An Observational Post-Authorization Safety Study of Temodar® (Temozolomide) and Severe Acute Liver Injury in the HealthCore Integrated Research Environment (MK-7365-295)

Study type

• Study topic:
  Disease /health condition

  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness

  Safety study (incl. comparative)
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Case-control

  Cohort

  Other
• Non-interventional study design, other:
  Post-Authorization Safety Study

Study drug and medical condition

• Name of medicine, other:
  Temodar

Population studied

• Short description of the study population:
  The source study population will include adult patients with two diagnoses of brain cancer (ICD-9-CM codes 191.xx) on different dates between 01 January 2006 through 30 September 2013 (or the most recent date for which sufficiently complete claims are available). The primary reason for requiring two diagnoses is because cancer diagnoses often appear as rule-out diagnoses, and a patient with only one diagnosis is less likely to be a true brain cancer case. This criterion could be relaxed to increase the number of cases, but it is anticipated this population will provide sufficient study size (Section 7.3 and Feasibility Assessment Report). Any patients exposed to temozolomide and who also have an inpatient diagnosis consistent with SALI after one diagnosis of brain cancer will not fulfil criteria for inclusion in the cohort but will be identified and enumerated. The index date for each patient will be defined as the latter of (1) the day after the second brain cancer diagnosis after six months of continuous enrollment with both medical and pharmacy coverage, or (2) completion of six months of continuous enrollment containing at least two brain cancer diagnoses. Subjects will be required to have at least six months of continuous enrollment prior to and including the index date in order to identify covariates including co-morbidities and medication use. Patients with more than two baseline brain cancer diagnoses before the index date will be included and classified as prevalent cases. Subjects with a potential SALI diagnosis during the six months prior to or including the index date, and patients aged less than 18 years or 100 years or greater on the index date will be excluded.; Inclusion Criteria; • At least two diagnoses of brain cancer on different dates during the study period from 01 January 2006 through 30 September 2013 (or most recent data available).; Exclusion Criteria; • Potential SALI diagnosis within six months prior to or including the index date.; • Less tha
• 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:
  Other
• Special population of interest, other:
  Brain cancer patients
• Estimated number of subjects:
  875

Study design details

• Main study objective:
  To assess the relation, if any, between temozolomide exposure and severe acute liver injury (SALI)
• Outcomes:
  To assess the relation, if any, between temozolomide exposure andSALI. Provide case narratives for temozolomide-exposed cases of SALI (e.g. demographics, clinical and pathological factors, comorbidities, and brain cancer treatment characteristics).
• Data analysis plan:
  This study will have two rounds of data analysis using data from the HealthCore Integrated Research Database (HIRD, Andover MA, US). An interim data analysis will occur after confirmed cases and their controls have been identified, this analysis will include effect estimation using exposure and covariate data available from automated claims data. Concurrently, a round of medical record reviews will be done to obtain information on certain covariates pertaining primarily to brain cancer and its treatment. After this information is obtained, it will be added to analytic files and effect estimation will be repeated on the expanded database. Effect estimation will be conducted using multivariate logistic regression models. All statistical analyses will be performed using Statistical Analysis Software (SAS) version 9.4 (SAS Institute, Cary, NC, US) and/or Stata® version 11.1 (Stata Corporation, College Station, TX, US).