"C" for clinical trial

臨床試驗

It is well known that clinical trial is an extremely expensive business.

Researchers involved in drug discovery are working hard each day to predict and extrapolate their preclinical trial data in order to ensure the compound they discovered to survive in clinical trials.

However, there are some interesting points that I read in ScienceDaily.com recently which could be helpful in explaining some failures in clinical trials.

For cancer cells, genetics alone is poor indicator for drug response

"Genetics are permanently heritable, while these protein levels are temporarily heritable," says Sorger. "But this temporary inheritance can make all the difference in the world when it comes to the effectiveness of certain medications."

"We knew that there were clearly factors at work here that were not genetic," says Spencer. "Genetic resistance would remain uniform in subsequent generations. But the factors at work here were clearly more dynamic."

"For decades biologists have had this notion that cells produce proteins in orderly, uniform ways, like an assembly line, but they don't," says Sorger. "Rather, cells produce proteins in fits and starts, and the timing and degree varies from one cell to the next—even cells that are identical in every way. This randomness is something that we're just beginning to appreciate."

Harvard Medical School (2009, April 14). For Cancer Cells, Genetics Alone Is Poor Indicator For Drug Response. ScienceDaily. Retrieved May 4, 2009, from http://www.sciencedaily.com­ /releases/2009/04/090413083417.htm

Just as no two humans are the same, a Purdue University scientist has shown treating mice more as individuals in laboratory testing cuts down on erroneous results and could significantly reduce the cost of drug development.

Mice have long been used as test subjects for treatments and drugs before those products are approved for human testing. But new research (done by Joseph Garner, a Purdue assistant professor of animal sciences, and professor Hanno Würbel of the Justus-Liebig University of Giessen in Germany) shows that the customary practice of standardizing mice by trying to limit environmental variation in laboratories actually increases the chance of getting an incorrect result.

"In lab animals, we have this bizarre idea that we can control everything that happens," Garner said. "But we would never be able to do that with humans, and we wouldn't want to. You want to know if a drug is going to work in all people, so you test it on a wide range of different people. We should do the same thing with mice."

Garner said human testing uses a broad range of subjects, giving scientists an idea of how a drug or treatment might affect different types of people. But scientists often use mice that are basically genetically identical and try to limit internal and external environmental factors such as stress, diet and age to eliminate variables affecting the outcome.

Purdue University (2009, March 31). Mice And Humans Should Have More In Common In Clinical Trials. ScienceDaily. Retrieved May 4, 2009, from http://www.sciencedaily.com­ /releases/2009/03/090330142422.htm

The mouse is a stalwart stand-in for humans in medical research, thanks to genomes that are 85 percent identical. But identical genes may behave differently in mouse and man, a study by University of Michigan evolutionary biologists Ben-Yang Liao and Jianzhi Zhang reveals.

"Everyone assumes that deletion of the same gene in the mouse and in humans produces the same phenotype (an observable trait such as presence or absence of a particular disease). That's the basis of using the mouse to study human disease," said Zhang, an associate professor of ecology and evolutionary biology.

"Our results show that may not always be the case." "To our surprise, 22 percent of the 120 human essential genes are nonessential in the mouse," Zhang said. "I expected there would be some, but I never expected the percentage to be so high."

University of Michigan (2008, May 15). Mice Can Do Without Humans' Most Treasured Genes. ScienceDaily. Retrieved May 4, 2009, from http://www.sciencedaily.com­ /releases/2008/05/080514124110.htm

Have you ever wonder is there any connection between the failure of a drug or compound in clinical trials with the price of a marketable drug?

Perhaps, this would trigger you to think about it......

When mouse testing creates a false positive, leading a researcher to believe a drug has worked, the drug could be sent to further animal testing and human clinical trials at a cost of millions of dollars. Drugs that fail in clinical trials cannot be marketed, and the money is wasted. To recoup those losses, drug companies must increase the costs of marketable drugs.

"Drugs aren't expensive because they're costly to make," Garner said. "They're expensive because the company has to recoup the costs of the other drugs that have failed in human clinical trials. Numbers are hard to estimate, but for every drug that reaches the marketplace, well over 100 have been abandoned at some point in their development." Purdue University (2009, March 31). Mice And Humans Should Have More In Common In Clinical Trials. ScienceDaily. Retrieved May 4, 2009, from http://www.sciencedaily.com­ /releases/2009/03/090330142422.htm

So, what is your comment??????