Drug Reaction Assessment Research Articles

Severe exacerbation of facial dermatitis with swelling following introduction of abrocitinib in a patient with atopic dermatitis

BackgroundAbrocitinib, an oral small-molecule Janus kinase 1 (JAK1) inhibitor, has been widely accepted for the treatment of moderate-to-severe atopic dermatitis (AD). Currently there is a paucity of data on the adverse events (AEs) after abrocitinib treatment, especially on rare events such as exacerbation of facial dermatitis, and their causal relationship and subsequent management remains poorly elucidated.Case presentationA 43-year-old female patient with moderate AD received dupilumab after failure of topical treatments. Facial dermatitis persisted and became refractory after dupilumab treatment, and the patient changed treatment to oral abrocitinib. Fifteen hours after the first dose of abrocitinib, she developed exacerbation of facial dermatitis with swelling. The patient was initially diagnosed as abrocitinib-induced hypersensitivity. However, a score of 3 of the Naranjo adverse drug reaction assessment indicates week correlation between abrocitinib therapy and exacerbation of facial dermatitis, and negative results from subsequent drug provocation test further suggests no causal relationship.ConclusionsThe present case report highlights the necessity of careful determination of abrocitinib-induced hypersensitivity, which should not be diagnosed simply based on the time sequence between drug exposure and symptom occurrence. In addition, caution should be exercised for drug withdrawal, especially when confirmative evidence is absent. Drug provocation test can be helpful and effective treatments could be continued unless severe AEs occur.

The Utility of the Liverpool Adverse Drug Reaction Assessment Tools in the Evaluation of Chemotherapy-Induced Nausea and Vomiting in Children

The Utility of the Liverpool Adverse Drug Reaction Assessment Tools in the Evaluation of Chemotherapy-Induced Nausea and Vomiting in Children

Abrupt increased serum creatinine in a hyperferritinemia patient treated with deferoxamine after cord blood transplantation: a case report with literature review

BackgroundErythrocyte transfusion is an indispensable component of supportive care after hematopoietic stem cell transplantation (HSCT). However, HSCT recipients are susceptible to the development of acute kidney injury (AKI) with multifactorial causes. We report a case of a rapid elevation in serum creatinine associated with deferoxamine after cord blood transplantation (CBT).Case presentationA 36-year-old Japanese male diagnosed with relapsed Philadelphia-positive acute lymphoblastic leukemia received CBT. At day 88 post-CBT, multidrug-resistant Pseudomonas aeruginosa (MDRP) was isolated from urine culture. Subsequently, colistin 200 mg/day was administered parenterally for treatment of epididymitis from day 91 to 117 post-CBT. Despite concomitant administration of potential nephrotoxic agents such as piperacillin-tazobactam, acyclovir, and liposomal amphotericin B, no development of AKI was observed during this period. At day 127 post-CBT, MDRP was detected in blood and urine cultures, and colistin 200 mg/day was re-started parenterally. Due to extremely higher ferritin level, deferoxamine was administered intravenously at day 133 post-CBT. While serum creatinine was 1.03 mg/dL before starting deferoxamine, the level increased to 1.36 mg/dL one day after commencing deferoxamine (day 134 post-CBT), and further increased to 2.11 mg/dL at day 141. Even though colistin was discontinued at day 141 post-CBT, serum creatinine continued to increase. Deferoxamine was withdrawn at day 145 post-CBT, when serum creatinine peaked at 2.70 mg/dL. In addition, no cylinduria is observed during the period of development of AKI. In adverse drug reaction (ADR) assessment using Naranjo probability score, the scores of 3 in deferoxamine and 2 in colistin, respectively, indicated “possible” ADR. However, while colistin-associated AKI manifested early onset, recovery time within 2 weeks after discontinuation and development of cylinduria, this case was discordant with the properties. Furthermore, in the literature review, development of AKI within 1 day, including sudden increase in serum creatinine or abrupt reduction in urine volume, was reported in 3 identified cases.ConclusionsWe considered the rapid creatinine elevation to be the result of deferoxamine rather than ADR caused by colistin. Therefore, careful monitoring of kidney function is required in recipients of HSCT treated with deferoxamine.

