Comment by lutusp | Hacker News Reader

Comment by lutusp | Hacker News Reader

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> Err why is a non lethal, not particularly damaging drug going to be an unethical drug trial?

Antidepression drugs, indeed all psychoactive drugs, are always a potential ethics issue. Consider the brouhaha that erupted when it was discovered that some antidepression drugs caused people to commit suicide or have suicidal thoughts:

http://www.medicinenet.com/script/main/art.asp?articlekey=31...

A quote: "The FDA has warned that children and adults taking antidepressants can become suicidal in the first weeks of therapy and that physicians should watch patients closely when first giving the drugs or changing dosages. The FDA is asking drug manufacturers to place explicit warnings about the drugs' side effects, including the risk of suicide, on their labels."

Any human-administered drug is a potential ethical issue, from vitamins upward. Imagine a study in which an experimental group is given a daily vitamin, and a control group is given a placebo but told they're receiving a vitamin. Several years go by and the relative health of the study participants is closely monitored.

Can you not see the ethical issue here? Can you not imagine the lawsuits that would result from the parents of those in the control group who perhaps didn't thrive as expected, or for some completely imaginary consequence having nothing to do with the vitamin study, but sufficient to sue for civil damages?

And finally, depression drugs are hardly "non lethal, not particularly damaging". They are a source of great controversy and have been the focus of a number of conflicts over the years.

Ketamine is a commonly used, fully tested anaesthetic. Every ambulance has a stock of it because it's the safest anesthetic to use in emergency situations. It's not an anti depressant, it's not approved as one. But the recent interest is because it can stop depression in hours whereas the anti depressants take days to weeks. So for suicidal individuals it's very important.

That's why it's normal these days, for clinical studies, for the control group to receive current best available treatment, rather than a placebo.

After all, what you're generally trying to find out is whether the new treatment is better than what you already have - just being better than a placebo isn't very informative.

If you're interested in this sort of thing, I strongly recommend reading Ben Goldacre's work[1].

[1] Start at badscience.net.

> That's why it's normal these days, for clinical studies, for the control group to receive current best available treatment, rather than a placebo.

That's one of the reasons such studies are so unreliable -- they depend on a comparison of two or more drugs that may operate in different ways, rather than comparing a drug to the absence of a drug.

The result is predictable -- unbiased meta-analyses show that antidepressants don't work:

http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fj...

This is not to say that wouldn't have been the outcome anyway, regardless of the methods used, only that testing two drugs at once introduces confounding factors.

They do this all the time with every drug the FDA tests. People have a disease and they use a control group that receives a placebo. It's the only way drugs are finally proven to work in humans.

> They do this all the time with every drug the FDA tests.

Not necessarily. Imagine testing a drug that's supposed to reduce the suicide rate among teenagers, and yes -- it's been done.

Compare suicide rates, write up the result, then spend the next five years in court listening to outraged parents.

The outcome is that these kinds of drugs are no longer tested on humans. Antidepressants are at the top of the list of drugs that are difficult to realistically test, which explains why they were falsely believed to work for so long. On that topic, a recent meta-analysis reveals that they don't work:

http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fj...

A quote: "Meta-analyses of antidepressant medications have reported only modest benefits over placebo treatment, and when unpublished trial data are included, the benefit falls below accepted criteria for clinical significance."

Translation: "we located all those studies the drug companies suppressed, and when they are included in a balanced analysis, it wipes out the scientific justification for prescribing these drugs."

By your argument, all control groups for testing treatments for anything debilitating is unethical. The answer to that is that medical ethics generally work on a basis of least harm, so if you have informed volunteers who might have negative effects from a given trial, this is deemed to be balanced out by the general benefit that rigorous drug trials can bring to the wider population.

As far as the issue with some anti-depressives and suicide, the main issue was that drug trials showing this had in some cases been systematically downplayed and in some cases suppressed outright by the companies seeking to profit from these drugs. So the problem there was not with the procedure of medical trials, but rather with the corruption of the procedure of medical trials, for profit.

> By your argument, all control groups for testing treatments for anything debilitating is unethical.

1. Never said it.

2. It's unethical unless one acquires informed consent from adults. Many of the adults in these studies don't understand enough to give informed consent, and many of the studies involve children.

> So the problem there was not with the procedure of medical trials, but rather with the corruption of the procedure of medical trials, for profit.

And that's the contextual background for any clinical study of antidepressants. Most adults think antidepressants work, but studies show that they don't work:

"Initial Severity and Antidepressant Benefits: A Meta-Analysis of Data Submitted to the Food and Drug Administration":

http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fj...

A quote: "Meta-analyses of antidepressant medications have reported only modest benefits over placebo treatment, and when unpublished trial data are included, the benefit falls below accepted criteria for clinical significance."

A situation ripe for exploitation.

You didn't use those exact words, but it would seem the logical extension of your argument. And to claim that any clinical study of antidepressants is corrupted for profit would seem to ignore the fact that the evidence you are using about anti-depressants not working comes from clinical studies. You can't have it both ways.

> You didn't use those exact words, but it would seem the logical extension of your argument.

It's essential in a discussion like this to quote the other person directly, word for word, as I have just done.

> And to claim that any clinical study of antidepressants is corrupted for profit ...

Circle where I ever said this anywhere. Want to have an imaginary debate? Make stuff up.

> would seem to ignore the fact that the evidence you are using about anti-depressants not working comes from clinical studies.

You're confused. Comparing industry-funded studies, in particular when only those with positive outcomes were even published, to a meta-analysis by non-industry sources that gather and analyze all studies, published and unpublished, is to compare apples and oranges.

No it isn't essential.

For the second, you said it was the contextual background of any clinical study, before then going on to compare clinical studies which you are now saying shouldn't be compared.

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