Compliance Corner: Complaints about FDA investigators are on rapid rise, raising concerns
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Complaints about FDA investigators are on rapid rise, raising concerns
Protocol deviation is biggest area of complaint
The Food and Drug Administration (FDA) has collected complaints about investigators for decades, but a look at the volume of complaints within the past eight years shows there are major compliance concerns at present.
"The rate of noncompliance continues to rise sharply," says Ken Getz, MBA, MS, a senior research fellow at Tufts Center for the Study of Drug Development, Tufts University in Boston, MA. Getz spoke about FDA compliance complaints at the 42nd Annual Meeting of the Drug Information Association, held June 18-22, 2006, in Philadelphia, PA.
Up until 1998, the FDA typically received about 10 complaints, annually, against investigators for noncompliance and fraud, Getz says.
Then in 1999, there was a 10-fold jump to 106 complaints. It's been uphill ever since, with the number of complaints reaching 266 in 2005, Getz says.
"It continues to rise every single year, so we have to think through what are some of the drivers of noncompliance and fraud," he says.
The rapid rise in complaints has changed the way the FDA investigates clinical trial sites, Getz notes.
"In the past, the FDA-conducted inspections primarily were driven by routine and unsolicited activity," he says. "But when the FDA receives a complaint, the agency takes it very seriously and treats these complaints as a priority."
So there's been a shift from inspections: prior to 2000, FDA inspections were mostly routine, and since 2000, they are mainly complaint-driven; this suggests the FDA's mindset also has shifted, Getz says.
"It's moved from a 'Let's see what we can uncover during a routine inspection,' to 'We're out here because they're guilty until proven innocent,'" Getz explains.
Another shift has been in who is making the complaints.
In early 2000, about one-third of all complaints were anonymous, and the largest portion of complaints came from site personnel, Getz says.
Now, only one in 10 complaints are anonymous, and 29 percent, which is the largest portion, come from IRB professionals, he says.
"The vast majority of the complaints are aimed at the investigator who signed the 1572 form, which is required by law for the investigator to complete before administering the study drug," Getz says.
Here are the other main sources of complaints to the FDA:
- 19 percent—site personnel, including study coordinators and administrative staff;
- 12 percent—sponsors or clinical research organizations;
- 9 percent—anonymous complaints, which might include disgruntled employees.
The shift from site personnel to IRB professionals in landing the top spot for filing complaints has occurred during an era of greater pressure being placed on IRBs, Getz notes.
"There is tremendous pressure on the IRB to demonstrate that it is being effective in monitoring compliance," Getz says. "So I think the IRBs have been sensitized to being even more careful to police human subject protections."
The industry buzz is that IRBs are overworked and overtaxed, working over capacity. IRB professionals take that criticism seriously and feel they have to be as careful as they can be, he says.
In 2005, the top complaint filed with the FDA was for protocol violations, which were cited on 34 percent of the complaints, Getz says.
Here are the other categories listed on FDA complaints:
- 27 percent — falsification of data;
- 12 percent — poor drug accountability;
- 10 percent — informed consent noncompliance;
- 8 percent — poor adverse event reporting.
"IRBs may be making the informed consent and adverse event reporting complaints," Getz says.
Similar complaint data from the Office of Human Research Protection (OHRP), covering complaints made between 1998 and 2002, finds that one-third of the complaints involved deficient IRB review, and 27 percent were about poor record keeping or reporting, Getz says.
"OHRP reports that one out of every five complaints they receive is for research conducted that has not yet received IRB approval," Getz says. "Some of these might be behavioral studies or studies where the investigator didn't think he or she needed approval."
Nonetheless, when pharmaceutical and clinical trial industry professionals hear the FDA and OHRP statistics, they typically are surprised, Getz says.
If they want to reduce noncompliance and reverse the FDA's complaint trend, then both clinical trial sites and sponsors should focus on investigator and trial staff training and education, Getz suggests.
"What the statistics tell me is we have to choose places to invest resources to reduce noncompliance, and we have a pretty clear roadmap," he says. "GCP and study management training need to be more effective."
Although sites might say their training and regulatory requirements are quite onerous, perhaps one of the problems is that the training is not tailored to the experience level of investigators, Getz says.
Instead of having experienced sites repeat the same training program annually, why not give them the option of undergoing training every three years, while giving novice investigators and sites additional training, he suggests.
"We need to re-evaluate the training and move inefficiency and redundancy out of it so it will be practical for investigators," Getz says. "We also need to simplify some of the guidelines to make those that relate to current compliance issues as effective as possible."
The Food and Drug Administration (FDA) has collected complaints about investigators for decades, but a look at the volume of complaints within the past eight years shows there are major compliance concerns at present.Subscribe Now for Access
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