Protecting the ‘lab rats’ in for-profit trials

While waiting to hear from graduate programs, recent University of Illinois at Chicago graduate Daniel Keltner, 26, makes his living participating in research studies.

But the man who has taken morphine derivatives and had researchers tinker with his sleep schedule said he would be reluctant to participate if a major drug company were involved.

"I would be wary of it just because if it's going to be by some pharmaceutical company, or whatever, obviously they're testing something new. It's experimental," said Keltner, of Palos Heights. He has been paid a combined $4,400 for his tests.

The history of clinical testing on human subjects has its share of horror stories, from the 1932-1972 Tuskegee tests that denied black men treatment for syphilis to more recent examples, such as the Prodisc lawsuits this year and last, in which it was revealed about half of the researchers were in a position to benefit financially from the artificial spinal disk's approval.

Less publicized are the thousands of clinical trials each day that save lives, result in new, powerful treatments or, as with the studies Keltner joins, simply result in a greater understanding of the human condition.

But the practice of human testing is changing. For-profit contract research organizations are handling more of the testing than ever before. The federal regulations, designed at a time when universities and hospitals handled the lion's share of clinical trials, are not changing and there is increasing concern that financial interests could compromise the integrity of research.

Clinical trials have become a multi-billion dollar industry, with the estimated cost of taking one drug to market between $200 million and $800 million. Today, 70 percent of clinical trials are done in the private sector rather than the traditional hospital or university, according to Gordon Ridley, associate vice chancellor for medical affairs at the University of Wisconsin.

Government agencies provide guidelines to ensure the safety of human subjects, but local boards - an increasing number of which are also private - are the ones reviewing the researchers' plans to protect the test subjects and ensuring that researchers follow the specified guidelines.

Members of for-profit research organizations and review boards say the private sector is helping bring potentially life-saving drugs to the market faster and more efficiently than could a university or hospital, which both are tied down with bureaucracy and hefty workloads.

While the medical community considers how to ensure test subject safety, the number of tests requiring human subjects remains high.

As of Wednesday, the U.S. National Institutes of Health reported that 13,251 studies in the United States were actively seeking volunteer test subjects. There were 1,612 studies looking for participants in Illinois alone.

 Changing market

In 1991, 80 percent of industry clinical trial money went to academic testing facilities, according to a 2000 New England Journal of Medicine article using data from the private Commonwealth Fund.

By 1998, only 40 percent of that money went to academia, with for-profit testing companies growing by leaps and bounds.

In 2001, contract research organizations - often called CROs for short - brought in $7 billion. By 2007, that went up to $17.8 billion, according to another New England Journal article, this time using data from the industry group Thomson CenterWatch.

It is not that the doctors and scientists at CROs are doing lower-quality work than the people behind university or hospital trials, said Dr. Thomas Schnitzer, Northwestern University rheumatology professor. It's what is done with the data when it's time to market the drug.

"The actual quality of [research] work is similar in the two areas," said Schnitzer, who has been involved in studies funded by drug companies and studies funded by universities.

Concerns about financial conflicts of interests have caused major medical journals to require researchers to name potential conflicts of interest before study results are even considered for publication, said Dr. Leo Epstein, deputy director for clinical research at Children's Memorial Research Center

Schnitzer said there is pressure for studies funded by private companies to produce positive results.

However, he said academically funded researchers "also face intense pressure to have positive results, [but] with a different goal."

"Ultimately they [drug companies] want to have a product and academia wants to answer a question, and I think it can lead to bias on both sides," Schnitzer said.

The problems with research funded by for-profit companies, Schnitzer said, come in the interpretation of the data and whether industry is providing a complete account of all the data, particularly when it comes time to market the drug.

"The kinds of things that happen in promotions. that is what is giving industry this terrible reputation in reality," Schnitzer said.

"Private companies have shareholders; part of their mission has to be to earn a profit.  Companies can spend all their time doing good science, but if they don't find a drug to market there is no money," said Epstein.

While the people behind industry studies have millions or even billions of dollars riding on approval, people behind academic studies have their own personal success and career recognition at stake, he said.

Representatives of several Chicago-based private CROs either did not return phone calls and e-mails or declined to comment.

Despite the qualifications and diligence each individual CRO might offer, former "professional guinea pig" Bob Helms said the sheer number of the for-profit companies helped him lie to get into high-paying studies that should have disqualified him.

"The typical routine for a guinea pig is to lie our faces off about when was the last time we did a study," said Helms, now editor of the online magazine Guinea Pig Zero. "They can't verify it one way or the other because they only know their own records of their own company."

Keltner said he could not recall if the studies he participated him in would have paid for his medical care if there were complications. Studies are not required to pay in such cases. As he has no health insurance, this concerned him.

 Procedure

There is a storm of government paperwork dealing with test subject safety.

The Food and Drug Administration has one set of rules; the Office for Human Research Protections, another.

But government regulators are not the ones reviewing a study's safety procedures to make sure they fit with the federal rules. That duty falls to a local institutional review board, or IRB.

Traditionally, a hospital or university would have its own IRB to review all its studies. This came from a desire for local review, rather than waiting for Washington to go through all studies, said OHRP spokeswoman Pat El-Hinnawy.

But the documents attesting to a study's compliance with federal rules do not go to the federal government. Once an IRB completes its review of how researchers plan to ensure subject safety, a report is submitted back to the researchers, not the FDA or OHRP.

"Actually, the documents never go to the government unless the study is audited," said Dr. Angela Bowen, CEO of the private Western Institutional Review Board.

Unless there is a complaint from a subject, academic IRBs rarely follow up to see if the researchers actually put the safety procedures in place, said Dr. Darren Gitelman, chairman of an IRB at Northwestern University.

"Generally, the assumption is that the investigators are doing what they said would be done," Gitelman said.

However, Bowen said that, in the private sector, the market over the last five to six years has led to studies demanding more oversight rather than less.

"Everybody wants to do an audit or everybody wants on-site visits," said Bowen, who founded WIRB 40 years ago. "That's not required by the regulations. It's just something that has become fashionable."

Keltner, however, is not concerned with the tangle of regulations ensuring his safety. He selects his studies based on his comfort level. He said has never felt his health was in danger.

Being a paid test subject has been a "great experience," Keltner said. He recommends it to college students looking to make some money.

"What's the only other option for a college student? Retail," Keltner said laughing.