Advertisement

The Role of the USA Food and Drug Administration in Clinical Research

  • Stephen P. GlasserEmail author
  • Carol M. Ashton
  • Nelda P. Wray
Chapter

Abstract

The USFDA is an agency of the US Department of Health and Human Services and is the nation’s oldest consumer protection agency whose function it is to review drugs before marketing, monitor marketed drugs, monitor drug manufacturing and advertising, protect drug quality, and to conduct applied research. It is charged with overseeing of not only human drugs and biologics, but also veterinary drugs, foods, medical devices, and radiopharmaceuticals, and as such serves as a watchdog over industry. This chapter discusses the historical development of the FDA, and what the FDA is today. The phases of research development (phase 0 through phase 5) leading to the marketing of a new drug, the role of the FDA in surgical interventions and medical device approval, and the FDA’s role in advertising and adverse event reporting are discussed.

Keywords

FDA history Drug development. Phase 0–3 trials Futility/feasibility trials. First in man trial Investigational Drug Application (IND) New Drug Application (NDA) International Conference on harmonization (ICH) Medical device approval Adverse event reporting FDA and advertising Off-label drug use 

References

  1. 1.
    Lewis S, Baird P, Evans RG, Ghali WA, Wright CJ, Gibson E, et al. Dancing with the porcupine: rules for governing the university-industry relationship. Can Med Assoc J. 2001;165:783–5.Google Scholar
  2. 2.
    Kurian RG, editor. The historical guide to American government. New York: Oxford University Press; 1998.Google Scholar
  3. 3.
    Swann R. History of the FDA. Available from: www.fda.gov/oc/history. Cited 5 Sept 2007.
  4. 4.
    Guidance for Industry. Available from: www.fda.gov/cber/guidelines
  5. 5.
    Thelithromycin. Wikipedia. Available from: www.en.wikipedia.org/wiki/Telithromycin
  6. 6.
    Brott TG, Hobson RW, Howard G, Roubin GS, Clark WM, Brooks W, et al. Stenting versus endarterectomy for treatment of carotid-artery stenosis. N Engl J Med. 2010;363:11–23. PMC2932446.PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    Compton 3rd WM, Cottler LB, Jacobs JL, Ben-Abdallah A, Spitznagel EL. The role of psychiatric disorders in predicting drug dependence treatment outcomes. Am J Psychiatry. 2003;160:890–5.PubMedCrossRefGoogle Scholar
  8. 8.
    FDA Amendment Act of 2007. Available from: www.fda.gov/oc/initatives/hr3580.pdf
  9. 9.
    The Mission Statement of the ICH. Available from: http://www.ich.org
  10. 10.
    Coronary Drug Project. Available from: www.fda.gov
  11. 11.
    Kummar S, Rubinstein L, Kinders R, Parchment RE, Gutierrez ME, Murgo AJ, et al. Phase 0 clinical trials: conceptions and misconceptions. Cancer J. 2008;14:133–7. doi: 10.1097/PPO.0b013e318172d6f3.PubMedCrossRefGoogle Scholar
  12. 12.
    Suntharalingam G, Perry MR, Ward S, Brett SJ, Castello-Cortes A, Brunner MD, et al. Cytokine storm in a phase 1 trial of the anti-CD28 monoclonal antibody TGN1412. N Engl J Med. 2006;355:1018–28.PubMedCrossRefGoogle Scholar
  13. 13.
    European Medicines Agency (EMEA). Available from: www.emea.europa
  14. 14.
    O’Donnell P. Not yet the last word on first-in-man. Appl Clin Trials. 2007;8:34–8.Google Scholar
  15. 15.
    Sullivan JT, McCarthy K. Decisions in first-in-human trials. Appl Clin Trials. 2010;2:58.Google Scholar
  16. 16.
    Palesch YY, Tilley BC, Sackett DL, Johnston KC, Woolson R. Applying a phase II futility study design to therapeutic stroke trials. Stroke. 2005;36:2410–4.PubMedCrossRefGoogle Scholar
  17. 17.
