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The FDA buries evidence of fraud in medical trials. My students and I dug it up

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Re: The FDA buries evidence of fraud in medical trials. My students and I dug it up

#101
I post a fair number of stories about regulation of medical treatments here on Hacker News. I see this one has attracted a lot of reader interest. The comments already posted as I post this comment point out that once someone sets up a regulatory program, the incentives become powerful to figure out ways to cheat the regulators. And, as usual, scientific research is hard (another topic I post a lot about here), and researchers all operate under incentives to publish interesting and hopeful results rather than acknowledge that their research program didn't show what the researchers hoped to show.

The submitted article identifies a specific problem in how the FDA doesn't publish identifying details of studies that its own inspectors discovered to have problems. Biomedical researchers, then, don't know which previous study findings are flawed, even though the FDA detected flaws, and much time and effort is wasted trying to pursue research results that don't reflect reality. That has to change.

Meanwhile, there is a different pattern of regulation for some products that consumers in the United States take regularly as they seek better health, namely "natural supplements." For natural supplements, the regulatory problem is far worse, because those products can go on the market with no research done on safety or effectiveness at all, and without even any guarantee that the product contains the labeled active ingredient,[1] a plain violation of the warranty of merchantability in the Uniform Commercial Code.

So the better trade-off for the consumer here is to amend existing law so that as drugs go through clinical trials, disclosure and peer review of FDA inspection findings during the trials is a condition for marketing approval. If manufacturers can't deal with that kind of regulation, tough. But it's only fair that natural supplement products, a multi-billion-dollar industry, should be regulated the same way.

(To answer a question asked in another comment, already well answered overnight in my time zone, yes, "science-based medicine" includes "evidence-based medicine," that is clinical trials, as a subset of practices that include also consideration of fundamental principles of science and statistical understanding of prior plausibility before interpreting clinical trial results. If a sample size is small enough, many implausible treatments can look like successes in a clinical trial, especially for subjective, patient-self-reported symptoms, but we shouldn't call such treatments effective until they have been replicated in larger samples and verified with independently gathered "hard endpoint" data about clinical signs.)

[1] "Searching for the supplement in your supplement"

http://www.sciencebasedmedicine.org/searching-for-the-supple...

Re: The FDA buries evidence of fraud in medical trials. My students and I dug it up

#102
post #52

How much of this could be solved by replication? Some sort of rule where we say, formally, not to take any study seriously unless it's been replicated? On the one hand, it's very bad that the FDA has covered this up. But on the other hand, there was science before the FDA. I may be interpreting the article wrong, but it seems as though the FDA is merely failing to prevent bad science. Presumably, journals that cited…

Clinical trials are very expensive to run. The only people financially interested in running them are the pharmaceutical companies trying to make new products available. Replication is hard enough to achieve in hard sciences where replicating a study might cost tens of thousands of dollars. Finding the money to replicate or refute a clinical trial for millions of dollars is very difficult.

Also, I don't think people do pure replications. People generally do replication with a twist, which is essentially a new branched experiment. Rather than confirm one specific part of a theory more than once, it's better to confirm various wings or implications of a theory.

Re: The FDA buries evidence of fraud in medical trials. My students and I dug it up

#103
post #84
post #77

Earlier quoted context omitted.

I think the real question most people want to know the answer to is: Is one of them a front for homeopathy, anti-vaccinations and/or Scientology, or are they both mostly imperceptibly different degrees of serious research? Downvoters: Please explain. I have no idea about what any of SBM or EBM is, and I hadn’t even heard about any of them before now. This is genuinely what I what to know when I encounter the terms.

