Improving the reporting of adverse drug reactions in the hospital setting

The US Food and Drug Administration (FDA) is perceived by the public as having a substantial responsibility to ensure drug safety; however, the FDA has limited resources for active surveillance and relies on voluntary reporting of adverse events and potential adverse drug reactions. Studies have shown that underreporting of adverse events and adverse drug reactions is widespread. Furthermore, a review of several studies demonstrates that most adverse drug reactions are reported by pharmacists and nurses, with physicians reporting the fewest. The hospital setting, with its clearly defined patient population observed around the clock, is an ideal setting in which to identify potential adverse drug reaction signals and to report them to either the drug manufacturer or the FDA. In this article we describe the present system for addressing adverse events, obstacles to reporting them, and the important role any hospital physician could play in reporting adverse events and potential adverse drug reactions.     

A patient's perspective: the impact of adverse drug reactions on patients and their views on reporting

What is known and objective: Adverse drug reactions to prescribed medication are relatively common events. However, the impact such reactions have on patients and their attitude to reporting such events have only been poorly explored. Previous studies relying on self‐reporting patients indicate that altruism is an important factor. In the United Kingdom, patient reporting started in 2005; though, numbers of serious reports remain low. Method: A purposive sample of fifteen patients who had been admitted to an inner city hospital with an adverse drug reaction were interviewed using a semi‐structured questionnaire. Patients were asked to relate in their own words their experience of an adverse drug reaction. Patient’s reactions to the information leaflet, adherence to treatment and use of other sources of information on medication were assessed. Interviews were recorded, and a thematic analysis of patients’ responses was performed. Results and discussion: Analysis of the patient interviews demonstrated the reality of being admitted to hospital is often a frightening process with a significant emotional cost. Anger, isolation, resentment and blame were common factors, particularly when medicines had been prescribed for acute conditions. For patients with chronic conditions, a more phlegmatic approach was seen especially with conditions with a strong support networks. Patients felt that communication and information should have been more readily available from the health care professional who prescribed the medication, although few had read the patient information leaflet. Only a minority of patients linked the medication they had taken to the adverse event, although some had received false reassurance that the drug was not related to their illness creating additional barriers. In contrast to previous studies, many patients felt that adverse drug reporting was not their concern, particularly as they obtained little direct benefit from it. The majority of patients were unaware of the Yellow Card Scheme in the UK for patient reporting. Even when explained, the scheme was felt too cold and impersonal and not a patient’s ‘job’. What is new and conclusion: Patients having a severe adverse drug reaction following an acute illness felt negative emotions towards their health care provider. Those with a chronic condition rationalized the event and coped better with its impact. Neither group felt that reporting the adverse reaction was their responsibility. Encouraging patients to report remains important but expecting patients to report solely for altruistic purposes may be unrealistic.     

护理人员药物不良反应监测知识、态度和行为现状调查

目的 了解护理人员对药物不良反应监测知识、态度和行为情况,为促进和加强我院护理人员对药物不良反应监测提供基础资料。方法 采用方便抽样法对198例护理人员进行问卷调查。结果 本研究共回收问卷164份,有效回收率为90.1%,护理人员对药物不良反应监测知识得分为6.95±1.82;154 (93.9%) 名护理人员认为要积极上报药物不良反应,128 (78.0%) 名护理人员认为上报药物不良反应是自身的职责,45.7%的护理人员不赞同将其作为临床工作的考核指标;67.7%的护理人员曾遇到药物不良反应,其中56.8%的护理人员将发现的药物不良反应上报至有关部门。结论 我院护理人员对监测药物不良反应的态度较为积极,但实际监测情况仍存在一定问题,尚需通过多种途径加强对护理人员药物不良反应监测相关知识的培训,激励护理人员主动监测和上报,促进临床安全用药。     

Effects of the COVID-19 Pandemic on Spontaneous Reporting: Global and National Time-series Analyses

