title: Predictors of non-adherence to systemic oral therapy for advanced hepatocellular carcinoma.
abstract: OBJECTIVE
  With increasing use and cost of oral oncology medications, patient non-adherence with oral therapy is of concern. This study evaluated non-adherence among patients receiving first-line oral therapy for hepatocellular carcinoma (HCC).
  
  
  METHODS
  This retrospective study used the employer-based MarketScan medical and pharmacy claims database (2005-2011) to identify adult patients with two or more diagnoses of HCC (ICD-9 155), and two or more filled prescriptions for sorafenib. Additional eligibility requirements were not having other previous cancers and a 4 month wash-out period prior to the index sorafenib date. Adherence was assessed using a modified proportion of days covered (PDC) measure with patient-specific sorafenib exposure from index date to treatment discontinuation. Non-adherence was categorized as PDC <85% (base case), with sensitivity analyses using an 80% cut-off and allowance for physician-directed therapy gaps. Logistic regression models were estimated to identify predictors of non-adherence.
  
  
  RESULTS
  A total of 1127 patients (median age = 61.0 years; 78.4% male) met eligibility criteria. Median duration of enrollment was 223 days and median sorafenib exposure was 121 days. Between 21.1% (PDC < 0.80) and 28.0% (PDC < 0.85) of patients were non-adherent. Higher age (p = 0.022), number of baseline medications (p = 0.003) and number of baseline comorbidities (p = 0.002) were associated with lower non-adherence, while prior procedures were associated with greater non-adherence (p = 0.002).
  
  
  CONCLUSIONS
  In this study using billing claims data, we were unable to evaluate patient severity in terms of clinical characteristics such as the Child-Pugh score. Similarly, we could not assess clinical outcomes such as tumor response, radiological progression or overall survival, although median duration of sorafenib exposure and duration of health plan enrollment respectively were found to be good proxies.
  
  
  CONCLUSIONS
  Using a modified PDC approach, 22-29% of patients were non-adherent. Identified predictors of non-adherence in HCC should be assessed for newly emerging oral therapies, and may be used to guide patient education and other adherence-enhancing initiatives.
authors.affiliation: Health Economics and Outcomes Research, Daiichi Sankyo Inc. , Parsippany, NJ , USA.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Mallick
authors.forename: Jennifer
authors.initials: J
authors.lastname: Cai
authors.forename: Jenifer
authors.initials: J
authors.lastname: Wogen
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D016208:Databases, Factual; D005260:Female; D006801:Humans; D007345:Insurance Claim Review; D008113:Liver Neoplasms / Q000188:drug therapy*; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives*; D010671:Phenylurea Compounds / Q000008:administration & dosage*; D012189:Retrospective Studies; D012737:Sex Factors; D000077157:Sorafenib
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib