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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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