spudit on April 11, 2011, 09:24:15 pm
Holt,
I am impressed with your honesty and guts for saying so.  I don't share that dislike but you are certainly welcome to your opinion.
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spudit on April 11, 2011, 09:27:01 pm
Xavin as I recall you had wisdom to share regarding pharmacuticals, geez, did I even spell it right? Help!
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Apollo-Soyuz on April 11, 2011, 10:30:24 pm
So children. Have the anarchists finally learnt that vaccines are not the big bad government trying to inject evil robots into your brain so they can control your brain and steal your guns and money?

I'm pretty sure they're not mind control nanobots.  I'm still scratching my head over the special H1N1 vaccine though. By all accounts things were going swimmingly, even the fact that a single dose would be all that needed, so since the gov ordered enough for two shots for everyone, there would be plenty to go around.

Then, all of a sudden, there wasn't enough vaccine, there were manufacturing issues, there were all sorts of excuses.  People lined up in soviet-style lines for the few rationed shots. It was almost like someone wanted to show the very worst parts of single-payer rationed healthcare before they decided to deem 0bamacare "passed" so they could see what was in the bill.

Yea, I'm still scratching my head over that one.

Holt on April 12, 2011, 08:08:37 am
You know it was more likely the company who manufactured the shots withholding supply to increase their profits. After all wasn't there only one company who held the patent?

Xavin on April 12, 2011, 08:14:53 am
Xavin as I recall you had wisdom to share regarding pharmacuticals, geez, did I even spell it right? Help!

Close enough that I didn't notice before you asked  :)
And I can offer experience, but I don't guarantee wisdom.

The conversation has drifted a bit from my area of direct experience[1] and whatever train of thought I had on Friday has been thoroughly derailed - but I'll try and pick some of it up (and if anyone has questions they'd like to throw at me then please do - I'll either do my best to answer or explain if I can't).

@mellyrn - I now see what you meant regarding "side effects". The thing is, there are some prety hefty practical obstacle to the level of blinding that you're talking about - unless you start treating people for conditions that they don't have then they know that whatever treatment you provide is intended to treat whatever condition(s) they have (and even then, unless they know that you might be giving them completely irrelevant treatments then the placebo effect will still occur regarding efficacy. And it will occur regarding safety regardless.)
It's also unnecessary, so long as the assumption holds[2] that the placebo effect is the same in both the placebo and active treatment arms - i.e. it doesn't matter if (say) 20% of your placebo patients will get better on their own if 20% of your active treatment patients will also do so. You're not looking for the absolute number (or proportion) of patients who get better, you're looking to see if a (statistically significant) larger proportion of the active treatment patients get better than do the placebo patients.
Note also that quite a lot of trials don't involve a placebo at all - instead they compare the experimental treatment to the current standard treatment instead, especially where it would be (generally regarded as) unethical to leave patients effectively untreated when a treatment is already available.
There are, of course, potential complications with this approach when the standard treatment comes in a different form to the experimental one (say the standard treatment is delivered by IV drip and you're trialling a pill) - the placebo effect differs between forms of treatment[3]. In that case you might give one group the real pill and a saline IV, while another group gets a sugar pill and the real IV.

Anyway, it's well past the point that I should be getting back to work, so I'll leave off for now. I may come back later and witter on about "Informed Consent". And possibly the International Conference on Harmonisation (of Technical Requirements for Registration of Pharmaceuticals for Human Use)

[1] For reference, I'm a "statistical programmer" - I (mostly get the computers to) do the analysis, summary, and reporting of clincal trials data. I'm not a statistician, or medically trained, but I work every day with people who are and you pick up a lot over the years - and the nature of the job means that you also end up with at least some knowledge of trial design, data collection, regulation etc.
It's probably unwise if I say who I work for - suffice to say that I've done this job for a couple of major pharmaceutical companies, and a couple of Contract Research Organisations (both large and small). Feel free to interpret my comments in light of this information.
[2] Although I agree that this is not necessarily true in all cases
[3] Generalising wildly, just getting a consultation with someone in a white coat has a beneficial effect. Getting a sugar pill has a better one. Getting a saline IV has a better one still. Combinations are more effective than each type of "intervention" on its own.

Xavin on April 12, 2011, 08:16:14 am
You know it was more likely the company who manufactured the shots withholding supply to increase their profits. After all wasn't there only one company who held the patent?

There were at least 2. And I'm pretty sure that at least one of them was turning them out as quickly as they could.

Holt on April 12, 2011, 08:18:52 am
Which isn't very quickly when you consider the time they had and the general timescale needed for vaccine manufacture.

J Thomas on April 12, 2011, 09:08:55 am

The conversation has drifted a bit from my area of direct experience[1] and whatever train of thought I had on Friday has been thoroughly derailed - but I'll try and pick some of it up (and if anyone has questions they'd like to throw at me then please do - I'll either do my best to answer or explain if I can't).

Thank you! [1]

Quote
@mellyrn - I now see what you meant regarding "side effects". The thing is, there are some prety hefty practical obstacle to the level of blinding that you're talking about - unless you start treating people for conditions that they don't have then they know that whatever treatment you provide is intended to treat whatever condition(s) they have (and even then, unless they know that you might be giving them completely irrelevant treatments then the placebo effect will still occur regarding efficacy. And it will occur regarding safety regardless.)

