Funding and financial sustainability of pharmacovigilance: suggested models for funding pharmacovigilance in resource-limited African countries.

Background: An important factor hindering the growth of pharmacovigilance (PV) in resource-limited settings is the lack of adequate funds to establish a functional National Pharmacovigilance System. Consequently, the crucial function of monitoring and ensuring the availability of safe medicines in these settings cannot be guaranteed considering the peculiarities of diseases and medicines used. Objectives: The objective of this paper is to provide an overview as to the availability of potential sources of funds, which could be explored to ensure Medicine Safety and to proffer a potential framework likely to ensure sustainable funding of PV in Africa. Methods/processes: The process of developing this framework entailed a review of PV financing in some developed economies, a landscape study of funding of PV in some African countries, an in-depth understanding of the PV system and the organisational structure and nexus between the regulatory agencies and National Pharmacovigilance Centre. Critical points for consideration included the sources of funds, revenue pool, the disbursement of funds, budgeting and expenditure profile and the legal framework. Consultative meetings, webinars and interviews with experts were carried out. Results: The findings showed that most of the PV systems were mainly integrated into the regulatory agencies regarding operational and fiscal governance with few facilities being independent of the regulatory agencies. The main source of funding was from the government with significant donor funding which is ad hoc and non-sustainable. Several potential sources were identified but yet to be exploited. There were no legal provisions for PV financing. A framework likely to ensure sustainable PV financing is suggested to capture all available sources of funding, mine the potential sources providing a sizeable pool of revenue to address its activities and enabling legal framework which will engender autonomy. Furthermore, it will address the nexus between the regulatory agencies and the PV outfits, thus enabling appropriate share of resources and blockage of diversions. Conclusion: In all, addressing the various elements identified in this study and providing the legal provisions which guarantees some degree of autonomy will provide a sustainable mechanism for PV funding in the resource-limited setting of Africa.

Funding models for pharmacovigilance in resource-limited African countries An important factor hindering the growth of pharmacovigilance (PV) in resource-limited settings following their entry into the WHO Programme of International Drug Monitoring is the lack of adequate funds to establish a functional National Pharmacovigilance System. This article provides an overview of various potential sources of funds in these settings and how they can be harnessed to fund PV. We undertook a review of PV financing in developed settings and carried out a landscape study of funding of PV in some African countries, as well as having an in-depth understanding of the PV system and the organisational structure. The nexus between the regulatory agencies and National Pharmacovigilance Centre was noted. We took into account the sources of funds, revenue pool, the disbursement of funds, budgeting and expenditure profile and the legal framework for the different African countries. We also identified the prevalent and potential sources of funds for PV. Consultative meetings, webinars and interviews with experts in PV were carried out as well. We discovered that most of the PV facilities were mainly integrated into the regulatory agencies regarding operational and fiscal governance with few facilities being independent of the regulatory agencies. The main source of funding was from the government with significant donor funding which is ad hoc and non-sustainable. Several potential sources were identified but yet to be exploited. There were no legal provisions for PV financing. We have now proposed funding models that may lead to increased revenue for PV in these countries as well as suggesting that a legal framework be provided to guarantee sustainability and address the nexus between the regulatory agencies and the PV outfits to ensure an appropriate share of resources and blocking diversions.

Educational intervention to improve the knowledge, attitude and practice of healthcare professionals regarding pharmacovigilance in South-South Nigeria.

BACKGROUND: Our aim in this study was to evaluate the effect of a combined educational intervention and year-long monthly text message reinforcements via the Short Messaging System (SMS) on the knowledge, attitude and practice (KAP) of healthcare professionals (HCPs) towards pharmacovigilance. METHODS: Six randomly selected teaching hospitals in the South-South zone of Nigeria were randomized in 1:1 ratio into intervention and control groups. The educational intervention consisted of delivering a seminar followed by sending monthly texts message reinforcements via SMS over 12 months. Then a semi-structured questionnaire regarding the KAP of pharmacovigilance was completed by HCPs working in the hospitals after the intervention. Data was analysed descriptively and inferentially. RESULTS: A total of 931 HCPs participated in the post intervention study (596 in the intervention and 335 in the control). The M:F ratio was 1:1.5. According to the KAP questionnaire, a significant difference was observed between the intervention and control groups, regarding knowledge of the types of adverse drug reactions (ADRs). ADR resulting from pharmacological action of the drug (85.6% versus 77%, p = 0.001), the fact that ADRs can persist for a long time; (60.1% versus 53.4%, p = 0.024) and a higher awareness of the ADR reporting form (48.7% versus 18.8%, p < 0.001). Most respondents in the intervention group (68.5% versus 60.6%, p = 0.001) believed they should report ADRs even if they were unsure an ADR has occurred, a greater proportion of HCPs from the intervention group had significantly observed an ADR (82% versus 73.4%, p = 0.001). Furthermore, of the 188 who had ever reported an ADR, 41% from the intervention group used the national ADR reporting form compared with 19.8% from the controls (p < 0.001). CONCLUSION: This educational intervention and the use of SMS as a reinforcement tool appeared to have positively impacted on the knowledge and practice of pharmacovigilance in South-South Nigeria with a less-than-impressive change in attitude. Continuous medical education may be required to effect long-lasting changes.

