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mechanab t1_irem5ru wrote

Old article, but is the author complaining about how clinical trials are done or the idea of intellectual property rights. Who knows, because the author doesn’t really get into the details of either. How is “knowledge” “owned”? Is he talking about parents? That is the opposite of owned knowledge, it requires disclosure of what would otherwise be kept secret. Corruption of clinical trials? Is that a common problem? If so how should it be addressed? The author is just going on some sort of rant.

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TheRoadsMustRoll t1_irf8twp wrote

>How is “knowledge” “owned”? Is he talking about parents?

he's talking about private organizations doing research and then keeping the information to themselves because its their intellectual property (since they did the work.)

its a bit of a conundrum because private industry has a great deal of capital to expend on research but their motivation is profit: if they can't own their discoveries then they won't invest. but that means if they find a cure for a disease they can keep it to themselves which defeats the purpose of motivating their research.

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DeliciousCanary4711 t1_irf5aq3 wrote

> Corruption of clinical trials? Is that a common problem?

LOL tell me you know nothing about the state of modern science...

https://en.wikipedia.org/wiki/Replication_crisis

> If so how should it be addressed? The author is just going on some sort of rant.

Someone ia ranting without being at all informed all right...

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acediac01 t1_irf7t4d wrote

I thought there was a follow up study on the "replication crisis" and when the follow up (people trying to replicate the studies) actually get in communication with the original study authors the replication failure rate went down to 10%. Still not great, but better.

From my pedestrian/bystander understanding, journals want the most succinct article to publish, so a lot of prerequisites or best practices that exist at one university or within one discipline are left out of the publication, with the understanding that they are known. When someone educated slightly differently follows up, they don't get the same result because, from the beginning, they didn't do the same experiment.

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DeliciousCanary4711 t1_irf9csv wrote

> follow up study

Go find it. Use the internet.

> a lot of prerequisites or best practices that exist at one university or within one discipline are left out of the publication

So you think journals are omitting methodology to save on what, printing costs?

The crisis is systemic: researchers are forced to 'publish or perish' while those dying from little understood causes are blocked from accessing said knowledge... the whole thing is designed to enrich few at the cost of the many imo, not to accurately conduct scientific investigation and communicate findings for the benefit of humans and our habitat.

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acediac01 t1_irff0sr wrote

Nah, I don't actually care. I grew up not trusting anyone or anything, I just know that the words replication crisis make for a great headline.

I don't disagree about the incentives for academic work being heavily perverted by the current climate, however I have yet to see anyone propose a fix that will actually be adopted by anyone but idealists. Just like open source software vs. M$ and Apple, you have true believers, and then people that are just there to make money. At the end of the day, eating is more important that holding to your ideals.

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DeliciousCanary4711 t1_irgyd0j wrote

> eating is more important that holding to your ideals.

That is an extremely morally dubious claim.

Opioid overdoses are the #1 cause of death for adults 18-45 in usa... the Sacklers didn't make that happen without many accomplices with impressive science titles.

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Wu-Tang_Hoplite t1_irf9ay2 wrote

You don’t replicate clinical trials…

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Wordweaver- t1_irfdo59 wrote

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Wu-Tang_Hoplite t1_irff5ca wrote

This paper does not discuss duplicating clinical trials. It would most likely be unethical to try to reproduce a clinical trial based on the adverse effects you uncover. If the first study is unclear you design a new trial but you don’t try to replicate it…

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Wordweaver- t1_irfgalh wrote

It discusses using real-world data to replicate the findings of RCTs, not duplicate the clinical trial. If you want exact duplications, RCTs should be done in heterogenous populations to be generalizable and things that work for one population may well be duplicated later in a different population

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Wu-Tang_Hoplite t1_irfio6x wrote

The paper is trying to provide support for a standard of enabling RWE to support RCT data in the FDA process which is a good thing. You don’t usually run RCTs in heterogeneous populations. You want a heterogeneous sampling of the population you are trying to treat, but depending on where you are on the world that changes ie There are ethnic and geographic differences in CYP enzymes that will change your study (if you are from a specific. Geographic/ethnic group you get 100 mg/kg if you are from group B you get 150 mg/kg). Clinical trials are designed around a specific question. Does my study meet my primary and secondary endpoints. If yes, then it supports approval for your drug. If no, then it discourages approval based on that study. Maybe you will need to do a different RCT. This is a different premise then, for example, research done in metal organic frameworks, providing support for a new battery material. This study contains the methods the authors used to create a new material, the experiment they did to test the energy storage capacity, and the result they obtained. This is the type of research it would be beneficial to reproduce.

