Rae Woods (00:02):
From Advisory Board, we are bringing you a radio advisory. My name is Rachel Woods. You can call me Rae. For decades, Alzheimer's research was centered around a single theory, the amyloid beta hypothesis. But this summer, that hypothesis was called into question after evidence of potential fraud. The question is, how much of a setback is this for Alzheimer's research and what does it mean for the rest of the scientific and medical community? Today I've invited two Advisory Board experts. We've got life sciences expert, Nick Hula and senior care expert, Miriam Sznycer-Taub. Together we're going to talk more about the fallout. Plus, how we can restore trust in medical research and where the industry might look to next, when it comes to memory care. Nick, Miriam, welcome to Radio Advisory.

Nick Hula (00:54):
Great to be here. Thanks for having us Rae.

Miriam Sznycer-Taub (00:56):
Hi, Rae. Nice to be back.

Rae Woods (00:57):
We are here in person. We're sitting around the same table, breaking bread, as it were. As we talk about... Gosh, we're here together for a depressing conversation.

Miriam Sznycer-Taub (01:09):
It's nice to be together to talk about it.

Rae Woods (01:11):
To talk about how things are bad?

Nick Hula (01:13):
Share this misery.

Rae Woods (01:30):
This last, I think it was July, news broke that some of the key research supporting the leading hypothesis for Alzheimer's was actually pretty darn manipulated. Tell us what actually happened.

Nick Hula (01:44):
To start, Alzheimer's disease, it is one of the top 10 leading causes of death in the United States. And most people who have it are never even diagnosed with it. It's probably a lot higher. But even though it is an incredibly deadly disease, one of leading causes of death in the United States, we don't actually know what causes it.

Rae Woods (02:04):
Still?

Nick Hula (02:05):
Still to this day. And for decades, we have had a hypothesis that it is these proteins called amyloid plaque. And for decades, there's a lot of research around what types of these plaques could potentially be causing Alzheimer's disease, how is this leading to memory loss? But there was never any definitive study that tied this amyloid plaque to memory loss. That is until 2006 when a study was done at a lab in University of Minnesota that showed in mice or a rats, not in humans, but in mice or rats, that a specific type of this amyloid plaque directly was related to cognitive decline in those rats.

Rae Woods (02:48):
But it turns out that's not the end of the story.

Nick Hula (02:50):
It turns out that's not the end of the story. Because for the decade and a half that follows, there was this big group of researchers who really believed in this amyloid plaque hypothesis. They turned to this study as proof.

Rae Woods (03:03):
Right.

Nick Hula (03:04):
However, this past year it came out that images from that 2006 study were essentially photoshopped.

Rae Woods (03:12):
Literally faked. They just took... Was it the graphs, the results, they were just cutting and slicing photos together.

Nick Hula (03:20):
No one has access to the raw data, so we can't know for sure. But there is overwhelming evidence that they were able to copy and paste pieces of the photo to make it look like their hypothesis was correct, when in reality it most likely was falsified.

Rae Woods (03:38):
Which is literally the opposite purpose of science and scientific advancement. And it's never a good thing when something like this turns out to be fraud. But why is it such a big deal for Alzheimer's? Nick, I feel like you were going down this path already when you said, "We don't actually even know the cause of this disease." And this was a hopeful moment of trying to point us towards a cause. Why is that such a big deal for patients suffering from Alzheimer's?

Miriam Sznycer-Taub (04:05):
I think Nick alluded to the size of the Alzheimer's patient population. It's over six million that we know have a diagnosis. And as Nick mentioned, it's a very underdiagnosed disease. There's probably millions more that are not diagnosed, but most likely have Alzheimer's and the number's growing. And unfortunately, once given a diagnosis of Alzheimer's, there's not a lot that can be done.

