As a sales and marketing person... I'll admit to a lot of blame for a lot of bad things... definitely playing with words to they point where they mean very little.

Selective publishing and "p-hacking" though, these are research/academia pathologies not marketing ones.

Study 329. GSK paid a PR company to ghostwrite a misleading paper, with the intent of concealing the fact that a) paroxetine is no more effective than placebo in the treatment of adolescent depression and b) paroxetine significantly increases the risk of suicide in adolescents.

GSK knew that their drug was worse than useless, they knew that children would die as a result, but they deliberately withheld damning data and misled clinicians. For this (and many, many other acts of deceit) they were fined a total of $3bn by the Department of Justice.

The paper has never been retracted and paroxetine is still widely prescribed to adolescents.

https://en.wikipedia.org/wiki/Study_329

"Why is youth suicide skyrocking since we starting giving them all anti-depressants that have a suicide as a side effect?"

"Sounds like they need more anti-depressants"

I understand why you are getting downvoted. Yet I think you make a valid and important point. Sure marketing and sales are putting a lot of pressure on, in that case RandD. But then RandD is, at some point, deciding to publish or find what is wanted. And, at least in my experience, good marketing people would rather not have falsified results and even if it is just for PR reasons.

Just blaming someone else, like marketing and sales, is quite often juat a lazy excuse to not have to look at oneself. Goes zhe other way round, so. Marketing saying "we didn't force them to find value X" might be literally true as marketing almost certainly didn't use these words. But pressure cam be applied in more than one way, it doesn't have to be explicit.

One good example is the series Chernobyl. Pressure from above to deliver certain things, ignoring truth until it's too late and then looking for someone to blame. Plant management did it with the reactor control crew and the political higher ups indirectly with plant management. So yes, all of them have to blamed. Not simply a communist problem as this thread about pharma R and D shows, right?

Well said. In fairness to the downvotes, I was bey tongue-in-cheek.

Whether for reasons of communist 5-year plans, capitalist pharmaceutical industries or even just the personal desires of an academic to prove a pet theory, publish or whatnot.. incentives and pressure to cheat exist. That's one reason why replication is so important.

Hasn't this been fixed with the requirement to pre-register trials? https://chrisblattman.com/2016/03/01/13719/

I'm not sure if every org requires it now or not, but if not then it seems like a question of time only.

> Hasn't this been fixed with the requirement to pre-register trials?

If it was that simple...

Preregistration is a step in the right direction, but there are still plenty of ways to game the system, particularly as it's not properly enforced: http://compare-trials.org/

But it is the necessary step to highlight the problem so that actions can be taken.

Also, you can safely assume that the large majority of outcomes that were not published were:\

- negative

- worse than negative (i.e. safety issues?)

- not properly designed

So if you compare the number of trials disclosed/not disclosed for each drug/each company that gives you a pretty good picture of who is doing what already.

With that data, it's then a lot easier to approach regulators to do something about it.

My assumption is that most unpublished trials were "no effect".

Be a drug company. Develop a "drug" that is really a placebo (has no effect). Do 10 trials. 8 are "no effect", 1 is positive (by chance), 1 is negative (by cance). Publish the positive drug. Market the drug as having positive effect. Sell the drug, make billions. It would take decades for enough other research (mostly "no effect") to accumulate before it becomes obvious that your drug actually has no effect.

That’s the whole point of preregistration. The nine unpublished trials can be assumed to be negative, or at least neutral, and were aware that they were done because of preregistration. Therefore regulators have the ability to reject the notion of the effectiveness because so few of the studies reported positive outcomes. In addition, any cancelled studies now taint the authors and sponsors with a (small) amount of suspicion that they are refusing to publish non-positive effects which, cumulatively, will cause their results to be further discounted. That will hopefully provide a strong incentive to publish neutral and negative results.

A drug that genuinely has no effect is actually pretty good; most drugs have some sort of risk and many are seriously dangerous. Rofecoxib is believed to have caused around 100,000 heart attacks and 30,000 deaths. Market approval for rofecoxib was based on misleading data and its withdrawal from the market was substantially delayed by misleading data.

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

From the results there it is clear that they failed to game the system since the gaming was detected. Getting to the point where regulators can actively use the preregistration information is the next step, but the foundation is there.

This really isn't true, certainly not as a blanket statement.

What Ioannidis is saying is that profit motivates pharma research. This is in a sense a tautology. Even then, Pharma do fund trials initiated by investigators not affiliated with the company.