Baseline assessment of pharmacovigilance activities in four sub-Saharan African countries: a perspective on tuberculosis.

BACKGROUND: New medicines have become available for the treatment of drug-resistant tuberculosis (DR-TB) and are introduced in sub-Saharan Africa (SSA) by the national TB programs (NTPs) through special access schemes. Pharmacovigilance is typically the task of national medicines regulatory agencies (NMRAs), but the active drug safety monitoring and management (aDSM) recommended for the new TB medicines and regimens was introduced through the NTPs. We assessed the strengths and challenges of pharmacovigilance systems in Eswatini, Ethiopia, Nigeria and Tanzania, focusing on their capacity to monitor safety of medicines registered and not registered by the NMRAs for the treatment of DR-TB. METHODS: Assessment visits were conducted to all four countries by a multidisciplinary team. We used a pharmacovigilance indicator tool derived from existing tools, interviewed key stakeholders, and visited health facilities where DR-TB patients were treated with new medicines. Assessment results were verified with the local NMRAs and NTPs. RESULTS: Most countries have enabling laws, regulations and guidelines for the conduct of pharmacovigilance by the NMRAs. The relative success of NTP-NMRA collaboration is much influenced by interpersonal relationships between staff. Division of roles and responsibilities is not always clear and leads to duplication and unfulfilled tasks (e.g. causality assessment). The introduction of aDSM has increased awareness among DR-TB healthcare providers. CONCLUSION: aDSM has created awareness about the importance of pharmacovigilance among NTPs. In the future, a push for conducting pharmacovigilance through public health programs seems useful, but this needs to coincide with increased collaboration with between public health programs and NMRAs with clear formulation of roles and responsibilities

Dedicated mobile application for drug adverse reaction reporting by patients with relapsing remitting multiple sclerosis (Vigip-SEP study): study protocol for a randomized controlled trial

BackgroundThe reporting of adverse drug reactions (ADR) by patients represents an interesting challenge in the field of pharmacovigilance, but the reporting system is not adequately implemented in France. In 2015, only 20 MS patients in France reported ADR due to first-line disease-modifying drugs (DMD), while more than 3000 patients were initiated on DMD.The aim of this study is to validate a proof-of-concept as to whether the use of a mobile application (App) increases ADR reporting among patients with relapsing-remitting multiple sclerosis (RR-MS) receiving DMD.Methods/designWe designed a multi-centric, open cluster-randomized controlled trial, called the Vigip-SEP study (NCT03029897), using the App My eReport France® to report ADR to the appropriate authorities in E2B language, in accordance with European regulations. RR-MS patients who were initiated on, or switched, first-line DMD will be included. In the experimental arm, a neurologist will introduce the patient to the App to report ADR to the appropriate French authorities. In the control arm, the patient will be informed of the existence of the App but will not be introduced to its use and will then report ADR according to the usual reporting procedures. Primary assessment criteria are defined as the average number of ADR per patient and per center. We assume that the App will increase patient reporting by 10-fold. Therefore, we will require 24 centers (12 per arm: 6 MS academic expert centers, 3 general hospitals, 3 private practice neurologists), allowing for an expected enrollment of 180 patients (alpha risk 5%, power 90% and standard deviation 4%).DiscussionIncreasing patient reporting of ADR in a real-life setting is extremely important for therapeutic management of RR-MS, particularly for monitoring newly approved DMD to gain better knowledge of their safety profiles. To increase patient involvement, teaching patients to use tools, such as mobile applications, should be encouraged, and these tools should be tested rigorously

Automatic Filtering and Substantiation of Drug Safety Signals

Drug safety issues pose serious health threats to the population and constitute a major cause of mortality worldwide. Due to the prominent implications to both public health and the pharmaceutical industry, it is of great importance to unravel the molecular mechanisms by which an adverse drug reaction can be potentially elicited. These mechanisms can be investigated by placing the pharmaco-epidemiologically detected adverse drug reaction in an information-rich context and by exploiting all currently available biomedical knowledge to substantiate it. We present a computational framework for the biological annotation of potential adverse drug reactions. First, the proposed framework investigates previous evidences on the drug-event association in the context of biomedical literature (signal filtering). Then, it seeks to provide a biological explanation (signal substantiation) by exploring mechanistic connections that might explain why a drug produces a specific adverse reaction. The mechanistic connections include the activity of the drug, related compounds and drug metabolites on protein targets, the association of protein targets to clinical events, and the annotation of proteins (both protein targets and proteins associated with clinical events) to biological pathways. Hence, the workflows for signal filtering and substantiation integrate modules for literature and database mining, in silico drug-target profiling, and analyses based on gene-disease networks and biological pathways. Application examples of these workflows carried out on selected cases of drug safety signals are discussed. The methodology and workflows presented offer a novel approach to explore the molecular mechanisms underlying adverse drug reactions

Intensive monitoring of duloxetine:results of a web-based intensive monitoring study

<p>Duloxetine (Cymbalta(A (R))) is a serotonin (5-HT) and norepinephrine (NE) re-uptake inhibitor indicated for the treatment of depression, diabetic peripheral neuropathic pain and general anxiety disorder. The aim of this study is to gain insight in the user and safety profile of duloxetine in daily practice, reported by patients via a web-based intensive monitoring system during their first 6 months of use.</p><p>First-time users of duloxetine were identified through the first dispensing signal in the pharmacy. Patient demographics and information about drug use and adverse drug reactions, ADRs, were collected through electronic questionnaires sent 2 and 6 weeks, 3 and 6 months after the start of duloxetine administration. ADRs were quantified and signal detection was performed on a case by case basis.</p><p>Three hundred and ninety-eight patients registered for the study; 69.1 % were female. Depression was the main indication. Three hundred and three patients (76.1 %) filled in at least one questionnaire and 78.9 % of these reported an ADR. Serious ADRs were reported by 4 patients. Three new signals were identified, amenorrhea, shock-like paraesthesias and micturition problems.</p><p>Web-based intensive monitoring is an observational prospective cohort study mirroring the use and ADRs of duloxetine in daily practice. This study indicates that duloxetine is a relatively safe drug as used by patients for six months in daily practice, but the aforementioned signals need to be evaluated in more detail.</p>