Let's say you run a drug company that's developing a promising new therapy for heart disease or brain cancer or hypertension. As most people know, the process of bringing that drug to market takes years and lots of money. The success rate is generally low. And there's no hope of selling it to the public until it has been thoroughly tested on perhaps thousands of volunteers in a rigorous, randomized clinical trial.

But what if you can't find enough volunteers?

This isn't a theoretical question. The number of people who are appropriate research subjects and willing to spend the time, unpaid, to test new therapies has declined sharply even as trials have become more complex and the Food and Drug Administration, among others, has demanded more data. More than 10 percent of trials in a sample taken in 2011 failed because researchers were unable to recruit even a single test subject.

Volunteer enrollment for the period 2oo4-2007 is down 16 percent when compared with enrollment in studies conducted between 2000-2003, according to the Center for Information and Study on Clinical Research  Participation (CISCRP), an independent nonprofit group.  Retention of people who volunteer for studies has dropped 21 percent in the same time.

"Part of it is that more [people] are being excused excluded than used to be," said Terri Hinkley, deputy executive director of the Association of Clinical Research Professionals, which represents 14,000 researchers, coordinators and study monitors around the world. Another problem, Hinkley said, is low public awareness of clinical trials, especially among minorities.

African-Americans make up only 5 percent of volunteers in trials, despite comprising 12 percent of the U.S. population. Hispanics are just 1 percent of volunteers, though they are 16 percent of the population. Mistrust still lingers among blacks as a result of the infamous Tuskegee experiment when the U.S. Public Health Service failed to treat men with syphilis it was studying for 40 years, Hinkley said.

The total number of registered studies listed on clinicaltrials.gov, which is run by the National Institutes of Health, rose from 5,636 in 2000 to 159,188 in 2013, in part because of new registration requirements. (The diamonds refer to the times when the requirements were expanded by medical journal editors and the FDA).

Many new medications must be tested on thousands of volunteers when they reach the third phase of testing. Those subjects first must be screened to make sure they have no other health problems or confounding issues that should keep them out of a study. Lipitor, which is used to treat high cholesterol, was tested on 20,000 people over 2 1/2 years, according to CISCRP. The allergy medication Allegra was in clinical trials for two years and tested on 3,600 people.

Researchers rely on physician referrals and various forms of advertising to recruit subjects for the four phases of research, but cannot pay people who enroll in Phase Three studies, the large clinical trials held before a therapy can be brought to market, because doing so could affect results. Drug companies and others have stepped up their outreach in recent years, particularly to minorities and women, in the hope of  recruiting people who have not traditionally volunteered.

"We have to rebuild some trust and have to rebuild our network," Hinkley said, with an emphasis on getting primary care physicians to refer their patients to clinical trials.