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Author(s)

Giulia CANCELLIERI, Piera POLIDORI

Why was it done?

Hospital pharmacist provides all management of investigational medical product(IMP), i.e. its conservation, distribution, return and destruction. However, each clinical trial involves different methods of managing the drug: this can mislead the pharmacist who has to manage multiple trials at the same time. With the aim of minimizing errors that may arise from the simultaneous management of different clinical trials, we have developed a method to classify clinical protocols by “risk index”.

What was done?

With the aim of minimizing errors resulting from management of clinical trials in hospital pharmacy, we have developed a method to classify experimental protocols into low-moderate-high risk(risk index). For each of these categories, standard procedures were then outlined in order to minimize the occurrence of any errors.

How was it done?

In order to determine risk index(ρ) we have identified all risks related to IMP’s management: pharmacological risk(φ), dependent on pharmacological characteristics of IMP; technological risk(α), if drug should be compounding; risk related to number of patients enrolled(np); risk inherent to the protocol(π), i.e. whether protocol involves placebo, or randomization, etc. These risks were then related through the formula created by us, ρ=φ+(α*np)+π: protocols are defined low-risk if ρ<50, moderate-risk if 51<ρ151. For each risk index, standard procedures were outlined in order to minimize risks, i.e.(for high-risk) inclusion of at least four pharmacists in “Delegation of Responsibilities Log”; scheduling monthly meetings with trial’s Monitor; dispensing of IMP with supervision by at least two pharmacists; etc.

What has been achieved?

We applied this method to 45 active trials in our hospital. For 3/45(6,7%) protocols, φ>75 because IMPs are carcinogenic; instead, 26/45(57,8%) protocols, involve IMP’s compounding; finally 29/45(64,4%) protocols are randomized and 14/29(48,3%) of these involve use of placebo. By applying aforementioned formula, we found that 3/45(6,7%) protocols are low-risk, 32/45(71,1%) moderate-risk, 10/45(22,2%) high-risk. For these 10, standard procedures were applied, to improve the safety of patients enrolled in a clinical trial.

What next?

We promote use of this method in other clinical centers, because we believe it can be a valid tool for risk minimization. Finally, we hope that we will receive numerous feedback from these centers to further improve the proposed method.

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Author(s)

Roberto Brunoro, Mariassunta Miscio, Girolama Iadicicco, Lorenzo Codato, Domenica Condello, Elisa Danieli, Viola Donadello, Alice Osto, Federica Pace, Giulia Valente, Francesca Venturini

Why was it done?

In our Italian University Hospital, we established the “Clinical Research Helpdesk” managed by the Clinical Research Unit. According to a daily schedule all personnel with an active role in clinical research can reserve an appointment with a pharmacist and administrative staff to ask questions for the submission of the necessary documentation for the Ethics Committee (EC) and for the evaluation of the study feasibility.

What was done?

In our Italian University Hospital, we established the “Clinical Research Helpdesk” managed by the Clinical Research Unit. According to a daily schedule all personnel with an active role in clinical research can reserve an appointment with a pharmacist and administrative staff to ask question for the submission of the necessary documentation for the Ethics Committee (EC) and for the evaluation of the study feasibility

How was it done?

The schedule is a Google Calendar tool which permits to generate slots of appointments. Researchers can access it by a link spread during a presentation event of the initiative. At each appointment the presence of a pharmacist for scientific counselling and a member of the EC scientific secretariat is guaranteed.

What has been achieved?

Since March 2022 the helpdesk accounts for 120 appointments with an average of 17 appointments/month. Typical questions are related to documental forms clinical trials rules and regulation counselling; in the last period support was requested also for practical issues, e.g., CE marking for investigational medical devices, feasibility evaluation, contract agreement and informed consent. After the helpdesk activation, the processing time for all the evaluation steps from the document presentation until EC submission, decreased by 50% compared to the previous year. The service increased study submission: the requests for evaluation of interventional studies received by the helpdesk increased by 15%, whilst for observational studies the percentage increase was 10%.

What next?

We are planning to expand this service to reach a complete management of clinical trials introducing a “RedCap team”, consisting of clinical pharmacists and biostatisticians who will help researchers in study design, Clinical Research Forms (CRFs) creation, statistical evaluation and data interpretation. A legal team for legal issues and contract agreement counselling will also be offered. The aim is to increase the visibility of our hospital, making it more attractive for clinical research.

