Prevalence and characterization of patients on polypharmacy across the three Area Vasta of the Tuscany Region (POLY-TUSC)

Study type

• Study topic:
  Other
• Study topic, other:
  Polypharmacy
• Study type:
  Non-interventional study
• Scope of the study:
  Drug utilisation

Non-interventional study

• Non-interventional study design:
  Cohort

  Cross-sectional

Study drug and medical condition

• Medical condition to be studied:
  Chronic disease

  Cardiovascular disorder

  Rheumatic disorder

  Inflammatory bowel disease

Population studied

• Short description of the study population:
  For each calendar year between 2023 and 2025 (the study period), a cohort of subjects enrolled in the Regional Health Service as of December 31 (the index date) will be selected. Exclusion criteria for this initial population include a baseline observation period of less than 3 years prior to the index date and an age under 40 years at the index date. Within this final study population, patients on polypharmacy will then be identified for each year of the study period.
• Age groups:
  • Adult and elderly population (≥18 years)

    • Adults (18 to < 65 years)

      • Adults (18 to < 46 years)
      • Adults (46 to < 65 years)
    • Elderly (≥ 65 years)

      • Adults (65 to < 75 years)
      • Adults (75 to < 85 years)
      • Adults (85 years and over)
• Special population of interest:
  Frail population

  Other
• Special population of interest, other:
  Adults affected by chronic diseases on (hyper)-polypharmacy

