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Re-using mendeliome data to explore pharmacogenomics implementation: pitfalls and opportunities.

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European Statement

Clinical Pharmacy Services

Author(s)

Eline Coene , Catharina Olsen, Mathijs Swaak, Freya Vaeyens , Frederik Hes , Stephane Steurbaut, Sonia Van Dooren , Pieter-Jan Cortoos

Why was it done?

Pharmacogenomics has a large potential to optimize individual patients’ both current and future drug therapies. In Belgian hospitals however, pharmacogenomics is still rarely used in clinical practice posing great opportunities for hospital pharmacies to explore this field and setting up new services.

What was done?

The Centre for Medical Genetics (CMG) of UZ Brussel, a 721-bed tertiary hospital in Brussels (Belgium), has been performing next-generation sequencing of mendeliomes for diagnostic purposes since 2016. Pharmacogenomic data is thus potentially available, but currently not further used. As hospital pharmacists, we wanted to explore the possibility of reporting pharmacogenomic information as ‘secondary findings’, in particular prevalence of actionable pharmacogenes and gene-drug interactions (GDIs) in our own population, and to determine required features and opportunities of a future pharmacogenomics project

How was it done?

Firstly, 14 pharmacogenes comprising 626 loci were selected based on available guidelines, clinical relevance and whether the gene was included in the mendeliome gene set. With the support of CMG, we then reviewed available data for patients with a mendeliome analysis between 01/03/2016 and 30/06/2020. To enable haplotype assignment, a Python script was developed displaying possible haplotypes with corresponding ‘matching score’ and ‘completeness score’. Where possible, phasing was done using pedigree information. Resulting phenotypes were finally further linked with medication histories, abstracted from patients’ electronic medical records in order to identify possible GDIs.

What has been achieved?

Pharmacogenomic data could be re-used for 536 individual patients, revealing that at least 76.9% had one or more actionable phenotype while 60 GDIs with varying relevance were found. CYP2C9 had the most actionable phenotypes (174/536) and was involved in 42 GDIs. However, not all phenotypes (e.g. copy-number variants) were detectable for CYP2C19 and CYP2D6 due to limitations of current mendeliome data and used platform.

What next?

Reusing genomic data has great potential and can be an ideal stepping-stone towards developing and implementing pharmacogenomics in other hospital pharmacies but requires a good interplay between pharmacists, geneticists and bio-informaticians. In our hospital this initiative has led to in-depth collaboration between pharmacy and medical genetics department focusing on validation and implementation of a pharmacogenomics-array coupled with implementation of a pharmacogenomics service, next to pharmacological use of whole-genome sequencing data.

New frontiers of hospital pharmacy: management and preparation of human tissues used in the surgery room

European Statement

Clinical Pharmacy Services

Author(s)

Andrea Ossato, Giuseppe Giovagnoni, Michele Giannini, Anna Francesca Spada, Francesca Realdon, Valeria Mezzadrelli, Lorenza Cipriano, Nicola Realdon, Teresa Zuppini, Roberto Tessari

Why was it done?

Since 1st October 2019, the regional tissue bank that supplies hospital, stopped sending ready-made tissue to the implant, preferring the shipment of tissues frozen at -80°C. For this reason, the hospital pharmacy developed a procedure for the management of orthopedic allografts ensuring a clear and safe supply chain reducing the waste raised from the obligation of immediate use of the thawed tissue.

What was done?

Hospital pharmacists, in agreement with the hospital administrators and the orthopedic surgery department, developed a new service characterized by procurement, processing, preservation, storage, thawing and preparation of human tissues and cells for orthopedic allografts, according to European and national legislation.

How was it done?

The management of orthopedic allografts took place as follows: was established a dedicated path for communications with orthopedic surgery and bank tissue; tissue thawing and washing was centralized in the clean-room of the hospital pharmacy and were guarantee adequate training of all personnel involved as well as complete standard operating procedure documentation for all stages of the process and appropriate control measures.

What has been achieved?

Evaluation of the process showed that it was favourable in terms of practicality, safety, traceability and cost saving. Especially, the centralization of tissue preparation within clean‐rooms with aseptic technique, allows microbiologically safer setups reducing clinical risk. A further guarantee of safety is given by the sterility process’s validation through Media Fill test. This organisation allowed us to reduce the waste through a more effectively management of the tissues shelf life and any missed surgery with a cost saving and an ethical behaviour.

What next?