Adverse Drug Reaction Monitoring and Assessment in Clinical Settings

Adverse Drug Reaction Monitoring and Assessment in Clinical Settings

Efficacy and safety of phenytoin versus clobazam as monotherapy for newly diagnosed epileptic patients

Background: Epilepsy is a chronic disorder characterized not only by recurrent seizures but also by a great variety of medical and psychosocial implications. Its burden to the patients and their families has been recognized and even the impact upon the community is vast. Aims and Objectives: The aim of the study was to compare the efficacy and safety of phenytoin and clobazam in monotherapy for the management of new onset, untreated epileptic patients. Materials and Methods: A 6 months, observational, comparative study was conducted on 60 adult patients with epilepsy. The eligible patients were given either phenytoin sodium (Group A; n=30) in a loading dose of 15 mg/kg orally, followed by 5 mg/kg/day maintenance dose for 6 months while Group-B (n=30) received clobazam in a dose of 1 mg/kg oral loading dose followed by 0.5 mg/kg/day. Seizure frequency was evaluated and compared with baseline at 1, 2, 3, 4.5, 6 months along with adverse drug reaction assessment. Results: In Group A mean pre-treatment baseline seizure frequency was 6.3±2.19 and for Group B 5.80±2.22. After 6 months, seizure frequency for Group A 2.30±1.99 and in Group B 1.30±1.91. In Group B, there was a significantly higher reduction in seizure frequency (P=0.001) than that of Group A. Both the drug groups significantly reduced the seizure frequency but Group B was found to be superior. Adverse drug reaction was more in Group A in comparison with Group B. The common side effects were drowsiness, weight gain, headache, tiredness, nausea and ataxia. Conclusion: Clobazam monotherapy had demonstrated better efficacy than phenytoin for the treatment of epilepsy and also well tolerated.

Molecular Fingerprinting by Single Cell Clone Analysis in Adverse Drug Reaction (ADR) Assessment.

Causality assessment for idiosyncratic ADRs mainly relies on epidemiology, signal detection and less often on proven or plausible mechanistic evidence of the drug at a cellular or organ level. Distinct clones of cells can exist within organs of individual patients, some conferring susceptibility to well-recognised Adverse Drug Reactions (ADRs). Recent advances in molecular biology have allowed the development of single-cell clonal techniques, including single-cell RNA sequencing (scRNA-seq) to molecularly fingerprint ADRs and distinguish between distinct clones of cells within organs in individuals, which may confer differing susceptibilities to ADRs. ScRNA- seq permits molecular fingerprinting of some serious ADRs, mainly in the skin, through the identification of Directly Expressed Genes (DEG) of interest within specific clones. Overexpressed DEGs provide an opportunity for targeted treatment strategies to be developed. scRN A-seq could be applied to a number of other ADRs involving tissues that can be biopsied/sampled (including skin, liver, kidney, blood, stem cells) as well as providing a molecular basis for rapid screening of potential therapeutic candidates, which may not otherwise be predictable from a class of toxicity/organ involvement. A framework for putative assessment for ADRs using scRNA-seq is proposed as well as speculating on potential regulatory implications for pharmacovigilance and drug development. Molecular fingerprinting of ADRs using scRNA-seq may allow better targeting for enhanced pharmacovigilance and risk minimisation measures for medicines with appropriate benefit-risk profiles, although cost-effectiveness and other factors, such as frequency/severity of individual ADRs and population differences, will still be relevant.

Oxaliplatin Induced Severe Hypoxemia, Chills and Hypersensitivity Reaction

Hypersensitivity reactions to platinum containing compounds are well described and potentially life threatening. The hypersensitivity reactions can occur either during, or shortly after the infusion of drug. The incidence increases with increase in the number of chemotherapy cycles. Hypersensitivity reactions can vary from mild reactions like rashes to severe reactions, which include laryngospasm, tachycardia, hypotension or hypertension. The combination of 5-flurouracil, leucovarin and oxaliplatin has been used in several studies to increase survival rates and reduce the risk of disease progression in patients with metastatic colorectal cancer (CRC) and stage III colon cancer. We report a case of patient treated with oxaliplatin who developed Severe Grade-III Toxicity including Hypoxemia, Chills and hypersensitivity reaction like rashes all over the body with itching sensation about few hrs after the oxaliplatin infusion. Patient tolerated 7 cycles of FLOT chemotherapy well. During cycle 8 chemotherapy after 50% infusion of oxaliplatin patient developed severe reaction to oxaliplatin such as breathlessness, shivering, hypersensitivity reaction like rashes all over the body and itching sensation. The drug infusion was stopped immediately, vitals were checked which shows BP: 170/110mmhg, Temperature 100⁰F, Spo2 85% RA. It was confirmed as grade 3 toxicity of oxaliplatin. The adverse drug reaction assessment was done using Naranjo’s causality assessment scale which showed ‘definite’ type of adverse drug reaction with oxaliplatin. Prompt recognition of this event and symptomatic treatment with supplemental oxygen and corticosteroids and prolonging the infusion time of oxaliplatin can lead to better patient compliance and lesser hypersensitivity reactions to these regimens.
 Keywords: Oxaliplatin, Colorectal cancer (CRC), Dyspnoea, Hypersensitivity reactions, Chemotherapy.

