NCHR Comments on the FDA’s Post-Marketing Pediatric-Focused Product Safety Reviews

Varuna Srinivasan, MBBS MPH, National Center for Health Research, September 28th 2018

Thank you for the opportunity to express our views on the FDA’s post-marketing pediatric-focused product safety reviews. The National Center for Health Research is a nonprofit think tank that conducts, analyzes, and scrutinizes research, policies, and programs on a range of issues related to health and safety. We do not accept funding from companies that make products that are the subject of our work.

We have the following concerns,

1. The FDA is well aware that using FAERS to determine the incidence of new or increased adverse reactions is inadequate, given the well-known problem of under-reporting. While FAERS is better than nothing and sometimes very useful, we believe that REMS strategies are needed to better inform physicians about the risks of these products for children, whether they are approved uses or off-label uses.

2. Although many drugs are indicated for use in certain age groups, many are widely used off label. Warnings regarding use for children, either because the risk: benefit ratio is unknown, or because relatively little is known about effectiveness or safety for children, should be at the top of the label, near any black box warnings. In addition, we strongly urge the FDA to require user-friendly informational booklets for parents to inform them of exactly what are the approved indications and warn them about the risks of off label uses.

3. ADHD drugs in this review such as Dyanavel XR, Adzenys XR-ODT, and Intuniv clearly increase the risk of psychiatric disturbances such as suicidal ideation, tactile hallucinations, labile affect, and anger. These adverse events need to be more prominently placed in the label of these drugs, and FDA should develop and evaluate effective REMS strategies for ADHD drugs, which should include but not be limited to user-friendly information booklets for parents.

4. In regards to the devices under review, specifically two neurostimulator devices Activa and Enterra, we see many possible problems with the way these devices function, such as premature battery discharge, shocks, and leads breakage. The rates of these malfunctions are higher than should be acceptable to the FDA or to the physicians prescribing these products. In addition to the problems caused by a product malfunction, additional surgeries to fix or replace components increases the risks for children to experience adverse events. Although the number of events reported in the safety summaries is small, these are based on voluntary reporting and are likely under-reported. We strongly urge the FDA to require user-friendly informational booklets for parents to inform them of the risks, because patients are not given labels for these devices.

For questions or more information, please contact Dr.Varuna Srinivasan, MBBS MPH at or at (202) 223-4000.