Standard treatment guidelines: Perception and utilization in a tertiary health care facility in South-South, Nigeria.

Background: The Nigerian National Standard Treatment Guidelines (NSTG) was introduced in 2008 and the second edition was launched in 2017. This study evaluated the level of awareness, acceptance, and use of this tool within the Nigerian health-care system. Methodology: This study was carried out at the University of Benin Teaching Hospital, Benin City, Nigeria. A semistructured questionnaire was administered to doctors in the hospital. Information sought included the biodata, awareness of the STG, publication and use of the STG, the perceived advantages and disadvantages, and suggestions on how to improve its use. Results: There were 155 respondents with a mean age of 34.1 ± 6.4 years and response rate of 77.5%. The level of awareness was 46.5%, with 21.9% having received lessons on the subject; 53.0% received lessons as students. Awareness of the date of the initial introduction of the STG at the national level was 4.5% with 1.3% aware of the current edition of the NSTG. The description of the STG was satisfactory in 27.7% participants. Again only 20.6% currently use the NSTG, with 12.3% rating the entire STG utilization as successful. Conclusion: There is low awareness and poor utilization of the STG among doctors in the facility which may be a reflection of the situation in other health facilities in the country. There is need to encourage the use of this clinical tool to ensure appropriate use of medicines and delivery of health care in resource-limited settings.

RésuméContexte: Les directives nationales nigérianes de traitement standard (NSTG) ont été introduites en 2008 et la deuxième édition a été lancée en 2017. Cette étude a évalué le niveau de sensibilisation, d'acceptation et d'utilisation de cet outil dans le système de santé nigérian. Méthodologie: Cette étude a été réalisée à l'hôpital universitaire du Bénin, Benin City, Nigeria. Un questionnaire semi-structuré a été administré aux médecins de l'hôpital. Les informations recherchées comprenaient les données biographiques, la connaissance du STG, la publication et l'utilisation du STG, les avantages et inconvénients perçus et des suggestions sur la manière d'améliorer son utilisation. Résultats: 155 personnes a été interrogés ayant un âge moyen de 34,1 ± 6,4 ans et un taux de réponse de 77,5%. Le niveau de sensibilisation était de 46,5%, 21,9% ayant suivi des cours sur le sujet; 53,0% ont reçu des cours en tant qu'étudiants. La connaissance de la date de la première introduction du STG au niveau national était de 4,5%, avec 1,3% conscient de l'édition actuelle du STG. La description du STG était satisfaisante chez 27,7% des participants. Encore une fois, seuls 20,6% utilisent actuellement le NSTG ; 2,3% estimant que l'utilisation de STG, en entier, était un succès. Conclusion: Les médecins de l'établissement sont peu sensibilisés et il y a l'utilisation faible de STG chez eux : ce qui peut refléter la situation dans d'autres établissements de santé du pays. Il est nécessaire d'encourager l'utilisation de cet outil clinique pour assurer l'utilisation appropriée des médicaments et la prestation des soins de santé dans les pays à ressources limitées.

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

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.

A profile of adverse effects of antihypertensive medicines in a tertiary care clinic in Nigeria.

BACKGROUND: There has been a dearth of comprehensive data on the profile of adverse reactions to antihypertensive medicines in the Nigerian setting despite increased use. OBJECTIVE: This study was aimed to characterize the adverse reactions experienced in the homogenously black African population. METHODS: The study was carried out at the University of Benin Teaching Hospital, Benin City, Nigeria, in consenting eligible hypertensive patients ≥18 years. Adverse reactions were sought using patient's self-report and a medicine-induced symptom checklist. RESULTS: A total of 514 patients (340 females) aged 22-97 years were studied. Thirteen percent, 27.6%, 26.7%, 22.0%, and 10.7% were on 1, 2, 3, 4, and ≥5 medicines, respectively, for control of their blood pressure with the frequency of adverse effects increasing proportionately up to four medicines. Adverse reactions to antihypertensive medicines were reported by a total of 93 (18.1%) patients. Diuretics - 27.9%, calcium channel blockers (CCBs) - 26.8%, and angiotensin-converting enzyme inhibitors (ACEIs) - 26.8% accounted for most of the adverse reactions seen, notably frequent micturition and headaches (CCB); excessive micturition and dizziness (diuretics); dry irritating cough (ACEI). Notable complaints for all patients using the checklist were increased frequency of micturition, reduction in libido, and headaches. The reactions resulted in the discontinuation and substitution of therapy in 49.5% of the patients. CONCLUSIONS: The characterization of these reactions in Nigerians requires further studies as frequent micturition reported is still a neglected complaint in antihypertensive therapy.

