Causality Assessment Tool Research Articles

Drug-Induced Liver Injury by Checkpoint Inhibitors: Benefit of a Causality Assessment Tool.

Drug-Induced Liver Injury by Checkpoint Inhibitors: Benefit of a Causality Assessment Tool.

Identifying Frequency of Mild Traumatic Brain Injury in Firefighters.

Background: Mild traumatic brain injury (mTBI) is a nationwide problem; yet, no firefighter mTBI data are available. Methods: In this cross-sectional study, we assessed retrospective head injuries using WHO guidelines. We captured mTBI frequency and examined firefighters' symptoms (e.g., using Ohio State University Traumatic Brain Injury Identification method, Brief Traumatic Brain Injury Screen, Warrior Administered Retrospective Causality Assessment Tool). Findings: Of 1,112 firefighters contacted, 60 responses were included. Most participants were White (80%), male (90%), former athletes (75%). 62% met mTBI symptom criteria. 75% reported at least one lifetime head injury. Number of head injuries and depression symptoms were associated (r = .36, p < .05). Conclusion/application to practice: Overall, it appears most firefighters have sustained at least one lifetime mTBI. Those with multiple head injuries may be at increased risk of depression. Occupational health professionals should be aware of firefighters' mTBI risk. Further research is warranted given findings.

A COMPARISON OF CAUSALITY ASSESSMENT TOOLS FOR SUSPECTED ADVERSE DRUG REACTIONS IN HOSPITALIZED PATIENTS AT A TERTIARY CARE HOSPITAL

Objective: The objective of the study was to compare six causality assessment (CA) tools for suspected adverse drug reactions (ADRs) reported in hospitalized patients at a tertiary care hospital in India.&#x0D; Methods: Intensive ADR monitoring was performed in indoor patients of two randomly selected medicine units. A detailed case report of each suspected ADR (n=120) was provided to six independent experts for CA using either visual analog scale (VAS) or WHO-UMC scale. Investigator assessed causality using Naranjo’s scale, Koh et al. scale, the French method, and Karch and Lasagna scale. Similar causality categories from these scales were coded for correlation. Agreement among experts and that between various CA tools were analyzed using Cohen’s kappa and Fleiss kappa. Reasons for disagreements among different scales were evaluated.&#x0D; Results: A variation was observed in the total number of drugs suspected to cause ADR by experts and investigator. “Likely” and “Plausible” causality were suggested frequently by experts using VAS whereas “Possible” causal association was frequent according to experts using the WHO-UMC scale and also by the investigator using algorithms except Koh et al. scale. None to the slight agreement was observed among experts who used VAS (k=0.117), whereas a substantial agreement was observed among experts using the WHO-UMC scale (k=0.707). A substantial agreement was observed between Karch and Lasagna scale and the French method (k=0.740). Both scales demonstrated moderate agreement with Naranjo’s scale. Disagreement among the WHO-UMC scale, the French method, and Karch and Lasagna scale were associated with polypharmacy, serious ADRs, non-availability of laboratory data, and skin and subcutaneous tissue ADRs.&#x0D; Conclusion: A higher inter-rater agreement with the WHO-UMC scale suggests its utility for CA of suspected ADRs in indoor patients. The French method and Karch and Lasagna scale can be used for CA in hospitalized patients as an adjunct to Naranjo’s scale. Factors associated with disagreement should be considered at the time of reporting ADRs and evaluating causality.

Natural Health Product-Drug Interaction Causality Assessment in Pediatric Adverse Event Reports Associated with Attention-Deficit/Hyperactivity Disorder Medication.

