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Assessment of the state of pharmacovigilance in the South-South zone of Nigeria using WHO pharmacovigilance indicators

Assessment of the state of pharmacovigilance in the South-South zone of Nigeria using WHO... Background: WHO pharmacovigilance indicators have been recommended as a useful tool towards improving pharmacovigilance activities. Nigeria with a myriad of medicines related issues is encouraging the growth of pharmacovigilance at peripheral centres. This study evaluated the status of pharmacovigilance in tertiary hospitals in the South-South zone of Nigeria with a view towards improving the pharmacovigilance system in the zone. Methods: A cross-sectional descriptive survey was conducted in six randomly selected tertiary hospitals in the South-South zone of the country. The data was collected using the WHO core pharmacovigilance indicators. The language of assessment was phrased and adapted in this study for use in a tertiary hospital setting. Data is presented quantitatively and qualitatively. Results: A total of six hospitals were visited and all institutions had a pharmacovigilance centre, only three could however be described as functional or partially functional. Only one centre had a financial provision for pharmacovigilance activities. Of note was the absence of the national adverse drug reaction reporting form in one of the hospitals. The number of adverse drug reaction reports found in the databases of the centres ranged from none to 26 for the previous year and only one centre had fully committed their reports to the National Pharmacovigilance Centre. There were few documented medicines related admissions ranging from 0.0985/1000 to 1.67/1000 and poor documentation of pharmacovigilance activities characterised all centres. Conclusion: This study has shown an urgent need to strengthen the pharmacovigilance systems in the South- South zone of Nigeria. Improvement in medical record documentation as well as increased institutionalization of pharmacovigilance may be the first steps to improve pharmacovigilance activities in the tertiary hospitals. Keywords: Pharmacovigilance, Adverse drug reaction reporting, Nigeria, Tertiary hospitals Background sensitisation campaigns using print and electronic media Pharmacovigilance in Nigeria commenced in the late 80s about medicine safety issues to health care workers and and early 90s initially in a tertiary hospital with some the public [3]. It has also carried out active surveillance preparatory activities at the national level prior to its through the cohort event monitoring on adverse reac- admission into the WHO program for international drug tions to antimalarials (artemisinin-based combination monitoring (PIDM) in 2004 [1, 2]. It has sustained its therapy) [4]. There has also been the introduction of activities through active training of healthcare workers, electronic devices to reduce substandard and falsified medical products which is a major contributor to ad- * Correspondence: [email protected] verse drug reactions in our setting. Department of Clinical Pharmacology and Therapeutics, University of Benin, The growth of pharmacovigilance in Nigeria has been Benin-City, Edo State, Nigeria propelled by a number of factors including the establish- Department of Medicine, University of Benin Teaching Hospital, Benin-City, Nigeria ment of the regulatory agency (National Agency for Food Full list of author information is available at the end of the article © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Opadeyi et al. BMC Pharmacology and Toxicology (2018) 19:27 Page 2 of 8 and Drug Administration and Control – NAFDAC) by Currently, the assessment of pharmacovigilance had Decree 15 of 1993 (as amended) now cited as Act Cap N1 been largely done at the national level using various laws of the Federal Republic of Nigeria 2004, the formula- tools including evaluating the attainment of minimum tion of the Nigerian National Drug Policy in 2005 [5]. This requirements for a national centre with interviews of was further clarified by the introduction of the Niger- focal persons [27], and recently the use of the Indicator ian pharmacovigilance policy document in 2012 firmly based Pharmacovigilance Assessment Tool (IPAT) indi- positing drug safety in national discussion [6]. The cators [28]. The more recent introduction of the WHO actualization of some of these goals has recorded pharmacovigilance indicators provides an opportunity significant progress with the formation of the zonal to assess pharmacovigilance activities at the national centres to cover the six geo-political zones in the centres [29]. These indicators targeted at the national country in 2012 [7]. centres perform self-evaluation and also identify areas Pharmacovigilance has a wide scope with increasing that require intervention. This approach may be ap- product concerns. The main focus in the Nigeria context plicable to zonal centres and its components which has been on adverse drug reactions, substandard and feed data to the national centres. It may also be most falsified medical products [3, 8–10]. Other areas yet to appropriate to identify problems at sub-national levels be fully addressed include medication errors [11], lack requiring attention [30]. of effectiveness reports, acute and chronic poisoning The status of the pharmacovigilance system in the [12, 13], assessing drug related mortality as well as tertiary centres is presently unknown as the WHO indi- abuse and misuse of medicines [3, 9]. The determin- cators and related metrics for evaluating these centres ation of the burden of these various problems has have just been recently released [29] and there is little or been poor as the major challenge to the growth of no data on the effectiveness and functionality of these pharmacovigilance in Nigeria has been that of under- centres at this time. Furthermore, the involvement of reporting as seen worldwide [14–16]. these centres in this self-appraisal will further facilitate Reporting of drug safety concerns by health-workers in their participation in measures to remedy identified Nigeria is voluntary and the reasons for under-reporting deficiencies with a view towards improving the quantity are partly due to fear of litigation, poor understanding of and quality of adverse drug reaction reports and other the subject matter, feeling that the “known” Adverse Drug areas in pharmacovigilance. This study intends to assess Reactions (ADRs) need not be reported, time constraints the status of pharmacovigilance structure, processes, and cumbersome reporting processes [17–21]. Lack of outcomes and impact in the South–South zone of Nigeria appropriate structures and deficient processes at the insti- using the newly introduced WHO pharmacovigilance tutional level may also contribute to the poor reporting indicators. rate as found in some studies [17, 21–23]. WHO advocates regional centres as an effective way of Methods enhancing pharmacovigilance activities [24] as observed Study setting and design in some areas of the world where this has been found to This study was carried out in the South-South Zone of improve the number and quality of reports [25, 26]. Nigeria which is located in the coastal region of Nigeria. The aims of the creation of the zonal centres was to It comprises six states namely Akwa-Ibom, Bayelsa, decentralize the activities of the National Pharmacovigi- Cross Rivers, Delta, Edo and Rivers with a population of lance Centre (NPC), e.g. distribution of ADR forms and 21,014, 655 million persons (Nigeria national census collection of the Individual Case Safety Reports (ICSRs) 2006). Health care professionals in all tiers of hospitals from reporters and perform preliminary evaluation with in this zone could send their reports either directly or prompt reporting, also transmission of acknowledge- through the zonal pharmacovigilance centre for onward ments and feedback information to the reporters and transmission to the national centre. The South-South zonal dissemination of information from the national centre pharmacovigilance centre is domiciled in the University of to the patients and health care workers. Furthermore, Benin Teaching Hospital, a tertiary hospital for research they were created to monitor the progress of pharma- and learning. covigilance activities at institutional levels as well as In Nigeria, heath care is delivered at three levels: support the training and capacity building for pharma- primary, secondary and tertiary. Tertiary care hospitals covigilance in the areas of their jurisdiction [6]. These provide the highest level of care and serve as referral cen- measures would further increase awareness about phar- tres for the secondary and primary centres. Furthermore, macovigilance and instil a sense of ownership among there are three main types of tertiary centres. Firstly: the the stakeholders regarding pharmacovigilance activities teaching hospitals, which provide teaching (to most cadres as well as bring closer to the reporters a centre close to in the health professions at undergraduate and postgradu- their practice. ate levels for medical, nursing, pharmacy students etc.) as Opadeyi et al. BMC Pharmacology and Toxicology (2018) 19:27 Page 3 of 8 well as for research and health care services. Secondly: The background information collected characteristics Federal Medical Centres which are mainly for health care of the hospitals: teaching hospital staff strength, i.e. services as well as providing residency training in some number of post registration health professionals in departments and lastly the specialty hospitals which different categories: doctors, nurses, pharmacists, spe- focuses on particular disease entities of public health im- cialist disposition, average out-patient attendance over portance such as neuro-psychiatric hospitals, orthopaedic the last year, total number of beds in the hospital. hospitals and ophthalmic hospitals among others. The structural indicators assessed the existence of key This study was directed at the teaching hospitals be- pharmacovigilance structures, systems and mechanisms cause they provide the widest access to all patients with in any of the settings studies. It details the basic infra- an inclusiveness of all cadres of health care workers. In structure needed to enable good pharmacovigilance the South-South zone there are eight teaching hospitals, activities. It assesses the enabling environment needed seven are government owned, and one privately owned. for pharmacovigilance activities. Eligibility criteria: teaching hospitals were used to en- The process indicators assessed the degree of pharma- sure inclusiveness of all clinical disciplines and staff covigilance activities in the various centres. It focussed complement. All six states in the zone were represented on the processes that describe the collection, collation, by a teaching hospital. An institutional approval was re- analysis and evaluation of ADR reports. The factors quired from the Chief Medical Director / Management influencing these processes were also considered. These prior to inclusion in the study. The study was subse- measures were assessed directly or indirectly. quently carried out in 6 tertiary health institutions The outcome/impact indicators measure the extent of selected through simple random sampling in the various realization of the pharmacovigilance objectives. The hos- states namely: pital records used in assessing the outcome/impact indi- cators include admission and discharge registers, death – University of Benin Teaching Hospital Benin-City, registers, International coding of disease registers where Edo State, (UBTH). available. Other requested details were: the total number – Delta State University Teaching Hospital Oghara, of outpatient visits in the previous year, the morbidity Delta State, (DELSUTH). and mortality statistics of each institution for the previ- – Niger Delta University Teaching Hospital Okolobri, ous year (to include the disease statistics of admitted Bayelsa State, (NDUTH). and deceased persons). Furthermore, to compute the – University of Port Harcourt Teaching Hospital, Port duration of hospital stay, the crude estimates of the Harcourt, Rivers State, (UPTH). duration of admission of patients with serious adverse – University of Uyo Teaching Hospital, Uyo, Akwa- reactions who were hospitalised was calculated from Ibom State, (UUTH). the adverse drug reaction reports obtained for the – University of Calabar Teaching Hospital, Calabar previous year. Cross-River State, (UCTH). Data analysis Prior to visiting the study sites for data collection, eth- Analysis was both qualitative and quantitative. All hospi- ical approval was obtained from the research and ethics tals participating in the study were described according committee of each of the selected tertiary hospitals. to each indicator. The core Structural indicators are Furthermore, the heads of the institution were contacted qualitative indicators with categorical data analysed de- for approval and access to the pertinent data. The focal scriptively. The presence or absence of the parameter persons in charge of pharmacovigilance in the institution measured was described for each institution. provided answers for the indicator assessments. Analysis of the core Process and Outcome Indicators are quantitative indicators reflecting rates of reports and actual numbers. They were calculated using frequencies Data collection and absolute numbers as dictated by the indicator. The The data were obtained using a modified WHO data data was analysed with descriptive statistics using Micro- collection form for pharmacovigilance indicators [29]by soft excel 2007. one of the researchers through interviews of the focal person for pharmacovigilance or the pharmacovigilance Results committee. The components of this form included the All six institutions were visited and the focal Pharma- background information, structural indicators, process covigilance persons or committees interviewed following indicators, outcome/impact indicators. The phrasing of a meeting with the various heads of the institutions. The the assessment questions was adapted to address the teaching hospitals in this study are all government tertiary hospital setting (Additional file 1). owned and serve as referral centres to the primary and Opadeyi et al. BMC Pharmacology and Toxicology (2018) 19:27 Page 4 of 8 secondary tier hospitals. However, they are of varying Core outcome/impact indicators sizes in terms of bed and staff complement. The demo- Unusual reports regarding the development of frequent graphic characteristics of the institutions at the com- micturition following use of amlodipine besylate was ob- mencement of the study late January to mid-March 2016 served in one of the centers and is being evaluated were as follows (Table 1). (Table 4). The number of medicine-related hospital ad- missions per 1000 admissions ranged from 0.00958/1000 to 1.67/1000 and there were no documentations of Core structural indicators medicine related deaths in the death registers in the Responses were obtained from the interviewed personnel various hospitals. The documentation of pertinent data for the assessment questions of the 10 structural indica- was inadequate, rendering calculation of other outcome/ tors for all the institutions studied. Three of the 6 insti- impact pharmacovigilance indicators in the institutions tutions had a standardised functional accommodation difficult (Table 4). for pharmacovigilance activities while 1 had non func- tional rooms and 2 had none. Only one hospital had Discussion regular financial provisions for pharmacovigilance. The This is the first published study evaluating the practice of secretariat in 4 centres had a full time staff to carry out pharmacovigilance in tertiary hospitals of the South-South pharmacovigilance activity while 2 had part time staff. zone of Nigeria using the WHO indicators. The study has Of note was the availability of an institutionalized ADR highlighted the strengths and weaknesses of the pharma- reporting form in one of the six centres (DELSUTH) covigilance sub-healthcare system in general. while a centre neither had copies of the national nor The study revealed that structures were gradually be- local forms available. There were no standard forms ing put in place and there was a general acceptance of available which addressed the subset of assessment ques- the need for pharmacovigilance in all the institutions tions covering the scope of pharmacovigilance in all of visited despite institutional challenges. The availability of the centers (Table 2). the newly developed Nigerian national pharmacovigi- lance policy in some of the centers is a testament to the Core process indicators will of the Nigerian government to institutionalize pa- The absolute number of ADR reports received among tient safety through good pharmacovigilance practice. the 6 hospitals in the previous year ranged from 0 to 26, It was observed that the UBTH performed better than two hospitals had no reports for the previous year 2015. the other hospitals within the zone, this was ascribed