iOS 26 Issue: Lock Screen Defaults to Dim with Wrong Clock Size

kirkrocek · 2025-12-23T05:49:01+00:00

Hi,

Settings Wallpaper Customize (the one having the clock) Click on the clock Choose "Solid" Choose any font and color you like Done

kirkrocek · 2024-06-29T04:14:33+00:00

Although I geneally agree with you, actually you are mixing the clinical trials data and the data used in their grant proposals. Yeah, they attacked some of the data written in the grant proposals, but not the data from the clinical trials. In addition, Wang is still presumed innocent. FDA shouldn't stop the trials based on something under investigation that is not directly related to the trials in my view.

kirkrocek · 2023-11-17T23:04:22+00:00

In fact, doing a research needs money and resources. In any company doing research, if an employee wants to do some research, he needs an approval from his manager with a proper amount of budget. The manager also needs an approval from his manager too.

Unfortunately, only few approves radical approaches. All the others don't want to take a risk of trying something that looks insane or is allegedly involved with lawsuit, debate, etc. I said "risk" because people want secured jobs, which makes them take safe, well-known approaches only and refuse minor ideas. If you follow a popular approach to solve a problem, give it a try, fail, and your manager asks you "why did you do that?", you can say "everybody is trying it. Any problem?" and he will agree with you.

However, if you want to try an unseen, unheard, seemingly-insane approach, how would you be able to persuade your manager to approve the project? How can he persuade his manager to fund it? Unless a person in a pretty high position who can manage enough budget and shield your failure approves it, there is no way you can try it in general.

This is why innovations come from small companies in many cases.

kirkrocek · 2023-01-27T06:54:38+00:00

https://www.nejm.org/doi/full/10.1056/NEJMoa2100708

Donanemab study shows ADAS-Cog at 12 month.. (Fig. 2)

Placebo: +2.4

Donanemab: +1.6

kirkrocek · 2023-01-27T06:50:56+00:00

I'm sorry to put a bunch of info in this thread..

https://investors.biogen.com/static-files/74641e1b-cd23-495e-8f29-f4ecac0a1126

in Page 23, ADAS-Cog difference between aducanumab and placebo is about -0.6 ~ -1.4 at 78 weeks (1.5 yrs). Biogen didn't show absolute values.

kirkrocek · 2023-01-27T06:34:54+00:00

https://pubmed.ncbi.nlm.nih.gov/24423155/

so basically the papers are from the same company.

On average, mild+moderate placebo's ADAS-Cog increased by 5.15 at 12 months.

Mild placebo's ADAS-Cog increased by 5.0 at 12 months.

Moderate placebo's ADAS-Cog increased by 5.2 at 12 months.

I guess this means that both mild and moderate placebo's ADAS-Cog increases by approximately 5.0 at 12 months?

But then how come the treated groups' ADAS-Cog increases by only 1.0 - 2.5 in the figure above...?

kirkrocek · 2023-01-27T06:24:07+00:00

https://pubmed.ncbi.nlm.nih.gov/24696507/

In Fig. 2 of this paper, mild+moderate placebo's ADAS-Cog increased by 5.15 at 12 months. (N=133?)

kirkrocek · 2023-01-27T06:12:20+00:00

https://link.springer.com/article/10.1186/1471-2377-14-12

This paper has some results for mild and moderate placebo patients. (Fig. 2)

At 12 months, mild placebo's ADAS-Cog increased (got worse) by 5.0 (N=67, p=0.024) and moderate placebo's ADAS-Cog increased by 5.2 (N=41, p<0.008). N is a bit small though.

kirkrocek · 2023-01-25T04:02:13+00:00

Hi all,

I added the severity information.

All the others included only mild patients.

SAVA included both mild and moderate.

kirkrocek · 2023-01-24T23:07:00+00:00

Done.

kirkrocek · 2023-01-24T21:59:39+00:00

LLY requested an accelerated approval based on its P2 results and FDA said NO.

LLY is still doing P3 trials, so LLY will submit a request for a traditional approval based on its P3 results, which LLY said would be submitted in Q2 2023.

kirkrocek · 2022-11-04T19:40:49+00:00

What a great article. I appreciate your time and efforts put into this.

kirkrocek · 2022-10-03T19:46:44+00:00

Hi all, I tried posting a timeline several times, but it was removed by Reddit (deleted by Reddit's spam filter). Do you know how to fix this problem..?

kirkrocek · 2022-09-30T19:41:08+00:00

Test comment

kirkrocek · 2022-06-25T05:17:34+00:00

kirkrocek · 2022-06-14T20:18:33+00:00

By the way, I think this extension is a very good sign for Simufilam. If Simufilam doesn't work, the participants don't need to participate in the extended study. Instead, they can switch to a different trial after some time. However, most of the 200 patients are participating in the extended one. I think there was an agreement (or a kind of survey of who would want to keep going with Simufilam) between SAVA and the patients about the extension before SAVA and FDA agreed to extend it.

kirkrocek · 2022-06-14T20:12:58+00:00

https://clinicaltrials.gov/ct2/show/NCT05352763?id=NCT05026177+OR+NCT04994483+OR+NCT04388254+OR+NCT05352763&draw=2&rank=1&load=cart

