Quality assessment of individual case safety reports in pharmacovigilance in Burkina Faso

. Pharmacovigilance is based on individual case safety reports. Our study is intended to be a contribution to good practices by the quality assessment of individual case safety reports sent to the National Center for Vigilance in Burkina Faso. We carried out a cross-sectional study which concerned individual case safety reports sent to the Center between 2009 and 2014. 302 individual case safety reports forms were identified and the rate of notifications per year and per million inhabitants was 2,9. The sex ratio was 0,83 in favor of women and the average age was 14,3. 320 drugs were listed with a predominance of antimalarials (37.8%) and antibiotics (19%). Adverse reactions were mostly cutaneous-allergic (37.9%) and general (25.2%). More than half of individual case safety reports were sent by pharmacists (58.6%) followed by nurses (29.5%) then doctors (6.6%). An analysis of the quality of the files according to WHO criteria gave 25.8% for grade A, 67.2% for grade B and 7% for grade C. The files were transmitted within 15 days in 54% cases. The description of the adverse drug reactions was in accordance with WHO ART terminology in 93.5%. Underreporting is a reality and special attention should be paid to collecting information on adverse drug events.


Introduction
The drug is an active substance capable of causing a modification of the biological activity resulting in the therapeutic effect which is a beneficial and desired effect. Along with this desired therapeutic effect, the drug is likely to cause adverse events [1]. Pharmacovigilance is the activity of monitoring, recording and evaluating as early as possible the adverse effects of drugs based on notifications from healthcare professionals but also from patients [2]. Its operation is based on the individual case safety reports of adverse events that may be caused by drugs. It is essential for spotting new or rare side effects: it is often said to be the cornerstone of pharmacovigilance [3]. Adverse drug reactions are estimated to be a significant cause of death in some countries, ranking between 4th and 6th place. The percentage of hospitalizations due to these reactions varies between 10 and 20%. This phenomenon has serious economic repercussions on health care services, and some countries devote as much as 15 to 20% of their health budget to drug-related problems [4]. The quality is an important characteristic of the notifications collected, the pharmacovigilance system developed must allow the acquisition of sufficient information for the scientific evaluation of the notifications [5]. To date, no study on the quality of individual case safety reports has been carried out in Burkina Faso. The present study aims to assess the quality of individual case safety reports in order to improve the quality of the filling in of notification forms for adverse drug events by professionals in Burkina Faso.

Study framework
We carried out the study at the National Center of Vigilance and Health Products (NCVPH). It covered all of the individual case reports sent to the center between 2009 and 2014. Type and period of study Our study is a retrospective descriptive study. The study concerned the pharmacovigilance sheets sent to the NCVHP from 2009 to 2014. The period of January 2015 enabled us to collect data within the NCVPH. Data collection and processing procedure The technique of data collection was to use the information available. Our data consisted of data from the notification forms completed by health professionals and sent to the NCVHP from 2009 to 2014. An exhaustive sampling of all notifications meeting the inclusion criteria was carried out, for a total of 302 files.
Inclusion criteria: all spontaneous notification forms sent to the NCVHP from 2009 to 2014 have been included.
Non-inclusion criteria: notification forms from active surveillance, clinical trials, etc. have not been included.

Ethics and deontology
A request for authorization to access and use data from the pharmacovigilance database has been sent to the NCVHP. The pharmacovigilance sheets were analyzed with respect for their confidentiality and anonymity. They have been reclassified in the archives of the NCVHP.

Results
We identified 302 individual case safety reports sent to the NCVHP between 2009 and 2014, the notification rate was 2.9. The average age of our patients was 14.3 years with extremes of. Patients aged 16 to 60 were the most affected by the side effects. The sex ratio was 0.83 in favor of women ( Figure 1, Figure 2). The number of drugs or drug combinations that caused an adverse event was 320 (Table I). In total, the drugs frequently implicated were antimalarials (37.8%), antibiotics (19%), ARVs (10.6%), analgesics-antipyretics (6.6%). Of the 302 notifications 325 symptoms were detected. Their distribution is shown in Table II. The most common adverse effects were cutaneousallergic (37.9%), systemic (25.2%), gastrointestinal (14.5%), hepatic (5.2%) and renal (4) effects. , 6%). More than half of the notifications were reported by pharmacists (177/302 or 58.6%) followed by nurses (29,5%), doctors (6,6%) and others practitioners. Individual case safety reports were sent less than 15 calendar days after notification in 54% of cases. The quality of the files is presented in Table III.   . In order to improve notification and data collection mechanisms, the notification of adverse events after marketing authorisation can be encouraged by involving all stakeholders (healthcare professionals, patients). Health authorities should undertake to promote the teaching of pharmacovigilance in the professional training of students in the health professions [11]. Also, field surveys can be carried out with professionals to determine the degree of influence of factors in underreporting.

