Drug Safety Monitoring Research Articles

Clinical pharmacy in Ukraine according to the healthcare professionals’ assessment

An anonymous questionnaire survey among healthcare professionals in Ukraine (n = 10737) showed contradictions in the attitude to the peculiarities of clinical pharmacy compared to a general pharmacy, the relation to the specialists who provide clinical pharmacy services, and the healthcare settings for them. The respondents considered the activity of clinical pharmacist necessary in 74.2%. The community pharmacies were identified as prior professional settings for clinical pharmacists in 55.3%; hospitals – 47.7%, hospital pharmacies – 45.0%. Among the directions of the clinical pharmacist’s activity at the hospital, monitoring of drug safety and efficacy was stated by 69.9%, provision of the pharmaceutical care – 50.5%, evaluation of pharmacotherapy – 42.1%, processing of the local drug formulary – 26.8%. The respondents saw prospects for the development of clinical pharmacy in Ukraine in 54.2%. Therefore, there were differences in views on the key issues of clinical pharmacy throughout Ukraine and the insufficient support for its prospects.

ZnO/Ag nanorods as a prominent SERS substrate contributed by synergistic charge transfer effect for simultaneous detection of oral antidiabetic drugs pioglitazone and phenformin

It is popular and promising to explore a prominent surface-enhanced Raman scattering (SERS) substrate for simultaneous determination of multiple analytes in drug safety and quality monitoring. To achieve the goal, in this work, we constructed a plasmonic metal/semiconductor oxide heterostructure by depositing Ag nanoparticles (NPs) on ZnO nanorods. The ZnO/Ag substrate exhibited prominent SERS performance by using rhodamine 6 G as the probe molecule, including transferable nature onto various available substrate, high enhancement factor, stability and uniformity. The synergistic charge transfer effect was systematically studied, including the effects of the Ag loading amount and laser wavelength, photoluminescence, UV–vis spectra and XPS analysis. The ZnO/Ag substrate was developed as a SERS probe for separate and simultaneous detection of two oral antidiabetic drugs (OADs), pioglitazone (PIO) and phenformin (PHE) in human urine. The detection limits were as low as 1 and 5 nM for PIO and PHE (respectively) with good selectivity and satisfactory recoveries. This type of SERS substrate will be suitable for rapid and noninvasive determination of OADs in clinic applications.

Polygonum multiflorum-Induced Liver Injury: Clinical Characteristics, Risk Factors, Material Basis, Action Mechanism and Current Challenges.

Polygonum multiflorum Thunb. (PM), called Heshouwu in China, is a popular Chinese medicine in clinical practice. Several clinical studies have been conducted to evaluate the traditional therapeutic claims and to study the potential therapeutic activity of PM in dyslipidemia and neurodegenerative diseases, highlighting available clinical evidence. In recent years, reports on clinical adverse reactions of Raw Radix P. multiflorum (RPM) and P. multiflorum Praeparata (PMP) have been on the increase, especially with respect to liver injury. Most liver injury cases had been assessed for causality using RUCAM (Roussel Uclaf Causality Assessment Method) in this paper. However, the components of PM responsible for the reported hepatotoxic effects have not yet been identified. Moreover, many of the reports are contradictory, while studies on the mechanism involved in PM-induced liver damage are not comprehensive. This study was aimed at reviewing the status of research on liver injury due to PM, including clinical characteristics, risk factors, material basis research and mechanism of action, with a view to understanding PM-induced hepatotoxicity, and taking reasonable and effective measures to prevent it. In short, quality control is still one of the major safety problems in TCM drug safety concerns. The model of safety monitoring and risk management of PM drugs is not yet developed. Indeed, the characteristics and risk factors associated with PM require both proper understanding and control of the risk by strengthening standardization of clinical applications, basic science research, quality control in manufacturing, active monitoring methodology and enhancement of international communication and cooperation. Measures should also be encouraged and implemented to promote healthy development of the TCM industry.

Dose-related adverse events in South African patients prescribed clofazimine for drug-resistant tuberculosis.

