The benefits and side effects of osteoporosis medications: A regression discontinuity study of primary care patients in the UK.

Date of Approval
Application Number
20_000109
Technical Summary

This study seeks to evaluate the benefits and adverse side effects of osteoporosis medications among primary care patients in the UK using the regression discontinuity (RD) method. The RD design can be used to assess the causal effect of osteoporosis medications on health outcomes by taking advantage of a decision rule used to determine patients’ eligibility for pharmaceutical treatment of osteoporosis. Specifically, we aim to (1) determine whether or not there is a substantial change in the probability of using osteoporosis medications between patients whose T-score for bone mineral density falls just below and above an arbitrary cut-off point as published in major clinical guidelines, (2) evaluate if patient characteristics are balanced within a small bandwidth surrounding the threshold, and (3) investigate whether associations between osteoporosis medications and patient outcomes are robust to different choices of bandwidth around the threshold. Patient outcomes include future bone density T-scores, probability/number of major osteoporosis fracture events, probability of any adverse side effects (e.g. musculoskeletal pain, osteonecrosis of the jaw, atypical thigh bone fracture, ulcer, and hypocalcemia), and all-cause mortality. We hypothesize that the use of osteoporosis medications decreases future T-scores for bone density, the probability/number of fractures, and mortality. We will estimate “fuzzy” RD models using a local linear regression and triangular weights to avoid overfitting the data and to give more influence to observations close to the threshold. In addition, we will use a mean squared error (MSE) optimal bandwidth that is empirically derived. We assess the sensitivity of the results using alternative bandwidths (e.g. bandwidths that are 50%, 75%, 125%, and 150% of the empirically derived bandwidth). Our findings will provide valuable insights into the real-life effects of osteoporosis medications on health, the unintended effects associated with these medications, and the heterogenous treatment effects by detailed patient subgroups.

Health Outcomes to be Measured

Primary outcomes (measured within five years from an index date): future bone density T-scores.

Secondary outcomes (measured within one year, five years, and ten years from an index date): Probability/number of major osteoporosis fracture events (e.g. vertebrae, humerus, wrist, femur, and hip fractures), all-cause mortality, probability of any osteoporosis-related unintended adverse side effects (including but not limited to musculoskeletal pain, osteonecrosis of the jaw, atypical thigh bone fracture, ulcer, and hypocalcemia); probability of at least one hospitalization for osteoporosis-related adverse side effects; number of hospitalizations for osteoporosis-related adverse side effects; probability of at least one all-cause emergency hospitalization; number of all-cause emergency hospitalizations; probability of at least one fracture-related hospitalizations; and number of fracture-related hospitalizations; probability of at least one osteoporosis-related hospitalizations; and number of osteoporosis-related hospitalizations. Other secondary outcomes include future bone density T-scores (measured within one year and ten years from an index date)

Collaborators

Till Bärnighausen - Chief Investigator - University of Heidelberg
Duy Do - Corresponding Applicant - University of Heidelberg
Anant Jani - Collaborator - University of Oxford
Christian Bommer - Collaborator - University of Heidelberg
Julia Lemp - Collaborator - University of Heidelberg
Justine Davies - Collaborator - University of Birmingham
Michaela Theilmann - Collaborator - University of Heidelberg
Pascal Geldsetzer - Collaborator - University of Heidelberg

Linkages

2011 Rural-Urban Classification at LSOA level;HES Accident and Emergency;HES Admitted Patient Care;HES Outpatient;ONS Death Registration Data;Patient Level Index of Multiple Deprivation