Translation, transcultural adaptation and validation to Brazilian Portuguese of tools for adverse drug reaction assessment in children

BackgroundChildren are more vulnerable to adverse drug reactions (ADRs) due to complex changes in the body during the growth process and lack specific pharmacoepidemiologic studies. Causality and Avoidability assessment of ADRs are relevant to clinical guidelines development and pharmacovigilance. This study aimed to translate and transcultural adapt two new tools—Liverpool Causality Assessment Tool (LCAT) and the Liverpool Avoidability Assessment Tool (LAAT)—to Brazilian-Portuguese and evaluate the psychometric properties of these tools to analyse ADRs in Brazilian children.MethodsThe validation of the cross-cultural adaptation of tools was obtained by the functional (conceptual, semantic, operational, and measurement) equivalence between the original and translated versions of each instrument. The translated version of LCAT and LAAT was applied to assessing the twenty-six case reports of suspected adverse drug reactions in a Brazilian teaching paediatric hospital. The inter-rater reliability (a pharmacist and a physician) was evaluated using Cronbach’s alpha. The exact agreement percentages (%EA) and extreme disagreement (%ED) were computed. Overall Kappa index was calculated with a 95% confidence interval.ResultsThere was a need to modify some terms translated into Portuguese for semantic and conceptual equivalence. The Cronbach’s alpha coefficient values obtained were 0.95 and 0.85, and the weighted Kappa (95% confidence interval) were 0.82 (0.67–0.97) and 0.68 (0.45–0.91) for LCAT and LAAT, respectively. The Brazilian-Portuguese versions of the LCAT and LAAT showed reliable and valid tools for the diagnosis and follow-up of ADRs in children.ConclusionThe methodological approach allowed the translation, transcultural adaptation, and validation to Brazilian-Portuguese of two easy and quick to perform tools for causality and avoidability of ADRs in children by a multidisciplinary expert specialist committee, including the authors of original tools. We believe these versions may be applied by professionals (patient safety teams) and researchers in Brazil in groups or by a single reviewer.Trial registrationThis study was evaluated and approved by the Research Ethics Committee (Instituto de Pediatria e Puericultura Martagão Gesteira – Federal University of Rio de Janeiro – Number: 3.264.238.

CASE STUDY ON IFOSMADIDE-INDUCED CYSTITIS

Adverse drug response elaborates, is response to the drug which is caused to an organ or tissue damage for normal dose in the patients for the prophylaxis, 22 years male patient was hospitalized with complaints of relapsed Hodgkin’s lymphoma (HL) using post-Adriamycin, Bleomycin, Binblastine, and Dacarbazine regimen. The patient had treated HL with ICE regimen, after 24 hours of treatment with prescribed the ICE regimen, The patient was observed with following symptoms like vomiting, painful burning micturition and laboratory investigations reported. Abnormal then we suggested Mesna 3 days for prophylactic course then symptoms were not found and patient was discharged. We conducted Adverse drug reaction (ADR) assessment was resulted as probable type and we can probably prevent this type of ADR.

A Comprehensive Evaluation of Studies on the Adverse Effects of Medications in Australian Aged care Facilities: A Scoping Review.

