Details
The U.S. Food and Drug Administration (FDA) initiated this study in the Sentinel System to determine the patterns of congenital cytomegalovirus infection (cCMV) diagnosis, trends in prescribing valganciclovir (vGCV) for treatment of cCMV and associated clinical outcomes (e.g. hearing and hematologic) for infants with cCMV. Congenital cytomegalovirus infection (cCMV), a rare pediatric disease, may be associated with serious audiologic and neurodevelopmental impairment. Although there are currently no FDA-approved agents to prevent or treat cCMV infection, clinical guidelines recommend vGCV treatment for six months, initiated within the first month of life in newborns with moderate to severe disease. It is unknown to what extent the off-label vGCV use for cCMV has become the standard of care. This knowledge gap impacts clinical development of antivirals for treatment of cCMV.
In a large cohort of infants (n=1500) with cCMV identified by claims data, 20% were treated with vGCV. Of the treated population, 17% were asymptomatic, 27% commenced treatment outside the first month of life, and 38% received treatment for longer than 6 months. Although clinical severity cannot be determined from claims data, these results suggest that vGCV treatment in the U.S. may extend beyond the current recommendation. Severe hematological events occurred infrequently. The proportion of infants with cCMV infection who had hearing loss increased over time, regardless of treatment. However, a subsequent analysis of patient charts suggested that only a subset (45%) of the children identified using claims data had confirmed cCMV infection, which limits the interpretability of results from that inquiry.
This Sentinel Study was also used to examine the availability of real-world data (RWD) to complement clinical trial data for regulatory decision-making. Results were reviewed for insights on the use of RWD to construct a historical control arm for a clinical trial, and if RWD could be used to complement clinical trial data for this rare pediatric disease.
Overall, the results of this study highlight the limitations of RWD and support the need for clinical trials for this indication.