Health Research Group Urges Prosecution of Abbott Labs for Concealing Death Data on Diet Drug Sibutramine (MERIDIA)

The Health Research Group wrote Department of Health and Human Services secretary Tommy Thompson on May 21, 2002, strongly urging the criminal prosecution of Abbott Laboratories for illegally withholding from the Food and Drug Administration (FDA) important information concerning eight deaths and other adverse effects related to its diet drug sibutramine (MERIDIA). Two months earlier we had petitioned to have this dangerous drug withdrawn from the market (see the May 2002 issue of Worst Pills, Best Pills News).

The basis for asking for the prosecution was an FDA report of an inspection of Abbott’s plant in Abbott Park, Illinois, conducted between March 21 and April 3 of this year which was obtained by the Health Research Group.

The FDA summarized in the beginning of the inspection report that 1) Abbott had filed adverse reaction reports with the FDA which were “either not accurate, not supported by source data, or ... missing additional information found in the source data” and 2) in addition to illegally withholding a report of the death of a patient using sibutramine, obstructed FDA attempts to get an autopsy report on another patient which could implicate sibutramine on instructions from the company’s attorneys.

The complete text of the letter to Secretary Thompson and the FDA inspection reports are available at http://www.citizen.org/publications/release.cfm?ID=7175 or by writing to the Health Research Group at 1600 20th Street NW, Washington DC 20009.

Excerpts from the report that are contained in the letter to Secretary Thompson follow. PLEASE NOTE: all round brackets ( ) that are blank inside, within quotes from the FDA inspection report refer to information removed by the FDA; information within square brackets [ ] are our explanations, based on other parts of the inspection report, about the meaning of the quoted material.

The FDA inspection found that “[one] death associated with Meridia was not reported and several records [involving seven other deaths] reviewed showed that the adverse drug information reported to the FDA was either not accurate, not supported by source data, or was missing additional information found in the source data.”

In addition, FDA inspectors found that “complete case files containing any documentation as to follow-up investigations conducted and information obtained therein [concerning deaths associated with Meridia] were missing.” The FDA also charged that “records relating to all adverse drug experiences known to you [Abbott], including raw data and any correspondence, have not been maintained for the required ( ) year period.”

Information in the inspection report concerning the deaths includes the following five cases. Two other cases had too much material removed to understand what had occurred:

• “ a) ( ) report ( ) documents that a ( ) patient who died several weeks after stopping Meridia was reported to the contract research organization ( ) formerly ( ) by a ( ) sales representative on 11/10/2000, however this adverse event was not reported to the FDA. This ( ) reported was located only after a query for all “deaths” related to Meridia stored on the ( ) computer system was requested to be performed during the inspection. Abbott had not performed this type of query prior to the inspection.”

• “c) ( ) dated 11/22/00, reports the death of ( ) taking Meridia who had adverse events of ( ) and ( ). A source document reports that the ( ) was in ( ) early ( ) and was not known to have any type of ( ). This information was not reported in the MedWatch report [the FDA’s adverse event reporting system].”

• “e) ( ) ed 1/18/99 reports the death of a ( ) patient taking Meridia who had adverse events of ( ). A follow-up MedWatch report , dated 4/8/99, states that further information is unavailable. However, source records document that attempts to obtain the autopsy report were discontinued per instructions from the ( ) legal department.”

• “f) ( ) dated 9/16/98, reports that ( ) patient with ( )n ( ) initiated Meridia for weight loss, was transferred to the hospital with ( ) date unknown, and subsequently died. In a MedWatch report, dated 4/7/99, the sponsor [Abbott] stated that it is likely that the patient expired due to complications of ( ), underlying ( ) however, the original ( ) report indicates that the patient’s preexisting conditions were unknown, and there is no source data documenting that the patient had preexisting ( ) prior to initiating Meridia therapy.”

• “g) ( ) dated 10/21/98, reports the death of a ( ) patient taking Meridia who had adverse events including ( )ecord dated 3/22/99 stated that the patient developed ( ) and the ( ) does not attribute the death to Meridia. There is no documentation of how or from whom this information was obtained.”

Under “Observation 3” in the FDA inspection report is a discussion of an additional death which occurred during a “postmarketing clinical investigation” [clinical trial]:

“Specifically, ( ) is an adverse event report of a ( ) patient who was in a blinded sibutramine vs. ( ) study from 9/23/98 until 2/21/01 and died suddenly on 2/22/01. The initial study, serious adverse event form reported the causality as unrelated. The form stated post mortem/autopsy report to follow. The review and evaluation of this event did not include documented attempts to obtain a copy of the autopsy report. The case was closed on 1/2/02. The blind was broken, and the patient had received sibutramine therapy.”

We informed Secretary Thompson that there are additional grounds for the criminal prosecution of Abbott. From our review of FDA’s adverse drug reaction data base we have found three cases, including one death, in which the company failed to notify the FDA of an adverse event within 15 days after the company became aware of it, as required by law. The one death, occurring in Great Britain, was reported to the FDA 41 days after the company became aware of it. In the two other cases, one was reported to the FDA 232 days after the company learned of it and the other 79 days later. All three incidents, acknowledged by the company to involve the kind of adverse event requiring a 15 day report, violate the law and regulations for which criminal sanctions can be imposed.

Abbott is not the only pharmaceutical manufacturer that has ever been found withholding or “massaging” adverse reaction reports submitted to the FDA. The current Abbott episode reveals one of the major weaknesses of the FDA’s postmarketing safety surveillance system: the huge majority (over 80 percent) of all adverse drug reaction reports are processed by drug companies before they are reported to the FDA. Drug companies have far too much control over important information that is vital to the public safety. There are two obvious solutions to this problem of information control.

First, all adverse drug reaction reports should be made directly to the FDA, not the manufacturers. This would require Congress to take an interest in public safety and adequately fund the FDA. Second, all companies engaging in such activity must be promptly and vigorously prosecuted, because patients in this country can be harmed by not having access to the full scope of information about the risks of sibutramine and other drugs.

What You Can Do

You must be extremely skeptical about claims made by representatives of drug companies, including doctors on their payrolls, that there is no evidence of a serious problem with a drug. The claim may be a fabrication to protect stock value and sales.