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How the FDA Could Change the Way It Approves Drugs

fivethirtyeight.com

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Re: How the FDA Could Change the Way It Approves Drugs

#31

Post by danieltillett »

refurb wrote: post #24
Alex3917 wrote: post #8

Earlier quoted context omitted.

Keep in mind also that as a patient you're allowed to take basically any drug you want, companies just aren't allowed to sell those drugs to other people and claim they treat a specific disease without FDA approval. So this whole article is basically just shilling for even less stringent requirements to market a drug as being effective, even though that hurdle is already trivially easy to overcome in these cases.

Don't forget the safety aspect of it as well. Even if a company wasn't claiming anything about their drug, if they sell something unsafe, they will get punished.

This apply to all products, not just medicines. If you sell any product that you know (or should have known) is unsafe then the tort lawyers will be after you as quick as a flash. There really is no need for additional product liability regulations for pharmaceuticals.

Re: How the FDA Could Change the Way It Approves Drugs

#32

Post by danieltillett »

refurb wrote: post #25
streptomycin wrote: post #6

Another concern with approving drugs more easily: you might then never find out if they really work or not. The reason we need very large, expensive, and strict clinical trials is because it's hard to see if a drug actually works or not otherwise - too many confounders. So if we pass drugs through with a higher error rate, we'll likely never know if some of them actually work or not. Maybe not a problem for a disease…

This has somewhat already been solved. Avastin works really well for colorectal cancer, so it was tried in a really small trial in breast cancer. There was a small signal there, so the FDA gave conditional approval with the agreement that the company would run a larger test to confirm the results. Well, they ran the bigger trial and it showed no benefit at all. The FDA rescinded conditional approval.

The crazy thing with the current regulations is the company would have been better off financially not ever doing the study. Since doctors can proscribe off-label, if they had not done the larger study they could have kept selling Avastin to breast cancer patients on the sly.

Avastin probably does work for some breast cancer patients if they have a cancer with the right mutations, but if the percentage is a small enough then the large study would not be able to detect this effect in the broad population.

Re: How the FDA Could Change the Way It Approves Drugs

#33

Post by danieltillett »

ccw9302 wrote: post #23

Per the paper, for drug application to treat pancreatic cancer, the threshold should be lowered to 27.9%. In other words, if a company wants to make money, it can randomly pick 4 non toxic compounds, and apply for FDA approval for treating of pancreatic cancer through click-trial, in average the company would get 4*0.279 ~=~ 1 compound approved and then market the medicine to the world that the medicine is effective.…

You have just pointed out the problem with all effectiveness trials. If you used the current threshold you can still do the same thing, you just need to test more non-toxic drugs.

A better approach would be to not have any effectiveness trials at all and just collect good data on all patients using the drug. If a drug really worked it would become obvious the more patients used the drug, while if it was worthless this would also become obvious. A new drug would start out unknown with only the most desperate trying it and overtime we would learn more and more about its effects and side-effects.

This bayesian approach was not possible in the past, but with modern technology it is now. We would get better drugs with better known side-effects at far lower costs.

Re: How the FDA Could Change the Way It Approves Drugs

#34

Post by BurningFrog »

refurb wrote: post #2

Instead, they say, the standards should take into account the severity of the diseases that the drugs seek to address. The FDA already does this. Take a look at the Duchenne's muscular dystrophy drugs currently up for review. One of them fail to show a statistically significant difference from the control group and the other one only had a single trial of 10 patients. The likelihood is that one or both of the drugs w…

You seem to confuse the severity of a disease with if there are any existing drugs to treat it.

Re: How the FDA Could Change the Way It Approves Drugs

#35

Post by schoen »

danieltillett wrote: post #33
ccw9302 wrote: post #23

Per the paper, for drug application to treat pancreatic cancer, the threshold should be lowered to 27.9%. In other words, if a company wants to make money, it can randomly pick 4 non toxic compounds, and apply for FDA approval for treating of pancreatic cancer through click-trial, in average the company would get 4*0.279 ~=~ 1 compound approved and then market the medicine to the world that the medicine is effective.…

You have just pointed out the problem with all effectiveness trials. If you used the current threshold you can still do the same thing, you just need to test more non-toxic drugs. A better approach would be to not have any effectiveness trials at all and just collect good data on all patients using the drug. If a drug really worked it would become obvious the more patients used the drug, while if it was worthless thi…

There's a great xkcd about the p-value interpretation issue.

https://xkcd.com/882/

So, how does the FDA deal with this issue today? Suppose the scientists wanted to market (some flavor) of jelly beans as a drug to cure acne (instead of to cause it), and they test 20 flavors and get evidence at p Does the FDA look for a causal mechanism that would make the drug effective? Or are the companies afraid to market things that they genuinely suspect are ineffective because they'll eventually get sued? Or is the FDA's effectiveness standard so strong that you just can't cost-effectively game it like this today? (The last possibility seems a little bit unlikely.)