    McCulloch P. Developing appropriate methodology for the study of surgical techniques. J Royal Soc Med. 2009;102:51–5.Google Scholar
  18. 18.
    Henderson L. The long arm of the FDA. Applied Clinical Trials, 2007 July.Google Scholar
  19. 19.
    DeMaria AN. The exportation of clinical research. J Am Coll Cardiol. 2009;53:1919–20. doi: 10.1016/j.jacc.2009.04.019.PubMedCrossRefGoogle Scholar
  20. 20.
    Lexchin J, Bero LA, Djulbegovic B, Clark O. Pharmaceutical industry sponsorship and research outcome and quality: systematic review. BMJ. 2003;326:1167–70.PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Perlis RH, Perlis CS, Wu Y, Hwang C, Joseph M, Nierenberg AA. Industry sponsorship and financial conflict of interest in the reporting of clinical trials in psychiatry. Am J Psychiatry. 2005;162:1957–60.PubMedCrossRefGoogle Scholar
  22. 22.
    Ridker PM, Torres J. Reported outcomes in major cardiovascular clinical trials funded by for-profit and not-for-profit organizations: 2000–2005. JAMA. 2006;295:2270–4.PubMedCrossRefGoogle Scholar
  23. 23.
    Steri J. Point/Counterpoint Editorial. Cardiology News. Feb 2009Google Scholar
  24. 24.
    Kaiser KA, Cofield SS, Fontaine KR, Glasser SP, Thabane L, Chu R, et al. Is funding source related to study reporting quality in obesity or nutrition randomized control trials in top-tier medical journals? Int J Obes. 2012;36:977–81. PMC3288675.CrossRefGoogle Scholar
  25. 25.
    Lee K, Bacchetti P, Sim I. Publication of clinical trials supporting successful new drug applications: a literature analysis. PLoS Med. 2008;5:1348–56. PMC2553819.Google Scholar
  26. 26.
    Ross JS, Tse T, Zarin DA, Xu H, Zhou L, Krumholz HM. Publication of NIH funded trials registered in ClinicalTrials.gov: cross sectional analysis. BMJ. 2012;344:d7292. PMC3623605.PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    Zuckerman DM, Brown P, Nissen SE. Medical device recalls and the FDA approval process. Arch Intern Med. 2011;171:1006–11. doi: 10.1001/archinternmed.2011.30.PubMedGoogle Scholar
  28. 28.
    Dhruva SS, Bero LA, Redberg RF. Strength of study evidence examined by the FDA in premarket approval of cardiovascular devices. JAMA. 2009;302:2679–85. doi: 10.1001/jama.2009.1899.PubMedCrossRefGoogle Scholar
  29. 29.
    Dhruva SS, Bero LA, Redberg RF. Gender bias in studies for Food and Drug Administration premarket approval of cardiovascular devices. Circ Cardiovasc Qual Outcomes. 2011;4:165–71. doi: 10.1161/CIRCOUTCOMES.110.958215.PubMedCrossRefGoogle Scholar
  30. 30.
    Institute of Medicine. Women’s health research: progress, pitfalls, and promise. Washington, DC: National Academies Press; 2010.Google Scholar
  31. 31.
    Maisel WH. Medical device regulation: an introduction for the practicing physician. Ann Intern Med. 2004;140:296–302.PubMedCrossRefGoogle Scholar
  32. 32.
    Kaplan AV, Baim DS, Smith JJ, Feigal DA, Simons M, Jefferys D, et al. Medical device development: from prototype to regulatory approval. Circulation. 2004;109:3068–72.PubMedCrossRefGoogle Scholar
  33. 33.
    Ashton CM, Wray NP. Comparative effectiveness research: evidence, medicine, and policy. New York: Oxford University Press; 2013. p. 80–96.CrossRefGoogle Scholar
  34. 34.
    Ramsey SD, Sullivan SD. Evidence, economics, and emphysema: Medicare’s long journey with lung volume reduction surgery. Health Aff (Millwood). 2005;24:55–66. doi: 10.1377/hlthaff.24.1.55.CrossRefGoogle Scholar
  35. 35.
    Brantigan OC, Mueller E. Surgical treatment of pulmonary emphysema. Am Surg. 1957;23:789–804.PubMedGoogle Scholar
  36. 36.
    Cooper JD, Trulock EP, Triantafillou AN, Patterson GA, Pohl MS, Deloney PA, et al. Bilateral pneumectomy (volume reduction) for chronic obstructive pulmonary disease. J Thorac Cardiovasc Surg. 1995;109:106–16; discussion 16–9.PubMedCrossRefGoogle Scholar