I think there are some things that could sometimes be done to palliate those problems, but most of them have social side effects. Like, in an institutional setting you could just add new pills to the pills patients are already taking and not mention it. But that sort of violates informed consent.

Quote
It's also unnecessary, so long as the assumption holds[2] that the placebo effect is the same in both the placebo and active treatment arms - i.e. it doesn't matter if (say) 20% of your placebo patients will get better on their own if 20% of your active treatment patients will also do so. You're not looking for the absolute number (or proportion) of patients who get better, you're looking to see if a (statistically significant) larger proportion of the active treatment patients get better than do the placebo patients.

This is where Mellyrn's side effects come in. If they can tell that they are in the experimental group and not the control group, it has a placebo effect. So if the medication has any detectable effect at all, then it isn't a sugar pill, and if it has an effect that they know the standard treatment doesn't, then they know it isn't the standard treatment. People who are hopeful will tend to hope the experimental treatment is better.

Take it a step further and consider the Hawthorne effect. Trying to do controlled studies in an industrial setting, the researchers found that workers behave different when they are being watched. So their control groups were very different from what went on when they weren't doing research. The very fact that an experiment is going on could be enough to produce a strong placebo effect, and that could interact with the drug response!

Quote
Anyway, it's well past the point that I should be getting back to work, so I'll leave off for now. I may come back later and witter on about "Informed Consent". And possibly the International Conference on Harmonisation (of Technical Requirements for Registration of Pharmaceuticals for Human Use)

My view is that informed consent is inconsistent with actual controlled experiments. So we need to get a large group of volunteers who decline informed consent. The collection of everybody who is on Medicaid would be ideal.

[1] For reference, I did the coursework for biostatistics and spent years associating with people who did that work, but did very little of it myself. I have applied those techniques to other problems.

spudit on April 12, 2011, 11:15:37 am
Placebo effect = voting????

Sorry, had to.
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Xavin on April 12, 2011, 11:21:56 am
Which isn't very quickly when you consider the time they had and the general timescale needed for vaccine manufacture.

I'm not sure what you think the timescales for vaccine manufacture are.

In the case of the H1N1 pandemic in 2009/2010 the WHO provided the seed strain for the vaccine to several manufacturers (I can find at least 5) at then end of May 2009.
Turning the seed strain into a working seed bank takes about 2 months.
Getting a standardised vaccine out of that takes another month or so and you can produce enough for clinical trials.
If the regulators are in a hurry you can get regulatory approval in another month and start ramping up production (or you can start doing that a little earlier, if you're prepared to accept the risk of it not getting approved and spending money on producing a big pile of vaccines you can't sell).
The EMEA was approving H1N1 vaccines for general use at the end of September 2009.
The manufacturer that I particularly know about was shipping vaccines in the first week of October 2009.
I am unaware of them having any manufacturing issues (and can't find any mention of them in a brief search). Other manufacturers may be a different story. I don't recall hearing about is, but it doesn't appear that the manufacturer that I am familiar with was one of the major suppliers in the US, so I may not have become aware of it at the time.
Note that by Jan 2010, those governments that had been sensible enough to include break clauses in their contracts were starting to cancel parts of their vaccine orders as it became clear that they weren't going to need such a widespread vaccination programme as they'd thought.

Note also that the US usually gets 90-120million doses of seasonal flu vaccine in a typical year. The predictions from the CDC in mid 2009 look to have been that they would get >100million dose each of both the standard seasonal flu vaccine and of the H1N1 vaccine, by early Nov 2009, despite the fact that producing the H1N1 vaccine slowed down production of the standard seasonal vaccine (even leaving aside the development and testing of the new vaccine, you're using the same production lines for it that you would for the standard vaccine. You don't just throw together a facility for producing vaccine on an industrial scale, you have to use what you already have or spend a lot of time - that you generally don't have - building new capacity. Which will then end up sitting idle once the pandemic is over).

Holt on April 12, 2011, 12:47:46 pm
Holt,
I am impressed with your honesty and guts for saying so.  I don't share that dislike but you are certainly welcome to your opinion.

Well they're an insular group who think they're better than everyone and often refuse to fully integrate into any society and seem to have an odd historical precedent for being money lenders and usurers.
What's not to hate?

quadibloc on April 12, 2011, 12:53:31 pm
They don't beat people up and steal their lunch money at knifepoint!

They have contributed to literature and music and art and science out of all proportion to their numbers!

What's not to like?

spudit on April 12, 2011, 12:57:40 pm
Gotta love the food, oy vay, what wonderful eats!
Vote Early and Vote Often
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Holt on April 12, 2011, 01:13:30 pm
They don't beat people up and steal their lunch money at knifepoint!

They have contributed to literature and music and art and science out of all proportion to their numbers!

What's not to like?

Tell you what. When they stop using a term for animal to describe anyone who isn't a Jew and stop being a destabilising factor in the middle east. Then I will like them.

J Thomas on April 12, 2011, 02:25:57 pm
They don't beat people up and steal their lunch money at knifepoint!

They have contributed to literature and music and art and science out of all proportion to their numbers!

What's not to like?

Tell you what. When they stop using a term for animal to describe anyone who isn't a Jew and stop being a destabilising factor in the middle east. Then I will like them.

Hey, blaming the middle east on Jews is like blaming US racism on WASPs. Or blaming the atrocities of the Union Army on Yankees.

It's like blaming the Mafia on Italians. There could be a little bit of a sort of truth to it, but it's another way to miss the point.

 

anything