Optimal drug levels and minimal toxicity are critical factors in improving treatment outcomes for patients prescribed new and repurposed medicine for drug-resistant (DR) tuberculosis (TB). The optimal dose and dose-related safety of clofazimine (CFZ), a repurposed medicine for DR TB, in the South African (SA) population are unknown. To report on dose-related adverse events in patients receiving CFZ plus a background regimen for DR TB. In a retrospective review of patient folders from 2012 to 2014, adverse events documented for patients receiving high- (≥200 mg) and low-dose (100 mg) CFZ in a centralised DR TB hospital in KwaZulu-Natal Province, SA, were investigated for an association between dose-weight interactions and adverse events. Of 600 patients included, 78.7% (n=472) weighed ≥50 kg. Of these, 17.4% (n=82) received 100 mg CFZ and 82.6% (n=390) received >200 mg. Of 128 patients (21.3%) who weighed <50 kg, 68.0% (n=87) received 100 mg CFZ and 32.0% (n=41) received ≥200 mg. Of 463 patients (77.2%) who were HIV-positive, 94.0% were on antiretrovirals. There was no difference between the dose-weight cohorts in the background regimen given in addition to high- or low-dose CFZ. The frequency and types of adverse events observed were similar to the published literature. When analysed per dose-weight cohort, patients weighing <50 kg and receiving high-dose CFZ (≥200 mg) had a 2.6 times higher risk of any adverse event (adjusted odds ratio (aOR) 2.57; 95% confidence interval (CI) 1.02 - 6.05; p=0.05: reference category <50 kg and 100 mg). Patients weighing <50 kg and receiving high-dose CFZ had a 3.3 times higher risk of gastrointestinal adverse events than patients weighing <50 kg and receiving 100 mg CFZ (aOR 3.30; 95% CI 1.51 - 7.19; p=0.003). A high risk of chest pain was observed in patients receiving high- and low-dose CFZ, irrespective of weight. Patients weighing <50 kg receiving high-dose CFZ had a slightly higher risk of adverse events related to the skin (aOR 1.2; 95% CI 0.55 - 2.62; p=0.7) There were no documented reports of the CFZ dose being reduced or the drug being stopped due to adverse events in the sample population. There is an association between dose-weight interaction and adverse events. The odds of any adverse event occurring were higher when low-weight patients (<50 kg) received high-dose CFZ (≥200 mg). Gastrointestinal and skin-related adverse events were more common when high-dose CFZ was used in patients weighing <50 kg. Chest pain was reported in patients receiving high- and low-dose CFZ, irrespective of weight, and may be a symptom of cardiac toxicity. Plasma concentrations of CFZ may be affected by drug-drug interactions, so active drug safety monitoring including electrocardiograms is recommended routinely when CFZ is part of the regimen.

Surveillance of adverse events in the treatment of drug-resistant tuberculosis: first global report.

The World Health Organization (WHO) recommends that countries implement pharmacovigilance and collect information on active drug safety monitoring (aDSM) and management of adverse events.The aim of this prospective study was to evaluate the frequency and severity of adverse events to anti-tuberculosis (TB) drugs in a cohort of consecutive TB patients treated with new (i.e. bedaquiline, delamanid) and repurposed (i.e. clofazimine, linezolid) drugs, based on the WHO aDSM project. Adverse events were collected prospectively after attribution to a specific drug together with demographic, bacteriological, radiological and clinical information at diagnosis and during therapy. This interim analysis included patients who completed or were still on treatment at time of data collection.Globally, 45 centres from 26 countries/regions reported 658 patients (68.7% male, 4.4% HIV co-infected) treated as follows: 87.7% with bedaquiline, 18.4% with delamanid (6.1% with both), 81.5% with linezolid and 32.4% with clofazimine. Overall, 504 adverse event episodes were reported: 447 (88.7%) were classified as minor (grade 1-2) and 57 (11.3%) as serious (grade 3-5). The majority of the 57 serious adverse events reported by 55 patients (51 out of 57, 89.5%) ultimately resolved. Among patients reporting serious adverse events, some drugs held responsible were discontinued: bedaquiline in 0.35% (two out of 577), delamanid in 0.8% (one out of 121), linezolid in 1.9% (10 out of 536) and clofazimine in 1.4% (three out of 213) of patients. Serious adverse events were reported in 6.9% (nine out of 131) of patients treated with amikacin, 0.4% (one out of 221) with ethionamide/prothionamide, 2.8% (15 out of 536) with linezolid and 1.8% (eight out of 498) with cycloserine/terizidone.The aDSM study provided valuable information, but implementation needs scaling-up to support patient-centred care.

