In the Implementation Phase all the study artefacts are created such as the Study Outline, Study Protocol, Cohort Definitions, Study Package.


Study Outline

Once agreement is reached between EMA and the DARWIN EU® CC to conduct a DARWIN EU® study, the Study Outline Form is completed describing aspects such as: Study Team, Data Sources, Choice of study type and related study design including methodological aspects, governance board approval and timelines.

The completed Study Outline Form is next submitted to the EMA for approval. Once the Study Outline Form is approved by the EMA, the protocol for the DARWIN EU® studies is generated.

The Study Outline as approved and signed-off by EMA is archived at the DARWIN EU® CC in a study specific project file.

Study Protocol Development

Once agreement is reached between EMA and the DARWIN EU® CC on the Study Outline, the Study Protocol is generated following the ENCePP code of conduct.

Upon completion of the Draft Study Protocol, this Study Protocol needs to be approved by the EMA. 

Once the Study Protocol is approved and signed-off by EMA, the study protocol is archived at the DARWIN EU® CC in a study specific project file.

Next, the final study protocol is uploaded to the EU PAS Register. 

Kick-off meeting

Following finalisation of the protocol and prior to study execution, a kick-off meeting is organised by the Study Project Manager/Principal Investigator with all study team members to explain the protocol, agree on roles, responsibilities and timelines for study execution. 

Governance Board Approval

Protocol approval at the study sites is often required to comply with the local implementation of relevant laws and directives in the various European states. Each data custodian is responsible for protocol approval from their local governance board prior to study execution as is specified in the Framework Contract with the Data Partner. 

Cohort Construction and Assessment

Where needed, a phenotype for the target and outcome cohorts that work across the included data sources is generated. This is facilitated through the Codelist Generator R package, the Phenotype Library in addition to the Cohort Diagnostics R package. The latter provides an in-depth characterisation of the phenotype definitions, secular trends over time, standard as well as orphan source codes (not included source codes that may be of interest), and cohort participant/s characterisation. 

Study Package Creation

The analysis pipeline for each study type as described within the Catalogue of Standard Data Analysis will be used and only needs to be instantiated with the cohorts of interest and the right parameter settings to obtain the Study Package. For example, for a study to estimate the incidence and prevalence of a health outcome the IncidencePrevalence Package is used and the parameters are set according to the protocol. Before study initiation, test runs of the analytics are performed on a subset of the data sources or on a simulated set of patients and quality control checks are performed. Once all the tests are passed, the final package is released as a private repository in the version- controlled Study Repository. This package is distributed to the data partners for local execution agains their OMOP CDM.