PurposeThe COVID-19 pandemic has been widely reported to present stress to medical systems globally and to disrupt the lives of patients and health care practitioners (HCPs). Given that spontaneous reporting heavily relies on both HCPs and patients, an understandable question is whether the stress of the pandemic has diminished spontaneous reporting. Herein, the hypothesis that the COVID-19 pandemic has negatively affected the spontaneous reporting of adverse drug events was assessed.MethodsSpontaneous-report counts from 119 weeks (January 1, 2018, to April 12, 2020) were identified using Pfizer's safety database and were analyzed. Autoregressive integrated moving-average models were fitted to aggregated and disaggregated time series (TSs). Model residuals were charted on individual-value and moving-range charts and exponentially weighted moving-average charts for the identification of statistically unexpected changes associated with the pandemic.FindingsOverall, the reporting of serious adverse events showed no unexpected decline. Total global reporting declined, driven by HCP reporting (of both serious and nonserious events), starting after week 8 of 2020 and exceeding model expectations by week 15 of 2020, suggesting the pandemic as an assignable cause. However, reporting remained within longer-term historical ranges. The TS from Japan was the only national TS that showed a significant decline, and an unusual periodicity related to national holidays. A few countries, notably Taiwan, showed unexpected statistical increases in reporting associated with the pandemic, commencing as early as week 3 of 2020. In the literature, the reporting of adverse drug events was stable. Ancillary findings included prevalent year-end/beginning reporting minima, with more reports from HCPs than from consumers.ImplicationsUsing data from a large-scale and diverse safety database from a pharmaceutical company, a significant global decline in total reporting was detected, driven by HCPs, not consumers, and reports of nonserious events, consistent with the pandemic as an assignable cause, but the reporting remained within long-term ranges, suggesting relative durability. Importantly, the analyses found no unexpected decline in overall reporting of serious events. Future avenues of research include the use of data from large-scale, publicly available spontaneous reporting systems for assessing the generalizability of the present findings and whether they correlate with impaired signal detection, as well as a follow-up analysis of whether the effects on spontaneous reporting abate after the pandemic.     

Life-threatening adverse drug reactions at admission to medical intensive care: a prospective study in a teaching hospital

Objective To assess the characteristics of life-threatening adverse drug reactions in patients admitted to medical intensive care unit and to define those that could facilitate early identification. Design A prospective 6-month observational study. Patients Of the 436 admissions to the teaching hospital medical intensive care unit, all patients aged over 15 years and who had received documented drug treatment were included (n = 405). Measurements Characteristics of patients [age, gender, underlying diseases, organ failure(s), drugs taken, Severity Acute Physiologic Score II, length of stay, outcome at discharge] were prospectively collected using a standardised questionnaire. A panel of experts assessed putative serious adverse drug reaction(s) for each drug taken and each organ failure at admission by using a standardised causality assessment method. Characteristics of patients with and without serious adverse drug reactions at admission were compared using univariate and then stepwise descending multivariate logistic regression. Results Of the 405 patients included, 111 (27.4%) presented an adverse drug reaction leading to organ failure. In 48% of cases adverse drug reactions were preventable, 23% were undiagnosed and 19% contributed to death. Age over 75 years [odds ratio (OR) 2.25; 95% confidence interval (CI) 1.15–4.38; p = 0.02], having more than three drugs (OR 6.90; 95% CI 1.44–33.00; p = 0.02) and a diagnosis of haematological malignancy (OR 6.19; 95% CI 2.07–18.53; p = 0.001) were independently associated with serious adverse drug reactions. Conclusions Preventable life-threatening adverse drug reactions were frequently involved in organ failure at admission to medical intensive care; many of them had not been identified. Financial disclosures: None Conflict of interest: None     

2014年我院120例药品不良反应报告分析

目的:了解我院药品不良反应(ADR)发生的特点及ADR报告情况,促进临床合理用药。方法 :对我院2014年上报的120例药品不良反应报告进行回顾性统计分析。结果:120例ADR报告中,涉及药物共有70个品种,其中抗微生物药引起的ADR最多,约占44.4%;ADR以皮肤及其附件损害最为常见;静脉给药方式引发的ADR最多,约占81.7%。结论:应加强ADR的监测,重视安全合理用药,以避免和减少药品不良反应发生。     

Spontaneous adverse event notifications by patients subsequent to the marketing of a new formulation of Levothyrox® amidst a drug media crisis: atypical profile as compared with other drugs

