Skip to main content

Advertisement

SpringerLink
Log in

Review of the regulations for clinical research in herbal medicines in USA

  • Feature Article
  • Published:
Chinese Journal of Integrative Medicine Aims and scope Submit manuscript

Abstract

In 2012, USA Food and Drug Administration (FDA) approved 39 new drugs, however, there are only two botanical drugs (one topical and one oral) approved by FDA since the publication of the FDA’s industry guidelines for the botanical drug product in June 2004. The approval shows the Western guideline can be used for herbal medicines, authors investigate current regulation on herbal medicine clinical research, identify challenges conducting clinical trials, and seek to produce some guidance for potential investigators and sponsors considering a clinical trial in this area. Key words were formulated for searching on Medline and FDA website to locate relevant regulations for clinical research in herbal medicines to understand current environment for herbal medicine usage and examine the barriers affecting herbal medicine in clinical trials. Authors critically explore case study of the 1st FDA approved botanical drugs, Veregen (sinecatechins), green tea leaves extract, a topical cream for perianal and genital condyloma. In consideration of current regulation environment in USA, based on the findings and analysis through the literature review and Veregen case study, authors produce and propose a Checklist for New Drug Application of Herbal Medicines for potential investigators and sponsors considering in a herbal medicine clinical trial.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. US Department of Health and Human Services, Food and Drug Administration, Centre for Drug Evaluation and Research. Botanical Review Team (BRT). Available at http://www.fda.gov/AboutFDA/CentersOffices/Office of Medical ProductsandTobacco/CDER/ucm090973.htm [Accessed on 10 March 2014]

  2. Capasso L. 5300 years ago, the Ice Man used natural laxatives and antibiotics. Lancet 1998;352(9143):1864.

    Article  CAS  PubMed  Google Scholar 

  3. Wilt TJ, Ishani A, Stark G, MacDonald R, Lau J, Mulrow C. Saw palmetto extracts for treatment of benign prostatic hyperplasia: a systematic review. JAMA 1998;280:1604.

    Article  CAS  PubMed  Google Scholar 

  4. Kaptchuk TJ. Acupuncture: theory, efficacy, and practice. Ann Intern Med 2002;136:374.

    Article  PubMed  Google Scholar 

  5. Blumenthal M. The ABC clinical guide to herbs. American Botanical Council. Thieme, New York 2003

    Google Scholar 

  6. Farnsworth NR, Akerele O, Bingel AS, Soejarto DD, Guo Z. Medicinal plants in therapy. Bull World Health Organ 1985;63:965–981.

    CAS  PubMed Central  PubMed  Google Scholar 

  7. Eisenberg DM, Davis RB, Ettner SL, Appel S, Wilkey S, Van Rompay M, et al. Trends in alternative medicine use in the United States, 1990–1997: results of a follow-up national survey. JAMA 1998;280:1569–1575.

    Article  CAS  PubMed  Google Scholar 

  8. Goldman P. Herbal medicines today and the roots of modern pharmacology. Ann Intern Med 2001;135:594.

    Article  CAS  PubMed  Google Scholar 

  9. Kaufman DW, Kelly JP, Rosenberg L, Anderson TE, Mitchell A. Recent patterns of medication use in the ambulatory adult population of the United States: the Slone survey. JAMA 2002;287:337.

    Article  PubMed  Google Scholar 

  10. Vapiwala N, Mick R, Hampshire MK, Metz JM, DeNittis AS. Patient initiation of complementary and alternative medical therapies (CAM) following cancer diagnosis. Cancer J 2006;12:467–474.

    Article  PubMed  Google Scholar 

  11. Kaptchuk TJ, Eisenberg DM. The persuasive appeal of alternative medicine. Ann Intern Med 1998;129:1061.

    Article  CAS  PubMed  Google Scholar 

  12. Marcus DM, Grollman AP. Botanical medicines-the need for new regulations. N Engl J Med 2002;347:2073.

    Article  PubMed  Google Scholar 

  13. Balunas MJ and Kinghorn AD. Drug discovery from medicinal plants. Life Sci 2005;78:431–441.

    Article  CAS  PubMed  Google Scholar 

  14. Jachak SM, Saklani A. Challenges and opportunities in drug discovery from plants. Current Sci 2007;92(9):7.

    Google Scholar 

  15. Chalasani N, Fontana RJ, Bonkovsky HL, Watkins PB, Davern T, Serrano J, et al. Causes, clinical features, and outcomes from a prospective study of drug-induced liver injury in the United States. Gastroenterology 2008;135:1924.

