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MULTIDISCIPLINARY CAR-T TEAM (submitted in 2019)

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European Statement

Clinical Pharmacy Services

Author(s)

MARGHERITA GALASSI, CHIARA DELLA COSTANZA , CLAUDIA TIRONE, SARA BERTOLI, ERNESTO RUFFINO, ELEONORA FERRARI, ELENA ALIPRANDI , VITO LADISA

Why was it done?

CAR-T cell therapies are a new advanced type of personalised immunotherapy against cancer. In the EU the authorised therapies are tisagenlecleucel and axicabtagene ciloleucel, both used in our centre as third line for the registered indication of diffuse large B-cell lymphoma. CAR-T therapies production and administration process consists of multiple stages: patient’s leukapheresis, genetic engineering of lymphocytes, lymphodepleting chemotherapy (LC), CAR-T cell infusion, monitoring of the patient. Considering the complexity of the procedure and the observance of specific schedules, these therapies should be administered in highly specialised centres complying with specific organisational requirements, with disposal of an adequate multidisciplinary team.

What was done?

A multidisciplinary team (CAR-T team) was constituted for the management of CAR-T therapies (Chimeric Antigen Receptor T). The pharmacist was included in the team for the planning and organisational phase of the process.

How was it done?

The pharmacist is responsible for the approval of the physician’s prescription, the LC preparation according to Good Manufacturing Practice (GMP), the LC distribution on scheduled time, the making available of treatments for supporting the patient until CAR-T infusion, and treatments after infusion for management of adverse events. At the arrival of the CAR-T product, the pharmacist is responsible for the check and release of it in good condition. The LC protocols foresee the administration of cyclophosphamide and fludarabine on the 5th, 4th and 3rd day before the CAR-T infusion, and are defined on the basis of the summary-of-product characteristics. The medications are provided locally and refunded by the national health system.

What has been achieved?

In our center 8 patients were treated with compassionate use of axicabtagene ciloleucel. The pharmacist’s presence in the multidisciplinary team was advantageous because, through validation of the therapies and verification of dosages, they guarantee further security to the patients. The high-tech automated centralisation and computerisation of chemotherapies at our centre ensured quality and safety of the preparations.

What next?

The realisation of defined paths and codified proceedings, the respect of fundamental timings for the success of the process and the chemotherapy preparation centralisation could lead to increased investment, decisive for obtaining a high quality product and process level. The experience, now limited to haematology, could be used for future CAR-T applications.

A QUALITY IMPROVEMENT PROJECT ON HEPARIN INFUSION SAFETY IN AN ACUTE TEACHING HOSPITAL (submitted in 2019)

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European Statement

Patient Safety and Quality Assurance

Author(s)

Anthony Hackett, Alice Oborne, Emma Ritchie, Caroline Broadbent, Rebecca Chanda, Karen Breen

Why was it done?

Anticoagulants such as UFH are recognised as high risk drugs. UFH requires frequent monitoring of the activated partial thromboplastic time ratio (APTTr), ensuring therapeutic anticoagulation and minimising adverse effects. UFH infusions and the APTTr were recorded using a paper based system. Incident reporting identified by the paper system resulted in inappropriate monitoring and management of UFH infusions, and dose omissions which could have resulted in harm.

What was done?

A Trust-wide electronic prescribing and medicines administration (EPMA) system was implemented in 2015. Complex infusions, e.g. unfractionated heparin (UFH) infusions, remained on paper due to EPMA functionality limitations. The complex infusion function was added into later EPMA upgrades. A multidisciplinary team (MDT) involving nursing, medical and pharmacy staff working within anticoagulation, EPMA and medication safety sought to design UFH infusions in EPMA.

How was it done?

Baseline audit (Paper-March 2016): Patients prescribed UFH infusions (n=14) were identified using SharePoint (e-reporting) by searching for the UFH infusion placeholder. Performance was measured against eight audit standards.
Re-audit (EPMA-March 2019): Patients prescribed UFH infusions (n=26) were identified using SharePoint by searching for those prescribed a UFH infusion on EPMA. Performance was measured against the same eight audit standards.
Chi square applied to results to test for statistical significance.
Incident rate per prescription: The Datix system was searched to identify heparin incidents reported during the data collection periods.

