Interventions to improve spontaneous adverse drug reaction reporting by healthcare professionals and patients:systematic review and meta-analysis

The aim of this study was to evaluate the effectiveness of interventions used for improving ADR reporting by patients and healthcare professionals. A systematic review of literature was conducted by searching Medline, Embase and Cochrane Central Register of Controlled of Trials. Meta-analysis of randomized controlled trials (RCTs; = 5) was conducted to estimate the pooled risk ratio for the effectiveness of interventions on ADR reporting rates. Data from observational studies were synthesized using narrative synthesis approach. A total of 28 studies were included. All except one study targeted healthcare professionals using educational, technological, policy, financial and/or mixed interventions. The results showed that financial and face-to-face educational interventions improved quality and quantity of ADR reporting when compared with interventions not involving face-to-face interactions. However, the quality of studies was generally low. Meta-analysis showed a statistically significant 3.5-fold overall increase in reporting of ADRs [RR 3.53; 95% CI (1.77,7.06)] in the intervention group compared to the control. There was a lack of consideration of theory and sustainability in the design of the interventions. There is a need to develop and test theory-based interventions and target patient reporting. More research needs to be conducted in the low- and middle-income countries.This study was funded by University of Birmingham

ADRIC: Adverse Drug Reactions In Children - a programme of research using mixed methods

Aims To comprehensively investigate the incidence, nature and risk factors of adverse drug reactions (ADRs) in a hospital-based population of children, with rigorous assessment of causality, severity and avoidability, and to assess the consequent impact on children and families. We aimed to improve the assessment of ADRs by development of new tools to assess causality and avoidability, and to minimise the impact on families by developing better strategies for communication. Review methods Two prospective observational studies, each over 1 year, were conducted to assess ADRs in children associated with admission to hospital, and those occurring in children who were in hospital for longer than 48 hours. We conducted a comprehensive systematic review of ADRs in children. We used the findings from these studies to develop and validate tools to assess causality and avoidability of ADRs, and conducted interviews with parents and children who had experienced ADRs, using these findings to develop a leaflet for parents to inform a communication strategy about ADRs. Results The estimated incidence of ADRs detected in children on admission to hospital was 2.9% [95% confidence interval (CI) 2.5% to 3.3%]. Of the reactions, 22.1% (95% CI 17% to 28%) were either definitely or possibly avoidable. Prescriptions originating in the community accounted for 44 out of 249 (17.7%) of ADRs, the remainder originating from hospital. A total of 120 out of 249 (48.2%) reactions resulted from treatment for malignancies. Off-label and/or unlicensed (OLUL) medicines were more likely to be implicated in an ADR than authorised medicines [relative risk (RR) 1.67, 95% CI 1.38 to 2.02; p  48 hours, the overall incidence of definite and probable ADRs based on all admissions was 15.9% (95% CI 15.0 to 16.8). Opiate analgesic drugs and drugs used in general anaesthesia (GA) accounted for > 50% of all drugs implicated in ADRs. The odds ratio of an OLUL drug being implicated in an ADR compared with an authorised drug was 2.25 (95% CI 1.95 to 2.59; p < 0.001). Risk factors identified were exposure to a GA, age, oncology treatment and number of medicines. The systematic review estimated that the incidence rates for ADRs causing hospital admission ranged from 0.4% to 10.3% of all children [pooled estimate of 2.9% (95% CI 2.6% to 3.1%)] and from 0.6% to 16.8% of all children exposed to a drug during hospital stay. New tools to assess causality and avoidability of ADRs have been developed and validated. Many parents described being dissatisfied with clinician communication about ADRs, whereas parents of children with cancer emphasised confidence in clinician management of ADRs and the way clinicians communicated about medicines. The accounts of children and young people largely reflected parents’ accounts. Clinicians described using all of the features of communication that parents wanted to see, but made active decisions about when and what to communicate to families about suspected ADRs, which meant that communication may not always match families’ needs and expectations. We developed a leaflet to assist clinicians in communicating ADRs to parents. Conclusion The Adverse Drug Reactions In Children (ADRIC) programme has provided the most comprehensive assessment, to date, of the size and nature of ADRs in children presenting to, and cared for in, hospital, and the outputs that have resulted will improve the management and understanding of ADRs in children and adults within the NHS. Recommendations for future research: assess the values that parents and children place on the use of different medicines and the risks that they will find acceptable within these contexts; focusing on high-risk drugs identified in ADRIC, determine the optimum drug dose for children through the development of a gold standard practice for the extrapolation of adult drug doses, alongside targeted pharmacokinetic/pharmacodynamic studies; assess the research and clinical applications of the Liverpool Causality Assessment Tool and the Liverpool Avoidability Assessment Tool; evaluate, in more detail, morbidities associated with anaesthesia and surgery in children, including follow-up in the community and in the home setting and an assessment of the most appropriate treatment regimens to prevent pain, vomiting and other postoperative complications; further evaluate strategies for communication with families, children and young people about ADRs; and quantify ADRs in other settings, for example critical care and neonatology

