Author(s)

Susana Redondo-Capafons, Laura Soriano, Irene López-Rico, Jorge Del Estal, Rocío Cebrián, Marcela Manriquez, Maria Reventós, Sandra Fernández-Molina, Mònica Gómez-Valent

Why was it done?

Before CTSS was performed, TSS were requested to Pharmacy Department for evaluation and decision. Because of complexity of these treatments, it was decided that it was necessary to evaluate them with other professionals to make a consensual decision.
In May 2019, CTSS was born. It is a multidisciplinary committee with 10 different health professionals: head of pharmacy, head of healthcare management, head of strategy and operations management, a clinical pharmacologist, five pharmacists and a secretary. Requesting doctors and heads of involved services are invited to explain TSS in the meeting.

What was done?

Committee (C) of Treatments in Special Situations (TSS) (CTSS) have been established. Requests are received by a specific email for the committee and a standard template was performed to be completed by requesting doctor (patient clinical information and evidence supporting request) and by Pharmacy Service (regulatory status of the drug, pharmacology and cost of treatment).

How was it done?

Some limitations as lack of human resources with exclusive dedication for making reports and lack of training in evaluation of this kind of treatments are the most important obstacles. Currently, each member is self-taught and under excessive work- pressure.

What has been achieved?

From May 2019 to August 2021, 273 treatments in 59 meetings sessions (average 4.63 evaluations/meeting) were evaluated.
The 91,6% of treatments were approved. In 95,9% of requests, one drug was evaluated.
There were 18 services involved, being oncology and hematology the most active departments.
Evaluated TSS were classified in six categories: 66,7% of requests were drugs without approved indication, 19,8% drugs approved indication pending price by government, 2,5% approved indication but denied funding by government, 1,8% foreign medicines, 4% compassionate use and 5.2% others according to criteria of each autonomous communities in Spain.

What next?

CTSS allows make a consensual decision between different professionals and establishes a flow to manage TSS requests. This multidisciplinary scenario generates knowledge and evidence in the use of these kind drugs reducing uncertainty in TSS use in relation to its efficacy and safety and, in cases of high budgetary impact-drugs, to minimize inequities of access by standardizing decision-making. Applicable to all hospitals.

Author(s)

Margareth Kristiansen, Viola Melvik, Jahn Olav Svartsund, Randi Trondsen, Lise Nystad

Why was it done?

Patients admitted to the unit often have long-term illnesses, extensive medication histories and lengthy medication lists at admission. Psychopharmaceuticals are largely metabolized by enzymes that have polymorphism. We wanted to investigate the degree of pharmacogenetic variation in our patients and if genetic testing would have an impact on medication treatment.

What was done?

We have investigated the degree of genetic variation in our patients and to what extent the genetic profile impacted the choice of medication treatment.

How was it done?

We started out educating the staff at the ward. In 2018, 37 of a total 40 admitted patients were genetically tested at admission. The implication of the test result was discussed during the morning rounds for each patient ensuring implementation.
Results from each genetic test were continuously entered into a database including age, gender and medications at admission and discharge. Change of medication due to the genetic test result was recorded.
26 (70%) of patients had a genetic profile that could impact the choice of medication treatment. As a result, half of the patients had changes made to their medications. A total of 27 changes were made in these patients.

What has been achieved?

We have established that patients at the geriatric psychiatry unit in Nordland Hospital Trust have a pharmacogenetic profile that affects medication treatment options. Testing has an impact on the choice of pharmacotherapy to such an extent that all patients are now genetically tested at admission.

What next?

Pharmacogenetic testing has proven easy to implement and at the same time of substantial benefit for many patients. We also use our experiences to educate and inspire health care professionals in the community setting including GP’s so they can understand, reuse the test results and identify when a pharmacogenetic test would be a useful tool to determine the most adequate choice of pharmacotherapy.

Author(s)

Francesco Falbo, Oscar Martinazzoli, Agnese Bruni, Rosanna Lettieri, Simona Polito, Luisa Zampogna, Valentina Marini, Michela Mazzucchelli, Marcello Sottocorno

Why was it done?

The involvement of the pharmacist featured:
– Drug supply and storage
– Medical devices (MD) and personal protective equipment supply
– The creation of a catalog of required drugs
– Medication supply chain management and dispensing
– Management of medical gases
– Evaluation of the effectiveness and safety of drug therapy.

What was done?

As the COVID-19 epidemic spread, temporary critical care hospitals have been opened in order to attend the incoming burden of infected patients. In April 2020, one of the largest ever temporary healthcare structure was created in only 10 days. The ark hospital was opened for nearly 10 months and hospital pharmacists supported the effort for the pharmacy management.

How was it done?

The development of a catalog of required drugs has been accomplished using the consumption analysis on drugs and MD in March 2020 of the permanent hospital Covid unit. Thus, we created a dynamic catalog – constantly updated – consisting of 530 drugs and 345 medical devices. The medical staff members of the temporary hospital filled a special form for extra-catalog material. Running a cost-effectiveness analysis, the pharmacist managed to evaluate the purchase, rather than recommend a valid alternative from the material on the catalog.
The pharmacy warehouse was planned by dividing the MDs categories. Likewise, the drugs were stored according to their pharmaceutical form and their alphabetical order.