What has been achieved?

Audit standard 2016 audit v 2019 audit
1-Baseline APTTr checked before starting infusion 93% v 100%, p=0.1
2-Received correct loading dose of heparin based on APTTr 79% v 96%, p=0.07
3-APTTr checked 6 hours after infusion started 72% v 100%, p<0.05
4-APTTr checked 6 hours after infusion titrations 86% v 96%, p=0.2
5-APTTr in target range within 24 hours 50% v 70%, p=0.2
6-APTTr checked 24 hourly after 2 consecutive APTTr’s in range 100% v 100%=no change
7-Patient receives a medical review 24 hrly 65% v 100%, p<0.05
8-Heparin syringe and giving set changed 24 hrly 65% v 100%, p<0.05

UFH related incidents reduced from one incident per 1.6 infusions, to one incident per 6.5 infusions following the implementation of an EPMA system.
UFH incidents as a proportion of all anticoagulant incidents reduced from 43% (March-2016) to 20% (March-2019).

What next?

Electronic solution’s for high-risk, complex infusions such as heparin prescribing and monitoring improved care, quality and safety. Further high-risk infusions such as insulin are being developed

MANAGING MEDICINES SHORTAGES ON A NATIONAL LEVEL – A MULTIDISCIPLINARY COLLABORATION BETWEEN WHOLESALER, HOSPITAL PHARMACIES AND PATIENT SAFETY ORGANISATION IN DENMARK (submitted in 2019)

European Statement

Selection, Procurement and Distribution

Author(s)

Christine Dinsen-Andersen, Hanne Fischer, Anita Gorm Pedersen, Dagmar Bertelsen, Marianne Hald Clemmensen

Why was it done?

Before the NTF was established, each hospital pharmacy made their own assessments and solutions to CMS. This led to a lack of coordination in the national supply and knowledge sharing. As the number of CMS increased, a need for a coordinated national initiative became evident. The aim of the NTF is to secure better communication to healthcare professionals and to establish clearly defined rolls and responsibility in the supply chain from wholesaler to hospital pharmacy. Patient safety aspects should be included in all relevant steps of the process.

What was done?

A National Task Force (NTF) for critical medicines shortages (CMS) have been established with the main objective to provide therapeutic and patient safety assessment of CMS on a national level. In addition to this the NTF takes considerations regarding the supply chain into account in the assessments.

How was it done?

To secure national engagement, members of the task force were appointed according to a consensus between the hospital pharmacies in Denmark. The NTF includes participants from 3 hospital pharmacies, the national wholesaler for hospital pharmacies and a patient safety organization. Based on challenges of geographical dispersion and different local practices, an effort was put into: • securing a systematic work flow, for the group; • creating a digital platform with access for members from different organizations; • agreeing on when a medicine shortage is critical.

What has been achieved?

• Early intervention – resulting in opportune solutions. • Agility in allocation of remaining stock between hospital pharmacies. • Optimisation of choice of alternative treatment during period of shortage. • Secure supply of alternative drugs on national level. • Initiate agreement between physicians on choice of alternative on a national level. • Attention to patient safety challenges – preventing adverse events.

What next?

Joined forces have resulted in coordinated and optimised solutions to managing CMS, enabling the hospital pharmacies to secure patient safety. Hence the NTF shall continue its work. Having a national unit as NTF provides the basis for coordinated initiatives and for corporation with health and medicines authorities and market authorization holders.

SAFE PRESCRIBING METRICS FOR HOSPITAL PHARMACY (submitted in 2019)

European Statement

Patient Safety and Quality Assurance

Author(s)

Oran Quinn, Anna Marzec

Why was it done?

Errors of miscalculation, doses inappropriate for renal function and at extremes of weight were reported when doses of medication were written as ‘mg/kg’ without stating the dose to be given e.g. Gentamicin 5mg/kg, Vancomycin 15mg/kg and Enoxaparin 1.5mg/kg.

What was done?