to Furthermore, the total number of reports in the local the activities of the pharmacovigilance team and system database ranged from 0 to 831. Cohort event monitoring that started off in the early 90s [2] and has been largely of antimalarials (artemisinin-based combination therapy) sustained by the commitment of the pharmacovigilance was carried out and completed in UBTH in the five committee, staff and management. It was also observed years preceding the analysis as a form of active surveil- that despite DELSUTH and NDUTH being relatively lance. There were limited numbers of reports on ADRs, smaller hospitals in terms of bed complement, they still medication errors, lack of therapeutic effectiveness etc. performed better than some larger hospitals. This suggests in most of the centers. Documentation of feedback and that interest of the key stakeholders in the pharmacovigi- causality assessment carried out on reports in the lance program is needed to sustain the development of centers was equally poor in this study (Table 3). the pharmacovigilance system. Table 1 Characteristics of the tertiary teaching hospitals in the South-South Zone Characteristic UCTH UUTH UPTH NDUTH DELSUTH UBTH Number of beds 610 499 782 148 250 701 Approximate number of health care workers (post registration) 1141 739 1028 253 532 1219 Consultant Clinicians 146 86 179 85 65 200 Doctors 359 124 210 53 150 335 Nurses 580 417 600 105 300 660 Pharmacists 56 19 39 10 17 24 Out-patient attendance in the previous year (2015) 81,624 114,523 114,277 32,906 22,540 179,255 Number of in-patient hospital admissions (2015) 7171 9679 10,145 2548 No data 11,324 UBTH University of Benin Teaching Hospital Benin-City, Edo State, UCTH University of Calabar Teaching Hospital, Calabar Cross-River State. UPTH University of Port Harcourt Teaching Hospital, Port Harcourt, Rivers State, UUTH University of Uyo Teaching Hospital, Uyo, Akwa- Ibom State. DELSUTH Delta State University Teaching Hospital Oghara, Delta State, NDUTH Niger Delta University Teaching Hospital Okolobri, Bayelsa State Opadeyi et al. BMC Pharmacology and Toxicology (2018) 19:27 Page 5 of 8 Table 2 Analysis of WHO Core Pharmacovigilance Structural Indicators of the six tertiary hospitals in the South-South zone of Nigeria Indicator Item Assessment UCTH UUTH UPTH NDUTH DELSUTH UBTH Hospitals with positive answers (n) CST1 Presence of pharmacovigilance centre/department / Yes No No No Yes Yes 3 unit with a standard accommodation. CST2 Availability of a copy of the Nigerian pharmacovigilance Yes No No Yes Yes Yes 4 policy CST3 Presence of Institutional Drug Therapeutic Committee Yes No No Yes Yes Yes 4 CST4 Availability of regular financial provision for the No No No No No Yes 1 pharmacovigilance Centre. CST5 Availability of human resources to carry out functions Yes Yes Yes Yes Yes Yes 6 of Pharmacovigilance Centre. CST6 Availability of standard ADR reporting form in the Yes Yes No Yes Yes Yes 5 institution. CP6a-e: Availability of relevant fields in standard ADR No No No No No No 0 reporting form for a) medication error, b) counterfeit/ substandard medicines, c) therapeutic ineffectiveness, d) suspected misuse, abuse, dependence on medicines, e) general public. CST7 A process is in place for collection, recording and analysis Yes No No No Yes Yes 3 of ADR reports CST8 Incorporation of pharmacovigilance into the orientation No No No No No Yes 1 programme curriculum of newly employed health care professionals CST8a: for Medical doctors No No No No No Yes 1 CST8b: for Dentists No No No No No Yes 1 CST8c: for Pharmacists Yes No No Yes No Yes 2 CST8d: for Nurses/Midwives; No No No No No No 0 CST9 Existence of a newsletter/information bulletin/website No No No No No Yes 1 as a tool for Pharmacovigilance information dissemination CST10 Existence of pharmacovigilance advisory committee or Yes No No Yes Yes Yes 4 an expert committee in the setting capable of providing advice on medicine safety. The items in CST6a-e were all considered separately and the answer was found to be No for each item. UBTH University of Benin Teaching Hospital Benin-City, Edo State; UCTH University of Calabar Teaching Hospital, Calabar Cross-River State; UPTH University of Port Harcourt Teaching Hospital, Port Harcourt, Rivers State; UUTH University of Uyo Teaching Hospital, Uyo, Akwa- Ibom State; DELSUTH Delta State University Teaching Hospital Oghara, Delta State; NDUTH Niger Delta University Teaching Hospital Okolobri, Bayelsa State; ADR Adverse Drug Reaction; WHO World Health Organization Interestingly, one of the centers (DELSUTH) modified reports. It is important to fund pharmacovigilance as the ADR form showing their own hospital logo and development of active pharmacovigilance programs, domiciling the ADR form to their setting. This showed provision of training, feedback, information dissemin- the willingness of the centre to improve patient safety ation and maintenance of the centers are useful tools in through a sense of ownership. The inclusion of health pharmacovigilance that require adequate finances [32]. facilities in the Nigerian national pharmacovigilance pol- Capacity development is required for the growth of icy was to increase their participation in the pharmacov- pharmacovigilance as shown in the review of three igilance activities [6]. The study revealed poor budgeting countries where insufficient manpower contributed to for pharmacovigilance as only a center (UBTH) had poor development of pharmacovigilance [27]. financial provision for pharmacovigilance. This was dis- The processes and outcomes were however poor in all tinct from the finding in Rwanda using the Indicator the facilities probably due to lack of awareness of meas- based pharmacovigilance assessment tool (IPAT) where uring indices to monitor and evaluate pharmacovigi- the hospitals studied had budgetary allocation for phar- lance. Again, the pharmacovigilance system in this macovigilance [31]. The availability of relevant staff and setting is still in their infancy and the requisite culture committees are paramount to the development of phar- to ensure effective operations yet to be established. macovigilance and the hospitals with developed com- However, it was noted that a cohort event monitoring of mittees and personnel disposition had slightly better antimalarials (artemisinin-based combination therapy) Opadeyi et al. BMC Pharmacology and Toxicology (2018) 19:27 Page 6 of 8 Table 3 Analysis of WHO Core Pharmacovigilance Process Indicators of the six tertiary hospitals in the South-South zone of Nigeria Indicator Item Assessment questions UCTH UUTH UPTH NDUTH DELSUTH UBTH CP1 Total number of ADR reports received in the previous year 16 0 0 1 9 26 CP2 Reports (current total number) in the local database 41 1 0 12 12 831 CP3 Percentage of total annual reports acknowledged/issued feedback 0 0 0 0 0 0 CP4 Percentage of total reports subjected to causality assessment in 0 0 0 0 0 84.6 the previous year. CP5 Percentage of total annual reports satisfactorily completed 18.8 0 0 0 77.8 84.6 and submitted to the local Pharmacovigilance Centre in the previous year. CP5a Percentage of reports committed to National Pharmacovigilance 0 0 0 0 0 100 Centre database from the local Pharmacovigilance centre CP6 Percentage of reports of therapeutic ineffectiveness received i 00 0 0 0 0 n the previous year CP7 Percentage of reports on medication errors reported in the 0 0 0 0 0 7.7 previous year CP8 Percentage of registered pharmaceutical industries having Only applicable at the level of National Pharmacovigilance Centre a functional Pharmacovigilance system? Not applicable in this study. CP9 Number of active surveillance activities initiated, ongoing 00 0 0 0 1 or completed in the last five years UBTH University of Benin Teaching Hospital Benin-City, Edo State; UCTH University of Calabar Teaching Hospital, Calabar Cross-River State; UPTH University of Port Harcourt Teaching Hospital, Port Harcourt, Rivers State; UUTH University of Uyo Teaching Hospital, Uyo, Akwa- Ibom State; DELSUTH Delta State University Teaching Hospital Oghara, Delta State; NDUTH Niger Delta University Teaching Hospital Okolobri, Bayelsa State; ADR Adverse Drug Reaction; WHO World Health Organization was conducted in UBTH as a part of a national pro- minimum requirements for a functional pharmacovigi- gram. This active surveillance of medicines used in a lance system by Maigetter et al. [27] which suggested a disease of public health importance is useful in more efficient and systematic monitoring for pharma- obtaining better insights into the safety and