Author(s)

José Luis Revuelta Herrero, Vicente Escudero, Roberto Collado, Belén Marzal, Ana Herranz, María Sanjurjo

Why was it done?

CAR-T cell-based therapies are advanced therapy medicinal products (ATMP) that are considered as drugs by the European regulatory authorities. ATMPs are usually associated with strong logistic and traceability requirements, serious adverse events and a high budget impact. Hospital pharmacists can help ensure a safe and efficient use of these drugs.

What was done?

A chimeric antigen receptor (CAR) T cell Therapy Committee was created in 2019 and it included members from the hematology, oncology, pediatric onco-hematology, hospital pharmacy, neurology, critical care medicine and immunology departments. An operating procedure defined the specific functions of the pharmacy department in the management of these drugs in the CAR-T cell program.

How was it done?

As some responsibilities might be shared with other professionals, it was key to define everyone’s contributions. In our case, an operating procedure with the responsibilities of the pharmacy department was developed based on the national and regional action plans for ATMPs in the national health system and the risk management plans for each drug. This operating procedure was reviewed and approved by the Committee.

What has been achieved?

The operating procedure was fully implemented and included the participation of hospital pharmacists in the following steps:
• Procurement: the inclusion of a patient in the program is agreed upon the Committee. The pharmacists provide a purchase order when all the requirements are met.
• Leukapheresis and shipment to the manufacturer: the apheresis is included in the computerized physician order entry (CPOE) and it is verified to confirm wash-out periods. Before the shipment, the pharmacists record the apheresis unique identifier and patient data.
• Product receipt: the pharmacists verify at receipt that the patient identity chain and the integrity of the product have been preserved.
• Bridge and lymphodepleting chemotherapy, CAR-T administration: specific protocols have been included in the CPOE. Prescriptions are verified by the pharmacists with special attention to the drug-free periods. After transporting the drug to the clinical unit and preparation, a pharmacy label for dispensing and administration is generated. This label includes a barcode for patient identity verification at bedside.
• Outcomes monitoring and pharmacovigilance: kits are provided to the clinical units for the management of CAR-T associated toxicities. Pharmacists are responsible for the adverse reactions reporting in coordination with clinicians.

What next?

We developed verification lists for each of the previous steps that have already been published (DOI: 10.3389/fonc.2021.636068). More ATMPs are expected to come and their management will require the participation of hospital pharmacists from different areas of expertise (procurement, clinical pharmacy, compounding etc).

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Author(s)

Rawa Ismail, Jesper van Breeschoten, Michel Wouters, Anthonius de Boer, Alfonsus van den Eertwegh, Maaike van Dartel, Caspar van Loosen, Doranne Hilarius

Why was it done?

Most drugs obtain approval based on limited numbers of highly selected patients and mostly surrogate outcomes. Little is known on hospital variation on the use of new treatments in daily clinical practice. Benchmark information can be used to limit between hospital variation and provides real world evidence on the value of these treatments.

What was done?

In the Dutch Institute for Clinical Auditing (DICA) medicines project, administrative data on the use of expensive drugs from hospital pharmacies were linked to clinical data from national quality registries and hospital declaration data. Data were visualised in six dynamic dashboards (lung cancer, breast cancer, rheumatic disorders, colorectal cancers, gynaecological cancers and metastatic melanoma), leading to insight into expensive drugs use and clinical outcomes in real-world practice.

How was it done?

The three data sources were linked using patient-specific data and provide real-world insights in anti-cancer drug use and outcomes. After linkage, data were validated by individual sessions with hospital pharmacists and medical specialists.

What has been achieved?

Hospital pharmacists and medical specialists gained insight into expensive drugs use and treatment patterns in patient groups, compared to other hospitals. The dashboards also contain information on outcomes such as toxicity, emergency admissions, time-to-next treatment and users receive signals when their use of expensive medicines deviates from the benchmark. An example of the information provided by the dashboards was the number of stage IV non-small cell lung cancer patients treated with only one or two gifts of pembrolizumab. All hospitals received a report on this subpopulation to improve their treatment approach. Other findings were differences in the adjuvant treatment of stage III colon carcinoma patients and the treatment duration of trastuzumab/pertuzumab as adjuvant treatment in breast cancer patients.