(04:30):
There's no cure. There's not even a ton of really effective treatments for the loss of memory and the loss of self. There's certainly treatments for some of the side effects and some of the other medical conditions that come along with it. And people had been looking to this research as a sign that we were going to find something that would be helpful. And this is a blow in unfortunately a series of blows to finding an effective treatment for Alzheimer's.

Rae Woods (05:04):
Because I'm guessing for the last 15 years, all research has followed in this hypothesis tailwinds and saying, "Ah, we've gotten closer." So if we are going to find effective treatments, if we're going to find a cure, we've got to keep going down this rabbit hole of the amyloid beta hypothesis. We've lost 15 years of time.

Miriam Sznycer-Taub (05:23):
Absolutely. There's some people who will say that this hypothesis took all the funding that was out there and there was very little room for scientists who wanted to research any of the other causes. Remember, we still don't actually know what causes Alzheimer's. We don't know what causes the memory loss. And this has, in some ways, kept other potential theories from receiving funding. And who knows, we could have seen curative or helpful pharmaceuticals that could have come out, had we been able to pursue some of these other theories.

Rae Woods (05:50):
Have we been looking for anything else?

Miriam Sznycer-Taub (05:52):
Exactly.

Rae Woods (05:54):
Who's going to jail for this? I'm kidding. We all probably watched the latest in the Theranos saga. I was a fan of, let's see, the book, the podcast, obviously, the most recent... Was it Hulu that it was on? Is this the next big series?

Nick Hula (06:14):
I don't know if this is Theranos level fraud, but it definitely could make a great documentary. I'm sure there's a role in here for Amanda Seyfried and for Naveen Andrews, I'm sure. But you're right. How many billions of dollars? And I think more important than the dollars, Miriam, you said it, is how many years have we spent investigating this hypothesis and investigating this approach? There are a lot of others. There are metabolic approaches, anti-inflammatory approaches that have received not as much spotlight and not as much attention from scientists, from people who are funding this research that, like we said, could have.

Rae Woods (06:52):
Nick, what do you think those organizations are going to do next? What does this mean for life sciences and pharmaceuticals in a world where they have to, maybe this is hyperbolic, but start over?

Nick Hula (07:02):
I think this reminds us of one of the big dangers of over-funding in one area of research, putting all your eggs in one basket. I'm sure for certain diseases where we are very certain about the causes of disease and they approach we need to take, that might make sense. But for a disease Alzheimer's where we didn't know, and at that point there were still questions about the amyloid hypothesis, even after the 2006 study, people still had trouble replicating it, which is the exact opposite of what science should be.

Rae Woods (07:34):
A hallmark of science is that you can replicate the results.

Nick Hula (07:35):
Exactly. It shows the dangers of overfunding in one area. But I think the second big impact on life sciences and why I think a lot of pharmaceutical manufacturers need to be thinking about, and a lot of other research organizations, is how do we prove the real world value of our therapies and our research moving forward? Because you look at different types of drugs that have come out that have used the amyloid approach. They have been, some have been FDA approved, we had Aduhelm, came out last year.

Rae Woods (08:08):
We should talk about Aduhelm because it has also been in the news for some not good reasons. Not for maybe as bad as this one, but was it last year that it came out that not only is this drug incredibly expensive, sure the FDA approved it, but does it even work?

Nick Hula (08:28):
Think about now what the FDA is responsible for because what it seems like now is that the FDA is going to take a look at something and say, "Is this drug safe? And is it effective?" Safety is safety, it's not going to kill people or it's probably not going to kill people. They're always some side effects you hear in the advertisements. And then, is it effective? As in does it do what it says it's going to do? For Aduhelm, Aduhelm aimed to reduce the amyloid plaque in the brain. And it did a great job.

Rae Woods (08:56):
It was based on this hypothesis that we now know is not true.

Nick Hula (09:02):
It was based on the hypothesis and did a great job of it. It did remove plaque from the brain.

Rae Woods (09:06):
But it didn't reduce the symptoms of Alzheimer's because it turns out that is not the underlying cause.