Since patients may report spontaneously adverse events associated with their medications, such notifications are constantly on the rise. In 2017, an unexpected rise of notifications associated with the marketing of a new formula of Levothyrox, differing from the 30‐year‐old drug only by minor elements, occurred in France amidst widespread media coverage. Not much, if any, scientific or pharmacological rationale was identified to explain that signal. This led us to focus on the profile and the clinical characteristics of these notifications and compare them to those associated with other drugs. We gathered all the spontaneous drug adverse event notifications associated with either Levothyrox^® or other drugs, that we received from patients in 2017, in the sanitary territory of ~2.3 M people we surveyed. Each notification was assessed by a multidisciplinary team. We compared the number of notifications, the number of symptoms described and their clinical characteristics. A total of 1 544 patient notifications were evaluated: 1 372 cases totaling 7 342 adverse events concerned Levothyrox^® new formula, as compared with 172 cases reporting 528 adverse events for all other drugs. The number of symptoms reported per notification was significantly higher for Levothyrox^® (5.4) than for other drugs (3.1, P < 0.001). Symptoms associated with Levothyrox^® belonged to more System Organ Classes and were often unrelated to the disease or treatment, as compared with those associated with other drugs. The distribution of the cases according to the number of symptoms described was starkly different, the Levothyrox^® distribution being unimodal. Health authorities must address this issue as such large atypical reporting disproportionally affects the European pharmacovigilance database.     

Physicians' attitudes towards voluntary reporting of adverse drug events

At the time a new drug is placed on the market, information on its therapeutic effect and toxicity is limited. Because of its simplicity and widespread use, the voluntary reporting by clinical physicians is the main method for detecting rare or unexpected adverse drug events (ADEs). However, the usefulness of this method may be compromised if the reporting rate is low. We present the results of a questionnaire‐based case‐control study carried out among 692 physicians from Galicia (north‐west region of Spain), in which we assessed their attitudes and opinions towards ADEs. In general, the Galician physicians think it is difficult to link a given ADE with a drug (P < 0.05) and have very heterogeneous opinions on the fact that very severe ADEs are known before the drug is commercialized. They globally disagree with the proposal that ADE reporting should be remunerated and the fact that ADE reporting can be risky for the physician. Some of the beliefs concerning ADEs are incorrect. It is crucial to improve the training of the physicians through active educational strategies based on personal contact.     

Disproportionality analysis of buprenorphine transdermal system and cardiac arrhythmia using FDA and WHO postmarketing reporting system data

Objective: Positive-controlled clinical studies have shown a dose dependent effect of buprenorphine transdermal system on QTc interval prolongation. This study provides assessment of the buprenorphine transdermal system and cardiac arrhythmia using US FDA and WHO postmarketing reporting databases.

Methods: Disproportionality analysis of spontaneously reported adverse events to assess whether the reporting rate of cardiac arrhythmia events was disproportionately elevated relative to expected rates of reporting in both FDA and WHO databases. Cardiac arrhythmia events were identified using the standardized Medical Dictionary for Regulatory Activities query for torsade de pointes and/or QT prolongation (TdP/QTP). The threshold for a signal of disproportionate adverse event reporting was defined as the lower 90% confidence limit ≥ 2 of the Empiric Bayes geometric mean in FDA database and as the lower 95% confidence limit of the Informational Component >0 in WHO database.

Results: There were 124 (<1%) and 77 (2%) cardiac arrhythmia event cases associated with buprenorphine transdermal as compared to 3206 (12%) and 2913 (14%) involving methadone in the FDA and WHO databases, respectively. In the FDA database methadone was associated with a signal of disproportionate reporting for TdP/QTP (EB05 3.26); however, buprenorphine transdermal was not (EB05 0.33). In the WHO database methadone was associated with a signal of disproportionate reporting for TdP/QTP (IC025 2.66); however, buprenorphine transdermal was not (IC025 ?0.88). Similar trends were observed in sensitivity analyses by age, gender, and specific terms related to ventricular arrhythmia.

Conclusions: The signal identified in the transdermal buprenorphine thorough QTc study, which led to a dose limitation in its US label, does not translate into a signal of increased risk for cardiac arrhythmia in real world use, as assessed by this method of analyzing post-market surveillance data.     

