Puzzleheaded_Soil275

OP, this is very noble of you but please be aware of the risks (e.g. legally having the nanny as a tenant) of doing this.

Unfortunately, if things turn south you are going to have a two-fold problem in that you have a live-in tenant with a very awkward situation AND you are going to be up the creek for childcare.

Almost certainly an oversight, think this has been in the IE criteria of every study I've ever worked on (50+).

A lot of the "rules of thumb" break down when your effective tax rate is 40-50% is one component of it.

Another component of it is if you ask a bank how much loan you can take out, the bank is going to tell you the largest number they think you can pay back (and they take your house anyway if you don't).

If you ask a realtor, the realtor gets a larger commission if they can push you into a more expensive home purchase. So despite whatever NAR bullshit they spit out about acting as a fiduciary, the economic incentives are not aligned with that of being a fiduciary. The economic incentives are aligned with you putting in a signed offer at a high price, and that offer being accepted.

Generally, <2x gross income is safe, as long as that income is fairly stable. The difference between "how much could I possibly spend on a home if I wanted" and "how much should I spend on a home" is often quite large. If you want to work into your 60s and have a badass house, that's an option to most physicians. But you don't have to do that-- going with a more modest house enables retirement (or pulling back) well before then for most physicians if you do things the right way.

"I don't see why they wouldn't continue to go down over the next 2 years. They will probably plateau some,"

Because labor inflation is likely entrenched as the labor pool has declined (boomers starting to die, more retiring) and the banks that bought 100s of billions of long term bonds at the bond market lows in 2021 are still hundreds of billions in the red.

And if rates do drop that much, it's because something broke.

I don't think the data says what you think it says on that one...

The SAHM "rule" exists because a move of +0.5% off the secular lows in unemployment has been predictive of the last several recessions. We have officially moved above that level at this point.

Granted, I wouldn't over-rely on one single jobs report, so August/Sept are important for monitoring the stability of that trend.

But you have to also be an idiot to think that uninversion of the deepest yield curve inversion in history AND a noticeable change in the trajectory of unemployment is "no real data supporting anything".

The SAHM rule is ascribed more power than it deserves, but this "There is no real data supporting anything but a return to pre-covid normalcy." is blatantly inaccurate.

From the sponsor perspective:

(1) FTE= buying a car (an employee)

(2) FSP = leasing a car

(3) outsource to CRO = rent a car.

"Additionally, in black communities there is often a distrust of experimental treatments, and for notable reasons"

This was my first thought when seeing this guidance. A bit rich that a lot of this originates with the Tuskegee trials, and then the FDA chastises sponsors for not having sufficiently diverse trials.

I would start the job hunt now, with the understanding that especially in more entry-level roles (which, roughly, I mean <5 years experience) and no sponsor-side experience, that it might very well take 6 months or longer for something worth jumping at comes your way. I would be quite surprised if you found a *good* job in this market in just a couple months. There's still opportunities out there with good companies, but it's noticeably slower across the board compared to even 2022.

That's perhaps unfortunate, but it's just the state of the job market right now in biotech. It's not great.

R is arguably better for non-GCP activities (and I frequently use it for that purpose, as it stands).

My point is that for most GCP activities, R offers no-to-minimal benefit for most organizations and requires blowing up the entire infrastructure.

CMO leaving doesn't mean much on it's own, as the reason can be quite important. He's 61 and makes like $5m/year probably. Sometimes people just want to go to the next chapter of their life.

will have to look into this, thanks!

Bring it on, robots.

But seriously, it will have it's place but I am not worried about it during the remainder of my career (~15 more years).

Even then, there are a LOT of questions that come up very frequently in my job that I have no idea how an LLM would provide a sensible answer to. I have a PhD and 10 years of experience, and often times it takes me several days of careful thought and lots of digging in various clinical and statistical journals to come up with the correct idea or all the viable options.

"An interim analysis lets you end the trial early if you show overwhelming evidence of efficacy"

This is not correct. Interim analysis is a blanket term for literally any interim, unblinded look at the data before the end of study.

Also, in practice, it is extraordinarily rare to actually terminate a trial early for efficacy. Even if one knows unequivocally from an interim analysis that a drug works, you very often would still complete the study for purposes of generating enough safety data to support your drug application, or collect more data to try to hit a secondary endpoint that may take more time to negotiate a stronger label.

