Concerned that too few new drugs are reaching the market and too much time is spent testing those that ultimately fail to win approval, the Food and Drug Administration announced rules Thursday for human testing that are intended to get effective drugs to the public more quickly, and possibly more cheaply.
Under the new guidelines, investigators will be allowed to give minute doses of experimental drugs to people earlier in the development process to see if the results are promising enough to warrant going forward with costly, full-scale clinical testing.
The FDA action was welcomed by scientific researchers and the drug industry. But some agency critics said they were concerned it could increase hazards for volunteers in clinical trials or facilitate the approval of drugs before their risks were understood.
The new system is designed to deal with a problem that not only has slowed getting helpful medicines to patients but has added billions of dollars in potentially avoidable expenses to the cost of prescription drugs.
Before a new drug can be put on the market, scientists must prove that it is effective and safe; of the thousands of compounds that researchers test, only a handful ever make it to the pharmacy shelf.
Over the last few years, FDA officials and others have noticed a pattern: Not only have fewer drugs made it through the required screening, but many of those that ultimately proved unfit for the market were eliminated near the end of the long development and testing process; they had failed to win approval after months or years, and after hundreds of thousands -- or sometimes millions -- of dollars had been spent.
Since testing costs on failed drugs cannot be recovered from sales, manufacturers pass them onto consumers in the form of higher prices for medicines that do make it to the market.
The FDA's new system is designed to help scientists more quickly identify the drugs that will turn out to be unmarketable.
Pharmaceutical research and development spending increased by about 250% in the last decade, approaching $39 billion last year. But the number of new drugs submitted for FDA approval went down during that period. Last year, for example, the agency approved 20 new drugs, compared with 36 in 2004.
"Drug development is very, very high-risk, and the failure rate is still too high," said Dr. Raymond Woosley, president of the C-Path Institute, a nonprofit organization based at the University of Arizona that aims to speed the development of drugs without compromising safety. "This is an important step toward getting greater efficiency and more modern science into the drug development process."
The FDA guidelines would enable researchers to test a "micro-dose" of an experimental drug on a small number of human volunteers to see how their bodies reacted. Such testing would replace some, though not all, of the early experiments now carried out on animals.
The results are expected to be more accurate than animal testing in predicting which compounds should go to full-scale clinical trials, used to establish whether a drug is safe for humans, its appropriate dosage and its effectiveness against a placebo.
The FDA's action did not affect the full-scale tests. But critics of the agency and the drug industry saw a potential danger in the guidelines.
"Last time they speeded up the process of drug approval it led to the approval of lethal drugs," said Vera Sharav of the Alliance for Human Research Protection, a patient advocacy group based in New York. "Now they are trying to fiddle around with the [earliest phase of] trials? Those, by definition, are the highest-risk."
The FDA already has a system for accelerated approval of drugs that show promise in the course of full clinical trials, said Dr. Sidney Wolfe of Public Citizen, a consumer advocacy group that frequently criticizes the FDA. He questioned whether the agency had a strong enough scientific argument for speeding the early stages of drug research.
Acting FDA Commissioner Dr. Andrew C. von Eschenbach said the agency had laid down rules to protect people who volunteered for such experiments and to make sure they were informed of potential risks. Some of the volunteers are expected to be patients with advanced forms of cancer and other serious illnesses.
Nine of every 10 experimental drugs, von Eschenbach said, fail in human studies. Drugs "behave differently in people than in animals," he said.
The FDA is "trying to remove some of the hurdles from the earliest phases of drug testing and development so researchers can more rapidly establish whether a new compound has benefits for people," he added.
Under the guidelines, the doses used in early human testing would be so small that they should not cause any ill-effects or benefits, Woosley said. But researchers would be able to gain useful information about how the experimental drug behaved in the body, he said.
In the case of a cancer drug, for example, they could learn through a biopsy whether it reached the site of a tumor.
"A micro-dose is about one-hundredth of the dose that would have any chance of doing anything," Woosley said. "With modern analytical techniques, you can find out if it went to the place where you want it to do its work. You can learn how long it stays in the body, without ever having to give a potentially effective or toxic dose. You are just much more intelligent about the drug when you decide whether to go to clinical trials."