Aduhelm - clinically meaningful difference

I posted earlier on the Medicare plan to restrict the expensive, nonfunctional Alzheimer’s drug, Aduhelm, to clinical trials.

Here is a much better article with broader ramifications.

https://www.medpagetoday.com/neurology/alzheimersdisease/966…

**Medicare Plans to Restrict Coverage of New Alzheimer's Drug**
**— Proposal would cover aducanumab (Aduhelm) in patients on qualifying clinical trials**

**by Judy George, Senior Staff Writer, MedPage Today January 11, 2022**

**Monoclonal antibodies targeting amyloid beta in Alzheimer's disease, including the newly approved drug aducanumab (Aduhelm), would be covered for people with Medicare only if they are enrolled in qualifying clinical trials, according to CMS plans announced Tuesday....**

**Trials must address whether using anti-amyloid antibodies in Alzheimer's results in a statistically significant and clinically meaningful difference in decline in cognition and function, in addition to studying adverse events associated with treatment....This harm may range from headaches, dizziness, and falls, to other potentially serious complications such as brain bleeds...** [end quote]

The mention of “clinically meaningful difference” is subtle but extremely important. It affects many other drugs, including cancer drugs, which measure physical factors that hypothetically correlate with desired clinically meaningful differences but do not necessarily produce the actual difference.

In the case of Aduhelm, it would force the clinical trials to measure cognition and function, not just the burden of amyloid beta in the brain (which can be measured by scans).

Biogen assumed that reducing amyloid beta clumps in the brain will improve cognition and slow the advance of Alzheimer’s disease because Alzheimer’s patients have a lot of amyloid beta. There’s no solid evidence that this is true, since many people without cognitive decline are found (on autopsy) to have a lot of amyloid in the brain. Also, Alzheimer’s disease is associated with tangles of tau protein in neurons that disrupt the function of the neuron but are completely unaffected by a drug that targets amyloid.

In the case of cancer, some (very expensive) chemotherapy drugs are correlated with Progression-Free Survival (PFS) but not necessarily with time to death. In that case, the treatment kills susceptible cancer cells but leaves mutated, resistant cancer cells that hide in a dormant state and then wake up later in a deadly metastatic form.

If the payers who control access to drugs, devices and procedures switched to evidence-based medicine where the criterion for approval was significant difference in the true endpoint (not a correlated but not necessarily causative factor), the practice of medicine would be dramatically changed. And payers (including Medicare) would save a huge amount of money.

See https://www.thennt.com/ and the book, “Ending Medical Reversal.” It’s rather startling how much medicine in this country is NOT evidence-based. Would people be willing to forego existing medical treatments that offer hope but NOT statistically-significant improvements, let alone cures?

As it is, under pressure from patient groups, the FDA already approves limited distribution of drugs without proof of efficacy if there’s no alternative as well as Emergency Use Authorizations. In addition, any drug that is already approved for any reason can legally be used off-label if a doctor prescribes it for any other reason.

Wendy

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Wendy,

We do not know which way this will turn out in the testing. We can not presume to know. It is early yet.

Past trials were of smaller numbers.

We have a massive population of Alzheimer’s patients. Even if only a smaller part of the population is somewhat responsive this is worth the follow through on. People where the drug wont work generally wont get the drug.

The NYT reported this differently this morning as Biogen reduced the drug’s price to $28,500 and the admin asked Medicare to reconsider the rate hike for Part B.

I have not read your links. I am not seeing that part of today’s story in your comments. Maybe I missed it, just scanning. The medical information being premature and not fully formed is deep in the weeds.

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This is naive and simplistic, especially considering that the FDA approved the drug before the Phase 3 clinical trial showed a statistically significant benefit. And because many FDA approved drugs show only a small (thought statistically significant) relative benefit to a small percentage of people who take them.

Wendy

3 Likes

This is naive and simplistic, especially considering that the FDA approved the drug before the Phase 3 clinical trial showed a statistically significant benefit. And because many FDA approved drugs show only a small (thought statistically significant) relative benefit to a small percentage of people who take them.

Wendy


Not everything is a conspiracy.

As this drug roles out, people it wont work it wont get it longer term. That might be a lot of people where the drug wont address their problems.

Those who benefit seriously need this drug. There but for the grace of god go I.

The heart of this discussion is only the costs involved in the Part B rate hike. The admin has asked the CMS to review this. As of this morning Biogen reduced the price to $28200(being accurate).

While not everything is a conspiracy not everyone is an angel. I get that.