What next?

The DICA medicines project is an example of good practice as it reuses available data sources without any additional registration burden. In the future, the dashboards will be extended with survival data and PROMs data. The focus of the program in the next year will be to include all hospitals in the Netherlands and to extend the dashboards with more features.

Author(s)

Cyril Magnan, Elise Betmont, Guillaume Saint Lorant, Hubert Benoist

Why was it done?

Evaluate the economic impact of improvement actions taken since 2017 on TSPs management.

What was done?

Cold chain is a major issue in the pharmaceutical industry as a growing number of its products are temperature-sensitive and also in hospitals. In 2017, 27 cold chain breaks were declared by care units (CU) within a French teaching hospital, resulting in a risk for patient care and a potential loss of 40,363 euros, of which 18,505 euros (45%) could be avoided. Following this first study, a set of measures have been implemented in our establishment in order to secure the cold chain.

How was it done?

Potential losses and avoided losses of TSPs have been analyzed continuously since 2017 according to the same methods in a teaching hospital with 1,600 beds. In case of a thermal excursion (ET), the pharmacy is, according to the institutional procedure, immediately warned by an electronic alarm day and night or by a call from the care service, making it possible to define the action required from the service concerning the methods of keeping TSPs.

What has been achieved?

Since 2017, a mobile isothermal enclosure has been implemented for the transport of TSPs during the day in the CU. Connected temperature-monitoring sensors have been installed on so-called “at-risk” refrigerators. The alarm reports to the pharmacy was instituted in order to intervene as quickly as possible. Part of the refrigerators has been renewed and awareness has been raised among all CUs for the good traceability of temperature readings, allowing a drop from 24% in 2018 to 65% of compliant traceability in 2019. Following these improvement actions, 53 ETs with a potential loss of 53,769 euros were declared in 2019, of which 39,753 euros of losses could be avoided. Currently, 74% of ET losses can be avoided compared to 43% in 2017.

What next?

This economic assessment of the potential losses and the avoided losses of PTs shows the positive impact of the various improvement measures taken since 2017 as well as education of the UDS to secure TSPs. A regional awareness was implemented thanks to a collaboration with the regional health agency in order to promote TSPs management in the hospitals.

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Author(s)

Camilla Munk Mikkelsen

Why was it done?

Including a CA in the evaluation is time-consuming and I wanted to evaluate whether the obtained drug recommendation was different from the result we could have achieved without the inclusion of a CA. The CA process includes data collection from clinicians within resource consumption per drug, including the costs of time usage of physician, nurse and patient, transportation expenses, monitoring costs, blood tests, co-medicine, utensils, shipping and hospital facilities. When a CA is included it is possible to take the derived costs associated with treatment of different drug dispensing forms and specific costs of treatment with various analogue drugs into account to achieve a recommendation upon the lowest total price including the tender price and the derived costs associated with the treatment.

What was done?

Tenders are made on ATC-level 5, but clinically equivalent therapeutic areas are evaluated on ATC-level 4. The analogue competition is an important strategic tool when conducting tenders and elaborating national recommendations on therapeutic areas (TA). Since 2017 the evaluation of TA has been based on a clinical evaluation, an economic evaluation and a tender. Previously the call for tenders was based on clinical evidence only. To evaluate whether the addition of a cost analysis (CA) to a tender evaluation would alter the drug recommendation of TA, a re-evaluation of the processed TA, evaluated from October 2018 until October 2019, was made on multiple sclerosis, rheumatoid arthritis and severe asthma.

How was it done?

The drug recommendations on TA made in the period was re-evaluated. Results from the cases with multiple sclerosis, rheumatoid arthritis and severe asthma were evaluated on clinical evaluation, tender price and finally with or without the CA.

What has been achieved?

From October 2018 to October 2019 three TA have ended the evaluation process. The recommendation of severe asthma had a similar outcome regardless of the process used. For multiple sclerosis and rheumatoid arthritis, the CA altered the drug recommendations.