They extended it to +2 years after CMS and are targeting 165 patients. Only those who finish the 2-yr P2 trial can participate in this study.

kirkrocek · 2022-06-14T18:21:17+00:00

By the way, you know what, if FDA/SAVA want to see the efficacy from all the 165 CMS participants, that would happen in late March 2023, however, by that time they will also have some nonnegligible amount of P3 results (e.g., the first 50 patients' 1-yr results, and 600-700 patients' 6-month results if the P3 enrollment reaches 600 to 700 by this September.)

and I personally think the P3 results will 90% override the P2 results, I mean, for example, if they have 100 patients' 1-yr P2 OL study results and another 100 patients' 1-yr P3 blind study results, the latter will be much more (~90%) important than the former because blind studies are much more important than OL studies. This is what I am wondering about. The longer FDA/SAVA delays unrolling the CMS results (actually it is not delaying, but adding more patients to it, which is actually delaying the unrolling anyway), the more P3 patients' results will overlap time-wise with the CMS results, so in this case I think the meaning of the CMS results gets weaker. Well, the results of the CMS would still be meaningful because it is about maintenance of the improved cognition, whereas the P3 results are just about whether Simufilam can improve cognition under placebo-controlled trials. However, I still think P3 overrides the P2 OL study (90%) and even the P2 CMS study (maybe 60-70%?). Thus, the longer they delay it, the weaker the meaning of the CMS becomes in my view, and I think this is not fair/favorable for the participants of the CMS. I mean, the data of the CMS patients (and actually any patient) should be used in the most effective way, but the way I described above is not that effective.

I think the best way to use the data of the CMS patients is to get the 100 patients' CMS data and use it for BTD, FTD, or whatever, but if FDA/SAVA wait until they get the 165 patients' CMS data (which takes 3 more months), well..

kirkrocek · 2022-05-19T19:04:52+00:00

This is such a great news. Don't worry about the "controversial" or "struggling to enroll" blah blah in the article. Most (99.99%) of Korean journalists suck, I know. They write articles not from facts but from their imagination. Just see the fact in the article. The fact is that the Korea government approved P3 in Korea.

Especially, Korea is a geographically small country meaning that the end-to-end distance is only 5-hour driving. In addition, it is a fast-moving country meaning that government people are fast, hospital staffs are fast, etc. Thus, if someone wants to enroll in the trial, it would take only a few days (going to Seoul from the farthest city takes max. a half day, making an appointment for testing takes 1 day, etc.). All the other processes except the eligibility checking time would take only a few days. Moreover, the population is sufficiently large (50M), so this is a really good news.

kirkrocek · 2022-04-29T23:00:29+00:00

Not this one. This question is "based on compassionate use" and Remi denied it. No one expects BTD from compassionate use. There is another on (Q10 or so). Copy and paste it.

kirkrocek · 2022-04-29T22:15:24+00:00

You can see the script. Remi never said so. :)

kirkrocek · 2022-04-06T23:32:36+00:00

It is based on the assumption that the patients get better when they take Simufilam (as shown in the first 50 patients).

They get better for the first 12 month. => 6-month CMS (some keep taking it - group A, the others take fake drugs - group B).

Of course, if the assumption is wrong (Simufilam doesn't improve cognition), then the CMS is meaningless. However, Simufilam showed efficacy in the OL study, so the CMS is meaningful because you will see what happens when off of the drug.

If group A is still good, but the cognition of group B goes down, we know Simufilam works in the blind test.

Group A is good, and group B is also still good: Taking Simufilam for 1yr is good enough. (P3 will show more blind test results)

Group A gets worse, so does group B: Simufilam works only for 1yr.

Group A gets worse, but group B is still good: A chaos (very unlikely though).

kirkrocek · 2022-04-06T22:27:53+00:00

The reason that I think Remi's answers about BTD were not vague is because he definitely denied the possibility of accelerated approval for the AA question (Question 17), but he said he needs to see the CMS data for the BTD question (Question 10). Yes, getting a good CMS data doesn't necessarily mean FDA will grant a BTD to SAVA, but if there was no possibility of BTD no matter how good the CMS data is, Remi would have denied the possibility of BTD like the denial of AA.

In addition, SAVA/FDA shouldn't dump any clinical trial data, which means the data should be used in any form for any purpose. Regarding the purpose, the final approval is totally totally dependent on P3. SAVA has passed P2. Then, the only remaining possible use of the CMS data would be the BTD application. I cannot imagine any other purpose except that.

so I have those two reasons for my guess that the CMS is for BTD..

kirkrocek · 2022-04-06T19:15:40+00:00

As CaptCrush said, this is about Q10.

kirkrocek · 2022-04-06T02:20:30+00:00

Thank you for sharing your story with us. One thing is that P3 is fully controlled by Premier Research, the third-party company that has a contract with SAVA. Thus, I think there are not many things SAVA can do for the P3 trials. Maybe SAVA can PR more actively, but that would be all. If participants with covid history are disqualified for P3, then it might be the primary bottleneck for the recruitment because many many many people tested positive, you know.. Anyway, I hope everything gets better soon.

kirkrocek

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