Drug Safety Issues Research Articles

Increasing the safe and effective use of medications

One of the most underreported health-related stories of 2013 was the increased emphasis that the federal government has placed on the issue of prescription drug abuse and drug safety. Ottawa was clear in the Speech from the Throne in October 2013 that it would undertake a series of measures to increase patient safety and reduce medication-related errors, an important promise when one considers that up to 1 in 9 hospitalizations result from adverse drug reactions (ADRs). The government is thus far living up to that commitment. Over the past year, we have seen the introduction of a variety of measures designed to strengthen drug safety and reduce prescription drug abuse, notably the following: In June, the federal government announced its plain language labeling initiative, to ensure that drug labels and safety information are available in plain language so Canadians can better understand how and when to take their medications. As part of this initiative, Health Canada is providing $3.2 million to the Institute for Safe Medication Practices Canada to study the reasons behind medication misuse. In December, the Minister of Health tabled in the House of Commons Bill C-17, the Protecting Canadians from Unsafe Drugs Act, otherwise known as “Vanessa’s Law” (named in honour of Vanessa Young, the daughter of Conservative Member of Parliament Terence Young, who died after taking a prescription drug that was later found to be unsafe and was withdrawn from the market). Among other things, this bill will provide the federal government with powers to recall medications proven to be unsafe, will require mandatory ADR reporting by hospitals (the definition of a reportable reaction will be decided as regulations are developed) and will compel drug companies to revise labels to clearly reflect health risk information, including updates for health warnings for children. Also in December, several Conservative Members of Parliament held consultations with stakeholders to develop a strategy on a national Take Back Your Medications day, which would be a national initiative aimed at encouraging Canadians to drop off any unused medications to designated locations, possibly including pharmacies. Although a federally run Take Back Your Medications day remains a longer-term objective, the Minister of Health has been open to the idea. Over the fall, the House of Commons Standing Committee on Health held hearings into the government’s role in addressing prescription drug abuse. The Committee has already heard from many witnesses, including CPhA, on how the government can continue to play a role in improving the safe and effective use of medications. A report from the Committee is expected in spring 2014, with possible additional actions after that. The Canadian Pharmacists Association (CPhA) has been at the forefront in supporting and encouraging these initiatives. CPhA provided input into the development of these initiatives, expressed its qualified support for measures addressing drug safety and continues to meet with Health Canada officials to provide feedback into policy in this area. During its appearance before the Standing Committee on Health, CPhA argued for such measures as expanding scope of practice so that pharmacists could address safety issues head-on, enhancing training opportunities for pharmacists and ensuring that regulations prevent the entry of drugs with high risks of addiction to market. There is no question that drug safety and appropriate use of medication are the top priority of pharmacists. Recent media stories have called into question the safety and efficacy of medications in Canada. By supporting these measures and continuing to have a dialogue with the federal government on additional ways in which medication safety can be improved, CPhA, on behalf of pharmacists across Canada, is making it clear that safety is priority number one for the profession. ■

Analysis of the Factors Influencing the Spontaneous Reporting Frequency of Drug Safety Issues Addressed in the FDA’s Drug Safety Communications, Using FAERS Data

Introduction Drug Safety Communications (DSCs), a major tool for risk communication used by the US Food and Drug Administration (FDA), are also designed to encourage spontaneous reporting. However, the effectiveness of this tool remains unclear.

