Author(s)

CAROL ANN JONES, NANNA CHRISTIANSEN

Why was it done?

Starting in mid-April 2020 as a result of the Coronavirus pandemic, a cluster of patients displaying multisystem inflammation and shock were admitted to our hospital. Similar cohorts have subsequently been reported internationally. Over a 6 week period, in which our institution cared for over 70 children with the newly described PIMS-TS, we developed new pharmacological treatment guidelines. Due to the novelty of the disease, treatment options were unclear and decisions were made by a multidisciplinary team (MDT) of clinicians and pharmacists.

What was done?

This good practice initiative describes the rapid and iterative development of a treatment pathway for the newly described Paediatric Inflammatory Multisystem Syndrome – Temporally associated with SARS-CoV-2 (PIMS-TS). Due to the similarity to Kawasaki disease and septic shock, the routine treatments for these conditions were considered as well as the experience of our adult colleagues, especially in terms of anticoagulation and hyper-inflammation seen in patients presenting with COVID-19. This ensured holistic management plans could be made to provide the highest quality of care.

How was it done?

A MDT of clinicians (intensivists, infectious diseases, cardiologists, rheumatologist, haematologists, endocrinologists) and pharmacists arranged daily meetings to discuss admitted patients as well as pulling together information to formulate a treatment guideline to enable the safe management of these patients. Version one of the treatment pathway was approved in April 2020, by beginning of June version 6 was published. The final treatment pathway included intravenous (IV) immunoglobulin, IV methylprednisolone, aspirin, venous thromboembolism (VTE) prophylaxis and immunomodulation therapy including tocilizumab, infliximab and anakinra.

What has been achieved?

A total of 74 patients have been successfully treated against the treatment pathway, and discharged from hospital. Managing a new condition with no published evidence on treatment was a huge challenge, especially given the large numbers and high acuity of patients. Collaborative learning and reflection has enabled us to develop a robust treatment pathway for our patients. We have witnessed MDT working at its best, united with the sole aim of combating this rare condition.

What next?

An ongoing coordinated effort is required to undertake paediatric research to understand PIMS-TS and establish the most effective treatment for this novel disease.

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Author(s)

Daniele Leonardi Vinci, Adriano Meccio , Alessio Provenzani, Piera Polidori

Why was it done?

The COVID 19 pandemic unprecedently challenged National Health Services to assure adequate patient care, despite a constantly escalating drugs demand. This complex situation requires appropriate planning to avoid misleading estimations, which would have consequences on patients and overall resources available.

What was done?

We created a tool to perform a timely estimation of the drug needs to treat the COVID-patients based on epidemiological forecasting.

How was it done?

The tool’s epidemiological forecasting was based on a compartmental model in which the population is divided into three compartments (Susceptible-Infectious-Removed, SIR), and transmission parameters are specified to define the rate at which persons move between stages. The appropriate data entry was guaranteed by the creation of a form in which users can enter information regarding: The population considered, the R0 calculation, the number of already known infected cases, the application of Non-Pharmaceutical Interventions and the number of hospital beds. The drugs need for the forecasted patients was calculated according to a list of critical care drugs compiled consulting previous published scientific works, national and international guidelines. The list includes 51 drugs belonging to different therapeutic group, such as: antiarrhythmics, antibiotics, antipyretics, antivirals, heparins, IV-fluids, local anesthetics, neuromuscular blockade agents, sedative agents and vasopressors. For each drug it was estimated the percentage average ICU uptake for therapeutic group and active principle.

What has been achieved?

A tool consisting of an excel template, that, based on the information inserted, automatically calculate the number of patients classified by the intensity of care (hospitalized not-ICU, Hospitalized ICU, ventilated, intubated or with shock) and creates a table that includes, for each drug to be used, the following information: therapeutic group, active principle, dosage considered, pharmaceutical form, total dosage for patients considered and total quantity of unit doses for patients considered. The tool is also made adaptable to different clinical situations, through the possibility of editing the assumptions adopted regarding the epidemiological and therapeutical parameters or the inclusion of new items in the drugs list.