Nick Hula (09:13):
Yes. Or at least we still have yet to prove that's underlying cause. Could it be in the far future we realize it is? Potentially. And that's where value comes in because value and efficacy are not the same thing when we're talking about the impact that drugs have on whomever. Value in this drug would have been if someone's cognitive decline was slowed because of this drug.

Rae Woods (09:34):
Their outcomes were better.

Nick Hula (09:35):
Their outcomes were better. But we didn't see that at all in this case, or very weak evidence to suggested.

Rae Woods (09:39):
Wait. But the FDA still approved. It is still a drug that if you were willing to pay for it, and I should say that a lot of the providers that we work with at Advisory Board came out with some big statements and said, "We're not going to offer it." Health Plans said, "We're not going to cover it." Although, I think Medicare is.

Nick Hula (09:53):
They said only if it's within a confirmatory trial, which is a very small population.

Rae Woods (10:00):
Very limited population.

Nick Hula (10:00):
Very limited population.

Rae Woods (10:02):
Then why did the FDA approve it?

Nick Hula (10:03):
Because the FDA is there to, again, judge safety and efficacy. And Aduhelm was safe and it was effective. And they said, "You know what? It's good. It's safe. It reduces plaque on the brain. This gets a thumbs up from us." It's up to other stakeholders throughout the healthcare industry to determine if something is valuable. The issue is value means something different to every stakeholder. To a patient, someone who is desperate to find anything to help cure or slow down this debilitating disease, I'm sure a drug like this, even if they're not a hundred percent sure of the outcomes, that's probably valuable. To a payer who's paying 50 plus thousand dollars a year for years on end for potentially tens if not hundreds of thousands of their members, and there's no guarantee that's actually going to make any of those people better.

Rae Woods (10:53):
That's risk. They're not going to take, absolutely not going to take.

Nick Hula (10:56):
The FDA's job is to say that safe is effective. It's up to everyone else to determine if it's valuable.

Miriam Sznycer-Taub (11:01):
The other wrinkle I'll throw in for diseases like Alzheimer's is this, there's patients, and Nick just talked about the value to patients, but Alzheimer's is a disease that disproportionately affects older adults, which means there are caregivers involved, there are their children, there are their spouses. And these people are also, in some ways, desperate for something that will help their loved ones. And you saw after Aduhelm was approved, a groundswell of support from patient and caregiver and advocacy organizations, really desperate for approval of Aduhelm because of the desire to try and the desire to have something, to grasp onto something of this disease, which is truly debilitating and very hard on both the patient as well as their family and friends, their loved ones. These are people who often have to leave their jobs, scope back their hours, spend a lot of their own money to care for their loved ones as they see this decline. That for the moment, again, we can't really stop.

Rae Woods (13:13):
If I think about the combination of Aduhelm, this drug that is incredibly expensive and ineffective, is that too strong of a term to use? Not very effective, maybe if I tone my language down a little bit.

Nick Hula (13:26):
Not valuable.

Rae Woods (13:27):
Not valuable, to use Nicks language here, and then add that to the news that's hit the media in a time, frankly, when people are paying a lot more attention to things happening in healthcare than perhaps ever before. I wonder if we're going to shift from a world where people are desperate to try anything to a world where this is one more reason not to trust science and not to trust medicine. Which comes back to how do we address that? If that's one of the ripple effects here, how can we advise health leaders listening to this podcast to start to build back some of that trust?

Miriam Sznycer-Taub (14:03):
I think a lot of it is going to fall onto clinicians. And I hate to say that because I feel like I'm adding yet another thing to people's plate who have so many things to do. But clinicians are the ones who are talking to patients, talking to family members. They're the ones that are entrusted to keep patients best interest and to help them figure out their best path. It's thinking about that relationship that clinicians have with their patients and building that back is probably the way that patients will start to see trust. And even if it's just in that one clinician that they're seeing, then that starts to build their trust back in the field of medicine again.