Aim: this scoping review was designed to identify studies that assess adverse drug reactions (ADRs) for older people in Australian aged care facilities. This review critically evaluates each published study to identify the risk of, or actual, adverse drug events in older people. Inclusion criteria: this review considered any clinical studies that examined the adverse effects of medications in older people who were living in aged care facilities. This review considered qualitative studies, analytical studies, randomized controlled trials (RCTs), descriptive cross-sectional studies, and analytic observational studies that explored the use of medications and their adverse effects on older people in clinical settings (including aged care facilities). Methods: an initial search of the PubMed (United State National Library of Medicine), OvidSP, EBSCOHost, ScienceDirect, Wiley Online, SAGE, and SCOPUS databases, with full text was performed, followed by an analysis of the article’s title and abstract. Additionally, MeSH (Medical Subject Headings) was used to describe the article. The initial round of the database search was based on inclusion criteria from studies that assessed tools or protocols aiming to identify the adverse effects of medications on the elderly population suffering chronic conditions or multiple co-morbidities. Two reviewers screened the retrieved papers for inclusion. The data presented in this review are in tabular forms and accompanied by a narrative summary which aligns with the review’s objectives. Results: seven studies were identified, and the extracted data from these studies were grouped according their characteristics and the auditing results of each study. Conclusion: it would be beneficial to design a comprehensive or broadly adverse drug reaction assessment tool derived from Australian data that has been used on the elderly in an Australian healthcare setting.

Safety of intravenous push thiamine administration at a tertiary academic medical center

ObjectivesIntravenous (IV) thiamine, administered using both diluted solution for infusion and undiluted solution for IV push, is used to correct low levels of thiamine. Although thiamine has a good safety profile, its IV administration is associated with rare cases of anaphylaxis. The objective of this analysis was to evaluate the incidence of anaphylaxis and IV site reactions associated with IV push thiamine. DesignA single-center, retrospective chart review was performed using electronic health records. Setting and participantsAll adult patients who received undiluted IV push thiamine between June 1, 2015, and July 31, 2017, were included. Patient demographics, IV access site, allergy history, and antihistaminic medication use before thiamine administration were collected. Outcome measuresAnaphylaxis was assessed while infiltration and phlebitis were evaluated using a standardized institutional grading system. All documented adverse events were adjudicated with the Naranjo Nomogram for adverse drug reaction assessment. ResultsA total of 8606 administrations in 2595 patients were evaluated; 5560 doses were administered peripherally, 1643 doses were administered centrally, and the line of administration was not documented for the remaining doses. Administrations included 7605 doses of 100 mg, 433 of 200 mg, 549 of 250 mg, and 19 of 500 mg. No anaphylactic or anaphylactoid reactions were observed. A total of 26 injection site reactions (0.30%) were noted in 19 patients (phlebitis, 12 events and infiltration, 14 events). Assessment with the Naranjo Nomogram classified 18 reactions to have a possible likelihood and 8 reactions to have a probable likelihood of being caused by IV push thiamine administration. ConclusionAdministration of IV push thiamine was not associated with any anaphylactic event and had a low incidence of IV site reactions. IV push thiamine in doses up to 250 mg appeared to be safe. There may be an indication for its safe administration with doses up to 500 mg, although more research is needed.

A rare case report on telmisartan-induced angioedema and mouth ulcers

A 67-year-old hypertensive female was hospitalized for painful, bleeding mouth ulcers, angioedema (lip swelling and glossitis), and dysphagia. A history reported by the patient and recent medication history revealed the onset of the symptoms on the initiation of telmisartan for hypertension. Telmisartan was discontinued, and the patient was managed symptomatically for pain, mouth ulcers, glossitis, and dysphagia. The symptoms completely resolved over 10 days of drug withdrawal. As per the World Health Organization and Naranjo adverse drug reaction assessment, telmisartan had a “Probable” association with the oral toxicity observed in this patient.

Study of adverse drug reaction and causality assessment of antidiabetic drugs

Background: Study about adverse drug reaction of antidiabetic drugs helps in ensuring maximum benefits of drug therapy.Methods: An observational study was carried out in patients attending tertiary care hospital in Kanyakumari district from August 2013 to August 2014. Adverse drug reactions due to the use of antidiabetic drugs were collected and adverse effects experienced by the patient was assessed using WHO scale, Naranjo scale, Schumock and Thornton scale and Hartwig and Siegel scale.Results: In this prospective study a total of 76 adverse events (41 male and 35 female) were identified. Most frequently observed adverse effect were hypoglycaemia and the less observed were pruritis. Maximum of 14 adverse effect were observed due to use of insulin. Combination of sulphonylurea and biguanides caused 28 adverse effects. Assessment of adverse effect using WHO scale showed 64% as probable, 16% possible, 7% conditional, 5% unclassifiable, 4% certain, and 4% unlikely. Relationship of adverse reaction to antidiabetic drugs using Naranjo scale showed 92% possibly, 5% probably and 3% as definite. Antidiabetic drug adverse effects were not preventable in 63%, definitely preventable in 19% and probably preventable in 18% as per modified Schumock and Thornton scale. Severity assessment of adverse effects were mild in 75%, moderate in 25% and no severe reactions according to modified Hartwig and Siegel scale.Conclusions: Adverse effect most commonly encountered during the study period were predictable, definitely preventable and without serious effects. Majority of the reactions were due to combination of antidiabetic drugs.

