Thread by @MariaGlymour

Thread about @manlyepic & my @jamaneuro commentary re one especially shameful aspect of the FDA approval of #aduhelm. Before working w/ @manlyepic on this, I knew it was bad, but I didn’t know how bad. doi:10.1001/jamaneurol.2021.3404 1/27

In @Biogen’s FDA filing, only 0.6% (ie 19 people) of 3285 trial participants identified as Black, 3% as Hispanic, 0.03% (1 person) American Indian or Alaska Native, and 0.03% as Native Hawaiian or Pacific Islander. Of 9% identified as Asian, 94% were recruited in Asia. 2/n

But it gets even worse: of those 19 Black participants, most were randomly assigned to control or low-dose treatment arms. FDA approved a medication with known increases in risk for brain bleeding after only 6 Black people had received the approve dose. How is that okay? 3/n

Why should race be considered in evaluation of safety and efficacy of drugs? Because racism affects people's bodies. 4/n

Racism is not just a bad thing that swirls around in the air but politely stays outside the body– racism harms people via many mechanisms in ways that are enduring and can make people more vulnerable to adverse effects of medications. 5/n

If differences in side effects of a drug are plausible across groups, those need to be evaluated before we just say “hey world, sprinkle this on your brain.” This is all the more galling because of huge racial disparities in Alzheimer’s: Black people bear a much larger burden. 6

Further – and sit down for this - @Biogen and #aduhelm advocates are suddenly very very worried about health care access disparities- inclusion in trials apparently didn’t matter so much, but equal access to this (largely ineffective) drug is a super-high priority. 7/n

The number of Black people in the @Biogen #aduhelm ad campaign is almost as many as the number of Black people who received the medication in their trials. 8/n

The demand for equal access to #aduhelm conveniently creates pressure for Medicare and Medicaid to pay for the medication’s $56,000 annual price tag. These systems are supposed to reduce disparities- not be mechanisms for large financial transfers to @Biogen. 9/n

One “cool” thing is that Biogen is also suddenly really worried about making sure everyone who might conceivably be eligible for their drug is brought into the fold of potential customers. 10/n

They fielded a major marketing campaign and are partnering wherever they can to ensure “access”- fielding screening tools that will encircle the largest possible group. 11/n

Forgot your keys? ….let us help you make an appointment with our Biogen-recommended doctor. Lost your train of thought? … You may be a candidate for aduhelm! Can’t remember the polite word for “bullshit”? …maybe you should see a neurologist. 12/n

Why does this make me so angry? Because true and good ideas from health disparities are being co-opted to line Biogen’s pockets. 13/n

Everyone *should* have access to high quality health care, but Biogen is manipulating that principle to extract a huge public subsidy for their ineffective drug- a subsidy that will likely be paid for by denying effective treatments to people who need them. 14/n

People who are on the path to developing dementia *should* receive timely and accurate information about their health. But sudden interest in increasing screening and diagnosis is a well-established industry gimmick to expand the pool of customers. 15/n

And I'm too midwestern to easily recognize chicanery, but when I think about it, it seems likely that Biogen has been working on this strategy for a long time. #Aduhelm was approved not because of its cognitive benefit, but because it reduced a biomarker for Alzheimer's. 16/n

When did that biomarker become defined as a sufficient marker for AD- even in people without cognitive deficits? It was defined so in this report: alz-journals.onlinelibrary.wiley.com/doi/10.1016/j.… 17/n

You may wonder if any of the authors had financial conflicts. They did. A lot. See Samantha Budd Haeberlein? Wonder who she works for? Biogen. She was one of the major Biogen execs in charge of getting #aducanumab approved. Well played Dr. Budd Haeberlein! 18/n

But maybe that doesn’t matter, because surely the panel considered financial conflicts & appropriately contextualized advocacy from corporate employees? Right? Weird thing, but the major findings of this report were presented at the 2017 AAIC meeting. alz.org/aaic/_download… 19/n

