about enforce study

The Danish COVID-19 vaccination program will include several new SARS-CoV-2 vaccines, and the programme is expected to commence in January 2021, assuming all approvals etc. are on track. According to the national vaccine plan (Udrulning af vaccination mod Covid-19), vaccination will initially be offered to people in specified risk groups, and to selected key workers in the health, elderly and social care sectors. As the development of the vaccines has been performed during a limited time period it will be important to continue to gather more information about safety and effect as they are being rolled out.

National cohort study of effectiveness and safety of SARS-CoV-2 vaccines (ENFORCE) is an equivalence trial to evaluate the effectiveness and safety of multiple new SARS-CoV-2 vaccines approved for use in the EU, and which are being offered at participating units.

The study is an open-labelled, non-randomised, parallel group, phase IV study with historical controls. A sub-study will be embedded within this master protocol addressing basic and translational research questions requiring additional sampling of biological material (under separate participant informed consent).

Study objectives
The primary objective of the study is to assess effectiveness of citizens being vaccinated with one of SARS-CoV-2 vaccines the government has purchased, and the Danish Medicines Agency has approved for use in Denmark. The study will compare and predict the durability of the minimal protective titre afforded by each of the vaccines against COVID-19 through conducting comprehensive high-throughput SARS-CoV-2 antibody analyses and in-depth characterization of the vaccine-induced cellular immune response.

The study has a number of secondary objectives. These can be classified in two main subgroups, those related to other assessment of effectiveness and those related to safety. The study will compare several outcomes between vaccine groups related to effectiveness.

Study population
The study population consists of consecutive consenting persons invited to be vaccinated at participating units throughout Denmark.

Enrolment will occur in phases. First phase will constitute a sample size of 10,000 persons initiating vaccination (assuming 4 vaccine groups of 2500 persons). Subsequent phases with larger sections of the population included may be implemented, providing a sound science justification, satisfactory conduct of first phase, and that additional funding has been secured. Also, if more than 4 vaccines will be applied, additional 2500 persons per vaccine can be included.

Participants will have 6 study visits and be followed for 2 years after the first vaccination, which offers the participants an extra close follow up on vaccine effectiveness. Safety data will be collected at study visits until 3 months after the first vaccination. Research samples will be collected at each study visit during the two year follow-up.

Primary outcome of the study is the minimal protective neutralising antibody titre (MPNAT); i.e. the minimum level of neutralising antibodies sufficient to protect the person from becoming infected. The vaccines are not part of the study set-up and citizens offered inclusion in the study will be offered the vaccine regardless of their participation in the study. There is therefore a limited risk of participation in the study.

If you have further questions regarding the study, please contact study personnel via email: enforce.rigshospitalet@regionh.dk.