toler- covigilance system. An awareness of regular pharma- ability pattern in our setting [4]. The need for the covigilance evaluations with pharmacovigilance indicators indicators could also be seen in a review of three national would translate to better pharmacovigilance processes and centers India, Uganda and South Africa using the WHO outcomes. Table 4 Analysis of WHO Core Outcome Pharmacovigilance Indicators in six tertiary hospitals in South-South zone of Nigeria Indicator Item Assessment questions UCTH UUTH UPTH NDUTH DELSUTH UBTH CO1 Number of signals generated in the 000001 last 5 years CO2 Number of regulatory notifications 000000 issued in the last year CO3 Number of medicine-related hospital 1.67 1.65 0.0985 0.3924 No data 0.97 admissions per 1000 admissions CO4 Number of medicine-related deaths Inadequate Inadequate Inadequate Inadequate Inadequate Inadequate per 1000 persons served by the data data data data data data hospital per year CO5 Number of medicine-related deaths Only applicable at the level of National Pharmacovigilance Centre per 100,000 persons in the population CO6 Average cost (US$) of treatment Inadequate Inadequate Inadequate Inadequate Inadequate Inadequate of medicine-related illness data data data data data data CO7 Average duration (Days) of medicine- Inadequate Inadequate Inadequate Inadequate Inadequate 5.86 days related extension of hospital stay data data data data data CO8 Average cost (US$) of medicine- Inadequate Inadequate Inadequate Inadequate Inadequate Inadequate related hospitalization. data data data data data data a b Calculated according to data from Table 1, Frequent micturition following use of amlodipine besylate is being evaluated in the centre UBTH University of Benin Teaching Hospital Benin-City, Edo State; UCTH University of Calabar Teaching Hospital, Calabar Cross-River State, UPTH University of Port Harcourt Teaching Hospital, Port Harcourt, Rivers State; UUTH University of Uyo Teaching Hospital, Uyo, Akwa- Ibom State; DELSUTH Delta State University Teaching Hospital Oghara, Delta State; NDUTH Niger Delta University Teaching Hospital Okolobri, Bayelsa State; ADR Adverse Drug Reaction Opadeyi et al. BMC Pharmacology and Toxicology (2018) 19:27 Page 7 of 8 The poor record keeping in all the facilities also made Additional file computations of the process and outcomes indicators dif- Additional file 1: Assessment of the state of Pharmacovigilance in the ficult to achieve. The documentation of medicine related South-South Zone of Nigeria using WHO Pharmacovigilance indicators. events especially adverse drug reactions were equally poor WHO Core Pharmacovigilance Indicators including changes made to in this study, this contributed to lack of data even in hos- phrasing of the assessment questions. (PDF 347 kb) pitals where the international coding of diseases was been done. This is not different from what has been reported in Abbreviations ADR: Adverse drug reaction; DELSUTH: Delta State University Teaching other studies about under-recognition of adverse drug Hospital Oghara, Delta State; ICSR: Individual case safety report; reactions and drug related events [33, 34]. It is imperative IPAT: Indicator based Pharmacovigilance Assessment Tool; NAFDAC: National to inculcate a more articulate approach to routine data Agency for Food, Drugs Administration and Control, Nigeria; NDUTH: Niger Delta University Teaching Hospital Okolobri, Bayelsa State; NPC: National gathering and documentation into the healthcare system. Pharmacovigilance Centre; UBTH: University of Benin Teaching Hospital Furthermore, planned prospective data collection pro- Benin-City, Edo State; UCTH: University of Calabar Teaching Hospital, Calabar cesses should be put in place to enable evaluation of the Cross-River State; UPTH: University of Port Harcourt Teaching Hospital, Port Harcourt, Rivers State; UUTH: University of Uyo Teaching Hospital, Uyo, Akwa- outcomes and impact of pharmacovigilance activities. Ibom State; WHO: World Health Organization In the utilization of the WHO pharmacovigilance indi- cators, it is evident that the scope of reportable incidents Acknowledgements by the facilities have been broadened and it is hoped that The authors thank the Chief Medical Directors of the various institutions visited as well as the members of the pharmacovigilance committees, units with the implementation framework of the Nigerian na- and staff of the hospitals. We are also grateful to the Director General of the tional pharmacovigilance policy, there would be a wider National Agency for Food Drugs Administration and Control (NAFDAC) HQ, dissemination of the roles that tertiary hospitals are to play Abuja and the South – South Zonal Staff for their kind assistance in carrying out this work. in the promotion of pharmacovigilance. The WHO phar- macovigilance indicators would be useful in assessing Funding other tertiary hospitals as it would enable the hospital The study was self funded. management develop a strategy towards improving patient Availability of data and materials safety through pharmacovigilance. It may also help iden- The datasets used and/or analysed during the current study are available tify areas that need urgent intervention or modification in from the corresponding author on reasonable request. the health information system management of the tertiary Authors’ contributions hospitals especially since it is recommended that the AOO conceptualised the study, modified the data collection tool, collected indicators be reapplied as needed in the facilities. and analysed data and wrote the initial manuscript. AFR reviewed the protocol, the data collection tool, analysed the data and revised the manuscript. AOI was part of the technical team that drafted the WHO Limitations Pharmacovigilance indicators, conceptualised the study, reviewed the study The WHO indicators have proven to be quite useful in protocol, analysed the data collected and also revised the manuscript. All this assessment. However, absence of trained pharmacov- authors revised and approved the final manuscript. igilance personnel hindered the provision of results for Ethics approval and consent to participate the pharmacovigilance process indicators in the centers. Ethical approval was obtained from the Ethics and research committees of Of note is the limitation of the structural pharmacovigi- all participating institutions: Delta State University Teaching Hospital Oghara: DELSUTH/HREC/2015/024, Niger Delta University Teaching Hospital Okolobri,: lance indicators to fully capture the functionality of the NDUTH/REC/0005/2015, University of Benin Teaching Hospital Benin-City: pharmacovigilance system. Furthermore, the overall poor UBTH:ADM/E22/2/VOL.VII/1245, University of Calabar Teaching Hospital, documentation in all centers limited the derivation of the Calabar: UCTH/HREC/33/360, University of Port Harcourt Teaching Hospital, Port Harcourt: UPTH/ADM/90/S.II/VOL.X/668 and University of Uyo Teaching indicators. Again the derivation of the outcome/impact in- Hospital, Uyo: UUTH/AD/S/96/VOL.XIV/357. The heads of the institutions dicator required in-depth survey which young pharmacov- equally gave approval for participation and access to pertinent publicly igilance systems are unable to execute. There might be a accessible data; including instructions to the person(s) in charge of pharmacovigilance at the various institutions who then gave verbal consent need to develop a scoring system to quantify the indices as approved by the ethics committees. All ethical considerations were duly thus highlighting the deficiencies in numerical terms. observed. Competing interests Conclusion The authors declare that they have no competing interests. This study has shown an urgent need to strengthen the pharmacovigilance systems in the South-South zone of Publisher’sNote Nigeria. The WHO pharmacovigilance indicators have Springer Nature remains neutral with regard to jurisdictional claims in been proven to be helpful in assessing the pharmacovigi- published maps and institutional affiliations. lance system in the zone. Improvement in medical record Author details documentation as well as increased institutionalization of Department of Clinical Pharmacology and Therapeutics, University of Benin, pharmacovigilance may be the first steps to improve 2 Benin-City, Edo State, Nigeria. Department of Medicine, University of Benin pharmacovigilance activities in the tertiary hospitals. Teaching Hospital, Benin-City, Nigeria. Inserm, Bordeaux Population Health Opadeyi et al. 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Assessment of the state of pharmacovigilance in the South-South zone of Nigeria using WHO pharmacovigilance indicators