Detection of adverse drug reactions: evaluation of an automatic data processing applied in oncology performed in the French Diagnosis Related Groups database

The aim of this study was to assess an automated detection method of serious adverse reactions induced by oral targeted therapy (OTT) in patients with cancer, performed in the French Diagnosis Related Groups (DRG) database. Patients with cancer of the Poitiers hospital who started an OTT between 2014 and 2015 were included. This study focused on adverse drug reaction which required inpatient hospitalization (ADR_h). All diagnoses coded in the DRG database for hospital stays that occurred within 3 months after OTT initiation were collected (potential ADR_h). Filters (exclusion criteria) were automatically applied on potential ADR_h to exclude diagnoses that were not adverse drug reactions (false positives). A pharmacovigilance review was carried out to identify ADR_h in the medical records (reported ADR_h). The sensitivity and specificity of the detection method were estimated for each filter combinations by comparison between potential and reported ADR_h. This study included 129 patients. The medical records review led to identify 19 ADR_h (all coded in the DRG database) in 14 patients. To maintain a 100% sensitivity of the method detection, the best specificity obtained was 58.3% (95% IC: [55.2–61.4]).The use of restrictive filters (‘drug’ in the diagnostic label, specific diagnosis code for adverse cancer drug reaction) resulted in a 97.8% specificity (95% IC: [96.6–98.5]) with a 38.2% sensitivity (95% IC: [23.9–55.0]). Our method has detected the third of ADR_h with an excellent specificity. Complementary experimentations in pharmacovigilance centers are necessary to evaluate the interest of this tool in routine in addition to spontaneous reporting.     

MILNACIPRAN FOR NEUROPATHIC PAIN AND FIBROMYALGIA IN ADULTS

ABSTRACT

Opioids are the cornerstone of pain management; however, their use is associated with a variety of adverse drug events (ADEs) ranging from nausea and vomiting to urinary retention and respiratory depression. The purpose of this review is to describe the frequency and cost associated with different types of opioid-related ADEs to better understand their economic impact. A search of studies published in journals from 1946 to December, 2013, was conducted using MEDLINE and EMBASE. A total of 20 articles were reviewed. Data reflect a substantial economic burden of opioid-related ADEs resulting in high hospital costs, prolonged hospital stays, and substantial health care resource usage. Nausea, vomiting, and constipation are frequent and increased costs occur in all types of pain (surgical, nonsurgical, cancer, noncancer) in both inpatients and outpatients. Given the large economic burden of opioid-related ADEs, prevention rather than treatment may be the most effective strategy.     

以医院药师为中心的药学服务降低药物不良反应发生率的效果

目的观察以医院药师为中心的药学服务降低药物不良反应发生率的效果。方法选取2017年5月至2019年5月在我院门诊药房用药治疗的120例患者为研究对象,随机将其分为对照组和观察组,每组60例。对照组采用常规用药指导,观察组在对照组基础上开展以医院药师为中心的药学服务。比较两组的应用效果。结果观察组的不良反应总发生率低于对照组(P<0.05)。观察组患者的满意度高于对照组(P<0.05)。观察组的用药依从率高于对照组(P<0.05)。结论以医院药师为中心的药学服务可以有效降低药物不良反应发生率,同时能够提高患者满意度和用药依从性,有助于促进患者康复。     

Adverse drug reactions: keeping up to date

The amount of published literature on adverse drug reactions is overwhelming; for example, the serial publication Side Effects of Drugs Annual lists and critically discusses over 3000 references each year. As a group, pharmacotherapeutics journals publish more papers on adverse drug reactions than journals that cover other fields, but even so they publish a minority of the total number of papers, and no single journal or group of journals can be highlighted as being a frequent source of primary information. Non-specialists must therefore rely on secondary literature (reviews) and tertiary literature (critical summaries) for information. Most of the primary published literature is in the form of anecdotal reports (30%) and formal studies or randomized controlled trials (35%). The anecdotal reports vary in quality; a new serial publication devoted to this type of article would bring some of the literature together and would improve the quality of reporting. Although many of the randomized controlled trials are of good quality and large enough to reveal benefit, most are too small to provide robust information about adverse drug reactions. Systematic reviews are too few in number (only 1.25% of publications on adverse drug reactions cited in Side Effects of Drugs Annual); more are needed.     