Rae Woods (14:43):
I appreciate that you're using the word clinician and not doctor. Because I think we default to the doctor patient relationship. And it might be that doctors actually have the best shot here because there is a lot of trust in that relationship.

(14:55):
But we also learned, frankly from Covid, from the last big moment where there was a lot of medical mistrust that still hasn't gone away. That systems can do a lot to support, first of all those doctors, but also support everyone else who might be interacting with the patient. Miriam, you just talked a lot about caregivers. I'm thinking social workers are going to interact with these families. I don't know to the extent that drivers are interacting with them, certainly nursing MAs, front desk staff, APPs, other members of the clinical team that have a role here in reestablishing that trust or even explaining what happened in terms that will make sense for people.

Miriam Sznycer-Taub (15:33):
Absolutely. I think Alzheimer's and other dementia is much like so many other things require a care team. It is not just a physician interacting with these patients, but as you said, they're interacting with all kinds of people throughout the medical community.

(15:47):
They're often receiving services in their home. There might be a home health nurse that's involved. And I think that there's a whole spectrum of people that can be trusted representatives of the medical community. But what I think we need to do is make sure that all of those clinicians have the facts. They have the answers to patients questions. They have the answers to family members questions. They can explain, "Hey, this is why we can't give your loved one Aduhelm right now. This is why this isn't working." We can't send these people in blind. We can't send these people in unprepared.

Rae Woods (16:26):
What's the role of PhRMA here though? I got to say, I mentioned that the doctor patient relationship is one that is usually rooted in trust. I can't usually say the same thing for PhRMA.

Nick Hula (16:36):
That's very true. I think the role for PhRMA here to start to build trust in the first place with a lot of patients is by doing two things. First is developing more real world evidence on the efficacy of their drugs.

Rae Woods (16:54):
The FDA's not going to do that, as we know.

Nick Hula (16:57):
The FDA is not going to do it. Even after a clinical trial where they said, "Yes, it's safe and it's effective, we've given the first place." Going on past that and taking a look at data on how this is actually playing out in patients over the course of five, 10 years. The second thing we need to be doing is doing a lot of these trials on a more diverse patient population because right now most trials are composed primarily of people of European descent. But we know that drugs impact people of different background, of different sexes, of different ethnicities differently. We need life scientist to be expanding their clinical trials to more of those underrepresented populations. Hard to do because that's going to take a lot of money. That's going to take a lot of time to do. But in order to build back that trust within the patients population over the course of the next decade, I think they need to develop that real world evidence and expand their trials to a more diverse population.

Rae Woods (17:56):
I actually want to take a step back because we've been focusing most of this conversation on the impact of the research itself, how it's going to affect the pharmaceutical pipeline, the role of life sciences, the impact on trust. I just want to take a step back and talk about this disease and talk about Alzheimer's. What bigger impact does this have on seniors and on memory care? And what can the industry do to support those people?

Miriam Sznycer-Taub (18:24):
All of us have to look at ways to support Alzheimer's and other dementia patients in ways that aren't necessarily all around PhRMA. I think I'd point to three things that I think the industry can do. The first is that we have to get better at diagnosing these patients. We don't actually know the true burden of Alzheimer's in this country. I mentioned the six million people earlier, but the number is almost certainly bigger.

(18:50):
There's some estimates that six million is actually only half of the population of older adults that actually has. The industry has to get better at improving diagnosis. And that is from both a clinical perspective, figuring out a better care pathway. There is a payment angle of figuring out how do we better reimburse for diagnosis. And there's certainly an angle of how do we have these tough conversations with seniors as they're starting to lose their memory and identify what is a normal sign of aging and what is potentially something that needs to get flagged for further investigation. The second thing, Nick already talked about, and that's improved clinical trials. I do think that in order to find better pharmaceutical options, both that will treat Alzheimer's, potentially cure it or better treat its side effects, we need clinical trials that are better representative of the senior population that is changing.

