What STAT readers think about Aduhelm, CTE and the Super Bowl, and more

STAT now publishes selected Letters to the Editor received in response to First Opinion essays to encourage robust, good-faith discussion about difficult issues. Submit a Letter to the Editor here, or find the submission form at the end of any First Opinion essay.

“Aduhelm was a mess — and it could happen again,” by Jason Karlawish

Thanks for a very clear and compelling explanation of what has gone wrong with the process for approving drug treatments for Alzheimer’s. Especially valuable is Dr. Karlawish’s insistence on the difference in the proper roles and incentives for the pharmaceutical companies and the FDA. We all want an effective treatment, and as fast as possible, but public agencies have to make sure we have one before approving one for public use. I’m suspicious whenever I hear any federal official talk about “public-private partnerships,” which is often code for “we have forgotten what we are here for.” FDA and NIH research should be funded entirely by tax dollars, to ensure objectivity, not the current mix of public and private dollars for translational research and trials. In the meantime, “ask your doctor” about walking for exercise, cognitive stimulation, social connections, clean air, and high-quality long-term supports and services for persons with impairment and their caregivers. For the time being, that’s what we have to offer, and public dollars would be better spent on assuring them for everyone rather than ineffective not-quite-treatment for the few.
— John Haaga, retired from the National Institute on Aging

***

Even blood pressure should not be used a surrogate endpoint. Even before the ALLHAT trial results caused internists to back off alpha-1-AR antagonists like prazosin for hypertension, we had plenty of evidence for ways to lower blood pressure without improving outcomes, or that worsen outcomes (sepsis, for example; also nitroprusside overdose, hemorrhage, cardiac arrest …).
— Joel Geerling, University of Iowa

***

“And yet, the FDA seems oblivious.” I would modify this statement slightly: The FDA is selectively oblivious. Clearly it violated its own rules and standards and created problems for the pharmaceutical industry, investors, insurance groups, state regulators and above all — for doctors treating people who are at risk or are suffering from Alzheimer’s disease/cognitive impairment. I commend the author for speaking out. Everyone with any stake in treating this enormously costly public health problem lost a lot. The parties at the FDA who were responsible should be forced to resign.
— Michael Doran

“Contact sports cause CTE. So why are Americans watching more football than ever?” by Adina Wise

One of the reasons I stopped watching both college and professional football is that I no longer wanted to be complicit in watching the players essentially destroy their long-term cognitive and physical well-being for my amusement. I believe most serious football fans are uninterested in the players as humans with lives that extend beyond their exploits on the field; the game itself rationalizes players as interchangeable cogs in a machine that must function to produce wins. As the aptly named Dr. Wise points out, the worst neurological effects of football are so far removed from the actual games that they are rarely considered by fans. Of course fans will focus on the fact that professionals are beloved and paid well for their sacrifice, and that even college players are compensated with scholarships and can now be paid for their endorsements. I think these facts are what allow fans to watch football essentially guilt-free. Football is a very entertaining game to watch and provides a readymade social gravity so strong that the game has become deeply embedded in the American cultural fabric. Unfortunately our collective short-term orientation and obsession with money and fame seem to matter more than caring for actual people.
— Henry Thorpe

“Former U.S. surgeons general: The U.S. should ban menthol cigarettes,” by Regina Benjamin and Jerome Adams

It is very clear by the evidence that to stop selling menthol cigarettes will save lives. The addiction is so strong that people have difficulty stopping on their own will. Really appreciate the clarity and data to point out the need to save lives. The former surgeon generals have made the case, maybe the White House will respond with a renewed haste.
— Danny Patterson, Gulf States Health Policy Center

“Medicare has different standards than the FDA. That’s how it should be,” by Diana Zuckerman

We have a general misunderstanding of safe and effective just as we do about the role of age, skin color, and other elements of diversity that make no sense. At best, drugs are relatively safe and relatively effective for some of the people some of the time. Biological age and calendar age don’t line up. We use them because they are convenient. Reality is more complex. We end up with population averages that mean very little to an individual patient. To pretend otherwise is nuts. We measure what we can measure and often not what we should measure. Cost matters. To be “fair” is out of reach for many because of the “fare.”
— Peter Kissinger, Purdue University, Inotiv, Phlebotics

“Where do we go from here on digital therapeutics?” by G. Luke Hartstein and John Torous

This was a thoughtful article. But it’s even more complex than the authors explained. Yes, digital therapeutics (DTx) companies can try to get “paid for like traditional drugs,” but it’s essential to note the price a traditional drug can fetch versus a software as medical device (SaMD) application. If an innovative drug is similar in principle to an innovative SaMD app, will society pay $10,000-100,000 per year for it like a drug? A lot of existential problems for DTx companies go away with a user base in the thousands and each user generating $10,000+ in annual revenue for the DTx company. E.g., 10,000 users x $10,000 per user per year = $100,000,000 in annual revenue — failure for an innovative drug from biopharma, but an order of magnitude better than any DTx company has achieved to date.

With that level of capital, DTx companies could start to build the distribution systems they need for their SaMD apps. Field sales, medical liaisons, payor teams, consumer marketing, et al — things every biopharma has with its level of capital, but no DTx company can afford. So you spend 10 years developing a DTx, running clinical trials, taking it through regulatory reviews, finally gaining approvals and market access … and then no clinician knows to prescribe/dispense it to their patients, nor is any patient aware of its existence, nor is any payor prepared to pay an equitable amount of money for it that they would for a drug. Remote monitoring reimbursement rates are so low that health care institutions at times don’t bother submitting for them because the administrative cost to the institution outstrips the reimbursement payment they would receive or is below their internal finance hurdle rate.

I am waiting for the first DTx company to price its SaMD app at $10,000+ and gain acceptance from payors. That will be the watershed moment for the DTx industry, and it might demand more ingenuity and innovation from DTx companies than the undifferentiated me-too efforts the industry has largely unveiled to date. Who will develop the first practice-changing DTx in their area of specialty?
— Topher Scott