Should we pay people to get vaccinated? Well, maybe.

This past week, a major US retail company, Dollar General, announced that it would pay its employees the equivalent of four hours’ salary if they would get the Covid-19 vaccine. That’s about $40, based on the average pay at Dollar General. The idea is to give employees an additional incentive, and also to cover the time they might need to take off work to get vaccinated.

This is an excellent idea. Let me explain why.

First, though, I should point out that several prominent economists, including Harvard’s Gregory Mankiw and the Brooking Institution’s Robert Litan, have already proposed paying people to be vaccinated–but their proposal is, frankly, terrible. So let’s start with that.

Now that we have two vaccines, from Moderna and Pfizer/BioNTech, with more on the way, we can finally see an end to this awful pandemic. At the moment we have a supply problem: there aren’t enough vaccines to go around. But soon, perhaps in a few months, we’ll have plenty of vaccines. Then the problem becomes getting enough people vaccinated to create “herd immunity.”

(Aside: herd immunity has been discussed ad nauseum this year, so I won’t get into any details, but it essentially refers to the situation where so many people are immune to the virus that it doesn’t spread any more. We probably need 60% of the population to be immune (estimates vary) in order to reach herd immunity.)

A well-informed person might think this won’t be a problem: billions of people are desperate to get the vaccine right now. But the anti-vaccination movement has been spreading misinformation about Covid-19 vaccines since the beginning of the pandemic, long before we even had a vaccine. (Yes, I know it’s patently ridiculous to make claims about a non-existent vaccine, but they did, aplenty. I’m not linking to any of their claims here because I don’t want to give them the traffic.)

As a result of the relentless anti-vax propaganda campaign, a substantial portion of the population is at least “vaccine hesitant,” meaning they’re not sure if they want the vaccine. They are worried primarily about safety, even though the data is very clear that these vaccines are remarkably safe. (It’s true that a tiny number of people have had allergic reactions, but this data is public and no one’s hiding it.)

So we need to convince some people that it’s in their own best interests to get vaccinated. A small number of deeply confused anti-vaxxers, such as the people behind the mis-named NVIC, are probably unreachable. They simply won’t listen, preferring to believe their own misinformation and conspiracy theories. But for the large number of people who are merely hesitant, a positive incentive might be just the thing to convince them to get vaccinated.

Enter the economists. Robert Litan first proposed paying people to take the vaccine back in August, and Gregory Mankiw strongly endorsed the idea, writing:

“what’s the best way to achieve herd immunity? Again, simple: Once a vaccine is approved, pay people to take it.”

Such confidence! Actually it’s quite a good idea in principle. But Litan and Mankiw then went off the rails, proposing that we pay everyone $1000 each to get the shot. Litan admitted that he didn’t have any data to support this particular amount, but he called it a “strong hunch.”

That’s a $300 billion program. Neither Litan nor Mankiw was bothered by this.

There are some gigantic problems with this proposal. First, because it’s such an enormous amount, it’s extremely unlikely that it will ever happen. It’s just the kind of hypothetical, pie-in-the-sky proposal that gives academics a bad name. Because it will never happen, Litan and Mankiw will never have their idea tested in real life, and no doubt they will continue to claim it would have worked.

Second, though, is a much bigger problem, as pointed out by economists George Loewenstein and Cynthia Cryder in the New York Times, and by medical ethicists Emily Largent and Franklin Miller in JAMA. The problem is that if you offer to pay a lot of money to do something, then people conclude “this is something you would not want to do without compensation.” In other words, it’s dangerous or somehow bad.

Thus a large payment may merely heighten people’s suspicions that the government (or “Big Pharma”) is up to no good, and that’s why they have to bribe people to take their suggestions. The last thing we need right now is to increase people’s mistrust of vaccines.

In addition, paying so much money for each shot is, as Largent and Miller point out, a bad investment. Sure, $300 billion is much less than Covid-19 is costing us right now, but it’s still a huge sum, and those funds could be better spent on many other things, such as helping to support states that are still struggling to set up facilities to administer the vaccine.

Now let’s go back to the Dollar General plan. Dollar General is paying the equivalent of four hours’ worth of salary, about $40 on average, to each employee who gets vaccinated. As I said above, this is an excellent idea.

Why is this better than the $1000 per person plan from the economists? First of all, it costs far, far less than the economists’ plan, which makes it far more likely to happen. Second, Dollar General is paying people to defray the actual costs–in time–that they will incur in order to get the vaccine. So it’s not so much a bribe as it is a modest reimbursement. Third, by providing a modest payment, they provide a relatively bigger incentive to low-income groups, and they avoid paying billions of dollars to high-income people who are already highly motivated to get the vaccine.