Spontaneous reporting of adverse drug reactions in geriatric patients in India

Background: In India, spontaneous reporting of adverse drug reactions (ADRs) by health-care professionals was initiated in 2010. The drug safety issues for geriatric population are critical due to age-related physiological, pharmacodynamic, and pharmacokinetic changes. Aims & Objective: To assess the spontaneous reports of ADRs observed in geriatric patients (over 65 years of age) in India from 1 July 2011 to 31 June 2013. Materials and Methods: The spontaneous reports of 4357 elderly patients (≥65 years) were retrieved at National Pharmacovigilance Centre from the database containing all ADR reports from 90 ADR Monitoring Centres (AMCs) in India under Pharmacovigilance Programme of India (PvPI) for 2 years. These reports were analyzed for various characteristics of patients, drugs, and ADRs using a search and analysis tool. Results: Of the 4357 geriatric individual case safety reports, more ADRs were reported in the male (57.77%) than in the female (41.38%) patients. Of the total geriatric patients, ADRs reported from 1120 (25.71%) patients were found to be serious, of which 8 (0.71%) were fatal. Cisplatin, carboplatin, cyclophosphamide, acetylsalicylic acid, and insulin were the common drugs prescribed to the elderly patients, and the most common ADRs reported were vomiting, diarrhea, and constipation. In geriatric population, ADRs mostly affected gastrointestinal system and skin and appendages system. Conclusion: This study from spontaneous reporting indicates the common ADRs in the geriatric patients in India, which will help health-care professionals to better understand the drug safety issues in elderly.

Use of big data for drug safety monitoring and decision making

빅데이터는 여러 가지 형태로 정의되고 있으나 대표적으 로 미국 IT리서치기업인 가트너는, 빅데이터는 의사결정의 기반을 강화하고 새로운 통찰이나 가치를 제공할 수 있도록, 비용-효과적이고 혁신적인 처리과정을 필요로 하는 큰 규모, 빠른 속도 및 높은 다양성을 가지는 의미한다고 정의 한 바 있다[1]. 최근 빅데이터를 분석하여 유용한 정보를 생성 할 수 있는 기술이 발전하면서 마케팅, 금융, 교육, 치안, 환 경, 교통, 농업, 보건의료 등 다양한 분야에 활용되고 있으며, 가트너는 빅데이터를 ‘21세기의 새로운 원유’라고 지칭하기 도 하였다. 미국에서는 빅데이터 진흥정책으로서 2012년 3월 19일 ‘빅데이터 RD such enormous collections of information on drugs and adverse drug reactions are stored in either a structured, a semistructured, or an unstructured form. Because of the nature of the emerging issue of drug safety, it is common for policy makers and healthcare professionals to make decisions without sufficient evidence. Big data may be used as an efficient pharmacovigilance tool, which enables us to recognize adverse drug reactions that may not have been identified in pre-marketing clinical trials, in order to capture the patterns of drug utilization and adverse events, and to predict the occurrence of adverse drug reactions. National surveillance systems using electronic health databases have been established successfully in the US and Europe. The Korea Institute of Drug Safety and Risk Management (KIDS) plans to establish a big data platform for pharmacovigilance in Korea. The big data may be effectively used for evidence-based regulatory and clinical decision making in the field of drug safety and risk management.

Combining machine learning systems and multiple docking simulation packages to improve docking prediction reliability for network pharmacology.

Increased availability of bioinformatics resources is creating opportunities for the application of network pharmacology to predict drug effects and toxicity resulting from multi-target interactions. Here we present a high-precision computational prediction approach that combines two elaborately built machine learning systems and multiple molecular docking tools to assess binding potentials of a test compound against proteins involved in a complex molecular network. One of the two machine learning systems is a re-scoring function to evaluate binding modes generated by docking tools. The second is a binding mode selection function to identify the most predictive binding mode. Results from a series of benchmark validations and a case study show that this approach surpasses the prediction reliability of other techniques and that it also identifies either primary or off-targets of kinase inhibitors. Integrating this approach with molecular network maps makes it possible to address drug safety issues by comprehensively investigating network-dependent effects of a drug or drug candidate.

Pharmacovigilance in Calabria (Italy): Local experiences resonate international relevance.

Pharmacovigilance and all drug safety issues are relevant for everyone whose life is touched in any way by medical interventions.[1] Pharmacovigilance is defined by the World Health Organization (WHO) as “the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other problem in the field of medicine.”[2] The main reason for having a world-wide active and functioning pharmacovigilance system is the need to ensure patients’ safety. In all therapeutic protocols patients’ wellness is the main objective. Several aspects of drug therapy such as appropriateness of medication prescribing, rationale of choice of the agents, cost-effectiveness of the chosen medications and safety must be considered before starting treatment. Drug related adverse effects threaten patient wellness. In the light of this, pharmacovigilance should be considered a mandatory activity of all countries.[3] Though, the history of pharmacovigilance started several years ago its implementation many countries is still found wanting. The international program pursued by WHO has greatly contributed to practice and standards and together with the various national centers, has been seen to improve the quality of pharmacovigilance. Like all other human activities, the dissemination of pharmacovigilance related knowledge and experiences play a crucial role for the development of this subject. The way to improve is to debate a specific aspect and compare different methodologies and points of view. This special issue fulfills this role by discussing the various aspects of pharmacovigilance in Italy.

