Dietary Supplements: Review of Health-Related Call Records for Users of Metabolife 356
Published: 2003-03-31T00:00:00

Fast Facts:

Highlights:
section_title: Why GAO Did This Study
paragraphs: 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.
section_title: What GAO Found
paragraphs: 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.

section_title: Letter
paragraphs: Medical experts have expressed concerns about the safety of dietary  supplements containing ephedra or ephedrine alkaloids, which are used by  millions of Americans annually. On February 28, 2003, the Food and Drug  Administration (FDA) announced several proposed changes to its  regulation of dietary supplements containing ephedra, including requiring  a product label warning that “Heart attack, stroke, seizure, and death have  been reported after consumption of ephedrine alkaloids.” As of  September 27, 2002, FDA had received approximately 1,800 adverse event  reports regarding consumers of dietary supplements containing ephedra.  Of these, 322 concerned Metabolife 356, a weight loss product first  marketed in 1995 by Metabolife International, a large manufacturer of  dietary supplements containing ephedra. Adverse event reports can signal  potential health problems that deserve additional investigation, but, on  their own, generally are not sufficient to establish that the reported  problems were caused by use of the product.
Metabolife International has also received complaints about adverse  health events among users of Metabolife 356. Between August and  December 2002, Metabolife International made available to the public  redacted copies of nearly 16,000 pages of documentation that it identified  as containing reports of adverse events among consumers of Metabolife  356. These complaints, which were received between May 1997 and July  2002, had not been previously released to FDA. Most of them were records  of calls received through a consumer health information phone line  established by Metabolife International in 1998 and staffed by its nurses.  Metabolife International officials told us that the phone line was  established to provide information to consumers regarding appropriate  use of Metabolife 356. In letters to the Texas Department of Health and  FDA, company officials described the phone line as a “safety monitoring  procedure” for the reporting of medical complaints. The call records  ranged from handwritten notes to printed versions of records that had  been entered into a database developed by Metabolife International. These  call records have been the subject of six previous reviews: 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, and one by the RAND  Corporation.
You asked us to review the content of all health-related call records made  public by Metabolife International. Specifically, you asked us to answer  the following questions. (1) To what extent was consumer information in  the call records comprehensive, interpretable, and consistently recorded?  (2) How many call records reported health-related problems, and how  many of those were serious? (3) How do our counts of reported serious  adverse events compare with those of other reviews for those events  counted by Metabolife International?
In responding to your request, we reviewed all the pages of documentation  voluntarily provided to us by Metabolife International. We did not  independently verify that we received all of the call records held by  Metabolife International. We excluded from our review call records that  duplicated other records.  To determine the extent to which consumer  information was comprehensive, interpretable, and consistently recorded  in the call records, we recorded information about the adverse event,  demographic information about the individual consumer, and other details  in the call record. Specifically, we recorded background information  similar to that used by FDA in the reporting of adverse events, including  age, sex, weight, height, the amount of Metabolife 356 used, the duration  of use, and whether any medical history was noted in the call record.
To assess how many call records reported health-related problems and  how many of those were serious, we first counted the number of call  records that reported at least one adverse event. Within this set of call  records, we then counted the number of reports of heart attack, stroke,  seizure, and death—the types of serious adverse events identified in FDA’s  proposed label warning. We also counted the number of reports of the   23 other types of adverse events that were described as serious or  potentially serious in FDA’s 1997 proposed rule on dietary supplements  containing ephedrine alkaloids. For call records that did not report any of  the above adverse events, we counted the number of records, but did not  count the number of other specific types of adverse events reported.
We classified events in the call records based solely on the words and  phrases therein; we did not attempt to diagnose a consumer’s condition or  to otherwise interpret the information presented. We did not apply  medical judgment in the process of classifying events and we did not  independently verify the accuracy of the information in the records or  determine the validity of the claims made in the call records. We also did  not attempt to determine whether Metabolife 356 caused the reported  adverse events. Our results may either overestimate or underestimate the  number and severity of adverse events because the call records generally  do not include medical diagnoses made by qualified professionals.