Integration of drug safety monitoring in tuberculosis treatment programmes: country experiences.

New drugs and shorter treatments for drug-resistant tuberculosis (DR-TB) have become available in recent years and active pharmacovigilance (PV) is recommended by the World Health Organization (WHO) at least during the early phases of implementation, with active drug safety monitoring and management (aDSM) proposed for this. We conducted a literature review of papers reporting on aDSM. Up to 18 April, 2019, results have only been published from one national aDSM programme. Because aDSM is being introduced in many low- and middle-income countries, we also report experiences in introducing it into DR-TB treatment programmes, targeting the reporting of a restricted set of adverse events (AEs) as per WHO-recommended aDSM principles for the period 2014-2017. Early beneficial effects of active PV for TB patients include increased awareness about the occurrence, detection and management of AEs during TB treatment, and the increase of spontaneous reporting in some countries. However, because PV capacity is low in most countries and collaboration between national TB programmes and national PV centres remains weak, parallel and coordinated co-development of the capacities of both TB programmes and PV centres is needed.

Successful implementation of bedaquiline for multidrug-resistant TB treatment in remote Papua New Guinea.

Bedaquiline (BDQ) was introduced in the multi-drug-resistant tuberculosis (MDR-TB) programme in Daru in remote Papua New Guinea in 2015, along with a core package of active drug-safety monitoring (aDSM). To assess interim results and safety of BDQ for the treatment of MDR-TB from 1 July 2015 to 31 December 2017. A retrospective cohort analysis of routine programme data. Of 277 MDR-TB patients, 77 (39%) received BDQ with a total of 8 serious adverse events including 5 (6.5%) deaths, of which 1 (1.3% QTcF prolongation, grade 3) was attributable to BDQ. Of 200 (61%) patients who did not receive BDQ, there were 17 (9%) deaths. Completeness of monitoring for the BDQ group was 90% for >5 electrocardiograms and 79% for ⩾2 cultures. In the interim result indicator analysis at month 6 in the BDQ and non-BDQ groups, there were respectively 0% and 1% lost to follow-up; 6.5% and 8.5% who died; 94% and 91% in care; and 92% and 96% with negative culture among those monitored. Early experience in Daru shows BDQ is safe and feasible to implement with aDSM with good interim effectiveness supporting the rapid adoption and scale-up of the 2019 WHO MDR-TB treatment guidelines in the programme and in similar remote settings.

International Drug Safety Monitoring

In the 1960s, following the Thalidomide Disaster, the World Health Organization (WHO) initiated the development of an international drug safety monitoring programme. The objectives of this WHO programme are to improve the quality and safety of pharmaceuticals, and to support public health programmes by providing information for effective assessment of the risk-benefit ratio of medicinal products. The paper outlines the main focus areas of the programme and the mechanism of interaction between the countries involved. It summarises the functions of the WHO Collaborating Centre for International Drug Monitoring located in Uppsala, namely, accumulation and assessment of data on efficacy, inefficacy and risks of medicinal products, which are communicated by the participating countries, and provision of reliable and coherent data to specialists. The paper provides a review of online resources and methods used by VigiBase — global database of adverse drug reactions — that make it possible to search and analyse the data statistically. It describes the functions of the national monitoring centres located in different regions, and their interaction with the WHO. The dissemination of objective and reliable medical information throughout the world, promotion of pharmacovigilance as a science, creation of international partnerships and pooling of expertise from different countries allow for a significant improvement in the safety of pharmacotherapy.

Monitoring drug safety: is the Yellow Card Scheme struggling?

In 2018, the Yellow Card Scheme reported a decline in the number of reported suspected adverse drug reactions, particularly among doctors and pharmacists. This article discusses the possible reasons for this and the action the MHRA is taking to improve reporting rates.