Investigation of Hepatobiliary Disposition of Doxorubicin Following Intrahepatic Delivery of Different Dosage Forms

Unresectable, intermediate stage hepatocellular carcinoma (HCC) is often treated palliatively in humans by doxorubicin (DOX). The drug is administered either as a drug-emulsified-in-Lipiodol (DLIP) or as drug loaded into drug eluting beads (DEB), and both formulations are administered intrahepatically. However, several aspects of their in vivo performance in the liver are still not well-understood. In this study, DLIP and DEB were investigated regarding the local and systemic pharmacokinetics (PK) of DOX and its primary metabolite doxorubicinol (DOXol). An advanced PK-multisampling site acute in vivo pig model was used for simultaneous sampling in the portal, hepatic, and femoral veins and the bile duct. The study had a randomized, parallel design with four treatment groups (TI-TIV). TI (n = 4) was used as control and received an intravenous (i.v.) infusion of DOX as a solution. TII and TIII were given a local injection in the hepatic artery with DLIP (n = 4) or DEB (n = 4), respectively. TIV (n = 2) received local injections of DLIP in the hepatic artery and bile duct simultaneously. All samples were analyzed for concentrations of DOX and DOXol with UPLC-MS/MS. Compared to DLIP, the systemic exposure for DOX with DEB was reduced (p < 0.05), in agreement with a slower in vivo release. The approximated intracellular bioavailability of DOX during 6 h appeared to be lower for DEB than DLIP. Following i.v. infusion (55 min), DOX had a liver extraction of 41 (28-53)%, and the fraction of the dose eliminated in bile of DOX and DOXol was 20 (15-22)% and 4.2 (3.2-5.2)%, respectively. The AUCbile/AUCVP for DOX and DOXol was 640 (580-660) and 5000 (3900-5400), respectively. In conclusion, DLIP might initially deliver a higher hepatocellular concentration of DOX than DEB as a consequence of its higher in vivo release rate. Thus, DLIP delivery results in higher intracellular peak concentrations that might correlate with better anticancer effects, but also higher systemic drug exposure and safety issues.

Defining a Reference Set to Support Methodological Research in Drug Safety

Methodological research to evaluate the performance of methods requires a benchmark to serve as a referent comparison. In drug safety, the performance of analyses of spontaneous adverse event reporting databases and observational healthcare data, such as administrative claims and electronic health records, has been limited by the lack of such standards. To establish a reference set of test cases that contain both positive and negative controls, which can serve the basis for methodological research in evaluating methods performance in identifying drug safety issues. Systematic literature review and natural language processing of structured product labeling was performed to identify evidence to support the classification of drugs as either positive controls or negative controls for four outcomes: acute liver injury, acute kidney injury, acute myocardial infarction, and upper gastrointestinal bleeding. Three-hundred and ninety-nine test cases comprised of 165 positive controls and 234 negative controls were identified across the four outcomes. The majority of positive controls for acute kidney injury and upper gastrointestinal bleeding were supported by randomized clinical trial evidence, while the majority of positive controls for acute liver injury and acute myocardial infarction were only supported based on published case reports. Literature estimates for the positive controls shows substantial variability that limits the ability to establish a reference set with known effect sizes. A reference set of test cases can be established to facilitate methodological research in drug safety. Creating a sufficient sample of drug-outcome pairs with binary classification of having no effect (negative controls) or having an increased effect (positive controls) is possible and can enable estimation of predictive accuracy through discrimination. Since the magnitude of the positive effects cannot be reliably obtained and the quality of evidence may vary across outcomes, assumptions are required to use the test cases in real data for purposes of measuring bias, mean squared error, or coverage probability.