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Author(s)

Kirsten Lykke Vorbeck, Laila Rabbani, Somia Mohammad, Anne Bøiehøj, Lene Sehested, Majken Cardel, Lone Skovhauge, Lisbet Emmery Jørgensen

Why was it done?

Having different sponsors with individual requirements and interpretations of rules, means a lot of work. The brochure aims to save time on answering questions by describing to every sponsor how Danish Hospital Pharmacies proceed. By demonstrating that we all do many things in the same way and ultimately have the same requirements, we hope to be able to encourage sponsors to adopt a more unified or aligned approach.

What was done?

Through a collaboration of Danish hospital pharmacies, a working group on clinical trials meet regularly to discuss general procedures and challenges to our handling of clinical trials. Via this a common presentation of how we handle clinical trials and what we can offer has been described in a brochure that is given out to sponsors, investigators, clinical trial units (CTUs), clinical wards, monitors etc. The brochure also serves as an inspiration catalogue to hospital pharmacy colleagues.

How was it done?

In the working group we have discussed processes and which administrative and quality requirements we find reasonable and called for (from our point of view and that of our sponsors). We appreciate that we cannot do everything in exactly the same way, but we have tried to include as much as possible in the brochure leaving it up to the individual pharmacy to supplement with local procedures.

What has been achieved?

The brochure is evidence of our cooperation within Denmark. It has been distributed to relevant partners and to “Trial Nation”, a national entry point for companies who wish to conduct clinical trials in Denmark. It is intended as general information and to be handed out to new potential sponsors. It has resulted in an aligned and time-saving procedure.

What next?

Hospital pharmacies are small players in the field of clinical trials but nonetheless important ones. Working together to find general procedures not only helps ourselves to identify good practices but also means we can create a smoother handling of the trials and that we stand stronger when meeting the different requirements from sponsors. This cooperative approach has met with a good response. It promotes further cooperation between all parties, and it is recommended to be implemented in other healthcare settings.

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Author(s)

Diane Le

Why was it done?

When the case for a study sponsored by the hospital has been filed a few months ago, the national agency authorizing trials raised the issue of health waltch, particularly the management of drug recalls. With the research department, which alerted us on the lack of resources for health alerts, and at the same time facing an international cease of some drugs, we set up a health alert and a regulatory watch system, to improve the quality of product and the patient’s safety.

What was done?

We set up a daily health and regulatory watch to stay abreast of any news. Regarding health watch, we included : studies for which the hospital is the sponsor ; studies for which the experimental treatments are not provided by the sponsor ; treatments used for adverse events and authorized by the sponsor.

How was it done?

Daily regulatory watch is carried out on the national legislation website with daily updates of national texts. If a new rule applies, it is written in a table to alert everyone.
Daily health watch is also carried out on the site of the national agency of drugs. Four types of information are recorded: drug shortages, alerts, recalls and releases.

What has been achieved?

Tables collecting those information are available on the pharmacy’s network so that anyone can read them, and can be shared with clinical research officers. To that day, some information has been collected due to a european legislation update on the clinical trials and has allowed us to anticipate what will change next year. We have not yet faced a drug recall but what has been done will allow us to react in the best way when this will happen.

What next?

The aim for carrying out regulatory and health watch is to allow us to quickly react and anticipate future problems, while keeping in mind the patient’s safety and the pharmacy practices improvement. This work was therefore completed with success, demonstrating the ability to react and the desire to deploy continuous improvement initiatives to strive for operational excellence and pharmaceutical. We now want to implement this work in the daily activity and extend it to other sectors.

Author(s)

Lorena Garcia Basas, Pablo Latorre Garcia, Eugenia Serramontmany Morante, Patricia Garcia Ortega, Pilar Rovira Torres, Laura Maños Pujol, Isabel Cidoncha Muñoz, Maria Queralt Gorgas Torner

Why was it done?

Increasing number of CT with IT, in different pathologies, with different tumor locations, contributes an increase in the complexity of drug compounding and procedures. Their preparation, administration and handling requirements differ from current therapies.

What was done?