To determine how our counts of reported serious adverse events compare  with those of other reviews, we examined the six previous reviews of  Metabolife International’s call records. In addition, we interviewed  Metabolife International and FDA officials. Appendix I describes our  methodology in more detail. We conducted our work from September 2002  through March 2003 in accordance with generally accepted government  auditing standards.
subsections: section_title: Background
paragraphs: Metabolife 356, which claims to raise the body’s metabolism and help  dieters lose weight while maintaining high energy levels, contains   32 ingredients, including ephedra, guarana (an herbal source of caffeine),  bee pollen, and caffeine. The product label recommends that adults take  one to two caplets two to three times per day or every 4 hours, not to  exceed eight caplets per day. Warnings on the product label suggest that a  health care professional be consulted by individuals who are using any  other dietary supplement, prescription drug, or over-the-counter drug  containing ephedrine alkaloids or who have, or have a family history of,  any of 11 health conditions, including heart disease, high blood pressure,  diabetes, recurrent headaches, and depression. The label also  recommends that persons should not use the product for more than   12 weeks and that exceeding the recommended amount may cause serious  adverse health effects including heart attack or stroke. Other possible side  effects mentioned on the label include rapid heartbeat, dizziness, severe  headache, and shortness of breath. The complete product label is in  appendix II.
The Dietary Supplement Health and Education Act of 1994 created a  framework for FDA’s regulation of dietary supplements as part of its  oversight of food safety. Dietary supplements are generally marketed  without prior FDA review of their safety and effectiveness.  Manufacturers of dietary supplements are responsible for ensuring the  safety of the dietary supplements they sell. Therefore, FDA relies on  voluntary reports of adverse events from consumers, health professionals,  and others in its effort to oversee the safety of marketed dietary  supplements.
Although there are no adverse event reporting requirements for  manufacturers of dietary supplements, there are such requirements for  many other products regulated by FDA. Various types of adverse events  associated with the use of human drugs and biologics, animal drugs,  animal feeds containing animal drugs, medical devices, infant formulas,  and radiation-emitting devices must be reported to FDA. In addition to  dietary supplements, other products regulated by FDA that do not require  adverse event reporting are foods, cosmetics, and color additives. (See  app. III for details about adverse event reporting requirements.)
Voluntary adverse event reporting systems can be valuable tools for  identifying potentially serious health issues that may be associated with  the use of a product and for maintaining ongoing surveillance. FDA has  used adverse event reports to identify issues for further investigation and,  as we previously reported, it has used adverse event reports to help  identify dietary supplements for which evidence of harm existed, and has  issued warnings and alerts for dietary supplements. However, by  themselves, adverse event reporting systems generally are not sufficient to  establish that a product caused the reported health problem. As we noted  in 1999, all voluntary surveillance systems, including FDA’s adverse event  reporting system, have certain weaknesses. These include  underreporting, reporting biases, difficulties estimating population  exposure, and poor report quality. For example, the Department of Health  and Human Services (HHS) Inspector General reported that a study  commissioned by FDA estimated that FDA receives reports for less than   1 percent of adverse events associated with dietary supplements.  In  addition, it is often difficult to rule out other possible explanations for the  event; for example, the event may have been caused by preexisting  medical conditions, or by the concurrent use of prescription drugs, over- the-counter drugs, or other supplements. For these reasons, data from  adverse event reports alone cannot be used to determine if the occurrence  of a symptom among product users is unusually high.
Between August and December 2002, Metabolife International released  copies of 15,948 pages of documents that it said contained call records  that reported adverse events associated with Metabolife 356 that the  company had received from May 1997 through July 2002. Some pages of  call records contained information about more than one call while others  did not contain reports of adverse events. Some pages were photocopies  or duplicates of other pages.
section_title: Consumer Information in Call Records Was Limited, Sometimes Difficult to Interpret, and Not Consistently Recorded
paragraphs: The information about reported adverse events in the 14,684 health-related  call records we examined was limited. Most of the call records we  reviewed did not completely record demographic or medical history  information about the consumer. 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.  Information was often inconsistent across different versions of the same  call record.
The call records contained limited information about reported adverse  events and consumers. 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. Most of the  call records we reviewed did not record information about the consumers’  sex, age, weight, or height. Eighty-eight percent of the call records did not  record at least one of these variables. In addition, information about the  amount of Metabolife 356 used and the duration of use was not recorded  in 27 and 33 percent of the call records, respectively. (See table 1.) The  absence of this information makes it difficult to assess whether the call  records represent a signal of health concerns related to the consumption  of Metabolife 356.
