Does metformin show a reduction of severe outcomes of COVID-19 or of Long COVID in the N3C Data Enclave

Contract Description

A recent clinical trial (COVID-OUT) demonstrated that metformin lowered the odds of emergency department visits, hospitalizations, or death by over 40% and also decreased the incidence of long COVID as diagnosed by a medical provider.  The fundamental question being asked is:  Does metformin reduce the incidence of severe outcomes of COVID-19 and/or prevent Long COVID?

https://www.nejm.org/doi/full/10.1056/NEJMoa2201662

https://www.medrxiv.org/content/10.1101/2022.12.21.22283753v1

Contract Aims

Does metformin reduce the incidence of severe outcomes of COVID-19 and/or prevent Long COVID?

Analysis Plan / Research Method

Be explicit about how your study design, research methodology, and analytical plan will address the overall research question and aims. See the detailed guidance on expectations at the submission portal when completing the relevant fields in your proposal.

Expected Results

See Deliverables

Inclusion Criteria

Be explicit about how your inclusion strategy will rigorously address the overall question and aims.

Exclusion Criteria

Be explicit about how your exclusion strategy will rigorously address the overall question and aims.

Phenotype

Please describe in detail the strategies for defining the two phenotypes of interest:  i) severe acute COVID and ii) long COVID. Be clear about how your phenotype definitions compare to the published literature on metformin and acute COVID/long COVID.  Be explicit about how phenotype definitions compare to inclusion criteria for COVID-19 clinical trials that have tested or are testing the effects of metformin on acute and/or long COVID.   Address the limitations and confounders of all phenotype definitions.  Be explicit on how certain phenotypes may underestimate the true incidence of disease in the electronic health record or may have changed over the time course of the COVID-19 pandemic in the electronic health record.

Deliverables

Written report within the N3C Enclave detailing the findings from analyses that support your conclusions and that address the overall research questions and aims.  Provide sufficient methodologic detail for independent replication of the work, and an interpretation of the findings and study limitations.  All code generated to complete the work will be made available in a deployable format with sufficient documentation/annotation for independent validation.  Figures and/or tables in a format specified by NCATS suitable for uploading to the N3C Public Health web site.