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Wordweaver- t1_irfismg wrote

Most of the replication crisis is from RCTs in social psych

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Wu-Tang_Hoplite t1_irfja0p wrote

I see the issue here. Reproducing RCTs in psychology = good idea. Reproducing RCTs in medicine = more often than not unethical (because you could design a better trial based on the previous one).

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DeliciousCanary4711 t1_irf9kc7 wrote

Sciece results can be replicated by definition.

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Wu-Tang_Hoplite t1_irf9wry wrote

Yes but clinical trials are studies run on humans and the goal is not to reproduce the results. The goal is to power the study well enough to show that you meet your endpoints. I completely agree that there is a replication crisis in reproducing research in the literature but talking about this in the same breath as clinical trials displays a fundamental lack of understanding about the drug approval process.

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DeliciousCanary4711 t1_irfcm0r wrote

Regardless of the purpose of a given study, if it isn't reproducible it isn't scientifically valid, full stop.

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Wu-Tang_Hoplite t1_irffutd wrote

Yes. No one is discounting that. Science should be inherently reproducible. The point I’m trying to make is that bringing up clinical trials in the same context and the general reproducibility crisis in science is comparing apples to oranges. You don’t publish the results of a clinical trial so someone can try to reproduce the trial. You share the results so that the next trial done on the same patient population can be designed to yield an even better outcome and as part of the drug/device approval process. If you run a new clinical trial on the exact same drug but you change the recruitment sites to attempt to change the characteristics of the patient population you recruit you are no longer reproducing a study. You are running a new study.

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DeliciousCanary4711 t1_irgz6oi wrote

> You share the results so that the next trial done on the same patient population can be designed to yield an even better outcome and as part of the drug/device approval process.

So what went wrong with this process re: oxycontin? Why was that drug approval process so flawed?

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Wu-Tang_Hoplite t1_irhccmh wrote

I don’t know much about the clinical trials run in OxyContin, but why do you think that the trials were flawed?

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DeliciousCanary4711 t1_irhdgdk wrote

Well the drug in question seems to have qualities that spawned a massive public health emergency, record settlements etc, if there is to be a discussion of a crisis in scientific credibility that seems like a reasonable starting point as OP points out. How does a defender of the pharma establishment explain the variance between trials vs real life outcomes? Gross incompetence seems unlikely?

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Wu-Tang_Hoplite t1_irhegn1 wrote

Clinical trials assess the safety and tolerability of a drug in the patient population when dosed correctly. I don’t know off the top of my head what follow-up studies are required for the approval of an analgesic. From my understanding OxyContin is safe when used as intended. The marketing campaign to get doctors to over-prescribe it is a completely different process which would not even begin until after the drug is approved (has passed clinical trials). To expand on this a little there are plenty of drugs with addictive potential that are legal to use (I.e dextromethorphan and Xanax). Just because there are negative side effects like to a drug (like addiction) does not mean it’s development process was flawed. All drugs have side effects.

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DeliciousCanary4711 t1_irhh103 wrote

You are shilling for an immoral nexus of pharm $, regulatory capture and corrupt science:

> FDA failure to obtain adequate evidence of effectiveness was not limited to oxycodone. Over the past 25 years, despite mounting evidence that a surge in opioid consumption was resulting in adverse public health consequences, the FDA continued to approve new opioid formulations for chronic pain based on efficacy trials utilizing a controversial methodology called enriched enrollment randomized withdrawal (EERW).26 Since its 2006 approval of oxymorphone, the FDA has relied on EERW as evidence of opioid efficacy for chronic pain.27 EERW trials differ from traditional double-blind, randomized, controlled studies. In an EERW trial, prior to randomization for a double-blind phase, all subjects are made physiologically dependent on the opioid in a 4- to 6-week open-label phase. Then only the patients who tolerated the opioid and found it helpful during the open-label phase are randomized to remain on the opioid or switch to a placebo. Critics of EERW have correctly described this methodology as “cooking the books” for 2 reasons.28 First, because only patients who tolerated the opioid and found it helpful are allowed to proceed to randomization, the study is not representative of the general population, and the results cannot be generalized to clinical practice. Second, because daily use of opioids causes physiological dependence, efficacy results are skewed in favor of the subjects who remain on the opioid. This is because opioid-dependent subjects who are switched to placebo experience opioid withdrawal symptoms, including increased sensitivity to pain. Moreover, switching opioid-dependent subjects to placebo renders the study not truly double-blind. The FDA’s decision to rely on EERW trial methodology is a consequence of the agency’s close ties to industry. In fact, the FDA’s decision to use EERW for analgesics was based on discussions at private meetings between FDA officials and pharmaceutical company executives hosted by an organization called Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT).29 Drug companies paid up to $35 000 each for the opportunity to attend IMMPACT meetings and interact with FDA staff.29 Yet, despite the uproar that followed public disclosure of the IMMPACT meetings, the FDA continues to rely on EERW trials as evidence that opioids are effective for chronic pain.

