Economic Evaluation of HLA-B*15:02 Genotyping for Asian Australian Patients With Epilepsy.

Importance: The HLA-B*15:02 allele has been associated with an increased risk of carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in specific Asian populations (including Han Chinese, Malaysian, Thai, and Vietnamese individuals). While HLA-B*15:02 genotype testing in Asian populations is recommended by several international prescribing guidelines, it is not subsidized by the Medicare Benefits Schedule in Australia. Objective: To evaluate the cost-effectiveness of HLA-B*15:02 genotyping in Asian Australian patients with epilepsy. Design, Setting, and Participants: A model with components of decision analysis and Markov simulation was developed to simulate clinical trajectories of adult Asian Australian patients with newly diagnosed epilepsy being considered for carbamazepine treatment. Cost-effectiveness and cost-utility analyses over a lifetime time horizon were conducted from the perspective of the Australian health care sector. The study was conducted in May 2023 and data analysis was performed from August 2023 to November 2023. Intervention: No HLA-B*15:02 genotyping and the empirical initiation of treatment with carbamazepine vs HLA-B*15:02 genotyping and the initiation of treatment with valproate in allele carriers. Main Outcomes and Measures: Life-years (LYs), quality-adjusted life-years (QALYs), and costs in 2023 Australian dollars (A$); incremental cost-effectiveness ratios. Results: HLA-B*15:02 screening was associated with an additional mean cost of A$114 (95% CI, -A$83 to A$374; US$76; 95% CI, -US$55 to US$248) and a reduction in 0.0152 LYs (95% CI, 0.0045 to 0.0287 LYs) but improvement by 0.00722 QALYs (95% CI, -0.0247 to -0.01210) compared with no screening, resulting in an incremental cost-effectiveness ratio of A$15 839 per QALY gained (US$10 523 per QALY). Therefore, universal genotyping for Asian Australian individuals was cost-effective compared with current standards of practice at the A$50 000 per QALY willingness-to-pay threshold. Sensitivity analyses demonstrated that the intervention remained cost-effective across a range of costs, utilities, transition probabilities, and willingness-to-pay thresholds. At the A$50 000 per QALY willingness-to-pay threshold, universal screening was the preferred strategy in 88.60% of simulations. Conclusions and Relevance: The results of this economic evaluation suggest that HLA-B*15:02 screening represents a cost-effective choice for Asian Australian patients with epilepsy who are being considered for treatment with carbamazepine.

Background rates for severe cutaneous reactions in the US: Contextual support for safety assessment of COVID-19 vaccines and novel biologics.

The global COVID-19 public health crisis has resulted in extraordinary collaboration to expeditiously develop vaccines and therapeutics. The safety of these biologics is closely monitored by the US Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention (CDC). Novel products may have limited safety data, and although serious medical outcomes associated with vaccination are rare, knowledge of background incidence rates of medical conditions in the US population puts reported adverse events (AEs) in perspective for further study. Although relatively minor vaccination skin reactions are common, rare instances of severe delayed hypersensitivity reactions such as erythema multiforme (EM), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and SJS/TEN overlap syndrome may occur. To aid in the assessment of these events, we performed a literature search in PubMed and Web of Science on the background incidence of EM, SJS, SJS/TEN, and TEN in the US population and on published reports of these conditions occurring post-vaccination. The US background annual incidence rates per million individuals of all ages ranged from 5.3 to 63.0 for SJS, from 0.4 to 5.0 for TEN, and from 0.8 to 1.6 for SJS/TEN. Since these conditions may overlap, some studies reported rates for EM/SJS/TEN combined, however we did not find studies with exclusive EM incidence rates. The published literature, including studies of reports submitted to the FDA/CDC Vaccine Adverse Event Reporting System (VAERS), describes post-vaccination EM, SJS, SJS/TEN and/or TEN as rare occurrences. The vaccines most frequently associated with these conditions were measles, mumps, and rubella; diphtheria, tetanus, and pertussis; and varicella. The majority of VAERS reports of EM, SJS, SJS/TEN, or TEN occurred in children within 30 days of vaccination. This review summarizes background rates of these disorders in the general population and published AEs among vaccine recipients, to support safety surveillance of COVID-19 vaccines and other biologics.

[Stevens-Johnson syndrome in a patient with positive lymphocyte transformation test]. / Síndrome de Stevens-Johnson en una paciente con prueba positiva de transformación linfocitaria.

BACKGROUND: Stevens-Johnson syndrome is a severe drug reaction. Sulfonamides have been associated with drug reactions, complications, sequelae, even death. CASE REPORT: A 40-year-old female patient with a medical history of endometriosis and recently diagnosed chronic inflammatory ulcerative colitis. She was treated at the Allergology service of the San Juan de Dios Hospital of the Costa Rican Social Security Fund, and after 20 days of treatment with sulfasalazine she had a severe drug reaction on the skin, compatible with Stevens-Johnson syndrome. The lymphocyte transformation test was positive, confirming sulfasalazine as the causative agent. CONCLUSION: The lymphocyte transformation test is a useful method that can confirm the causative agent and prevent important complications in the future.

ANTECEDENTES: El síndrome de Stevens-Johnson es una reacción medicamentosa severa. Las sulfamidas se han asociado con reacciones medicamentosas, complicaciones, secuelas, incluso la muerte. REPORTE DE CASO: Paciente femenina de 40 años, con antecedentes médicos de endometriosis y colitis ulcerativa crónica inflamatoria de reciente diagnóstico. Fue atendida en el servicio de Alergología del Hospital San Juan de Dios de la Caja Costarricense del Seguro Social, y luego de 20 días de tratamiento con sulfasalazina tuvo una reacción medicamentosa severa en la piel, compatible con síndrome de Stevens-Johnson. La prueba de transformación linfocitaria resultó positiva, con lo que se confirmó la sulfasalazina como el agente causal. CONCLUSIÓN: La prueba de transformación linfocitaria es un método útil que puede confirmar el agente causal y prevenir complicaciones importantes a futuro.

Lifetime risk, life expectancy, loss-of-life expectancy and lifetime healthcare expenditure for Stevens-Johnson syndrome/toxic epidermal necrolysis in Taiwan: follow-up of a nationwide cohort from 2008 to 2019.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) not only cause acute, devastating mucocutaneous reactions but also have long-lasting implications on survivors' lives. OBJECTIVES: To quantify the lifetime burden of SJS/TEN. METHODS: The cumulative incidence rate (CIR), life expectancy (LE), loss-of-life expectancy (LoLE) and lifetime healthcare expenditure (HE) for SJS/TEN were estimated over the period from 2008 to 2019 using data from the National Health Insurance Research Database of Taiwan and life tables of vital statistics. RESULTS: In this nationwide cohort of 6552 incident SJS/TEN cases, a trend towards a decrease in the CIR was observed between 2008 and 2019. Compared with the general population, patients with SJS/TEN experience a tremendous loss of 9.43 (1.06) [mean (SEM)] years of LE after diagnosis of SJS/TEN. Male patients with SJS/TEN had higher LoLE [10.74 (1.22) vs. 7.69 (1.43) years] and annual HE than females. Younger age at diagnosis of SJS/TEN was associated with longer LE but greater LoLE and higher lifetime HE. Patients with intensive care unit admission on diagnosis, malignancy, diabetes mellitus, end-stage renal disease and SJS/TEN-associated sequelae experienced substantially greater LoLE and HE per life year. CONCLUSIONS: Patients with SJS/TEN suffer substantial loss-of-LE and HE, particularly young patients, compared with the general population. These data provide a reference estimate of the lifetime burden of SJS/TEN to help health authorities evaluate the cost-effectiveness of future preventive and treatment strategies to minimize the burden of SJS/TEN.

A Comprehensive Assessment of Long-Term Complications in Patients with Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis.

INTRODUCTION: Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and SJS/TEN overlap syndrome are rare severe hypersensitivity reactions that lead to epithelial sloughing. Studies investigating the chronic multisystem effects of these syndromes and assessing patients in terms of quality of life (QOL), depression, and anxiety in the pediatric population are limited. In this study, we aimed to investigate the long-term effects of these diseases from a multisystem perspective. METHOD: Sixteen pediatric patients diagnosed with SJS, TEN, and SJS/TEN overlap syndrome were evaluated between September 2020 and March 2021. Physical and eye examinations were performed. To evaluate QOL and psychological status, Children's Dermatology Life Quality Index (CDLQI), Screen for Child Anxiety-Related Emotional Disorders (SCARED), and Children's Depression Inventory (CDI) were conducted. The patients' general characteristics, symptoms, and examination findings at their first admission were retrospectively obtained from the hospital's electronic records. RESULTS: Nineteen percent of the patients were female (n = 3). There were 7 patients (44%) with the diagnosis of SJS, 5 patients (31%) with TEN, and 4 patients (25%) with SJS/TEN overlap. The median follow-up time of the subjects was 6.5 years. The most common sequelae in the chronic period were skin changes (n = 13, 81%). Hyperpigmentation was the most common skin change (n = 9, 56%). In the last evaluation, 9 cases had eye involvement. In two cases, eye examination was normal in the acute phase, while ocular involvement was present in the chronic period. In 4 (50%) patients, there was height and/or weight percentile loss. Three patients' SCARED scores and 2 patients' CDI scores were high. According to the CDLQI survey, SJS, TEN, or SJS/TEN overlap syndrome had a small to moderate effect on the QOL in the 43% (n = 6) of the patients. The ANA values of 3 patients (60%) were positive at the follow-up and negative at the first admission. CONCLUSION: SJS, TEN, and SJS/TEN overlap syndrome may cause sequelae even after a long time of the onset of the disease. Patients' QOL and psychological status can be affected negatively. Ocular symptoms may develop in the follow-up, even without involvement in the acute period. Patients with SJS, TEN, and SJS/TEN overlap syndrome should be followed up in the chronic period and approached multidisciplinary.

Integrating real-world data in cost-effectiveness analysis of universal HLA-B*15:02 screening in Malaysia.

AIMS: Despite the availability of newer antiseizure medications, carbamazepine (CBZ) remains the gold standard. However, patients of Asian ancestry are susceptible to CBZ-related severe cutaneous adverse reactions. Universal HLA-B*15:02 screening is a promising intervention to address this. With the increasing recognition of integrating real-world evidence in economic evaluations, the cost-effectiveness of universal HLA-B*15:02 screening was assessed using available real-world data in Malaysia. METHODS: A hybrid model of a decision tree and Markov model was developed to evaluate 3 strategies for treating newly diagnosed epilepsy among adults: (i) CBZ initiation without HLA-B*15:02 screening (current practice); (ii) universal HLA-B*15:02 screening prior to CBZ initiation; and (iii) alternative prescribing without HLA-B*15:02 screening. The model was populated with real-world inputs derived from the Malaysian population. From a societal perspective, base-case analysis and sensitivity analyses estimated the costs and outcomes over a lifetime. Incremental cost-effectiveness ratios were calculated. RESULTS: In the base-cases analysis, universal HLA-B*15:02 screening yielded the lowest total costs and the highest total quality-adjusted life years (QALYs) gained. Compared with current practice, universal screening was less costly by USD100 and more effective by QALYs increase of 0.1306, while alternative prescribing resulted in 0.1383 QALYs loss at additional costs of USD332. The highest seizure remission rate (56%) was estimated for universal HLA-B*15:02 screening vs. current practice (54%) and alternative prescribing (48%). CONCLUSION: Our study suggests that universal HLA-B*15:02 screening is a cost-effective intervention in Malaysia. With the demonstrated value of real-world evidence in economic evaluations, more relevant standardization efforts should be emphasized to better inform decision-making.

Assessment of Need for Improved Identification of a Culprit Drug in Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis.

Importance: Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a severe hypersensitivity reaction. Identifying a culprit drug is critical for patient care, yet identification is based on clinical judgment. Data are limited on the accuracy in or approach to identifying a culprit drug. Objective: To evaluate patient allergy list outcomes, current approaches in identifying culprit drugs, and potential methods of improving culprit drug identification. Design, Setting, and Participants: This retrospective cohort study spanned 18 years (January 2000 to July 2018), was conducted at Brigham and Women's Hospital and Massachusetts General Hospital (Boston), and included patients with clinically and histologically confirmed cases of SJS/TEN overlap and TEN. Main Outcomes and Measures: This study descriptively analyzed potential culprits to SJS/TEN, patients' allergy lists, and currently used approaches that led to those lists. It then tested the theoretical contribution of incorporating various parameters to allergy list outcomes. Results: Of 48 patients (29 women [60.4%]; 4 Asian [8.3%], 6 Black [12.5%], 5 Hispanic [10.4%], and 25 White [52.1%] individuals; median age, 40 years [range, 1-82 years]), the mean (SD) number of drugs taken per patient at disease onset was 6.5 (4.7). Physicians labeled 17 patients as allergic to a single culprit drug. Comparatively, 104 drugs were added to allergy lists across all patients. Physicians' approaches relied largely on heuristic identification of high-notoriety drugs and the timing of drug exposure. Use of a vetted database for drug risk improved sensitivity. Algorithm for Drug Causality for Epidermal Necrolysis scoring was discordant in 28 cases, labeling an additional 9 drugs missed by physicians and clearing 43 drugs labeled as allergens by physicians. Human leukocyte antigen testing could have potentially affected 20 cases. Consideration of infection as a culprit was limited. Conclusions and Relevance: The results of this cohort study suggest that currently used approaches to identify culprit drugs in SJS/TEN are associated with overlabeling patients allergic to likely nonculprit drugs and less commonly missed possible culprit drugs. Incorporation of a systematized unbiased approach could potentially improve culprit drug identification, although ultimately a diagnostic test is necessary.

Postmarket Assessment for Drugs and Biologics Used in Dermatology and Cutaneous Adverse Drug Reactions.

Postmarket surveillance is critical for the identification of rare safety risks, which are unlikely to be identified during clinical trials and the drug development program. Rare adverse drug reactions with the potential for serious outcomes, including fatalities, include the severe cutaneous adverse reactions of Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms. Dermatologists play an important role in the diagnosis of these serious drug reactions and contribute to drug safety by reporting cases of suspected cutaneous adverse drug reactions.

Agreement Among Different Scales for Causality Assessment in Drug-Induced Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis.

BACKGROUND AND OBJECTIVE: Identification of the offending drug is crucial and challenging in cases of severe cutaneous adverse drug reactions (CADR) like Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Poor reproducibility and varying levels of agreement have been observed among different causality assessment tools (CATs) in assessing severe CADRs. This study was conducted to examine the agreement among four different CATs in assessing cases of drug-induced SJS, TEN and SJS/TEN overlap. METHODS: All cases of drug-induced SJS, TEN and SJS/TEN overlap, which were reported between January 2012 and January 2020, were identified from the ADR register at an ADR monitoring centre. Causality assessment was done in these reported cases using the following CATs: The World Health Organization-Uppsala Monitoring Centre (WHO-UMC) scale, Naranjo algorithm, Liverpool algorithm and Algorithm of drug causality for epidermal necrolysis (ALDEN). Weighted kappa (κw) test was used to evaluate the agreement among four CATs. RESULTS: A total of 30 cases of drug-induced SJS, TEN and SJS/TEN overlap were included in our analyses. The most common offending groups of drugs were anticonvulsants (46.7%), antimicrobials (40%) and nonsteroidal anti-inflammatory drugs (13.3%). Of the anticonvulsants, phenytoin (13.3%), carbamazepine (10%), and valproate (10%) were the commonly reported offending drugs. Poor agreement was observed among the four different causality assessment scales. CONCLUSION: Discrepancies were observed among four different CATs in assessing drug-induced SJS and TEN. A CAT, which is more specific to drug-induced SJS and TEN, simple, user-friendly with limited subjective interpretation, incorporating new immunological and pharmacogenetic markers, is necessary.

Assessment of Treatment Approaches and Outcomes in Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: Insights From a Pan-European Multicenter Study.

