Clinical Sites Need Documented Electronic Compliance Programs

May 23, 2006

Clinical trials sponsors considering a potential clinical site can gauge whether a site has a strong edata compliance programit by how well it documents training and standard operating procedures (SOPs), said an industry expert.

“I’m not suggesting that if [a site] doesn’t have a compliance program they aren’t ethical, but [without a documented program] how can they demonstrate it” to a sponsor, Yvonne McCracken, chief operating officer at Carolinas Research Associates said to attendees at the Association of Clinical Research Professionals (ACRP) conference in Phoenix.

The good news for sites is that sponsors aren’t demanding “bells and whistles” in a clinical program. They just want something solid, she said.

When it comes to developing good SOPs, it is not necessary to get them all done at once, McCracken said. “Start with one and build on it,” she advised. Unfortunately, many sites are “afraid of SOPs” in part because they get overwhelmed and think they are more complicated than they really are. But starting with SOPs at the outset can speed a trial and reduce wasteful back-and-forth queries, she noted.

Sponsors also expect sites to have a documented, effective compliance program that travels throughout the company culture. “The company culture must honor the program, otherwise it won’t be successful,” she said.

With increasing regulatory and financial pressure to get trials done right, computer system validation at the site level is becoming more and more important to sponsors, McCracken said. Even though 21 CFR Part 11 is not “totally finished,” the FDA still expects clinical trials to be conducted in such a way that their data is secure, she said.

Trial oversight cannot be overlooked in a compliance program. Sponsors should determine who at a trial site reports to whom regarding quality assurance (QA) issues, McCracken said. It is better if the QA person reports directly to management and not to the people he or she may be auditing internally, she added.

Auditing is a big piece of the QA puzzle. If it is done properly, it should be able to tell the site and the sponsor early on if there are problems. It can also alert sponsors and sites quickly if training has been weak or insufficient, she added.

In addition, effective auditing can cut the length of monitoring visits by a third, McCracken said. Monitoring visits are important, however, because they allow sites to respond more quickly to questions and concerns raised by a sponsor.

Enforcement Consequences

Finally, no compliance program is complete without clear enforcement components. “No one likes to think about it,” McCracken admitted. But an important part of the compliance program and its SOPs is clearly highlighting what is expected and what the consequences are for failing to meet the trial standards, she said. Part of that enforcement SOP should detail who at the site is charged with responding to FDA or sponsor queries. For sites, a slower response time does not inspire confidence in those asking the questions, she noted.

The value of SOPs is even more critical since many site investigators are inexperienced in conducting clinical trials, noted Michael Jay, director of Grants and Budgets at Rx Trials Institute. In fact, more than 60 percent of investigators have conducted only one trial or have been involved in conducting trials for less than one year, according to research conducted by Rx Trials. “This is a pretty green industry,” he said.

And a 2001 FDA report concluded 70 percent of site deficiencies can be traced back to investigator noncompliance, McCracken noted. “Source documents are not being organized or are inaccurate,” she said. Preventive SOPs can enhance a compliance program and help investigators, she added. — Michael Causey