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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

#51
post #47
post #44

Earlier quoted context omitted.

I can't think of many industries pushing for laws to force you to ingest their product. Eating McDonald's is not a prerequisite for admittance to pre-school.

Are you trying to imply that vaccines being mandatory is the result of lobbying and not just because it's an extremely important tragedy of the commons problem?

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.

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

#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 these experiments didn't replicate that and knew they weren't replicated. Is science too complex and expensive to replicate these days? If so, is it even still science?

(Those are actual questions, not rhetorical ones. I don't know the answers here).

Edit: For some reason, at present my comment seems to be the top comment. I don't want to detract from the story itself. The actual issues at the FDA raised by the article deserve discussion.

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

#53

Tokenadult, Out of curiosity, given that you've said in your previous comments that you believe medical questions are best answered with 'science-based medicine', which is a philosophy that explicitly rejects evidence-based medicine: do you believe that the FDA covering up scientific fraud is bad, or do you agree with the FDA's argument that it's justified? Also, do you still believe that "It's an exaggeration (contr…

Question (not being sarcastic): what's the difference between 'science-based medicine' and 'evidence-based medicine'? I did a quick Wikipedia search, but the former just redirects to the latter.

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

#54
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.

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

#55
post #44
post #22

Earlier quoted context omitted.

To be honest I can't think of many industries which place public health scientific merit at their top priorities either. You could say the same thing about the food and beverages industries, and Soylent too if you care about mentioning stuff that makes HN tick often.

I can't think of many industries pushing for laws to force you to ingest their product. Eating McDonald's is not a prerequisite for admittance to pre-school.

This is one of those bizarre comments that arise, I think, from a society being halfway between socialism and full-blown privatized capitalism.

Consider: Eating McDonalds could certainly be a prerequisite for admittance to McPreSchool, the worlds largest hypothetical private preschool system.

Consider also: your government operating as a corporation. Public health is a massive drain on government resources. Vaccines have VERY researched positive impact on public health. If government were a private corp then hell yes they would require vaccinations.

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

#56
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.

So can we still call it science, or not? And if not, what do we call it?

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

#57

Earlier quoted context omitted.

The oped piece you cited does not support your assertion that the "FDA is incompetent and corrupt". They may be, but that is a pretty hefty accusation and requires more evidence. Nor, honestly, does it support the "getting a drug approved is more dependent on how much money you want to spend than on whether it works" claim, or the "some drugs that may be effective are delayed for years and years". Developing a drug i…

> The original link cites corruption at the hospital level, which does seem like the weakest link in the system. If corruption stopped at the hospital there, then this wouldn't happen at the FDA: > As David Ross, the FDA official in charge of reviewing Ketek’s safety, put it, “In January 2003, over reviewers’ protests, FDA managers hid the evidence of fraud and misconduct from the advisory committee, which was fooled…

"FDA managers hid the evidence of fraud and misconduct from the advisory committee, which was fooled into voting for approval" -> Yes, that sounds super sketchy. The actual testimony doesn't, though it's one sided (below).

The redactions are not surprising to me. The FDA is a regulatory agency that deals with very sensitive and confidential information. They are not a criminal agency, and this isn't some district attorney asking for the information.

