Yet Another Piece about ADUHELM
Or 'what's one thing we can learn from Biogen's troubled launch'
tl;dr -
ADUHELM’s challenges showcase how a system designed to work on evidence may conflict with growing patient advocacy & engagement in their own healthcare
Market context: As the fifth leading cause of death in the US, Alzheimer’s Disease (AD) represents a total cost burden to system of over $270B in direct healthcare costs1 and has a difficult history of clinical innovation with multiple high-profile failures2 and unclear long-term efficacy of current options3; these factors easily make AD a blockbuster opportunity for new, innovative agents
Approval history: ADUHELM’s path to approval began in March 2019, with the manufacturer stopping Phase III trials due to futility4 - basically, when a trial is likely to fail - and began seeking FDA counsel in June5 on whether a path to approval still existed based on additional analysis; after a contentious process in which an FDA advisory panel declined to endorse approval6, ADUHELM was approved in the US in June, 20217
It should be noted that, as a point of comparision, the European Medicines Agency (EMA) recommended refusal of market authorization for the product in December, 20218
Biogen last reported ADUHELM revenue to be $0.3M in its Q3 2021 financial results9; CEO Michel Vounatsos rationalized the poor performance via poor reimbursement10 as opposed to price or questions on efficacy
One main factor - often overlooked - is the influence of patient organizations on the FDA decision to approve; among other activities,11 patient organizations rallied to host various connection points with FDA officials emphasizing the unmet need & burden of illness; as one senior leader noted, ‘you cannot be unmoved by hearing the stories of people who face this disease, the crushing realities of it every day.’12
With growing patient involvement within the design, development & approval of healthcare interventions, questions remain on how should patient input be considered in regulatory decision-making
On one hand, the patient experience is invaluable in assessing the true benefit of new healthcare innovations that may be missed only be relying on traditional clinical trial endpoints; on the other hand the urgency of patient needs - a ‘desperation’ for new options13 - may lead to the approval of ineffectual products that ultimately detriment patients by failing their expectations, and the system at large by being wasted spend
Ultimately, patient input in the development & launch of new healthcare innovations is vital - the question is what is the best process for assessing new options that both respects & seriously considers their perspectives while not straying too far from clear & established scientific measures of efficacy & utility
Woof.
You know, as I was writing this, I was reflecting how this is such an unpopular thing to even broach in healthcare. Over the past twenty plus years14, the idea that patients should be more in control of their healthcare has grown tremendously popular. Gone are the days where patients are considered passive in their role in healthcare; the modern trend is that patients should be continuously involved in every stage of care, from co-creation of healthcare systems15, working hand-in-hand with innovators16, and even as a part of the modern coordinated care team.17 Certainly, the rhetoric of ‘putting patients back in control’ has become a rallying cry for the extremely overheated digital health sector18, as consumerism supports popular B2C go-to-market business models. It also taps into something deep & fundamental in all of us - the desire to self-determine. After all, for something as important as our health, why shouldn’t we have more of a voice? More of a say?
The ADUHELM situation reminds us all that, like most ideas, the value of greater patient involvement in healthcare doesn’t automatically result in optimal outcomes. To be more blunt, greater patient involvement requires the right processes & technology to truly translate the trend into realizable value. This involves asking tough questions, like what’s the best way to marry traditional efficacy measures with patient experience? How correlated are the two? How much causation is there between the two? And the hardest question of all - when should the patient experience not be considered in at a decision point? Ouch. I winced just writing that.
But it’s also a critical point to explore. Taken to the extreme, reliance only on the patient experience and their desires & wants in healthcare can lead to challenges. Aside from the ADUHELM story above - where the understandable desperation surrounding AD resulted in maybe, not the best outcome for anyone involved (certainly not Biogen!), another example of the ‘dark side’ of patient involvement is of course, use of dubious products like ivermectin for COVID-1919. There are real risks when empowered patients are let loose into the wild without the right support systems, and the key takeaway of some of these situations is not ‘patients should not be trusted with their own healthcare’ but ‘incorporation of patient feedback into healthcare - whether in the facets of their immediate experience or the development of new innovation - needs to be done judiciously & thoughtfully.’
