Assessment of pharmacy professionals’ knowledge and practice on the management and dispensing of investigational drugs in clinical trials

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Indeed, David and Alan (2021) listed four types of barriers that cite: procedural, structural, infrastructural, and synchronicity.The interactive effects of these barriers contribute to increasing inefficiency of the process (David and Alan, 2021;Colinand Alan, 2021).In addition of these barriers it is important to identify the barriers associated with the pharmacy professional knowledge and practices.The organization of the management and dispensing of pharmaceuticals in clinical trials must be based on a quality assurance system.Pharmacists, as they take on the increasing responsibilities required by these new roles, should actively seek to improve their professional skills (Agence, 1997).In some northern countries like France the regulatory and legislative framework places the holding and dispensing of investigational medicinal products for clinical trials under the responsibility of the hospital pharmacist unlike developing countries where regulation is weak (Philippe and Solange, 2000).
Burkina Faso is a developing country with hospital facilities that can contribute to training and research into new therapies through clinical trials.There is, however, a low level of involvement of hospitals in the conduct of clinical trials.
According to the 2013 report, only 25/495 European & Developing Countries Clinical Trials Partnership/EDCTP clinical research projects in 2013 were conducted in research centers (European and Developing Countris Clinical Trials, 2013).
The same observation is made in most African countries (Julien, 2015).The literature surrounding the development of standardized quality measures to assess site performance in clinical trial consortia is sparse (Marius et al., 2021).
There is in general a lack of data on the knowledge, and practices of health workers in the management and dispensing of medicines and other practical aspects of care in African countries and in Burkina Faso in particular (Susannah et al., 2013;Hervé et al., 2013) .
With the aim of creating a specific unit for the management of clinical trials in our hospitals, like the hospitals in the north, we evaluated the level of knowledge and practice of pharmacy professionals in the management and dispensing of experimental medicines.This evaluation of the organisation and pharmaceutical performance is part of the self-evaluation.

Study type and duration
This was a cross-sectional study that took place from 15 January 2018 to 30 June 2018 in three university hospital center (CHU) in the city of Ouagadougou (CHU Yalgado Ouédraogo, CHU pédiatrique Charles De Gaulle, CHU de Tingandogo).The validation phase of the questionnaire from January to February, then the data collection phase took place from March to April and the data analysis took place from May to June 2018.Tarnagda et al. 101

Study sample
The study population was hospital pharmacy staff.A census of all available qualified personnel such as specialist pharmacists, general pharmacists and state pharmacy assistants was carried out beforehand in each university hospital.

Inclusion criteria
These included: 1. Be a pharmacist or pharmacy technician 2. Be staff in the hospital pharmacy of the hospital surveyed 3. Be present in the hospital during the survey period 4. Have at least three months of service in the hospital

Exclusion criteria
These included: 1. Staff who are not pharmacists or pharmacy technicians 2. Pharmacist or pharmacy technician with less than 3 months of service in the hospital 3. Pharmacist or pharmacy technician refusing to participate in the study 4. Professionals on leave or secondment not included.

Questionnaire development, validation
Data were collected using a physical questionnaire and the technique of self-administration of questionnaires was used.The questionnaire was validated after a pre-test.The questionnaire was developed with reference to hospital pharmacist quality manuals and good dispensing practice processes in pharmacology.The items on operating procedures in part A of the questionnaire were intended for pharmacy managers.The items in part B of the questionnaire were intended for staff and managers.Closed questions were used to facilitate the exploitation of our results regarding staff knowledge and attitude on dispensing (appendix).

Study variables
These included: 1. Socio-professional characteristics (qualification and years of professional experience) 2. The number of participations in clinical trials, etc, 3. The list of regulatory documents available in the UHC. 4. The level of knowledge of staff in the practical management of investigational medicinal products (dispensing process and management of the pharmaceutical file) 5.The availability of management procedures, dispensing procedures for trial medicines and quality manuals A descriptive analysis of the data was conducted.Proportions were used to estimate levels of knowledge about clinical trial management and good practice in dispensing investigational medicines during clinical trials.

Ethical and regulatory considerations
Authorization was obtained from each director of the three university hospitals.Data relating to personnel were collected

Socio-professional characteristics of the staff surveyed
A total of 30/41 staff meeting the inclusion criteria participated in the study.The majority of the staff had been in the profession for more than 10 years (Table 1).

Staff experience in conducting a clinical trial
Approximately 35% (14/41) of staff reported having been involved in the conduct of a clinical trial.About 21.4% (8/41) of staff reported having received training on clinical trials Only 10% of staff had ever been involved in the selection of a site for a clinical trial and 25% in the closure of the trial.Thirty percent of staff reported having participated in trial set-up meetings (Table 2).

Assessment of the level of knowledge of the clinical trial pharmaceutical record
Less than half of the staff surveyed had knowledge of the various mandatory documents that should be available in the hospital pharmacy during the conduct of clinical trials.
The individual level of knowledge of each document in the trial pharmaceutical record varied from document to document (25-60%) (Table 3).

Evaluation of the knowledge and practice of dispensing medicines
All hospital pharmacy staff had a good command (56.6 to 76.6¨%) of the different stages of the act of dispensing medicines.The rate of compliance with good dispensing practices varied.Thus, for systematic compliance with each of the dispensing procedures, the proportions were disparate (validation of prescriptions after a pharmaceutical analysis (60-76%); provision of prescribed medicines to patients (56.6-76.6%);advice and pharmacovigilance practices (60-76.6%);management of treatment returns (60-76.6%).