Background: Some pediatric patients with attention-deficit/hyperactivity disorder (ADHD) use natural health products (NHPs) such as herbal remedies. Although herbal remedies are generally considered to be safe when they are used appropriately, they may contain active components that can interact with medications being used concurrently, with potential for NHP-drug interactions leading to adverse events. Objectives: The objectives of this study were (1) to identify adverse event reports (AERs) involving commonly used herbal remedies and ADHD prescription medicines in children and adolescents; (2) to evaluate the quality of collected AERs; and (3) to assess whether NHP-drug interactions can be causally linked to reported adverse events. Methods: We systematically searched the FDAble database (FDAble.com) for herbal remedies commonly used by patients (4-18 years old) also taking ADHD drugs from 1997 to 2015. We assessed the completeness of the AERs and used three causality assessment tools modified for NHPs (Naranjo Adverse Drug Reaction Probability Scale, HORN Drug Interaction Probability Scale, and World Health Organization Uppsala Monitoring Centre Scale). Results: Of the 23 identified AERs involving both an herbal remedy and an ADHD prescription medication, most involved multiple (>3) substances with inadequate detail to assess multiple potential interactions. Following data extraction and evaluation of completeness, five AERs involving only one herbal remedy and one ADHD medication were evaluated for causality. An NHP-drug interaction was assessed to be probable in one case and to be possible in another. Both these reports involved a methylphenidate formulation and St. John's wort. Conclusions: Eighteen of the 23 identified AERs involving both an herbal remedy and an ADHD drug also involved other multiple ingredient products. The reporting quality was poor for the five AERs examined. Further research is needed to study the interaction between St. John's wort and methylphenidate.

Correction to: Adverse drug reaction causality assessment tools for drug-induced Stevens-Johnson syndrome and toxic epidermal necrolysis: room for improvement.

The correct name of the 9th Author is David J. Margolis. The original article was corrected.

Development and preliminary validation of an instrument to enable laypersons to assess suspected side effects from medicines.

Research into causality assessment tools enabling patients to assess suspected adverse drug reactions (ADRs) is limited. Supporting patients with tools could improve their confidence in discussions with health professionals and encourage reporting of suspected ADRs to regulators. This study describes development and preliminary validation of an instrument: Side Effect Patient ASsessment Tool (SE-PAST). SE-PAST was developed from survey and interview data involving patients experiencing suspected ADRs. It included 10 statements enabling causality assessment, covering timing, additional information sources, and experiences, with four options: yes/no/don't know/not applicable. Scoring and weighting resulted in four categories of causal association: highly probable, probable, possible, unlikely. Validation involved obtaining feedback from 31 individuals experiencing an ADR. Further validation involved online distribution through patient support groups and comparison of reported symptoms to known ADRs. Validators found SE-PAST easy to read (31), to understand (27), and to complete (29). A total of 294 respondents completed SE-PAST online, with 98% completing eight or more causality assessment statements. Symptoms were categorised as highly probable (46; 16%), probable (80; 62%), possible (44; 15%), and unlikely (21; 7%). A total of 221 respondents identified one suspected medicine, with 95% of these reporting at least one symptom known to be an ADR. Of 227 providing feedback, 139 (61%) found SE-PAST useful, 160 (71%) felt motivated to discuss their experience with a health professional, and 136 (60%) were encouraged to report to the regulator. SE-PAST was easily completed and understood by people experiencing suspected ADRs and could be useful in encouraging patient reporting to health professionals and agencies.

Tools for causality assessment in drug-induced liver disease.

There are three liver-specific causality assessment tools currently available to guide clinical diagnosis of Drug-Induced Liver Injury (DILI): Roussel-Uclaf Causality Assessment Method (RUCAM), Digestive-Disease-Week Japan 2004 scale (DDW-J), and Clinical Diagnostic Scale (CDS). The purpose of this review is to assess these tools and discuss how to improve the causality assessment process as a whole. Existing DILI-specific causality assessment tools are surprisingly similar and exhibit only minor differences in point allocation. But difference in threshold for likelihood of being DILI. We reviewed the literature on currently used causality assessment tools, identified areas for future improvement, and herein propose approaches for refinement. Opportunities to improve current models, as well as the assessment process, in general, include in particular provision of more precise clinical detail and to perhaps add new components to scoring systems. For example, the incorporation of drug-specific clinical signature patterns, accounting for a drug's inherent hepatotoxicity potential, and/or incorporation of other drug properties to scoring systems may allow enhancement. Further, more systemic exclusion of competing diagnoses is needed. Finally, causality assessment processes will likely benefit from a data-driven and computer-assisted approach. Current tools used for DILI adjudication are imperfect. Avenues to improve these tools are described.