Re: How the FDA Could Change the Way It Approves Drugs

#36

Post by BurningFrog »

streptomycin wrote: post #6

Another concern with approving drugs more easily: you might then never find out if they really work or not. The reason we need very large, expensive, and strict clinical trials is because it's hard to see if a drug actually works or not otherwise - too many confounders. So if we pass drugs through with a higher error rate, we'll likely never know if some of them actually work or not. Maybe not a problem for a disease…

It is very hard to believe that it is impossible to collect data from regular use. That should generate vastly more data.

Besides, the proposal is not to approve all drugs easier. Drugs for same conditions would be harder to approve under the proposed model.

Re: How the FDA Could Change the Way It Approves Drugs

#37

Post by BurningFrog »

ccw9302 wrote: post #23

Per the paper, for drug application to treat pancreatic cancer, the threshold should be lowered to 27.9%. In other words, if a company wants to make money, it can randomly pick 4 non toxic compounds, and apply for FDA approval for treating of pancreatic cancer through click-trial, in average the company would get 4*0.279 ~=~ 1 compound approved and then market the medicine to the world that the medicine is effective.…

1. A false positive rate of 27.9% is not the same thing as approving 27.9% of all applications.

2. The full clinical trials still cost hundreds of millions of dollars.

Re: How the FDA Could Change the Way It Approves Drugs

#38

Post by ccw9302 »

BurningFrog wrote: post #37
ccw9302 wrote: post #23

Per the paper, for drug application to treat pancreatic cancer, the threshold should be lowered to 27.9%. In other words, if a company wants to make money, it can randomly pick 4 non toxic compounds, and apply for FDA approval for treating of pancreatic cancer through click-trial, in average the company would get 4*0.279 ~=~ 1 compound approved and then market the medicine to the world that the medicine is effective.…

1. A false positive rate of 27.9% is not the same thing as approving 27.9% of all applications. 2. The full clinical trials still cost hundreds of millions of dollars.

false positive rate 27.9% means: if the drug is not effective (at all), there is 27.9% probability that the drug would be approved by FDA.

Re: How the FDA Could Change the Way It Approves Drugs

#39

Post by danieltillett »

schoen wrote: post #35
danieltillett wrote: post #33

Earlier quoted context omitted.

You have just pointed out the problem with all effectiveness trials. If you used the current threshold you can still do the same thing, you just need to test more non-toxic drugs. A better approach would be to not have any effectiveness trials at all and just collect good data on all patients using the drug. If a drug really worked it would become obvious the more patients used the drug, while if it was worthless thi…

There's a great xkcd about the p-value interpretation issue. https://xkcd.com/882/ So, how does the FDA deal with this issue today? Suppose the scientists wanted to market (some flavor) of jelly beans as a drug to cure acne (instead of to cause it), and they test 20 flavors and get evidence at p Does the FDA look for a causal mechanism that would make the drug effective? Or are the companies afraid to market things t…

This is a good question and one that is hard to know. In theory you need to have some mechanism of action, but drugs do get approved without one, or more commonly with a wrong one. Quite a few of the drugs in the psychiatric field are little more than placebos-with-bad-side-effects that got lucky.

As far as I know nobody has ever been sued over a drug that didn’t work. From a purely legal perspective you would better selling a sugar pill than a real drug that worked and caused 1 in 100,000 people to drop dead.

Re: How the FDA Could Change the Way It Approves Drugs

#40

Post by [deleted] »

danieltillett wrote: post #19
pinaceae wrote: post #17

Earlier quoted context omitted.

refuting your BS would take far longer than you vomiting this utter, utter nonsense into HN. just please never take any drug approved by the FDA ever.

Glad to see reason is alive and well on HN. Don’t both trying to provide an argument, just hurl personal abuse. Since I live in Australia I don’t ever take any drug that is approved by the FDA (this is the job of the TGA). Even if I did live in the USA, I fail to see me advocating for less regulation of the drug approval process somehow prevents me using a drug that has been approved in the past. I am advocating for…

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