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Biomedicine; Pharmacology/Toxicology
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Abstract

Background: WHO pharmacovigilance indicators have been recommended as a useful tool towards improving pharmacovigilance activities. Nigeria with a myriad of medicines related issues is encouraging the growth of pharmacovigilance at peripheral centres. This study evaluated the status of pharmacovigilance in tertiary hospitals in the South-South zone of Nigeria with a view towards improving the pharmacovigilance system in the zone. Methods: A cross-sectional descriptive survey was conducted in six randomly selected tertiary hospitals in the South-South zone of the country. The data was collected using the WHO core pharmacovigilance indicators. The language of assessment was phrased and adapted in this study for use in a tertiary hospital setting. Data is presented quantitatively and qualitatively. Results: A total of six hospitals were visited and all institutions had a pharmacovigilance centre, only three could however be described as functional or partially functional. Only one centre had a financial provision for pharmacovigilance activities. Of note was the absence of the national adverse drug reaction reporting form in one of the hospitals. The number of adverse drug reaction reports found in the databases of the centres ranged from none to 26 for the previous year and only one centre had fully committed their reports to the National Pharmacovigilance Centre. There were few documented medicines related admissions ranging from 0.0985/1000 to 1.67/1000 and poor documentation of pharmacovigilance activities characterised all centres. Conclusion: This study has shown an urgent need to strengthen the pharmacovigilance systems in the South- South zone of Nigeria. Improvement in medical record documentation as well as increased institutionalization of pharmacovigilance may be the first steps to improve pharmacovigilance activities in the tertiary hospitals. Keywords: Pharmacovigilance, Adverse drug reaction reporting, Nigeria, Tertiary hospitals Background sensitisation campaigns using print and electronic media Pharmacovigilance in Nigeria commenced in the late 80s about medicine safety issues to health care workers and and early 90s initially in a tertiary hospital with some the public [3]. It has also carried out active surveillance preparatory activities at the national level prior to its through the cohort event monitoring on adverse reac- admission into the WHO program for international drug tions to antimalarials (artemisinin-based combination monitoring (PIDM) in 2004 [1, 2]. It has sustained its therapy) [4]. There has also been the introduction of activities through active training of healthcare workers, electronic devices to reduce substandard and falsified medical products which is a major contributor to ad- * Correspondence: [email protected] verse drug reactions in our setting. Department of Clinical Pharmacology and Therapeutics, University of Benin, The growth of pharmacovigilance in Nigeria has been Benin-City, Edo State, Nigeria propelled by a number of factors including the establish- Department of Medicine, University of Benin Teaching Hospital, Benin-City, Nigeria ment of the regulatory agency (National Agency for Food Full list of author information is available at the end of the article © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Opadeyi et al. BMC Pharmacology and Toxicology (2018) 19:27 Page 2 of 8 and Drug Administration and Control – NAFDAC) by Currently, the assessment of pharmacovigilance had Decree 15 of 1993 (as amended) now cited as Act Cap N1 been largely done at the national level using various laws of the Federal Republic of Nigeria 2004, the formula- tools including evaluating the attainment of minimum tion of the Nigerian National Drug Policy in 2005 [5]. This requirements for a national centre with interviews of was further clarified by the introduction of the Niger- focal persons [27], and recently the use of the Indicator ian pharmacovigilance policy document in 2012 firmly based Pharmacovigilance Assessment Tool (IPAT) indi- positing drug safety in national discussion [6]. The cators [28]. The more recent introduction of the WHO actualization of some of these goals has recorded pharmacovigilance indicators provides an opportunity significant progress with the formation of the zonal to assess pharmacovigilance activities at the national centres to cover the six geo-political zones in the centres [29]. These indicators targeted at the national country in 2012 [7]. centres perform self-evaluation and also identify areas Pharmacovigilance has a wide scope with increasing that require intervention. This approach may be ap- product concerns. The main focus in the Nigeria context plicable to zonal centres and its components which has been on adverse drug reactions, substandard and feed data to the national centres. It may also be most falsified medical products [3, 8–10]. Other areas yet to appropriate to identify problems at sub-national levels be fully addressed include medication errors [11], lack requiring attention [30]. of effectiveness reports, acute and chronic poisoning The status of the pharmacovigilance system in the [12, 13], assessing drug related mortality as well as tertiary centres is presently unknown as the WHO indi- abuse and misuse of medicines [3, 9]. The determin- cators and related metrics for evaluating these centres ation of the burden of these various problems has have just been recently released [29] and there is little or been poor as the major challenge to the growth of no data on the effectiveness and functionality of these pharmacovigilance in Nigeria has been that of under- centres at this time. Furthermore, the involvement of reporting as seen worldwide [14–16]. these centres in this self-appraisal will further facilitate Reporting of drug safety concerns by health-workers in their participation in measures to remedy identified Nigeria is voluntary and the reasons for under-reporting deficiencies with a view towards improving the quantity are partly due to fear of litigation, poor understanding of and quality of adverse drug reaction reports and other the subject matter, feeling that the “known” Adverse Drug areas in pharmacovigilance. This study intends to assess Reactions (ADRs) need not be reported, time constraints the status of pharmacovigilance structure, processes, and cumbersome reporting processes [17–21]. Lack of outcomes and impact in the South–South zone of Nigeria appropriate structures and deficient processes at the insti- using the newly introduced WHO pharmacovigilance tutional level may also contribute to the poor reporting indicators. rate as found in some studies [17, 21–23]. WHO advocates regional centres as an effective way of Methods enhancing pharmacovigilance activities [24] as observed Study setting and design in some areas of the world where this has been found to This study was carried out in the South-South Zone of improve the number and quality of reports [25, 26]. Nigeria which is located in the coastal region of Nigeria. The aims of the creation of the zonal centres was to It comprises six states namely Akwa-Ibom, Bayelsa, decentralize the activities of the National Pharmacovigi- Cross Rivers, Delta, Edo and Rivers with a population of lance Centre (NPC), e.g. distribution of ADR forms and 21,014, 655 million persons (Nigeria national census collection of the Individual Case Safety Reports (ICSRs) 2006). Health care professionals in all tiers of hospitals from reporters and perform preliminary evaluation with in this zone could send their reports either directly or prompt reporting, also transmission of acknowledge- through the zonal pharmacovigilance centre for onward ments and feedback information to the reporters and transmission to the national centre. The South-South zonal dissemination of information from the national centre pharmacovigilance centre is domiciled in the University of to the patients and health care workers. Furthermore, Benin Teaching Hospital, a tertiary hospital for research they were created to monitor the progress of pharma- and learning. covigilance activities at institutional levels as well as In Nigeria, heath care is delivered at three levels: support the training and capacity building for pharma- primary, secondary and tertiary. Tertiary care hospitals covigilance in the areas of their