Both the amount of product used and duration of use were recorded for   60 percent of the calls reporting adverse events. Relatively few of these  records involved consumers who reported taking too much Metabolife 356  or using it for too long a period. Specifically, among call records  containing information on the amount of product used or duration of use,  99 and 91 percent of consumers, respectively, reported using the product  within the guidelines recommended on the label.
The format of the call records varied from brief handwritten notes to typed  notations to printed versions of a form used by Metabolife International. In  general, less information was recorded for the one-third of call records  that were handwritten than all other types of records. For example, calls  recorded on a typed form more frequently recorded additional information  such as recommendations by Metabolife International to discontinue  Metabolife 356 (62 percent) or contact a doctor (54 percent) than did  those on handwritten forms (13 percent and 8 percent, respectively).
Further, it was often difficult to read handwritten call records. We could  not always determine how many calls were reported on a single page since  there was rarely a clear delineation of events. Because handwritten call  records did not follow a template, we were unable to determine if some  information was medical history or symptom information, or if a number  was a weight, heart rate, or blood pressure.
Information in call records was sometimes inconsistent. Where duplicate  call records were available, information about consumers and their usage  of Metabolife 356 was sometimes presented differently in the different  records of the same consumer call. In addition, Metabolife International  officials told us that its nurses sometimes used several different terms to  document the same type of adverse event.
section_title: Metabolife International Had Thousands of Call Records Reporting Adverse Events Associated with Metabolife 356
paragraphs: We found that 14,684 of the Metabolife International call records reported  at least one adverse event. Ninety-two of these were for the serious  adverse events identified in the proposed label warning for dietary  supplements containing ephedra that FDA announced on February 28,  2003. Other adverse events reported included significant elevation of  blood pressure, abnormal heart rhythm, loss of consciousness, and  systemic rash. We cannot establish that any of the reported adverse events  were caused by the use of Metabolife 356.
subsections: section_title: Reports of Adverse Events Identified as Serious in FDA’s Proposed Label Warning
paragraphs: 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).
section_title: Other Adverse Events
paragraphs: In its 1997 proposed rule on dietary supplements, FDA also identified  other types of adverse events as serious or potentially serious. Table 3  shows our counts for almost all such events. The serious and potentially  serious types of adverse events described in FDA’s June 4, 1997, proposed  rule were reported to the agency prior to June 7, 1996. FDA officials report  that some other types of adverse events not included in the table may be  considered serious or potentially serious but had not been reported to  FDA during the time period considered by its proposed rule.
In addition, the 14,684 call records with health-related reports presented a  broad range of types of adverse events. Many of the call records contained  reports of jitters, insomnia, hair loss, bruising, menstrual irregularities, and  sexual dysfunction, as well as vague references to events such as “side  effect” or “felt sick.” Some reported blood in stool, blood in urine, or blood  clots. There were also some reports of visits to emergency departments  and hospital admissions. Some call records contained reports of diseases  such as pulmonary embolus (a blockage of an artery in the lungs), multiple  myeloma, and inflammation of heart tissue.
section_title: Causal Role of Metabolife 356 Cannot Be Established
paragraphs: 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. For example, for many adverse event  reports it is difficult to rule out other possible explanations for the event— the event may have been caused by preexisting medical conditions, or by  the concurrent use of prescription drugs, over-the-counter drugs, or other  dietary supplements. In addition, the limited information available in the  Metabolife International call records means that we cannot confirm that a  particular adverse event occurred, much less identify a specific cause for  it.
section_title: Findings of Different Reviews of Metabolife International Call Records Vary
paragraphs: All the reviews of the Metabolife International call records, including ours,  counted reports of serious adverse events. 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.