What next?

Our tool represents an opportunity for the immediate and efficient estimation of the drugs necessary to assist the COVID19 patients during emergency scenarios. It will be periodically updated as new evidences will be available.

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Author(s)

Xando Díaz-Villamarín, Ana Pozo-Agundo, Paloma García-Navas, Celia Castaño-Amores, Alba Antunez-Rodriguez, Cristina Lucía Dávila-Fajardo

Why was it done?

Pharmacogenetics (PGx) has the potential to predict patient´s drug response. Many genetic polymorphisms have been associated with variable drug response. This has been demonstrated with the highest level of evidence in fact many of them have been included in clinical dosing guidelines such as those from the Dutch Pharmacogenomics Working Group (DPWG) and Clinical Pharmacogenetics Implementation Consortium (CPIC). Actually, many drug labels include the recommendation about genotyping specific single nucleotide polymorphisms (SNP) prior to drug prescription.

What was done?

We have implemented pharmacogenetic tests in our hospital for a total of nine drugs.

How was it done?

Our hospital provides a PGx test service according to the following workflow. Physicians order the PGx test to the Pharmacy Unit, we take a saliva sample with sterile-cotton tipped swabs and send them to the Genomic Unit at Genyo. There, we extract the DNA and genotype the variants of interest. Genetic results are reported back to the Pharmacy Unit within 48-72 hours. After genotype-phenotype-recommendation translation according to the CPIC and DPWG dosing guidelines, we upload the dosing recommendation as a PGx report to the electronic patient´s medical history.

What has been achieved?

Since 2012, 2414 patients have benefited from our PGx test service for at least one drug-gene interaction. These tests have been requested by seven hospital departments with regard to a total of nine different drugs. We have reported 932 PGx dosing recommendations: Clopidogrel with 2013 genotyped patients and 845 dosing recommendations; Azathioprine with 208 and 21; Capecitabine: 48 and 1; 5-FU: 5 patients without recommendations; Tamoxifen: 117 and 48; Trastuzumab: 34 and 15; Irinotecan: 4 and 2; Simvastatin/Atorvastatin: 2 genotyped patients and no recommendations.

What next?

Since the first PGx test in 2012, we have been able to implement PGx tests in daily clinical routine in our hospital affecting 9 drugs. 2414 patients have benefited from this service and we are working on the implementation of new polymorphisms affecting drug response to expand our services.

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Author(s)

Grainne Johnston, Jennifer Brown

Why was it done?

The High Tech Scheme (HTS) in Ireland facilitates access to high cost drugs with proven cost benefit for patients. Combined national expenditure on adalimumab (Humira®) and etanercept (Enbrel®) exceeded €190 million in 2017. Biosimilar versions of both drugs are available, however largely not utilised. The most cost effective options for each drug were designated as the Best Value Biologic (BVB). Prescribing a BVB option offers the opportunity to save a considerable amount of money for the state.

What was done?

The Mater Misericordiae University (MMUH) Integrated Medicines Optimisation Pharmacist (IMOP) provided education and removed barriers to initiate biosimilar prescribing of adalimumab and Enbrel in the MMUH.

How was it done?

The MMUH IMOP was delegated to assist with implementation of BVBs prescribing.
The MMUH IMOP generated Patient Information Leaflets in relation to BVB switching.
The IMOP reviewed out-patients currently prescribed Humira® or Enbrel®, and provided education and information on switching from the originator to the BVB

What has been achieved?

Prior to the IMOP intervention, no patients in the MMUH had been prescribed a BVB.
Following IMOP intervention, between June 26 and September 27, 2019:
• 291 Humira® or Enbrel® patients were scheduled to attend MMUH rheumatology, gastroenterology and dermatology clinics.
• Of these, 64% (n=185) were switched to a BVB. An additional 19 patients were newly commenced on a BVB.
• The IMOP educated and counselled 91% (n=92), 93% (n=53) and 48% (n=13) of patients switched to a BVB in rheumatology, gastroenterology and dermatology respectively.
The largest contributing factor identified for patients not being prescribed a BVB was, no review by the IMOP prior to medical review; 65% (n=35), 59% (n=10) and 86% (n=12) for rheumatology gastroenterology, and dermatology respectively.

