5 ms·

This is completely wrong. Dosage studies happens between Phase 2 and Phase 3 trials (and Phase 4 "post marketing" too) and are the most expensive, longest and

This is completely wrong. Dosage studies happens between Phase 2 and Phase 3 trials (and Phase 4 "post marketing" too) and are the most expensive, longest and most scientific process that arguably any business engages in in the entire world. Phase 1 is a safety test in healthy ~men. These seek to find the maximum dose before adverse effects appear in the healthiest humans. Phase 2 is a safety/dosage test in a much larger and varied sample. We know dose ranges and begin testing them for efficacy in a varied population. Phase 3 is the big one. It's a randomized, controlled, double blind test of SPECIFIC dosages in SPECIFIC target populations to scientifically prove efficacy over placebo. The dose we take is not a "BEST GUESS" It is the result of a billion dollars of scientific study and that PRECISE NME (new molecular entity) has been studied, at that PRECISE dose, in a target population, for it's effectiveness, and it must be better than existing-treatments and better than placebo. It should be highlighted that this process takes on average 10 years, costs $1 billion dollars, and has a success rate (success meaning FDA approval) of about 1 in 10,000 attempts (hence the price tag). Source: Drugs: From Discovery to Approval, Second Edition http://onlinelibrary.wiley.com/book/10.1002/9780470403587 http://onlinelibrary.wiley.com/book/10.1002/9780470403587

maxerickson 9y ago
Do all 10,000 attempts go through all the testing? Or are many weeded out before $1 billion has been spent?
- civilitty 9y ago
  The $1 billion dollar cost per drug is risk adjusted, so it includes all failed attempts at clinical trials and compounds that didn't make it through pre-trial screening. Edit: The $1 billion number is meaningless outside the context of large pharmaceutical companies. The cost for phase 3 trials is in the tens or hundreds of millions of dollars so the floor is a wide range and there have been instances of companies getting incredibly lucky and developing a drug for much less than a full billion.
PixelB 9y ago
Sounds like you don't know what you are talking about. Your source is a book written with heavy influence by the Pharmaceutical industry to justify the obscene costs of their drugs, making billions in profits off of sick, poor people. You are the one who is completely wrong. The dosages most certainly do start out with a "best guess" in the pre-clinical phase. For any given drug we would guess at the doses based on our calculations, and give a range on either end. If we thought the effective dose would be 1 mg/kg, we would run an LD50 of doses much higher than that, 10mg/kg, 100mg/kg. Sometimes our guesses would be wrong, and the low dose animals would die as a result. After figuring out a safe dose, we would then split it further into different dosing groups to test the effectiveness of the compound. Most people in the field are underpaid, overworked, and do sloppy work Please talk to someone who has actually worked in the Pharma research field, they will tell you most of what they do is just guessing.. why do you think only 1 in 10,000 make it through? It's all a guess until the end, and even then we're often not sure. Look at anti-depressants. We still don't know how a lot of those work but prescribe them to millions of people regardless. How do you think they determined the dose when they don't know how the drug works?
- gph 9y ago
  >It's all a guess until the end, and even then we're often not sure. Look at anti-depressants. We still don't know how a lot of those work but prescribe them to millions of people regardless. How do you think they determined the dose when they don't know how the drug works? We know how antidepressants work, the chemical reaction is well known and can be quantified at different doses. We just don't know why they work because we don't understand why/how the brain works. Pedantic but important difference.
  - tpm 9y ago
    No, we don't know the antidepressive mechanism of antidepressants, therefore we don't know how they work. Understanding some neurochemical reactions and biological adaptations they cause is not enough. (We also don't have a complete understanding of depressive disorders, we don't really have very effective medication/therapy for many depressive people, etc.)
- 9y ago
JohnJamesRambo 9y ago
Please see papers like- https://www.ncbi.nlm.nih.gov/pubmed/14714120 https://www.ncbi.nlm.nih.gov/pubmed/14714120 No difference in response between people taking 20 mg prozac daily vs. every third day.
learntofly 9y ago
Why are drugs almost exclusively dosed in multiples of 5, ie 50mcg, 250mg? Surely this introduces a margin of error vs the "perfect" dose.
- AstralStorm 9y ago
  Come on, metabolism itself is reasonably variable even with controlled diet and perfect adherence. In reality, even more so.

maxerickson 9y ago

Do all 10,000 attempts go through all the testing? Or are many weeded out before $1 billion has been spent?

civilitty 9y ago
The $1 billion dollar cost per drug is risk adjusted, so it includes all failed attempts at clinical trials and compounds that didn't make it through pre-trial screening. Edit: The $1 billion number is meaningless outside the context of large pharmaceutical companies. The cost for phase 3 trials is in the tens or hundreds of millions of dollars so the floor is a wide range and there have been instances of companies getting incredibly lucky and developing a drug for much less than a full billion.

PixelB 9y ago

Sounds like you don't know what you are talking about. Your source is a book written with heavy influence by the Pharmaceutical industry to justify the obscene costs of their drugs, making billions in profits off of sick, poor people. You are the one who is completely wrong. The dosages most certainly do start out with a "best guess" in the pre-clinical phase. For any given drug we would guess at the doses based on our calculations, and give a range on either end. If we thought the effective dose would be 1 mg/kg, we would run an LD50 of doses much higher than that, 10mg/kg, 100mg/kg. Sometimes our guesses would be wrong, and the low dose animals would die as a result. After figuring out a safe dose, we would then split it further into different dosing groups to test the effectiveness of the compound. Most people in the field are underpaid, overworked, and do sloppy work Please talk to someone who has actually worked in the Pharma research field, they will tell you most of what they do is just guessing.. why do you think only 1 in 10,000 make it through? It's all a guess until the end, and even then we're often not sure. Look at anti-depressants. We still don't know how a lot of those work but prescribe them to millions of people regardless. How do you think they determined the dose when they don't know how the drug works?

gph 9y ago
>It's all a guess until the end, and even then we're often not sure. Look at anti-depressants. We still don't know how a lot of those work but prescribe them to millions of people regardless. How do you think they determined the dose when they don't know how the drug works? We know how antidepressants work, the chemical reaction is well known and can be quantified at different doses. We just don't know why they work because we don't understand why/how the brain works. Pedantic but important difference.
- tpm 9y ago
  No, we don't know the antidepressive mechanism of antidepressants, therefore we don't know how they work. Understanding some neurochemical reactions and biological adaptations they cause is not enough. (We also don't have a complete understanding of depressive disorders, we don't really have very effective medication/therapy for many depressive people, etc.)
9y ago

JohnJamesRambo 9y ago

Please see papers like- https://www.ncbi.nlm.nih.gov/pubmed/14714120 https://www.ncbi.nlm.nih.gov/pubmed/14714120 No difference in response between people taking 20 mg prozac daily vs. every third day.

learntofly 9y ago

Why are drugs almost exclusively dosed in multiples of 5, ie 50mcg, 250mg? Surely this introduces a margin of error vs the "perfect" dose.

AstralStorm 9y ago
Come on, metabolism itself is reasonably variable even with controlled diet and perfect adherence. In reality, even more so.