Identification of critical points concerning intratumoral treatments (IT) preparation in patients with cancer included in clinical trials (CT).

How was it done?

Ongoing CT with IT in our unit were reviewed to identify critical points regarding prescription and preparation process. 14 trials with IT, 8 (57%) of which have ongoing patients were identified. Two of these trials are “first in human”. The critical points were:

• Nature of the IT: virus (4, 29%), nanoparticles (3, 21%), ribonucleic acid (2, 14%), cyclic dinucleotides (2, 14%), monosaccharides (1, 7%), phospholipids (1, 7%) and proteins (1,7%).Particularly, virus have special safety measures and transport conditions
• Dosing units: mcg (4, 29%), plaque-forming unit/mL (PFU/mL)(3, 21%), mL (3, 21%), mg (2 14%), ng (1, 7%), 50% Tissue Culture Infectious Dose (TCID50)(1, 7%).
•  Prior dilution before filling the syringe: 8 (57%) of our preparations require at least one prior dilution.
•  Drug volume to prepare according to the tumor size: 8 (57%) IT preparations depend on the tumor size.
•  Depending on the depth of the target tumor lesion (visceral or superficial), different size of needle is required. This is important because different priming volumes of the needles are necessary.

What has been achieved?

The whole information necessary for a complete prescription, validation and correct preparation goes further than information usually needed for current therapies such as chemotherapy. The results of the study of the critical points allow us to elaborate the standardized operational procedures (SOP) for each CT and IT.  These SOPs include the necessary information for a correct preparation for each IT, reducing risk of mistakes and achieving uniformity in the process.

What next?

These types of therapies represent a challenge, and pharmacists have an important role in developing new procedures. Communication between radiology, oncology and pharmacy departments in a multidisciplinary teamwork is essential. This information may be useful to other centers due to the lack of experience and SOPs to work with this type of therapy.

Author(s)

Eugenia Serramontmany Morante, Patricia Garcia Ortega, Lorena Garcia Basas, Pablo Latorre Garcia, Pilar Rovira Torres, Laura Maños Pujol, Isabel Cidoncha Muñoz, M. Queralt Gorgas Torner

Why was it done?

The provision of outpatient oncology services by pharmacists is still limited, but it is an emerging role. It can add value while increasing the quality of patient care required, maximizing the likelihood of achieving positive outcomes and thus improving the patient’s quality of life. It is important to incorporate clinical pharmacists into outpatient clinics to ensure the safe use of investigational drugs and guarantee the best treatment for the patient.

What was done?

The oncology clinical trials pharmacy team initiated an outpatient clinic at a tertiary hospital. This enabled review of patients’ medications, monitoring of interactions, appropriate oral chemotherapy counseling, design of medication diaries and instructions, discussion of side effects, as well as other dietary and daily living recommendations.

How was it done?

A multidisciplinary team was formed: pharmacy, medical, nursing, ancillary and administrative staff, to discuss circuits and strategies to address outpatient pharmacy clinic.
The pharmaceutical care program was implemented gradually during 6 months, first in phase I, then phases II and III clinical trials.
Factors including appointment scheduling, patient prioritization, clinic room availability as well as detailed definition of pharmaceutical activity were discussed, in order to have a standard procedure for all patients included in a clinical trial.
The group continued to meet weekly to further discuss the progress of the pharmaceutical care program and any obstacles and unforeseen events.

What has been achieved?

Medication has been dispensed to 8447 patients in the outpatient pharmacy, of which 1172 patients have been attended by the clinical pharmacist during the first 8 months (January-August 2021) of the programme’s implementation.
Pharmaceutical care at the first day of treatment has been provided to 275 patients to explain how to take the treatment and resolve doubts. The concomitant medication of 312 patients has been reviewed for the screening and 425 telephone queries about concomitant medication have been resolved.

What next?

The evolutionary change in cancer care along with the increase in the number of clinical trials and its complexity will emphasize the need to include the oncology pharmacist in the cancer care team. The role of a clinical pharmacist is vital to ensure the safety and controlled use of the drug, ensuring the best possible outcomes.

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Author(s)

FRANCESCA VAGNONI, ANDREA MARINOZZI, SABRINA GUGLIELMI, CHIARA CAPONE, FRANCESCA MURA, ADRIANA POMPILIO, SIMONE LEONI

Why was it done?

