GlaxoSmithKline executive German Pasteris is in charge of an Alzheimer's treatment that is years from reaching the market, if it ever does. But he already wants to make sure the global healthcare system will pay for it.

Pasteris is one of 25 executives appointed last year to shepherd the British drugmaker's experimental medicines. He consults insurance companies and former officials from national health agencies about the Alzheimer's drug on the best way to show its value to patients.

In the past, that meant proving that a drug worked, and did so safely, so that health regulators would approve it. But as governments in the United States and Europe look to slash spending and avert a debt crisis, Glaxo and its rivals want to make sure their medicines are a must-have for patients.

To do it, they are seeking input from the people who hold the purse strings earlier than ever in the clinical research process, in some cases five years or more before regulators would even look at a product, executives told Reuters.

"The ultimate goal was not optimal reimbursement and access," Pasteris said. "Today it is."

These views are shaping more clinical trials, such as which products to test against and study goals to pursue. And that's having major ramifications for the business of Big Pharma.

"If you're going to go out there with a drug that you don't know whether it's better than what's out there, what are you trying to do? Who are we all trying to kid?" said Angus Russell, CEO of British drugmaker Shire. His company has more than doubled its "pharmaco-economic" staff focusing on the value of medicine in the past few years.

Russell said companies "all over the industry" are dropping experimental products they fear will not gain strong reimbursement. For example, Glaxo abandoned a diabetes treatment in mid-stage development in 2009.

Pharmaceutical investors are also a huge source of pressure, with little forgiveness on Wall Street when it comes to medicines that cost hundreds of millions of dollars to develop, but do not get widely used once they reach the market.

Even smaller players are changing their ways.

Ron Cohen, CEO of Acorda Therapeutics, regrets not consulting insurers early about its Ampyra, the first drug to help multiple sclerosis patients walk better.

Now, Acorda plans to hold discussions with health insurers once products reach mid-stage development and is getting informal input earlier -- including for a potential multiple sclerosis treatment yet to enter human testing.

"I have no question that the entire industry is moving toward this sort of model," Cohen said.

As drug manufacturers invite marketing input earlier than before, some fear they risk the very innovation that leads to landmark new medicines.

Industry experts point to advances that took time to prove their worth or worry that drugmakers may abandon categories where "good enough" medicines already exist, like depression, partly because it's not worth the economic risk.

"There is a concern that in five, 10 years we won't have anything really new for patients with major mental illnesses, and that would be absolutely a tragedy," said Dr. Alan Schatzberg, former president of the American Psychiatric Association. "It's an unfortunate outcome that we are slowing drug development."

Glaxo, which brought antidepressants Paxil and Wellbutrin to market, is one company to pull away from the field. Atul Pande, who leads Glaxo's neuroscience research, says the science has not advanced enough to identify new ways to significantly improve treatment, but he acknowledged the reimbursement fears.

Closer Ties

In this climate of soaring healthcare costs, the drug industry has been sharply criticized for launching expensive new medicines that proved only slightly better than their predecessors. Health insurers and government agencies pushed back, and now drug companies are forging closer ties with those "payors".

This year alone, Pfizer allied with insurer Humana to research elderly health; AstraZeneca and HealthCore, a unit of insurer WellPoint, agreed to study how to economically treat disease; and Sanofi signed on pharmacy benefit manager Medco Health Solutions Inc.

Sanofi may soon overtake Pfizer as the world's top drugmaker. CEO Chris Viehbacher says the industry's new crop of drugs must demonstrate "why is this better than what we've already got."

"In defining value - in whose eyes? So you need a payor perspective," he said.

A closer relationship to payors allows access to vast databases of medical claims to see how drugs are used once they are approved. Drugmakers can learn which medicines they should be comparing their own products to and what goals they should seek in clinical trials.