A Cross-Sectional Pilot Study on Pharmacovigilance to Improve the Drug Safety in Bangladesh

The monitoring of drug safety is a crucial element for the effective use of medicines to maintain high-quality medical care. The aim of this study was to analyze the adverse drug reactions (ADRs) as well as improve drug safety through pharmacovigilance (PV) in Bangladesh. The research work was conducted on the basis of a questionnaire by taking interviews of targeted stakeholders including academicians, doctors, pharmacists, manufacturers of drugs and directorate general of drug administration (DGDA) personnel. The study was conducted on 496 participants at Dhaka Metropolitan Dhaka, Rajshahi and Khulna Divisions from July 2015 to June 2018. Outcomes showed that among the interviewed populations 23% were female and 77% were male. Among participants, 66.9% of the interviewee was postgraduate degree holders. 62.7% respondents were familiar with the word element PV and 37.3% were ignorant of it. The major problem of DGDA to spreading the knowledge of PV was less manpower (73.9%). Among the factors that must be stopped to avoid the ADRs were the unethical practice of the healthcare professionals (50%). The topmost prioritized component was an education for knowledge (71.4%). It was found that many of the facilities for adverse drug reaction monitoring (ADRM) were absent in Bangladesh. The manpower and strength of DGDA must be increased to perform adequate monitoring and control as per the need of the country. We recapitulate that more research and development programs on PV activities in the country to improve the quality healthcare services is needed.

Drug Safety Evaluation in China.

This review aimed to introduce the regulations management and current situations of drug safety evaluation in China. The nationwide implementation of good laboratory practice and good clinical practice guarantees the quality of pre-marketing drug safety evaluation. In recent years, post-marketing drug safety monitoring is changing from passive mode to the combination of active and passive monitoring. A national adverse drug reaction monitoring sentinel alliance has been created to actively identify, report, and evaluate adverse reactions, with more than 1.4 million cases reported in 2017. But the quality of the reports is not optimal, with few reports from drug manufacturers, low rate of severe reports, and trend of lag reporting. Drug safety evaluation in China is transitioning from passive monitoring to a combination mode. Drug pharmacovigilance is a powerful tool for active monitoring, but participation by drug manufacturers would be essential to an effective drug safety evaluation system.

Crohn's & Colitis Australia inflammatory bowel disease audit: measuring the quality of care in Australia

Australia has among the highest prevalence of Crohn disease and ulcerative colitis in the world. Management of the chronic gastrointestinal disorders results in significant societal costs and the standard of care is inconsistent across Australia. To audit the quality of care received by patients admitted for inflammatory bowel disease (IBD) across Australia against national IBD standards. A retrospective cross-sectional survey and clinical audit was undertaken assessing organisational resources, clinical processes and outcome measures. This study was conducted in Australian hospitals that care for inpatients with Crohn disease or ulcerative colitis. The main outcome measures were adherence to national IBD standards and comparison of quality of care between hospitals with and without multidisciplinary IBD services. A total of 71 hospitals completed the organisational survey. Only one hospital had a complete multidisciplinary IBD service and 17 had a partial IBD service (IBD nurse, helpline and clinical lead). A total of 1440 inpatient records was reviewed from 52 hospitals (mean age 37 years; 51% female, 53% Crohn disease), approximately 26% of IBD inpatient episodes over a 12-month period in Australia. These patients were chronically unwell with high rates of anaemia (30%) and frequent readmissions (40% within 2 years). In general, care was inconsistent, and documentation was poor. Hospitals with a partial IBD service performed better in many processes and outcome measures: for example, 22% reduction in admissions through emergency departments and greater adherence to standards for safety monitoring of biological (89% vs 59%) and immunosuppressive drugs (79% vs 55%) in those hospitals than those without. Patients admitted to hospital suffering from IBD are young, chronically unwell and are subject to substantial variations in clinical documentation and quality of care. Only one hospital met accepted standards for multidisciplinary care; hospitals with even a minimal IBD service provided improved care.