DEVELOPMENT AND VALIDATION OF A NOVEL METHOD FOR CAUSALITY ASSESSMENT USING SUSPECTED ADVERSE DRUG REACTIONS TO ANGIOTENSIN-CONVERTING ENZYME INHIBITORS

Objectives: The study has been designed to develop, test reliability, and construct validity of a novel versatile causality assessment tool (VCAT) method.&#x0D; Methods: The study included 427 literature case reports of angiotensin-converting enzyme inhibitors with suspected adverse drug reactions from 1990 to February 25, 2016. The causality of these cases was assessed independently by 3 raters in 3 phases of the study. Kappa (k) and intra-class correlation Intraclass Correlation Coefficient (ICC) were used to test reliability and validity of the VCAT method.&#x0D; Results: Intra-rater reliability was high between Phase I and Phase III (k=0.84–0.93; % agreement: 92.3–96.3%). Inter-rater agreement was good in Phase I (k=0.87–0.89, % agreement: 93.7–94.1%, ICC: 0.975) and Phase III (k=0.85–0.89, % agreement: 93–94.4%, ICC: 0.973). Validity was proved by the high agreement observed between Phase I and Phase II (k=0.78–0.94; % agreement: 89.7–97.2%; p&lt;0.001); and between Phase II and Phase III (k=0.8–0.9; % agreement: 90.2–94.8%; p&lt;0.001).&#x0D; Conclusion: VCAT method is a standardized causal assessment tool that gives valid and reproducible results. It has shown good agreement with the expert judgment method. This method may overcome the limitations enthralled with existing methods of causality assessment.

Clinical profile and comparison of causality assessment tools in cutaneous adverse drug reactions

Background:Cutaneous adverse drug reactions (CADRs) are probably the most frequent of all manifestations of drug sensitivity. As a considerable number of new drugs are periodically introduced into the market, the incidence of CADR is likely to increase. The pattern of CADR and the causative drugs is likely to change accordingly. There is no uniformly accepted and reliable method of objectively assessing the causal link between drug and adverse reaction.Aim:To study the clinical patterns and causative drugs and compare causality assessment [World Health Organization (WHO) and Naranjo algorithm] of CADR among patients attending the dermatology department.Materials and Methods:This is a cross-sectional hospital-based study in which all patients with suspected CADR attending the dermatology department of a tertiary care center over a 9-month period were evaluated using the causality assessment criteria recommended by the WHO-Uppsala Monitoring Centre (UMC) and Naranjo scale. The severity of the reaction was assessed using Adverse Drug Reaction Severity Assessment Scale (modified Hartwig and Siegel scale).Results:A total of 200 consecutive patients with CADR were evaluated. The causality assessment for a drug as per WHO scale yielded 63 (31.5%) cases as certain, 12 (6%) as probable, and 125 (62.5%) as possible, whereas Naranjo scale showed 26 (13%) cases to be definite, 138 (69%) as probable, and 36 (18%) as possible. There was poor agreement between the two scales. Fixed drug eruption was the most common pattern of CADR (82.41%). The average number of drugs received by patients was 2.09. The most common suspected drug group was antimicrobials (n = 170; 40.5%), followed by nonsteroidal anti-inflammatory drugs (n = 148; 35.3%) and antiretroviral drugs (n = 41; 9.7%). Fixed drug eruption was most commonly caused by paracetamol. Antiepileptics and antimicrobials were the most common suspects among severe cutaneous adverse reactions.Limitations:Multiple concomitant drug usage by patients and inability to provoke all patients/measure drug levels in blood resulted in higher number of drugs with causal association as probable/possible.Conclusion:WHO-UMC scale was found to be easier to apply and evaluate, with greater practical utility. Poor agreement between the two commonly used scales emphasizes the need for a consistent and uniform causality assessment tool.

DEVELOPMENT AND VALIDATION OF A NOVEL METHOD FOR CAUSALITY ASSESSMENT USING SUSPECTED ADVERSE DRUG REACTIONS TO ANGIOTENSIN-CONVERTING ENZYME INHIBITORS

