Louise E Bracken

Adverse drug reactions and off-label and unlicensed medicines in children: a nested case?control study of inpatients in a pediatric hospital

BackgroundOff-label and unlicensed (OLUL) prescribing has been prevalent in pediatric practice. Using data from a prospective cohort study of adverse drug reactions (ADRs) among pediatric inpatients, we aimed to test the hypothesis that OLUL status is a risk factor for ADRs.MethodsA nested case?control study was conducted within a prospective cohort study. Details of all medicines administered were recorded, including information about OLUL status. The odds ratio for OLUL medicines being implicated in a probable or definite ADR was calculated. A multivariate Cox proportional hazards regression model was fitted to the data to assess the influence that OLUL medicine use had on the hazard of an ADR occurring.ResultsA total of 10,699 medicine courses were administered to 1,388 patients. The odds ratio (OR) of an OLUL medicine being implicated in an ADR compared with an authorized medicine was 2.25 (95% confidence interval (CI) 1.95 to 2.59). Medicines licensed in children but given to a child below the minimum age or weight had the greatest odds of being implicated in an ADR (19% of courses in this category were implicated, OR 3.54 (95% CI 2.82 to 4.44). Each additional OLUL medicine given significantly increased the hazard of an ADR (hazard ratio (HR) 1.3 95% CI 1.2 to 1.3, P <0.001). Each additional authorized medicine given also significantly increased the hazard (HR 1.2 95% CI 1.2 to 1.3, P <0.001).ConclusionsOLUL medicines are more likely to be implicated in an ADR than authorized medicines. The number of medicines administered is a risk factor for ADRs highlighting the need to use the lowest number of medicines, at the lowest dose for the shortest period, with continual vigilance by prescribers, in order to reduce the risk of ADRs.

Incidence, characteristics and risk factors of adverse drug reactions in hospitalized children – a prospective observational cohort study of 6,601 admissions

BackgroundAdverse drug reactions (ADRs) are an important cause of harm in children. Current data are incomplete due to methodological differences between studies: only half of all studies provide drug data, incidence rates vary (0.6% to 16.8%) and very few studies provide data on causality, severity and risk factors of pediatric ADRs. We aimed to determine the incidence of ADRs in hospitalized children, to characterize these ADRs in terms of type, drug etiology, causality and severity and to identify risk factors.MethodsWe undertook a year-long, prospective observational cohort study of admissions to a single UK pediatric medical and surgical secondary and tertiary referral center (Alder Hey, Liverpool, UK). Children between 0 and 16 years 11 months old and admitted for more than 48 hours were included. Observed outcomes were occurrence of ADR and time to first ADR for the risk factor analysis.ResultsA total of 5,118 children (6,601 admissions) were included, 17.7% of whom experienced at least one ADR. Opiate analgesics and drugs used in general anesthesia (GA) accounted for more than 50% of all drugs implicated in ADRs. Of these ADRs, 0.9% caused permanent harm or required admission to a higher level of care. Children who underwent GA were at more than six times the risk of developing an ADR than children without a GA (hazard ratio (HR) 6.40; 95% confidence interval (CI) 5.30 to 7.70). Other factors increasing the risk of an ADR were increasing age (HR 1.06 for each year; 95% CI 1.04 to 1.07), increasing number of drugs (HR 1.25 for each additional drug; 95% CI 1.22 to 1.28) and oncological treatment (HR 1.90; 95% CI 1.40 to 2.60).ConclusionsADRs are common in hospitalized children and children who had undergone a GA had more than six times the risk of developing an ADR. GA agents and opiate analgesics are a significant cause of ADRs and have been underrepresented in previous studies. This is a concern in view of the increasing number of pediatric short-stay surgeries.

Development of the Liverpool Adverse Drug Reaction Avoidability Assessment Tool

Aim To develop and test a new tool to assess the avoidability of adverse drug reactions that is suitable for use in paediatrics but which is also applicable to a variety of other settings. Methods The study involved multiple phases. Preliminary work involved using the Hallas scale and a modification of the existing Hallas scale, to assess two different sets of adverse drug reaction (ADR) case reports. Phase 1 defined, modified and refined a new tool using multidisciplinary teams. Phase 2 involved the assessment of 50 ADR case reports from a prospective study of paediatric inpatients by individual assessors. Phase 3 compared assessments with the new tool for individuals and groups in comparison to the ‘gold standard’ (the avoidability outcome set by a panel of senior investigators: an experienced clinical pharmacologist, paediatrician and pharmacist). Main Outcome Measures Inter-rater reliability (IRR), measure of disagreement and utilization of avoidability categories. Results Preliminary work—Pilot phase: results for the original Hallas cases were fair and pairwise kappa scores ranged from 0.21 to 0.36. Results for the modified Hallas cases were poor, pairwise kappa scores ranged from 0.06 to 0.16. Phase 1: on initial use of the new tool, agreement between the two multidisciplinary groups was found on 13/20 cases with a kappa score of 0.29 (95% CI -0.04 to 0.62). Phase 2: the assessment of 50 ADR case reports by six individual reviewers yielded pairwise kappa scores ranging from poor to good 0.12 to 0.75 and percentage exact agreement (%EA) ranged from 52–90%. Phase 3: Percentage exact agreement ranged from 35–70%. Overall, individuals had better agreement with the ‘gold standard’. Conclusion Avoidability assessment is feasible but needs careful attention to methods. The Liverpool ADR avoidability assessment tool showed mixed IRR. We have developed and validated a method for assessing the avoidability of ADRs that is transparent, more objective than previous methods and that can be used by individuals or groups.