One in five US neurologists unaware of drug safety issues

One in five US neurologists unaware of drug safety issues

Osteoporosis: From Bone Biology to Individual Treatment Decision

Osteoporosis is a bone metabolic disease with increasing prevalence in ageing societies. Herein we reviewed recent epidemiologic findings and their impact in the individual patient management. In addition we dissected the major disease mechanisms which have uncovered new potential therapeutic strategies. Using MeSH terms (osteoporosis, epidemiology, Portugal, Europe, pathogenesis, osteoblasts, osteoclasts, osteocytes, immune system, obesity, therapy, randomized controlled trial, efficacy, safety) as keywords. We have reviewed original studies, reviews and position papers indexed in PubMed. Osteoporosis is increasingly prevalent, but recently an age-adjusted rate of fracture plateau was reached. A new fracture risk assessment tool was developed, FRAX™, which integrates the contribution of clinical risk factors associated with fragility fractures. It can be used either independently or in combination with bone mineral density. Osteoporosis treatment is offered only to a fraction of the affected individuals. In addition, 40% of the patients receiving Osteoporosis medication had a previous fracture. Relevant safety issues of different drugs used in Osteoporosis have been detected in post-marketing experience. Finally, advances in the understanding of the molecular pathways involved in Osteoporosis led to the development of new drugs Despite the existence of diagnostic tools and several effective treatments, Osteoporosis treatment is still offered only to a fraction of the affected individuals and mainly to a population with advanced disease. New and more effective treatments might change this scenario.

Leishmaniasis in the era of tumor necrosis factor alpha antagonist therapy – a research agenda for Europe

A number of published case reports suggest an association of tumor necrosis factor (TNF) alpha antagonist use and manifest leishmaniasis. Despite increasing popularity of antagonising TNF alpha for the treatment of autoimmune disorders, systematic research on the risk of opportunistic leishmaniasis in patients receiving these drugs is lacking. This perspective identifies areas of uncertainty regarding the safety profile of TNF alpha antagonist drugs and their clinical use in patients at risk of leishmaniasis. Then, we reflect on how current pharmacovigilance activities in Europe could be enhanced to help reduce these uncertainties. Our aim is to stimulate a debate about this important drug safety issue with potential consequences for patients receiving TNF alpha antagonists living in or travelling to areas endemic for leishmaniasis.

Development of a Novel Regulatory Pharmacovigilance Prioritisation System: An Evaluation of Its Performance at the UK Medicines and Healthcare products Regulatory Agency

The prioritisation of drug safety issues for further evaluation or regulatory action is critical to ensure that acceptable timelines and appropriate resource allocation are defined to meet public health and regulatory obligations. Our objective was to develop, pilot and implement a novel tool for prioritising pharmacovigilance issues within the Medicines and Healthcare products Regulatory Agency (MHRA). An initial system was developed empirically and then piloted over a 10-month period in the pharmacovigilance signal management meeting at the MHRA that discusses potential pharmacovigilance issues, and determines, through consensus, their priority and a timescale for action. The priority assigned by the tool was compared with the priority decided by collective judgement at the meeting. Once an acceptable level of concordance between the tool and the meeting had been achieved, the finalised tool was implemented into routine use at the MHRA, with an evaluation of its performance conducted after the first year. The Regulatory Pharmacovigilance Prioritisation System (RPPS) tool prioritises pharmacovigilance issues according to the following four broad categories, each with four inputs: strength of evidence, public health implications, agency regulatory obligations and public perceptions. A weighted scoring system links the inputs to a pre-defined number of points where if a threshold is reached then the points are awarded. The overall priority is determined by the sum of all points obtained from each of the inputs. The pilot study included a total of 73 pharmacovigilance issues during the 10-month study period, with an overall exact agreement between the RPPS priority and the collective judgement of the meeting of 60.3%. Where exact agreement was not obtained, the RPPS generally prioritised the issues slightly higher than the meeting. Over the first year following implementation, the RPPS achieved an overall exact agreement of 82.2%. Following the pilot study and implementation at the UK MHRA, the RPPS has provided a systematic approach to drug safety issue prioritisation that should help to reduce the subjectivity of reliance on individual judgement.