jurisdiction [6]. These provide the highest level of care and serve as referral cen- measures would further increase awareness about phar- tres for the secondary and primary centres. Furthermore, macovigilance and instil a sense of ownership among there are three main types of tertiary centres. Firstly: the the stakeholders regarding pharmacovigilance activities teaching hospitals, which provide teaching (to most cadres as well as bring closer to the reporters a centre close to in the health professions at undergraduate and postgradu- their practice. ate levels for medical, nursing, pharmacy students etc.) as Opadeyi et al. BMC Pharmacology and Toxicology (2018) 19:27 Page 3 of 8 well as for research and health care services. Secondly: The background information collected characteristics Federal Medical Centres which are mainly for health care of the hospitals: teaching hospital staff strength, i.e. services as well as providing residency training in some number of post registration health professionals in departments and lastly the specialty hospitals which different categories: doctors, nurses, pharmacists, spe- focuses on particular disease entities of public health im- cialist disposition, average out-patient attendance over portance such as neuro-psychiatric hospitals, orthopaedic the last year, total number of beds in the hospital. hospitals and ophthalmic hospitals among others. The structural indicators assessed the existence of key This study was directed at the teaching hospitals be- pharmacovigilance structures, systems and mechanisms cause they provide the widest access to all patients with in any of the settings studies. It details the basic infra- an inclusiveness of all cadres of health care workers. In structure needed to enable good pharmacovigilance the South-South zone there are eight teaching hospitals, activities. It assesses the enabling environment needed seven are government owned, and one privately owned. for pharmacovigilance activities. Eligibility criteria: teaching hospitals were used to en- The process indicators assessed the degree of pharma- sure inclusiveness of all clinical disciplines and staff covigilance activities in the various centres. It focussed complement. All six states in the zone were represented on the processes that describe the collection, collation, by a teaching hospital. An institutional approval was re- analysis and evaluation of ADR reports. The factors quired from the Chief Medical Director / Management influencing these processes were also considered. These prior to inclusion in the study. The study was subse- measures were assessed directly or indirectly. quently carried out in 6 tertiary health institutions The outcome/impact indicators measure the extent of selected through simple random sampling in the various realization of the pharmacovigilance objectives. The hos- states namely: pital records used in assessing the outcome/impact indi- cators include admission and discharge registers, death – University of Benin Teaching Hospital Benin-City, registers, International coding of disease registers where Edo State, (UBTH). available. Other requested details were: the total number – Delta State University Teaching Hospital Oghara, of outpatient visits in the previous year, the morbidity Delta State, (DELSUTH). and mortality statistics of each institution for the previ- – Niger Delta University Teaching Hospital Okolobri, ous year (to include the disease statistics of admitted Bayelsa State, (NDUTH). and deceased persons). Furthermore, to compute the – University of Port Harcourt Teaching Hospital, Port duration of hospital stay, the crude estimates of the Harcourt, Rivers State, (UPTH). duration of admission of patients with serious adverse – University of Uyo Teaching Hospital, Uyo, Akwa- reactions who were hospitalised was calculated from Ibom State, (UUTH). the adverse drug reaction reports obtained for the – University of Calabar Teaching Hospital, Calabar previous year. Cross-River State, (UCTH). Data analysis Prior to visiting the study sites for data collection, eth- Analysis was both qualitative and quantitative. All hospi- ical approval was obtained from the research and ethics tals participating in the study were described according committee of each of the selected tertiary hospitals. to each indicator. The core Structural indicators are Furthermore, the heads of the institution were contacted qualitative indicators with categorical data analysed de- for approval and access to the pertinent data. The focal scriptively. The presence or absence of the parameter persons in charge of pharmacovigilance in the institution measured was described for each institution. provided answers for the indicator assessments. Analysis of the core Process and Outcome Indicators are quantitative indicators reflecting rates of reports and actual numbers. They were calculated using frequencies Data collection and absolute numbers as dictated by the indicator. The The data were obtained using a modified WHO data data was analysed with descriptive statistics using Micro- collection form for pharmacovigilance indicators [29]by soft excel 2007. one of the researchers through interviews of the focal person for pharmacovigilance or the pharmacovigilance Results committee. The components of this form included the All six institutions were visited and the focal Pharma- background information, structural indicators, process covigilance persons or committees interviewed following indicators, outcome/impact indicators. The phrasing of a meeting with the various heads of the institutions. The the assessment questions was adapted to address the teaching hospitals in this study are all government tertiary hospital setting (Additional file 1). owned and serve as referral centres to the primary and Opadeyi et al. BMC Pharmacology and Toxicology (2018) 19:27 Page 4 of 8 secondary tier hospitals. However, they are of varying Core outcome/impact indicators sizes in terms of bed and staff complement. The demo- Unusual reports regarding the development of frequent graphic characteristics of the institutions at the com- micturition following use of amlodipine besylate was ob- mencement of the study late January to mid-March 2016 served in one of the centers and is being evaluated were as follows (Table 1). (Table 4). The number of medicine-related hospital ad- missions per 1000 admissions ranged from 0.00958/1000 to 1.67/1000 and there were no documentations of Core structural indicators medicine related deaths in the death registers in the Responses were obtained from the interviewed personnel various hospitals. The documentation of pertinent data for the assessment questions of the 10 structural indica- was inadequate, rendering calculation of other outcome/ tors for all the institutions studied. Three of the 6 insti- impact pharmacovigilance indicators in the institutions tutions had a standardised functional accommodation difficult (Table 4). for pharmacovigilance activities while 1 had non func- tional rooms and 2 had none. Only one hospital had Discussion regular financial provisions for pharmacovigilance. The This is the first published study evaluating the practice of secretariat in 4 centres had a full time staff to carry out pharmacovigilance in tertiary hospitals of the South-South pharmacovigilance activity while 2 had part time staff. zone of Nigeria using the WHO indicators. The study has Of note was the availability of an institutionalized ADR highlighted the strengths and weaknesses of the pharma- reporting form in one of the six centres (DELSUTH) covigilance sub-healthcare system in general. while a centre neither had copies of the national nor The study revealed that structures were gradually be- local forms available. There were no standard forms ing put in place and there was a general acceptance of available which addressed the subset of assessment ques- the need for pharmacovigilance in all the institutions tions covering the scope of pharmacovigilance in all of visited despite institutional challenges. The availability of the centers (Table 2). the newly developed Nigerian national pharmacovigi- lance policy in some of the centers is a testament to the Core process indicators will of the Nigerian government to institutionalize pa- The absolute number of ADR reports received among tient safety through good pharmacovigilance practice. the 6 hospitals in the previous year ranged from 0 to 26, It was observed that the UBTH performed better than two hospitals had no reports for the previous year 2015. the other hospitals within the zone, this was ascribed