Objectives: The study has been designed to develop, test reliability, and construct validity of a novel versatile causality assessment tool (VCAT) method.Methods: The study included 427 literature case reports of angiotensin-converting enzyme inhibitors with suspected adverse drug reactions from 1990 to February 25, 2016. The causality of these cases was assessed independently by 3 raters in 3 phases of the study. Kappa (k) and intra-class correlation Intraclass Correlation Coefficient (ICC) were used to test reliability and validity of the VCAT method.Results: Intra-rater reliability was high between Phase I and Phase III (k=0.84–0.93; % agreement: 92.3–96.3%). Inter-rater agreement was good in Phase I (k=0.87–0.89, % agreement: 93.7–94.1%, ICC: 0.975) and Phase III (k=0.85–0.89, % agreement: 93–94.4%, ICC: 0.973). Validity was proved by the high agreement observed between Phase I and Phase II (k=0.78–0.94; % agreement: 89.7–97.2%; p&lt;0.001); and between Phase II and Phase III (k=0.8–0.9; % agreement: 90.2–94.8%; p&lt;0.001).Conclusion: VCAT method is a standardized causal assessment tool that gives valid and reproducible results. It has shown good agreement with the expert judgment method. This method may overcome the limitations enthralled with existing methods of causality assessment.

Novel Approaches to Causality Adjudication in Drug-Induced Liver Disease

Drug induced liver injury (DILI) is a complex diagnosis dominantly based of exclusion. Currently available causality assessment instruments are considered to be suboptimal. Expert opinion appears to be best method to adjudicate causality, but is impractical to implement on a wide scale basis. Thus, new approaches are needed, for example improving the specificity of current scoring systems. A further option would be to develop a system that utilizes computer-based scoring - which would reduce human error. Additionally, it would be ideal to have available drug specific scoring systems, based on drugs' characteristic "phenotypes" (presentation and pattern of injury). Eventually, a validated system could be integrated within the electronic health information system. This review highlights an avenue to an improved Causality Assessment Tool.

Safety of Dexamethasone for Nausea and Vomiting Prophylaxis in Children Receiving Hematopoietic Stem Cell Transplantation.

Many children undergoing hematopoietic stem cell transplantation (HSCT) experience chemotherapy-induced nausea and vomiting (CINV) despite receiving prophylaxis. Guideline-consistent CINV prophylaxis includes dexamethasone, but uncertainty with regard to safety potentially limits the use of dexamethasone in children. We describe immediate adverse events (AEs) attributable to dexamethasone given for CINV prophylaxis to children during HSCT conditioning. Children enrolled in a previous prospective study were retrospectively analyzed. Objective parameters related to specific AEs occurring within 5 days of dexamethasone administration were abstracted from health records and graded according to the Common Terminology Criteria for Adverse Events version 4.03 (CTCAE v4.03). Their association to dexamethasone was assessed using the Liverpool Causality Assessment Tool. Forty-six children (median age, 10.2 y) were eligible for analysis. The most frequent AEs attributable to dexamethasone (Liverpool Causality Assessment Tool category of probable or definite) were hyperglycemia (63%; CTCAE v4.03 grade 3: 2%), hypertension (52%; CTCAE v4.03 grade 3: 15%), and bradycardia (46%; CTCAE v4.03 grade 3: 0%). Other AEs included dyspepsia or gastroesophageal reflux disease (24%) and alterations in mood and behavior (9%). No AE exceeded CTCAE v4.03 grade 3 in severity. In children undergoing HSCT who received dexamethasone for CINV prophylaxis, immediate AEs attributable to dexamethasone were most often of minor clinical importance and transient.

Drug-Induced Liver Injury: Why is the Roussel Uclaf Causality Assessment Method (RUCAM) Still Used 25Years After Its Launch?

Launched in 1993 and partially based on the results of an international consensus meeting organized under the auspices of the Council of International Organizations of Medical Sciences (CIOMS), the Roussel Uclaf Causality Assessment Method (RUCAM) is the most used causality assessment tool worldwide for the diagnosis of drug-induced liver injury (DILI) and herb-induced liver injury (HILI) in a large number of epidemiological studies, case reports, and case series. The 25-year experience of RUCAM use confirmed that the success was due to its objective, standardized, and liver-injury-specific approach structured with defined key elements derived from a series of DILI cases with positive rechallenge. Using this series, the validation procedure avoided arbitrary definitions and confirmed scores to key items. The algorithm provides a quantitative causality grading of highly probable, probable, possible, unlikely, or excluded relationship between the liver injury and the suspected product(s). Despite challenges, prospective use of RUCAM fosters case data completeness and transparent causality adjudication in real time, as opposed to subjective opinion resulting from several rounds by experts lacking defined key elements and scores. In 2016, RUCAM was updated with specification of alcohol use and Hepatitis E Virus (HEV) biomarkers and simplified item handling to further reduce inter-observer variability. RUCAM-based probable and highly probable DILI and HILI cases are essential for the detection of new hepatotoxins, confirmation of new biomarkers, description of clinical features and risk factors, and determination of incidence in pharmacoepidemiological studies. This article is intended to encourage systematic use of sophisticated causality assessment methods such as RUCAM to improve DILI and HILI case evaluation and to increase confidence in published cases.