What has been achieved?

The materials requirements planning was achieved in 15 days, including medical supply ordering and the pharmacy warehouse organization. Pharmacists ensured the optimization of resources, the availability, safety and optimal use of medicines and MDs, as well as the monitoring of the adverse drug reactions (ADR). Hence, all patients received the appropriate pharmacotherapy. The pharmacist played a key role in the good functioning of the ark hospital in collaboration with all the medical team.

What next?

In conclusion, a new protocol and standard of care for managing health emergency will be the following and challenging step.

Author(s)

SILVIA CORNEJO-UIXEDA, M JOSE MARTINEZ-PASCUAL

Why was it done?

The anticholinergic burden is the cumulative effect of concomitantly taking multiple drugs with anticholinergic properties. It estimates the risk of suffering anticholinergic adverse effects. Anticholinergic scales are lists that rank the anticholinergic potential of drugs into categories.

What was done?

Our aim is to know the use of drugs with anticholinergic effect (ACD) in a regional hospital.

How was it done?

Observational study in patients older than 70 years admitted to a regional hospital from January to September 2021. We reviewed the medication of the patients looking for ACD. Then, we calculated anticholinergic burden with the “Drug Burden Index” available in: http://www.anticholinergicscales.es/calculate. The variables collected were: age, gender, number of drugs with anticholinergic effect, if ACD were prescribed before hospitalization, readmission, anticholinergic burden, risk of suffering anticholinergic effect and anticholinergic symptoms.

What has been achieved?

average 81 years (70-100), 102 (56% woman), 46 (25%) did not have any ACD. 58 patients had 1 ACD, 56 patients 2 ACD, 12 patients 3 ACD, 8 patients 4 ACD, 2 patients 5 ACD. Of patients with ACD, anticholinergic burden average was 0.98 in surgical patients (medium risk) and 1 in medical patients (elevated risk). 68 patients had medium risk and 68 patients elevated risk. We found constipation in 17 patients, somnolence in 6 patients, and disorientation in 2 patients. ACD used were the following (surgical vs. medical patients): Antidepressants: 3 vs.10, benzodiazepines: 28 vs. 33, opioids: 17 vs. 27, antiemetics: 13 3 vs. 38, Antipsychotics: 4 3 vs. 49, antihistamines: 2 vs. 2, antiepileptic: 0 vs 9, other: 0 vs. 3.
56 patients (31%) were prescribed the same ACD that they took before hospitalization. Only 17 patients were readmitted in hospital in less than a month.
We just made 2 interventions. We proposed to lower the dose in one case. In another, we proposed give metoclopramide just if necessary.

What next?

Most of hospitalized patients have ACD prescribed. Half of them had a high risk. However, just a few had anticholinergic reactions. This could be explained because we only had the information of electronic history and maybe some of them were not collected.

Author(s)

Irene Lizano, Ferran Montpart, Elisenda Pomares, Guillem Saborit-Canals, Míriam Fernández

Why was it done?

Treprostinil is a prostacyclin analogue indicated for the treatment of PAH. A recent retrospective study analyzed drug safety events observed in the clinical trials of oral and subcutaneous (SC) treprostinil. This analysis showed that higher treprostinil doses were associated with lower PAH-related hospitalization rates, compared to lower doses.

What was done?

To estimate annual pulmonary arterial hypertension (PAH)-related hospitalization costs in patients treated with different treprostinil doses in nine European countries (Belgium, France, Germany, Italy, Poland, Portugal, Spain, The Netherlands and the United Kingdom).

How was it done?

A cost estimation model was developed to calculate hospitalization costs in patients with PAH who were treated with treprostinil at different doses. Annual hospitalization rates were gathered from a retrospective analysis of an oral and SC treprostinil global safety database. Patients were categorized into three groups based on total daily dose: low, medium and high. Low dose was defined as <4.0 and <1.9 mg/day (9.0 and >7.6 mg/day (>30 ng/kg/min). PAH-related hospitalization costs were included and, when not available, heart failure-related costs were considered as it is the main cause of hospitalization in PAH patients. Mean annual hospitalization costs per dose were calculated using annual PAH-related hospitalization rates (0.9 for low dose, 0.4 for medium dose, and 0.3 for high dose) and unit costs per hospitalization in each country. All costs were obtained from national databases or published literature and were expressed in 2021 euros.

What has been achieved?

Mean annual PAH-related hospitalization costs ranged from €1,649 to €8,382 for low dose, from €733 to €3,726 for medium dose, and from €550 to €2,794 for high dose. Thus, hospitalization costs for high-dose patients were 3 times lower than for low-dose patients (mean difference €2,610) and 1.3 times lower than those for medium-dose patients (€435).

What next?

High doses of treprostinil result in lower hospitalization costs than low and medium doses in patients with PAH. Therefore, an appropriate drug titration might lead to potential cost savings in various European settings.

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.

Pdf

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.