    Article  PubMed Central  PubMed  Google Scholar 

  16. Chen ST, Dou JH, Temple R, Agarwal R, Wu KM, Walker S. New therapies from old medicines. Nat Biotechnol 2008;26:1077–1083.

    Article  CAS  PubMed  Google Scholar 

  17. Navarro VJ. Herbal and dietary supplement hepatotoxicity. Semin Liver Dis 2009;29:373.

    Article  CAS  PubMed  Google Scholar 

  18. Niharika S, Padmavati M, Satyahari Dey. Herbal drugs: standards and regulation. Fitoterapia 81:462–471.

  19. Sood A and Prasad K. Challenges conducting clinical trials with herbal products in oncology. in Alaoui-Jamali M, ed. Alternative and complementary therapies for cancer: integrative approaches and discovery of conventional drugs. Springer 2010;New York:403–416.

    Chapter  Google Scholar 

  20. Weinstein DH, Twaddell WS, Raufman JP, Philosophe B, Mindikoglu AL. SlimQuick?-associated hepatotoxicity in a woman with alpha-1 antitrypsin heterozygosity. World J Hepatol 2012;4:154.

    Article  PubMed Central  PubMed  Google Scholar 

  21. Cardellina JH II. Challenges and opportunities confronting the botanical dietary supplement industry. J Nat Prod 2002;65:1073–1084.

    Article  CAS  PubMed  Google Scholar 

  22. Ernst E. Second thoughts about safety of St John’s wort. Lancet 1999;354:2014–2016.

    Article  CAS  PubMed  Google Scholar 

  23. Vanherweghem JL, Depierreux M, Tielemans C, Abramowicz D, Dratwa M, Jadoul M, et al. Rapidly progressive interstitial renal fibrosis in young women: association with slimming regimen including Chinese herbs. Lancet 1993;341:387–391.

    Article  CAS  PubMed  Google Scholar 

  24. Depierreux M, Van Damme B, Vanden Houte K, Vanherweghem JL. Pathologic aspects of a newly described nephropathy related to the prolonged use of Chinese herbs. Am J Kidney Dis 1994;24:172–180.

    Article  CAS  PubMed  Google Scholar 

  25. Crone CC, Wise TN. Use of herbal medicines among consultation-liaison populations. A review of current information regarding risks, interactions, and efficacy. Psychosomatics 1998;39:43.

    Article  Google Scholar 

  26. Newall CA, Anderson LA, Phillipson JD, eds. Herbal medicines. A guide for health-care professionals. London: The Pharmaceutical Press; 1996:6.

    Google Scholar 

  27. Saxena PK, Cole IB, Murch SJ. Approaches to quality plant basedmedicine: significance of chemical profiling. In: Verpoorte R, et al, eds. Applications of plant metabolic engineering. Netherlands: Springer; 2007:311.

    Chapter  Google Scholar 

  28. Bennett DA Jr1, Phun L, Polk JF, Voglino SA, Zlotnik V, Raffa RB. Neuropharmacology of St. John’s Wort (Hypericum). Ann Pharmacother 1998;32:1201.

    Article  PubMed  Google Scholar 

  29. Müller WE, Singer A, Wonnemann M, Hafner U, Rolli M, Schäfer C. Hyperforin represents the neurotransmitter reuptake inhibiting constituent of hypericum extract. Pharmacopsychiatry 1998;31Suppl 1:16.

    Article  PubMed  Google Scholar 

  30. Singer A, Wonnemann M, Müller WE. Hyperforin, a major antidepressant constituent of St. John’s Wort, inhibits serotonin uptake by elevating free intracellular Na+1. J Pharm Exp Thera 1999;290:1363.

    CAS  Google Scholar 

  31. Gilroy CM, Steiner JF, Byers T, Shapiro H, Georgian W. Echinacea and truth in labeling. Arch Int Med 2003;163:699.

    Article  Google Scholar 

  32. Harkey MR, Henderson GL, Gershwin ME, Stern JS, Hackman RM. Variability in commercial ginseng products: an analysis of 25 preparations. Am J Clin Nut 2001;73:1101–1106.

