D. Gillespie, K. Hood, A. Williams, R. Stenson, C.S.J. Probert and A.B. Hawthorne Clinical Trials Methodology Conference, Bristol 2011

Transcription

1 Use of the Medication Event Monitoring System for assessing medication adherence for chronic conditions: Results from a 12 month trial of patients in remission with ulcerative colitis D. Gillespie, K. Hood, A. Williams, R. Stenson, C.S.J. Probert and A.B. Hawthorne Clinical Trials Methodology Conference, Bristol 2011

2 Drugs don t work in patients who don t take them - C. Everett Koop

3 Background : Medication adherence The extent to which patients take their medication as prescribed by their healthcare providers Typically lower in patients with chronic conditions Link between poor adherence and poor outcomes Factors associated with poor adherence

4 Background : Measuring medication adherence Method Assumption/s Advantages Disadvantages Self-report Patients are not always Patient is honest in their Simple. Cheap. honest. Recall is not always report. Recall is perfect. perfect. Prescription refills Patients are adherent if they Data available through May request refills if request more medication at centralised patient refill prompted by clinician. correct intervals. records. Tablet counts Difference between no. Patients can forget to (or tablets ideally taken and no. Simple. Cheap. purposely not) bring tablets returned tablets equates to back. no. tablets taken. Blood level monitoring Drug level in patient s blood indicates patient has recently taken the drug. Only measure where consumption of medication can be confirmed. No information about adherence between monitoring. An event equates to the Electronic monitoring Provides insight into patterns Expensive. Monitoring correct quantity of (e.g. MEMS) of adherence. system can be impractical. medication being consumed.

5 Background : Ulcerative Colitis (UC) Chronic Inflammatory Bowel Disease (IBD) - Loose, bloody stools Estimated to affect per 100,000 Peak age of onset Relapse-remitting

6 The CODA study: Main trial Population: Intervention: Comparison: Outcome: 213 Patients with ulcerative colitis who had been in remission for at least 4 weeks but not more than 2 years Three 800mg Mesalazine tablets (Asacol) given once daily (OD) One 800mg Mesalazine tablet given three times daily (TDS) Relapse rate during the 12 month follow-up period Non-inferiority of the OD versus TDS regimen confirmed - No significant difference in terms of adverse event rates Average daily dose (from tablet counts) marginally higher in patients on OD regimen - Almost a quarter of patients had no tablet count data Patient reported adherence higher on OD regimen - OD patients found it significantly easier to remember to take their medication

7 The CODA study: Adherence sub study More intensive monitoring of adherence Adherence measured using the Medication Event Monitoring System (MEMS) - Cap electronically recorded time and date of each opening - Data uploaded at each trial visit Sub group of trial patients participated (n=58) Sub study outcomes: - Impact of adherence on relapse rates - Comparison of main trial and sub study adherence data - Comparison of weekday and weekend adherence - Comparison of adherence near and away from trial visit dates - Modelling of adherence over time Fig. Example of a MEMS bottle Percentage of days adherent higher in OD group - OD Median 97% (IQR: 93 98%), TDS Median 55% (IQR: 34 86%), p < Adherence did not significantly influence relapse, after controlling for trial arm

8 Results: Comparing MEMS with tablet counts

9 Results: Comparing MEMS with self-report

10 Results: Weekday v weekend adherence Regression analysis - Dependent variable: (Weekday adherence Weekend adherence) - Intercept: Overall difference - Trial arm: Impact of dosing regimen on difference Variable Coefficient Standard error p-value Intercept <0.001 Once daily trial arm Three times daily trial arm Reference category Significantly higher adherence on weekdays than on weekend No significant impact of dosing regimen

11 Results: Adherence around visit dates Regression analysis - Dependent variable: (Visit date adherence Non visit date adherence) - Intercept: Overall difference - Trial arm: Impact of dosing regimen on difference Variable Coefficient Standard error p-value Intercept Once daily trial arm Three times daily trial arm Reference category No significant difference between visit date and non visit date adherence No significant impact of dosing regimen

12 Results: Adherence over time Weekly Small but adherence significant over decrease the trial over period time analysed by fitting multilevel linear growth model Once daily trial arm significantly associated with higher adherence Two Interaction level model: between observations time and trial (weekly arm adherence) not significant within patients Assumed equal correlation between time points Random intercepts and random slopes Variable Coefficient Standard error p-value Intercept <0.001 Time (in weeks) Trial arm (once daily) Trial arm (three times daily) Time x Trial arm (once daily) Time x Trial arm (three times daily) <0.001 Reference category Reference category

13 Summary MEMS cap opening data correlated well with tablet counts and self-report MEMS provides more detailed assessment of adherence patterns than other methods Adherence significantly better on weekdays than at weekends - Small but significant effect. Such analysis may be better suited to studies with a shorter follow-up Some indication of better adherence around visit dates - Small but non-significant effect Small but significant decrease in adherence over time - Adherence higher for patients on once daily regimen - No significant difference in the rate of decline between trial arms

14 Implications Adherence is poor in patients - on complex dosing regimens - for long periods of time - when it impacts on their daily life Targets for interventions to improve adherence - If safe to do so! Improve adherence improve patient outcome Drugs don t work in patients who don t take them

15 Questions Funding: The trial was supported by an unrestricted educational grant from Warner Chilcott Pharmaceuticals Ltd. Contact details: