Industry Review of Best Practices for Risk Management of Drug-Induced Liver Injury from Development to Real-World Use.

The relative treatment benefit of a drug for patients during development, marketing authorization review, or after approval includes an assessment of the risk of drug-induced liver injury (DILI). In this article, the Pharmacovigilance and Risk Mitigation Working Group of the IQ-DILI Initiative launched in June 2016 within the International Consortium for Innovation and Quality in Pharmaceutical Development presents and reviews three key topics for essential risk management activities to identify, characterize, monitor, mitigate, and communicate DILI risk associated with small molecules during drug development. The three topics are: (1) Current best practices for characterizing the DILI phenotype and the severity and incidence of DILI in the treatment population, including DILI identification, prediction and recovery. (2) Characterization of the relative treatment benefit for patients who will be exposed to a drug and the attendant risk of DILI in conjunction with existing global risk mitigation strategies. (3) Implementation of risk mitigation strategies during drug development highlighting patient factors, healthcare settings and site of product administration, and prescriber and healthcare provider factors. Industry guidance is provided for assessing whether the product labeling is sufficient to minimize the risk of DILI or whether a United States Food and Drug Administration (FDA) Risk Evaluation and Mitigation Strategy (REMS) or European Medicines Agency (EMA) Risk Management Plan (RMP) with additional Risk Minimization Measures (aRMM) is needed.

The relative treatment benefit of a drug for patients during development, marketing authorization review or after approval includes an assessment of the risk of drug-induced liver injury (DILI). Reported incidences of DILI range from 0.74 to 19 per 100,000, and laboratory criteria and/or clinical outcome determine the severity of DILI. At least 10% of patients who develop jaundice caused by DILI (Hy's Law cases) develop liver failure (i.e., severe DILI). A drug's liver safety profile can be assessed using Evaluation of Drug-Induced Serious Hepatotoxicity Plots. Specific recommendations for monitoring DILI in the post-marketing setting depend on characterization of the phenotype during drug development. Risk mitigation tools include additional educational mechanisms, and risk minimization measures include Elements To Assure Safe Use (ETASU) for healthcare professionals, administration sites, and patients. The overall aim of risk management is to ensure that the benefit of a particular product exceeds the risks as far as possible for the individual patient and for the target population.

Validation of two case definitions to identify pressure ulcers using hospital administrative data.

OBJECTIVE: Pressure ulcer development is a quality of care indicator, as pressure ulcers are potentially preventable. Yet pressure ulcer is a leading cause of morbidity, discomfort and additional healthcare costs for inpatients. Methods are lacking for accurate surveillance of pressure ulcer in hospitals to track occurrences and evaluate care improvement strategies. The main study aim was to validate hospital discharge abstract database (DAD) in recording pressure ulcers against nursing consult reports, and to calculate prevalence of pressure ulcers in Alberta, Canada in DAD. We hypothesised that a more inclusive case definition for pressure ulcers would enhance validity of cases identified in administrative data for research and quality improvement purposes. SETTING: A cohort of patients with pressure ulcers were identified from enterostomal (ET) nursing consult documents at a large university hospital in 2011. PARTICIPANTS: There were 1217 patients with pressure ulcers in ET nursing documentation that were linked to a corresponding record in DAD to validate DAD for correct and accurate identification of pressure ulcer occurrence, using two case definitions for pressure ulcer. RESULTS: Using pressure ulcer definition 1 (7 codes), prevalence was 1.4%, and using definition 2 (29 codes), prevalence was 4.2% after adjusting for misclassifications. The results were lower than expected. Definition 1 sensitivity was 27.7% and specificity was 98.8%, while definition 2 sensitivity was 32.8% and specificity was 95.9%. Pressure ulcer in both DAD and ET consultation increased with age, number of comorbidities and length of stay. CONCLUSION: DAD underestimate pressure ulcer prevalence. Since various codes are used to record pressure ulcers in DAD, the case definition with more codes captures more pressure ulcer cases, and may be useful for monitoring facility trends. However, low sensitivity suggests that this data source may not be accurate for determining overall prevalence, and should be cautiously compared with other prevalence studies.