The Additional Value of an E-Mail to Inform Healthcare Professionals of a Drug Safety Issue: A Randomized Controlled Trial in the Netherlands

The usefulness and the impact of Direct Healthcare Professional Communications (DHPCs, or 'Dear Doctor letters') in changing the clinical behaviour of physicians have been debated. Changes in the current risk communication methods should preferably be based on the preferences of the healthcare professionals, to optimize the uptake of the message. The aim of this study was to assess whether safety issues are communicated more effectively with an additional e-mail sent by the Dutch Medicines Evaluation Board (MEB) than with the DHPC only. A randomized controlled trial was conducted amongst ophthalmologists and hospital pharmacists in the Netherlands, who were the target group of a DHPC that was issued for pegaptanib, a drug that is administered intra-ocularly in patients with macular degeneration. The intervention group (N = 110) received the pegaptanib DHPC, as well as the MEB e-mail. The control group (N = 105) received the traditional paper-based DHPC only. Two weeks later, the study population received an invitation to fill out an online questionnaire. Questions were asked about the respondents' knowledge and attitude regarding the pegaptanib issue, and any action they had consequently taken. Additional questions were asked about their satisfaction with the DHPC and the e-mail, and their preferred source of such information. Forty respondents (18.6%) completed the questionnaire. Eighty-one percent of the respondents in the intervention group (N = 21) and 47% of the control group (N = 19) correctly indicated that a serious increase in intra-ocular pressure could be caused by pegaptanib injections (Fishers' exact test, p = 0.046). Nine respondents in the intervention group versus none of the control group respondents indicated that they had taken action in response to the pegaptanib safety issue (Fishers' exact test, p = 0.01). The majority of both the intervention group and the control group confirmed that they would like to receive an MEB e-mail with safety information about drugs in the future (90 and 95 %, respectively). The results of this study indicate that an additional e-mail might strengthen the uptake of the safety information provided to healthcare professionals, who prefer to receive an e-mail from the MEB as a source of such information, as well as the DHPC. This study may serve as a starting point for new strategies to improve risk communication regarding safety issues associated with drugs and its impact on prescribing.

The Future of Population-Based Postmarket Drug Risk Assessment: A Regulator’s Perspective

The US Food and Drug Administration emphasizes the role of regulatory science in the fulfillment of its mission to promote and protect public health and foster innovation. With respect to the evaluation of drug effects in the real world, regulatory science plays an important role in drug risk assessment and management. This article discusses opportunities and challenges with population-based drug risk assessment as well as related regulatory science knowledge gaps in the following areas: (i) population-based data sources and methods to evaluate drug safety issues; (ii) evidence-based thresholds to account for uncertainty in postmarket data; (iii) approaches to optimize the integration and interpretation of evidence from different sources; and (iv) approaches to evaluate the real-world impact of regulatory decisions. Regulators should continue the ongoing dialogue with multiple stakeholders to strengthen regulatory safety science and address these and other critical knowledge gaps.

SP0137 Using Multiple International Healthcare Databases (The EU-ADR Project)

Knowledge of the safety profile of drugs prior to marketing is limited because of the small and selective groups of individuals included in clinical trials. A life-cycle approach to surveillance...

PRM63 - Using a claims data-based sentinel system to identify drug safety and outcomes issues: Methodology and results of analysis on five million lives

PRM63 - Using a claims data-based sentinel system to identify drug safety and outcomes issues: Methodology and results of analysis on five million lives

Su1139 Awareness Among Practitioners Regarding the Safety of Inflammatory Bowel Disease Medications During Pregnancy