There are several possible reasons for the slightly different counts of  serious adverse events in the different reviews. First, the call records  themselves are often difficult to understand and interpret. Second, not all  of the reviews included the same set of call records, both because some  were completed before all of the Metabolife International call records  were released and because the reviews adopted different procedures for  identifying and discarding duplicate records. Third, the reviews used  different definitions of particular events or established different thresholds  for categorizing a particular event. For example, we included reports of  “convulsions” in our count of seizures, while some other reviews may not  have. Specifically, the counts we report in table 4 for our review and the  reviews by Metabolife International and Karch include reports of  convulsions, while it is not clear if the other reviewers’ counts did.  Similarly, we did not count as a report of a heart attack a call record that  reported “heart attack?”, while at least one other review did.
section_title: Agency and Metabolife International Comments and Our Evaluation
paragraphs: We provided a draft of this report to FDA and Metabolife International for  their review. 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. In addition, FDA  pointed out that, when combined with other information, adverse event  reports can help establish that an adverse event was caused by a particular  health product. FDA’s comments are included as appendix IV. FDA also  provided technical comments, which we incorporated as appropriate.
In its comments, Metabolife International was primarily concerned about  our use of the term “adverse events” to describe the health-related  complaints that were reported in the call records we reviewed. We believe  that our use of the term is accurate and consistent with its use by FDA and  others in the field. Metabolife International also wanted us to clarify that,  while it did identify some call records as containing references to types of  specific adverse events that have been categorized as serious by others, it  has not identified any call records as reporting “serious adverse events.”  We have made revisions so as not to imply that Metabolife International  labeled these events as serious adverse events. Metabolife International  also made other comments, which we incorporated as appropriate.
As agreed with your office, unless you publicly announce its contents  earlier, we plan no further distribution of this report until 30 days from the  date of this report. At that time, we will send copies to the Secretary of  HHS, the Commissioner of FDA, and others who are interested. We will  also provide copies to others upon request. In addition, the report will be  available at no charge on GAO’s Web site at http://www.gao.gov.
If you or your staff have any questions, please contact me at (202) 512- 7119. Another contact and major contributors to this report are listed in  appendix V.
section_title: Appendix I: Scope and Methodology for Categorizing the Call Records
paragraphs: 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. During our review we removed duplicate call  records and records that did not report health-related events. For each  record we recorded demographic information about the individual  consumer, other details about the call record and the consumer, and  categorized the reported events.
subsections: section_title: Call Records And Supplementary Information
paragraphs: From August 2002 through December 2002, Metabolife International  voluntarily provided to us 15,948 pages of documentation relating to  reports of adverse events among consumers of Metabolife 356. Most of  these records were from calls made to the company’s consumer health  information phone line from May 1997 through July 2, 2002. Other records  included e-mail messages and letters that had been sent to the company.  Nurses on the staff of Metabolife International documented the calls to the  consumer HealthLine in a variety of formats. The records included  handwritten notes on a page, typed and handwritten letters, forms with  handwritten entries, e-mails, and printed versions of records that had been  entered into a database developed by Metabolife International. Many kinds  of forms were used to record calls, ranging from simple forms with few  spaces or check boxes to full-page forms with multiple boxes for  consumer and event-related information. Metabolife International officials  told us that health complaints that were noted on product return forms  that it received were not in the call records provided to us.
Metabolife International also provided to us copies of 46 redacted medical  records and a list of corresponding call records. After reviewing these  records we found 8 that were not associated with other call records. Five  of these records contained enough information to determine the nature of  the adverse event and were coded in the same way as other call records.  The other medical records were used as additional sources of information  for documenting the events and consumer information reported in their  corresponding records.
While most pages of call records contained information about a single call,  some included information about multiple calls on the same page, other  calls spanned multiple pages, and some did not include any report of  adverse events. Records that spanned multiple pages were often letters to  the company, some of which were sent with additional information (such  as medical bills). Records that did not report an adverse event were either  incomplete printouts of other records from the database, product  questions, complaints about not losing weight, or reports of consumer  satisfaction. As a result, the number of pages of call records that we  received from Metabolife International does not correspond to the number  of reports of adverse events.
The call records and medical records we received were redacted by  Metabolife International to remove personal identifying information such  as name, phone number, address, fax number, and e-mail address to  protect consumer privacy. Metabolife International officials told us that in  the process of redacting the records, some relevant adverse event  information was also inadvertently removed.
section_title: Exclusion of Duplicate and Nonhealth-Related Call Records
paragraphs: Metabolife International officials told us that there were duplicate call  records in the set of call records they provided to us. Some duplicate  reports were photocopies of the same call record. In other cases, there  were multiple versions of the same call record in different formats.  Metabolife International officials reported these multiple versions were  the result of nurses taking handwritten notes and later entering the same  information directly into a database established in September 1999.
