Today's Wall Street Journal had a front page article on how Bayer could not replicate the results of 64% of 67 studies published in academic journals in trying to develop drugs based on what the journals said worked. Of particular interest to me was how Angen was going to develop a new cancer drug based on blocking the STK33 protein to deal with KRAS gene cancer because of studies published by Harvard Medical School in 2009 in the "prestigious journal Cell". After six months and a full team of researchers working on it, could not reproduce the results. In fact, the control group of cells had the same cancer growth as the blocked cells. The Harvard researcher has moved to Germany where she continues to claim that she can reproduce her results even though nobody else can.
According to the article, this is ultra common and that almost none of the cancer TX highlighted in the papers ever work out. The on line article is behind a pay wall and even though I'm a subscriber, I'm blocked from it for some reason.
There are lots of reasons, but WSJ speculates it is that the academic study authors, unlike pharmaceutical companies, rarely conduct experiments in a "blinded" manner. This makes cherry picking statistical findings that support a positive result more likely. As a result, the success rate of Phase 2 human trials -where a drugs' efficacy is measured, has fallen to 18% from 28% in the last two years.
The WSJ article is more nuanced than my summary
Charm

After a day of email exchanges of WSJ canned emails from tech support that gave contradictory reasons that I patiently but with increasing sarcasm pointed out; I lucked out and a techie actually read my diagnosis of the problem (the log at the authenticating server had not been updated -something that happened daily at my old IT shop) and fixed it.
Here is the fuller excerpt although I can not link thru the pay firewall and share the article (it is very nice technology when it works) This should also be out in Science magazine now.
[quote]When companies trying to find new drugs come up against the nonreproducibility problem, the repercussions can be significant.

A few years ago, several groups of scientists began to seek out new cancer drugs by targeting a protein called KRAS. The KRAS protein transmits signals received on the outside of a cell to its interior and is therefore crucial for regulating cell growth. But when certain mutations occur, the signaling can become continuous. That triggers excess growth such as tumors.

The mutated form of KRAS is believed to be responsible for more than 60% of pancreatic cancers and half of colorectal cancers. It has also been implicated in the growth of tumors in many other organs, such as the lung.

So scientists have been especially keen to impede KRAS and, thus, stop the constant signaling that leads to tumor growth.

In 2008, researchers at Harvard Medical School used cell-culture experiments to show that by inhibiting another protein, STK33, they could prevent the growth of tumor cell lines driven by the malfunctioning KRAS.

The finding galvanized researchers at Amgen, who first heard about the experiments at a scientific conference. "Everyone was trying to do this," recalls Dr. Begley of Amgen, which derives nearly half of its revenues from cancer drugs and related treatments. "It was a really big deal."

When the Harvard researchers published their results in the prestigious journal Cell, in May 2009, Amgen moved swiftly to capitalize on the findings.

At a meeting in the company's offices in Thousand Oaks, Calif., Dr. Begley assigned a group of Amgen researchers the task of identifying small molecules that might inhibit STK33. Another team got a more basic job: reproduce the Harvard data.

"We're talking about hundreds of millions of dollars in downstream investments" if the approach works," says Dr. Begley. "So we need to be sure we're standing on something firm and solid."

But over the next few months, Dr. Begley and his team got increasingly disheartened. Amgen scientists, it turned out, couldn't reproduce any of the key findings published in Cell.

For example, there was no difference in the growth of cells where STK33 was largely blocked, compared with a control group of cells where STK33 wasn't blocked.

What could account for the irreproducibility of the results?

"In our opinion there were methodological issues" in Amgen's approach that could have led to the different findings, says Claudia Scholl, one of the lead authors of the original Cell paper.

Dr. Scholl points out, for example, that Amgen used a different reagent to suppress STK33 than the one reported in Cell. Yet, she acknowledges that even when slightly different reagents are used, "you should be able to reproduce the results."

Now a cancer researcher at the University Hospital of Ulm in Germany, Dr. Scholl says her team has reproduced the original Cell results multiple times, and continues to have faith in STK33 as a cancer target.

Amgen, however, killed its STK33 program. In September, two dozen of the firm's scientists published a paper in the journal Cancer Research describing their failure to reproduce the main Cell findings.

Dr. Begley suggests that academic scientists, like drug companies, should perform more experiments in a "blinded" manner to reduce any bias toward positive findings. Otherwise, he says, "there is a human desire to get the results your boss wants you to get."

Adds Atlas' Mr. Booth: "Nobody gets a promotion from publishing a negative study." [/quote]

Very interesting - thanks for sharing that. This is not the first targeted therapy that has been a bust but, IMO, targeted therapy will be the 4th treatment choice, in the future, once they finally unlock the secrets to it.

The advantage of the type of whitepaper data, published by the researcher, from a regulatory perspective, would enable them to get a "fast track" with the FDA for an NDA (New Drug Approval). This is the fastest way to conduct the different tracks to validate safety and efficacy. It is typically only granted for treatment of life threatening or incurable diseases. Double blind studies would be part of the data required by the FDA in the first phase of testing. The FDA actually has to ok the clinical trial protocols, is proactive in them and frequently changes them based on preliminary test results, data, etc. This is also the reason that some drugs are removed from the market after their approval by the FDA. Typically it takes about 10 years for a new drug to get FDA approval, if not on the fast track, and even longer for OTC drugs.

It may appear to look insidious that the researcher moved to Germany but in reality this happens quite often as the EU is less stringent on testing on human subjects. Quite a few clinical trials are done in Europe. Our litigious society stymies human trials very often in the US. Besides, nobody wants the placebo!

Also, most drugs (and their indications for use) are found by "accident" anyway. It is very bold to target a specific condition.

I don't really pay a lot of attention to preliminary data based on animal studies, which most of the raw data is based on. It does make for sensational headlines on slow news days (and is a welcome departure from politics ;-)