Impact of comorbidity on adverse drug reaction profile in a cohort of patients treated with Artemisinin combination therapies for uncomplicated malaria in Nigeria.

Artemisinin-based combination antimalarial therapy (ACTs), is still highly effective in uncomplicated falciparum malaria, however, there remain some concerns in relation to its safety and tolerability. Comorbid disease conditions may influence susceptibility to adverse drug reactions (ADRs) as the presence of multiple disease conditions may predisposes patients to ADRs due to the use of many medicines. There is therefore need to assess the impact of comorbidities on the ADR profile of malaria patients treated with ACTs. The study was carried out in health care facilities spread across Nigeria. From the database of over 10,000 patients recruited into an initial cohort, data for 1000 patients with comorbidities was extracted and matched with a control group of 1000 randomly selected patients with no comorbidity. There were 1105 adverse drug reactions in all, of which 66.2% were recorded in patients with comorbidity, and 34% are patients without comorbidity. The mean age of patients with comorbidities was 38.3 ± 17.5 years and 23.8 ± 17.2 for those without comorbidity. Out of the 979 patients with comorbidity, 36% were hypertensive, 2.2% hypertensive-diabetes, 16.4% peptic ulcer disease, 10.4% HIV/AIDS, 4.4% diabetes and 4.3% were asthmatic. Patients with comorbidity were three times more likely to have adverse drug reaction than those without comorbidity (Odds ration = 2.96; 95% CI = 2.23-3.93). HIV/AIDS and osteoarthritis were significantly associated with development of adverse drug reactions. Probability was <0.0001. Age, weight, and height of patients were also found to be risk factor for development of adverse drug reactions.

Antihypertensive Medicines Prescriptions before and after the Nigeria Hypertension Society Guidelines and Prescriber's Awareness of the Guideline.

OBJECTIVES: The Nigerian hypertension guideline (2005) was based on 1999 ISH/WHO and the 2003 Sub-Saharan Africa hypertension guidelines. The changes in the prescribing pattern of physicians before and following the introduction of these guidelines as well as physicians' awareness of the guidelines in Southern Nigeria are unknown. SUBJECTS AND METHODS: A retrospective study of antihypertensive prescriptions and a cross-sectional descriptive study of the physicians' awareness of the guidelines. The study was carried out at a tertiary health facility in Southern Nigeria and reviewed the case records (1999-2008) of 3379 hypertensive patients who had attended the medical outpatient clinic; it also assessed the awareness of 48 postregistration doctors working in the same hospital using a self-administered questionnaire. RESULTS: Calcium channel blockers were the most prescribed class over the entire period (44.7%-69.2%) while angiotensin-converting enzyme inhibitors prescriptions increased by 325% (11.8%-51.5%). Annual prescriptions of diuretics increased steadily from 38% in 1999 to a peak of 58% in 2005. A total of 37/48 doctors responded, and a high proportion (32/37; 86.5%) were aware of the national guidelines, but only 13/37 (35.1%) were satisfied with the recommendations. Diuretics were stated as the most preferred class of antihypertensive medicines by 26/37 (70.3%) of respondents. CONCLUSIONS: The findings suggest disconnect in the prescribers' knowledge of recommendations in the guidelines, their stated preferences for medicines, and the observed findings in the case records. This may be due in part to the observed dissatisfaction of doctors with the guidelines.

Efficacy of initiating therapy with amlodipine and hydrochlorothiazide or their combination in hypertensive Nigerians.