Challenges in the assessment of adverse drug reactions in children and neonates

Summary Adverse drug reactions (ADRs) are common in children and it is often difficult to distinguish ADRs from other underlying conditions. Children range from preterm neonates to adolescents with changing patterns of disease, pharmacokinetics and pharmacodynamics. The continuous development during childhood presents a challenge to developing, prescribing and administering age-appropriate medicines. Paediatric ADRs can be difficult to characterize. There is a lack of agreed definitions, which are needed so that data on ADRs can be consistently reported and reliably interpreted. Many of the adult tools to assess causality and avoidability are difficult to apply in paediatrics. Paediatric ADRs are under-reported in spontaneous reporting systems, and there is little research. Steps addressing the challenges include the Liverpool causality and avoidability assessment tools, improved definitions and more paediatric drug research following the introduction of Paediatric Regulation in 2007, requirement for risk assessment and after marketing surveillance. Advances in assessing susceptibility through pharmacogenomics offer hope of avoiding ADRs.

Causality or Relatedness Assessment in Adverse Drug Reaction and Its Relevance in Dermatology.

Causality assessment essentially means finding a causal association or relationship between a drug and drug reaction. Identifying the culprit drug or drugs can be lifesaving or helpful in preventing the further damage caused by the drug to our body systems. In dermatology practice, when it comes to cutaneous adverse drug reaction, this is much more important and relevant because many aetiologies can produce a similar cutaneous manifestation. There are multiple criteria or algorithms available as of now for establishing a causal relationship in cases of adverse drug reaction (ADR), indicating that none of them is specific or complete. Most of these causality assessment tools (CATs) use four cardinal principles of diagnosis of ADR such as temporal relationship of drug with the drug reaction, biological plausibility of the drug causing a reaction, dechallenge, and rechallenge. The present study reviews some of the established or commonly used CATs and its implications or relevance to dermatology in clinical practice.

The Challenges of Adverse Drug Reaction Evaluation

Prevention of adverse drug reactions (ADRs) is the essence of Pharmacovigilance and its precise diagnosis is crucially a primary step, which still remains a challenge among specialists. The objective here is to investigate and offer a notion of commonly used and the developed methods of causality assessment tools for the diagnosis of ADRs and discuss their pros and cons. There are several recognized ways for assessment methods with decisive factors of causality evaluation, all the information regarding reasons allocating causality, the advantages and limitations of the appraisal methods were extracted and evaluated. Expert judgment is typically based on the decisive factor on which algorithms are based, nevertheless in imprecise manner. The probabilistic methods use the similar principle; however, connect probabilities to each measure. Such approaches are quite skeptical and liable to generate cloudy causation results. The final evaluation is quite intricate due to numerous inherent shortcomings in causality assessment tools. Thus we are still looking for developing a high quality assessment tool (very specific, but at the same time, sensitive enough) which can meticulously establish suitable diagnostic criteria for ADRs with universal acceptance to improvise the fundamental aspect of drug safety.

Deaths and parasuicides associated with mefloquine chemoprophylaxis: A systematic review.

Mefloquine is recommended in international health guidelines for preventing malaria in travellers. Reports of psychosis and suicide are often alluded to but are not clearly established. We carried out a systematic review of the literature to identify and critically appraise any reported death or parasuicide associated with mefloquine prophylaxis. We developed a comprehensive search that included publications up to 11 July 2017. We included case studies but excluded newspaper reports. Two authors independently appraised each death or parasuicide against a standardised causality assessment tool. The protocol was registered on PROSPERO (CRD42016041988). We identified 527 articles that required full-text retrieval; of these 17 were unique publications that reported deaths or parasuicide. Eight unique publications had sufficient detail to be included in causality assessment. We identified 2 deaths with a probable association that appeared to be idiosyncratic drug reactions; we categorised the remaining 8 deaths as "unlikely" to be related to mefloquine, or "unclassifiable". There was one parasuicide with a possible causal association. There were 9 additional publications that searched spontaneous drug reporting databases; none provided sufficient detail to perform a causality assessment. Overall, the number of deaths that we could reliably attribute to the prophylactic use of mefloquine is very low.