The testimony: """ After considering the fact that the investigation results were preliminary and we had not received formal recommendations about how to take the results into account in review of the application, and the fact that only in very rare cases do inspection results from individual sites lead to the exclusion of an entire large clinical trial, FDA decided to hold the Advisory Committee meeting as planned. The Agency made this decision, knowing that any advice from the Committee would have to be later taken into account in the context of additional information about the integrity of data from Study 3014. It is not unusual for more information to come to FDA for review after an Advisory Committee meeting is held about an application. The Advisory Committee voted that the safety and efficacy of the requested indications had been demonstrated, based on the information it was provided, including Study 3014, and limited international post-marketing data provided at the meeting. Although the Advisory Committee recommended approval, on January 23, 2003, (two weeks after the Advisory Committee meeting) FDA issued another approvable letter to the sponsor because of the remaining questions about the safety of Ketek. The letter specifically noted the unresolved data integrity issues associated with Study 3014 (issues confirmed in the final clinical inspection summary of the Agency's audits of the first three clinical trial sites) and the incomplete post- marketing safety data from foreign countries. FDA noted that the final decision regarding approval of each indication would be made after a review of the information and analyses requested in this letter. On March 3, 2003, during a closed session of the Advisory Committee convened to discuss other matters, FDA briefly explained that an approvable letter was issued because the Agency wanted to see more information about data from Europe and Latin America. With regard to Study 3014, FDA explained that there were unresolved inspectional issues. Third Cycle. The sponsor submitted a complete response to the approvable letter in October 2003. The October 2003 submission addressed issues of Study 3014 and included post- marketing reports for spontaneous adverse events for approximately four million prescriptions for patients in other countries where Ketek had already been approved. Upon completing the review of the sponsor's October submission, including the findings from the additional audits of clinical trial sites summarized in a March 2004 memorandum from the Division of Scientific Investigations, the Agency decided that it could not rely on Study 3014 to support approval of Ketek because of the systemic failure of the sponsor's monitoring of the clinical trial to detect clearly existing data integrity problems. Accordingly, Study 3014 was dropped for consideration in making the decision whether to approve Ketek. The Agency considered data from other clinical trials and the international post-marketing experience to conclude there was adequate evidence of safety. """

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

#58
post #51
post #47

Earlier quoted context omitted.

Are you trying to imply that vaccines being mandatory is the result of lobbying and not just because it's an extremely important tragedy of the commons problem?

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 responsibility. So, sure: Big Bharma employs lobbying as part of their business strategies. This is both unsurprising and irrelevant to the overall societal benefit of high immunisation rates.

> edit: obviously lobbying is not 100% responsible for all vaccinations laws, but it's partly so and increasing

But how can you tell that the number of vaccination laws passed due to lobbying is increasing? Or possibly you just meant that lobbying dollars are increasing. But higher dollar values alone would tell us nothing about the relative success of that lobbying in getting laws passed. For example, perhaps the laws were going to be passed regardless, and the increased spend is illusory, being attributable to a general trend of increased lobbying spend in US big-business, inflation, or other factors. In an environment where lobbying is the norm, I think gauging the "effectiveness" of lobbying spend, especially for something which lots of people generally seem to support anyway, is a hard problem.

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

#59
post #53

Tokenadult, Out of curiosity, given that you've said in your previous comments that you believe medical questions are best answered with 'science-based medicine', which is a philosophy that explicitly rejects evidence-based medicine: do you believe that the FDA covering up scientific fraud is bad, or do you agree with the FDA's argument that it's justified? Also, do you still believe that "It's an exaggeration (contr…

Question (not being sarcastic): what's the difference between 'science-based medicine' and 'evidence-based medicine'? I did a quick Wikipedia search, but the former just redirects to the latter.

Science Based Medicine is a movement to improve Evidence Based Medicine with a stronger focus on scientifically rigorous evidence. It's not in opposition to EBM.

To quote the SBM blog's about page:

"Good science is the best and only way to determine which treatments and products are truly safe and effective. That idea is already formalized in a movement known as evidence-based medicine (EBM). EBM is a vital and positive influence on the practice of medicine, but it has limitations and problems in practice: it often overemphasizes the value of evidence from clinical trials alone, with some unintended consequences, such as taxpayer dollars spent on “more research” of questionable value. The idea of SBM is not to compete with EBM, but a call to enhance it with a broader view: to answer the question “what works?” we must give more importance to our cumulative scientific knowledge from all relevant disciplines."

You can find the original Science Based Medicine announcement on their blog http://www.sciencebasedmedicine.org/hello-world/ and there's a decent bit of background on Pain Science https://www.painscience.com/articles/ebm-vs-sbm.php as well.

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

#60
post #56

Earlier quoted context omitted.

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.

So can we still call it science, or not? And if not, what do we call it?

Well, technically they are replicating the study over 50+ different hospitals until they reach some confidence interval on the safety data. If you get fraud in a small fraction of them, it should not (and if you read the actual testimony, does not) impact the net result.
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