I suggest we adopt a version of Dollar General’s plan for the entire U.S. population. Why not offer a cash payment of $20 to everyone who gets the vaccine, and pay it immediately? Obviously there would be some logistical challenges to this–we’d need security procedures to make sure the $20 payments were actually handed out and not stolen–but it would be far simpler than arranging the $1000 payments so blithely proposed by the academic economists. And it would only cost $6 billion rather than $300 billion.

A payment of $20 provides a small positive incentive, and it can be justified as paying people for the time they spend getting the shot. Because it won’t seem like a bribe, it will be much less likely to raise suspicions that the vaccine is harmful (which it isn’t, I hasten to add).

So Litan and Mankiw were sort of right: paying people might encourage more people to get vaccinated. But they’re wildly wrong about the size of the payment, which other economists and bioethicists have pointed out would likely create distrust. Dollar General is getting it right: let’s offer everyone a small cash payment if they’ll take the time to get the vaccine. It might just work.

A meditation on the year to come

A mountain in the Eiger valley, Switzerland.

So we've just experienced one of the hardest years in the past 50. The world is still reeling, but we have reasons to hope that our lives on this planet will get better–much, much better–in 2021. Entering the new year, I'm offering this brief meditation (a technique that I would have dismissed in years past, but that I've discovered during the pandemic) with my hopes for better times ahead. Vaccines will soon free us, at long last, from the prison of social distancing that the virus has imposed on the entire population. Emerging from our months of isolation, what will we do first? Next?

Let's imagine, as we meditate, that we will travel, as many of us desperately long to do. On a train, or a plane, or just in a car, finally going somewhere far away with a close companion, with no masks required. Viewing the sights, taking photos, eating at a crowded restaurant, or just walking through a shopping district filled with people. Enjoying the freedom that we took for granted for our whole lives, until the pandemic shut everything down in March of 2020. Sipping an Aperol spritz on a terrace with a scenic mountain view.

Everything we've lost will return again. Let's imagine, closing our eyes for a few moments, what we'll do once we get beyond these last months of the pandemic, once we are free again. Anything is possible, and the future will be better.

Closing the barn door after the virus has escaped

When will we learn? For the past two or three weeks, the world has been fretting over a new Covid-19 virus variant, one that UK Prime Minister Boris Johnson announced was significantly more transmissible than other variants.

Johnson’s announcement has led multiple other countries, including the U.S. and France, to temporarily ban travel from the UK. As scientists began testing for the new variant, at least 3 states in the US–California, Colorado, and Florida–have already reported that they are detecting the new variant too. Expect many more states (and other countries) to report finding the variant in the coming days.

In the UK, the new variant was first detected in September, and by November one-fourth of the cases in London were caused by this variant. That does seem worrisome.

My first reaction upon hearing of this new variant was to ask whether it really is more transmissible or not. The evidence is very preliminary, and it’s still not peer-reviewed, but a very new study from a week ago says that yes, the new variant is 56% more transmissible.

Okay then, that’s not great. But there’s no evidence that the new variant (known variously as B117 or VOC 202012/01) is more deadly, or that the vaccine won’t work against it. It just spreads faster.

My second reaction was about these new travel bans. Why would anyone think that the variant was only in the UK, merely because the UK was open about reporting it? Unless we really know that to be a fact, travel bans are a classic case, as the adage goes, of closing the barn door after the horse (the virus) has escaped.

So has the B117 virus has already spread well beyond the UK? Yes, it appears so.

In a new study released just two days ago on medRxiv, scientists at Helix, a company that has tested millions of samples for the presence of the SARS-CoV-2 virus, looked back at their testing data over the past several months. They found that evidence of the B117 virus in the US extends back at least to October. They also found that the variant is now spreading in the eastern US, in Massachusetts, Ohio, and Florida.

An important caveat is that Helix’s tests weren’t specifically looking for the B117 strain. They instead looked at two key deletions in the spike protein (which I’ve discussed before) that the B117 strain contains, and that their tests can also detect. It might be that they found slightly different strains that shared these deletions, but even if the strains they detected weren’t identical to B117, it’s possible they were equally infectious.

So yes, the new strain seems to be in the US already, and it seems that it’s been here since October. And if it’s been in the UK since September, and the US since October, well then it’s a darned good bet that it’s pretty much everywhere. Banning travel from the UK not only punishes the UK for openly sharing its findings, but it also may prevent other countries from sharing information about newer strains of the virus, should those emerge.