to Furthermore, the total number of reports in the local the activities of the pharmacovigilance team and system database ranged from 0 to 831. Cohort event monitoring that started off in the early 90s [2] and has been largely of antimalarials (artemisinin-based combination therapy) sustained by the commitment of the pharmacovigilance was carried out and completed in UBTH in the five committee, staff and management. It was also observed years preceding the analysis as a form of active surveil- that despite DELSUTH and NDUTH being relatively lance. There were limited numbers of reports on ADRs, smaller hospitals in terms of bed complement, they still medication errors, lack of therapeutic effectiveness etc. performed better than some larger hospitals. This suggests in most of the centers. Documentation of feedback and that interest of the key stakeholders in the pharmacovigi- causality assessment carried out on reports in the lance program is needed to sustain the development of centers was equally poor in this study (Table 3). the pharmacovigilance system. Table 1 Characteristics of the tertiary teaching hospitals in the South-South Zone Characteristic UCTH UUTH UPTH NDUTH DELSUTH UBTH Number of beds 610 499 782 148 250 701 Approximate number of health care workers (post registration) 1141 739 1028 253 532 1219 Consultant Clinicians 146 86 179 85 65 200 Doctors 359 124 210 53 150 335 Nurses 580 417 600 105 300 660 Pharmacists 56 19 39 10 17 24 Out-patient attendance in the previous year (2015) 81,624 114,523 114,277 32,906 22,540 179,255 Number of in-patient hospital admissions (2015) 7171 9679 10,145 2548 No data 11,324 UBTH University of Benin Teaching Hospital Benin-City, Edo State, UCTH University of Calabar Teaching Hospital, Calabar Cross-River State. UPTH University of Port Harcourt Teaching Hospital, Port Harcourt, Rivers State, UUTH University of Uyo Teaching Hospital, Uyo, Akwa- Ibom State. DELSUTH Delta State University Teaching Hospital Oghara, Delta State, NDUTH Niger Delta University Teaching Hospital Okolobri, Bayelsa State Opadeyi et al. BMC Pharmacology and Toxicology (2018) 19:27 Page 5 of 8 Table 2 Analysis of WHO Core Pharmacovigilance Structural Indicators of the six tertiary hospitals in the South-South zone of Nigeria Indicator Item Assessment UCTH UUTH UPTH NDUTH DELSUTH UBTH Hospitals with positive answers (n) CST1 Presence of pharmacovigilance centre/department / Yes No No No Yes Yes 3 unit with a standard accommodation. CST2 Availability of a copy of the Nigerian pharmacovigilance Yes No No Yes Yes Yes 4 policy CST3 Presence of Institutional Drug Therapeutic Committee Yes No No Yes Yes Yes 4 CST4 Availability of regular financial provision for the No No No No No Yes 1 pharmacovigilance Centre. CST5 Availability of human resources to carry out functions Yes Yes Yes Yes Yes Yes 6 of Pharmacovigilance Centre. CST6 Availability of standard ADR reporting form in the Yes Yes No Yes Yes Yes 5 institution. CP6a-e: Availability of relevant fields in standard ADR No No No No No No 0 reporting form for a) medication error, b) counterfeit/ substandard medicines, c) therapeutic ineffectiveness, d) suspected misuse, abuse, dependence on medicines, e) general public. CST7 A process is in place for collection, recording and analysis Yes No No No Yes Yes 3 of ADR reports CST8 Incorporation of pharmacovigilance into the orientation No No No No No Yes 1 programme curriculum of newly employed health care professionals CST8a: for Medical doctors No No No No No Yes 1 CST8b: for Dentists No No No No No Yes 1 CST8c: for Pharmacists Yes No No Yes No Yes 2 CST8d: for Nurses/Midwives; No No No No No No 0 CST9 Existence of a newsletter/information bulletin/website No No No No No Yes 1 as a tool for Pharmacovigilance information dissemination CST10 Existence of pharmacovigilance advisory committee or Yes No No Yes Yes Yes 4 an expert committee in the setting capable of providing advice on medicine safety. The items in CST6a-e were all considered separately and the answer was found to be No for each item. UBTH University of Benin Teaching Hospital Benin-City, Edo State; UCTH University of Calabar Teaching Hospital, Calabar Cross-River State; UPTH University of Port Harcourt Teaching Hospital, Port Harcourt, Rivers State; UUTH University of Uyo Teaching Hospital, Uyo, Akwa- Ibom State; DELSUTH Delta State University Teaching Hospital Oghara, Delta State; NDUTH Niger Delta University Teaching Hospital Okolobri, Bayelsa State; ADR Adverse Drug Reaction; WHO World Health Organization Interestingly, one of the centers (DELSUTH) modified reports. It is important to fund pharmacovigilance as the ADR form showing their own hospital logo and development of active pharmacovigilance programs, domiciling the ADR form to their setting. This showed provision of training, feedback, information dissemin- the willingness of the centre to improve patient safety ation and maintenance of the centers are useful tools in through a sense of ownership. The inclusion of health pharmacovigilance that require adequate finances [32]. facilities in the Nigerian national pharmacovigilance pol- Capacity development is required for the growth of icy was to increase their participation in the pharmacov- pharmacovigilance as shown in the review of three igilance activities [6]. The study revealed poor budgeting countries where insufficient manpower contributed to for pharmacovigilance as only a center (UBTH) had poor development of pharmacovigilance [27]. financial provision for pharmacovigilance. This was dis- The processes and outcomes were however poor in all tinct from the finding in Rwanda using the Indicator the facilities probably due to lack of awareness of meas- based pharmacovigilance assessment tool (IPAT) where uring indices to monitor and evaluate pharmacovigi- the hospitals studied had budgetary allocation for phar- lance. Again, the pharmacovigilance system in this macovigilance [31]. The availability of relevant staff and setting is still in their infancy and the requisite culture committees are paramount to the development of phar- to ensure effective operations yet to be established. macovigilance and the hospitals with developed com- However, it was noted that a cohort event monitoring of mittees and personnel disposition had slightly better antimalarials (artemisinin-based combination therapy) Opadeyi et al. BMC Pharmacology and Toxicology (2018) 19:27 Page 6 of 8 Table 3 Analysis of WHO Core Pharmacovigilance Process Indicators of the six tertiary hospitals in the South-South zone of Nigeria Indicator Item Assessment questions UCTH UUTH UPTH NDUTH DELSUTH UBTH CP1 Total number of ADR reports received in the previous year 16 0 0 1 9 26 CP2 Reports (current total number) in the local database 41 1 0 12 12 831 CP3 Percentage of total annual reports acknowledged/issued feedback 0 0 0 0 0 0 CP4 Percentage of total reports subjected to causality assessment in 0 0 0 0 0 84.6 the previous year. CP5 Percentage of total annual reports satisfactorily completed 18.8 0 0 0 77.8 84.6 and submitted to the local Pharmacovigilance Centre in the previous year. CP5a Percentage of reports committed to National Pharmacovigilance 0 0 0 0 0 100 Centre database from the local Pharmacovigilance centre CP6 Percentage of reports of therapeutic ineffectiveness received i 00 0 0 0 0 n the previous year CP7 Percentage of reports on medication errors reported in the 0 0 0 0 0 7.7 previous year CP8 Percentage of registered pharmaceutical industries having Only applicable at the level of National Pharmacovigilance Centre a functional Pharmacovigilance system? Not applicable in this study. CP9 Number of active surveillance activities initiated, ongoing 00 0 0 0 1 or completed in the last five years UBTH University of Benin Teaching Hospital Benin-City, Edo State; UCTH University of Calabar Teaching Hospital, Calabar Cross-River State; UPTH University of Port Harcourt Teaching Hospital, Port Harcourt, Rivers State; UUTH University of Uyo Teaching Hospital, Uyo, Akwa- Ibom State; DELSUTH Delta State University Teaching Hospital Oghara, Delta State; NDUTH Niger Delta University Teaching Hospital Okolobri, Bayelsa State; ADR Adverse Drug Reaction; WHO World Health Organization was conducted in UBTH as a part of a national pro- minimum requirements for a functional pharmacovigi- gram. This active surveillance of medicines used in a lance system by Maigetter et al. [27] which suggested a disease of public health importance is useful in more efficient and systematic monitoring for pharma- obtaining better insights into the safety and