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Why Drugs That Work in Mice Don't Work in Humans

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Re: Why Drugs That Work in Mice Don't Work in Humans

#91

Post by ericd »

dalbasal wrote: post #49

"Only 14% of drugs that are tested on humans succeed in demonstrating effectiveness[1], and all of these are drugs that have been found efficacious in animals, so successful animal studies are very far from a guarantee by themselves." Regardless of the reason, this seems fine/workable. Animal studies are a step in the funnel. I assume the step from petri dish to mouse is similar. I wonder how many false negatives get…

If the overlap is that small, for me it begs the question of how many drugs would work in humans, but are ruled out because they fail on mice.

Re: Why Drugs That Work in Mice Don't Work in Humans

#92

Post by sctb »

jimmy1 wrote: post #51

We discard aborted fetuses because they are "clump of cells" and Planned Parenthood already sells off their body parts, why not take the next logical leap and test in utero of a woman that doesn't want their baby? (It's a serious question, regardless of the fact that society has reached the point where we do not apply intristic value to a baby inside the womb, only outside the womb and "wanted", biologically speaking…

We detached this subthread from https://news.ycombinator.com/item?id=19269700.

> Eschew flamebait. Don't introduce flamewar topics unless you have something genuinely new to say. Avoid unrelated controversies and generic tangents.

https://news.ycombinator.com/newsguidelines.html

Re: Why Drugs That Work in Mice Don't Work in Humans

#93

Post by eqwqewe »

rajadigopula wrote: post #25
dtech wrote: post #2

Except for maybe the last paragraph, this is not new information to basically anyone performing studies. The problem is we don't have any ethically and scientifically better alternatives.

There is an alternate. To wake up from the ignorant direction the so called studies are taking the human kind to. And stop calling it science. Dr. B.M. Hedge suggested long ago that all the studies done on animals or humans are wrong and inefficient in so many fronts. His words - According to ayurveda, human body can be classified into around 200 types based on the K/P/H balance of a body. A medicine that works for o…

Dr. Hedge sounds like a quack.

Re: Why Drugs That Work in Mice Don't Work in Humans

#96

Post by mattkrause »

Balgair wrote: post #87
leemailll wrote: post #42

Model animals are used in researches mostly due to two reasons: cost, which is always a big hurdle for academic studies; and reproduction, especially for inbred mice. The use of inbred mice often is because the behavior and activity of the mice is well-characterized, high availability, and genetically more consistent. However, the second part nowadays is often challenged and they are not that consistently genetically…

For those that are interested, the Animal Welfare Act of 1966 (an the many amendments to it) specifically spell out the animals that can be used for research and testing. There aren't that many of them, hence why rats and mice are so popular, as they are some of the few animals that can be used for testing. The AWA is structured such that all animals are covered by default, and only a few species are specifically exc…

While I agree that animal research is well-regulated in the US, many of the details in your comment aren't quite right.

The Animal Welfare Act specifies the minimum standards of care for research and exhibition of most species of mammals. Birds, rats, and mice aren't covered by the AWA, nor are "cold-blooded" animals. These are covered by other regulations from the Office of Laboratory Animal Welfare (OLAW; for federally-funded projects) or AAALAC (private funding). Farm animals are also not included, unless they are being exhibited or used for research.

The AWA requires research institutes to form an Institutional Animal Care and Use Committee (IACUCs), which includes scientists as well as clergy and members of the community. This is usually different from the Institutional Review Board (IRB), which regulates research involving human subjects. The idea is admittedly similar though.

The AWA does not limit the species involved in research. In theory, you could propose to set up a grizzly bear colony or something and the University of California has (had?) a hyena colony for a while. The IACUC is responsible for making sure that animals receive the care required by the AWA, OLAW, and other standards, so they might turn you down if suitable resources are not available or other, more humane approaches could be used (e.g., use a species that is less affected by captivity).

Re: Why Drugs That Work in Mice Don't Work in Humans

#97

Post by JohnJamesRambo »

dtech wrote: post #2

Except for maybe the last paragraph, this is not new information to basically anyone performing studies. The problem is we don't have any ethically and scientifically better alternatives.

I've been in science quite some time and worked with lots of rats in animal care facilities and this is the first time I've heard of the fact that mice need 30 deg. C instead of normal room temperatures to avoid stress.