What should we do in response to the new strain? The most effective action will be to roll out vaccines even faster, something that public health authorities across the US are trying to do. So far it is not going well, in part because we have no consistent national strategy. It’s not too late to fix that.

But let’s not pretend that travel restrictions now will do anything to keep this new strain locked up. They’re just closing the barn door after the horse has escaped. Or “Vijgen na pasen” as they say in Flemish, or “arriver apr├Ęs la bataille” in French. There’s an idiom for this behavior in every language, it seems.

These new RNA vaccines are a triumph for science and medicine

This week the FDA approved a second vaccine against SARS-CoV-2, the virus that causes Covid-19. We now have two highly effective vaccines, one from BioNTech and Pfizer, and the other from Moderna. A third vaccine, from Oxford University and AstraZeneca, is very close to approval.

The two new vaccines, both based on RNA, are both remarkably effective. Below I’ll summarize some of the numbers, which have been published for the world to see.

This is a scientific triumph. Less than a year ago, no one outside China even knew this virus existed. The genome of the virus was first released in January, and within a few months scientists had designed the first vaccines. Clinical trials were launched immediately, and larger trials followed, leading us to where we are today: two new vaccines, tested and validated in tens of thousands of people, now being manufactured and shipped to billions.

For anyone who might be skeptical, or who just might want to know more, the test results are being published openly. The New England Journal of Medicine has a dedicated website with dozens of papers and audio summaries, including results from the large-scale (Phase 3) trials of the Pfizer vaccine.

Before getting into the numbers, let’s summarize what these two new vaccines are. (I wrote about this in July, if you want to read my previous explanation.) Both of them are RNA vaccines, which is itself a dramatic breakthrough. RNA vaccines have been discussed for years, but the technology was never employed for human vaccines until now.

Here’s how they work: our immune system (which is super-complicated, as Ed Yong explained in The Atlantic) recognizes microscopic invaders and destroys them. Once you’ve been infected with Covid-19, the immune system swarms over the viral particles and basically learns what they look like. SARS-CoV-2 has a protein all over its surface called “Spike,” so that’s what the immune system recognizes.

Once you’ve fought off the infection, the immune system remembers what Spike looks like. If you’re infected again, it can respond far more quickly, so you won’t get sick. This is what we call acquired immunity.

So for vaccines, the trick is to teach your immune system to recognize Spike. One way to do that is to manufacture lots and lots of the Spike protein, and put that in the vaccine (sort of–I’m greatly oversimplifying here).

But with modern genomics technology, we can use a different approach. Every cell in your body has machinery inside it to translate RNA into proteins. As soon as we had the SARS-CoV-2 genome, back in January, we knew the genetic code for Spike. So rather than make the protein, what if you just made the RNA, which is far easier and faster to manufacture, and injected that into people? Do our own cells then translate the RNA and make the Spike protein?

Well yes, they do. And not only that, but–as the Modern and Pfizer clinical trials have now proven–our immune system recognizes that the Spike protein is foreign (it’s complicated) and launches an attack.

So to make an effective RNA vaccine, you simply have to inject enough RNA so that the immune system responds. That’s what both the Modern and BioNTech/Pfizer vaccines have done.

Now let’s look at the numbers. As reported in NEJM just two weeks ago, the Phase 3 trail for the Pfizer vaccine tested 43,448 volunteers, of whom 21,720 got the vaccine and 21,728 got a placebo. At the time of the report, 162 people who received the placebo had become sick with Covid-19, but only 8 people in the vaccine group got sick. That’s a 95% reduction in illness, a remarkably good result. They also reported that 10 people had “severe” illness, and 9 of those ten were in the placebo group.

How about the Moderna vaccine? This vaccine has almost identical efficacy, published in a preliminary report a few weeks ago as 94.5%. Just a few days ago, an FDA review panel approved the vaccine and confirmed that its efficacy was above 94%. And the Modern vaccine doesn’t need the super-cold freezers that the Pfizer vaccine needs, which makes it easier to distribute.

Both vaccines have minimal side effects in most people, mostly soreness at the injection site, and sometimes headaches or chills, which subside within a day. RNA is quickly degraded in the body, so there’s no reason to expect any lingering side effects from these vaccines.

There’s also growing evidence that immunity lasts for many months, if not years. Another report in NEJM, on the Moderna vaccine, contains some of the latest data, which shows that immunity is still strong after 4 months. Of course, with a brand-new vaccine, we simply have to wait to see if the immunity lasts for years, but all signs are positive right now.