Online reporting system for transfusion-related adverse events to enhance recipient haemovigilance in Japan: A pilot study

BackgroundA surveillance system for transfusion-related adverse reactions and infectious diseases in Japan was started at a national level in 1993, but current reporting of events in recipients is performed on a voluntary basis. A reporting system which can collect information on all transfusion-related events in recipients is required in Japan.MethodsWe have developed an online reporting system for transfusion-related events and performed a pilot study in 12 hospitals from 2007 to 2010.ResultsThe overall incidence of adverse events per transfusion bag was 1.47%. Platelet concentrates gave rise to statistically more adverse events (4.16%) than red blood cells (0.66%) and fresh-frozen plasma (0.93%). In addition, we found that the incidence of adverse events varied between hospitals according to their size and patient characteristics.ConclusionThis online reporting system is useful for collection and analysis of actual adverse events in recipients of blood transfusions and may contribute to enhancement of the existing surveillance system for recipients in Japan.     

Adverse drug reactions: treatment burdens and nurse-led medication monitoring

Gabe M.E., Davies G.A., Murphy F., Davies M., Johnstone L. & Jordan S. (2011) Journal of Nursing Management  19, 377–392
Adverse drug reactions: treatment burdens and nurse-led medication monitoring Aim This paper focuses on adverse drug reactions and the potential for introduction of nurse-led medication monitoring. Background The prevention of patient harm caused by health-care organizations was accorded international priority over a decade ago, yet adverse drug reactions remain a significant treatment burden to patients. Evaluation This paper reviews the literature to summarize existing knowledge and understand treatment burdens associated with adverse drug reactions. Key issues While epidemiological studies explore the magnitude and complex nature of adverse incidents in health-care organizations, the monitoring of prescribed medications and their adverse effects remains an area of concern. Nurse-led medication monitoring has been highlighted as an initiative to minimize unnecessary drug-related patient harm. Conclusion This paper indicates that nurses are well-placed to monitor and reduce drug-related morbidity, and builds upon previous work which prioritizes the monitoring of prescribed medicine in a nurse-led adverse drug reaction profile. Implications for nursing management Nurse-led medication monitoring presents a unique opportunity to curtail unnecessary treatment burdens. However, important considerations including, patients’ and professionals’ time, added paperwork, nurse education and training and inter-professional communication need to be explored. Further work is now needed to establish the clinical gains and patient outcomes of nurse-led medication monitoring.     

130例不良反应报告分析及合理用药建议

目的:对130例临床药物不良反应报告进行回顾性分析,得出我院不良反应发生的特点,并对合理用药进行建议,以减少我院不良反应发生率。方法:对130例不良反应从性别、年龄、给药途径、药物分类等方面进行统计分析。结果:我院不良反应特点是在老年人和儿童中发生率较高,分别为33.08%和16.15%;女性(66.15%)多于男性(33.85%);发生不良反应最高的药物种类依次为抗菌药物(38.46%)、中成药(37.69%)及营养药物(6.92%),发生率较高品种为阿奇霉素、头孢呋辛、血塞通、生脉、痰热清、热毒宁,且20岁以下抗菌药物不良反应发生率高(42.00%),育龄期妇女中成药不良反应发生率高(30.61%)。结论:在合理用药中,建议我院应重点监护儿童中抗菌药物使用,育龄期女性中成药使用,老年人中成药和抗菌药物使用,并对阿奇霉素、头孢呋辛、血塞通、生脉、热毒宁、痰热清、疏血通7个品种建立重点监测制度,降低不良反应发生率。     

Investigating the link between drug consumption and adverse events reporting in France

The objective of this study is to examine the potential association between drug use and adverse event reporting in France. A number of drug users and cases reported were extracted from the French Health Care Insurance database (Open Medic) and the French pharmacovigilance database. We performed two separate mixed-effect models (with a drug used or reporting rate as dependent variables) with a random intercept for drug classes. We selected 62 drugs from 10 drug classes, for which 177 364 cases were reported in the French pharmacovigilance database in 2020. The results showed a strong association between drug users and the number of reported cases in France among each drug class (P < 0.01). Within a drug class, the number of reported cases is, therefore, a proxy for the exposure to a given drug in the population. This finding could be useful to approximate and compare drug exposure from pharmacovigilance databases.