IMPORTANCE: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe drug reactions associated with a high rate of mortality and morbidity. There is no consensus on the treatment strategy. OBJECTIVE: To explore treatment approaches across Europe and outcomes associated with the SJS/TEN disease course, as well as risk factors and culprit drugs. DESIGN, SETTING, AND PARTICIPANTS: A retrospective pan-European multicenter cohort study including 13 referral centers belonging to the ToxiTEN ERN-skin subgroup was conducted. A total of 212 adults with SJS/TEN were included between January 1, 2015, and December 31, 2019, and data were collected from a follow-up period of 6 weeks. MAIN OUTCOMES AND MEASURES: Risk factors for severe acute-phase complications (acute kidney failure, septicemia, and need for mechanical ventilation) and mortality 6 weeks following admission were evaluated using a multivariable-adjusted logistic regression model. One tool used in evaluation of severity was the Score of Toxic Epidermal Necrolysis (SCORTEN), which ranges from 0 to 7, with 7 the highest level of severity. RESULTS: Of 212 patients (134 of 211 [63.7%] women; mean [SD] age, 51.0 [19.3] years), the mean (SD) body surface area detachment was 27% (32.8%). In 176 (83.0%) patients, a culprit drug was identified. Antibiotics (21.2%), followed by anticonvulsants (18.9%), nonsteroidal anti-inflammatory drugs (11.8%), allopurinol (11.3%), and sulfonamides (10.4%), were the most common suspected agents. Treatment approaches ranged from best supportive care only (38.2%) to systemic glucocorticoids (35.4%), intravenous immunoglobulins (23.6%), cyclosporine (10.4%), and antitumor necrosis factor agents (3.3%). Most patients (63.7%) developed severe acute-phase complications. The 6-week mortality rate was 20.8%. Maximal body surface area detachment (≥30%) was found to be independently associated with severe acute-phase complications (fully adjusted odds ratio [OR], 2.49; 95% CI, 1.21-5.12; P = .01) and SCORTEN greater than or equal to 2 was significantly associated with mortality (fully adjusted OR, 10.30; 95% CI, 3.82-27.78; P < .001). Cyclosporine was associated with a higher frequency of greater than or equal to 20% increase in body surface area detachment in the acute phase (adjusted OR, 3.44; 95% CI, 1.12-10.52; P = .03) and an increased risk of infections (adjusted OR, 7.16; 95% CI, 1.52-33.74; P = .01). Systemic glucocorticoids and intravenous immunoglobulins were associated with a decreased risk of infections (adjusted OR, 0.40; 95% CI, 0.18-0.88; P = .02). No significant difference in 6-week mortality was found between treatment groups. CONCLUSIONS AND RELEVANCE: This cohort study noted differences in treatment strategies for SJS/TEN in Europe; the findings suggest the need for prospective therapeutic studies to be conducted and registries to be developed.

Genotyping HLA alleles to predict the development of Severe cutaneous adverse drug reactions (SCARs): state-of-the-art.

Introduction: Pharmacogenomics has great potential in reducing drug-induced severe cutaneous adverse drug reactions (SCARs). Pharmacogenomic studies have revealed an association between HLA genes and SCARs including acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN).Areas covered: Pharmacogenomics-guided therapy could prevent severe drug hypersensitivity reactions. The US Food and Drug Administration (FDA), Clinical Pharmacogenetics Implementation Consortium (CPIC), and Dutch Pharmacogenetics Working Group (DPWG) provided guidelines in the translation of clinically relevant and evidence-based SCARs pharmacogenomics research into clinical practice. In this review, we intended to summarize the significant HLA alleles associated with SCARs induced by different drugs in different populations. We also summarize the SCARs associated with genetic and non-genetic factors and the cost-effectiveness of screening tests.Expert opinion: The effectiveness of HLA screening on a wider scale in clinical practice requires significant resources, including state-of-the-art laboratory; multidisciplinary team approach and health care provider education and engagement; clinical decision support alert system via electronic medical record (EMR); laboratory standards and quality assurance; evidence of cost-effectiveness; and cost of pharmacogenomics tests and reimbursement.

Cost-effectiveness analysis of genotyping for HLA-B*15:02 in Indonesian patients with epilepsy using a generic model.

Carbamazepine (CBZ)-induced Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are strongly associated with the HLA-B*15:02 allele. Screening HLA-B*15:02 before CBZ administration might prevent CBZ-induced SJS/TEN by enabling clinicians to prescribe alternative therapy for positive patients. Similar to other Southeastern Asian countries, HLA-B*15:02 is highly prevalent in Indonesia. Therefore, we assessed the economic value of HLA-B*15:02 screening before CBZ prescription to patients with epilepsy in Indonesia. A generic cost-effectiveness model and decision support tool, developed to enable users to perform an initial cost-effectiveness analysis from a healthcare provider/payer perspective, were used to assess the value of HLA-B*15:02 genotyping. The incremental cost-effectiveness ratio of adopting universal HLA-B*15:02 screening was 656,444,671 Indonesian Rupiah (IDR)/quality-adjusted life year (QALY) gained for patients compared with 2,634,975,574 IDR/QALY gained for providing valproic acid (alternative drug) without screening. Thus, neither HLA-B*15:02 screening nor substitution with VPA meets the Indonesian threshold for cost effectiveness. However, the improved outcomes with this test in other Asian countries may inform the desirability of implementation in Indonesia even with suboptimal cost-effectiveness.

Assessment and Comparison of Performance of ABCD-10 and SCORTEN in Prognostication of Epidermal Necrolysis.

