Existing research on the association of statins (a cholesterol lowering medication) and metformin (an oral diabetes medication controlling blood sugar levels) on cancer and death are inconsistent, with conflicting results reported between observational studies and randomized clinical trials. Clinical trials often do not recruit a sufficient number of participants or do not follow participants up for a long period in order to comprehensively evaluate the risk-benefit profile of these drugs, particularly for rare outcomes such as cancer. Given the widespread use of these medications, even rare outcomes can lead to high absolute numbers and therefore raise serious public health concerns. Our research will use large existing health datasets, such as the Clinical Practice Research Datalink, combined with novel analytical and statistical methods to see if a relationship between these two medications and cancer or death exists.
We will leverage the CALIBER dataset of linked CPRD, HES and ONS data to examine the effect of statins and metformin on the risk of cancer incidence and mortality. We will use this observational data to mimic the eligibility criteria, treatment strategies, and outcomes of a clinical trial. We will then estimate the effects of initiating therapy and of initiating and continuing therapy. To study the effect of treatment initiation, we will emulate a series of nested trials comparing initiators vs. non-initiators of the medications of interest. To study the effect of treatment initiation and continuation, we will implement and compare two approaches (g-methods) to adjust for time-varying confounding: inverse-probability weighting and the parametric g-formula.
Primary exposures: - Statin use - Metformin use Primary outcomes: - Cancer incidence - All-cause and cancer-specific mortality
Spiros Denaxas - Chief Investigator - University College London ( UCL )
Xabier Garcia-de-Albeniz - Corresponding Applicant - Harvard University
Barbra Dickerman - Collaborator - Harvard University
Michail Katsoulis - Collaborator - Farr Institute of Health Informatics Research
Miguel Hernan - Collaborator - Harvard University
HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation;Practice Level Index of Multiple Deprivation