EBM is meant to be serious science, but there's been a real effort to co-opt it for quackery. SBM is an attempt to inject science back into it. The difference comes down to how they treat evidence. For example, homeopathy states that a remedy becomes stronger the more dilute it becomes - i.e. the lower the dose, the stronger the effect. This defies the dose-response relationship between an active ingredient and its e…

for the record: homeopathy does not do well with EBM either.. (as in quality double blind studies)

Re: The FDA buries evidence of fraud in medical trials. My students and I dug it up

#104

A related and very interesting story is this article[1] on Ranbaxy. Basically this company was corrupt and fraudulent from the top down. Falsifying data, copying competitor information as their own, etc. Or encouraging internationally traveling employees to privately import medicines to India for them. Or asking doctors on staff to write prescriptions for everyone in the office to boost sales figures. The FDA applied…

A bit more happened, last year the FDA started making unannounced visits to their production plants in India. When I checked on this about a month ago, it appeared that every Ranbaxy plant in India had been shut down. This Google search will provide a lot of info, https://www.google.com/search?q=Ranbaxy+flies that's "flies" as in those disease spreading insects. One of the articles had a picture of a man unloading dung from a cart with a Ranbaxy plant in the not too distant background....

I pay attention to this because I take a lifesaving maintenance medicine that my medical plan currently sources from Sun :-(. Since that and another important drug I take went generic over the last few years, my doctor has been very happy with my reporting that to me, they seem to be bioequivalent. He's in a field when generics of one class of drugs, the anti-convulsants, are notorious for not being easily substituteble with brand name.

Ah, a bit more on that fabulous Fortune article: their First World drug mules were being asked to deliver First World brand name manufactured drugs so that Ranbaxy could falsify equivalence tests. One US executive left the company after the 2nd "wow, these guys are so good their data matches the brand names's point to point" "coincidence".

Re: The FDA buries evidence of fraud in medical trials. My students and I dug it up

#105
post #51

Earlier quoted context omitted.

I'm pointing out that pharma can either be treated like every other company and held to similar standards or they can act like scientists if they want mandated use of their products. And yes, pharma does lobby for laws to mandate vaccinations. edit: obviously lobbying is not 100% responsible for all vaccinations laws, but it's partly so and increasing.

Fine, but obviously it's not only the vaccine manufacturers who are pushing for things like mandatory vaccinations for public school enrolment (except where unable, e.g. immunocompromised children unable to tolerate the vaccination itself). It's also, y'know, people with an interest in promoting public health, people who understand the concept of herd immunity, and people who have a reasonably tuned sense of social r…

And people freaking old enough to remember when the only vaccination was for smallpox.

I just discussed this with my 81 year old father, who along with everyone else stood in line for the first polio vaccinations; that was the big fear for adults who'd survived the other things children are immunized for like measles, e.g. FDR lost almost all the use of his legs from it when he was 39 and counted himself lucky. I myself was born early enough that I got a lot of vaccinations as they first became available, and my parents, my mother a former RN, were very happy about this state of affairs.

Seriously, you might as well read Kippling's The Gods of the Copybook Headings in favor as anything else about this rank insanity. As well as gain a much more sympathetic view of the "less enlightened" of the world and history, as we arrogantly view them.

Re: The FDA buries evidence of fraud in medical trials. My students and I dug it up

#106
post #28

Both honestly and sadly, I think nobody is actually legitimately surprised by this. The pharmaceutical industry is a profit machine that will do anything to ensure that it remains profitable. If anyone hasn't seen John Oliver's latest video, it's on the whole marketing to doctors thing and touches upon the pharmaceutical industry and I highly recommend watching it: https://www.youtube.com/watch?v=YQZ2UeOTO3I - he sum…

The pharmaceutical industry is a profit machine that will do anything to ensure that it remains profitable. But this isn't about the pharmaceutical industry, it's about the FDA. The FDA is clearly catching these companies doing wrong, so why are they covering it up? And if you think the FDA and the pharmaceutical industry are in bed with each other, I would have to disagree (coming from the industry). The company I u…

"The FDA is just starting to think about inspecting those plants."

