Clinical trials (CTs) are considered the cornerstone of clinical research into drugs.1 According to recent data published by the Spanish pharmaceutical industry association (Farmaindustria), Spain is one of the most prolific European Union countries in terms of performance of CTs,2 with a steady growth in the number of CTs carried out every year.

Although Good Clinical Practice (GCP) guidelines3 entrust principal investigators with the responsibility of managing investigational medicinal products (IMPs), the current Spanish legislation delegates drug reception, custody and dispensing functions to hospital pharmacy departments (HPDs).4

The responsibility of managing a growing number of CTs, some of them highly complex and requiring individualized and specific storage, handing and management has created a situation where the clinical trial units (CTUs) of HPDs are faced with an increasing demand of material resources and specialized staff.

At the same time, the excessive bureaucratization of the processes related with the conduct of CTs together with the need to adapt to the specific requirements and procedures of different CT sponsors also constitute a formidable challenge for HPDs, as it is often the case that the scarce resources available must be assigned to procedures that not only lack any added value but also jeopardize the safety of patients and of the professionals involved in managing IMPs.

From the standpoint of the pharmaceutical industry (PhI), IMP management optimization is construed as a way of enhancing the eligibility of a country, in this case Spain, to host CTs, which has for many sponsors been an important priority since the implementation of the EU Clinical Trials Regulation.5

Against this background, the Clinical Trials Working Group (GTEC) of the Spanish Society of Hospital Pharmacists (SEFH) considers it essential to establish communication channels with the PhI, insofar as it is pharmaceutical companies that sponsor most of the CTs performed in Spain. The final goal would be to come up with a consensus regarding the procedures to be followed and the criteria to be applied, optimize processes involved in the management of investigational medicines, and increase the quality of such management processes, eliminating superfluous tasks.

The Guide to Excellence for the Conduct of Clinical Trials in Hospital Pharmacies6 resulted from an initiative of Farmaindustria and the Hospital Affairs Section of the General Council of Pharmacist Associations, further to a multidisciplinary meeting held in July 2019 where a document called Decálogo de Criterios de Excelencia para la realización de Ensayos Clínicos (Ten standards for the conduct of high-quality clinical trials) was drafted.7 One of the standards in this document made reference to the importance that HPDs be involved in the performance of CTs.

After an initial meeting in November 2020, attended by PhI representatives and hospital pharmacists, including several members of GTEC, a list was drawn up of the issues which, in the participants' opinion, required urgent action with respect to the relationship between the PhI and HPDs. The document was divided into six problem areas, each assigned to a joint working group made up of members of the PhI and of the hospital pharmacy community. The six working groups created were required to work on the following areas:

• •

  Communication

• •

  Document harmonization and standardized working procedures

• •

  Platform standardization

• •

  Process improvement

• •

  Comparator drug supplies

• •

  Process digitalization

The working groups presented their conclusions in March 2021 and, after that, a joint drafting committee (DC) was created to work on preparing a final document. The DC decided that the document be structured in guideline form as this would not only make it intuitive and didactic, but it would also make it a flexible document capable of accurately conveying the conclusions of the different working groups.

Further to a series of consensus meetings of the DC, the document was finally released to the public in April 2022.

The DC decided that the most didactic way to structure the Guide would be to follow the typical chronological order of a CT, dividing the document into three sections: 1) pre-study phase, 2) initiation phase, and 3) execution and closure. Each of these stages was developed from different points of view, adapting the initial thematic distribution to a simpler and clearer structure. Each section was structured around the following themes:

• 1.

  Communication.

• 2.

  Documents and processes.

• 3.

  Investigational drug.

• 4.

  Platforms, systems and digitalization.

Four support infographics were also included to assist readers in the preparation of the different documents and the implementation of the different processes.

In what follows a detailed description is provided of the most significant aspects under each of the themes from which the three development phases of a CT were analyzed. Reference is made both to the points included in the Guide and to those which, although discussed by the working groups, were finally excluded from the Guide for reasons of brevity or because it was decided to leave them for future development and discussion.

Documents and processes

GCP guidelines3 describe the documents to be included in the investigator site file, while the CT is underway and once it has been completed. However, it is not clear nor there is general agreement on the contents or the format of a CT's pharmacy file.

HPDs with a high volume of CTs should be able to avail themselves of a practical, safe and efficient way of managing all the documents generated. At the same time, standards should be developed regarding minimum documentation requirements and the format in which documents must be stored, which not be accepted by all sponsors.

The Guide stipulates the minimum set of documents to be delivered by the sponsor to the HPD and lays emphasis on the importance that the HPD should make available a welcome leaflet with basic information on the way the CTU operates as well as a checklist of the different topics to be discussed during the initiation visit.

Table 2 shows a proposal of the minimum set of documents to be included in the pharmacy file of a CT at the pre-study, initiation and development phases.

Table 2.

Proposed contents of pharmacy records in the context of clinical trials (physical and/or digital records).

