Frequently asked questions

The SIGMA Consortium is an alliance of European research centers of excellence in pharmacoepidemiology and regulatory grade real-world evidence (RWE). Members of the SIGMA Consortium have extensive experience in collaborating in over 80 multicountry/multidatabase studies under the principles of the European Network of Centers for Pharmacoepidemiology and Pharmacovigilance (ENCePP). Past and current examples of collaborative experience can be found at https://sigmaconsortium.eu/collaborative-experience/ .

Our main objective is to provide independent quality evidence about safety of interventions by improving research methodologies, fostering collaboration among member organizations, and ensuring the overall quality of research outputs given the diversity of health care systems in Europe.

The SIGMA Consortium performs pharmacoepidemiologic, RWE studies in Europe and other countries on a contract basis. The study requesters can be of various types including the pharmaceutical industry, regulatory authorities, or academia.

Ten European countries are represented by SIGMA Members and collaborators: Denmark, Finland, France, Germany, Italy, Netherlands, Norway, Spain, Sweden, and the United Kingdom. Members and Collaborators of the SIGMA Consortium have extensive research experience and protocol-based access to 14 data sources for the conduct of RWE/pharmacoepidemiology studies. The description of the data sources can be found at: SIGMA protocol-based data access

The SIGMA Consortium is formed by a group of 14 leading research institutions and universities with extensive collective expertise and experience in the conduct of pharmacoepidemiologic and real-world evidence research. You can find our leading experts at: SIGMA Network - Sigma Consortium

Some key projects include the development and implementation of various PASS (Post-Authorization Safety Studies) and PAES (Post-Authorization Effectiveness Studies) for different medicinal products, and other types of projects such as infrastructure and guidance development studies. These projects are listed in SIGMA’s network registration in the HMA-EMA Catalogue: SIGMA Studies - HMA-EMA Catalogue of RWD Studies

To request a proposal, you can submit a study request form which can be found at SIGMA Study Request. You can submit the request directly through the website or download it and send it via email to info@sigmaconsortium.eu.

Upon receipt of a study request, the SIGMA Office reviews the form for initial applicability. If the study meets the requirements of a SIGMA project, the SIGMA Office distributes the form to the Member Organisations, who are asked to express their interest in leading or participating in the project. Roles within the project, such as Project Coordinating Centre (PCC), Principal Investigator (PI) Centre, and Research Sites, are assigned based on expressions of interest and specific criteria, such as the participation in previous projects, and any specific requests from the study funder. Once the study team is endorsed by the Board, the designated PCC leads the proposal development. If the proposal is accepted, the PCC enters into a research agreement with the study funder and executes Work Orders under the SIGMA Consortium Agreement with each participating Member Organisation in the study. Each Member Organisation carries out the tasks assigned to them in the Project Agreement and Work Orders. The PCC coordinates the project, ensuring that all deliverables are met and that the project is conducted according to the highest quality standards. This process ensures that the SIGMA Consortium can effectively manage and execute research projects, leveraging the expertise and resources of its member organisations. The SIGMA model of collaboration is depicted in graphic format in this link: SIGMA Process - Sigma Consortium

The PCC is the SIGMA Member Organisation that will coordinate the proposal and, if awarded, will contract with the study funder and coordinate the project from a contractual and project management perspective, both with the study funder as well as with the rest of research sites in the study. The PCC also manages communications between the involved parties in the project. The PI Centre is the SIGMA Member Organisation that will provide the PI for the project and lead the project scientifically including developing the common protocol and statistical analysis plan, integration of analysis, reporting, and dissemination of the consolidated study results. Oftentimes the PCC is the same organization as the PI centre. Research Sites will lead the Project implementation in a specific population/data source including contributing to the development of the common protocol and statistical analysis plan, leading site-specific study documents and applications, implementing the analysis plan in the specific site, and contributing to the reporting and dissemination of the consolidated results.