The other issue you have is just because you think the evidence is strong enough to support an approval doesn't mean the regulator will agree with you. Once the trial is terminated, that's it, unless you run another study (at the cost of several more years and a couple hundred million dollars). So if you were going to do it, the pathway would be to conduct the interim analysis first, seek a regulatory meeting first (e.g. you can request a Type A/Type D meeting with the FDA to discuss things like this, I forget the exact distinction off hand) to ask if they find the evidence convincing, and THEN maybe terminate the study if they say yes.

But imagine you are running an oncology study or something similar and you get a significant result on PFS at an interim analysis. You terminate the study early, only for the agency to turn around and say that although you have hit statistical significance they do not find it to be clinically meaningful, and they really want to see a survival benefit to support approval (and yes, regulators do change their minds at times). You are 100% SOL if you've already terminated the study.

There have been some notable exceptions, such as during the COVID pandemic, but at an industry level it is extremely rare to truly terminate a study early for efficacy.

Sure, but as I explained there is a large swath of things where it's a solution in search of a problem for standard clinical trial reporting. Standard clinical trial reporting, for the most part, is not that technical. There are some very specific things (e.g. multiple imputations) that get semi-technical and yes, R may be able to do more efficiently.

But as far as me going out and blowing up our entire infrastructure just because I think R is a superior language to SAS? Not a chance.

Programming documentation, IMO, would be an infinitely more useful application of LLMs to clinical trials reporting. If an LLM could look at an analysis plan and protocol, and generate a programming specification document instantly, that would save my programmers a shitload of time.

" Given the increasing popularity of R, with pharma companies already submitting clinical trial results in R, this trend is clear. I believe there will be a significant market for companies to transition from SAS to other open-source languages as LLMs can expedite this process- saving time and money on these migrations."

From what you've written, it's apparent you have never spent a day working on the pharma side of the industry as a programmer.

I can only speak from my perspective, which is as Sr Director of stats/programming at a mid size biotech. But at least in that section of the market, this doesn't make any sense for me to do right now, and I am highly doubtful it will make sense for me to do in 5 years either. And I say this as someone that uses R quite a bit in industry-- for simulations, exploratory analyses, ad hoc analysis, etc.

The reason is as follows-- we have tons of processes and templates that are built around SAS infrastructure, and that infrastructure is not really that expensive once it's up and running. Yes, I do have to pay for a SAS license for my programmers. The yearly SAS license comes out to about 5% of my department's budget, and less than 0.1% of the overall R&D spend of my company. But all of my legacy code, etc. already does what I want it to do for clinical trial reporting. And the things that require custom one-off programming are way above anything an LLM would know how to program from scratch right now anyway.

Secondly, the overall cost of stats and programming is a relatively small part of the overall cost of running a clinical trial. For a certain large ongoing phase 3 study I am working on, it's about 1% of the overall budget of the trial.

For a larger, legacy pharma that might be able to scale these things, I can see where moving to an all R-based platform might make sense. But even then, you have to keep in mind that "regulations" generally don't just mean a single regulator like the FDA. All these regulators conduct database reviews differently, and they all conduct inspections differently. If an FDA or EMA inspector shows up, I know pretty well what to expect from them with our SAS based system. There is no incentive whatsoever for me to suddenly switch over to an R platform and add another layer of uncertainty to our submission.

No co-sleeping before 6am in our house. Never have, never will. If they do wake up and it's after 6, they can come in and snuggle until 7ish when we're normally getting up anyway.

Although there is a danger associated with it when kids are under 1 (smothering), it's not my place to judge someone.

All my friends that have let their kids start co-sleeping have not managed to get the kids back into their bed through the night and it's become a permanent thing. That's a no from me.

Yeah, I wasn't 100% sure and then I got to that line.

Sorry OP to say this, but you gotta nope the fuck outta here IMO. You don't have kids, there is absolutely no reason to commit the rest of your life to this person, unless you are 100% sure the trust can be repaired. This is just my opinion, and it is completely up to you whether you think the relationship is irreparably damaged. But whatever you do, do not let this person gaslight you into saying "it was only a kiss" or "it was no big deal" or whatever the fuck they try to say.

Keep in mind, her admitting to kissing him could very well just be the tip of an iceberg. They may well have boinked, you really have no way of ever knowing the truth about that. But think about it-- she may think if she admits to doing something lesser, you will not dig for more details.

That is exponentially worse than simply admitting they did something to betray you and being cognizant of the damage they did to the relationship. Saying "it's not a big deal" or anything similar just means that not only did they fuck up massively, they are trying to manipulate you into not realizing they fucked up.

If you do divorce, geta lawyer and sue for every cent of spousal support that you can.