toler- covigilance system. An awareness of regular pharma- ability pattern in our setting [4]. The need for the covigilance evaluations with pharmacovigilance indicators indicators could also be seen in a review of three national would translate to better pharmacovigilance processes and centers India, Uganda and South Africa using the WHO outcomes. Table 4 Analysis of WHO Core Outcome Pharmacovigilance Indicators in six tertiary hospitals in South-South zone of Nigeria Indicator Item Assessment questions UCTH UUTH UPTH NDUTH DELSUTH UBTH CO1 Number of signals generated in the 000001 last 5 years CO2 Number of regulatory notifications 000000 issued in the last year CO3 Number of medicine-related hospital 1.67 1.65 0.0985 0.3924 No data 0.97 admissions per 1000 admissions CO4 Number of medicine-related deaths Inadequate Inadequate Inadequate Inadequate Inadequate Inadequate per 1000 persons served by the data data data data data data hospital per year CO5 Number of medicine-related deaths Only applicable at the level of National Pharmacovigilance Centre per 100,000 persons in the population CO6 Average cost (US$) of treatment Inadequate Inadequate Inadequate Inadequate Inadequate Inadequate of medicine-related illness data data data data data data CO7 Average duration (Days) of medicine- Inadequate Inadequate Inadequate Inadequate Inadequate 5.86 days related extension of hospital stay data data data data data CO8 Average cost (US$) of medicine- Inadequate Inadequate Inadequate Inadequate Inadequate Inadequate related hospitalization. data data data data data data a b Calculated according to data from Table 1, Frequent micturition following use of amlodipine besylate is being evaluated in the centre UBTH University of Benin Teaching Hospital Benin-City, Edo State; UCTH University of Calabar Teaching Hospital, Calabar Cross-River State, UPTH University of Port Harcourt Teaching Hospital, Port Harcourt, Rivers State; UUTH University of Uyo Teaching Hospital, Uyo, Akwa- Ibom State; DELSUTH Delta State University Teaching Hospital Oghara, Delta State; NDUTH Niger Delta University Teaching Hospital Okolobri, Bayelsa State; ADR Adverse Drug Reaction Opadeyi et al. BMC Pharmacology and Toxicology (2018) 19:27 Page 7 of 8 The poor record keeping in all the facilities also made Additional file computations of the process and outcomes indicators dif- Additional file 1: Assessment of the state of Pharmacovigilance in the ficult to achieve. The documentation of medicine related South-South Zone of Nigeria using WHO Pharmacovigilance indicators. events especially adverse drug reactions were equally poor WHO Core Pharmacovigilance Indicators including changes made to in this study, this contributed to lack of data even in hos- phrasing of the assessment questions. (PDF 347 kb) pitals where the international coding of diseases was been done. This is not different from what has been reported in Abbreviations ADR: Adverse drug reaction; DELSUTH: Delta State University Teaching other studies about under-recognition of adverse drug Hospital Oghara, Delta State; ICSR: Individual case safety report; reactions and drug related events [33, 34]. It is imperative IPAT: Indicator based Pharmacovigilance Assessment Tool; NAFDAC: National to inculcate a more articulate approach to routine data Agency for Food, Drugs Administration and Control, Nigeria; NDUTH: Niger Delta University Teaching Hospital Okolobri, Bayelsa State; NPC: National gathering and documentation into the healthcare system. Pharmacovigilance Centre; UBTH: University of Benin Teaching Hospital Furthermore, planned prospective data collection pro- Benin-City, Edo State; UCTH: University of Calabar Teaching Hospital, Calabar cesses should be put in place to enable evaluation of the Cross-River State; UPTH: University of Port Harcourt Teaching Hospital, Port Harcourt, Rivers State; UUTH: University of Uyo Teaching Hospital, Uyo, Akwa- outcomes and impact of pharmacovigilance activities. Ibom State; WHO: World Health Organization In the utilization of the WHO pharmacovigilance indi- cators, it is evident that the scope of reportable incidents Acknowledgements by the facilities have been broadened and it is hoped that The authors thank the Chief Medical Directors of the various institutions visited as well as the members of the pharmacovigilance committees, units with the implementation framework of the Nigerian na- and staff of the hospitals. We are also grateful to the Director General of the tional pharmacovigilance policy, there would be a wider National Agency for Food Drugs Administration and Control (NAFDAC) HQ, dissemination of the roles that tertiary hospitals are to play Abuja and the South – South Zonal Staff for their kind assistance in carrying out this work. in the promotion of pharmacovigilance. The WHO phar- macovigilance indicators would be useful in assessing Funding other tertiary hospitals as it would enable the hospital The study was self funded. management develop a strategy towards improving patient Availability of data and materials safety through pharmacovigilance. It may also help iden- The datasets used and/or analysed during the current study are available tify areas that need urgent intervention or modification in from the corresponding author on reasonable request. the health information system management of the tertiary Authors’ contributions hospitals especially since it is recommended that the AOO conceptualised the study, modified the data collection tool, collected indicators be reapplied as needed in the facilities. and analysed data and wrote the initial manuscript. AFR reviewed the protocol, the data collection tool, analysed the data and revised the manuscript. AOI was part of the technical team that drafted the WHO Limitations Pharmacovigilance indicators, conceptualised the study, reviewed the study The WHO indicators have proven to be quite useful in protocol, analysed the data collected and also revised the manuscript. All this assessment. However, absence of trained pharmacov- authors revised and approved the final manuscript. igilance personnel hindered the provision of results for Ethics approval and consent to participate the pharmacovigilance process indicators in the centers. Ethical approval was obtained from the Ethics and research committees of Of note is the limitation of the structural pharmacovigi- all participating institutions: Delta State University Teaching Hospital Oghara: DELSUTH/HREC/2015/024, Niger Delta University Teaching Hospital Okolobri,: lance indicators to fully capture the functionality of the NDUTH/REC/0005/2015, University of Benin Teaching Hospital Benin-City: pharmacovigilance system. Furthermore, the overall poor UBTH:ADM/E22/2/VOL.VII/1245, University of Calabar Teaching Hospital, documentation in all centers limited the derivation of the Calabar: UCTH/HREC/33/360, University of Port Harcourt Teaching Hospital, Port Harcourt: UPTH/ADM/90/S.II/VOL.X/668 and University of Uyo Teaching indicators. Again the derivation of the outcome/impact in- Hospital, Uyo: UUTH/AD/S/96/VOL.XIV/357. The heads of the institutions dicator required in-depth survey which young pharmacov- equally gave approval for participation and access to pertinent publicly igilance systems are unable to execute. There might be a accessible data; including instructions to the person(s) in charge of pharmacovigilance at the various institutions who then gave verbal consent need to develop a scoring system to quantify the indices as approved by the ethics committees. All ethical considerations were duly thus highlighting the deficiencies in numerical terms. observed. Competing interests Conclusion The authors declare that they have no competing interests. This study has shown an urgent need to strengthen the pharmacovigilance systems in the South-South zone of Publisher’sNote Nigeria. The WHO pharmacovigilance indicators have Springer Nature remains neutral with regard to jurisdictional claims in been proven to be helpful in assessing the pharmacovigi- published maps and institutional affiliations. lance system in the zone. Improvement in medical record Author details documentation as well as increased institutionalization of Department of Clinical Pharmacology and Therapeutics, University of Benin, pharmacovigilance may be the first steps to improve 2 Benin-City, Edo State, Nigeria. Department of Medicine, University of Benin pharmacovigilance activities in the tertiary hospitals. Teaching Hospital, Benin-City, Nigeria. Inserm, Bordeaux Population Health Opadeyi et al. 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