Optimise patient outcomes through working collaboratively within multidisciplinary teams and using the limited health systems resources responsibly, are two main goals expressed by the last European Statements of Hospital Pharmacy (ESHP). This study demonstrated how the centralization of tissues management in the hospital pharmacy make the process more efficient and safer and thus comply with the ESHP’s goals; leading to a clinical advantage for patients and better economic impact for the hospital.

CLINICAL PHARMACOKINETICS OF ANTI-TNF THERAPY: OUR FIRST EXPERIENCE IN INFLAMMATORY BOWEL DISEASE

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European Statement

Clinical Pharmacy Services

Author(s)

María Mar Alañón Pardo, Alejandro Marcos de La Torre, Beatriz Proy Vega, Adrián Pérez Facila, María Luisa Moreno Perulero, Clara Notario Dongil

Why was it done?

Numerous publications have demonstrated a correlation between serum concentrations (Cs) of anti-TNF drugs and the therapeutic response and a wide interindividual variability in pharmacokinetics among patients with IBD. TDM permits dosage individualization and optimization of anti-TNF therapy.

What was done?

Pharmacokinetic monitoring (TDM) of anti-TNF therapies (infliximab/adalimumab) in inflammatory bowel disease (IBD) was implemented in our hospital by a multidisciplinary team of pharmacists, gastroenterologists and clinical analysts.

How was it done?

A computer platform was developed within the hospital electronic records system to manage consultations of gastroenterologists with the Clinical Pharmacokinetics Unit (CPU) of the Pharmacy Department. Variables in this electronic interconsultation system were: “anti-TNF drug”, “concomitant immunomodulator (IMM)”, “diagnosis”, “reason for consultation”, “date of last dose”, “date of extraction”, “weight/height”, and “observations”. Laboratory tests ordered from the Department of Clinical Analysis on the electronic request form included blood count, Cs of infliximab/adalimumab, albumin, C-reactive protein and faecal calprotectin. Quantum Blue® lateral flow immunoassay was used to quantify Cs of the anti-TNF drugs; when undetectable, the presence of anti-drug antibodies (ADAs) was investigated.
The CPU developed pharmacotherapeutic recommendations based on therapeutic algorithms, pharmacokinetic/pharmacodynamic principles and population models implemented using MW-Pharm++® software, which incorporates the principle of Bayesian estimation. For a correct interpretation of the Cs observed, adherence to anti-TNF ± IMM regimens was evaluated using electronic dispensing records and the self-administered Morisky-Green questionnaire.

What has been achieved?

Since its implementation (January 2019 – August 2020), the CPU has responded to 269 consultations on 121 patients treated with infliximab (46.3%) or adalimumab (53.7%): 70.2% were prescribed with IMM (89.4% with thiopurines); 93.4% adhered to the anti-TNF regimen and 82.4% to the IMM. Baseline anti-TNF Cs were subtherapeutic in 37.2% of patients, therapeutic in 35.5% and supratherapeutic in 27.3%. ADAs were positive in 28.6% of patients with undetectable anti-TNF Cs (n=28). A large proportion (84.8%) of consultations were related to proactive monitoring (to optimise treatment) and the remainder were reactive (after treatment failure). A very high percentage (89.9%) of the gastroenterology specialists accepted recommendations.

What next?

Extend TDM to other biological therapies and immune-mediated diseases.

DELIVERY OF SPECIALISED MEDICINES IN MEDICINE POST BOXES – A PILOT STUDY

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European Statement

Clinical Pharmacy Services

Author(s)

Maja Kirstine Brøns, Gitte Borup

Why was it done?

The purpose was to move medicine collection from the outpatient clinics to a MPB in order to reduce CO2-emission, due to less kilometers traveled by patients, to increase equal access to healthcare services, and to reduce physical patient contact during a global pandemic.

What was done?

This was a pilot study that investigated a method for, and patient satisfaction with, delivery of specialized cost-free hospital medicines via Medicine Post Boxes (MPB) in rural areas.

How was it done?

The project was initiated by clinical pharmacists, who acted as interdisciplinary liaisons, who understood the clinical aspect of the medical treatment, the importance of good distribution practice and the logistic capacity at the hospital pharmacy. Having completed clinical controls via telephone, the clinic forwarded the information needed to the hospital pharmacy. Initially, all requisition forms were checked by clinical pharmacists to ensure complete information was given, and that documentation was performed properly. Once fully implemented, a task shifting onto pharmaconomist was done concerning the control of the requisitions, however initiation of cooperation and problem solving with the clinic was maintained as a pharmacist task.

What has been achieved?