Re: Why Drugs That Work in Mice Don't Work in Humans

#98

Post by Balgair »

mattkrause wrote: post #96
Balgair wrote: post #87

Earlier quoted context omitted.

For those that are interested, the Animal Welfare Act of 1966 (an the many amendments to it) specifically spell out the animals that can be used for research and testing. There aren't that many of them, hence why rats and mice are so popular, as they are some of the few animals that can be used for testing. The AWA is structured such that all animals are covered by default, and only a few species are specifically exc…

While I agree that animal research is well-regulated in the US, many of the details in your comment aren't quite right. The Animal Welfare Act specifies the minimum standards of care for research and exhibition of most species of mammals. Birds, rats, and mice aren't covered by the AWA, nor are "cold-blooded" animals. These are covered by other regulations from the Office of Laboratory Animal Welfare (OLAW; for feder…

Thank you for the clarifications!

Re: Why Drugs That Work in Mice Don't Work in Humans

#99

Post by busyant »

fredophile wrote: post #71
ramraj07 wrote: post #60

Earlier quoted context omitted.

14% is bad when you consider that the NEXT step after preclinical experiments is basically clinical trials (and Phase I is not to test efficacy ) which effectively costs several hundred millions of dollars or more. And the pharmas would just add the cost of 86% failed trials to the other meds that do pass, so they effectively pass the cost of their bad decisions to us. I worked in a lab that studies antibody therapeu…

I've always assumed that the reason for the low rate of success at that stage was just a result of things that work on rats not working on humans. Your post is suggesting that there is some evidence available before testing on people that would help increase this rate but gets ignored. I haven't seen anyone express this view before and would like to learn more about it. Would you please elaborate on what kind of info…

I am not the parent, but I worked at a few biotech startups.

My impression is that you are _mostly_ correct (a lot of animal models for disease don't accurately reflect the analogous state in humans).

However, I was privy to a situation similar to that described by the person to whom you replied.

* A start-up that I worked at developed a "candidate drug" to treat a condition (I don't want to get too detailed).

* The drug was good at ameliorating the disease in our simple models, but we also had a strong suspicion that the drug would be toxic in humans, higher animals.

* A decision was made that we would determine if the drug was toxic in three different species of large animal (I think we chose some type of monkey, dogs and I don't remember).

* Our "go/no-go" decision was: If the drug was NON-toxic in at least 2 of the 3 animal species, we would move to clinical (human) trials.

* 6 months later, we got the results: drug was NON-toxic in 1 of the 3 species.

* This looks like "no-go", right?

* Wrong. Board of directors put pressure on the CEO and senior management ("We put 8 figures of our hard-earned $ into round B and you promised us clinical trials over a year ago.").

* CEO folded like an accordion and got everyone to agree that we should proceed w/ Phase I trials (small n of humans tested, primarily to determine toxicity and maximum tolerated dose) despite the results of the animal studies.

* Phase 1 trial starts. Everyone gets sick (maybe 10 patients) after about 5 days of taking the drug. Trial is halted.

* We go back to square 1.

CEO should have never folded under the pressure because it was a waste of money, time, and it put people at risk.

I've only seen this once (going to trial with a risky drug), so I think it is a rare event.

edit2: Ironically, this is an example of a situation where the animal-studies CORRECTLY predicted what would happen in humans.

Re: Why Drugs That Work in Mice Don't Work in Humans

#100

Post by dragonwriter »

busyant wrote: post #99
fredophile wrote: post #71

Earlier quoted context omitted.

I've always assumed that the reason for the low rate of success at that stage was just a result of things that work on rats not working on humans. Your post is suggesting that there is some evidence available before testing on people that would help increase this rate but gets ignored. I haven't seen anyone express this view before and would like to learn more about it. Would you please elaborate on what kind of info…

I am not the parent, but I worked at a few biotech startups. My impression is that you are _mostly_ correct (a lot of animal models for disease don't accurately reflect the analogous state in humans). However, I was privy to a situation similar to that described by the person to whom you replied. * A start-up that I worked at developed a "candidate drug" to treat a condition (I don't want to get too detailed). * The…

> CEO should have never folded under the pressure because it was a waste of money, time, and it put people at risk.

At the same time, he board of directors should never have exerted the pressure, for the same reasons.

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