O-24 Adrin 1 methodology study: adverse drug reactions in neonates: what are the best ways to evaluate suspected adverse drug reactions in neonates?

Background There are 90 000 babies admitted to neo-natal care units in the UK annually, and many of these require medications.1 Use of unlicensed and off-label medications is common in neonatal units, with accounting for up to 90% medicines.2 The incidence of adverse drug reactions (ADRs) in children is estimated to range between 0.6% and 16.8%, but the data specifically for neonates is limited.3 A number of tools exist to help clinicians to assess the causality of ADRs, but few have been validated in neonatal settings. This study aims to compare three existing methods for assessing causality of ADRs in a neonatal setting and to compare the outcomes be-tween tests and raters. Methods Following ethical approval, data were col-lected prospectively on suspected ADRs occurring in a tertiary neonatal care unit in the north of England over a five week period. Summaries of these cases were pre-sented to two investigators who undertook three sepa-rate causality assessments of each case using the Karch and Lasagna algorithm(KL), the Liverpool ADR Causality Assessment Tool (LCAT), and the New Adverse Drug Re-actions Algorithm for Infants in Neonatal Intensive Care Units(NAINICU).4,5,6 Inter-rater and inter-test statisti-cal analyses were performed. Results Causality assessments have been undertaken on 21 ADR cases reported from the unit to date. The KL algorithm rated 14.3% of cases as definite/likely, NAINICU 42.9% definite and LCAT 0% definite. Inter-rater reliability Kappa scores were 0.131, 0.136 and 0.294 for the 3 tools respectively. Inter-test reliability was greatest between the KL algorithm and the LCAT (Kappa 0.211) and least between NAINICU and LCAT (Kappa −0.149). Conclusion These three tools produced varied causali-ty assessment outcomes when used on neonatal ADRs. Marked inter-test and inter-rater variability was noted. The study is continuing to collect cases to help determine the optimal way to assess causaility in this popualtion.

Diagnosing Post Traumatic Stress Disorder: Using a Physiological Computing Method and Apparatus

Background: Post traumatic stress disorder (PTSD) is typically diagnosed using self-reports and physician interviews and observations. For example, the US military has used the Warrior Administered Retrospective Causality Assessment Tool (WARCAT), which is a self-report method for diagnostics. Methods: To help correct for associated deficiencies in self-reports, we utilized a computerized dual-task method and central nervous system (CNS) monitoring of reactions by participants who viewed troubling scenes. Results: We found evidence to support unreported PTSD reactions to these incidents. Furthermore, we used a computerized technique to induce cognitive load to distract participants from the purpose of the assessment to gain more accurate assessments. Conclusion: We conclude that using a computer apparatus is more effective in diagnosing PTSD than psychological instrumentation.

Adverse Drug Reactions in Children

Adverse drug reactions (ADRs) are a common clinical problem in both paediatric and adult medicine. ADRs are a frequent cause of hospitalization and one of the leading causes of morbidity and mortality. The aim of the study was to prospectively identify the ADRs causing hospital admission of children and identification of the risk factors and involved drugs. All patients aged 19 years or under admitted to hospital were included in the study, and all admissions for ADRs were prospectively screened for a period of 9 months. Suspected ADRs were subsequently evaluated, and causality assessment was undertaken to determine whether each suspected reaction was possible, probable or definite. The assessment of ADR causality was performed using the Naranjo algorithm, the Liverpool ADR Causality Assessment Tool and the Edwards and Aronson causality assessment method. During the study period, 2903 admissions were identified; of these, there were 143 admissions of patients with an oncological disease. Sixty-four admissions (2.2%) were caused by an ADR. Anticancer chemotherapy accounted for 35% of the cases, followed by antibiotics (18%). The use of different scoring systems does not lead to the differences in the numbers of ADR-diagnosed patient but may result in differences in the determination of the level of certainty. The majority of the ADR-diagnosed patient affected the hematopoietic and gastrointestinal systems; the drugs most frequently involved were cytotoxic agents and antibiotics. The most important risk factors identified were female sex and oncological disease. ADRs cause a small but substantial proportion of children’s hospital admissions. Preventing avoidable ADRs requires careful adherence to good prescribing practice.