(19:47):
And lastly, I think there's a lot the industry can do around disease management that's not pharmaceutical. This is around ensuring that patients with Alzheimer's have access to behavioral health specialists, to help with a lot of the behavioral health side effects that come with the disease. Supporting caregivers, helping relieve some of the burden that comes with having to care for people with this disease.

(20:08):
And thinking about better residential support. As much as seniors want to age in place, there's a point at which folks with Alzheimer's really cannot live safely in their home. And at the moment, we don't have enough safe, healthy spaces for these people to go. I think there's lots of opportunities for really everyone in healthcare to think about how to better support this growing population with Alzheimer's.

Rae Woods (20:31):
And opportunities beyond the pharmaceutical pipeline, which hopefully we started off by saying this is a tough conversation, but I actually think that provides some hope because there are things that health leaders can do. And I actually want to end with giving each of you a moment to speak directly to different stakeholders within healthcare. Nick, I'm going to start with you. What's the big thing that you want the life sciences leaders, who are listening to this podcast, to do as a result of this conversation?

Nick Hula (20:59):
Think about how you're communicating the value of your drug. I'm not talking about its safety or its efficacy. Think about how you're communicating the value, what that actually means to making patients better. And think about how you are framing that to patients, to providers and payers because it's probably going to be different messaging for each one of those.

Rae Woods (21:21):
What about the payer? Do we have a thought on what our payer listeners should be doing?

Miriam Sznycer-Taub (21:27):
I think I'll speak I guess directly to Medicare Advantage Plans here.

Rae Woods (21:30):
Sure.

Miriam Sznycer-Taub (21:30):
Because as, certainly all listeners of this podcast know, Medicare Advantage is growing. It's rapidly becoming the dominant way in which seniors are receiving their Medicare benefits. And for MA plans, if they haven't already started thinking about how they're going to care for their beneficiaries with Alzheimer's, they need to think about it. Seniors with Alzheimer's have higher medical spend than seniors without Alzheimer's. That's because they're hospitalized more. They have higher pharmaceutical spend, they have higher post acute spend, really across the board. And there're opportunities for Medicare Advantage Plans to think about how they can work with these patients, work with their physicians and caregivers, to better manage these patients to ensure that they're not having unnecessary hospitalizations.

(22:16):
MA plans can also help with that diagnosis problem. If we can get more people with Alzheimer's appropriately diagnosed, then we can ensure that they're getting the treatments that they need. And I think there's a real opportunity for MA Plans there.

Rae Woods (22:29):
What about for the care delivery arm?

Miriam Sznycer-Taub (22:31):
Care delivery is more than just a physician. And with Alzheimer's, it's honestly more than just the care team and the expanded care team, this is caregivers as well. The more that we can support, especially unpaid caregivers, those family and friends that are giving up time and money to support these patients, however we can better support them, I think will ultimately improve the quality of life for patients with Alzheimer's.

Rae Woods (23:00):
Nick, Miriam, thanks for coming to Radio Advisory in person.

Nick Hula (23:05):
Thanks for having us literally here. Not figuratively, literally.

Miriam Sznycer-Taub (23:09):
Thanks Rae. Thanks Nick. It was so nice to see both of you live in person.

Rae Woods (23:13):
I know.

(23:18):
The story for Alzheimer's doesn't end here. There are more therapeutics in the pipeline. In fact, some are still relying on the amyloid hypothesis, which in the end may even be the right answer. But what's clear to me is that we have to think bigger. We need more inclusive trials. We need to expand our therapeutic pipeline, and we need more holistic resources for patients and for families. And remember as always, we're here to help.

(24:04):
They have... Hold on. I lost where I was going with that. I had it in my mind.

Nick Hula (24:14):
I could see you going in your head, doing a script in your head. That was fant