A quality improvement initiative to resolve issues with prescribing medications dosed by weight. Nursing staff were identified as ‘gate-keepers’ who could refuse to administer medication inappropriately prescribed. Identification, agreement, education and feedback were necessary to change prescribing practice and support nursing staff. Hospital doctors were required to calculate and prescribe the total dose to be given. Feedback was given by monthly bulletin.

How was it done?

Support from key stakeholders was sought to endorse the initiative. Verbal and written education was given to nursing, medical and pharmacy staff to implement the initiative on an agreed date. Refusal to administer medication unsafely prescribed was key to successful implementation. Patient’s weight was not always available and additional equipment was provided to overcome this problem. The risk of withholding treatment was considered and an escalating referral process was recommended contacting the Senior House Officer, then Registrar and ultimately the patients Consultant to avoid lengthy delays to patient treatment. Nurses felt supported in refusing to administer medication.

What has been achieved?

A point prevalence study of all inpatients was carried out monthly to ascertain the level of compliance Mar-19 Apr-19 May-19 Jun-19 Jul-19 Aug-19 % of patients with total dose prescribed correctly 67.0 86.7 96.7 100.0 100.0 88.9 87.5. Results showed overall improvement from March to August and full compliance in May and June. Success was achieved through a multidisciplinary approach involving all key stakeholders, a forcing function and support from and for front line staff.

 

What next?

This initiative has been further developed to become ‘Monthly Safe Prescribing Metrics’.
Other prescribing metrics such as using ‘iu’ dosing for Insulin, prescribing appropriately for patients at extremes of weight and using the abbreviation ‘mcg’ for medications dosed in ‘micrograms’ were included. Initiatives to improve all metrics are ongoing.
Safe prescribing metrics could help to positively influence prescribing culture in other healthcare settings.

HERA – A NEW TOOL FOR THE QUALITATIVE AND PHARMACOECONOMICAL EVALUATION OF GENERIC DRUG PRODUCTS BEFORE CHANGING BRANDS (submitted in 2019)

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European Statement

Selection, Procurement and Distribution

Author(s)

Steffen Amann, Rudolf Bernard, Georg Berndt , Meike Bindemann, Myga Brakebusch, Jörg Brüggmann, Frank Dörje, Miriam Gyalrong-Steur, Anita Kellermann, Markus Müller, Elfriede Nusser-Rothermundt, Rainer Riedel, Eva Tydecks

Why was it done?

Given rising cost-pressure and increasing numbers of supply shortages, changes between generics have become daily practice in hospital pharmacies. To ensure constant treatment quality and patient safety, the equivalence of a potential new product with the current one must be guaranteed before changing brands. So far there has been no transparent, standardised tool for the comparison of generics workable in everyday clinical practice. Developing such a tool was our project’s aim.

What was done?

We developed an Excel-based tool for the qualitative and pharmacoeconomical evaluation of generics before changing brands (aut-idem substitution) in hospitals.

How was it done?

A working-group of pharmacists from seven hospitals developed the “HERA” tool (HTA-evaluation of geneReric phArmaceuticals). Starting from a base version, 22 generic products were assessed with the tool during five evaluation rounds. Based on these results the instrument was gradually refined. Within HERA‘s Excel matrix a potentially to-be-used generic is compared with the current one. The economic evaluation is based on unit prices and prescription volumes, but also includes process costs associated with the product change. The assessment of pharmaceutical quality is based on 34 criteria from six areas (licensed uses, drug substance, dosage form and excipients, handling, safe design, packaging and storage). The objective quality evaluation is complemented by the assessment of hospital-specific features. Complex substitutions – e.g. associated with a handling change – require involvement of the medical staff using the product. The purchasing decision is taken based on the synopsis of pharmaceutical quality and economic evaluation.

What has been achieved?

The standardised evaluation of product differences before substitutions allows for the early identification of potential problems of brand changes and helps avoiding them for the benefit of patient safety. HERA also guarantees reproducibility and transparent, QM-compliant documentation of product changes. The pharmacies of our purchasing group now routinely use HERA for the assessment of generics before intended brand substitutions. Each evaluation is conducted in one pharmacy and shared with the others via data-cloud.