Metabolife International gave us lists of those call records it believed to be  duplicates. Over the course of our review, it identified more than   2,200 records for which there were at least one duplicate. Metabolife  International officials reported that they identified the duplicates on the  basis of the name of the consumer. Duplicates may have included  subsequent calls about different events from the same individual. We  examined the duplicate call records identified in the lists provided  throughout our review by Metabolife International. Because identifying  information was removed, we examined the date of the call record,  demographic information about the consumer (such as age, height, weight,  the amount of the product used, and duration of use), and event details to  determine if they were duplicate records. Where this information was the  same or similar, we considered the records to be duplicates and excluded  the extra records from our review. We did, however, include in our  analysis any additional information that appeared on the duplicate  records. For example, if one version included height and another weight,  we recorded both of these.
We agreed with Metabolife International that most of the more than   2,200 records it identified as duplicates were, in fact, duplicates. However,  we did not exclude records that represented multiple calls from the same  consumer for different events if the dates on the call records differed by  more than a few days or the symptoms were clearly different. During the  course of our review, we also identified duplicates not previously  identified by Metabolife International, including photocopied records and  records that used identical language in event descriptions. We do not  know if all duplicate call records were identified.
We also excluded from our analysis records in which there was no health  complaint or the health complaint could not be clearly determined. We  also excluded call records that reported third-hand knowledge of adverse  events (such as a friend of a friend who experienced an adverse event). In  addition, we did not count call records that clearly referred to nutrition  bars or other ephedra-free products manufactured by Metabolife  International. In total, we determined that the 15,948 pages of  documentation provided by Metabolife International contained   14,684 separate health-related call records.
section_title: Classification of Records and Data Entry Procedures
paragraphs: We classified the adverse events reported in each call record and entered  the appropriate codes into a database. We classified the reported adverse  events as either one of the events FDA identified as serious in its   February 28, 2003, announcement regarding a proposed label warning for  dietary supplements containing ephedra (heart attack, stroke, seizure, or  death) or as an other adverse event. All serious events reported within a  particular call record were counted. Therefore an individual could have  reported multiple serious adverse events, though this happened in few  records. For other adverse events, we documented whether the call record  reported one or more adverse events. We did not count the number of  reports for every type of event reported in the record. 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. The  set of events identified by FDA in the proposed rule is not an exhaustive  list of the adverse events that may be associated with the use of dietary  supplements containing ephedrine alkaloids. FDA officials told us that  some other types of adverse events may be considered serious or  potentially serious but had not yet been reported to FDA during the time  period considered by its proposed rule.
We did not apply medical judgment in the process of identifying and  classifying events. Our classification of events in the call records was  based solely on the words and phrases therein; we did not diagnose a  consumer’s condition or otherwise interpret the information presented.  For example, if a report said “poss. heart attack,” “heart attack symptoms,”  or “heart attack?”, we did not classify it as a heart attack since it was not  clear that a heart attack was reported. Also, while we counted “blood  pressure 210/120” as an instance of significantly elevated blood pressure  because it reported measurements greater than 160 systolic or 100  diastolic, we did not place in the same category call records that reported  only “high blood pressure” because they did not contain the specific  measurements needed for that determination. We used MEDLINE Plus  Medical Encyclopedia definitions to further clarify individual symptoms  related to these categories. We also did not attempt to determine whether  Metabolife 356 caused the reported adverse events.
section_title: Appendix II: Metabolife 356 Label
section_title: Appendix III: Requirements for Reporting Adverse Events to FDA
paragraphs: Adverse events about many types of products regulated by FDA are  required to be reported to the agency. Such products include human drugs,  biologics, animal drugs, animal feeds containing animal drugs, medical  devices, infant formulas, and radiation-emitting devices. There are,  however, no reporting requirements for adverse events associated with  other products regulated by FDA, including food and food additives,  dietary supplements, cosmetics, or color additives. (See table 5.)
section_title: Appendix IV: Comments from the Food and Drug Administration
section_title: Appendix V: GAO Contact and Staff Acknowledgments
subsections: section_title: GAO Contact
section_title: Acknowledgments
paragraphs: Carolyn Feis Korman, Chad Davenport, Julian Klazkin, and Roseanne  Price also made major contributions to this report.