The FDA provides little oversight of clinical trials conducted in the U.S., the Department of Health and Human Services Office of Inspector General (OIG) reported Friday.
The agency inspects only 1 percent of the estimated 350,000 U.S. clinical trial sites, the OIG said. Because of a lack of an internal clinical trial registry, the FDA is unable to identify all ongoing clinical trials, the inspector general reported.
Congress attempted to remedy that problem by passing legislation on Sept. 21, enacted on Sept. 27, that requires the FDA to build such a registry. However, the lack of a clinical trial registry is not the agency's only problem, the OIG said, noting that regulators are inconsistent in the manner in which the FDA tracks inspections of trial sites.
Even though the agency has six databases to track clinical trial inspections, none of those systems include complete information, and the FDA inconsistently classifies inspections, the inspector general said.
To better coordinate and track inspections, the OIG recommended that the FDA create a "cross-center database" that includes "timely and complete information."
The OIG also criticized the FDA for failing to have a registry of institutional review boards (IRBs). "By identifying all IRBs overseeing clinical trials, FDA could target IRBs more effectively for inspection," the inspector general told regulators.
The FDA depends on 200 bioresearch monitoring investigators to conduct trial site inspections, the OIG said.
Bioresearch monitoring inspections are not required by federal regulations, the OIG noted, adding that the FDA decides when to assign them. In most cases, the FDA warns violators of the need to correct an action at a clinical site by sending a letter.
In fact, of the 348 clinical site violations found by regulators between 2000 and 2005, the FDA used a warning letter in 244, or 70 percent, of the cases as its form of action.
The agency then relies on the sites to voluntarily notify the FDA when a violation has been fixed.
However, the OIG said, the FDA rarely conducts follow-up inspections to ensure violators have complied, and when regulators do conduct inspections, they fail to properly document them.
The OIG also noted that the FDA conducts most of its inspections of clinical trial sites after a study has been completed. "In light of this, FDA cannot ensure that sponsors, clinical investigators, and IRBs are taking the necessary actions to protect human subjects during the trials," asserted Sen. Charles Grassley (R-Iowa), ranking member of the Senate Finance Committee and the lawmaker who called for the OIG investigation.
In a letter sent last week to FDA Commissioner Andrew von Eschenbach, Grassley noted that after investigators have identified a serious violation at a clinical trial site, regulators at the Center for Drug Evaluation and Research (CDER) often "downgrade" that violation to a lesser charge.
"To add insult to injury, CDER would make these downgrade changes without systematically tracking its reasons for the change," Grassley charged.
He demanded to know what the agency was doing to ensure that "corrective actions are taken and sustained" by clinical trial sites that violate government regulations.
Grassley also insisted on knowing the status of a rule proposed by the FDA in June 2006 regarding the reporting of clinical trial fraud.
In his letter to von Eschenbach, Grassley noted that he has been investigating circumstances surrounding the FDA's April 2004 approval of Ketek (telithromycin), an anti-infective marketed by Sanofi-Aventis for pneumonia, and false data that was submitted as part of a clinical trial used for the approval of the drug.
Alabama physician Maria Anne Kirkman-Campbell was charged on Aug. 29, 2003, with falsifying clinical trial data in study 3014, a randomized, open-label comparative study of Ketek.
She pleaded guilty to one count of mail fraud and was sentenced on March 25, 2004, to 57 months in federal prison and was fined $557,251. Kirkman-Campbell also was ordered to pay restitution of $925,774 to Sanofi-Aventis.