Shekelle P, Morton, S., Maglione M, et al.  Ephedra and Ephedrine for Weight Loss and Athletic Performance Enhancement: Clinical Efficacy and Side Effects. Evidence Report/Technology Assessment No. 76 (Prepared by Southern California Evidence-based Practice Center, RAND, under Contract No
290-97-0001, Task Order No. 9). AHRQ Publication No. 03-E022. Rockville, MD: Agency for Healthcare Research and Quality. February 2003.

Contents

Cover

Title Page

Reference Cite

Preface

Acknowledgement

Structured Abstract

Contents

Summary

Evidence Report

Chapter 1. Introduction

      Purpose
      Scope of Work
      Background
            The Problem of Obesity
            Enhancing Physical Performance
      History and Pharmacology

Chapter 2. Methodology

      Original Proposed Key Questions
           Weight Loss
           Athletic Performance
           Safety Assessment
      Technical Expert Panel
          Assessment of Adverse Events
      Literature Search
          Additional Sources of Evidence
      Article Review
          Extraction of Study-Level Variables and Results
      Meta-Analysis
          Selection of Trials for Meta-Analysis
          Stratification of Interventions
           Weight Loss Effect Size
          Performance of Meta-Analysis
          Analysis of Dose
          Publication Bias
           Meta-Regression
      Safety Assessment
          Controlled Trial Adverse Events
           Case Report Adverse Events
      Peer Review

Chapter 3. Results

      Results of Literature Search
           Efficacy Analysis
          Adverse Events Analysis
      Efficacy
           Weight Loss
           Athletic Performance
      Safety Assessment
          Controlled Trials
           Case Reports

Chapter 4. Limitations

Chapter 5. Conclusions

      Efficacy
           Weight Loss
           Athletic Performance
      Adverse Consequences

Chapter 6. Future Research

References

Evidence Tables

Acronyms

Appendix 1. Bibliography

Appendix 2. Metabolife Serious Adverse Events

Appendix 3. Reviewer Comments

Tables

Table 1. Herbs containing caffeine commonly combined with ephedra in products marketed for weight loss or improved physical performance

Table 2. Technical expert panel members

Table 3. Technical expert panel suggestions about data collection

Table 4. Measures used in assessing causality

Table 5 Ephedra/ ephedrine search methodology 

Table 6 Ephedra/ephedrine search methodology additional databases

Table 7. Categories of adverse events

Table 8. Report reviewers

Table 9. Weight loss trial inclusion results

Table 10. Ephedrine versus placebo

Table 11. Publication bias tests

Table 12. Ephedrine + caffeine versus placebo

Table 13. Ephedrine + caffeine versus ephedrine

Table 14. Ephedrine versus another active weight loss therapy

Table 15. Ephedra versus placebo

Table 16. Ephedra + herbs containing caffeine versus placebo

Table 17. Meta-regression results

Table 18. Exercise trials by Bell and colleagues

Table 19. Summary table of meta-analysis of adverse events reported controlled trials 

Table 20. Summary table of other of adverse events reported in controlled trials 

Table 21. Distribution of adverse events in the FDA file according to the Excel Spreadsheet 

Table 22. Evidence table of case reports 

Table 23. Summary of adverse events with ephedra consumption 

Table 24. Summary of adverse events with ephedrine consumption 

Table 25. Summary of adverse events not reviewed in detail 

Table 26. Summary data of key variables from Metabolife file analysis 

Table 27. Comparison of serious cases identified by RAND and by Metabolife

Table 28. Summary of Metabolife medical records 

Figures

Figure 1. Screening form for literature
Figure 2. Quality review form for literature
Figure 3a. Adverse events analysis form for death, MI, stroke cases
Figure 3b. Adverse events analysis form for seizure cases
Figure 3c. Adverse events analysis form for psychiatric cases
Figure 4. Brief data collection form for case reports
Figure 5. Examples of MIPER files
Figure 6. Example of duplicate case
Figure 7. Metabolife record screener form
Figure 8. Literature flow
Figure 9. Ephedrine versus placebo forest plot
Figure 10. Ephedrine versus placebo funnel plot
Figure 11. Ephedrine + caffeine versus ephedrine alone forest plot
Figure 12. Ephedrine + caffeine versus placebo funnel plot 
Figure 13. Ephedrine + caffeine versus ephedrine alone forest plot
Figure 14. Ephedra + herbs containing caffeine versus placebo forest plot
Figure 15. Ephedra + herbs containing caffeine versus placebo funnel plot
Figure 16. Effect sizes by comparison group
Figure 17a. Flow of evidence for adverse events analysis, part 1
Figure 17b. Flow of evidence for adverse events analysis, part 2
Figure 17c. Flow of evidence for adverse events analysis, part 3
Figure 18. Flow of MIPER ID Numbers