What next?

We have published a paper on HERA and presented it at the German Hospital Pharmacists congress in 2018. Our aim is to create a network of colleagues with shared access to all colleagues’ HERA product evaluations to reduce the workload for the individual pharmacies.

PHARMACEUTICAL ALGORITHMS TO PERFORM MEDICATION PHARMACEUTICAL ANALYSIS (submitted in 2019)

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European Statement

Patient Safety and Quality Assurance

Author(s)

Arnaud Potier, Béatrice Demoré, Alexandre Dony, Emmanuelle Divoux, Emmanuelle Boschetti, Laure-Anne Arnoux, Cédric Dupont, Jean-Christophe Calvo, David Piney, Virginie Chopard, Nathalie Cretin, Edith Dufay

Why was it done?

Drug iatrogenia costs global health systems $52 billion annually. The third global patient safety challenge aims at reducing the global burden of iatrogenic medication-related harm by 50% within 5 years [1]. Pharmaceutical analysis is a fundamental activity, a regulatory obligation in many countries but remains a challenge. This practice is highly variable. A graphic definition of the target pharmaceutical analysis has been formalised in December 2017 which sets the basis for its digitalisation, effectively implemented since January 2019. The aim is to build a corpus of the most relevant PA to facilitate clinical pharmacist practice.

What was done?

A computerised clinical pharmacy tool is integrated into the health information system of our group of hospitals (5000 beds) to promote efficiency of pharmaceutical analysis in order to improve patient safety. Pharmaceutical algorithms (PA) are conceptualised to improve drug related problems (DRP) detection and their resolution through pharmaceutical intervention (PI) according to a defined conduct to be held: anamnesis of subjective and objective elements of appreciation, DRP characterisation and PI transmission. Pharmaceutical analysis is performed by the use of PharmaClass® (Keenturtle). This software has been interfaced with 5 health data flow of two health facilities (1000 of the 2000 beds were tested): identity and patient flow, medication data, laboratory results examination, medical history, physiological constants. PA are partially encoded as rules in Pharmaclass® that issues alerts analysed by a pharmacist.

How was it done?

Health data are lacking of semantic interoperability which Pharmaclass® aims at overcoming from Electronical health record (EHR) queries in real time. A corpus of PA has been structured integrating the conduct to be held. PA were created by modeling the pharmaceutical experiment with the thread of criticality. PA were validated by consensus.

What has been achieved?

80 PA were encoded into Pharmaclass®: 40 are targeting serious adverse drug events. 1516 alerts were analysed and 539 PI transmitted during the 9-month test period.

What next?

This practice is applicable to any pharmaceutical analysis that uses data from an EHR. Clinical pharmacy societies should host and take care of updating corpus of PA. Its educational interest should be exploited. A European interest group for artificial intelligence in clinical pharmacy is being created.

THE IMPACT OF A WARD SATELLITE PHARMACY ON CLINICAL PHARMACY SERVICES AND POTENTIAL COST BENEFIET (submitted in 2019)

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European Statement

Patient Safety and Quality Assurance

Author(s)

Thewodros Leka, iun Grayston, Mashal Kamran, Biljana Markovic

Why was it done?

The Carter report recommended that about 80% of hospital pharmacist time should be spent on the wards to provide clinical pharmacy services. However, in our hospital’s surgical specialty at the time of this report, it was found that only 33% of pharmacist’s time was spent on clinical pharmacy services. This had a negative impact on:
• rate of medication errors and near misses
• supply of critical medicines
• pharmacist participation in productive ward rounds
• timely discharge of patients home

What was done?

The Pharmacy department made a successful business case to the Hospital executives to open a Satellite pharmacy to serve 4 surgical wards. The proposal was to recruit a dedicated clinical pharmacist and Medicines Management Technician, and set-up a dispensing satellite pharmacy.

How was it done?

The business case indicated that if funded, the new satellite pharmacy team would: • improve clinical pharmacy key performance indicators • improve patient safety • deliver a potential cost benefit Funding limitation was an obstacle and we have to convince the board.