Background: Inflammatory Bowel Disease (IBD) frequently occurs in females of childbearing age. It is important to have the disease in remission at the time of conception and throughout the pregnancy. The benefits of medical therapy to maintain remission during pregnancy outweigh the risks of cessation in majority of the cases. Physicians involved in the care of pregnant IBD patients may not have the correct information regarding the safety of IBD drugs. We conducted a local survey to assess the knowledge and awareness among various practitioners regarding the safety issues of drugs used to treat IBD in the pregnant patients. Methods: 111 practitioners (Family Medicine (FM) n=35, Internal Medicine (IM) n=22, OB/GYN n=22, GI-General n=23, and GI-IBD Specialist n=9) were quizzed on the FDA classification of common IBD drugs and the need for caution with live vaccines in neonates of mothers receiving biologics during pregnancy. They were also given two scenarios in managing a patient with IBD desiring to become pregnant: 1) the patient being managed with thiopurines and 2) the patient being managed with biologics. For each scenario, physicians were asked if they would inform the patient to 1) only take current medications as symptoms arise, 2) not take the medications under any condition, 3) continue taking the medication as previously prescribed, 4 and 5) discontinue one and start a differentmedication. The percentage of practitioners among the different groups was compared using either χ2 or Fisher's exact test as appropriate. The p-value was adjusted for multiple comparisons. Results: GI-General and IM were less likely to answer correctly more than one question regarding the FDA classification of IBD drugs compared to FM and OB/GYN practitioners (27% vs. 74%, p,0.0005) and GI-IBD (27% vs. 56%, p=0.43). GIs (GI-General and GIIBD) are more likely to advise their patients to continue taking their current medications (biologics and thiopurines) during pregnancy compared to non GIs (IM, FM, OB/GYN) (biologics: 84% vs. 45%, p,0.0005; thiopurines: 66% vs. 14%, p,0.0005)( figure). Only 45% of OB/GYN correctly identified the safety issues regarding administration of live vaccines in neonates of mothers receiving biologics. There was no difference between GIs and non GIs with regard to the safety knowledge of administering live vaccines (63% vs. 59%, p= 0.83). Overall, 79% of physicians surveyed said they would change their practice based on the educational section at the end of the survey. Conclusion: Practitioners involved in the care of pregnant patients may not have the correct knowledge regarding the safety and management of IBD drugs during pregnancy. Bringing awareness through appropriate education can result in the greater likelihood of physicians following best practice guidelines.

Choice of Baseline in Parallel Thorough QT Studies

Although the ICH E14 Guidance [1] was adopted in 2005 there is still much debate on the appropriate baseline needed to adjust for the variable nature of the QT interval and its heart rate corrected value (QTc) in the parallel Thorough QT (TQT) study. Numerous reports have documented the influence of circadian rhythm [2], food ingestion [3], sleep [4], and autonomic tone [5] on the QT/QTc interval. In the absence of baseline measurements, these factors can make it difficult to interpret QT effects of the study drug. In this issue of Drug Safety Dr. Zhang and colleagues [6] advocate the use of a time-matched baseline in parallel TQT studies to maximize the precision and accuracy of point estimates for QTc effects. Their recommendation is based on analyses of commonly used baseline correction methods using a large data set of parallel TQT studies submitted to the FDA for statistical review by sponsors. One assumption in the choice of baseline is that it should have no influence on the magnitude of QT effects (high accuracy) and it should minimize the uncertainty of the effects (high precision). Both accuracy and precision are important for the interpretation of a TQT trial. As a result, there is much focus on the implications of using different baseline adjustments in the parallel TQT study and understanding the role each baseline definition can have in determining the outcome of the trial as either positive or negative. The distinction between a positive or negative TQT study is based on the upper bound of the 95 % one-sided confidence interval (CI) for the largest time-matched mean difference in QTc between drug and placebo (baseline adjusted). If these (double-delta) DDQTc values exclude 10 ms at all study times the result is a negative TQT study [1]. Intensive ECG monitoring is then hardly ever required in subsequent trials (phase II/III). Conversely, drugs for which an effect exceeding 10 ms cannot be excluded almost always require additional QT interval monitoring in target patients including dose-concentration effects, outlier analysis, changes in mean QTc values, analysis of QTc in subgroups of interest, and identification of individuals who develop a markedly prolonged QTc. The need for additional ECG monitoring in late phase trials can add millions to drug development and may ultimately pose financial limitations on the number of medications which can be developed [7]. The importance of correctly adjusting for baseline in the TQT study is therefore evident.