So yes, these are really good vaccines. I will get mine as soon as I can, although I expect I’ll have to wait several months because of short supply.

(The Oxford/AstraZeneca vaccine, a more traditional protein-based vaccine, has also shown positive results, either 62% or 90%, depending on the dosage regimen, but the 90% results are based on fewer cases. Even so, it is clearly effective and it should be approved soon, at least in the UK. So we might soon have 3 vaccines.)

A note to anti-vaxxers: no, you cannot catch Covid-19 from these vaccines. They don’t contain the virus! They only have a fragment of RNA from one protein, and the virus has RNA that encodes 28 other proteins. It’s simply impossible for the virus to self-assemble without the rest of its genome.

But hey, if you don’t want the vaccine, go to the back of the line. Most of the world is desperate for it.

The success of RNA vaccines is a huge win for science, but even more, it’s a huge win for the human population. We’re still many months away from vaccinating the whole world, but with two highly effective vaccines, we can finally have hope to end this pandemic.

New Nature open access policy is little more than a money grab

We scientists love to publish papers, and we get especially excited when our papers appear in “top” journals. The journals know this, and sometimes it seems they just want to see how much they can get scientists to grovel.

That’s what I was thinking a couple of weeks ago, when the publishers of Nature announced that they will charge authors €9,500 ($11,500) to publish a paper as open access, meaning readers can get the paper without a subscription. They called this, without a trace of irony, their “gold open access option.”

$11,500??? Sadly, the Nature publishers were not kidding.

This is outrageous. $11,500 is more than scientists earn in a year in some countries, as Forbes blogger Madhukar Pai pointed out. What’s truly outrageous is that they’re asking for this payment from a community that does all the work for them for free. If Nature is going to treat scientists like suckers, it’s time we stopped playing along.

Let’s back up a minute and look at how the academic publishing system works. (When I explain this to non-scientists, they are often flabbergasted.) Consider: a typical science paper describes experiments that cost tens or hundreds of thousands of dollars, most of which comes from government grants (the most common source of funding) or from private foundations. Scientists write the paper and then submit it to a journal. The journal, in turn, asks other scientists to review the paper, which they do, using their own time and expertise.

All of this–the scientific experiments, the writing, and the reviewing–is done for free, from the journal’s perspective.

Journals then claim copyright on the papers and charge fees to anyone who wants to read them. Not a bad deal for them: virtually all the labor is free. Scientific journals, most of which are owned by a small number of large, for-profit publishers, are very, very profitable.

The whole system, as Berkeley professor Mike Eisen explained in a recent interview in Science, “was built for the printing press.” When journals had to print everything on paper and ship the journals to libraries around the world, it kind of made sense. They were providing a valuable service for science, and it does cost money to print and deliver all those journals.

For over two decades, though, we have been distributing papers electronically, and there’s almost no need for paper copies. One might expect that journals would change their model, but they haven’t. In fact, they’re even more profitable now than they were before the Internet.

Not content with their enormous profits, it now seems that Springer Nature wants to suck even more money out of academic science. It’s true that Nature publishes some highly prestigious scientific journals, but their announcement of this new “gold” open access policy just drips with self-congratulation. “Research published in Nature and the Nature research journals is downloaded ... over 30 times more than papers in a typical journal,” they write. (Who wants to publish in a “typical” journal after reading that?) They also claim to be an “innovator in open access,” which is, frankly, nonsense. Springer and the other for-profit journals have been fighting open access since the mid-2000s, and this latest announcement is yet one more salvo in their battle against it.

(Or maybe Springer thinks that charging $11,500 to make a paper open access is an innovative move? It does take chutzpah, I’ll grant them that.)

The open access movement, which I’ve long been a part of, wants to make all scientific research freely available to anyone, with no costs or delays. As every scientist knows, science only progresses by sharing its discoveries, and barriers such as subscription fees serve only to slow down that progress. Given that most research is paid for by the public, it makes no sense at all to allow for-profit journals to control access. The only reason they still do is because they’ve done so for decades, and it’s hard to change an entrenched system.

Nature’s outrageously high fee also excludes virtually every scientist from low and middle-income countries, as fellow Forbes blogger (and scientist) Madhukar Pai wrote last week.