In order to evaluate whether amlodipine or hydrochlorothiazide would be preferable to initiate therapy, 90 untreated hypertensive Nigerians of both genders aged 31-86 years with blood pressure >160/90 and ≤180/120 mm Hg were recruited into a randomized 48-week study. Patients, 30 each in amlodipine, hydrochlorothiazide, and amlodipine-hydrochlorothiazide groups, were treated, respectively, with amlodipine 5 mg for 6 weeks and the dose increased to 10 mg till week 12, after which hydrochlorothiazide 25 mg was added; hydrochlorothiazide 25 mg till week 6, after which amlodipine 5-10 mg was added; and amlodipine 5-10 mg + hydrochlorothiazide 25 mg. Body mass index, blood pressure, heart rate, and 24-hour urine volume were evaluated at baseline and at the end of weeks 1, 3, 6, 12, 24, 36, and 48. The primary efficacy variables were decreased in mean trough sitting diastolic and systolic blood pressure such that blood pressure < 140/90 mm Hg was regarded as normalized. At week 48 in the amlodipine group, 27 patients versus 25 patients in the hydrochlorothiazide group had diastolic blood pressure <90 mm Hg (90% vs. 83.3%; P <.03). In the amlodipine group, 23 patients versus 20 patients in the hydrochlorothiazide group had blood pressure < 140/90 mm Hg (76.7% vs. 66.7%; P <.01). In the amlodipine-hydrochlorothiazide group, 27 patients (90%) and 15 patients (50%) had diastolic blood pressure <90 mm Hg and blood pressure < 140/90 mm Hg, respectively. This study has demonstrated that a regimen of amlodipine to which hydrochlorothiazide is subsequently added provides superior efficacy on blood pressure control when compared with a regimen of hydrochlorothiazide to which amlodipine is subsequently added or with ab initio amlodipine-hydrochlorothiazide combination therapy.

Specific features of medicines safety and pharmacovigilance in Africa.

The thalidomide tragedy in the late 1950s and early 1960s served as a wakeup call and raised questions about the safety of medicinal products. The developed countries rose to the challenge putting in place systems to ensure the safety of medicines. However, this was not the case for low-resource settings because of prevailing factors inherent in them. This paper reviews some of these features and the current status of pharmacovigilance in Africa. The health systems in most of the 54 countries of Africa are essentially weak, lacking in basic infrastructure, personnel, equipment and facilities. The recent mass deployment of medicines to address diseases of public health significance in Africa poses additional challenges to the health system with notable safety concerns. Other safety issues of note include substandard and counterfeit medicines, medication errors and quality of medicinal products. The first national pharmacovigilance centres established in Africa with membership of the World Health Organization (WHO) international drug monitoring programme were in Morocco and South Africa in 1992. Of the 104 full member countries in the programme, there are now 24 African countries with a further nine countries as associate members. The pharmacovigilance systems operational in African countries are based essentially on spontaneous reporting facilitated by the introduction of the new tool Vigiflow. The individual case safety reports committed to the WHO global database (Vigibase) attest to the growth of pharmacovigilance in Africa with the number of reports rising from 2695 in 2000 to over 25,000 in 2010. There is need to engage the various identified challenges of the weak pharmacovigilance systems in the African setting and to focus efforts on how to provide resources, infrastructure and expertise. Raising the level of awareness among healthcare providers, developing training curricula for healthcare professionals, provisions for paediatric and geriatric pharmacovigilance, engaging the pharmaceutical industries as well as those for herbal remedies are of primary concern.

Prescription writing in public and private hospitals in Benin City, Nigeria: the effects of an educational intervention.

BACKGROUND: Writing a prescription is a vital part of the process of rational therapeutics; a badly written prescription could undermine a clinical consultation. OBJECTIVES: To determine how far prescriptions meet accepted standards, identify factors underlying poor prescription writing, intervene by educational methods, and evaluate the effects of intervention. METHODS: Prescriptions (1,197) were collected retrospectively from 40 doctors (public and private hospitals). Handwriting was assessed using a rating scale. Intervention was by face-to-face education and group seminar in public hospitals, and face-to-face education only in private hospitals, with impact evaluation 4 to 6 weeks later. Non-parametric statistics were used to assess differences in means for pre- and post-intervention values. RESULTS: At baseline, more prescriptions from private hospitals had hospitals' addresses (p=0.005) and patients' ages (p=0.015); more from public hospitals were signed (p=0.001) and 20% of prescriptions were clearly legible. Post-intervention, more prescriptions from public hospitals were signed (p=0.017); more from private hospitals had the doses (p=0.04) and routes (p=0.05) of administration, and the intervention group in private hospitals wrote patients ages more frequently than controls (p=0.05). Doctors who had group seminar wrote frequencies and routes of administration (p=0.03 and 0.04 respectively) more than those who had face-to-face education. Handwriting worsened (p=0.04, 0.02 in public and private hospitals respectively). Poor quality of prescriptions was blamed partly on heavy workload and non-availability of prescription order blanks. CONCLUSIONS: Prescriptions lacked details and most were not clearly legible. Intervention resulted in modest changes, which in public hospitals were more significant among doctors who had group seminars.