The management of CT requires thorough documentary evidence and well-organized reporting system in compliance with the Good Clinical Practice. Since 2009, the entire onco-haematology workflow is fully-controlled by information technology devices and robotic systems to prevent medication errors and guarantee data integrity. The implementation of APOTECAtrial was aimed to extend the same level of control to CTs.

What was done?

In 2018, a clinical trial (CT) managing system (APOTECAtrial) was integrated into the existing fully-automated workflow of the chemotherapy production unit. APOTECAtrial was developed to enable real-time visualization of CT-related data and trace the processing of investigational (IMP) and non-investigational (NIMP) medical products, such as delivery, assignment, preparation, return, and disposal.

How was it done?

A team of hospital pharmacists, physicians, clinical data managers, and IT specialists analysed the CT workflow and defined the system specifications. Data related to IMP/NIMPs (both for parenteral and oral administration), patients enrolled, and investigator/sponsor affiliations were entered into APOTECAtrial and sorted by CT. The onco-haematology unit’s electronic prescribing system was bidirectionally interfaced with APOTECAtrial. Aseptic preparation of patient-specific injectable therapies was implemented in the supporting device for manual preparation that checks dosage accuracy and identity by photographic and barcode recognition.

What has been achieved?

Since 2018, the overall number of CTs managed was 95. In total, 81 IMPs/NIMPs and 135 patients were entered into the system, while 2740 injectable therapies were prepared, 690 oral medications and 60 pre-filled syringes delivered. The following major objectives were achieved: automated inventory accounting and stock management, reduced manual time-consuming activities (i.e. documentation, transcription), standardized reports in digital not-editable format, and full traceability. In addition, audit trail tool tracks all user edits and changes performed at any stages of the CT management by electronically recording user’s name, date, and time. APOTECAtrial was evaluated by clinical research associates (CRA), clinical research organizations (CRO) and CT sponsors and approved for use in the daily clinical practice.

What next?

The project represents a good example of multidisciplinary collaboration focused on improving the quality of the processes in healthcare settings. The implementation of information technology and automation ensures improved data integrity, safety, and working efficiency, which are key determinants for managing CTs in hospital pharmacies.

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Author(s)

Paula Arrabal-Durán, Carmen Herrero-Domínguez-Berrueta, María Norberta Sánchez-Fresneda, Ana Mur-Mur, Ana Herranz-Alonso, María Sanjurjo-Sáez

Why was it done?

MI and PI are normally recorded in Hospital Pharmacy Services as a method for evaluating safety. Nevertheless, classical methods for reporting MI do not allow for a correct classification in the field of clinical trials. The reason is their more complex processes involving drugs compared to the processes in daily clinical practice. If there are no specific categories, the information obtained by recording usually gets lost and could not reflect exactly what occurred. In September 2016, a clinical tool to notify MI and PI was implemented in the Pharmacy Service, with the aim of unifying their classification criteria and gathering complete information for analysis and further implementation of improvement measures.

What was done?

A database to notify medication incidents (MI) and pharmaceutical interventions (PI) in the Clinical Trials Unit was developed in the Pharmacy Service of a tertiary hospital.

How was it done?

All the processes involving drugs in clinical trials were evaluated by a Failure Mode and Effects Analysis (FMEA). For each process, the possible incidents and their resulting effects on the patient were recorded. After that, a database was designed in Microsoft® Access with defined lists of choices to allow pharmacists notify both MI and PI that occur in the Clinical Trials Unit.

What has been achieved?

A database with the following information has been implemented:

a) Identification of the MI:
1. Date of the MI.
2. Number of patient.
3. Clinical Trial protocol.
4. Investigational product.
b) Process in which the MI took place (16 options).
c) Process in which the MI was detected (16 options).
d) Process that caused the MI (24 options).
e) Person who detected the MI (9 options).
f) Did any PI take place? (Yes/No).
g) PI performed (12 options).
h) Did the MI reach the patient? (Yes/No).
i) MI that reached the patient (21 options).
j) Patient outcome (8 options).
k) Effect in the clinical trial (4 options).

What next?

The implemented notification system will be further expanded and adapted over time.
Future aim is to analyse MI for establishing improvement measures and checking their results.