The utility of drug reaction assessment trials for inhaled therapies in patients with chronic lung diseases.

Current guidelines recommend a Drug Reaction Assessment (DRA) before beginning inhaled therapies to assess for bronchoconstriction and tolerability. There is limited evidence to support this recommendation. In this study we aimed to establish the predictors of successful DRAs in different patient groups using a cohort of all DRAs performed in adults between 2011 and 2016 at the Royal Brompton Hospital. Spirometry, age, gender, height, and underlying lung disease were recorded. A multivariable logistic regression model was constructed to ascertain variables associated with successful DRAs. There were 1492 DRA trials using hypertonic saline (32%), antimicrobials (63%), or rhDNase (5%). The majority of patients (94%, n = 1408) passed the DRA. Mean FEV1% predicted was 58.03 (SD 23.36). Female sex, type of inhaled product, and FEV1% predicted were established as significant predictors for DRA success. An FEV1% predicted > 55% was associated with greater probability of DRA success (Odds Ratio [OR]: 2.96 (1.80,4.86) p < 0.0001). Those receiving dry powder, inhaled antibiotics were more likely to pass the DRA compared to nebulised antibiotics (OR: 3.99 (1.38,11.51) p = 0.01)). This study classifies distinct patient groups with varying baseline risks which can be used to predict tolerability when adding an inhaled product to their management plan. Some "low risk" patients may in future be able to self-assess their tolerability for inhaled therapies at home to avoid unneeded hospital monitoring.

Taking the challenge: A protocolized approach to optimize Pneumocystis pneumonia prophylaxis in renal transplant recipients.

While trimethoprim-sulfamethoxazole is considered first-line therapy for Pneumocystis pneumonia prevention in renal transplant recipients, reported adverse drug reactions may limit use and increase reliance on costly and less effective alternatives, often aerosolized pentamidine. We report our experience implementing a protocolized approach to trimethoprim-sulfamethoxazole adverse drug reaction assessment and rechallenge to optimize prophylaxis in this patient cohort. We retrospectively reviewed 119 patients receiving Pneumocystis pneumonia prophylaxis prior to and after protocol implementation. Forty-two patients (35%) had 48 trimethoprim-sulfamethoxazole adverse drug reactions documented either at baseline or during the prophylaxis period, of which 83% were non-immune-mediated and 17% were immune-mediated. Significantly more patients underwent trimethoprim-sulfamethoxazole rechallenge after protocol implementation (4/22 vs 23/27; P=.0001), with no recurrence of adverse drug reactions in 74%. In those who experienced a new or recurrent reaction (26%), all were mild and self-limiting with only 1 recurrence of an immune-mediated reaction. After protocol implementation, aerosolized pentamidine-associated costs were reduced. The introduction of a standard approach to trimethoprim-sulfamethoxazole rechallenge in the context of both prior immune and non-immune-mediated reactions was safe and successful in improving the uptake of first-line Pneumocystis pneumonia prophylaxis in renal transplant recipients.

Azathioprine-Induced Pancytopenia and Septic Complications: A Probable Cause of Death

Azathioprine, an immunosuppressant which is widely used in the management of the autoimmune neuromuscular disorder. Myasthenia gravis is known to cause myelotoxicity. A 55-year-old male recently diagnosed with myasthenia gravis and chronic kidney disease was put on azathioprine (100 mg/d) along with pyridostigmine and prednisolone. When the treatment was initiated, the hematological reports revealed normal levels of blood count. However, approximately within 3 weeks of continuing the prescribed drugs, the patient was readmitted for complaints of loose watery stools, weakness, and giddiness. Clinical investigations revealed severe pancytopenia, suspecting to be related to azathioprine. The suspected drug (azathioprine) was withdrawn, and the management for pancytopenia was initiated. However, on the second day of hospitalization, the patient underwent cardiac arrest and septic shock which lead to death. Adverse drug reaction assessment revealed a plausible and causal relationship of azathioprine with pancytopenia and other adverse effects seen in this patient.