What next?

BVB prescribing can save vital health funds for the state while maintaining patient care. The MMUH IMOP is now progressing to adopt BVB prescribing for a number of other biological medicines at significant savings for the MMUH and state.

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Author(s)

SOFIA KONSTANTINIDOU, VANGELIS KARALIS

Why was it done?

Tyrosine kinase inhibitors (TKIs), like erlotinib and gefitinib, are widely used in anticancer therapy. However, after long term administration of TKIs, resistance is observed in the majority of patients. Thus, it is necessary to be able to define individualised dosage regimens for TKIs in cancer patients. Nowadays, modelling and simulation approaches represent the most powerful tool in the hands of clinical pharmacists towards precision medicine.

What was done?

Population pharmacokinetic (PK) – pharmacodynamic (PD) modelling was utilised to simulate erlotinib and gefitinib dosage regimens for non-small cell lung cancer. In silico clinical trials with virtual patients, of several resistance levels, were simulated in order to optimise pharmacotherapy and get better therapeutic outcomes.

How was it done?

The utilised PK/PD model and average parameter values were obtained from the study of Eigenmann and colleagues. This model was fully validated using statistical criteria and goodness of fit plots. In order to simulate many possible conditions that may occur in clinical practice, several different values of erlotinib and gefitinib clearance, absorption rate, pharmacodynamic characteristics (like tumor volume), and resistance were assessed. In addition, several dosage schemes were simulated. The entire modelling work was performed in Monolix® 2019R1.

What has been achieved?

Concentration vs. time and effect vs. time plots for the virtual patients were simulated for a variety of conditions and tumour resistance levels. For both TKIs, decrease of body clearance led to higher plasma concentrations, as well as more intense and longer duration of the effect (i.e. tumour volume shrinkage). Enhanced drug effect on resistant cells resulted in a decrease in tumour volume. In addition, a variety of concentration-time profiles were simulated, making it possible to choose the best regimen for each patient.

What next?

In this study, the use of modelling techniques led to the simulation of many conditions of patients and adjustment of dosage regimens according to their needs. Wider application of in silico methods using virtual patients will allow the design of the most appropriate individualised dosage schemes tailored to the patients’ requirements.

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Author(s)

Beatriz Zurita Alonso, Marta Martí Navarro, Monica Estelrich, Alejandro Ballestero Corominas, Anna Badell Giralt, Diana Patricia Vera Rodríguez, Milagros Ricse Salcedo, Roxana Rubio Vargas

Why was it done?

The use of biosimilar drugs has been a breakthrough to improve the sustainability of the health system. Although since 2015 position papers have been published by some scientific societies, there is no clear consensus about the recommendation for a switch from the original drug to its biosimilar. The rate of biosimilar use in our country is one of the lowest in Europe.

What was done?

The pharmacy service led the creation of a working group formed by rheumatologists, gastroenterologists, dermatologists and pharmacists to promote the use of biosimilar drugs in our hospital.

How was it done?

The working group wrote a consensus document in which it was jointly decided to start all new biological treatments with biosimilars. In addition, it was decided that the prescribers would determine which patients were candidates for switch to a biosimilar based on clinical criteria. If the drug is administered subcutaneously, the pharmacist is responsible to explain the reason for the change and the management of the new device to the patient. In case of disagreement, the original is kept and communicated to the prescribing physician. If the drug is administered intravenously, it is the physician who informs the patient about the change.

What has been achieved?

From May 2019 to September 2019, 17 switches were made: 4 infliximab (66.7%), 9 adalimumab (10.1%) and 4 rituximab (80.0%). This measure led to an economic saving of €111,106.96 per year. Twenty new treatments with biosimilars were started: 1 with etanercept, 2 with infliximab, and 17 with adalimumab. This supposed an economic saving of €141,826.36/year if we compare with the cost of the original drug. The rate of antiTNF biosimilars increased from 33% to 48% in 5 months. None of the patients refused the use of a biosimilar. By now, all treatments maintain their effectiveness without safety issues. This optimisation of treatments will allow the hospital to treat a greater number of patients and invest in innovative treatments.