Medicines in schools: a cross-sectional survey of children, parents, teachers and health professionals

Objectives To describe how individual schools manage medicines and strategies for implementation of guidance, to determine the nature of problems perceived by children, parents, teachers and healthcare professionals (HCPs) in relation to medicines management in schools and to highlight differences between these perceptions. Design A cross-sectional survey study in which questionnaires were completed by children, their parents and carers, groups of HCPs and head teachers. Results There were 158 respondents to this survey. The management of medicines varies between schools and this reflects how policy guidance is interpreted and is revealed by the differences in experience described. Head teachers acknowledge that there is a lack of expertise about medicines among their staff and they rely on interpretation of and adherence to policy and procedure and compliance with training was used as a measure of good medicines management. There are inconsistencies in how information about medicines is communicated between the healthcare team, families and schools, and there is evidence that this communication is not always timely or effective. This results in problems with medicines at school. Parents emphasised the need for staff at school to understand their child’s condition and their medicines. Conclusions There are differences between how individual schools manage medicines and interpret policy guidance and discrepancies between the views of each stakeholder group. There is some evidence that medicines management does not always meet the needs of children and their families. Fewer than half of parents and HCPs are satisfied with how medicines are dealt with in schools.

PO-0926 Are Group Assessments Superior To Individual Avoidability Assessments? A Test Of The Liverpool Adverse Drug Reaction Avoidability Assessment Tool

Background There is currently no standardised method for determining avoidability of adverse drug reactions (ADRs) and many of the established tools are not suitable for use in paediatrics. We have developed a new tool; the Liverpool ADR avoidability assessment tool (LAAT). Initial testing showed mixed inter-rater reliability. Aim To test the hypothesis that group assessments are superior to individual avoidability assessments. Methods Participants were assigned either to a consensus group or to individually assess avoidability for a purposive sample of 20 ADR cases. Individual participants (nurses, pharmacists and doctors) independently assessed the cases. Groups took part in multidisciplinary meetings to assess the cases and reach consensus. The results were compared to the ‘gold standard’ (the avoidability outcome set by a panel of senior investigators). An ethnographic approach was taken; the consensus meetings were overseen by a facilitator and non-participant observations of the meetings were recorded. Post consensus meeting semi-structured interviews were conducted with the group members. Qualitative and quantitative analyses were carried out. We examined the extent to which individuals and groups agreed with the ‘gold standard’ using percentage exact agreement (%EA) (Figure 1). Results Agreement ranged from 35–70%. The mean agreement for individuals was 54% and 47% for the consensus groups. Conclusion In assessing avoidability of ADRs individual assessments had better agreement with the ‘gold standard’ evaluation than group assessments. Qualitative analysis of meeting observations and participant interviews may help identify reasons for this and inform the optimisation of the LAAT for assessment of ADR avoidability. Abstract PO-0926 Figure 1

DEVELOPMENT OF AN ADVERSE DRUG REACTION AVOIDABILITY ASSESSMENT TOOL

Aim To develop and test a new adverse drug reaction (ADR) avoidability assessment tool (AAT) that is more suitable for use in paediatrics but which is also generalisable and applicable to a variety of other settings. Methods The new AAT was based on the Hallas scale1 and the initial draft of the tool was developed via a consensus approach. Phase one consisted of three parts (defining the tool, modifying the tool and refining the tool) involving two multidisciplinary teams (MDT) each comprising a research childrens nurse, paediatrician and pharmacist. Phase two involved the independent assessment of 50 ADR cases reports of adverse drug reactions from a paediatric inpatient study by six reviewers acting independently. Results Phase 1: the assessment of 20 ADR cases by two MDTs showed agreement between the groups on 13/20 cases with a kappa score of 0.29 (95% CI −0.04 to 0.62). Group members commented that a mixture of professions was needed to give a full assessment of avoidability. Phase 2: the individual assessment of 50 ADR case reports by six individual reviewers where pair-wise kappa scores ranged from poor to good (0.12 to 0.75) and percentage exact agreement (%EA) ranged from 52–90%. Stronger agreement was found within professions than between professions. Conclusion The new AAT showed mixed inter-rater reliability (IRR) in the individual assessment phase; further testing in a group setting is required to develop and validate the tool. The next step in the development process will be to investigate how groups make decisions and the factors that influence decision making.