Study type

Study topic

Disease /health condition

Study type

Non-interventional study

Scope of the study

Disease epidemiology
Drug utilisation
Safety study (incl. comparative)

Data collection methods

Primary data collection
Non-interventional study

Non-interventional study design

Cohort
Study drug and medical condition

Name of medicine, other

Levothyroxine

Study drug International non-proprietary name (INN) or common name

LEVOTHYROXINE

Anatomical Therapeutic Chemical (ATC) code

(H03AA01) levothyroxine sodium
levothyroxine sodium

Medical condition to be studied

Hypothyroidism
Population studied

Short description of the study population

The study will be carried out in BIFAP (http://www.bifap.org), a longitudinal population-based database managed by the AEMPS that contains data from the anonymised medical records of patients treated by primary care physicians (MAP) belonging to the Spanish National Health System (SNS).
Nine autonomous communities collaborate by providing data.
Currently, BIFAP includes health records of around 12 million patients covering almost 25% of the Spanish population, with an average follow-up of 8.5 years.
The BIFAP population is representative of the Spanish population in terms of age and sex.

Age groups

Adults (18 to < 65 years)
Adults (65 to < 75 years)
Adults (75 to < 85 years)
Adults (85 years and over)

Estimated number of subjects

100000
Study design details

Main study objective

To estimate the prevalence and incidence of global hypothyroidism as well as treated and untreated hypothyroidism with levothyroxine in the study period (2013-2023)

Setting

Health records of around 12 million patients covering almost 25% of the Spanish population between 2013 and 2023.
1. Incident cohort of treated hypothyroidism: patients who receive levothyroxine treatment for the first time without a diagnosis of previous hypothyroidism or with a diagnosis of subsequent hypothyroidism. The date of first prescription of levothyroxine will be the start date for follow-up to events of interest, and that person-time will be assigned to the incident cohort of hypothyroidism treated. See below for patients who are first diagnosed with hypothyroidism and then treated with levothyroxine.
2. Untreated incident hypothyroidism cohort: patients from the incident hypothyroidism cohort who receive a first diagnosis of hypothyroidism and without any levothyroxine dispensation during the entire follow-up period. The date of first diagnosis of hypothyroidism will be the start date for follow-ups to events of interest, and that person-time will be assigned to the incident cohort of untreated hypothyroidism.
Control population cohort: From the same study population where we identified the hypothyroidism cohort, a random sample of 4 individuals matched by each patient in the hypothyroidism cohort with the same year of birth and sex will be selected, assigning them the start date of their respective match (they will not have a history of hypothyroidism or substitution treatment before the start date for follow-ups to events of interest).

Comparators

Patients diagnosed of hypothyroidism and treated with levothyroxine
Patients diagnosed of hypothyroidism and not treated with levothyroxine
Control matched population

Outcomes

Thyroid function control
Atrial fibrillation
Heart failure
Vertebral fracture or crushing, fracture of the femur, pelvis and wrist
Osteoporosis and/or initiation of osteoporosis drugs
Affective disorders
Insomnia
Cognitive impairment

Data analysis plan

Incidence-prevalence measure: The incidence rate of total hypothyroidism, as well as treated and untreated hypothyroidism in each year of the study period will be estimated by dividing the number of incident cases identified throughout each year by the number of person-years of follow-up accumulated during this same year. We will also calculate the prevalence in each year of the study period.
Event of Interest Measure: We will estimate the incidence rates for each event by dividing the number of people with events by the total number of person-years of follow-up, stratified by age, sex, and study cohort, assuming a Poisson distribution to estimate the confidence intervals of these incidences.
In addition, we will perform a Kaplan and Meier survival analysis to study the cumulative risk of each event in the different cohorts throughout the study period. Next, a Cox proportional hazards multivariate regression model will be used to assess the association of each event with treated and untreated hypothyroidism adjusted for event-specific risk factors.