Interpreting DART studies

DART studies are used to identify risks, some of which are not shared by different species, and do not consider the benefit to individual humans and society. Therefore, nonclinical animal data may not always accurately predict outcomes in humans, as biological differences may result in varied effects across species.

International regulatory organizations and groups developing clinical guidelines may have different thresholds for risk tolerance when interpreting DART findings. An example is efavirenz (EFV), a non-nucleoside reverse transcriptase inhibitor used to treat HIV, that was originally avoided in the first trimester of pregnancy due to animal data and case reports suggesting an increased risk of neural tube defects in women exposed to EFV during early pregnancy. Regulatory authorities and the World Health Organization (WHO) have issued the opposite guidance (see case study below).

Efavirenz case study

Between 2011–2014, retrospective case studies, meta-analyses, and prospective registry data showed the incidence of such defects was comparable to rates observed in non-EFV regimens and HIV-negative populations.

In 2016, the WHO took a weight-of-evidence approach and endorsed EFV-based regimens for first-line treatment among women of childbearing potential including conception and early pregnancy when the risk for neural tube defect is greatest.

To date, both the U.S. Food and Drug Administration (FDA) (United States of America) and the European Medicines Agency continue to advise avoidance of pregnancy while taking EFV and advise against its use during the first trimester.