**All data access from third-parties will be subjected to an** **application**
within _EDCMixRisk_ , that will be examined by the management of the
consortium (Project Steering Committee). In evaluating these applications, the
Project Steering Committee will also consider whether involving the Ethics
Advisory Board of the project in its decision-making process. In addition,
beneficiaries have agreed to (i) grant the power of veto for the release of
any data to those who produce them, (ii) release all data produced by the end
of the project, (iii) leave open the possibility that data produced by one
beneficiary may be released upon its request.

The **Controlled** **Access** model guarantees that data potentially leading
to reidentification of donors can only be accessed and used by researchers
that are granted permission and the necessary credentials by the management of
_EDC-MixRisk_ . This allows having the data used only for purposes that are
examined in advance by _EDC-MixRisk_ , and ensures the project’s compliance
with the highest EU ethical standards, those currently followed by other big
projects and funding institutions (e.g. the Cancer Genome Atlas, the
International Human Epigenome Consortium), as well as with cutting edge
bioethical standards for collections of biological samples and/or data (see
Mascalzoni et al. 2014).

The same kind of controlled access will be extended to the sharing of
**specimens** , by ensuring that all members or partners collecting and
accessing samples comply with the same standards.

Access to _EDC-MixRisk_ ’s database will be conditional upon acceptance of a
number of requirements granting **full compliance** with national and EU
legislation (Directive 95/46/EC, Directive 2004/23/EC) protecting the privacy
and autonomy of patients/donors, as well as committing the recipient of the
data to accept that they will not attempt to re-identify sample donors. Upon
future revisions of the DMP, beneficiaries will also consider including a
specific requirement against ‘dual-use’ for access to _EDC-MixRisk_ ’s data.

The project management and Beneficiary 11 have already started to collect all
relevant documentation regarding the ethical approval of the experimental
procedures within _EDCMixRisk_ . As of today, the following documentation has
been received and is currently under review:

  1. Ethics approvals from Beneficiary 1 (KI) on the use of foetal tissues and ovarian cells including informed consent forms if relevant (in Swedish only); 

  

  2. Ethics approvals from Beneficiary 2 (KU) regarding the Selma cohort including informed consent forms and authorisations for processing personal; 

  

  3. Ethics approval from Beneficiary 6 (UU) for the experimental part of their subprojects. 

  

  4. Ethics approval from Beneficiary 8 (ULEI) regarding the LIFEchild cohort. 

  

  5. Ethics approval from Beneficiary 9 (UoA) regarding animal experiments 

  

  6. Ethics approvals from Beneficiary 11 (IEO) on the use of hESC (delivered upon finalization of grant agreement). 

  

  

The completion and delivery of following documents is instead in the course of
being finalized:

  1. Additional material regarding details on the Ethical approvals from Beneficiary 8 (ULEI) regarding the LIFE Child study cohort including informed consent forms and authorisations for processing personal data, as well as biobanking; 

  

  2. Copies of authorisations for animal experiments from Beneficiaries 3 (UGOT) and 7 (CNRS). Copies of authorisations for the supply of animals and the animal 

  

  

experiments, as well as copies of training certificates/personnel licences of
the staff involved in animal experiments, should be shortly delivered to
project management.

#  Future tasks

As recognised by the H2020 Guidelines, the DMP should also provide a detailed
description of data flows within the project on a dataset by dataset basis,
and should reflect the current state of affairs within the consortium about
the data that are produced and shared.

The **Controlled** **Access** model adopted by _EDC-MixRisk_ requires the full
development of an infrastructure that is able to grant the foreseen level of
control on the datasets (and their access), by establishing credentials for
all beneficiaries and potential external collaborators (both present and
future), as well as devising the suitable strategies for periodic
decisionmaking by project management over granting of authorizations.

The amount and sensitivity of data and samples that will be used by _EDC-
MixRisk_ requires careful consideration and a specific attention to the
procedures for their collection, sharing and management.

In order to facilitate the evolution of data infrastructures in _EDC-MixRisk_
, so as to streamline data flow within the project and while complying with
the H2020 Guidelines, we list a number of tasks and questions for project
management and beneficiaries:

  1. Establish dataset reference and name: project beneficiaries should provide the unique identifiers for the datasets (to be) produced. 

  

  2. Provide dataset description: describe the data that will be generated or collected, their origin, nature and scale, to whom they could be useful, whether they are codified (if yes, describe the codification process), and whether beneficiaries intend to use them in a scientific publication. We envisage that the type of data produced by the project will include: 

    1. General patient information such as gender and age, 

  
  

  

  

Clinical data (e.g. potential diagnosis, standard biomarkers across the two
cohorts),

  2. Sample identifiers, 

  

  3. Gene expression data (at various levels of coverage depth, and hence with different implications for reidentification etc.), 

  

  4. Genome or exome sequence files, 

  

  5. Epigenetic data (DNA methylation, histone modifications, non coding RNAs) 

  

  

  3. Provide dataset potential integration: are project beneficiaries knowledgeable about the existence (or not) of similar data and the possibilities for their integration with those produced in _EDC-MixRisk_ ? 

  

  4. Describe standards and metadata: provide references to existing suitable standards for datasets in the relevant discipline. 

  

  5. Design and implementation of data sharing infrastructure: as of today, _EDC-MixRisk_ does not dispose of a common infrastructure for data sharing. Upon establishment of this common platform the management of the project should then update the DMP by including information about: 

    1. access procedures 

  

    2. outlines of technical mechanisms for transfer, sharing and dissemination 

  

    3. necessary software(s) and other tools for enabling use 

  

    4. definition of the controlled access application form 

  

    5. identification of the repository where data will be stored, and the type of repository, e.g. the Science in Risk Assessment and Policy (SciRap) and Information Platform for Chemical Monitoring (IPChem) data bases. 

  
  

  

  6. Strategies for archiving and preservation (including storage and backup): describe the procedures that will be put in place for long-term preservation of the data, as well as indicate the type of data that beneficiaries foresee for inclusion in a publication and that should thus be preserved, what is the approximated end volume of datasets, what are the associated costs for the project and how these are planned to be covered 

  

  7. Interoperability of data and quality standards: provide a strategy for the potential standardisation of data in the project, such as the adoption of common codifications or software(s), for the sake of allowing data exchange between researchers, institutions, and organisations within and outside the project. 

  

  

The accomplishment of these technical tasks will enable the establishment of
the data flow within _EDC-MixRisk_ , fulfilling the DMP’s function of
implementing data quality, sharing and security within a Controlled Access
policy.