What next?

These results indicate a great opportunity to offer biological treatment to a higher number of patients every year. Therefore, our objective is to achieve the switch of remaining patients as it could generate an additional saving of €630,072.28 per year.

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Author(s)

Maria Rautamo, Niina Laihanen , Laura Lehtola

Why was it done?

Erysipelas was the most commonly treated infectious disease at the home hospital unit in 2015. Previously the standard treatment was broad-spectrum antibiotic cefuroxime three times daily. The infectious disease specialist wanted to improve the antibiotic stewardship by shifting from cefuroxime to a continuous infusion of narrow spectrum benzylpenicillin. The aim of the initiative was also to improve patient care and reduce the number of treatment visits and thus overall treatment costs.

What was done?

The production unit at the hospital pharmacy began preparing elastomeric pumps containing benzylpenicillin for Helsinki city home hospital unit for the treatment of outpatients suffering from erysipelas. A pilot study was conducted in November 2018 before further implementation of the elastomeric pumps.

How was it done?

A benzylpenicillin 10 million IU infusion solution was prepared and transferred to elastomeric pumps (Folfusor LV10, Baxter) in the production unit at the hospital pharmacy. The production method was developed by pharmacists at the hospital pharmacy in cooperation with Baxter and the formulation as well as stability information was received from Baxter. The pilot study was planned and executed in cooperation with Helsinki city home hospital unit. The batch size of prepared elastomeric pumps was 7 pumps a week and the overall pilot period consisted of 5 weeks. A total of 8 patients were treated during this period. The opinions of nurses and patients about the use of elastomeric pumps were investigated through a questionnaire. The impact on treatment costs were also evaluated.

What has been achieved?

Elastomeric pumps containing benzylpenicillin have been implemented as a standard treatment for erysipelas at the home hospital unit. Cost savings from the pilot period of 5 weeks were 125 nurse visits corresponding to approximately 100 hours of work as well as 200 km of driving for nurses to patients’ homes. The patients were very pleased with the elastomeric pumps and the fact that the pump had to be changed only once daily.

What next?

Production and delivery of elastomeric pumps containing benzylpenicillin has expanded to other home hospital units. The implementation of elastomeric pumps containing other active ingredients is under investigation.

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Author(s)

Ana Soares, Armando Alcobia

Why was it done?

Several clinical practice guidelines for LC recommend that multidisciplinary teams should be used to plan patients’ treatment. The evolution of thoracic oncology, namely the increasing knowledge of the diverse histologic and molecular phenotypes in non-small cell LC, has been driven to more complex treatment algorithms in recent years. This complexity increases the need for a multidisciplinary approach in therapeutic decision-making, which must be individualised and based on the best information available. The pharmacist’s inclusion in the multidisciplinary team is essential and was formerly proposed by the Pneumology Director to the Hospital Administration Board.

What was done?

A hospital pharmacist is a permanent member of the lung cancer (LC) multidisciplinary team, which has met weekly since January 2016, to plan the management and treatment of LC patients in our hospital. The pharmacist brings updated information about the efficacy and safety of drug treatments, its cost-effectiveness and its availability. The pharmacist improves communication with the Pharmacy and Therapeutic Committee.

How was it done?

The multidisciplinary team meets weekly to discuss the diagnosis and treatment options of LC patients, and includes a dedicated group of professionals: pulmonary oncologists, a thoracic surgeon, a radiation oncologist, a radiologist, a pathologist, a nuclear medicine specialist, a hospital pharmacist, a palliative care physician and an oncology nurse.

What has been achieved?

About 240 cases, corresponding to 200 patients were discussed per year. An average of 110 solicitations to the Pharmacy and Therapeutic Committee were made. The multidisciplinary team grants a systematic approach to diagnosis and therapeutics, in compliance with evidence-based guidelines, improves communication and coordination between professionals and short waiting times for the patient.

