Oversight of Right-to-Try and Expanded Access Requests for Off-Trial Access to Investigational Drugs.

For decades, the U.S. Food and Drug Administration (FDA) has provided an "expanded access" pathway that allows patients who meet qualifying conditions to gain access outside a clinical trial to an investigational medical product being tested to see if it is safe and effective for a specific use. The Right to Try (RTT) Act, enacted in 2018, created a second mechanism for off-trial, or non-trial, access to investigational drugs. In contrast to the expanded access pathway, the federal RTT pathway does not require the involvement of the FDA or an institutional review board (IRB). Given that physicians, drug manufacturers, and medical institutions now have a choice whether to assist individual patients through the expanded access or the federal RTT pathway, we review the differences between these options and discuss the benefits and burdens of IRB involvement in requests to access interventions through the pathways. We also suggest ways in which IRB oversight may be further improved.

Oxidative Stress Levels in the Brain Are Determined by Post-Mortem Interval and Ante-Mortem Vitamin C State but Not Alzheimer's Disease Status.

The current study highlighted several changes in measures of oxidative stress and antioxidant status that take place in the mouse brain over the course of 24 h post-mortem. Ascorbic acid (vitamin C) and glutathione both decreased significantly in cortex in as little as 2 h and malondialdehyde levels increased. Further change from baseline was observed up to 24 h, including carbonyl and sulfhydryl formation. The greatest changes were observed in brains that began with low ascorbic acid levels (gulo−/− mice) compared to wild-type or 5XFAD mice. Cortical samples from nine Alzheimer’s Disease cases and five controls were also assayed under the same conditions. Post mortem intervals ranged from 6 to 47 h and all samples had low ascorbic acid levels at time of measurement. Malondialdehyde levels were lower in Alzheimer’s Disease cases. Despite a strong positive correlation between ascorbic acid and glutathione levels, no other correlations among oxidative stress measures or post mortem interval were observed. Together the data suggest that molecular changes occurring within the first hours of death may mask differences between patient groups. Care must be taken interpreting studies in human brain tissue where ante-mortem nutrient status is not known to avoid bias or confounding of results.