Fortunately it's a lot better than that. They have been inspecting them for a long time, but infrequently and preannounced, and even then caught some in the act. After the gross, top to bottom fraud of Ranbaxy, they started doing unannounced visits, which has resulted in every one of their plants in India being shut down: https://news.ycombinator.com/item?id=9043423

Re: The FDA buries evidence of fraud in medical trials. My students and I dug it up

#107
post #64

Earlier quoted context omitted.

How much of this could be solved by replication? The FDA won't approve a drug without at least two positive phase III trials (some exceptions for oncology and other fatal diseases).

Two positive trials, but if there are additional negative trials those can be ignored. There is no requirement to combine all available trials in a meta-analysis. Very easy for the pharm company to come up with some excuse to throw away "bad" data.

I don't disagree, but I also don't think it's a bad thing. Most of the time the multiple failed trials occur in diseases where our current tools for measuring effect suck (CNS drugs). The FDA acknowledges this. Keep in mind that drug companies must submit all clinical trial data to the FDA (including all of the failures). It's not like the drug companies are pulling a fast one on the FDA. The FDA is looking at the totality of the evidence and making a call.

Re: The FDA buries evidence of fraud in medical trials. My students and I dug it up

#108
post #105

Earlier quoted context omitted.

Fine, but obviously it's not only the vaccine manufacturers who are pushing for things like mandatory vaccinations for public school enrolment (except where unable, e.g. immunocompromised children unable to tolerate the vaccination itself). It's also, y'know, people with an interest in promoting public health, people who understand the concept of herd immunity, and people who have a reasonably tuned sense of social r…

And people freaking old enough to remember when the only vaccination was for smallpox. I just discussed this with my 81 year old father, who along with everyone else stood in line for the first polio vaccinations; that was the big fear for adults who'd survived the other things children are immunized for like measles, e.g. FDR lost almost all the use of his legs from it when he was 39 and counted himself lucky. I mys…

[deleted]

Re: The FDA buries evidence of fraud in medical trials. My students and I dug it up

#109
post #28

Both honestly and sadly, I think nobody is actually legitimately surprised by this. The pharmaceutical industry is a profit machine that will do anything to ensure that it remains profitable. If anyone hasn't seen John Oliver's latest video, it's on the whole marketing to doctors thing and touches upon the pharmaceutical industry and I highly recommend watching it: https://www.youtube.com/watch?v=YQZ2UeOTO3I - he sum…

The pharmaceutical industry is a profit machine that will do anything to ensure that it remains profitable. But this isn't about the pharmaceutical industry, it's about the FDA. The FDA is clearly catching these companies doing wrong, so why are they covering it up? And if you think the FDA and the pharmaceutical industry are in bed with each other, I would have to disagree (coming from the industry). The company I u…

> But this isn't about the pharmaceutical industry, it's about the FDA. The FDA is clearly catching these companies doing wrong, so why are they covering it up?

There's some overlap, right? http://geke.us/PharmaVenn.001.jpg

Re: The FDA buries evidence of fraud in medical trials. My students and I dug it up

#110
post #108
post #105

Earlier quoted context omitted.

And people freaking old enough to remember when the only vaccination was for smallpox. I just discussed this with my 81 year old father, who along with everyone else stood in line for the first polio vaccinations; that was the big fear for adults who'd survived the other things children are immunized for like measles, e.g. FDR lost almost all the use of his legs from it when he was 39 and counted himself lucky. I mys…

[deleted]

Fair enough; my comment was intended as an addition to your list of "It's also, y'know, people with an interest in promoting public health, people who understand the concept of herd immunity, and people who have a reasonably tuned sense of social responsibility." with examples in living history. Plus you can't get away from the concept of "good science" and people who don't accept the concept at all in this domain, especially the ones who can be accurately plotted by Whole Foods locations and otherwise claim to respect "science".

Let me add that at least in theory, vaccines receive the strictest regulation of all drugs, since the they're given to ostensibly healthy people.

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