ISPE August 2017 Montreal2018-08-16T12:09:41+00:00

Project Description

33rd International Conference on Pharmacoepidemiology & Therapeutic Risk Management (ICPE), Montreal, August 2017

Abstract 517

Abstract 517: Utilisation and safety of deferasirox (Exjade®) in older adults: results from a post authorisation safety study (PASS)

Sandeep Dhanda, Deborah Layton, Vicki Osborne, Saad Shakir

Background: A UK PASS examined the safety and use of deferasirox prescribed in primary care in England. Deferasirox is an oral iron chelating agent indicated for treating chronic iron overload from repeated blood transfusions in patients (pts) with beta thalassaemia major and chelation therapy in other non-transfusion-dependent thalassaemias. Whilst dosing recommendations for elderly pts (≥65 yrs) are the same as for younger age groups (2 yrs+), research has shown higher frequency of adverse reactions in the former. Closer monitoring for adverse events is recommended for this pt subgroup.


 A supplementary analysis to examine the utilisation and safety of deferasirox in pts aged ≥65 yrs.


An observational cohort study. Pts identified from dispensed prescriptions (Rx) of deferasirox Sept 06-Sept 14. Outcome data collected from prescribing general practitioners via questionnaires sent ≥6 months after 1st dispensed Rx. Summary descriptive statistics calculated; % denominator ≥65 yr subgroup, unless specified.


Evaluable cohort=122 pts (median age 23 yrs (IQR 11-61)). Twenty-seven pts aged ≥65 yrs (22.1% cohort); 17 male (63.0%). Starting dose specified for 12 pts ≥65 yrs (44.4%); 8 initiated on 10mg/kg/day and 4 pts on 20mg/kg/day. Frequent reasons for prescribing include myelodysplastic syndrome (n=13), iron overload (n=3) and aplastic anaemia (n=2). Majority of pts had treatment initiated by a specialist (n=22, 81.5%). Serum creatinine (SCr) was reported for 6 pts ≥65 yrs (22.2%) prior to starting; 3 were > reference range (female >90 μmol/L; male >110 μmol/L). SCr was also reported for 6 pts after starting treatment, exceeding the reference in 3 female pts (66-75 yrs, SCr 96-116µmol/L; baseline (bl) unknown) and 1 male pt (78 yrs, SCr 137 µmol/L; bl unknown). There was also an additional report of an increased SCr in a 74 yr old female pt without prior renal disease (SCr 135μmol/L; bl SCr 69μmol/L). A positive de-challenge was observed and the event was reported as a suspected adverse reaction to deferasirox.


These results show that deferasirox is being prescribed in older adults in England, with limited evidence of systematic monitoring in this pt subgroup. Despite recommendations for at least once monthly monitoring, missing data on renal measurements both prior to starting and during treatment were observed, in addition to events of raised SCr. Considering the small cohort of older adults, results should be put into context with other research evidence.

Abstract 868

Abstract 868: Multi­Level Modelling (MLM) in Specialist Cohort Event Monitoring (SCEM) Studies

Deborah Layton, Debabrata Roy,Sarah E. Marley, Saad A. W Shakir

Background: Prescribing guidelines (PG) influence treatment choice based on patient (pt) factors. Clinical use is also influenced by non-pt factors. MLM can provide insight into sources of variability in healthcare, where hierarchical structures exist. A SCEM study is investigating the safety and use of rivaroxaban (R) in clinical use, with a warfarin (W) cohort for context.


Ad-hoc MLM to explore influences on prescribing anticoagulants.


Data on 53 NHS acute trusts in England/Wales (e.g population size, PG) were linked to interim SCEM pt demographic and drug utilization data, and prescriber details (e.g degree, specialism). MLM was applied to 1006 (55%) R vs. 816 W (45%) adult pts nested in 514 prescribers, nested in trusts. The binary outcome was R or W treatment. Variance components were expressed as median ORs (median relative increase in odds of R treatment if pt changed prescriber/trust) and proportional change in variance (PCV) between models when successively adding fixed effects (pt/prescriber/trust). If treatment choice was dominated by pt factors, having accounted for their effects, variance between prescribers and trusts would be comparatively low.


Differences between trusts and prescribers in trusts are important in treatment choice; trust being more influential (MORTRUST(T)=6.9; MORPRESCRIBER(P)=3.9). Some pt factors had a relatively large effect on odds of treatment choice, e.g cerebrovascular accident [OR 2.0 (95%CI 1.3,3.0)]. Adjusting for pt factors, MORT=7.8 (PCV=20%); MORP=4.5 (PCV=14%). Adjusting for prescriber factors, MORT=7.1 (PCV=-8%); MORP=3.8 (PCV=-19%). Adjusting for trust factors did not improve the model performance.


In this exploratory analysis, treatment variability appears dominated by differences between trusts and prescribers; most notably trusts. Some pt factors were important in treatment choice, but PCV between models suggest that accounting for pt differences does not fully explain the variance between prescribers and between trusts. This study highlights the utility of MLM in exploring non-pt factors. This interim analysis will be superseded on completion of the SCEM study.

Abstract 981

Abstract 981: Passive Enhanced Safety Surveillance in children receiving Fluenz Tetra vaccination in England during the early 2016 influenza season

Lorna Hazell, Saad AW Shakir, Andrew Finlay, Hannah Coulter, Robert S Brody and Dennis Brooks

Background: Fluenz® Tetra is a quadrivalent, live attenuated, intranasal, influenza vaccine recommended for use in children aged 2 to 17 years vaccinated as part of the seasonal influenza immunisation campaign in the UK. Following a successful pilot in 2015, we report results from a second season of passive enhanced safety surveillance (ESS) for 2016.


To measure and assess the frequencies of suspected adverse drug reactions (sADRs) in children receiving Fluenz® Tetra during the early 2016 influenza season in England.


Vaccinees or parents/guardians received a Safety Report Card (SRC) to return if children experienced sADRs after vaccination with Fluenz® Tetra. At participating sites, 47 general practices and 44 primary schools in England, immunisation teams recorded numbers of SRCs distributed. The study was approved by an NHS Research Ethics Committee (Brighton and Sussex NRES Committee).


Between 24th September 2016 and 30th November 2016, 14,511 children were vaccinated at study sites, with eight different vaccine lots used. In total, 12,610 SRCs were issued for 5,501 children (43.6%) aged 2 to 4 years, 6,457 (51.2%) aged 5 to 10 years, 651 (5.2%) aged 11 to 17 years and one child (0.1%) aged outside the 2 to 17 year old licensed age-group. Of 135 SRCs returned, 112 reported at least one sADR. The most frequently reported sADRs were rhinorrhoea (n=30), pyrexia (23), headache (20) and cough (19). No serious sADRs were reported and no sADRs were reported within the immune system organ class. The pattern of sADRs in the current ESS season was similar to that reported in the 2015 season.


Reporting of sADRs via ESS remains low (~1%). No evidence from the limited data available suggests an increased frequency of minor expected events or other safety signals compared to ESS data from the 2015 season. The ESS method appears to achieve the requirement for a monitoring method to detect possible immunogenic sADRs for each year’s vaccine.

Study co-sponsored by DSRU and AstraZeneca.

Contact Info

Drug Safety Research Unit Bursledon Hall, Blundell Lane, Southampton, SO31 1AA, U.K.

Phone: +44 (0)23 80 40 86 00

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