Technical specifications for hospital-based intensive monitoring of post-marketing Chinese patent medicine

In 2013,China pharmaceutical regulatory department issued guiduance on postmarketing drug safety monitoring for industry. It aimed to encourage industry to carry out postmarketing drug safety monitoring including hospital-based intensive monitoring of postmarketing Chinese patent medicine. Subsequently,more and more such kind of studies have been performed all over China. However,in view of the current situation in this field,the development of hospital-based intensive monitoring of postmarketing Chinese patent medicine lacks standardization,such as unreasonable design,omission of reports about adverse drug reactions,inadequate process of quality control,non-standardized interpretation of adverse reactions,etc. Therefore,it is necessary to formulate relevant technical specifications to guide this area. The developing of this technical specification refered to the international post-marketing safety monitoring model and advanced design concepts and methods. We developed it under the guidance of relevant laws,regulations and technical documents in China. Meanwhile the characteristics of Chinese patent medicines and the real situation in this area were considered. The aim of this technical specification is to obtain the incidence,type,degree and clinical manifestation of adverse drug reactions of Chinese patent medicines,to find new risk signals of adverse reactions,to identify risk factors,and to provide a basis for the formulation of risk management and control plans. This specification has been approved by China association of Chinese medicine which is numbered T/CACM011-2016.

Служба мониторинга безопасности лекарственных препаратов в организациях-разработчиках / производителях лекарственных средств для ветеринарного применения

The danger of animal complications due to drug therapy increases the responsibility of developers/manufacturers for the safety of medicinal products for veterinary use, including those in civilian circulation. At the time of making a decision on the state registration of a drug, information obtained during its preclinical and clinical studies on undesirable reactions and side effects cannot be complete, since these studies are limited to a small number and similarity of experimental animals and a relatively short duration of experiments. In addition, with long-term use of the drug may be delayed adverse side reactions that can occur months and years after exposure of the drug to a living organism. Considering this, the pharmacovigilance system should function effectively in the producer (or developer) of the drug, the main task of which is monitoring monitoring of drug safety during the pre-registration period, tracking and analyzing data on the effect of the drug when it is in public circulation, and taking adequate measures to prevent adverse effects of drug therapy. As a result of the analysis, data on regulatory and methodological documents on the organization of monitoring the safety of pharmacological drugs were systematized, recommendations prepared with the provisions of international and domestic legislative regulatory and information documents related to the methodology of organizing pharmacovigilance and monitoring drug safety were prepared.

Monitoring Drug Safety in Rheumatoid Arthritis Prevention Trials

This commentary discusses issues particular to drug safety monitoring in prevention trials. Although the general approach to safety assessment applies across all clinical trials, prevention trials pose special challenges given that the patient population is currently asymptomatic or experiencing only mild symptoms of the targeted disease. This sways the risk-benefit analysis balance toward minimal acceptable risk. Definition of the predisease state with validated biomarkers or other assessment tools is essential. The timing and required length of exposure to the disease intervention to produce an effect requires special methodologic considerations. In addition, prevention trials generally have a longer duration with higher dropout rates. As a result, there is an enhanced focus on lessening patient burden in regard to data collection and finding ways to minimize the safety signal to noise ratio to enable product causality assessment. To meet these challenges, clinical safety monitoring in prevention trials involves 3 essential steps: safety planning, systematic data collection and evaluation, and transparent communication of safety information. We discuss some of these issues using historical experience with primary prevention cardiovascular trials and then focus on unique issues surrounding patient populations at risk for rheumatoid arthritis.

A study of patterns of adverse drug reactions in a tertiary care hospital of Andhra Pradesh, India