The requirements for a SIGMA study are as follows: The PI and the coordinating centre must be members of SIGMA. Additionally, the protocol must be developed or co-authored by at least one SIGMA member. Furthermore, all work must be conducted according to SIGMA principles, which includes adherence to the ENCePP Code of Conduct.

The study requester has the opportunity to indicate on the study request form their preference for a PCC in case they have one.

Yes, non-SIGMA research partners can be subcontracted on a project basis, as long as the core roles of PCC and PI are fulfilled by a SIGMA Member. Further, adherence to all other SIGMA project requirements must be fulfilled (please see details in question "What are the requirements for a SIGMA study?" above.

SIGMA does not provide direct access to data because it operates as a consortium of research centres of excellence with specialized knowledge and skills to conduct research in accordance with all European and country-level laws and data protection requirements.

This depends on the warranted insights that need to be generated to sufficiently inform the decision on whether and how to proceed with a study. We distinguish 3 categories of feasibility evaluations: 1. Basic: informal assessment of data availability on key study variables and simple counts (e.g. number of patients with disease of interest); 2. Intermediate: more detailed/specific counts of patients or drugs on which a simple selection query is performed (e.g. of the patients with a specific disease of interest, how many received a test/drug of interest), or basic counts + a targeted literature search on e.g. prevalence/incidence of a disease; 3. Complex: detailed/specific counts/variable completeness details during a feasibility study that is based on more complex queries (e.g. of the patients with specific disease, how many received the test/drug of interest, and can be detected in various care settings, and how complete is this data/what are potential limitations). Medium and Complex feasibility assessments may have a cost associated with them.

The SIGMA Consortium uses state-of-the-art methodologies, including causal inference with target trial emulation, propensity score-based approaches to confounding control, and other advanced methods in pharmacoepidemiology. SIGMA Consortium members follow and contribute to the ENCePP Guide on Methodological Standards in Pharmacoepidemiology and ISPE good practice guidance, ensuring scientific rigor in addition to transparency and ethical conduct. Our studies align with GVP module VIII principles, focusing on post-authorization safety and public health protection. By integrating these methods and guidelines, we produce high-quality, reliable research to inform decision-making and improve patient outcomes.

Yes, we work with common data models (CDMs) to ensure efficient and privacy-preserving execution of common protocols in multiple European data sources. SIGMA members have experience in mapping to various standard and ad-hoc CDMs, including the ConcePTION harmonisation pipeline, BRAHMS, OMOP, Sentinel, and TheShinISS.

SIGMA is a consortium of legal entities who share a Consortium Agreement which defines the way we collaborate, operate including the rights and obligations of the Members.

Confidentiality within the SIGMA Consortium is governed by the Confidentiality clause in the Consortium Agreement, ensuring all Member Organisations adhere to strict confidentiality obligations. For external parties and SIGMA Collaborators, confidentiality is managed through bilateral Confidential Disclosure Agreements (CDAs). These agreements protect any confidential information exchanged and ensure that the same ethical and conduct principles are followed. When sharing information with study funders, the SIGMA Consortium can use its bilateral CDA template or accommodate the funder's CDA templates, ensuring flexibility and compliance with specific requirements.

Membership is subject to nomination and approval. To become a member of the SIGMA Consortium, ENCePP Organizations with proven experience in pharmacoepidemiology and RWE can apply by submitting a written request to the SIGMA Office at info@sigmaconsortium.eu. The SIGMA Office will then provide detailed information on the membership requirements. After receiving this information, organizations can complete a membership request form. The application process includes meeting specific eligibility criteria and agreeing to the Consortium's terms and conditions.

You can contact the SIGMA Consortium through several methods. For general inquiries or study requests, you can reach out to the SIGMA Office through this website’s contact form, or via email at info@sigmaconsortium.eu. Additionally, you can submit a proposal request form. If you need to get in touch with specific individuals, you can contact the SIGMA Office co-leads, Carla Franzoni, Director of Epidemiology, Project Management at RTI Health Solutions, and Josine Kuiper, Senior Business Development Manager at PHARMO Institute for Drug Outcomes Research.