A Health Literate Patient-focused Approach to the Redesign of the Raltegravir (ISENTRESS) Pediatric Kit and Instructions for Use.

BACKGROUND: Limited data exist regarding how medications for pediatric use can be developed to minimize medication errors. The integrase inhibitor raltegravir was developed for use in neonates (≥2 kg). Anticipating that neonatal administration would be performed primarily by mothers with varying degrees of health literacy, a health literate, patient-focused, iterative process was conducted to update/redesign the raltegravir granules for oral suspension pediatric kit and instructions for use (IFU) for neonatal use to be ready for regulatory submission. METHODS: Prototypes of an updated/redesigned raltegravir IFU were systematically assessed through multi-stage, iterative testing and evaluation involving untrained lay individuals with varying levels of health literacy, healthcare professionals and health literacy experts. RESULTS: This iterative process resulted in numerous refinements to the IFU and kit, including wording, layout, presentation, colored syringes and additional instructional steps. The revised raltegravir pediatric kit and IFU (to include neonatal dosing) were approved by the US Food and Drug Administration in 2017 and the European Union in 2018. No reported medication errors related to IFU utilization had been reported as of March 2021, reflecting >3 years of commercial use worldwide. CONCLUSIONS: This patient-focused process produced health literate instructions for preparing and administering an antiretroviral for neonatal use with complex dosing requirements. Testing demonstrated that lay users with a range of health literacy levels were able to accurately mix, measure and administer the product. This process demonstrates how a neonatal medication can be optimized for use through collaboration between the infectious disease expert community and a manufacturer.

ALBI score and outcomes in patients with hepatocellular carcinoma: post hoc analysis of the randomized controlled trial KEYNOTE-240.

AIMS: This post hoc analysis evaluated albumin/bilirubin (ALBI) score, an objective measure of liver function, in patients receiving pembrolizumab plus best supportive care (BSC) compared with placebo plus BSC in the KEYNOTE-240 study. METHODS: Patients with confirmed hepatocellular carcinoma (HCC) and progression after/intolerance to sorafenib, Child-Pugh class A liver function, and Eastern Cooperative Oncology Group performance status of 0-1 were randomly assigned 2:1 to pembrolizumab 200 mg or placebo intravenously every 3 weeks plus BSC for ⩽35 cycles or until confirmed progression/unacceptable toxicity. Outcomes were assessed by ALBI grade. RESULTS: Of 413 patients, at baseline 116 had an ALBI grade 1 score (pembrolizumab, n = 74; placebo, n = 42) and 279 had an ALBI grade 2 score (n = 193; n = 86). Change from baseline in ALBI score to the end of treatment was similar in both arms [difference in least squares mean, -0.039; 95% confidence interval (CI): -0.169 to 0.091]. Time to ALBI grade increase was similar in both arms [median for pembrolizumab versus placebo: 7.8 versus 6.9 months; hazard ratio (HR) = 0.863 (95% CI: 0.625-1.192)]. Regardless of baseline ALBI grade, a trend toward improved overall survival was observed with pembrolizumab [grade 1: HR = 0.725 (95% CI: 0.454-1.158); grade 2: HR = 0.827 (95% CI: 0.612-1.119)]. CONCLUSION: Pembrolizumab did not adversely impact liver function compared with placebo in patients with HCC, as measured by changes in ALBI scores. A trend toward improved overall survival was observed with pembrolizumab in both ALBI grade groups. ClinicalTrials.gov identifier: NCT02702401.