Background: Pharmacovigilance Programme of India (PVPI) is a step towards participation in WHO programme for International Drug Safety Monitoring. Pharmacovigilance (PV) system is an integral part of drug therapy, which helps in detection, monitoring and designing strategies to minimize the occurrence of Adverse Drug Reaction (ADRs). The present study is done to study the patterns of ADRs in a tertiary care government hospital.Methods: A total of 327 suspected ADR reports submitted to the pharmacovigilance unit at department of pharmacology under PVPI were evaluated for a period of two years with respect to age, sex, causative drug, organ system involvement and seriousness of ADRs. The causality assessment was done using WHO assessment method.Results: Female patients experienced more (54.13%) ADRs. The highest percentage (49.24%) of ADRs were seen in age group of 18-44 years, followed by 45-60 years (33.33%). Medicine department reported the maximum number (42.20%) of ADRs. Antimicrobial agents (27.83%) were the commonest group of drugs causing ADRs, followed by anti psychotics (15.90%) and analgesic drugs (10.70%). Skin is the major organ system affected (30.28%). Causality assessment revealed (51.99%) of the ADRs were possible. Majority of the ADRs (79.82%) were nonserious and (20.18%) were serious requiring hospitalization. Death occurred in five patients.Conclusions: The results suggest that there is under reporting and there is a need to create awareness among health care professionals(HCP) about the importance of Pharmacovigilance .The data also helps in designing strategies for framing policies towards safer use of drugs in future.

Alectinib versus crizotinib in untreated Asian patients with anaplastic lymphoma kinase-positive non-small-cell lung cancer (ALESIA): a randomised phase 3 study

Anaplastic lymphoma kinase-positive (ALK-positive) disease occurs in approximately 5% of all patients with non-small-cell lung cancer, with a similar incidence reported in Asian patients. This study is the first phase 3 randomised trial recruiting only Asian patients to compare alectinib with crizotinib as a first-line treatment for ALK-positive non-small-cell lung cancer with 600 mg of alectinib twice per day. This study assessed consistency of the progression-free survival benefit with the global phase 3 ALEX study. In this randomised, open-label, phase 3 study done at 21 investigational sites in China, South Korea, and Thailand, Asian patients, aged 18 years or older, with ALK-positive non-small-cell lung cancer were randomly assigned (2:1) to twice-daily oral alectinib (600 mg) or crizotinib (250 mg). Patients were randomly assigned via a block-stratified (block size three) randomisation procedure, done centrally via an interactive voice or web response system, with stratification by Eastern Cooperative Oncology Group performance status and baseline CNS metastases. Clinical staff and the funder's drug safety and medical monitoring staff had access to treatment assignments. The independent review committee was masked to treatment assignment, and funder personnel did not have access to efficacy and safety summaries by treatment group, before the formal reporting of study results. Patients with asymptomatic CNS metastases were permitted. The primary endpoint was investigator-assessed progression-free survival. The primary analysis population for efficacy was the intention-to-treat population, defined as all randomly assigned patients. The primary analysis population for safety was defined as all patients who received at least one dose of study medication. This trial is registered with ClinicalTrials.gov, number NCT02838420. Between Aug 3, 2016, and May 16, 2017, 187 patients were randomly assigned to treatment: 125 to alectinib and 62 to crizotinib. Median follow-up was 16·2 months (IQR 13·7-17·6) in the alectinib group, and 15·0 months (12·5-17·3) in the crizotinib group. Investigator-assessed progression-free survival was significantly prolonged with alectinib versus crizotinib (hazard ratio [HR] 0·22, 95% CI 0·13-0·38; p<0·0001; median progression-free survival not estimable vs 11·1 months). Independent review committee-assessed progression-free survival was also significantly longer in the alectinib group compared with the crizotinib group (HR 0·37, 0·22-0·61; p<0·0001). The proportion of patients who achieved an objective response was 114 (91%) of 125 with alectinib, and 48 (77%) of 62 with crizotinib, with a longer duration of response for alectinib than crizotinib (HR 0·22, 95% CI 0·12-0·40; p<0·0001). Time to CNS progression (cause-specific HR 0·14) and the percentage of patients who achieved a CNS objective response with measurable or non-measurable baseline CNS lesions were improved (32 [73%] of 44 patients treated with alectinib vs five [22%] of 23 patients treated with crizotinib). Despite longer treatment duration with alectinib than crizotinib (14·7 months vs 12·6 months, respectively), fewer patients had grade 3-5 adverse events (36 [29%] of 125 vs 30 [48%] of 62, respectively) or serious adverse events (19 [15%] of 125 vs 16 [26%] of 62, respectively). Our results align with ALEX, confirming the clinical benefit of 600 mg of alectinib twice per day as a first-line treatment for ALK-positive non-small-cell lung cancer. F Hoffmann-La Roche.

