Cheaper, big populations of treatment naive patients, the future of pharma sales in these countries plus motivated investigators who can sometimes double their salaries and access to top science and free drugs, government support (faster approvals, less bucreaucracy, even grants)-- sounds almost too good to be true. And it is... people are now asking questions like:

Is the quality of the data as reliable as that from a top U.S. medical center?

Is it safe to extrapolate common clinical effects from studying patients with different lifestyles and genetic profiles?

Are ethical standards in testing new drugs properly upheld in poorer countries?

In the United States, in 2008, 78% of all subjects participating in trials to support drug applications submitted to the FDA were enrolled at foreign sites. In Europe, 61% of patients in pivotal trials submitted to the EMEA between 2005 and 2009 come from third countries. A further 11% of patients were enrolled in studies in Eastern European countries that are now members of the European Union. The number of Polish patients involved in such trials rose fivefold over the period, while Hungary was up 3-1/2 times. However the number of research sites actually inspected by EMA or FDA officials remains "tiny." Between 2005 and 2009, EMEA dealt with data linked to pivotal studies from 44,034 clinical trial sites, but it carried out only 44 cGCP inspections outside Europe and North America. The U.S. FDA, meanwhile, inspected 0.7% of foreign clinical trial sites in 2008, against 1.9% of domestic sites.

Why this fuss now ? High profile AZ's Brilinta -- a potential megablockbuster has been
been approved in more than 30 countries, including the EU, but has been delayed in the US. While the big trial known as PLATO (18,000-patient trial) found Brilinta was clearly superior to Plavix at preventing cardiovascular deaths globally, people in North America actually seemed to do worse on the new drug. (Poland and Hungary together accounted for 21% of all subjects studied in the trial -- more than double the United States and Canada combined.)

Why did North American patients do worse ?

One theory is that U.S. heart patients get given more aspirin alongside other medicines and this may somehow interfere with Brilinta's effectiveness. But this might just be chance, since the North American sub-group accounted for only 9.7% of patients and too small to draw any statistically sound conclusions. What now? We'll know on the 20th July.

What do others say?

Dr. Rory Collins, a professor of medicine at the University of Oxford and co-director of its Clinical Trial Service Unit, is a big fan of the power that Chinese clinical research can bring to medicine and is deeply impressed by how far the country has come in two decades.

6 years ago, Collins's Oxford team led a huge 46,000-patient study in China to test the blood thinner Plavix and a beta-blocker in the emergency treatment of heart attacks. They found that adding Plavix to aspirin produced further benefit, while the beta-blocker metoprolol did not. That important discovery has since gone on to influence medical practice around the world.
"That study would never have been done if we couldn't have run this very streamlined trial in China at very low cost," says Collins, who is currently working on another pivotal heart drug study for Merck that contains no U.S. patients.

"My preference would be not to do any trial in North America because it is so inefficient and so costly." Western Europe may be a bit better but Collins and many other researchers are highly critical of the bureaucratic obstacles there as well, following the introduction of the European Union's 2004 clinical trials directive, which has led to a mountain of extra paperwork for each trial. The aim of the EU directive is to harmonize standards and protect subjects.

So how much cheaper? Back in 2008, ex GSK CEO Jean-Pierre Garnier said a midsize company with 60,000 patients in clinical trials could save $600 million a year by switching 50 percent of its trials to low-cost places such as India and Latin America. A top-rate academic medical center in India would charge just $1,500 to $2,000 per patient case report, while a second-rate U.S. center would bill $20,000, he said.

In practice, things are a bit different, according to Kenneth Getz, senior research fellow at the Tufts Center for the Study of Drug Development in Boston. Getz reckons the per patient cost of running a trial in India and China is probably about half what it would be in Western Europe or the United States -- a big margin, of course, but considerably less than Garnier had suggested. And then there is the considerable extra cost of managing multiple studies across myriad sites and the increased operating costs and the inefficiencies, which can sometimes result in delays in some parts of the world.Reputational issues

http://www.reuters.com/article/2011/05/06/us-pharmaceuticals-trials-idUSTRE7450SV20110506 ( Reuters)