A Multicenter Evaluation of Off-Label Medication Use and Associated Adverse Drug Reactions in Adult Medical ICUs.

Prior research indicates that off-label use is common in the ICU; however, the safety of off-label use has not been assessed. The study objective was to determine the prevalence of adverse drug reactions associated with off-label use and evaluate off-label use as a risk factor for the development of adverse drug reactions in an adult ICU population. Multicenter, observational study : Medical ICUs at three academic medical centers. Adult patients (age ≥ 18 yr old) receiving medication therapy. All administered medications were evaluated for Food and Drug Administration-approved or off-label use. Patients were assessed daily for the development of an adverse drug reaction through active surveillance. Three adverse drug reaction assessment instruments were used to determine the probability of an adverse drug reaction resulting from drug therapy. Severity and harm of the adverse drug reaction were also assessed. Cox proportional hazard regression was used to identify a set of covariates that influenced the rate of adverse drug reactions. Overall, 1,654 patient-days (327 patients) and 16,391 medications were evaluated, with 43% of medications being used off-label. One hundred and sixteen adverse drug reactions were categorized dichotomously (Food and Drug Administration or off-label), with 56% and 44% being associated with Food and Drug Administration-approved and off-label use, respectively. The number of adverse drug reactions for medications administered and the number of harmful and severe adverse drug reactions did not differ for medications used for Food and Drug Administration-approved or off-label use (0.74% vs 0.67%; p = 0.336; 33 vs 31 events, p = 0.567; 24 vs 24 events, p = 0.276). Age, sex, number of high-risk medications, number of off-label medications, and severity of illness score were included in the Cox proportional hazard regression. It was found that the rate of adverse drug reactions increases by 8% for every one additional off-label medication (hazard ratio = 1.08; 95% CI, 1.018-1.154). Although adverse drug reactions do not occur more frequently with off-label use, adverse drug reaction risk increases with each additional off-label medication used.

Safety of Compounded Calcium Chloride Admixtures for Peripheral Intravenous Administration in the Setting of a Calcium Gluconate Shortage

Calcium gluconate is preferred over calcium chloride for intravenous (IV) repletion of calcium deficiencies in the inpatient setting. In the setting of a national shortage of IV calcium gluconate, our institution implemented a compounded calcium chloride admixture for IV administration. The objective of this analysis is to evaluate the peripheral infusion site safety of compounded IV calcium chloride admixtures in adult inpatients. A total of 222 patients, encompassing 224 inpatient admissions, from April to June 2011 were retrospectively reviewed. Sterile preparations of calcium chloride in 5% dextrose (600 mg/250 mL and 300 mg/100 mL) were used during the study time period. Adverse infusion site reactions were assessed using an institutional infiltration and phlebitis grading system. A total of 333 doses were administered peripherally. In all, 4 (1.8%) patients experienced a moderate to severe infusion site reaction, with 3 due to phlebitis and 1 due to infiltration. Naranjo Nomogram for Adverse Drug Reaction Assessment classified all 4 reactions to have a possible link to calcium chloride administration. Peripheral administration of compounded calcium chloride admixtures in 5% dextrose is associated with a low incidence of IV infusion site reactions and can be considered as an alternative in the event of a calcium gluconate shortage.

Réactualisation de la méthode française d’imputabilité des effets indésirables des médicaments

A tripartite group, entitled « CRI » (for Cercle de réflexion sur l'imputabilité), involving French pharmacovigilance staff from the French network of the Regional centers of pharmacovigilance, from pharmaceutical companies, and from French Health Authorities (Agence française de sécurité sanitaire des produits de santé) has worked to update the French drug reaction assessment method. Following assessment of strengths and weaknesses of the previous method, several points for improvement are proposed : a more precise wording and a more discriminating scale for some of the chronological and semiological criteria, a wider distribution of the intrinsic score from 5 to 7 levels, a new bibliographic scale for differentiating expected and unexpected adverse drug reactions, and a new informativness scale. This updated method would lead to a more relevant assessment of relationship between a drug and the occurrence of an adverse reaction. Furthermore, this method is a teaching tool to assess the level of relationship between a drug and the occurrence of an adverse reaction.

The value of case series in adverse drug reaction assessment

Summary Case studies are recognized as important tools for monitoring drug safety, particularly after the drug is licensed and being used widely. Recently, criteria have been formulated to ensure that published case reports and case series are robust, but these are not always met in practice.