‘We’re excited to partner with the new administration on some non-partisan issues here that are absolutely critical for our country.’
So this isn’t impotent bloviating, it’s someone with some influence.
This would be nice:
2.B. UPDATE THE GENERAL DRUG APPROVAL FRAMEWORK TO INCORPORATE PROGRESSIVE APPROVALS.
The basic concept of a Phase III clinical trial that requires thousands of patients across numerous facilities, and hundreds of millions of expense, dates to the mid-20th century. Yet it still forms the basis for the FDA deciding which patients are allowed to have the freedom to take the treatments they want and those that are denied their rights to choose which substances they put inside their bodies. Despite the tremendous advances in real-world data and real-time analytics that exist, the FDA hasn’t undertaken a wholesale re-thinking of our general drug approval frame.
During the initial AIDS crisis in the 1980s, scores of patients fought the FDA for the right to access experimental but life saving treatments; they were successful in winning an accelerated approval process. Still, these processes are limited, and have frequently required FDA leadership to “overturn” risk averse FDA staffers in spite of clear evidence that the FDA’s risk aversion is costing lives (see here). When the FDA does occasionally reduce regulatory requirements, it has been shown to clearly save lives. It is well within the authority of each FDA center (CBER, CDER and CDRH) to determine what constitutes “safe and effective” since there is no single bright line scientifically. There are always tradeoffs, no therapy is without risk and no therapy is guaranteed to work all of the time.
What would a first principles approach to drug approvals look like? It would ensure a few things:
Transparency as the default. Trials and reviews must produce statistical evidence that patients, doctors, and payors can independently assess—restoring trust in medicine through openness, not secrecy.
Approval as the default once safety is established. Especially for acute or life-threatening diseases, delays should require justification, not progress.
Robust post-approval monitoring. Faster approvals must be paired with real-time data collection and public reporting to catch issues early and continuously refine risk-benefit assessments.
Approvals should be progressive, allowing access at the earliest possible opportunity while maintaining a high standard of transparency for patients and physicians to make informed choices.
Would it work? Evidence suggests payers, providers and patients are quite capable of making independent judgments about the cost and benefit of drugs. One example: the FDA approved Aducanumab, an Alzheimer’s drug. Despite FDA approval, payers and patients both rejected the drug; as the benefits shown in clinical trials were so small that nobody showed interest. On the flip side, patients and doctors are also able to judge when a drug is better than whatever a single FDA staffer has said; a perfect example of this is semaglutide (Ozempic). Approved in 2017 for diabetic patients, the world was able to see the profound benefits in obesity rapidly, and doctors facilitated access to millions of patients despite the FDA not approving semaglutide in weight loss for 4 years in 2021. The FDA sought a phase 3 trial rather than simply collecting post-approval data from the millions of patients taking it.
Summing up (trigger warning):
Conclusion
The sorts of reforms we lay out here would require an unusually bold administration - and a bold Congress to ensure the reforms are enduring throughout administrations. But they would save lives, perhaps millions of lives, with an abundance of medical interventions. And so far, this administration has had no problem being bold!
Competition and speed would flourish within the FDA and HHS, and the faster access and lower cost would embolden innovators outside of the government, drawing hundreds of billions of dollars more of risk-taking capital into the US biotech sector. Let’s tilt the playing field back towards investing and manufacturing therapies in the USA. Bold leadership can catapult the US back into the lead for biomedical and biological innovation - but it requires standing up to the internal bureaucracy who have “always done it this way”, and don’t want competition or major change: something that no FDA or HHS leader has managed to do in recent memory.
There are great minds and bold leaders willing to rethink how we do things who have come together to run the HHS, and in particular, the FDA. We are hopeful that the exciting leaders in this new administration will make major changes, and are eager to assist. Millions of lives, and the world’s greatest engine of biotech innovation, hangs in the balance!