What next?

In order to balance resource consumption on performing CA and the economic impact on the outcome, the plan is to identify TA where it isn’t meaningful to conduct a cost analysis. In all other areas a CA will be included in the standard procedures.

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Author(s)

Vanesa Alonso Castro, Beatriz López Centeno, Daniele Alioto, Angela Gil Martin, Ignacio Martin Casasempere, Maria Segura Bedmar, Ainhoa Aranguren Oyarzábal, Maria Jose Calvo Alcántara

Why was it done?

The European Society for Medical Oncology (ESMO) has developed the ESMO-Magnitude of Clinical Benefit Scale (ESMO-MCBS) to assess the magnitude of clinical benefit for cancer medicines. In the CORRECT trial, regorafenib has an ESMO-MCBS score of 1 (questionable benefit). It is necessary to assess the effectiveness and safety of regorafenib treatment in real clinical practice.

What was done?

To describe the implementation of a centralised registry (CR) for all patients with metastatic colorectal cancer (mCRC) being treated with regorafenib in a Regional Health Service (RHS).

How was it done?

A working team including oncologists, hospital pharmacists and RHS professionals developed the CR for patients with mCRC starting treatment with regorafenib in 2019. The variables selected were: age, sex, ECOG, primary tumour location, number of metastatic sites, presence of liver or brain metastases, RAS-mutation status, BRAF-mutation status, previous lines, follow-up variables (dose, type of response and adverse events), date and reason for withdrawal.

What has been achieved?

The CR is available for all professionals in the RHS in April 2019 and it is compulsory to include all patients starting treatment in 2019. Forty-nine patients were included (59.2% males). The median age was 68 years. The baseline characteristics of the patients were: − 36.7% and 63.3% of patients had ECOG 0 and 1 respectively; − 79.4% had the primary tumour in the left colon; − 36.7% had 3 or more metastatic sites; −71.4% and 2.0% had liver and brain metastases respectively; − RAS gene was mutated in 57.1% of patients and undetermined in 2.0%; − BRAF gene was mutated in 4.1% of the patients and undetermined in 34.7%; −in 65.3% of patients regorafenib was the fourth line or later therapy. With median treatment duration of 2.5 months, 42.9% of patients had discontinued treatment: 30.6% had progressive disease, 8.2% had adverse events and 4.1% had died.

What next?

The experience obtained with this registry has allowed us to know the use profile of this drug in all hospitals of RHS. A comprehensive assessment of the collected data and a longer follow-up period are necessary to assess the effectiveness and safety of regorafenib treatment in real clinical practice.

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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.

Author(s)

Alison Anastasi, Karl Farrugia

Why was it done?

This was done as a tender was being issued also for medicines that still had a patency and had no competition and the prices quoted for were higher than other international external reference prices. Thereby a new pricing reimbursement system was undertaken and items procured were studied intensively before choosing the right procurement model. The main point was thinking outside the box inducing interest in international companies who were willing to support and assist the innovative local systems by participating in the new systems leading to improved access and better value for money.

What was done?

In September 2016, a workshop and strategy meeting was organised at WHO Denmark to discuss global procurement strategy and share country practices. Malta was one of the facilitators and invited speakers. In the past years tendering was the main system for procurement. However, on having a thorough understanding of medicines and non-pharmaceuticals, market strategy, and patency other processes have been studied and adopted. The models involve negotiations, pay per use systems, and pay per performance models.

How was it done?

This was done by setting multidisciplinary teams within the hospitals and by having good research methodology skills. This led to smoothing the gaps between the actual horizon scanning, health technology assessments and final choice of procurement strategy. International liaison, partnership with the industry, and relevant focus groups with annual seminars made this possible as mixed experts met and gave their best shot at this new system. The fact that no one size fits all made procurement more interesting and from one cycle to the other there is a learned curve that brings successful results.

What has been achieved?

