A timely reminder -- in 2006 Dr Craig Morris produced a frightening summary of the manner in which potentially dangerous drugs and chemicals "slip through" the regulatory system -- occasionally due to scientific fraud by the applicants for approvals, and occasionally due to failures on the part of the regulators. In the Appendix to a letter to Nancy Beck of the Office of Information and Regulatory Affairs, he revealed what can happen when powerful corporations like Monsanto want approvals, when "friendly" laboratories are encouraged to provide the scientific results which they know their clients expect, and when regulators fail to exercise due diligence or are pressurized to speed up the approvals process.............
"The U.S. regulatory system for chemical products is tailor-made for fraud. The subjects are arcane, the results subjective, the regulators overmatched, and the real work conducted by – or for – the manufacturers themselves."
"............. Adrian Gross, an alert FDA pathologist, started asking questions after he saw a rat study of the arthritis drug Naprosyn that looked too good to be true. In the ensuing months, federal regulators found evidence that dozens of its studies had been faked. Among other transgressions, sick animals were listed as healthy or were not included in order to achieve favorable test results. Some reports were total fabrications based on no study at all. Ultimately, hundreds of studies were declared invalid."
"In the report they wrote about the inspection, members of the team said they uncovered evidence that Monsanto, the manufacturer of alachlor and many other toxic chemicals, may have known about the fakery."
“ITB were hell-bent on providing their clients with favorable reports. They did not care about good science. It was about money. They really had what was almost an assembly line for acceptable studies.”
"The investigators said that in one of the studies ..... extra lab mice were added to skew the sample, a bit of trickery that was left out of the final report to the EPA. Even more serious accusations involved two rodent studies of monosodium cyanurate ........ in which inspectors found evidence that missing raw data had been replaced by after-the- fact invented records, that animal deaths had been deliberately concealed, and that the final reports included claims about procedures and observations that never happened."
"In all three cases, the investigators wrote in an internal memo, there was evidence that Monsanto executives knew that the studies were faked but sent them to the FDA and the EPA anyway."
"..........studies with null or negative findings are systematically withheld from publication, while studies with positive findings are not."
"Doses of comparison drugs can be rigged to favor a new drug, and duration of treatment can be carefully selected to favor a new drug. Some studies narrow the range of side effects. Often the principal investigator simply has little role in a study’s design, and just receives prepackaged instructions from the company."
"Since 1990, more major drugs have been withdrawn for substantial unexpected safety problems than ever before in such rapid succession. Sometimes this has been the result of premarketing studies that were too small to detect important but rare side effects. Some of the problems may have stemmed from the FDA’s attempts to speed up its approval process."
"The courts are still considering how much of the Rezulin tragedy was produced by willful malfeasance versus what could be called passive-aggressive surveillance: foot-dragging in following up on signals of a potential hazard. As scores of cases approached trial, the manufacturer’s zeal to protect its molecule instead of patients followed what could be called the FDA defense, a gambit seen in many drug product liability suits. In that strategy, a company maintains a bare- bones adverse- events reporting department, staffed on the front lines by people with little or no training in epidemiology or clinical matters. Once its drug is approved for marketing, the company doesn’t proactively investigate how appropriately it is being used, or what side effects occur in patients who take it. When reports of those adverse events are nonetheless sent in spontaneously by doctors or patients, the company passes them along to the FDA as required by law, with minimal or no further scrutiny. It’s widely known that the FDA division on the receiving end of these reports has traditionally been underpopulated and overworked, partly because of earlier industry opposition to allocating any of its user-fee funds to support those activities. Eventually, if an important side effect does surface, company officials can respond as many have in court, saying, in effect: “We didn’t notice a worrisome pattern. We obeyed the regulations and sent FDA all the reports we received. They never made us do a study, or send out a warning, or take the drug off the market. So it’s not our fault if anyone got hurt.”
"............a U.S. regulatory agency can ignore the latest science, and its own scientific staff, to produce an inflated “cost-benefit” regulatory analysis favoring a particular industry..."
"The Food and Drug Administration is sometimes too slow in picking up safety problems once drugs are on the market and in responding to emerging danger signals, a federal study concluded in a report to be released today."
C. Craig Morris, Ph.D. 15 May 2006 Bureau of Transportation Statistics Research and Innovative Technology Administration US Department of Transportation Washington, DC 20590
Dr. Nancy Beck Office of Information and Regulatory Affairs Appendix A