Pre-study /initiation phase of the clinical trial	Protocol	Current version at the time of the initial visit.
	Pharmacy handbook	The HPD must be handled a written record of all the required information and/or materials related to the IMP:- Storage conditions.- Preparation conditions (if appropriate).- Administration conditions.- Label and package type model, allowing HPDs to decide how much storage space is necessary.
	Safety Data Sheet or its equivalent	Document providing information on the safety conditions required for handling of the IMP.
	Legal documents	Regulatory Agency (AEMPS) approvalFavorable opinion by the Ethics CommitteeSite Agreement
	HPD documents	Resumés and GCP training certificates of the HPD staff in charge.
		Internal delegation document: A record must be kept of the staff involved in managing the investigational drug (preparation, dispensing etc.) who are not included in the CT's task delegation form.
		Valid calibration certificates for the temperature probes used in the storage facility.
In the course of the clinical trial	Updating of reference documents	Changes to the protocol, the pharmacymanual or other documentswhich may affect the procedures of the HPD.
	Source documents and registries	Source documents (in physical or digital format) related to reception/dispensing-preparation/return of IMPs.
		IMP accountability forms (in physical or digital format).
		Temperature records

GCP: Good clinical practice; AEMPS: Spanish Agency of Medicines and Medical Products; CEIM: Ethics Committee for Drugs Research; HPD: hospital pharmacy department.

As regards the information factsheet to be made available by the HPD, infographic 1 of the Guide (Fig. 1) contains a proposal of the minimum items of information it should include: contact data, opening hours, description of the facilities and work procedures.

Fig. 1.

Monitor initiation handbook provided by HPDs.

(0,95MB).

During the CT initiation visit, all agreements regarding the handling of the IMP and the responsibilities of the HPD staff must be concluded. The initiationvisit should not be a replica of the initiationvisit with the research team, attendance of the monitor assigned to the HPD is required, and its duration and contents must beadapted to the CT's complexity.

Infographic 2 of the Guide includes the aspects and documentation that should ideally be shared with monitors during their initiation visit to the HPD (Fig. 2).

Fig. 2.

Monitor welcome package prepared by HPD's CTUs.

(0,59MB).

One of the chief milestones achieved has been the acceptance by CT sponsors of the individual hospitals' specific accountability logs provided that they contain the minimum items of information required by the GCP guidelines. Infographic 3 of the Guide (Fig. 3) contains the minimum set of information to be included in an accountability log.

Fig. 3.

Accountability record of the investigational medicine.

(0,66MB).

Several organizations, among them SEFH, have published quality guidelines and procedural recommendations for the proper management of IMPs at HPDs.10–14 Nonetheless, to the best of our knowledge, none of them are the result of a consensus with pharmaceutical companies, which tend to be the sponsors of CTs. The value of the Guide discussed in this study is precisely that it is the result of a joint effort between pharmacists and the PhI and that it paves the way for further collaboration between sponsors and HPDs.

New developments such as digitalization of documents and processes, decentralization of CTs, the use of telepharmacy in the context of CT, the development of CTs on advanced therapies and more effective management of hazardous drugs, among others, may no doubt benefit from close communication and collaboration with the PhI. However, GTEC believes that much work remains to be done to speed up processes, reduce red tape and eliminate activities which not only contribute no added value but also interfere with the quality of IMP management, undermining the safety of both patients and those handling IMPs.

Some examples include deficiencies in the labeling and the appropriateness of the IMP dosage forms, restrictions to the use of closed drug transfer systems, the problems inherent in long-term storage at HPDs of potentially hazardous leftover IMPs, and duplicate accounting of IMPs.

In this regard, GTEC is currently working hand in hand with principal investigator representatives and CT coordinators, monitors and sponsors on the preparation of a do's and don'ts document aimed at improving the quality and efficiency of HPD's CTUs.

It would be of the essence for collaboration between HPDs and the PhI to continue in the future, in the form of permanent or temporary working groups or one-off projects such as the one discussed in this study. Other parties, such as regulatory authorities and CT coordinator groups, should also be involved in any joint initiatives undertaken so as to discuss, and agree on issues of common interest.

Lastly, HPD should be equipped with the staff, infrastructure and resources required to achieve the standards of excellence needed in a continuously-evolving environment such as that of the conduct of CTs. Investments made in the HPD's CTUs will also be a great boon for hospitals themselves as they will no doubt benefit from the innovations introduced, the knowledge generated, and the potential investments attracted, as well as from an increase in their ability to develop their own high-quality investigations. HPD's CTUs will only be able to train their staff to the desired standard and attract the resources needed to face the challenges of the future if they enjoy the support of hospital and foundation managers and if they secure the support of hospital pharmacists, raising their awareness about the importance of excellence.

The Guide to Excellence for the Conduct of Clinical Trials in Hospital Pharmacies is the first consensus document developed by the PhI and the hospital pharmacy profession for the management of IMPs.

The establishment of an open dialog between hospital pharmacists and the PhI and other agents involved in the conduct of CTs facilitates an effective approach to the different issues contemplated in the Guide, and makes it possible to address other present and future challenges to improve the efficiency and quality of managing the medications used in CTs in our country.

The leadership of hospital pharmacists as experts in the management of IMPs should be used as a tool to increase their visibility and make it possible for HPDs to be assigned the human and material resources they need to pursue excellence.

Below is a list of the contributing authors, who have read and approved the final version of the article and have agreed for it to be submitted to the Revista. Next to each author's name and ID# is a description of the specific tasks they carried out.

Pilar Suñé Martín, ID# 43686923X: definition of the intellectual content, design, analysis and coordination of the project and writing of the manuscript. José Manuel Carretero-Abascal, ID# 28455136 L: definition of the intellectual content, design, analysis and interpretation of the project and final review of the manuscript with significant contribution. Cristina González-Pérez, ID# 47.033.105-Z: design, analysis and interpretation of the project and final review of the manuscript with significant contributions.

This project received no external funding.