    CAS  Google Scholar 

  33. Brazier NC and Levine MA. Drug-herb interaction among commonly used conventional medicines: a compendium for health care professionals. Am J Thera 2003;10:163.

    Article  Google Scholar 

  34. Estes JD, Stolpman D, Olyaei A, Corless CL, Ham JM, Schwartz JM, et al. High prevalence of potentially hepatotoxic herbal supplement use in patients with fulminant hepatic failure. Arch Surg 2003;138:852.

    Article  PubMed  Google Scholar 

  35. Tsai HH, Lin HW, Pickard AS, Tsai HY, Mahady GB. Evaluation of documented drug interactions and contraindications associated with herbs and dietary supplements: a systematic literature review. Int J Clin Pract 2012;66:1056–1078.

    Article  CAS  PubMed  Google Scholar 

  36. Kennedy J. Herb and supplement use in the US adult population. Clin Ther 2005;27:1847.

    Article  PubMed  Google Scholar 

  37. Bonkovsky HL. Hepatotoxicity associated with supplements containing Chinese green tea (Camellia sinensis). Ann Intern Med 2006;144:68.

    Article  PubMed  Google Scholar 

  38. Javaid A, Bonkovsky HL. Hepatotoxicity due to extracts of Chinese green tea (Camellia sinensis): a growing concern. J Hepatol 2006;45:334.

    Article  CAS  PubMed  Google Scholar 

  39. Molinari M, Watt KD, Kruszyna T, Nelson R, Walsh M, Huang WY, et al. Acute liver failure induced by green tea extracts: case report and review of the literature. Liver Transpl 2006;12:1892.

    Article  PubMed  Google Scholar 

  40. Piscitelli SC, Burstein AH, Chaitt D, Alfaro RM, Falloon J. Indinavir concentrations and St John’s wort. Lancet 2000;355:547–548.

    Article  CAS  PubMed  Google Scholar 

  41. Knüppel L and Linde K. Adverse effects of St. John’s Wort: a systematic review. J Clin Psych 2004;65:1470.

    Article  Google Scholar 

  42. Johne A, Brockmöller J, Bauer S, Maurer A, Langheinrich M, Roots I. Pharmacokinetic interaction of digoxin with an herbal extract from St John’s wort (Hypericum perforatum). Clin Pharmacol Ther 1999;66:338–345.

    Article  CAS  PubMed  Google Scholar 

  43. Moore LB, Goodwin B, Jones SA, Wisely GB, Serabjit-Singh CJ, Willson TM, et al. St. John’s wort induces hepatic drug metabolism through activation of the pregnane X receptor. Proc Natl Acad Sci USA. 2000;97:7500–7502.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  44. Sugimoto K, Ohmori M, Tsuruoka S, Nishiki K, Kawaguchi A, Harada K, et al. Different effects of St John’s wort on the pharmacokinetics of simvastatin and pravastatin. Clin Pharmacol Ther 2001;70:518–524.

    Article  CAS  PubMed  Google Scholar 

  45. Mathijssen RH, Verweij J, de Bruijn P, Loos WJ, Sparreboom A, et al. Effects of St. John’s wort on irinotecan metabolism. J Natl Cancer Inst 2002;94:1247–1249.

    Article  CAS  PubMed  Google Scholar 

  46. Mueller SC, Majcher-Peszynska J, Uehleke B, Klammt S, Mundkowski RG, Miekisch W, et al. The extent of induction of CYP3A by St. John’s wort varies among products and is linked to hyperforin dose. Eur J Clin Pharmacol 2006;62:29–36.

    Article  CAS  PubMed  Google Scholar 

  47. Gordon RY, Becker DJ, Rader DJ. Reduced efficacy of rosuvastatin by St. John’s Wort. Am J Med 2009;122:e1.

    Article  PubMed  Google Scholar 

  48. Nieminen TH, Hagelberg NM, Saari TI, Neuvonen M, Laine K, Neuvonen PJ, et al. St John’s wort greatly reduces the concentrations of oral oxycodone. Eur J Pain 2010;14:854–859.

    Article  CAS  PubMed  Google Scholar 

  49. Blendon RJ, DesRoches CM, Benson JM, Brodie M, Altman DE. Americans’ views on the use and regulation of dietary supplements. Arch Intern Med 2001;161:805–810.

