Goals per work package
Work package 1
The overall objective of WP1 is to create and maintain the conditions needed to achieve the objectives and deliverables of the CARING Project. Specific objectives are to:
• establish and maintain the governance structure of CARING
• develop the global CARING Management Plan and implement the overall strategy of the project
• issue progress reports and budget reviews
• do the day-to-day administrative and financial management of the programme
Work package 2
Objectives are to:
• conduct a systematic review on the risk of cancer and different cancer types associated with diabetes mellitus, in order to estimate the background risk of cancer in the patient population using insulins
• conduct a systematic review of clinical trials and epidemiological studies on the risk of cancer associated with the use of insulin and insulin analogues
• identify methodological issues and research gaps of available clinical trials and epidemiological studies
• conduct a systematic review of the published pre-clinical in vitro and in vivo evidence for plausible mechanisms underlying the risk of cancer associated with insulin and insulin analogues
Work package 3
The overall aims are to:
• determine the advantages/disadvantages of multi-database studies over a single database study (of similar size)
• determine the statistically best design for multi-database studies
More specific aims are to:
• review statistical techniques that can be used in multi-database studies
• perform simulation studies that will evaluate the performance of different statistical techniques to deal with inter-database variability in the completeness of data, data quality and variability in exposure and outcomes
• analyze and combine the data from the different sources using different approaches for confounder control and aggregation levels
• explore heterogeneity between countries, characteristics of databases and healthcare systems
Work package 4
The objectives are to:
• study the influence of potential confounders on the association between insulin (type, dose, duration) and cancer risk in observational studies in the literature
• identify potential confounders available in the databases and quantify the strength of their association with insulin use and cancer risk, individually and combined
• quantify the influence of the available confounders on the association between insulin use and cancer risk in the databases, individually and combined
• develop methods for external adjustment for unmeasured confounders in databases with missing information on certain confounders
• do sensitivity analyses of risk estimates using external adjustment for confounders of single country/single database studies
Work package 5
The aims are to:
• determine whether diabetic breast cancer patients have a specific breast cancer subtype defined by clinically used immunohistochemical tumour markers
• study whether diabetic breast cancer patients have a specific tumour profile (or tumour subtype) compared to non-diabetic breast cancer patients, and whether this may be related to specific pathways (e.g. IGF), using CGH profiling
• study whether the use of insulin and insulin analogues are related to specific pathways in breast tumours of diabetic patients
Work package 6
Objectives are to:
• determine associations between new insulin and insulin analogues use and risk of cancer and different cancer types. Exposure effects of daily dosage, time and/or intensity of insulin treatment on the likelihood of developing cancer will be studied
• study the hazard patterns of cancer risk associated with the use of insulin and insulin analogues
• develop a clinical risk score for the prediction of cancer in users of insulin and insulin analogues
Work package 7
The aims are to:
• raise awareness of the project among key stakeholders and influencers
• communicate the findings of the project to the scientific community, regulators, policymakers and to the healthcare sector across Europe
• interact with related national, European and international projects for mutual benefit concerning exchange of research expertise and dissemination of results