Rather than a move to support open access, this new fee is little more than a money grab. It’s actually even worse: in addition to the new $11,500 open access fee, Nature also announced an option (they call it a “new OA pilot”) whereby you pay them $2,600 for a preliminary review, and they evaluate your paper for six of their journals. In this option, they might reject your paper outright, and you’re out $2,600 with nothing to show for it. If they think it’s worthy, you pay the remainder of the open access fee later. Gee, this seems like a great idea–paying $2,600 for something that currently is free. Thanks, Nature!

Of course, Nature journals will still allow scientists to publish papers the old-fashioned way, where they don’t pay the €9,500 fee and where the journal then owns the paper. Rather than doing that, or paying the outrageous fee, let’s hope this money grab makes scientists look elsewhere for a place to publish their findings. And while we’re at it, let’s tell the Nature editors we won’t be reviewing for them any longer, not while they’re charging this ridiculous $2,600 fee for a service that we scientists have been providing for free. I’ve already done that once, and I plan to continue until they drop this idea.

A new study out of Denmark tried to measure the benefits of masks. It didn't go so well.

Social media has been abuzz this week over a new study out of Denmark about the effectiveness of masks on the risk of getting Covid-19. Depending on what news source you looked at, you might have heard that masks might not protect the people wearing them, or that wearing masks doesn’t prevent the spread of the virus. You might also have read the near-immediate backlash in which scientists pointed out all the evidence that masks really do work.

I read the study. It doesn’t prove anything, as even its own authors admit.

Let’s dig into the actual results just a bit to see what all the fuss is about.

The study was conducted in Denmark in April and May of this year, and what it tried to do (not very effectively) was to measure the effect of a recommendation to wear masks. That’s right, they weren’t really measuring the benefits of masks directly at all!

The study enrolled about 6000 volunteers, and for half of them they recommended wearing masks whenever they went outdoors. They also provided masks to those volunteers. For the other half, they didn’t do anything. At the time (March and April), Denmark was recommending social distancing, but universal mask wearing wasn’t recommended.

Quite a few people dropped out, so in the end they only had 4862 people in the two groups, about 2400 per group.

What did they measure? Well, they did an antibody test (far from perfect, but let’s not digress) at the beginning of June to see whether or not people were infected with SARS-CoV-2, the virus that causes Covid-19.

(Note that they DID NOT measure how well the masks might have protected anyone else in the community. They were only measuring whether a mask might protect the wearer.)

And the results? 42 people in the mask-recommendation group were infected, and 51 people in the no-recommendation group were infected. (That’s 1.8% versus 2.1% of each group.) So there was a small reduction, but it was not statistically significant, which means we really can’t say if the mask recommendation helped prevent infection.

The study authors admitted this themselves, writing: “the findings are inconclusive ... compatible with a 46% decrease to a 23% increase in infection.” In other words, the results could mean that masks reduce self-infections by 46% or increase them (bizarre as that sounds) by 23%.

In other words, this experiment doesn’t tell us much. If it weren’t about Covid-19, I doubt that the Annals of Internal Medicine would have published it. (A commentary by my colleagues at Hopkins and Stanford suggested that Annals was right to publish it, as long as scientists “carefully highlight the questions that the trial does and does not answer.”)

Now some big caveats. First, in the mask recommendation group, only 46% of the participants wore masks as recommended. Second, the study didn’t ask if anyone in the no-recommendation group wore masks. Third, the study relied on self-reporting to determine who was actually wearing their masks consistently–that is, they simply asked the participants to tell them how often they wore their masks.

What? Imagine if you were studying the use of seat belts to reduce injuries, and only 46% of the people you told to wear seat belts wore them properly. On top of that, imagine that you relied entirely on self-reporting to determine who was actually wearing the seat belts. This study design is nearly worthless if you want to know the true benefits of seat belts.

So the Danish mask study was inconclusive, as its own authors report. Therefore it would be a huge mistake, scientifically speaking, to take this non-result and conclude that masks do not protect you. It would be an even bigger mistake to conclude that the study showed that masks don’t benefit the community. Unfortunately, that didn’t stop these two Oxford University scientists from jumping to exactly that conclusion. They claimed, in an article in The Spectator, that the study showed that “wearing masks in the community does not significantly reduce the rates of infection.” This is dead wrong. The study wasn’t even measuring community rates of infection.

(For an excellent Twitter-take on what the study does not prove, see this thread from The Health Nerd.)

And as the CDC has documented, multiple studies have already shown that masks are highly effective at limiting the spread of Covid-19. And a study last summer pointed out that increasing the use of masks by just 15% “could prevent the need for lockdowns and reduce associated losses of up to $1 trillion” in the U.S. alone. So yes, it’s a good idea to wear a mask.

