Implementing a specialist paediatric clinical pharmacology service in a UK children's hospital

Aims Royal College of Paediatrics and Child Health subspecialist training in Paediatric Clinical Pharmacology and Therapeutics has been delivered in the UK for 20 years, but no specialist clinical services have been set up previously. Methods Prospective audit and service evaluation of paediatric clinical pharmacology service pilot phase and dedicated service at a UK children's hospital. Results Pilot scheme (May–October 2019), then weekly service (established June 2020). Service covers the High Dependency Unit, and inpatients with polypharmacy. The pilot demonstrated high levels of acceptance, with 89% of suggested medication changes agreed by lead clinical team, and success, with 97.5% of suggested changes continued until discharge/pilot completion. Economic analysis estimated direct annualised cost savings on medications of up to £10 000. After 20 ward rounds of the established service, 270 potential medication changes were identified, 213 were carried out (78.9%). The most common were deprescribing (n = 143), prescribing (n = 47) and dose adjustment (n = 8). Seventy‐five different medications were deprescribed, most commonly chloral hydrate (n = 12), Lactulose, ibuprofen, Bio‐Kult and sodium alginate (all n = 4). The percentage of inpatients prescribed ≥10 medications decreased from 38.5 to 32.1%, while the subset prescribed ≥20 medications decreased from 11.0 to 5.67%. The mean number of medicines prescribed decreased from 9.0 to 8.0, while the median was unchanged at 7. Annual Yellow Card reports of suspected adverse drug reactions more than doubled (n = 66). Conclusion A UK model for subspecialist paediatric clinical pharmacology service delivery has demonstrated a positive clinical impact and could be replicated at other UK secondary/tertiary children's hospitals.


| INTRODUCTION
Clinical Pharmacology is a distinct medical specialty that examines all aspects of the relationship between drugs and humans. In the National Health Service (NHS), it is the only medical specialty focusing on the safe, effective and cost-effective use of medicines. 1 Within adult medicine, clinical pharmacology has established how it contributes to NHS clinical service delivery, academic research, and undergraduate/postgraduate teaching. 2 The Royal College of Paediatrics and Child Health (RCPCH) in the UK has developed and delivers an accredited subspecialist training scheme in paediatric clinical pharmacology and therapeutics. 3,4 The areas covered by this training, as well as roles for paediatric clinical pharmacologists in academia and teaching have been developed. 5 However, unlike other countries, a clinical service has not been developed in the UK, with subspecialists in the UK contributing clinically via general paediatric consultant posts or in specialist positions (e.g. National Poisons Centre). Across Europe and in North America, centres of excellence exist where paediatric clinical pharmacology services are well established and contribute to patient care directly. [6][7][8] Children and young people (CYP) deserve medical treatments that are of the same quality and safety as adults. Within paediatrics, despite formularies such as the British National Formulary for Children, there is evidence that prescriptions for similar conditions in CYP in different healthcare settings or geographical areas vary considerably, indicating that there are still considerable improvements to be made in implementing rational prescribing in the UK. 9 In addition, the number of medications prescribed is increasing, such that 8% of all CYP take 2 or more medicines. 10,11 As treatments improve, the number of CYP surviving with complex conditions is also increasing, 12 and these CYP have increased likelihood of problematic polypharmacy. The use of unlicensed and off label medications can be necessary in paediatric practice. 13 New medications, and new indications for older medicines, require scrutiny at trust level on drugs and therapeutics committees.
Adverse drug reactions (ADRs) are responsible for 3% of all paediatric admissions, and complicate 15% of inpatient stays, 14,15 but reporting to spontaneous reporting schemes to identify these suspected harms remains low. 16,17 There are initiatives and new technologies (e.g. deprescribing and pharmacogenomics) related to children's medicines that will require evaluation, and if appropriate, integration into NHS services. There is therefore a need for specialist paediatric clinicians whose focus is on the safe and effective use of medicines.
Pharmacists are another key group of healthcare professionals who contribute to the safe and effective use of medications in CYP, and there are many examples of improvements led and/or delivered by clinical pharmacists including identifying and preventing medication errors, identifying and reporting ADRs, and medicines reconciliation. [18][19][20][21] Recently, pharmacists in paediatrics have also participated and led druggles, a prescribing-or drugs-themed huddle on paediatric wards. [22][23][24] Additional services by paediatric clinical pharmacologists need to aware of these schemes, and ensure the work adds value rather than repeating existing work.
The aim of this work is to describe the clinical pharmacology service pioneered at a secondary/tertiary/quaternary children's hospital in England, and present prospective audit and quality improvement data related to the services activities.     Table 2.

| METHODS
Prescriptions for 75 different medications were changed. One medication intervention was reversed afterwards by the team as the patient developed low magnesium levels, and the supplements were restarted. The medications that were changed on 3 or more occasions are shown in Table 2 In addition, 27 urgent drug requests requiring rapid review (24-48 h) and response were received and responded to. Additionally, time has been dedicated to support trust committees and groups managing specific medication issues (e.g. sodium valproate, cannabis-containing medications).  reporting in the trust (Figure 2). ADRs reported on the pharmacology ward round, and captured through promotional activity and monthly emails are shown in Table 3. Of the 52 medications suspected overall, there were 46 different drugs, with none included on more than 3 reports, and only a single vaccine reaction noted. The types of suspected ADRs reported were not formally scored for severity, but included clinically significant events such as anaphylaxis, acute kidney injury, intracranial haemorrhage, and demyelinating illness.   The annualised cost savings shown here are using the trust costs, so represent a lower estimate of the potential savings for CCGs if the service were expanded. They also do not include any potential indirect cost savings from reduced potential for ADRs, drug-drug interactions etc. While the data presented here do appear very positive, we do acknowledge that due to the service being commenced in the middle of the COVID-19 pandemic, the clinical situation overall, and the inpatients present in the hospital, may not be representative of a normal winter period in the north-west of England. However, the service will continue to prospectively audit their intervention data to monitor changes in inpatient case mix, and track any improvements that are sustained. The delivery of this service has also thrown into sharp relief the lack of data supporting clinicians wishing to deprescribe medications in paediatrics. This has led to ongoing academic research about how to develop such guidance, and how to disseminate it effectively to where it is needed.

| Spontaneous reporting of suspected ADRs
The suspected ADRs identified were from a wide range of drugs, and the pattern of medications differs markedly from both the overall Yellow Card Reports for children and neonates in the UK, 16 but also those from CYP themselves, 27 demonstrating the necessity of having multiple routes of reporting to capture the full range of possible ADRs.