Thankfully, there are people out there thinking about these issues (some of them in the citations below) and have proposed different solutions & frameworks. I’ll add my own idea to this - I believe that effective incorporation of patient feedback in the development of new healthcare innovations comes from establishing a relationship framework between patient feedback & other types of data in terms of levels of evidence. If this sounds familiar, it’s cause … well, levels of evidence have been a thing in healthcare for a very, very long time - like so:
Evolving Levels of Evidence frameworks like this to incorporate the patient experience can solve many issues. For one thing, it instantly provides a relational understanding behind how patient experience should be considered in tandem with other data used to make healthcare decisions. For another, it adds legitimacy to the patient experience as something that should always be considered, putting it at the same metaphysical level as an expert opinion or a cohort study. Finally, it encourages a key behavior change by creating an incentive for HCPs to ask more about the patient experience (because if you don’t … well, you’re not really doing evidence-based medicine anymore, are you, and you want to because you want to be good at your career!). Of course, there are many complexities to even doing this - are there conditions where the patient experience is more or less important (like rare diseases?) is one example complication - but seems like an elegant solution to me! Given that I’m not a clinician, however, I’ll leave it to the healthcare professionals of the world to figure this out (and hey, if you guys are already doing this, then call me uninformed & feel free to correct me by reaching out on Twitter or something).
What am I, however, is a strategist - one who is particularly interested in making sure that the healthcare system I and the people I love participate in gets more effective & efficient over time, not less. That means the incorporation of patient experience & feedback into healthcare in a more fundamental way - but not in the current way, a way which may result in more ADUHELMs. I don’t think attaining greater importance of the patient experience at the cost of a greater chance at ineffective product approvals - and all the costs associated with it - is particularly worth it, especially if we can accomplish that first goal more effectively with just a little bit of thoughtfulness.
Hopefully, we’ll get there together someday.
(And yes, I might have some Oracle x Cerner fanfiction in the works. Stay tuned.)
https://www.ajmc.com/view/economic-burden-of-alzheimer-disease-and-managed-care-considerations; based on $305B total cost burden minus $33B representing indirect costs (i.e. caregiver burden, etc.)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6966425/
https://www.ncbi.nlm.nih.gov/books/NBK279356/
https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.12213
https://www.fda.gov/media/143502/download
https://www.nytimes.com/2020/11/06/health/aducanumab-alzheimers-drug-fda-panel.html
https://www.fda.gov/news-events/press-announcements/fda-grants-accelerated-approval-alzheimers-drug
https://www.ema.europa.eu/en/medicines/human/summaries-opinion/aduhelm
https://investors.biogen.com/static-files/4e5e45f7-9bd1-412a-a7f1-fc5366b2f3cd
https://www.fiercepharma.com/pharma/biogen-reports-paltry-aduhelm-sales-300k-obviously-disappointing-says-ceo-vounatsos
https://changingaging.org/blog/trust-at-stake-alzheimers-associations-role-in-fdas-approval-of-aduhelm/
https://www.statnews.com/2021/06/16/qa-ceo-alzheimers-association-on-aduhelm/
https://medicalethicshealthpolicy.med.upenn.edu/uploads/attachments/ckv73ht4g8c0us1le6nmaky0o-largent-and-lynch-paper-10-25-21.pdf
https://pubmed.ncbi.nlm.nih.gov/11126470/
https://journalofethics.ama-assn.org/article/co-creation-health-systems-design/2017-11
https://www.mea.boehringer-ingelheim.com/press-release/boehringer-ingelheim-and-ashoka-host-co-creation-workshop-under-making-more-health
https://www.urmc.rochester.edu/strong-memorial/patients-families/health-care-team/being-part-of-the-team.aspx
https://transcarent.com/posts/transcarent-raises-series-B-funding-round
https://themedicinemaker.com/business-regulation/seriously-yall-stop-it