It’s also simply common sense that if you wear a mask, the amount of virus that you breathe in or out will be reduced. You’re not just protecting yourself, you’re also protecting everyone around you.

Until we can get this pandemic under control, we all need to wear masks in public. It’s utterly ridiculous that this has become a political issue, as it has in the U.S. To those who think mask wearing somehow limits their personal freedom: get over it. When you see a red light at a busy intersection, do you race through it because you need the “freedom” to drive like a crazy person? No. Civilized society requires everyone to follow some basic rules to protect each other, and during a pandemic, wearing a mask is one of them. And to those who think that wearing a mask somehow shows their civic virtue? No, that’s wrong too. To use the same example, stopping at a red light doesn’t prove that you’re virtuous.

It’s just a mask. It’s not a political statement. Get over it.

New Alzheimer's disease fails, then works, then fails again


 Alzheimer’s disease is one of the most devastating conditions of old age. By recent estimates, more than 5 million people in the U.S. have Alzheimer’s, and managing the disease will cost over $300 billion in 2020. As the population ages, this problem is growing worse, and yet we still have no effective treatment.

You might have seen rosy-looking ads for Alzheimer’s treatments, but nothing really works, not yet at least. That’s why many people were excited about the possibilities of a new drug, aducanumab, that showed early signs of being able to reduce the accumulations of “plaques” in the brain.

Background: in people with Alzheimer’s, a protein called beta-amyloid accumulates in the brain, forming plaques that seem to disrupt brain function. (This hypothesis is not fully proven, but it is widely considered credible.) Thus one way that we might treat Alzheimer’s would be to reduce or eliminate beta-amyloid plaques. That’s what Biogen’s new drug, aducanumab, is intended to do.

Biogen has run two separate trials, called “EMERGE” and “ENGAGE,” to test whether or not aducanumab (ADU for short) worked.

Here’s where things get murky. Back in March of 2019, both trials were halted due to “futility,” because ENGAGE was showing no benefits for the new drug. In EMERGE, the high-dose patients seemed to be getting some benefit, but Biogen had specified ahead of time that if either trial was failing, that would mean the drug wasn’t working. Thus they halted the trials, disappointing as it was.

Fast forward to October of 2019, though, and Biogen had a new story. They went back and looked at a subset of the patients in ENGAGE (the study that had failed), and said that there was a benefit after all, if they looked only at the high-dose patients. This past July, Biogen went to the FDA and applied for approval for ADU.

Just this past week, two very conflicting announcements about ADU appeared. First, on Wednesday, the FDA’s internal scientists released a very rosy report, saying that the data from one of the trials were “robust and exceptionally persuasive.” For the second trial, the scientists said that even though the drug initially seemed to fail, a closer review led them to conclude that overall, ADU did provide a benefit.

Biogen shares rose 45% that day, adding $17 billion to the company’s value.

Then on Friday, a panel of independent, external scientists released their conclusions, which resoundingly rejected the drug. The external panel said that the data from the two trials was unconvincing, and they pointed out “multiple red flags” in the analysis.

(Trading in Biogen stock was halted during the Friday meeting, but at the end of the day it was close to the high it reached on Wednesday.)

So what happened? It appears to be a classic case of cherry-picking: when the data from the ENGAGE study didn’t pan out, the company re-analyzed a subset of the data and found a more-positive picture.

That’s not really kosher, as explained by a separate group of scientists in a paper published just a few days ago in the journal Alzheimer’s & Dementia. In this paper, David Knopman and colleagues, from the Mayo Clinic and Stanford Medical School, analyzed data that Biogen has released from its two trials. (The trials haven’t been published, but some of the findings were released in a publicly-available slide presentation that the authors relied upon.)

Knopman and colleagues explained that after two conflicting trials, there simply isn’t enough evidence that ADU works, and they also offer alternative explanations for the positive findings. They argue that the best Biogen can do is to “perform another trial of high‐dose ADU of at least 78‐weeks duration,” which could determine whether or not the positive results were real or just coincidence.

It’s somewhat mysterious that the FDA’s internal panel released their rosy report about ADU on Wednesday, only to be slapped down just two days later by an independent outside panel of scientists. After reading the negative views of the external panel and the analysis in the paper by Knopman and colleagues, I’m very skeptical that ADU has any clinically significant effect. If it had a truly robust effect, it simply wouldn’t be so hard to tease it out.

So we still don’t have a good treatment for Alzheimer’s, but the world still needs one.