1. Eli Lilly’s Experimental Alzheimer’s Drug Fails in Large Trial
By PAM BELLUCK
New York Times
NOV. 23, 2016

2. Previously shown promise
An experimental Alzheimer’s drug that had previously appeared to show promise in slowing the deterioration of thinking and memory has failed in a large Eli Lilly clinical trial, dealing a significant disappointment to patients hoping for a treatment that would alleviate their symptoms.
The failure of the drug, solanezumab, underscores the difficulty of treating people who show even mild dementia, and supports the idea that by that time, the damage in their brains may already be too extensive. And because the drug attacked the amyloid plaques that are the hallmark of Alzheimer’s, the trial results renew questions about a leading theory of the disease, which contends that it is largely caused by amyloid buildup.

3. Other clinical trials still underway
No drug so far has been able to demonstrate that removing or preventing the accumulation of amyloid translates into a result that matters for patients: stalling or blocking some of the symptoms of dementia. “It’s not going to be disease-modifying therapy for mild patients, so that’s heartbreaking,” said Dave Ricks, the incoming president and chief executive of Eli Lilly.
There are clinical trials underway with several similar drugs made by other companies, and two large trials with solanezumab are in the works. Experts said on Wednesday that they still held out hope for those studies, noting that many involve people who are at high risk for Alzheimer’s but do not display symptoms.

4. Not a significant difference
Solanezumab had previously failed in two large clinical trials involving patients with mild or moderate Alzheimer’s disease. But when Lilly reported the results of those trials in 2012, the company said the drug did have an effect in a subset of patients with mild symptoms. So it started another trial with 2,100 patients with mild dementia caused by Alzheimer’s.
In a news release on Wednesday, the company said that although some of the effects looked promising, “patients treated with solanezumab did not experience a statistically significant slowing in cognitive decline compared to patients treated with placebo.”

5. What they usually do … They usually use some kind of a survival model.
To the right you have a model of survival with AML (Acute Myelogenous Leukemia)
This is sometimes called a Kaplan-Meier graph (or curve) because it tells you the number of weeks survived.
Alternative is the probability of dying.

6. KM-curves Drawn here they are non-parametric.
What we have on lower right is a comparison of two curves.
There are various ways to compare curves, most of which are related to:
Log-likelihood functions if you are doing parametric stuff
Bootstrapping tests if you are not

7. Differences and stop rules
You would recognize the types of hypothesis tests that are done. You have a LL (test) and LL (placebo)
-2 (Difference of LL tests) ~ Χ2 (number of restrictions).
With simple t type of test, it is number of restrictions = 1.
IF patients get worse with treatment (in some statistical sense), most trials have a STOP rule.

8. Hope springs eternal …
Dr Reisa Sperling is leading a trial, called Anti-Amyloid Treatment in Asymptomatic Alzheimer’s (A4), which has funding from Lilly and the federal government, had hoped to reach its goal of about 1,150 patients by the middle of next year,
“I have several patients within my practice who were hoping to take this drug,” she said. But she said it was at least encouraging that patients taking solanezumab in Lilly’s trial did show improvement, just not enough to be statistically significant, and she plans to evaluate the data to see if changes should be made to the design of the A4 (Anti-Amyloid Treatment in Asymptomatic Alzheimer’s) trial that she is leading.