Importance: Epidermal necrolysis is a rare severe cutaneous drug reaction associated with high mortality. The ABCD-10 score (age, bicarbonate, cancer, dialysis, 10% body surface area), a new prognostic score for mortality in epidermal necrolysis, was recently developed and validated in the US. However, to our knowledge, it remains to be externally validated in other cohorts. Objective: To assess ABCD-10 among patients in a contemporary Asian cohort and compare its performance with the Score of Toxic Epidermal Necrosis (SCORTEN) and study the associations of time and immunomodulatory therapy with the performance of ABCD-10 and SCORTEN. Design, Setting, and Participants: This retrospective cohort study was conducted over a 17-year period from January 2003 to March 2019 and included 196 patients with epidermal necrolysis who were recruited from Singapore General Hospital, the national referral center for epidermal necrolysis. Main Outcomes and Measures: In-hospital mortality. Discrimination and calibration of each risk score were assessed and compared using the area under the receiver operating characteristic curve and calibration plot, respectively. Results: Among 196 patients (median [interquartile range] age, 56 [42-70] years; 116 women [59.2%]), 45 (23.0%) did not survive to discharge. All risk factors in ABCD-10 were significantly associated with in-hospital mortality. However, dialysis before admission, the most heavily weighted factor in ABCD-10, performed weaker in this cohort (odds ratio, 3.7; 95% CI, 1.0-13.2, P = .04). Although the discrimination of ABCD-10 and SCORTEN did not differ (area under the curve: ABCD-10, 0.78; 95% CI, 0.72-0.85; vs SCORTEN, 0.77; 95% CI, 0.69-0.84; P = .53), the calibration of ABCD-10 was poorer compared with SCORTEN. From graphical analysis of the calibration plots, ABCD-10 showed mortality underestimation at lower score ranges and overestimation at higher score ranges. By contrast, SCORTEN was generally well calibrated, although at higher score ranges mortality may be overestimated. Assessment of calibration plots showed that there was increasing overestimation of mortality by SCORTEN during the later period or when immunomodulatory therapy was used compared with patients treated with supportive care alone. Calibration of ABCD-10 remained poor even during the later period or among patients treated with immunomodulatory therapy. Conclusions and Relevance: In this cohort of patients, the performance of SCORTEN was superior to ABCD-10 in mortality prognostication in epidermal necrolysis. However, it did display time-associated deterioration in calibration leading to overestimation of mortality risk. Future studies may consider revising the existing SCORTEN given its current good discrimination.

General characteristics, economic burden, causative drugs and medical errors associated with medical damage litigation involving severe cutaneous adverse drug reactions in China.

WHAT IS KNOWN AND OBJECTIVE: To investigate the general characteristics, economic burden, causative drugs and medical errors associated with litigation involving severe cutaneous adverse drug reactions (SCADRs) in China, with the aims of improving rational medication use and reducing the extent of damage from SCADRs. METHODS: This study analysed 150 lawsuit judgements involving SCADRs from 2005 to 2019, collected from China Judgments Online. RESULTS AND DISCUSSION: In total, 50% of lawsuits stemmed from SCADRs occurring in general hospitals. The average time elapsed from the date of occurrence of the SCADRs to the end of litigation procedures was 1055 days. Of the patients involved, 51% were female and more than two thirds (69%) were under 60 years old. The most common outcome of SCADRs was death (39%), followed by disabilities (30%). The average responsibility of the medical provider was 48 ± 29%. The average amount of compensation was $43 424. Of the cases studied, 51% of SCADRs were Stevens-Johnson syndrome or toxic epidermal necrolysis, which together accounted for 75% of cases with known clinical subtype. The overall average economic burden of SCADRs was $99 178, of which indirect costs made up the largest proportion (more than 60%). The most common causative drug groups were antimicrobial drugs (49%), Chinese patent medicine and Chinese herbal medicine (17%), and antipyretic analgesics (16%). Finally, 61% of medical errors were found to stem from violation of duty of care, 20% from violation of informed consent and 18% from violations related to the medical record writing and management system. WHAT IS NEW AND CONCLUSION: Severe cutaneous adverse drug reactions not only severely affect patient survival and quality of life, but also impose a heavy economic burden in terms of health care and societal costs. Medical providers should be better educated on strategies to reduce risk to patients and establish mechanisms of risk sharing and management.