title: Adherence to raloxifene therapy: assessment methods and relationship with efficacy.
abstract: Response to therapy depends on patient compliance but accurate assessment is difficult and adequate levels of adherence are uncertain. Adherence to raloxifene treatment may be assessed more accurately by electronic monitoring than by counting returned tablets. The level of adherence is positively associated with the degree of bone response.
  
  
  BACKGROUND
  Adherence to study medication is usually estimated by counting returned tablets. This method relies on subjects' honesty and may be inaccurate. We aimed to assess adherence more accurately, and examine its effect on measures of bone response, by using electronic monitoring.
  
  
  METHODS
  Osteopenic women, ages 50 to 80, were prescribed daily raloxifene for 2 years. Electronic bottle caps (Medication Event Monitoring System (MEMS), Aardex) recorded the date and time on opening. Returned tablets were also counted. We measured bone mineral density (BMD) in duplicate at the spine and hip at baseline and 2 years. We also measured urinary N-terminal cross-linked telopeptide of type I collagen (NTX) at baseline, 1 and 2 years. We calculated the percentage changes in BMD and NTX from mean baseline to mean follow up measurements. Percentage adherence was assessed by both methods for 71 subjects that completed the study.
  
  
  RESULTS
  The two methods correlated significantly (p <0.001, Spearman's rho = 0.73) but the tablet count showed a higher median adherence than the MEMS caps (95.7 vs. 85.0%, p <0.001), with greater divergence at lower adherence levels. MEMS adherence in 65 subjects with complete data correlated with NTX response (p <0.01, rho = -0.33) but with BMD response only at the femoral neck. However, adherence in the lowest quartile was associated with poorer BMD response at all sites (p <0.05).
  
  
  CONCLUSIONS
  Tablet counts may give similar results overall but conceal substantial individual non-adherence. Monitoring caps may assess adherence more accurately than tablet counts and would be the preferred method in clinical trials. The degree of adherence is associated with both bone turnover and BMD responses to anti-resorptive therapy.
authors.affiliation: Academic Unit of Bone Metabolism, Mellanby Centre for Bone Research, University of Sheffield, Sheffield, UK, j.finigan@sheffield.ac.uk.
authors.forename: J
authors.initials: J
authors.lastname: Finigan
authors.forename: K
authors.initials: K
authors.lastname: Naylor
authors.forename: M A
authors.initials: MA
authors.lastname: Paggiosi
authors.forename: N F
authors.initials: NF
authors.lastname: Peel
authors.forename: R
authors.initials: R
authors.lastname: Eastell
mesh_terms: D015502:Absorptiometry, Photon / Q000379:methods; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000652:urine; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001862:Bone Resorption / Q000503:physiopathology / Q000517:prevention & control / Q000652:urine; D024042:Collagen Type I / Q000652:urine; D004334:Drug Administration Schedule; D016903:Drug Monitoring / Q000295:instrumentation / Q000379:methods*; D004349:Drug Packaging; D055615:Electrical Equipment and Supplies; D004739:England; D005260:Female; D006801:Humans; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy* / Q000503:physiopathology / Q000652:urine; D010455:Peptides / Q000652:urine; D020849:Raloxifene Hydrochloride / Q000008:administration & dosage / Q000627:therapeutic use*; D013607:Tablets
chemical_list: D015415:Biomarkers; D050071:Bone Density Conservation Agents; D024042:Collagen Type I; D010455:Peptides; D013607:Tablets; C052929:collagen type I trimeric cross-linked peptide; D020849:Raloxifene Hydrochloride