Surveillance of adverse events in the treatment of drug-resistant tuberculosis: A global feasibility study

The World Health Organization launched a global initiative, known as aDSM (active TB drug safety monitoring and management) to better describe the safety profile of new treatment regimens for drug-resistant tuberculosis (TB) in real-world settings. However, comprehensive surveillance is difficult to implement in several countries.The aim of the aDSM project is to demonstrate the feasibility of implementing national aDSM registers and to describe the type and the frequency of adverse events (AEs) associated with exposure to the new anti-TB drugs.Following a pilot study carried out in 2016, official involvement of TB reference centres/countries into the project was sought and cases treated with bedaquiline- and/or delamanid-containing regimens were consecutively recruited. AEs were prospectively collected ensuring potential attribution of the AE to a specific drug based on its known safety profile.A total of 309 cases were fully reported from 41 centres in 27 countries (65% males; 268 treated with bedaquiline, 20 with delamanid, and 21 with both drugs) out of an estimated 781 cases the participating countries had committed to report by the first quarter of 2019.

PO 8438 KNOWLEDGE, ATTITUDE AND PERCEPTIONS ON ADVERSE DRUG EVENTS REPORTING AMONG PATIENTS AND HEALTHCARE PROVIDERS IN RURAL UGANDA

BackgroundDrug regulatory authorities promote patient safety by, among other ways, monitoring adverse drug events (ADEs). Reporting of ADEs in Uganda is below the average for a well-performing system. Enhancing patients’ understanding of and involving them in reporting ADEs improves drug safety and treatment outcome monitoring. The objective of this study was to describe the knowledge, attitude, and practice of patients and healthcare workers regarding ADEs and ADEs reporting.MethodsA cross-sectional survey was carried out among 1034 respondents from randomly selected households and 327 health workers at health facilities in the Iganga Mayuge Health and Demographic Surveillance Site (IMHDSS). The IMHDSS, located in Uganda, covers 90,000 people living in 17,000 households.ResultsOver half of respondents (59%) sought treatment from private drug shops, 37% from either clinic, health center or hospital, while 4% sought treatment from herbalists, friends or relatives. Over half (56%) were aware of ADEs, 57% expressed willingness to report an ADE while 43% did not know what to do when it occurs. Almost half (46%) could not differentiate between an ADE and the symptoms, and for those who could, the majority (76%) were willing to report it. Only 34% had ever reported an ADE when it occurred to them. Of those who reported, 43% had their drugs changed, 31% were only counseled while 11.5% continued taking the same medication. Among healthcare workers, 95% knew about ADEs, but only 35% had ever reported. Reasons for not reporting were: fear of being victimised or sued (35%); lack of adequate knowledge about ADE (26%); 20% thought it would disappear shortly; and 14% did not find it necessary to report.ConclusionPatients seek their treatment from private providers. Patients want to report ADEs, but they do not have adequate knowledge. Healthcare workers’ reasons for not reporting are subjective. Dedicated pharmacovigilance-related interventions at community level would improve community members’ knowledge and hence ADE reporting rate.

Challenging MDR-TB clinical problems – The case for a new Global TB Consilium supporting the compassionate use of new anti-TB drugs

MDR-TB is a growing challenge worldwide, and an obstacle to TB elimination. It is apparent that TB is being replaced by small but growing number of resistant cases with an anticipated 2 million cases of MDR-TB within the next two decades. One of the potential causes of MDR-TB is iatrogenic and we risk losing our new drugs through inexperience and repetition of basic errors of adding single active drugs to failing regimens. Discussion of MDR-TB cases with senior colleagues is not only best practice; it is now embedded in the WHO and many national and local guidelines.TB Consilia act as gatekeepers to the new drugs, monitor guideline adherence and mandate active drug safety monitoring. TB Consilia are also excellent educational tools.TB Consilia are now recommended by funding bodies, the WHO and manufacturers of drugs available for compassionate use in the hope that these drugs will be protected and will continue to be useful in the future. This article briefly discusses Consilia, their origin and evolution and gives some examples of how they operate.