Comparative Expedited Regulatory Programs of U.S Food & Drug Administration and Project Orbis Partners.

Project Orbis was initiated in May 2019 by the Oncology Center of Excellence to facilitate faster patient access to innovative cancer therapies by providing a framework for concurrent submissions and review of oncology products among international partners. Since its inception, Australia's Therapeutic Goods Administration (TGA), Canada's Health Canada (HC), Singapore's Health Sciences Authority (HSA), Switzerland's Swissmedic (SMC), Brazil's National Health Surveillance Agency (ANVISA), United Kingdom's Medicines and Healthcare Products Regulatory Agency (MHRA), and most recently Israel's Ministry of Health (IMoH) Medical Technologies, Health Information, Innovation and Research (MTIIR) Directorate, have joined Project Orbis. While each country has its own expedited review pathways to bring promising therapies to patients, there are some similarities and differences in pathways and timelines. FDA's fast-track designation and MHRA's marketing authorization under exceptional circumstances (MAEC) allow non-clinical and limited clinical evidence to support approval under these programs. HC's Extraordinary Use New Drug (EUND) pathway allows granting exceptional use authorization with limited clinical evidence. ANVISA, HSA, MTIIR, and TGA do not have standard pathways that allow non-clinical evidence and limited clinical evidence. While there is no definite regulatory pathway for HSA, the current framework for approval does allow flexibility in the type of data (non-clinical or clinical) required to demonstrate the benefit-risk profile of a product. HSA may register a product if the agency is satisfied that the overall benefit outweighs the risk. All Project Orbis Partner (POP) countries have similar programs to the FDA accelerated approval program except ANVISA. Although HSA and MTIIR do not have defined pathways for accelerated approval programs, there are opportunities to request accelerated approval per these agencies. All POP countries have pathways like the FDA priority review except MHRA. Priority review timelines for new drugs range from 120 to 264 calendar days (cd). Standard review timelines for new drugs range from 180 to 365 cd.

Zinc supplementation for treating diarrhea in children: a systematic review and meta-analysis.

OBJECTIVE: To update the available evidence about zinc use for treating diarrhea in children and to assess its effect on the malnourished population, a subgroup that has not been fully explored in previous analyses. METHODS: A systematic review was performed of randomized clinical trials that assessed children up to 5 years old with acute diarrhea who received zinc supplementation. Controls received a placebo or oral rehydration therapy. After searching the main databases, without language restrictions, two independent reviewers selected eligible studies, extracted the data, and assessed the risk of bias of included studies. Meta-analyses were calculated using Mantel-Haenszel or inverse variance random effects. RESULTS: Eighteen of 1 041 studies retrieved were included in the review (n = 7 314 children). Zinc was beneficial for reducing the duration of diarrhea in hours (mean difference [MD] = -20.12, 95% confidence interval [CI] = -29.15 to -11.09, I² = 91%). The effect was greater in malnourished children (MD = -33.17, 95% CI = -33.55 to -27.79, I² = 0%). Diarrhea prevalence on days 3, 5, and 7 was lower in the zinc group. The incidence of vomiting was significantly greater in the group that received zinc than in the control group. Included randomized controlled trials were of low risk of bias in most domains assessed. CONCLUSIONS: Oral zinc supplementation significantly decreases diarrhea duration and has a greater effect on malnourished children. Zinc supplementation seems to be an appropriate public health strategy, mainly in areas of endemic deficiencies.