Characteristics of individual case safety reports Patients
The most affected age groups in our study were represented by patients aged 16 to 60 years. The sex ratio was 0.83 in favor of the female sex. The pharmacovigilance report of the Morocco anti-poison and pharmacovigilance center (MAPC) in 2005 also showed that patients aged 16 to 60 were the most affected by adverse drug reactions [12]. The sex ratio was 0.28 in favor of the female sex. This can be explained by the special attention given to the care of children and the elderly. This could limit the risk of side effects occurring during treatment.

Drugs
The most incriminated drug classes were antimalarials (37.8%), antibiotics (19%), ARVs (10.6%), analgesics-antipyretics (6.6%). This can be explained by the frequency of conditions for which these drugs are indicated. Malaria is the first reason for consultation in Burkina [6]. These patients are more exposed to drugs and therefore likely to manifest adverse reactions. We have different results in the literature probably related to the study setting. Soukho-kaya and col in 2006 in Mali had found that anti-diabetics were responsible for adverse effects in 48.6% and anti-tuberculosis drugs in 21.3%. Indeed, it was carried out in an internal medicine department which mainly deals with metabolic and endocrine diseases [13]. In the CAPM report, oral contraceptives are the most incriminated (37.5%) followed by non-steroidal anti-inflammatory drugs (13%) and antibiotics (11%). Antiparasitics have a low rate (1%) [12]. In the study of Keita KB. in Mali in 2012, ARVs were the most notified with a rate of 56.3%. They were followed by antibiotics with 31.3% then nonsteroidal anti-inflammatory drugs 18.8%. There were no antimalarials [14]. This study was carried out within the National Center for Support against Disease and concerned the leprology / animal services, the support and counseling unit and the dermatology service. Drug eruptions are the most frequently encountered side effects and the drugs responsible are mostly ARVs. There are no and digestive (29.8%) effects. The CAPM report in 2005 also showed that the majority of the effects were cutaneous (27%), gastrointestinal (18%) and neurological 16.5%). One of the limitations of premarketing studies is the fact that they cannot detect all of the adverse effects of a drug in terms of their frequency and nature [17]. Indeed, during laboratory tests, certain effects may escape the experimenter given the constitution, physiology but also the difficulty of qualifying or apprehending the effect in animals. An effective and permanent integration of pharmacovigilance in the diagnosis and treatment of pathologies is desirable. It could contribute to the prevention of adverse effects, especially avoidable, and to better safety in the use of medicines.

Notifiers
Pharmacists reported more individual case safety reports with a rate of 58.6%. This is due to the fact that in the profile of notifiers, in particular general practitioners and general pharmacists, we have included interns in medicine or pharmacy. The improvement in quality is explained by an increasingly effective knowledge of individual case reports through periodic training of health professionals. These trainings show participants the need to report adverse drug reactions detected in daily practice. The solutions to further improve the quality of notifications are the same for undernotification. Indeed, improving the notification rate implies an incentive for quality notifications.

Conformity of the description of adverse effetcs to WHO-ART terminology
The description of the adverse drug reactions was consistent in 93.54% of the effects described, i.e. the terms used in the description of the adverse reaction correspond to the terms adopted by WHOART. The non-compliant cases were mainly related to the absence of the adverse event described.

Conclusion
Pharmacovigilance in Burkina Faso is essentially based on the individual case safety reports of suspected adverse reactions by health professionals to pharmacovigilance structures. This study consisted in the quality assessement of the information collected through the pharmacovigilance sheets. Adverse effects were mainly cutaneous-allergic (37.9%), general (25.2%), gastrointestinal (14.5%). The drugs in question belong to the classes of antimalarials (37.8%), antibiotics (19%) and ARVs (10.6%). Pharmacists made the most notifications with 58.6% followed by nurses (29.5%). The majority of inividual case reports were of good quality and the percentage of notifications from pharmacists was the highest. This study can contribute to the feedback of information to health