Malta achieved better competition, uninterrupted sourcing, investments and stable pricing with continuous yearly reductions. From negotiations of patented medicines Malta saved approximately 1.5-2 Million Euro per year since 2013. With respect pay per use systems such as the total knee replacements Malta gave a capped price and ended up paying half of what is used to pay and companies managed to bid for the set price. In renal dialysis the cycle involved payment per patient service thereby reducing wastage, storage, and ordering of consumables and this will render a cost saving of 5Million Euro throughout cycle. The new processes launched for multiple sclerosis will dictate that whoever reaches the cheapest price ranking will be used to start the patients clinically and the pay per cure cycle for Hepatitis C will lead to savings and complete eradication in five years time.

What next?

Malta is one of 6 small EU Member States so besides its size and geography there are other elements were it triggers the procurement department to think of innovative ways to treat our patients and as yet remaining sustainable. There are other projects in the pipeline however, Malta is sharing its good practice with the industry, with the WHO and other international fora so that certain elements are taken on board as standardised systems for equality of service and treatment in all countries.

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Author(s)

Ane Hornbaek Mortensen

Why was it done?

Previously, a quarterly report showing adherence to national treatment guidelines was issued to all hospital administrations in our region. It was their responsibility to forward this to the appropriate specialists/consultants. This often failed and even when it was done, our experience showed that it wasn’t read by the consultants. Consequently, prescription patterns didn’t change despite the report highlighting the wards that weren’t complying with the national treatment guidelines.

What was done?

Short newsletters including graphs/tables showing the ward’s degree of adherence to national treatment guidelines were emailed to the chief consultant of the specific ward.

How was it done?

In our region a 6-person analytical team, which includes 3 hospital pharmacists, monitors adherence to national treatment guidelines issued by our national council for the use of expensive hospital medicines (RADS). Based on the results, the analytical team decides which newsletters to write. The hospital pharmacists in the analytical team are responsible for writing the newsletters and emailing them direct to the relevant specialist/consultant.

What has been achieved?

It seems as if the introduction of more targeted information has led to more rapidly changing prescription patterns. One example is oral iron chelating agents to hematological patients where a RADS guideline was issued recommending that all new patients should receive deferipron instead of deferasirox. This information was initially issued through the usual channels (via hospital administration) but no change in the use of deferipron/deferasirox was seen. This only happened after emailing a newsletter directly to the chief consultants of the three hematology wards in our region, showing the current use of deferipron/deferasirox and the potential cost reduction. Nine months and three newsletters later the percentage of deferipron use on the hematology wards increased from 2% to 27%, leading to a 22% cost reduction. Target was 25% deferipron (the guideline only covered new patients). The total increase in the percentage of deferipron use on hospitals in our region was 351% compared to an increase of between 0 and 19% in the other four national regions.

What next?

Continued and increased use of targeted communication in the health care system is required to ensure that specific information reaches the relevant players.

Author(s)

H. Thoong

Why was it done?

PETC admits approximately 15 000 patients per year and is a high user of high cost drugs. Traditionally, a pharmacist provided a clinical and supply service with no technical support. Frequently, prescriptions were written late, dispensed items were lost and patients waited unnecessarily to receive treatment. Furthermore, patient non-attendance and medication re-supply due to misplacement of original dispensed items led to stockpiling of medicines.

What was done?

A pharmacy technician (PT) coordinated medication service was introduced onto the Paediatric Elective Treatment Centre (PETC) to decrease patient waiting time (PWT) and drug wastage.

How was it done?

Prior to admission, patients requiring medication were identified by a PT. If medication had been prescribed, this was transcribed onto a pharmacy order form. The prescription chart and order form were clinically checked by a pharmacist. If the drug had not been prescribed, prescribers were contacted. The medication was dispensed and delivered to the ward in advance. The PT ensured all required medication was readily available on the ward. Data on PWT, time to process medication orders, cost of unused drugs and number of items available prior to attendance were collected for a 6 month period.

What has been achieved?

Total cost savings achieved due to returned unused medication amounted to £82 074.

What next?

To extend the role of the PT in PETC. Therefore, the PT will undertake basic medication reconciliation, assessment of patients’ own drugs and notify the clinical pharmacist of patients requiring a full medication review.