[srean]

As far as I know, US laws require that the `x` number of trials demonstrate the effectiveness of the drug and failured dont need to be reported. But this does not make sense to me, and I welcome the European laws. In the US system, even if I have a coin biased badly against coming up heads, if I toss it enough number of times I will get `x` heads. The tosses cost money and that is then used to justify the patent system.

One of the oft repeated justification for the absurd levels of IP protection and patent extensions that pharma enjoys is the huge cost of trials. But if huge development costs are the reason for these protections to exist, guess what, these costs will continue to remain huge. Its just self perpetuating.

Patents are primarily a preemptive measure against a hypothetical scenario. The hypothesis is that unless market pressures are cordoned off, innovation will stop. It is a believable hypothesis but not a quantitative one, and this exactly where we need a quantitative one. How many years exactly does one need to subvert the market so that a satisfactory level of innovation is maintained ? Nobody knows. In these scenario what we need is a feedback system, and pretty much the only scalable and fair apparatus that we have for such feedback on economic affairs is the market.

So rather than subverting the market, market should be explicitly and actively involved to work out this trade-off. How exactly this is to be done needs to be worked out.

There could be a futures market on patents on drugs undergoing testing: competitors can promise to buy the patent to the (drug,usecase) pair at a particular price (even if its a dud) and if the owner decides not to sell the owner pay a particular compensation. Such measures will spread the risk. There should be mechanisms for a company to raise money for testing in lieu of rights over the product.

The initial period of validity of a patent should be short, like 3~6 years, following which the patent is on the market. Entities can bid to bring the patent to public domain. The owner(s) bids to retain it. Whoever wins gets the balance. Of course the "bring it to public domain" bidders will bid less because profitability is less when its in the public domain, but market decides who gets to own it. If the owner(s) think they can still extract lots of profit from the drug, bid high. We should stop handing out blank checks without a feedback loop, that is just bad design.

[Alex3917]

In the US you need two trials showing that a drug is effective, but you can have an unlimited number showing that it's not effective. Also it doesn't need to be shown to be effective against a disease, it can just be effective at reducing some number that correlates with a disease. And you don't need to show that it's effective in the longterm, only for up to 6 weeks - it could make the disease dramatically worse in the longterm, and that's fine even if the drug is meant for longterm use.

There are some rules trying to get all new trials registered, but the rules aren't followed at all and the FDA doesn't enforce them.

[refurb]

Wow, there is a long that is incorrect in your comment.

1. You are right that typically you need two registrational trials for approval and yes you can have many trials that show it doesn't work.

2. You are incorrect that you don't need to show it works against a disease. Sometimes you can show that you are impacting a biomarker (which I assume is what you mean by "some number"), but there must be evidence that changing the biomarker impacts the disease. Without that evidence you will not get approval.

3. You are incorrect you only need to show its effective for up to six weeks. If that were true, why would drug companies be running multi-year trials for cholesterol drugs? You typically need to show its effective for however long the drug is taken, but a follow-up period is also required.

[Alex3917]

2) C.f. statins. There are any number of books that talk about this. Overdosed America comes to mind, but you'd be hard pressed to find any recent book about the pharma industry that doesn't talk about statins.

3) C.f. SSRIs, and Robert Whitaker's book anatomy of an epidemic.

[refurb]

2) You are correct that new drugs can be approved by showing a lowering of LDL (biomarker), but that's only because the link between LDL lowering and cardiac risk reduction has already been demonstrated.

The best example I can give you right now are the drugs in development to treat Duchenne's muscular dystrophy. These drugs work by increasing the levels of a biomarker called dystrophin. The FDA recently came back and said "nope, not enough evidence that increasing dystrophin will improve patient's conditions, therefore we will not approve your drug".

As for the length of depression trials, it has been established that 6-week trials provide enough evidence to support an improvement in patients. [1]

Therefore, a 12-week trial is not necessary for all older patients; rather, the degree of improvement in the first 4 to 6 weeks identifies patients who are highly likely to benefit from continuing antidepressant treatment as well as those who very probably should have their treatment regimen altered at that point.

However, the depression drugs also run trials for long-term use: "Cymbalta is indicated for the treatment of major depressive disorder (MDD). The efficacy of Cymbalta was established in four short-term and one maintenance trial in adults [see Clinical Studies (14.1)]."

[1]http://www.ncbi.nlm.nih.gov/pubmed/16027559

[refurb]

As far as I know, US laws require that the `x` number of trials demonstrate the effectiveness of the drug and failured dont need to be reported.

That is not correct. When you submit an NDA to the FDA, you need to include every piece of clinical trial data you've obtained so far. This includes trials that you've either ended early or failed to show any effect at all.

The FDA doesn't look kindly upon a company that hides any clinical trial data.

How many years exactly does one need to subvert the market so that a satisfactory level of innovation is maintained ?

We have some data on that, but we can't predict the future. I can't find the stat right now, but only about 1 in 3 drugs approved by the FDA actually produce an overall positive return.

[euroclydon]

> even if I have a coin biased badly against coming up heads, if I toss it enough number of times I will get `x` heads.

I'm pretty sure a "trial" is a statistically significant study of many patients. So in this case, your analogy to the coin is flawed. A better analogy would be x groups of 10,000 coin flips, and to take the average of each group in x. Now, no such average would favor the less probably side of the coin.

[srean]

No, grouping over many patients does not eliminate the loop hole at all. The 'coin' was my analogy for the event that a trial was deemed successful (according to some statistical test of hypothesis). If all that I need is to demonstrate is 2 trials that show statistically significant benefits, I can do that expenses permitting (unless the probability of benefit using my candidate drug is exactly 0). The key is that I am allowed unlimited trials where my candidate may not only show no statistically significant benefit but also show worse performance. If only the decision to accept my candidate is based on all the trials together is this hole plugged. My understanding is that FDA does not do this. 2 strikes and you are in, regardless of failure in the other trials.