Pharmacological treatments associated with increased or decreased risk of developing age-related macular degeneration: signal detection

Date of Approval
Application Number
21_000417
Technical Summary

Aims: To explore whether there are medications in current use which are associated with an increased or decreased risk of subsequent development of age-related macular degeneration (AMD). This is intended as an exploratory pharmacovigilance study, to detect statistical signals for drug associations with AMD development, and highlight potential drug associations for further exploration. Following the analysis, after identifying drug classes with statistically significant and potentially clinically important associations with AMD, the findings will be discussed at a workshop with researchers and clinicians to identify clinically/biologically plausible associations warranting further investigation. We will also perform a similar exploratory analysis looking at comorbidities preceding a diagnosis of AMD.

Methods/design: We will perform case-control studies with a range of exposures to evaluate possible associations between various medications or morbidities and subsequent development of AMD. To limit false discovery rate, we will use the Benjamini-Hochberg p-value correction for false discovery rate due to multiple testing to select associations with corrected alpha < 0.05.

Outcome: AMD

Exposures: Drugs: All drugs available in the database’s product dictionary will be designated according to their ATC codes. Comorbidities: A list of 90 morbidities.

Participants: Adults aged 40 years and over and registered with the general practice for at least one year before the index date (start of follow-up) will be included. Cases will be patients with a primary care record of AMD identified by relevant Read codes. Each patient with AMD will be matched to control patients without AMD at the time of AMD diagnosis for age (± 1 year), sex, BMI (±2 kg/m2), smoking status, exposure window, and follow-up period (± 1 year).

Covariates: In addition to matching, we will adjust for age, sex, BMI, smoking status and comorbidity score to account for residual confounding.

Health Outcomes to be Measured

Age-related macular degeneration

Collaborators

Nicola Adderley - Chief Investigator - University of Birmingham
Nicola Adderley - Corresponding Applicant - University of Birmingham
Anuradhaa Subramanian - Collaborator - University of Birmingham
Ji Eun Diana Han - Collaborator - University of Birmingham
Krishna Gokhale - Collaborator - University of Birmingham
Krishnarajah Nirantharakumar - Collaborator - University of Birmingham
Tom Taverner - Collaborator - University of Birmingham