During the COVID-19 pandemic, flexibility became an immediate need for sponsors, CROs, clinical sites, and patients in clinical trials. Quick adjustments had to be made, along with finding new ways to make sure that patients had the appropriate care, oversight of the clinical sites continued to be managed, and drug supply and accountability were maintained. Because of this, the Direct-to-Patient approach grew, and is projected to grow significantly over the next few years. As more and more DCTs come on board, it is important to remember that clear roles and responsibilities and experienced management are vital to success. This article covers ways to mitigate risk in DTP studies, how DTP studies mitigate operational risks, putting DTP into practice, and more.