Consumer Information in Call Records Was Limited, Sometimes Difficult to Interpret, and Not Consistently Recorded

The information about reported adverse events in the 14,684 health-related  call records we examined was limited. Information about age, sex, weight,  height, the amount of product used, and the duration of use was frequently  not recorded. Handwritten call records were difficult to read and interpret. In some cases the evidence for a report of an  adverse event was a single health-related word on the call record, such as  “seizure” or “stroke.” In addition, demographic and medical history  information was not consistently recorded in the call records. Both the amount of product used and duration of use were recorded for   60 percent of the calls reporting adverse events. Metabolife International Had Thousands of Call Records Reporting Adverse Events Associated with Metabolife 356

We found that 14,684 of the Metabolife International call records reported  at least one adverse event. Other adverse events reported included significant elevation of  blood pressure, abnormal heart rhythm, loss of consciousness, and  systemic rash. Reports of Adverse Events Identified as Serious in FDA’s Proposed Label Warning

We counted 92 reports of heart attack, seizure, stroke, or death—the  serious adverse events identified in FDA’s proposed label warning for  dietary supplements containing ephedra (see table 2). Causal Role of Metabolife 356 Cannot Be Established

We cannot establish that any of the adverse events reported in the  Metabolife International call records were caused by the use of Metabolife  356. As we noted earlier, adverse event reports by themselves are  generally not sufficient to establish that a health problem was caused by  the use of a particular product. None of the reviews reported  identical tabulations of these events. For the set of adverse events that  Metabolife International counted—heart attack, stroke, seizure, death, and  cardiac arrest—our counts are similar to those of the other reviews (see  table 4). In total, we counted 96 such events, Metabolife International  counted 78, and the counts of the other reviews ranged from 65 to 107. FDA asked us to clarify that it has not conducted its own  review of the Metabolife International call records, that we only reviewed  reports of adverse events contained in the Metabolife International call  records, and that we did not review other reports of adverse events among  users of Metabolife 356 that have been received by FDA. Another contact and major contributors to this report are listed in  appendix V.

Appendix I: Scope and Methodology for Categorizing the Call Records

We reviewed call records and supplementary information voluntarily  provided to us by Metabolife International to (1) determine the extent to  which information was comprehensive, interpretable, and consistently  recorded in the call records, and (2) count the number of call records  reporting health-related problems associated with Metabolife 356, and how  many of them were serious. Most of  these records were from calls made to the company’s consumer health  information phone line from May 1997 through July 2, 2002. Nurses on the staff of Metabolife International documented the calls to the  consumer HealthLine in a variety of formats. We did, however,  count the number of all but 1 of the 24 other types of adverse events that  were described as serious or potentially serious in FDA’s June 4, 1997,  proposed rule on dietary supplements containing ephedrine alkaloids.
Why GAO Did This Study

Dietary supplements containing ephedra, such as Metabolife 356, have been associated with serious adverse health-related events. In a February 28, 2003, announcement, the Food and Drug Administration (FDA) proposed that dietary supplements containing ephedra include a statement on their label warning that "Heart attack, stroke, seizure, and death have been reported after consumption of ephedrine alkaloids." GAO was asked to review health-related call records that Metabolife International--the manufacturer of Metabolife 356--collected from consumers from May 1997 through July 2002. Most of the records were from calls to a consumer phone line the company maintained. Metabolife International voluntarily provided the call records to GAO. Specifically, GAO (1) examined the extent to which consumer information in the call records was comprehensive, interpretable, and consistently recorded, (2) counted the number of call records reporting types of adverse events that FDA had identified in 1997 as serious or potentially serious, and (3) compared GAO's findings to those of six other reviews of the call records, including one by Metabolife International.

What GAO Found

Adverse event reports generally are not sufficient on their own to establish that reported problems are caused by the use of a particular product, but can signal potential health problems that deserve investigation. The information in the Metabolife International call records was limited. Call records were sometimes difficult to understand, and consumer information was not consistently recorded. In some cases, the evidence for a report of an adverse event was limited to a single word on the record. Most call records also did not record complete information about potentially relevant items such as the consumer's age, sex, weight, and height. Information about both the amount of product used and the duration of use was recorded for 60 percent of the call records. Handwritten call records were difficult to read and understand. By GAO's categorization, 14,684 of the call records contained reports of at least one adverse event. GAO found that there were 92 reports of the serious adverse events identified in FDA's proposed label warning--18 reported heart attacks, 26 reported strokes, 43 reported seizures, and 5 reported deaths. Other types of adverse events identified as serious or potentially serious by FDA in 1997 that were reported in the call records included significant elevation in blood pressure, abnormal heart rhythm, loss of consciousness, and systemic rash. Because of the inherent limitations of adverse event reports and the incomplete nature of these call records, it can not be established from the information available to GAO that the adverse events reported were caused by Metabolife 356. All of the reviews of Metabolife International call records--one by Metabolife International; three by consultants commissioned by Metabolife International; one by the minority staff of the Committee on Government Reform, House of Representatives; one by the RAND Corporation; and one by GAO--found reports of serious adverse events, although none reported identical results. For the set of adverse events counted by Metabolife International--heart attack, stroke, seizure, death, and cardiac arrest--GAO's counts were similar to those of the other reviews. GAO counted 96 such reports and the counts of the other reviews ranged from 65 to 107. In commenting on a draft of this report, FDA discussed the value of reports of adverse events in helping to understand the causes of such events.