membership.
Proposals for research projects
Proposals for a new I4C project should be forwarded to the coordination center with the following elements: title, background, research questions, design, main variables, statistical method and project organization including name and affiliation of the principal investigator (PI). The coordination center will prepare the proposal for decision by the steering group, and follow up further execution of the project with the principal investigator.
Federated analyses
To protect the cohort participants’ personal integrity, many cohorts have made the decision that data on an individual level cannot be exported to others. However, aggregated (group level) results from statistical analyses can be shared without restrictions, and without formal agreements. This is the basis for I4C’s change from operating with a data coordination center to a system of federated analysis, which means that a certain analysis is performed locally in each cohort based upon an agreed plan. The aggregated results are sent to the principal investigator for the project and meta-analyzed or presented cohort-wise in a publication. Each cohort is responsible for establishing a valid legal basis, including ethical approval. PIs of specific projects must specify their funding sources, whether through their institution's internal funds or through external funding. They are encouraged to apply for funding to cover I4C expenses. I4C doesn’t hold any funds.
Projects that require the analyses of biospecimens from each participating cohort, can agree on the use of a central institution for analysis. This will require a material transfer agreement and data sharing agreement from each cohort to such an institution. Analytic results can then be returned to each cohort and included in federated analyses.
Publication of results
The principal investigator in each project has primary responsibility for drafting the first version of an I4C publication. Authorship should be in accordance with the recommendations for the conduct, reporting, editing, and publication of scholarly work in medical journals as issued by the International Committee of Medical Journal Editors (5). The final version of the publication should be viewed and commented upon by the steering group before submission.
The document was agreed upon at the I4C Steering Committee Meeting May 22 2025.
References
- Brown RC et al. The International Childhood Cancer Cohort Consortium (I4C). Int J Epidemiol 2007;36:724-30.
- Tikellis G et al. The International Childhood Cancer Cohort Consortium (I4C): A research platform of prospective cohorts for studying the aetiology of childhood cancers. Paediatr Perinat Epidemiol 2018;32:568-83.
- International Childhood Cancer Cohort Consortium (I4C) Policies and Procedures Manual, version as of 1918 based on the original version from March 2013.
- New cohort update