Patient safety in Europe: medication errors and hospital-acquired infections

The Report was commissioned by the European Federation of Nurses Associations (EFN) in November 2007 in order to support its policy statements on Patient Safety (June 2004). In that statement the EFN declares its belief that European Union health services should operate within a culture of safety that is based on working towards an open culture and the immediate reporting of mistakes; exchanging best practice and research; and lobbying for the systematic collection of information and dissemination of research findings. This Report adressess specifically the culture of highly reliable organisations using the work of James Reason (2000). Medication errors and hospital-acquired infections are examined in line with the Reprt´s parameters and a range of European studies are used as evidence. An extensive reference list is provided that allows EFN to explore work in greater detail as required

Evidence and Extrapolation: Mechanisms for Regulating Off-Label Uses of Drugs and Devices

A recurring, foundational issue for evidence-based regulation is deciding whether to extend governmental approval from an existing use with sufficient current evidence of safety and efficacy to a novel use for which such evidence is currently lacking. This extrapolation issue arises in the medicines context when an approved drug or device that is already being marketed is being considered (1) for new conditions (such as off-label diagnostic categories), (2) for new patients (such as new subpopulations), (3) for new dosages or durations, or (4) as the basis for approving a related drug or device (such as a generic or biosimilar drug). Although the logic of preapproval testing and the precautionary principle—first, do no harm—would counsel in favor of prohibiting extrapolation approvals until after traditional safety and efficacy evidence exists, such delays would unreasonably sacrifice beneficial uses. The harm of accessing unsafe products must be balanced against the harm of restricting access to effective products. In fact, the Food and Drug Administration\u27s (FDA\u27s) current regulations in many ways reject the precautionary principle because they largely permit individual physicians to prescribe medications for off-label uses before any testing tailored to those uses has been done. The FDA\u27s approach empowers physicians, but overshoots the mark by allowing enduring use of drugs and devices with insubstantial support of safety and efficacy. This Article instead proposes a more dynamic and evolving evidence-based regime that charts a course between the Scylla and Charybdis of the overly conservative precautionary principle on one hand, and the overly liberal FDA regime on the other. Our approach calls for improvements in reporting, testing, and enforcement regulations to provide a more layered and nuanced system of regulatory incentives. First, we propose a more thoroughgoing reporting of off-label use (via the disclosure of diagnostic codes and detailing data) in manufacturers\u27 annual reports to the FDA, in the adverse event reports to the FDA, in Medicare/Medicaid reimbursement requests, and, for a subset of FDA-designated drugs, in prescriptions themselves. Second, we would substantially expand the agency\u27s utilization of postmarket testing, and we provide a novel framework for evaluating the need for postmarket testing. Finally, our approach calls for a tiered labeling system that would allow regulators and courts to draw finer reimbursement and liability distinctions among various drug uses, and would provide the agency both the regulatory teeth and the flexibility it presently lacks. Together, these reforms would improve the role of the FDA in the informational marketplace underlying physicians\u27 prescribing decisions. This evolutionary extrapolation framework could also be applied to other contexts

Can the Heinrich ratio be used to predict harm from medication errors?