What next?

The next step is to systematise real-world data collecting, from the patients treated, to better understanding the effectiveness of treatment options and the real impact of the multidisciplinary team in patient outcome, ideally, extending it onto a national level.

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Why was it done?

The consumption of medicine for the treatment of wAMD, DME and RVO is increasing. The medicines used are in the top five of the most expensive drugs in Denmark. With the prospect of more patients, greater costs and the introduction of new drugs in the field, there was a need to develop a national treatment guideline.

What was done?

An expert committee prepared a national treatment guideline including a clinical medicine comparison report for the treatment of wet age-related macular degeneration (wAMD), diabetic macular oedema (DME) and retinal vein occlusion (RVO). The aim was to create uniform treatment across the country and to trigger competition between medicines in the hope of achieving lower prices.

How was it done?

An expert committee consisting of physicians, clinical pharmacist, clinical pharmacologist and medicine procurement pharmacist was appointed. The committee prepared a national treatment guideline including a clinical medicine comparison report based on existing clinical evidence and Danish practice. The committee reached the conclusion that the anti-vascular endothelial growth factor (VEGF) drugs ranibizumab and aflibercept are ranked equally in terms of effect and side effects. The choice of anti-VEGF should be determined solely by price and dosage. A tender was prepared in alignment with the guidelines. This result led to the development of a medicine recommendation, which was passed onto hospital pharmacies, clinical pharmacists and physicians to ensure implementation in the clinic. Feedback from the clinics concerning estimated consumption was forwarded to the drug suppliers and was continuously monitored by the procurement pharmacist to ensure compliance at the clinics.

What has been achieved?

The clinicians switched patients to the new first-line choice. The market share of first-line treatment was 89% compared to 25% before the guideline. Two tenders were published based on the guideline. The first resulted in a price reduction of 28%, the second a reduction of 54%. Total actual savings in the first tender (based on a 31-month contract period) was €38m. In the second tender (based on the first 12 months of the contract period) was €35m.

What next?

New medicines are expected to be approved in the near future. We will continue to use and develop national treatment guidelines in combination with tender procedures and proper implementation of guidelines to obtain better and cheaper treatment options for patients.

Author(s)

Gregorio Romero Candel, Maria Jesus Sanchez Cuenca , Nieves Cano Cuenca, Jose Marco del Rio , Julian Castillo Sanchez, Luna Carratala Herrera

Why was it done?

The healthcare provided in the SSC is not fully integrated into the structures of the National Health System. These patients present a higher risk of adverse events related to pharmacotherapy, due to patient factors, with the treatment, the health system and the institutionalisation. The integral approach of the pharmaceutical benefit was necessary for improving the efficiency, safety, health and economic results due to the process using drugs and other health products in the SSC.

What was done?

A pharmacotherapeutic benefit model has been started through the hospital pharmacy to the Socio-Sanitary Centres (SSC) of our health area. A pharmacotherapeutic management system based on the evaluation and selection of drugs and diet therapy items has been established.

How was it done?

An adherence protocol was made to the hospital pharmacy service, with the benefits that were to be provided to them. A guide was prepared with drugs and nutritional supplements that were available to them according to the Pharmacotherapeutic Guide of the Hospital Pharmacy Service, thus guaranteeing the most efficient products. A request model of both drugs and dietotherapics was developed for the SSC, assigning each centre one day per month to request the order and another day of dispensation. Finally, a calendar of distribution routes for each SSC was prepared.

What has been achieved?

For 12 months, eight SSC have been assigned to this programme, with 538 patients. Twelve shipments have been made to each centre, which have been provided with a total of 682,484 units of 223 active ingredients. The dispensation in diet therapy contained 28,045 units of 13 specialties. It has been possible to improve the pharmacotherapeutic coverage of these patients and reduce the expenditure on drugs in the area through centralised supply.

What next?

Development of follow-up programmes for patients with high health or economic impact drugs. Also, the adherence of new SSC, as well as increasing the dispensing portfolio, and achieving the integration of information systems, to have a total traceability from the patient to the different assistance levels.