What has been achieved?

We achieved 60−90% improvement in the objectives set in the business case as illustrated in Table 1 and 2. The pharmacy team won the annual quality improvement award of 2018. Table 1: Clinical Pharmacy Service improvement Clinical pharmacy services Service rate pre-satellite pharmacy Service rate post satellite pharmacy % of service improvement Medication errors 16/month 6/month 63% Pharmacist interventions 20/month 80/month 75% Pharmacist participation in ward round 6/month 50/month 88% Time to dispense discharge summaries 90 minutes/discharge summary 20 minutes/discharge summary 77% Number of patients counselled 15/month 75/month 80% Pharmacist available in the ward 1.5 hrs/day 7.5 hrs/day 80% Time taken to supply critical medicines 1 hour 5 minutes 91% Table 2: Potential Cost-benefit savings achieved Activities Cost-benefit savings/year (€) Reducing length of stay of patients €17,000 Reducing repeat dispensing €16,000 Effective use of nursing time €11,000 Reducing prescribing errors €103,000 Total Savings €147,000.

What next?

• Weekend working.
• Service improvements can be transferred to acute medical units and downstream medical wards. Reference Carter report.

IMPLEMENTATION OF A MEDICATION SAFETY AGENDA AT TWO HOSPITAL SITES IN RESPONSE TO WORLD HEALTH ORGANISATION (WHO) PATIENT SAFETY CHALLENGE ‘MEDICATION WITHOUT HARM’ (submitted in 2019)

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European Statement

Patient Safety and Quality Assurance

Author(s)

Meenal Patel, Sheena Patel, Peta Longstaff

Why was it done?

• Initiative introduced and on-going since 2017
• To increase and embed medication safety awareness
• To address under-reporting of medication-related incidents, with feedback
• To embed medication safety in education programmes and clinical practice

What was done?

A local medication safety agenda implemented across two hospital sites in response to World Health Organisation (WHO) patient safety challenge ‘Medication without Harm’.

How was it done?

• Medication safety group (MSG) introduced with local strategy, involving junior medical staff for frontline feedback • Medication safety metrics changed to allow benchmarking with peers as per NHS Improvement’s Model Hospital data • ‘Plan, Do, Study, Act’ model applied to improve transfer of care from hospital to rehabilitation unit following external incidents • Monthly analysis of incidents with harm, exploring reasons for under-reporting • Optimisation of incident reporting system to improve staff feedback following investigations • Near miss error log introduced in pharmacy with shared learning • Mitigation of medication-related risks e.g. medications safe storage action plan • Medication safety bulletins, patient safety newsletters and top tips guide introduced covering focal themes • ‘Safe prescribing’ mandatory induction training for junior doctors to support prescribing of high risk medicines and compliance to patient safety alerts • Hospital-wide education on lessons learnt from incidents • Medication safety resources for staff to access • Nursing quality round on medication safety • Electronic missed doses realtime report developed to tackle omitted/delayed critical medication doses • Medication safety awareness (MSA) week held to increase awareness on focal themes

What has been achieved?

• Multidisciplinary MSG with assurance on meeting WHO global challenge. • Monthly analysis of medication safety data to allow learning, collaboration and benchmarking against peers. • Positive staff feedback on bulletins/newsletters with staff involvement/engagement. • Training programmes embedded with safe prescribing education. • Improved hospital safety metrics: Following MSA week, a 5% and 21% increase in medication-related incident reporting occurred at each site which has been sustained. Reporting rates doubled at one site following success of MSA week. • In 2018-19, local target achieved for reported medication-related incidents per 100,000 finished consultant episodes and medication-related incidents with harm

What next?

• Collaborative multidisciplinary working raising the profile of pharmacists acting as medication safety officers
• Implementing medication safety measures from NHS Patient Safety Strategy 2019
• Initiatives for safer culture, safer systems and safer patients

THE IMPACT OF AN ELECTRONIC ALERT IN PREVENTING DUPLICATE ANTICOAGULANT PRESCRIBING (submitted in 2019)

European Statement

Patient Safety and Quality Assurance

Author(s)

Alison Brown, Gillian Cavell, Nikita Dogra, Cate Whittlesea

Why was it done?

