Timing of DART studies

Current timing of DART studies

DART studies are often delayed until late in clinical development (late phase III) following current regulatory guidelines, when the intended dose has been selected, there are promising safety and efficacy data in non-pregnant women using effective contraception, and the company has committed to bringing a drug to licensure.

Until DART testing has been completed, there are requirements for the use of highly effective contraceptives (defined as failure rate <1% per year) for study participants of childbearing age, mandatory withdrawal of women from pre-licensure trials if they become pregnant, and exclusion of pregnant and lactating women from enrolment in clinical trials.

For many existing medications, safety data during lactation are not available as lactation endpoints may not be included in DART protocols nor clinical trials and these data are not required prior to drug licensure.

Proposed approach for timing of DART studies

The HIV and TB consensus processes identified an alternative approach for the initiation and completion of DART studies. In both processes, it was suggested that DART studies should be initiated and completed sooner in the drug-development process so that phase III clinical trials could be performed that would allow:

• women who become pregnant to remain on a study drug after re-consenting if the risk–benefit ratio is favourable for the mother and unborn child; and
• enrolment of women who are already pregnant into late phase III clinical trials (or parallel substudies) to collect initial PK and safety data.

The applicability of the suggested approaches for other diseases, including non-communicable diseases, will need to be explored in more detail.