Persistence of statin treatment – the impact of analytic method when estimating drug survival

Background: There is ample evidence for several pharmaceutical treatments that adherence in terms oftreatment duration and dose is suboptimal. The actual drug intake cannot be observed directly in prescriptiondatabases, which only register drug redeemed and a limited number of patient characteristics. Consequently,the actual dose and duration of treatment must be inferred from observed redemptions. Persistence can thenbe expressed as treatment duration (also referred to as drug survival).Method: We used data from the Norwegian Prescription Database (NorPD) on redemptions of statins (ATCcodeC10AA) for the period 2010-2019 to explore three methods for determining prescription durations andin turn persistence (treatment duration): (i) The DDD-method using the number of DDD redeemed; (ii) Thedose-unit approach using the number of tablets redeemed; (iii) The reverse waiting time distribution method(WTD), which estimates prescription duration as the 90th percentile of the distribution within which patientsin ongoing treatment will have a new subsequent redemption. The three methods for estimating prescriptionduration were then used to estimate treatment duration using Kaplan Meier (KM) survival functions. For theDDD-method and the dose-unit approach we conducted sensitivity analyses assuming that one DDD or onetablet would last for 1.00, 1.25 or 2.00 days. We also tested the impact of grace periods in sensitivity analyses.Results: Treatment duration and drug survival varied substantially for the same patients depending on thechosen method, duration of a DDD or a tablet, and inclusion of grace periods. The 25th percentile of treatmentduration was 100 days for the DDD approach with one DDD per day, 100 days with the dose-unit approachwith one tablet per day and 453 days with the WTD approach.Conclusion: When estimating treatment duration from prescription databases one should be aware that thesemeasures of persistence are highly influenced by the chosen methodology. The choice of method should beinformed by the clinical context with a preference for use of methods based on a formal model.

APPROPRIATE DOSE ROUNDING OF CYTOKINE MODULATORS FOR PAEDIATRIC RHEUMATOLOGY INPATIENTS

BackgroundCytokine modulators (adalimumab, infliximab, etanercept, anakinra, canakinumab, rituximab, tocilizumab and abatacept) are high-cost biologics used primarily in paediatrics to treat patients with juvenile idiopathic arthritis.1 Funding mechanisms are unreliable and inconsistent hence appropriate dose rounding is a key cost-saving measure.2 However, there is a lack of evidence-based guidance for dose rounding in paediatrics.3 Aims and objectivesDetermine if 100% of inpatient cytokine modulator prescriptions in rheumatology are dose rounded up or down to the nearest whole vial, pen or syringe if within 5 or 10% of the dose for patients less or more than 10 kg respectively.Establish financial impact of drug wastage due to failures in dose rounding.MethodRetrospective data collection of electronic prescriptions for all cytokine modulators prescribed for rheumatology inpatients from January 2011 to December 2014. Prescriptions analysed using a five step process to determine if doses could have been rounded to nearest whole dose unit. Cost of waste resulting from failure to dose round also calculated.ResultsOnly 35% (380/1100) of prescriptions rounded to the nearest whole dose unit therefore audit standard not met. 97% (698/720) of all prescriptions not dose rounded were for tocilizumab and infliximab with approximate annual wastage of £11,000. Unexpected and significant unavoidable wastage identified due to lack of paediatric-friendly dose unit sizes, particularly for canakinumab (approximately £740,000/year).DiscussionAppropriate dose rounding does not appear to be common practice. Raising awareness and educating rheumatology and pharmacy teams as well as establishing local dose banding or rounding guidelines may improve future results. Tocilizumab is available in 80 mg, 200 mg and 400 mg vials therefore there is scope for flexibility in dose rounding if combinations are used appropriately. Unavoidable waste may be reduced through use of pharmacy central intravenous additive service (CIVAS) for preparation or use of biosimilars.