Anticoagulants are high-risk drugs. An NHS England Patient Safety Alert was published in 2015 highlighting harm from inappropriate co-prescription of anticoagulants1.

What was done?

A ‘duplicate anticoagulant alert’ (Anticoagulant MLM) was implemented within our electronic prescribing system (EPMA) to alert prescribers if co-prescription of two or more anticoagulants was attempted, with the intention of preventing the completion of a potentially harmful prescription. We conducted a retrospective review of the impact of the Anticoagulant MLM on preventing co-prescription of low-molecular weight heparin (LMWH) and direct oral anticoagulants (DOACS)

How was it done?

The study took place in a 950 bed UK acute teaching hospital. A report of all Anticoagulant MLM alerts generated for adult inpatients between 26th June 2017 and 8th October 2018 was extracted from EPMA. Data on drugs prescribed, alert acceptance or override and duplicate anticoagulant administration were collected. Where alerts were overridden, appropriateness of the override was assessed by an anticoagulation specialist pharmacist. Ethics approval was not needed.

What has been achieved?

The Anticoagulant MLM triggered on 894 occasions; 113 in response to attempted prescription of a LMWH for a patient already prescribed a DOAC. 65 of 113 alerts were overridden (duplicate prescription completed). 48 alerts were accepted (duplicate prescription avoided). Of the 65 overridden alerts, consecutive doses of both anticoagulants were scheduled appropriately. No duplicate doses were administered in 44 cases (44/65, 67.7%). 15 duplicate prescriptions were either cancelled before administration or not administered concurrently (15/65, 23.1%). Duplicate doses were administered against 6 prescriptions (6/65, 9.2%), on 3 occasions. No patient harm was identified. The alert prevented inappropriate co-prescription of anticoagulants to 48 patients. Overrides were justified in 44 cases. Anticoagulants were correctly prescribed for 92/113 (81.4%) patients. It was outside the scope of this project to investigate why alerts were overridden. ‘Alert fatigue’2 and alert frequency3 are recognised factors limiting the effectiveness of electronic alerts in changing a planned course of action.

What next?

The alert remains in place as a barrier to error. Further work is needed to identify reasons for anticoagulant alert overrides.

PARENTERAL NUTRITION: HOW TO PREVENT THE NEXT MISTAKE? (submitted in 2019)

European Statement

Patient Safety and Quality Assurance

Author(s)

saif salah

Why was it done?

In Carmel Medical Center, the infusion pack is delivered by a pharmacist according to the prescription given from PN staff, and afterwards the infusion instructions are recorded by one of the department physicians in the patient EHR. Recently there have been several mistakes that have been reported, which made it urgent to check matching between PN staff decision and the record of instructions in the EHR.

What was done?

Recognise the mismatch between the electronic health record (EHR) instructions for delivery of parenteral nutrition (PN), against the actual delivery by the pharmacy according to prescription from PN staff and characterisation of these cases in terms of mismatching.

How was it done?

Issuing a report of the PN doses delivered by the electronic system called “UNIT-DOSE” in the pharmacy according to the name of patient and days of treatment of 2018 vs. electronic instructions that have been recorded by one of the department physicians in the “Kamelyon” system or “Meta Vision ” The parameters examined were: type of solution, composition, volume, supplements-additives (electrolytes, vitamins, trace elements), infusion rate and method of infusion (central / peripheral). Infusion rate was examined separately as a follow-up by a nutritionist.

What has been achieved?

From our research, we found a significant difference between computerised recording of PN instructions and what the patient actually received. This is due to the separation between the hand-written prescription by the PN staff and the computerised instruction recording by the treatment team. This may constitute a danger to patients.

What next?

Examination and follow-up by the pharmacist is important for identifying and treating errors of this nature appropriately. Guidance sessions for the treating staff should be conducted in the different departments. The prescription must be matched by the PN staff to the computerised instruction by placing a prescription pattern. Set up protocols in the computerised system that guide the treatment staff in the department to record the correct instructions.

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