When President-elect Trump took office the first time, his choices to lead agencies like HHS, CMS and the FDA sent clear signals to the health care industry that he'd enact a pretty orthodox GOP health agenda.

Why it matters: Trump's nominations for top health care positions so far signal a starkly different — and likely unpredictable — agenda for his second term.

• This time around, he's started with a group of nominees — Robert F. Kennedy Jr. and Mehmet Oz — new to Trumpworld and unfamiliar with government bureaucracy. Their views and resumes are nearly the exact opposite of their predecessors.
• The remaining wild card is whom Trump chooses to staff the agencies around those people, assuming they get confirmed by the Senate, which could make a huge difference given their government inexperience.

Flashback: Trump's first HHS secretary was former Rep. Tom Price, who chaired multiple influential House committees during his tenure, including the Republican Policy Committee.

• After Price resigned due to a scandal around his use of private jets, Trump appointed Alex Azar to lead the agency. Azar was formerly an Eli Lilly executive and deputy HHS secretary.
• Price was criticized by Democrats for both his ethics and his policy views, especially relevant as he'd be helming the agency during Republicans' attempt to repeal and replace the Affordable Care Act. Azar was criticized for being too friendly with the pharmaceutical industry.

Those complaints are a far cry from the objections to Kennedy's nomination, which include his history of criticizing vaccines and his conspiratorial ideas about Big Pharma's role in America's chronic health issues.

• And Kennedy's focus on upending the health care agencies and addressing rising rates of chronic disease in America has just about nothing in common with the first Trump administration's focus on insurance reforms.
• Kennedy's interest in cracking down on America's food supply also wasn't a priority for the first Trump administration.

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Trump's pick for CMS was Seema Verma, who had previously worked with then-Indiana governor Mike Pence on a Medicaid program in the state. His choice to lead the FDA was Scott Gottlieb, a resident fellow at AEI who'd served previous stints at the FDA.

• Verma's tenure at CMS was characterized by her attempts to add work requirements to Medicaid and to allow states to receive funding in the form of block grants for the program — both very traditional Republican ideas.
• Oz is primarily known for his television appearances and his promotion of healthy lifestyles. But he also has a history of promoting misinformation at times, and his views on CMS's primary responsibilities — Medicare and Medicaid policy — are pretty unclear.

It's still not known who Trump will appoint to lead the FDA, though I've been hearing all week that it's going to be Johns Hopkins professor Marty Makary. Then again, the rumor mill was pretty adamant someone else was going to be CMS administrator until Oz was announced, so remember: Speculation is just speculation until Trump makes it official.

• Makary's profile became more public during the pandemic, when he criticized some COVID vaccine policies.

Yes, but: Kennedy and Oz's apparent lack of interest or experience in some topics, like health insurance or hospital payments, may leave room for some more traditional agendas, if people are put in place who know how to enact them.

• And their outsider, provocateur status is a good thing, some argue.
• "I think that there needs to be some political will to take on the special interests in the health care industry and disrupt the status quo, and these picks reflect, in my view, a willingness to go against the health care industry," one former Trump administration official told me.

The intrigue: There were plenty of more conventional names on everyone's shortlist for Trump's picks to lead the agencies, and those options would have looked a lot more similar to Trump 1.0's picks than his eventual choices.

• There are now questions about whether he intends to appoint anyone from the more traditional arm of the party — or anyone with enough experience to know how to translate ideas into bureaucratic action.

• 🥣 For obvious reasons, I clicked this story in the Wall Street Journal: How Froot Loops Landed at the Center of U.S. Food Politics. (This is also, more broadly, a good backgrounder on the fight over artificial dyes.)
• 💰 The health care industry is pushing to be carved out of any new tariffs once Trump takes office, Stat reports.
• 🩺 California has set a goal for insurers to direct 15% of their spending to primary care over the next decade — a large jump from the current 7% spending rate, KFF Health News reports.