Focus group interviews with doctors and nurses from the clinics expressed satisfaction with the flexibility of conducting clinical controls over the phone, and not having to handle the practical part of ordering, documenting and handing out medicines. No concerns of patient safety were expressed, and a wish for full coverage for medicine delivery via MPB was stated. A survey among the patients using the MPB was conducted: A total of 148 respondent participated of whom 98 % stated being ’very pleased’ or ’pleased’ with the service. Also, 98 % felt safe to ’a very high degree’ or ’high degree’ with using the MPB and 99 % wished to use the MPB again. Estimates of CO2 reduction have not yet been calculated.

What next?

MPB’s should be available in urban areas also, as it increases flexibility for the patients and healthcare professionals. The goal is to include all suitable clinics and patients who receive long term treatment with hospital medicines

PANDEMIC CRISIS COVID 19: THE DRUGS HOME DELIVERY AS A TOOL FOR ADHERENCE AND COMPLIANCE

European Statement

Clinical Pharmacy Services

Author(s)

BARBARA RE, MARTA DEL VECCHIO, CLAUDIA LAURIA PANTANO, ELIROSA MINNITI , VITO LADISA

Why was it done?

The covid-19 pandemic and the lockdown made it difficult and very often not possible to access hospital pharmacies for dispensing of drugs for cancer treatment

What was done?

Drugs homedelivery has been implemented for fragile patients and at risk both oncological and hemato-oncological, all over the italian territory

How was it done?

Through the telemedicine program, in agreement with the oncologist, patients unable to reach the pathology doctor’s office are contacted and the project explained to them. If the patient accepts the delivery at home, paths with specialized couriers have been activated, in compliance with the GDPR, which ensure the delivery of medicines within 48 hours. Upon delivery The Pharmacist contacts the patient to ensure that they have been received the medicines and reinforces how you take the drug and the potential side effects that need to be reported to doctor and / or pharmacist

What has been achieved?

In the period from March to September 2020, 501 deliveries were made, of which 301 in the regional territory and 200 in the national territory. 423 patients were contacted, A Customer Satisfaction was activated to which 90% of patients with a high degree of acceptance of the service responded

What next?

The Homedelivery service has shown that integrating telemedicine, with the collaboration oncologist and pharmacist, allows, when possible, to avoid fragile patients having to go to the hospital every month to collect the drug needed for their treatment. Furthermore, the role of the pharmacist will be increasingly central in the home clinical management of this patient population to assure Adherence and Compliance even in at Home setting.

INTEGRATED ONCOLOGY PHARMACY UNIT IN MULTIDISCIPLINARY TEAM

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European Statement

Clinical Pharmacy Services

Why was it done?

There was a previous collaboration between the pharmacy and medical oncology but with many problems due to the physical separation between the two units. There was a lack of knowledge of the needs of both services.

What was done?

To provide integral cancer care to the patients. We prepare the standard or investigational treatments the day of analysis and medical consultation. In the pharmacy consultation, we provide information and training to patients and their caregivers about the use of antineoplastic, evaluate their polytherapy and complementary and alternative therapy, drug interactions, conciliation, dispense doses and adjusted to help improve treatment and adherence and tolerance amounts.

How was it done?

Change of hospital, creation of new onco-hematology unit(2003), good feedback, and integration in clinical sessions.

What has been achieved?

The pharmacist reviews each chemotherapy order in relation to all known factors concerning the patient. If questions arise, the physician originating the order is contacted. Orders are verified with a protocol, standard regimen or standard dosing guidelines. The oncology pharmacist contributed to the design of chemotherapy protocols by electronic prescribing program (Farmis_Oncofarm®) and supportive care protocols. Activity (2013):22.770 preparations of intravenous chemotherapy, 9.651 patients consulting pharmacy. Reusing cytostatics in a centralized pharmacy preparation unit (Nplate®saving:129.910€(31.7%)), the preparation of parenteral mixtures at the pharmacy department minimises costs compared to preparation on wards (estimated saving 2.500.000€).The unit is also actively engaged in clinical trials (166 trials) and other research projects (pharmacogenetics and adherence with electronic monitoring system) with several publications (∑IF=84). It is a reference model clinical and teaching, oncology pharmacy unit is a preceptor to residents, staffs of other hospitals. Realisation of the annual attendance course. Unit Growth: 2 oncology pharmacist(BCOP),1 haematology pharmacist (BCOP),1 paediatric pharmacist, 3 nurses,1 technician and 1 investigator. Implantation of Standard UNE 179003 on Risk Management for Patient and ISO9001. 0.5 % errors and avoiding incidents. High average patient satisfaction(93%).

What next?

Allow direct patient interaction through a econsultation platform and twitter. A staff preceptorship and traceability system for the preparation and administration(barcode) implement.

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