    Article  CAS  PubMed  Google Scholar 

  50. Sadovsky R, Collins N, Tighe AP, Brunton SA, Safeer R. Patient use of dietary supplements: a clinician’s perspective. Curr Med Res Opin. 2008;24:1209–1216.

    Article  PubMed  Google Scholar 

  51. Glisson JK, Walker LA. How physicians should evaluate dietary supplements. Am J Med 2010;123:577–582.

    Article  PubMed  Google Scholar 

  52. Peng T. Convergence: where West meets East. Nature 2011;480:S84–S86.

    Article  Google Scholar 

  53. Wadman M. Centre turns away from healing herbs. Nature News. 2009;7. Doi:10.1038/462711a. Published online 07 December 2009

    Google Scholar 

  54. Wu KM, Ghantous H, Birnkrant DB. Current regulatory toxicology perspectives on the development of herbal medicines to prescription drug products in the United States. Food Chem Toxicol 2008;46:2606–2610.

    Article  CAS  PubMed  Google Scholar 

  55. Douillard JY, Shepherd FA, Hirsh V, Mok T, Socinski MA, Gervais R, et al. Molecular predictors of outcome with gefitinib and docetaxel in previously treated non-small-ell lung cancer: data from the randomized phase III INTEREST trial. J Clin Oncol 2010;28:744–752.

    Article  CAS  PubMed  Google Scholar 

  56. Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 2004;350:2129–2139.

    Article  CAS  PubMed  Google Scholar 

  57. Paez JG, Jänne PA, Lee JC, Tracy S, Greulich H, Gabriel S, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 2004;304:1497–1500.

    Article  CAS  PubMed  Google Scholar 

  58. van Wietmarschen HA, Yuan K, Lu C, Gao P, Wang J, Xiao C, et al. Systems biology guided by Chinese medicine reveals new markers for sub-typing rheumatoid arthritis patients. J Clin Rheumatol 2009;15:330–337

    Article  PubMed  Google Scholar 

  59. van Wietmarschen HA, Reijmers TH, van der Kooij AJ, Schroën J, Wei H, Hankemeier T, et al. Sub-typing of rheumatic diseases based on a systems diagnosis questionnaire. PLoS One 2011;6:e24846.

    Article  PubMed Central  PubMed  Google Scholar 

  60. van Wietmarschen HA, Dai W, van der Kooij AJ, Reijmers TH, Schroën Y, Wang M, et al. Characterization of rheumatoid arthritis subtypes using symptom profiles, clinical chemistry and metabolomics measurements. PLoS One 2012;7:e44331.

    Article  PubMed Central  PubMed  Google Scholar 

  61. Koren MJ. Statin use in a “real-world” clinical setting: aggressive lipid lowering compared with usual care in the Aggressive Lipid-Lowering Initiation Abates New Cardiac Events (ALLIANCE) trial. Am J Med 2005;118Suppl:16–21.

    Article  PubMed  Google Scholar 

  62. Gagnier JJ, Boon H, Rochon P, Moher D, Barnes J, Bombardier C. Reporting randomized, controlled trials of herbal interventions: an elaborated CONSORT statement. Ann Intern Med 2006;144:364–367.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Herose Clinical Centre, 190 Clemenceau Ave, #03-24, SSC, Singapore, 239924, Singapore

    Tony Yuqi Tang

  2. Department of Law, School of Humanities, Inner Mongolia University of Technology, 49 Aimin Street, Hohhot, 010051, China

    Fang-zhou Li  (李方舟)

  3. School of Nursing, Midwifery & Social Care, Faculty of Health, Life & Social Sciences, Edinburgh Napier University, Sighthill Campus, Sighthill Court, Edinburgh, EH11 4BN, UK

    Janyne Afseth

Authors
  1. Tony Yuqi Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fang-zhou Li  (李方舟)
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Janyne Afseth
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tony Yuqi Tang.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tang, T.Y., Li, Fz. & Afseth, J. Review of the regulations for clinical research in herbal medicines in USA. Chin. J. Integr. Med. 20, 883–893 (2014). https://doi.org/10.1007/s11655-014-2024-y

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11655-014-2024-y

Keywords

Search

Navigation