https://journalofethics.ama-assn.org/article/how-fda-failures-contributed-opioid-crisis/2020-08

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Wu-Tang_Hoplite t1_irhhqrl wrote

I qualified my statement that I was not familiar with these clinical trials so I don’t know why you think this is some sort of gotcha. I’m not advocating for the current mechanisms we used to fund science and develop new drugs. The entire process socializes the risks and privatizes the profits.

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DeliciousCanary4711 t1_irhi1wk wrote

You said

> Just because there are negative side effects like to a drug (like addiction) does not mean it’s development process was flawed

Either the process is flawed, or killing a ton of people was the intention.

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Leemour t1_irfkjgd wrote

Meta studies exist today as a means to mitigate the issue. Typically what gets into a meta study and is verified, then it gets further studied and researches build on those findings, but if it doesn't make into the study or serious faults are pointed out, then it is either ignored or someone tries to falsify/verify the claims of the original study.

This issue is being addressed; it's not a growing, awkward problem like climate change or overconsumption.

There is also an issue with resources. Just how much resources are we to waste just to verify the verification of a verification, etc. ? Some research is much more expensive than others, so we can't just have the same blanket standard for all.

It is a problem, but it is not like modern science is anywhere close to fraud; we just have an unprecedented wealth of new reports and too few people with not enough resources to verify each.

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DeliciousCanary4711 t1_irh0urd wrote

> It is a problem, but it is not like modern science is anywhere close to fraud

Within certain fields ie psychology, the meta studies mentioned in OP are showing 50% non reproducibility. That is a major problem.

Think about it - was oxycontin nonaddictive? Do SSRIs work? Vioxx? Phen-Phen? Adderall?

There is a crisis ongoing.

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Leemour t1_iri00z4 wrote

No, my man... meta studies are just doing their job in that case and are weeding out the nonsense from the good research.

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DeliciousCanary4711 t1_iriwitk wrote

I thought peer review was supposed to weed out the nonsense, not a meta study decades after the subject causes a massive wave of fatalities?

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Leemour t1_irix8bn wrote

No, peer review =/= metastudy =/= drug approval. These are different processes with different functions and responsibilities. Not to mention therapists don't rely on questionable research in psychology without informing their patients that they are taking part in a study or questionable method that has X% success rate with possible complications.

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DeliciousCanary4711 t1_iriyfep wrote

>therapists don't rely on questionable research in psychology

Yes they do, that's the point - whole medical industries are based on fictions.

https://www.nature.com/articles/s41380-022-01661-0

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Leemour t1_iriywex wrote

Do you even understand what the article is saying? This has nothing to do with "whole medical industries are based on fictions" or the efficacy of antidepressants.

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DeliciousCanary4711 t1_irizjok wrote

Yes I can read, can you?

> The chemical imbalance theory of depression is still put forward by professionals [17], and the serotonin theory, in particular, has formed the basis of a considerable research effort over the last few decades [14]. The general public widely believes that depression has been convincingly demonstrated to be the result of serotonin or other chemical abnormalities [15, 16], and this belief shapes how people understand their moods, leading to a pessimistic outlook on the outcome of depression and negative expectancies about the possibility of self-regulation of mood [64,65,66]. The idea that depression is the result of a chemical imbalance also influences decisions about whether to take or continue antidepressant medication and may discourage people from discontinuing treatment, potentially leading to lifelong dependence on these drugs [67, 68].

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Leemour t1_irj0iuh wrote

I can't believe I have to point this out: what do you think professional means here? Researchers, therapists or both, what is the difference? In what world can the therapist force a patient off of a demonstrably effective antidepressant (despite the patients wishes!!!) when such comprehensive metastudy was lacking? General public view does not coincide with scientific consensus/discussion either, so again, what part of this is telling you it's a sham?

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DeliciousCanary4711 t1_irj1qxi wrote

The 'scientific consensus' was and is wrong, people have been medicated with ineffective and dangerous drugs while effective treatment eg ketamine isn't being widely used for treatment. This didn't happen by accident.

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Leemour t1_irj79dg wrote

That's not what the study you quoted says.

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DeliciousCanary4711 t1_irjgecr wrote

Yes the last post was my original opinion backed by the study excerpt I helpfully posted for your education previous to that.

