[2] In 2025, President-elect Donald Trump nominated O'Neill to serve as United States deputy secretary of health and human services.
He then served as Principal Associate Deputy Secretary of HHS from November 2007 to October 2008, where he provided advice on policy and programming, helped manage HHS, and his policy portfolio focused on FDA, NIH, AHRQ, the Office of Public Health and Science, BARDA, global health, and the President's Management Agenda.
[7][9] He was a board member of the SENS Research Foundation[9] and was appointed CEO of the organization in October 2019,[10] remaining in that position until July 2021.
[13][14] In November 2024, President-elect Trump said he intended to nominate O'Neill to serve as deputy secretary of health and human services under Robert F. Kennedy Jr., both of whom would need confirmation by the United States Senate.
"[4] While at HHS, O'Neill opposed FDA regulation of some companies that use mathematical algorithms to perform complex laboratory-developed tests.
"In order to regulate in this space, FDA had to argue that an algorithm, a series of numbers that match up to things, is a medical device," he said.