Pharmacovigilance as a tool for safety and monitoring: a review of general issues and the specific challenges with end-stage renal failure patients.

Pharmacovigilance is instrumental in helping to ensure patient safety for both newly released drugs and those that are well established in the market. However, while pharmacovigilance procedures are strictly regulated in the clinical trial setting, post-marketing adverse event reporting is not well implemented or enforced. As such, the underreporting of adverse events, in relation to drugs that are on the market, is estimated to be in the region of 90%. The identification of drug safety issues in patients with complex diseases and extensive comorbidities is therefore particularly challenging. Dialysis patients – those with end-stage renal disease and often other comorbidities such as diabetes, hypertension, and cardiovascular disease – are a population with significant treatment challenges. Patients receive dialysis using complex medical devices (eg, a peritoneal dialysis home cycler) and also receive a range of pharmaceutical agents as part of dialysis itself (eg, peritoneal dialysis solutions). Many of the pharmaceutical agents used to treat these patients have been developed in populations without these complications and, therefore, an extensive knowledge of potential problems and contraindications in the dialysis population is lacking. It is important that the nephrology community understands the concept of pharmacovigilance – the pharmacologic science relating to the detection, assessment, understanding, and prevention of adverse effects, particularly long-term and short-term side effects, of medicines. Health care professionals (HCPs) and providers, pharmaceutical companies, global regulatory agencies, and the patients themselves all play unique and critical roles in this process. This review defines the science of pharmacovigilance and the process of adverse event reporting, highlights the new directions that pharmacovigilance has taken, and provides insight for HCPs managing dialysis patients into the important role that they play in helping to shape the understanding of a drug’s safety profile in order to continually enhance patient safety.

Systematic Collection of Patient-Reported Adverse Drug Reactions: A Path to Patient-Centred Pharmacovigilance

1 IntroductionOver the past 15 years, evidence has mounted that patientself-reporting of symptomatic adverse drug reactions isboth feasible and informative. Multiple recent reports havedescribed programmes internationally in which patientself-reports provide data beyond reporting by health pro-fessionals [1–5]. Various models have been used and thereare several essential lessons to be learned from theseexperiences, in addition to work using patient-reported datain related contexts such as clinical trials and routine clin-ical practice.2 It is Essential to Systematically Collect Informationfrom Patients Rather than Rely on SpontaneousReportingMany adverse event reporting systems rely on volun-tary (spontaneous) reports by patients and/or clinicians.Although submitted information can be informative insome cases, the denominator of potential reporters isunknown, and many adverse reactions are missed due tolack of interest, willingness, availability, or awareness ofstakeholders to report. As a result, the absolute number ofreports collected via these systems is generally low andoften does not reflect the experience of patients comparedwith systematic collection [6]. Patients are not engaged aspartners in the data collection enterprise.Systematic elicitation of information from patientsprovides a known denominator and a more comprehensivepicture within a population. This can be achieved in limitedpopulations via registries, or through wide implementationusing existing or envisioned infrastructure to engagepatients. The paper by Leone et al. in this issue of DrugSafety [7] describes successful implementation of a regio-nal programme through the mechanism of local pharma-cies. Information is systematically elicited from patientswho are engaged by their local pharmacists. This approachdoes more than use an existing infrastructure of localpharmacies for distribution of questionnaires–it creates apartnership between practitioners and patients in anendeavour to understand the experience of both the indi-vidual patient and the broader population.This programme mirrors successful engagement approa-ches in other contexts, such as clinical trials where datamanagers form relationships with patients to encouragereporting, or routine practice settings where customizedinvitation letters are sent to patients from their doctor ornurse.3 Backup Data Collection Systems ReduceMissing DataA lesson learned from the collection of patient-reportedinformation in prospective clinical trials and registries isthat the frequency of missing patient reports is highlydependent on how this information is collected. In partic-ular, data can be recovered from those who are initiallyunable or unwilling to self-report, through the use ofbackup data collection methods. These may include elec-tronic reminders via mail, email or telephone, with ahuman call to those who continue not to report. This