The purpose of this study was to establish whether, for medication errors, there exists a fixed Heinrich ratio between the number of incidents which did not result in harm, the number that caused minor harm, and the number that caused serious harm. If this were the case then it would be very useful in estimating any changes in harm following an intervention. Serious harm resulting from medication errors is relatively rare, so it can take a great deal of time and resource to detect a significant change. If the Heinrich ratio exists for medication errors, then it would be possible, and far easier, to measure the much more frequent number of incidents that did not result in harm and the extent to which they changed following an intervention; any reduction in harm could be extrapolated from this

Chapter Evolving Roles of Spontaneous Reporting Systems to Assess and Monitor Drug Safety

This chapter aims to describe current and emerging roles of spontaneous reporting systems (SRSs) for assessing and monitoring drug safety. Moreover, it offers a perspective on the near future, which entails the so-called era of Big Data, keeping in mind both regulator and researcher viewpoints. After a panorama on key data sources and analyses of post-marketing data of adverse drug reactions, a critical appraisal of methodological issues and debated future applications of SRSs will be presented, including the exploitation and challenges in evidence integration (i.e., merging and combining heterogeneous sources of data into a unique indicator of risk) and patient’s reporting via social media. Finally, a call for a responsible use of these studies is offered, with a proposal on a set of minimum requirements to assess the quality of disproportionality analysis in terms of study conception, performing and reporting

Factors associated with underreporting of adverse drug reactions by health care professionals: a systematic review update

Introduction Underreporting is a major limitation of the voluntary reporting system of adverse drug reactions (ADRs). A 2009 systematic review showed the knowledge and attitudes of health professionals were strongly related with underreporting of ADRs. Objective Our aim was to update our previous systematic review to determine factors (sociodemographic, knowledge and attitudes) associated with the underreporting of ADRs by healthcare professionals. Methods We searched the MEDLINE and EMBASE databases for studies published between 2007 and 2021 that met the following inclusion criteria: (1) published in English, French, Portuguese or Spanish; (2) involving health professionals; and (3) the goal was to evaluate factors associated with underreporting of ADRs through spontaneous reporting. Results Overall, 65 papers were included. While health professional sociodemographic characteristics did not influence underreporting, knowledge and attitudes continue to show a significant effect: (1) ignorance (only serious ADRs need to be reported) in 86.2%; (2) lethargy (procrastination, lack of interest, and other excuses) in 84.6%; (3) complacency (the belief that only well tolerated drugs are allowed on the market) in 46.2%; (4) diffidence (fear of appearing ridiculous for reporting merely suspected ADRs) in 44.6%; and (5) insecurity (it is nearly impossible to determine whether or not a drug is responsible for a specific adverse reaction) in 33.8%, and the absence of feedback in 9.2%. In this review, the non-obligation to reporting and confidentiality emerge as new reasons for underreporting. Conclusions Attitudes regarding the reporting of adverse reactions continue to be the main determinants of underreporting. Even though these are potentially modifiable factors through educational interventions, minimal changes have been observed since 2009Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This study has been funded in part by the Instituto de Salud Carlos III (ISCIII) through the project PI19/01006, cofinanced by FEDER, European UnionS

Evolving Roles of Spontaneous Reporting Systems to Assess and Monitor Drug Safety

This chapter aims to describe current and emerging roles of spontaneous reporting systems (SRSs) for assessing and monitoring drug safety. Moreover, it offers a perspective on the near future, which entails the so-called era of Big Data, keeping in mind both regulator and researcher viewpoints. After a panorama on key data sources and analyses of post-marketing data of adverse drug reactions, a critical appraisal of methodological issues and debated future applications of SRSs will be presented, including the exploitation and challenges in evidence integration (i.e., merging and combining heterogeneous sources of data into a unique indicator of risk) and patient’s reporting via social media. Finally, a call for a responsible use of these studies is offered, with a proposal on a set of minimum requirements to assess the quality of disproportionality analysis in terms of study conception, performing and reporting