At the 2017 AAIC conference, we naively asked if the financial COI of the co-author list might create the perception of bias. That question elicited sooo much pearl-clutching hmphing and hmming and of course not and how could you ever question our motives?? 20/n

And the next week all of the COI statements were posted online with the draft report (doi.org/10.1016/j.jalz…). All those statements were dated from July/Aug 2017! After they’d written the report! Did they not even get people to sign disclosures before they wrote the report? 21/n

People with major financial COI should not co-author major scientific guidelines. Disclosure is the minimum, the absolute minimum required for credibility… was not even that embarrassingly low standard met here in this statement? 22/n

Would a less conflicted set of co-authors have insisted on better evidence on these biomarkers-evidence in more diverse research participants? We will never know. You just can’t tell if the possibility of making millions of dollars influenced someone’s judgment or not. 23/n

But it doesn’t matter- Biogen got their biomarker defined as a marker of disease even in cognitively healthy people – so if you make the biomarker go away, you must have cured the disease – and then they got their drug approved. 24/27

And many scientists have fallen in line hailing this as a breakthrough because FDA approved. It’s only a breakthrough if it improves the lives & well-being of people affected by AD (and by "people" I don't mean just white people). The evidence isn’t there to support that. 25/27

.#aduhelm was the final step in a long process of nearly entirely ignoring a large fraction of human beings in research to #EndAlz. A culture change is needed, so that everyone-all scientists, all advocates, and all health care professionals-insist on inclusive research. 26/27

Also posting the citation list before we shortened for journal requirements:
1. Mayeda ER Alz Dement 12(3):216-224. doi:10.1016/j.jalz.2015.12.007
2. Chen C Alz Dement Transl Res Clin Interv. 2018;4:510-520. doi:10.1016/j.trci.2018.08.009

3. US FDA CDER. FDA clinical review of aduhelm: application number: 761178Orig1s000. Published online June 6, 2021. accessdata.fda.gov/drugsatfda_doc…

4. Bailey ZD, Krieger N, Agénor M, Graves J, Linos N, Bassett MT. Structural racism and health inequities in the USA: evidence and interventions. The Lancet. 2017;389(10077):1453-1463. doi:10.1016/S0140-6736(17)30569-X

5. Yao J. Med Care. 2019;57(4):262-269. doi:10.1097/MLR.0000000000001079
6. Brickman AM Arch Neurol. 2008;65(8):1053-1061. doi:10.1001/archneur.65.8.1053
7. Barnes LL Neurology. 2015;85(6):528-534. doi:10.1212/WNL.0000000000001834

8. Barnes LL Nat Rev Neurol. 2015;11(4):190-191. doi:10.1038/nrneurol.2015.38
9. Joseph A. Q&A: The CEO of the Alzheimer’s Association on the approval of Aduhelm. STAT. Accessed July 19, 2021. statnews.com/2021/06/16/qa-…

10. Cubanski Kaiser Family Foundation. Published June 10, 2021. Accessed July 21, 2021. kff.org/medicare/issue…
11. Rossetti HC Arch Clin Neuropsychol. 2017;32(2):238-244. doi:10.1093/arclin/acw095

12. Moca News | MoCA – Cognitive Assessment. Accessed July 19, 2021. mocatest.org/moca-news/
13. Biogen and Eisai launch multiple initiatives to help patients with Alzheimer’s disease access ADUHELMTM | Biogen. Accessed July 19, 2021. investors.biogen.com/news-releases/…

14. Is it a senior moment or a talk to the doctor moment? Accessed July 19, 2021. itstimeweknow.com/en_us/home/wha…

15. Moynihan RN, Cooke GPE, Doust JA, Bero L, Hill S, Glasziou PP. Expanding Disease Definitions in Guidelines and Expert Panel Ties to Industry: A Cross-sectional Study of Common Conditions in the United States. PLOS Med. 2013;10(8):e1001500. doi:10.1371/journal.pmed.1001500

16. Jack CR, Bennett DA, Blennow K, et al. NIA-AA Research Framework: Towards a Biological Definition of Alzheimer’s Disease. Published 2017. alz.org/aaic/_download…