How the FDA Could Change the Way It Approves Drugs • Hacker News Board

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

#21

Post by danieltillett » Thu, Sep 03, 2015, 11:43 PM UTC

ccw9302 wrote: post #20

ikeboy wrote: post #9

On a related topic, http://www.fdareview.org argues that much of the FDA is more harmful than useful; in particular the efficacy requirement. Does anyone know good counterarguments?

Without FDA, consumers would be flooded with misleading drug ads and waste lots of money on ineffective drugs. US is really lucky to have FDA.

As if the USA does not have this already!

Actually you would see far fewer ads since you would remove the ability and need for advertising. The reason drugs are advertised now is because the drug companies have so few new drugs to sell (no drug off-patent is ever advertised). They need to maximise the returns from the few drugs they have to sell. If hundred of new drugs came out each year then mass marketing would not work since the market for each drug would be too small.

Yes there would be more “ineffective” drugs, but if you and your doctor had the choice of dozens of drugs for your disease which one would you choose - the one for which had no evidence that it worked, or the one where the drug company has scientific evidence? Even if they did not need to do trials for the approval process, pharmaceutical companies would still do them to convince doctors and patients.

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

#22

Post by ikeboy » Thu, Sep 03, 2015, 11:51 PM UTC

ccw9302 wrote: post #20

ikeboy wrote: post #9

On a related topic, http://www.fdareview.org argues that much of the FDA is more harmful than useful; in particular the efficacy requirement. Does anyone know good counterarguments?

Without FDA, consumers would be flooded with misleading drug ads and waste lots of money on ineffective drugs. US is really lucky to have FDA.

This doesn't address the point at all. That site isn't recommending getting rid of the FDA as far as I see, just changing certain parts.

Also, they have an analysis of the advertising aspect.

In other words, Dr. Pepine thought that the FDA restrictions preventing the advertising and promotion of aspirin for heart attack patients were responsible for the deaths of tens of thousands of people.

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

#23

Post by ccw9302 » Fri, Sep 04, 2015, 12:21 AM UTC

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.

They give weight/cost to type I and type II error, and their whole analysis can be changed if the weights changed.

I would treat the paper as a research-toy, self fulfillment. Try to change policy based on the paper would be absurd.

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

#24

Post by refurb » Fri, Sep 04, 2015, 12:42 AM UTC

Alex3917 wrote: post #8

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…

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.

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

#25

Post by refurb » Fri, Sep 04, 2015, 12:45 AM UTC

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.

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

#26

Post by refurb » Fri, Sep 04, 2015, 12:47 AM UTC

zeveb wrote: post #10

> A patient with a seriously life-threatening disease like lung cancer is perhaps more willing to gamble on a risky drug in pursuit of a cure, while someone with a disease that has a high survival rate such as diabetes presumably cares more about avoiding adverse side effects. If he's more willing to gamble, then why not just let him do it ? The FDA's job should be to enforce truth-in-labelling (which means drugs wit…

If he's more willing to gamble, then why not just let him do it?

They already do. It's called expanded access programs. If a patient is going to die, they can ask the FDA for permission to take an unapproved drug. The FDA says yes 99% of the time.

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

#27

Post by refurb » Fri, Sep 04, 2015, 12:51 AM UTC

danieltillett wrote: post #4

The real source of the problem is at the preclinical stage. The requirements here are so strict that almost no drugs make it out of mice and dogs and into humans for actual testing.

That's not true at all.

Pre-clinical only requires that you show a drug is not toxic and has a potential benefit. Most drugs fail because they are either toxic or don't do anything.

Why would you loosen those regulations?

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

#28

Post by gwern » Fri, Sep 04, 2015, 1:15 AM UTC

Original paper: http://papers.ssrn.com/sol3/papers.cfm?abstract_id=2641547

Previous discussion: https://news.ycombinator.com/item?id=10145606

Also a long post on MR: http://marginalrevolution.com/marginalrevolution/2015/08/is-...

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

#29

Post by danieltillett » Fri, Sep 04, 2015, 1:20 AM UTC

refurb wrote: post #27

danieltillett wrote: post #4

The real source of the problem is at the preclinical stage. The requirements here are so strict that almost no drugs make it out of mice and dogs and into humans for actual testing.

That's not true at all. Pre-clinical only requires that you show a drug is not toxic and has a potential benefit. Most drugs fail because they are either toxic or don't do anything. Why would you loosen those regulations?

If only that was all you had to show in the preclinical stage.

The bigger problem is you can’t show either of these with preclinical testing. If you could then there would be no need for human testing.

The reality is most of preclinical testing outside of certain drug classes (e.g. antibiotics) is not that helpful for knowing if a drug will cause problems in humans or will even work. It has got so bad that most drugs on the market would not get through current preclinincal testing requirements.

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

#30

Post by danieltillett » Fri, Sep 04, 2015, 1:27 AM UTC

refurb wrote: post #26

zeveb wrote: post #10

> A patient with a seriously life-threatening disease like lung cancer is perhaps more willing to gamble on a risky drug in pursuit of a cure, while someone with a disease that has a high survival rate such as diabetes presumably cares more about avoiding adverse side effects. If he's more willing to gamble, then why not just let him do it ? The FDA's job should be to enforce truth-in-labelling (which means drugs wit…

If he's more willing to gamble, then why not just let him do it? They already do. It's called expanded access programs. If a patient is going to die, they can ask the FDA for permission to take an unapproved drug. The FDA says yes 99% of the time.

You can only get access to the drug if the company gives it to you. The hard-nosed response of the company is to never say yes since you run the risk of the patient having a side-effect unrelated to your drug that can kill it when you try to get FDA approval. If you care about helping the most people then risking your drug this way is crazy.