Comparative Effectiveness and Safety of Drugs used in Rare Neuromuscular and Neurodegenerative Diseases (CAESAR)

Study type

• Study type:
  Non-interventional study
• Scope of the study:
  Drug utilisation

  Effectiveness study (incl. comparative)

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Medical condition to be studied:
  Amyotrophic lateral sclerosis

  Progressive muscular atrophy

  Pseudobulbar palsy

  Progressive bulbar palsy

  Upper motor neurone lesion

  Motor neurone disease

  Myasthenia gravis
• Additional medical condition(s):
  Other RNDs might be included during the study

Population studied

• Age groups:
  • Paediatric Population (< 18 years)

    • Neonate

      • Term newborn infants (0 – 27 days)
    • Infants and toddlers (28 days – 23 months)
    • Children (2 to < 12 years)
    • Adolescents (12 to < 18 years)
  • 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)
• Estimated number of subjects:
  5000

Study design details

• Main study objective:
  Objective 1. describe the prescriptive patterns of the study drugs in patients affected by RND and identify patient characteristics associated to these patterns in the three Italian regions (Tuscany, Umbria, Lazio), accounting for over 10 million residents. Objective 2. comparative evaluation of the effectiveness and safety of drugs used for the treatment of RND, with a focus on specific agents
• Outcomes:
  Overall and cause specific mortality, Admission to intensive care unit, Remission from corticosteroid use, discontinuation after a period of prescriptions with corticosteroids for systemic use, Adverse drug reactions (serious infections, autoimmune disease) - to be defined, Respiratory failure and tracheotomy (for ALS patients), Thymoma, thymectomy, myasthenia gravis crisis, use of intravenous immunoglobulins, plasmapheresis (for MG patients)
• Data analysis plan:
  Data will be organised and managed through a common data model. Analysis will be performed running the shared scripts at local level and pooling aggregated data at the end. Drug utilization will be defined on the basis of DDDs, using different indicators: prevalence of use (by dividing the number of drug users by the overall resident population), prevalence of use among patients in the cohort (by disease for single drugs), DDDs per 1000 users per day (the mean number of doses consumed every day by 1000 patients included in the cohort). CER will be performed through a propensity matched cohort design (head-to-head comparison between different drug groups/drugs). Patients in the compared exposure groups will be propensity matched. A group of patients not treated with any of the drugs will also be defined and compared. Intention-to-treat and As-treated analyses will be performed using Cox proportional Hazard models (HRs and 95%CIs).