Availability of medication management and dispensing procedures
The various management and dispensing activities were not subject to written standard operating procedures previously available in the hospital pharmacy (Table 4).Name of the procedure Available on days Available not updated Procedure of procedures 0/3 0/3 Procedure for dispensing clinical trial medicines to outpatients 0/3 1/3 Batch acceptance procedure for clinical trials 0/3 0/3 Batch manufacturing procedure for clinical trials 0/3 0/3 Procedure for destruction of clinical trial batches 0/3 0/3 Procedure for recording the ambient temperature of batches for clinical trials 0/3 0/3 Storage procedure between 2 and 8°C 0/3 0/3 Procedure to be followed in the event of a temperature excursion in the storage of clinical trial batches 0/3 0/3 Procedure for recording non-conformities 0/3 0/3 Monitoring follow-up procedure 0/3 0/3 Procedure for conducting the annual review 0/3 0/3 Procedure for using the SOFTWARE 0/3 0/3 Procedure for editing production sheets 0/3 0/3 Training procedure for new interns 0/3 0/3 Source: Study data

DISCUSSION
The pharmaceutical professionals were pharmacists and state pharmacy technicians managing the experimental medicines in the country's university hospitals.The organisation of the hospital pharmacy implies the definition of a profile of the personnel necessary for the proper functioning of the clinical trial.The qualities of the staff should be related to the profile and level of activity.This same profile is observed in hospitals in northern countries (Agence, 1997;Chistel et al., 2019).However, more than half of the staff have never been involved in conducting clinical trials.This could be explained by the scarcity of clinical trials in our hospitals but also by the regulatory environment compared to developed countries (Les Entreprises du Médicament, 2016Médicament, , 2018;;Vincent et al., 2008).Studies have demonstrated the importance of pharmacist involvement in the success of clinical trials.Indeed, according to Destrumelle et al. (1997), 93% of investigators rated the participation of pharmacists in clinical trial set-up meetings as positive and 65% were satisfied with the pharmaceutical activities during trial closure (1997).According to ICH E6 R1, the pharmacist or other appropriate person designated by the investigator/ institution should maintain records of product delivery to the trial site, inventory at the site, use by each subject, and return to the sponsor or disposal of unused product (International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, 2016) Some hospitals use the expertise of the in-house pharmacy in the management of experimental research to ensure the coordination of international multicenter clinical trials, but also the subcontracted manufacture of experimental drugs (Jihyun et al., 2016;Farshid, 2008).In our context, there are ministerial decrees and orders governing the granting of clinical trial authorizations.However, the texts framing the role of hospitals and hospital practitioners in clinical trials, such as the good clinical practice guidelines, remain limited (Ministère de la Santé, 2010aSanté, , b, 2013)).The level of individual knowledge of each document in the trial's pharmaceutical dossier varied from document to document.Trial documentation should be filed, with an individual file for each trial.The storage of files and their indexing comply with the rules of confidentiality and archiving of clinical trials.All documentation must be known by the users and the various participants (Agence, 1997).Dispensing is an important time for the drug specialist to better inform the patient about their treatment.Compliance with procedures ensures that the right medicine is given to the right patient at the right time.Analysis of the responses on good dispensing practice showed that the risk of error was between 24.4 and 40% during prescription validation and between 23 and 43.4% during the provision of experimental drugs to patients at the time of advice and pharmacovigilance.Dispensing a medicine to a patient involves: Reviewing the prescription, collecting, counting and packaging the medicine, and dispensing it to the patient.The dispenser must explain to the patient precisely and clearly how to take the medicine.This is crucial.Medicines are only effective if they are taken correctly (Flaubert, 2005).Authors assessing the knowledge and practices of hospital practitioners have found the same pattern (Mohamed et al., 2013).In contrast, a study in an Asian school setting showed that pharmacy students had basic knowledge of clinical research (Natsuko et al., 2017).The lack of standard operating procedures for dispensing and managing investigational medicinal products in accordance with the rules of good clinical practice and the lack of experience with clinical studies could explain the respondents' level of knowledge (Ministère de la santé et des solidarités, 2006).Written procedures are a requirement for quality and performance testing according to ICH E6 (R1) (International council for harmonisation of technical requirements for pharmaceuticals for human use, 2016).

Conclusion
At clinical research site all persons involved in the implementation of any aspect of a clinical research study must be appropriately qualified to perform their tasks in accordance with good clinical practice of ICH requirements.The various hospital pharmacies surveyed meet this requirement but the knowledge and practice experience of staff is relatively low.The drafting of procedures and guides, as a support for good practice, is necessary to improve the management and dispensing of experimental medicines.Ongoing training of staff in addition to training appropriate to their field is necessary before receiving protocol-specific training on the activities related to each study.These actions will form a good basis in the process of creating a clinical research unit in our hospitals.

IV. Quality Assurance in the Hospital
manual for the pharmacy A18 Procedure of procedures A19 Procedure for dispensing clinical trial medicines to outpatients A20 Receipt procedure for clinical trials batches A21 Batch manufacturing procedure for clinical trials A22 Procedure for destruction of clinical trial batches A23 Procedure for raising the ambient temperature of batches for clinical trials A24 Storage procedure at 2 to 8°CA25Procedure to be followed in the event of a temperature excursion in the storage of clinical trial batches A26 Procedure for recording non-conformities A27 Monitoring follow-up procedure A28 Procedure for conducting the annual review of clinical trials A30 Procedure for the training of interns

Table 1 .
Socio-professional characteristics of the agents surveyed.

Table 2 .
Level of experience and field of clinical trials (n=30 respondents).
Source: Study data anonymously according to a code assigned to each.

Table 3 .
Assessment of staff's knowledge of the pharmaceutical dossier.

Table 4 .
List of clinical trial management procedures.