Mary Chris Jaklevic is a reporter-editor at HealthNewsReview.org. She tweets as @mcjaklevic.
News organizations rightly reported the numerous asterisks attached to a small mid-stage study of a potential Alzheimer’s treatment highlighted at this week’s Alzheimer’s Association International Conference.
As some stories reported, the study was a Phase 2 trial that hasn’t been peer reviewed or published in a journal, in which the drug didn’t meet its primary goal of showing a benefit after 12 months of treatment.
Also widely reported was that numerous similar attempts to clear amyloid plaques associated with Alzheimer’s have failed to pan out. That’s important since other experimental therapies have had encouraging early results but didn’t work in a Phase 3 trial.
But the question remains: Why did this experimental drug — BAN2401 — attract an avalanche of news coverage?
Headlines used words like “hopes,” “promise,” and “benefit.” But for consumers, at this point in time, it’s tough to see what the fuss is about.
Part of the answer may lie in our collective desperation for an effective treatment, as pointed out by Eric Topol, MD, on Twitter.
We’re so desperate for an #Alzheimers drug, that it’s front page @nytimes, even though it’s just less amyloid by imaging and many trial method/result wartshttps://t.co/Z2AujZbpmi by @PamBelluck pic.twitter.com/40AW6FALzA
— Eric Topol (@EricTopol) July 26, 2018
But another explanation is less benign and hinges on the huge financial stakes, not just for the two companies developing this particular drug but for others working on similar plaque-busters as well as makers of PET scans that detect plaque and research institutions that are trying to find a way to arrest the disease.
“I call it the Alzheimer’s industry complex,” said HealthNewsReview.org contributor Susan Molchan, MD, who has written about the push to promote brain scans and drugs to diagnose and treat Alzheimer’s. “It’s a potentially huge market and that’s why these companies, despite all the decades of failures, persist.”
Molchan, a psychiatrist and former clinical researcher at the NIH, said while many medical experts quoted in news stories aren’t part of the BAN2401 research, they or their institutions may receive funding from companies that stand to profit if a new Alzheimer’s treatment wins FDA approval.
Everyone wants a drug that will provide meaningful benefits to patients, but danger lurks in the enormous incentives to make marginal drugs seem more beneficial than they really are.
“There are other amyloid drugs out there. Once one gets approved, it will make it easier for others,” Molchan said.
This context often isn’t acknowledged in news stories about potential treatments.
Laudably, nearly all stories we read provided at least some caveats, including previous failures in the field and the need for a definitive positive study.
The developers of BAN2401, Eisai Co. and Biogen Inc., reported in December that the drug had flunked its primary goal of producing a measurable result after 12 months.
On Wednesday the companies unveiled what they portrayed as rosier secondary outcomes, showing after 18 months the drug reduced amyloid plaques and improved cognition and function, although the study was so small that the cognitive benefit could have been due to chance.
Some news outlets did a particularly good job of conveying the limitations of the evidence.
The Associated Press’s Hopes rise again for a drug to slow Alzheimer’s disease
reported that the trial was “considered a flop” because it didn’t meet its main goal, and further wrote:
There are lots of caveats about the work, which was led by company scientists rather than academic researchers and not reviewed by outside experts. The study also was too small to be definitive and the results need to be confirmed with more work, dementia experts said.
The AP also asked what the purported benefit might mean for patients: “It’s unclear how much of a difference a 30 percent slowing of decline makes — whether it allows someone to continue to bathe or feed himself, for instance.”
Meanwhile, the Wall Street Journal’s Alzheimer’s Drug Shows Benefit, But Some Experts Say More Testing Needed contained this critical reporting:
Using an older measure that is widely accepted in the Alzheimer’s disease research field, known as ADAS-COG, (drugmaker) Eisai said the highest dose of the drug conferred 47% less decline in patients’ disease at 18 months, versus placebo.
But with another older measure known as the clinical dementia rating, the 26% improvement wasn’t statistically significant, meaning it could have been due to chance.
This month the Journal ran another strong story about BAN2401, which we reviewed.
STAT’s upbeat headline — Experimental Alzheimer’s drug significantly slowed patients’ cognitive decline, buoying hopes for treatment — was somewhat out of step with the story’s more skeptical text, which noted the experimental drug “failed its primary goal. Four doses of BAN2401 didn’t outperform placebo, and the high dose was tested on just 161 patients.”
CNN’s Experimental Alzheimer’s drug stirs hope after early trials explained a potential study flaw in that patients with the APOE4 gene, a risk factor for Alzheimer’s, were less likely to be in the beneficial high-dosage group, which may have skewed the results.
One glaring exception to the measured coverage was Fortune’s teasing World Leaders Want to End Alzheimer’s by 2025. A New Drug Breakthrough Means We Just Might, which called the findings a “milestone moment” and “proof of concept” for clearing plaque.
Other news outlets that covered the story:
Some did a better job than others at emphasizing that the drug failed to meet its primary endpoint, as mentioned in an Alzheimer’s Association news release. That’s disappointing because shifting the objective of a trial introduces the potential for researchers to create positive-sounding results by cherry-picking the outcome measures that they report.
There could have been dozens of secondary outcomes that were tracked by researchers but not revealed to the public.
“It’s important to say what you’re going to do beforehand to minimize bias. If you are making modifications in your protocol, which would include extending the study or your statistical analysis, it can get to the point where it can seem fudged and massaged,” Molchan said.
A couple of angles went largely unexplored.
For example, it’s not fully clear how many patients dropped out of the study and who they were, which could have left a disproportionate share of healthier people who were not going to decline in the treatment group.
The AP was the only outlet we saw that touched on this, reporting that “effects leading to discontinuation of treatment occurred in 19 percent of those on the high dose and 6 percent of the dummy treatment group. Cases of brain swelling, which have been seen in other treatments targeting the plaques in the brain, occurred in two people in the placebo group and 16 of those in the high dose group.”
And while several news outlets mentioned brain abnormalities experienced by some patients in the trial, none brought up the unknown long-term side effects that could come with taking the drug over decades.
While many news outlets noted the impact of this research on the companies’ stock prices, neglected was the potential cost to consumers and society if the drug were to be approved, which could be enormous given the high cost of new drugs and the millions of people at risk of Alzheimer’s.
“Anybody with a minor memory complaint” could seek testing to see if they would benefit from such a drug, Molchan noted. And PET scans, which can run $6,000 or more, would be part of the work up required for prescribing.
Future news coverage should strive to examine the big picture of what will happen if one these amyloid-busting drugs does win approval. Specifically, how good are the benefits for individual patients, and what is the cost to society?
“We don’t want a drug approved that has a big effect on amyloid but just squeaks by on the cognitive stuff, because it’s going to cost Medicare zillions of dollars between the drug and the scans, and most people with dementia have a number of processes going on,” Molchan said.