Welcome to philosophy.

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Leemour t1_irjkqop wrote

It does not support your conclusions, that is the problem.

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DeliciousCanary4711 t1_irjmnvf wrote

The whole serotonin theory of depression is false but the $20,000,000,000 SSRI industry marches on. It's a very clear case of corrupt science.

Worshiping science is unscientific and leads to immoral outcomes, you should stop doing that.

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Leemour t1_irjpa50 wrote

Alright tinfoil hatter. Totally wasnt trying to tell you that you need to read carefully what researchers publish, that peer review is not the same thing as doing a meta study and all of this is separate from what the process of the medical community and drug administration selecting their treatment methods and drugs.

The meta study is major in the sense that it debunks seratonin theory altogether, but there were many psychologists and therapists who already knew that. Even the article points out that this myth was/is chiefly believed by the general public. Regardless of this, the drugs go through a drug trial, which is different from all of this; they worked for a certain amount of people, so it passed the test, maybe not for the reasons we understand, but if it works, then it works and despite this study its not wise to force these drugs off the shelf when they work in drug trials.

You, not understanding the nuance of these things only proves your ignorance. The hysteria is just cherry on top.

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DeliciousCanary4711 t1_irk7oby wrote

> tinfoil

Solid argument. No you!

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Leemour t1_irk9dtt wrote

2 words is all you could read... well done

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[deleted] t1_irf9p94 wrote

[deleted]

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DeliciousCanary4711 t1_irfays6 wrote

> dangerous misinformation

Oh! Better alert the guardians!

> doing science, especially biological science, is very difficult to fully control

It wasn't brand-related enzymatic variance that caused oxycontin to be proclaimed non addictive. You're trying to obscure the argument with overtechnicality and moralistic finger wagging. How dare I criticise science? Bud, you're in the wrong sub.

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[deleted] t1_irfcmm4 wrote

[deleted]

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DeliciousCanary4711 t1_irfdyya wrote

> you’re directly trying to link “corruption” with the reproducibility crisis

Data that doesn't reflect objective reality is by definition corrupted, but yes of course human-related financial corruption is a major factor- from the clinic to the corpotate pharm boardroom. How could it possibly not be a factor, given human nature? What other explaination would you propose for the scientific vetting of oxycontin?

> I’m a career scientist

Who funds your grants?

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[deleted] t1_irff3jf wrote

[deleted]

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DeliciousCanary4711 t1_irgyxt0 wrote

> Additionally, you’re fixated on just this oxy question for some reason.

Leading cause of death for 18-45 adults in usa. No big deal?

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iiioiia t1_irfgyfk wrote

>Wondering about my funding, implying that despite a decade of training to become a scientist, and all the experience after, I’m really just in it for the money and so am willing to push false narratives.

This is one possible interpretation, but there are many other possibilities.

Do they not cover the difference between subjective and objective reality in science and philosophy curriculum these days? Or how about psychology - did heuristics get covered at all in your studies?

> I can’t help you.

Whether you can help yourself seems like a more pressing issue.

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VitriolicViolet t1_irgnpeu wrote

>How could it possibly not be a factor, given human nature? What other explaination would you propose for the scientific vetting of oxycontin?

you already made up your mind apparently so i dont know why your here.

if you cant think of any possible reasons oxy was passed other then money then god help you (its not like oxy has any medical applications. ffs using your logic all painkillers are designed to make money. fuck me you probably think pharma likes cancer and wouldnt cure it if they could).

'drugs are bad m'kay' isnt an argument and neither is shameless appeals to conspiracy.

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DeliciousCanary4711 t1_irh18k5 wrote

> you already made up your mind apparently so i dont know why your here.

I find the argument made in the OP to be logical and persuasive.

> if you cant think of any possible reasons oxy was passed other then money then god help you (its not like oxy has any medical applications. ffs using your logic all painkillers are designed to make money. fuck me you probably think pharma likes cancer and wouldnt cure it if they could).

Oxycontin is more addictive with similar efficacy compared to other opioids. Why do you think it was pushed, if not for the billions of usd profit?

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iiioiia t1_irfgrok wrote

>As far as whether I’m in the right place, I’m a career scientist with a bonus philosophy degree, I might have a clue.

This may provide some very valuable insight into the metaphysical nature of reality.

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Vast-Material4857 t1_irg15q2 wrote

The replication crisis is in the field of psychology not biology.

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[deleted] t1_irgpdeb wrote

[deleted]

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Vast-Material4857 t1_irgz2wh wrote

Then you have no idea what you're talking. The replication crisis refers to a specific attempt to recreate major cornerstone studies in the field of psychology.

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