Study design details

• Study design:
  Observational cohort study to identify and describe patients on polypharmacy and hyper-polypharmacy within each of the three Tuscan Area Vasta over the 2023–2025 period.
• Main study objective:
  Primary: ; - To quantify the number of patients on polypharmacy by ASL grouped by reference Area Vasta, and to describe their demographic profile, chronic disease copay exemption status, and most frequent drug combinations.; ; Secondary:; - To describe the demographic and clinical profile of polypharmacy patients receiving care in RSA and/or ADI by Area Vasta.; - To describe the demographic and clinical profile of polypharmacy patients by Area Vasta, restricting the analysis to patients with cardiovascular, rheumatological, or gastroenterological diseases.; - To perform a qualitative and quantitative assessment of elderly polypharmacy patients exposed to PIMs or drug-drug interactions, according to the 2023 American Geriatrics Society Beers Criteria.;
• Setting:
  The study population consists of all individuals covered by the Regional Health Service (Servizio Sanitario Regionale) of the Tuscany Region, Italy. The analysis targets the population distributed across the various regional Local Health Units (Aziende Sanitarie Locali, ASLs), which are aggregated into the three regional administrative healthcare areas known as Area Vasta (Central, North-West, and South-East Area Vasta).; The study covers a three-year period from 2023 to 2025. Cohorts are defined annually, selecting subjects enrolled in the registry as of December 31st (index date) for each calendar year of interest.; Inclusion Criteria: Subjects must be aged 40 years or older at the index date and must be registered with the Tuscan Regional Health Service. ; Exclusion Criteria: Individuals with a baseline observation period of less than 3 years prior to the index date are excluded. ; Within this final population, patients on polypharmacy and hyper-polypharmacy are identified. Polypharmacy is defined as the dispensation of ≥5 different active substances (at the 4th level of the Anatomical Therapeutic Chemical [ATC] classification) within the same month for at least 3 out of the 12 months preceding the index date. Hyper-polypharmacy is defined using the same timeframe requirement but with a threshold of ≥10 different 4th-level ATC codes.; Since this is a descriptive study, there are no randomized treatment arms.
• Comparators:
  The study is an observational study. ; The population of interest is stratified by the following variables to evaluate variations in prescribing models: ; Age Groups: Stratified into three specific bands: adults (40–64 years), elderly (65–84 years), and very elderly (≥ 85 years). ; Geographical Areas: Stratified by ASL and grouped by the three regional Area Vasta (Center, North-West, South-East). ; Setting of Care: patients receiving community-based care versus highly frail patients defined as having at least 1 day of care within a Nursing Home (RSA - Residenze Sanitarie Assistenziali) and/or Integrated Home Care (ADI - Assistenza Domiciliare Integrata) during the year of interest. ; Clinical Comorbidities (Chronic Disease Exemptions): Sub-analyses are restricted to patients with specific exemption codes for chronic cardiovascular, rheumatological, or inflammatory bowel diseases (IBD), recorded during the second and third year preceding the index date.
• Outcomes:
  The primary outcome is the annual prevalence of polypharmacy and hyper-polypharmacy among patients aged 40 years or older in the Tuscany Region during the 2023–2025 period. This outcome will be reported overall and stratified by ASL grouped into the three regional Area Vasta (Central, North-West, South-East), as well as by predefined age groups (40–64, 65–84, ≥ 85 years).; Characterization of Frail Populations: The annual prevalence, clinical-demographic profile (sex and age distribution), and chronic disease burden among polypharmacy patients in RSA and/or ADI. ; Characterization of Chronic Disease Sub-cohorts: The prevalence and clinical-demographic description of patients on polypharmacy with specific exemptions for chronic cardiovascular, rheumatological, or IBD. ; Prevalently Dispensed Therapeutic Patters: Identification and distribution (frequencies and percentages) of the top 5 most frequently used active molecules (5th-level ATC dispensed ≥3 times a year) and the top 10 most common drug combinations (grouped by 4th-level ATC codes) within the polypharmacy cohorts. ; PIMs: In the subset of polypharmacy patients, the frequency and percentage of individuals exposed to PIMs (e.g., anticholinergics, NSAIDs, antipsychotics, long-acting sulfonylureas, digoxin, and sliding-scale insulin) independent of comorbidities, identified via ATC codes from the 2023 AGS Beers Criteria. Potential DDI: In the subset of polypharmacy patients, the frequency and percentage of individuals exposed to high-risk therapeutic regimens involving DDI ( oral anticoagulants + NSAIDs; ≥3 concurrent anticholinergic drugs; ACE inhibitors/ARBs + NSAIDs + diuretics; antiplatelets + NSAIDs without a proton pump inhibitor), identified according to the 2023 AGS Beers Criteria.
• Data analysis plan:
  This is a descriptive drug-utilization study. Therefore, endpoints are reported as pharmacological and appropriateness metrics (prevalence, drug combination frequencies, and PIM exposure criteria) derived from regional administrative healthcare databases.; The distribution of continuous variables will be expressed as mean (standard deviation, SD) and/or median (interquartile range, IQR). Categorical variables will be reported as frequencies and percentages.; The trend in the annual prevalence of patients on polypharmacy within each Area Vasta will be observed over the study period (2023-25). The annual prevalence of patients on polypharmacy will be calculated as the number of patients on polypharmacy in the year of interest divided by the reference covered population in the same year.; Patients on polypharmacy identified over the 2023–2025 period will be characterized in terms of sex, age, care setting (≥1 day in a RSA and/or ADI during the year of interest), presence of chronic disease exemptions in the 2nd and 3rd year prior to the index date, most frequently used drugs, and combinations of drugs grouped according to the 4th level of the ATC/DDD classification system. The analysis will be stratified by the patient's ASL, and ASL will be grouped and categorized according to the three regional Area Vasta.; In secondary analyses, the same descriptive approaches outlined above will be applied to specific subsets of the study population, namely: i) patients with at least 1 day in an RSA and/or ADI during the reference year, and ii) patients with a recorded cardiovascular, gastroenterological, or rheumatological chronic disease exemption in the 2nd and 3rd year prior to the index date, respectively.; Finally, among patients on polypharmacy aged ≥ 65 years, those exposed to PIMs independent of comorbidities and to therapeutic regimens at risk of potentially drug-drug interactions will be identified, according to the 2023 AGS Beers Criteria.
• Summary results:
  As of the current registration date, data extraction and statistical analyses have not yet been finalized. ; The results of study will provide: ; annual and stratified (by age group, Local Health Authority, and Area Vasta) prevalence rates of polypharmacy and hyper-polypharmacy among the Tuscan population aged ≥ 40 years for the 2023–2025 period; demographic and clinical characterization of complex patient subgroups, specifically individuals in RSA, ADI, or with specific chronic disease; Frequency and distribution of top therapeutic regimens, potential DDI, and exposure to PIMs based on the 2023 AGS Beers Criteria.