  37. 37.
    Tunis SR, Pearson SD. Coverage options for promising technologies: Medicare’s ‘coverage with evidence development’. Health Aff. 2006;25:1218–30.CrossRefGoogle Scholar
  38. 38.
    Fishman A, Martinez F, Naunheim K, Piantadosi S, Wise R, Ries A, et al. A randomized trial comparing lung-volume-reduction surgery with medical therapy for severe emphysema. N Engl J Med. 2003;348:2059–73.PubMedCrossRefGoogle Scholar
  39. 39.
    Kolata G. Medicare says it will pay, but patients say ‘no thanks’. The New York Times on the Web. 2006:C1, C4. Available from: www.nytimes.com
  40. 40.
    Cooley DA, Al-Naaman YD, Carton CA. Surgical treatment of arteriosclerotic occlusion of common carotid artery. J Neurosurg. 1956;13:500–6.PubMedCrossRefGoogle Scholar
  41. 41.
    Winslow CM, Solomon DH, Chassin MR, Kosecoff J, Merrick NJ, Brook RH. The appropriateness of carotid endarterectomy. N Engl J Med. 1988;318:721–7.PubMedCrossRefGoogle Scholar
  42. 42.
    North American Symptomatic Carotid Endarterectomy Trial Collaborators. Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. N Engl J Med. 1991;325:445–53.CrossRefGoogle Scholar
  43. 43.
    Endarterectomy for asymptomatic carotid artery stenosis. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study. JAMA. 1995;273:1421–8.Google Scholar
  44. 44.
    Barnett HJ, Taylor DW, Eliasziw M, Fox AJ, Ferguson GG, Haynes RB, et al. Benefit of carotid endarterectomy in patients with symptomatic moderate or severe stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators. N Engl J Med. 1998;339:1415–25.PubMedCrossRefGoogle Scholar
  45. 45.
    Halm EA, Tuhrim S, Wang JJ, Rojas M, Hannan EL, Chassin MR. Has evidence changed practice?: appropriateness of carotid endarterectomy after the clinical trials. Neurology. 2007;68:187–94.PubMedCrossRefGoogle Scholar
  46. 46.
    Blackshear JL, Cutlip DE, Roubin GS, Hill MD, Leimgruber PP, Begg RJ, et al. Myocardial infarction after carotid stenting and endarterectomy: results from the carotid revascularization endarterectomy versus stenting trial. Circulation. 2011;123:2571–8. PMC3173718.PubMedCentralPubMedCrossRefGoogle Scholar
  47. 47.
    Moseley JB, O’Malley K, Petersen NJ, Menke TJ, Brody BA, Kuykendall DH, et al. A controlled trial of arthroscopic surgery for osteoarthritis of the knee. N Engl J Med. 2002;347:81–8.PubMedCrossRefGoogle Scholar
  48. 48.
    Kirkley A, Birmingham RB, Litchfield RB, Giffin JR, Willits KR, Wong CJ, et al. A randomized trial of arthroscopic surgery for osteoarthritis of the knee. N Engl J Med. 2009;361:1097–107. doi: 10.1056/NEJMoa0708333.Google Scholar
  49. 49.
    Katz JN, Brophy RH, Chaisson CE, de Chaves L, Cole BJ, Dahm DL, et al. Surgery versus physical therapy for a meniscal tear and osteoarthritis. N Engl J Med. 2013;368:1675–84. PMC3690119.PubMedCentralPubMedCrossRefGoogle Scholar
  50. 50.
    Wenner DM, Brody BA, Jarman AF, Kolman JM, Wray NP, Ashton CM. Do surgical trials meet the scientific standards for clinical trials? J Am Coll Surg. 2012;215:722–30. PMC3478478.PubMedCentralPubMedCrossRefGoogle Scholar
  51. 51.
    Weinstein JN, Tosteson TD, Lurie JD, Tosteson AN, Hanscom B, Skinner JS, et al. Surgical vs. nonoperative treatment for lumbar disk herniation: the Spine Patient Outcomes Research Trial (SPORT): a randomized trial. JAMA. 2006;296:2441–50.PubMedCentralPubMedCrossRefGoogle Scholar
  52. 52.
    Brody BA. The ethics of biomedical research: an international perspective. New York: Oxford University Press; 1998.Google Scholar
  53. 53.
    Kim SY, Frank S, Holloway R, Zimmerman C, Wilson R, Kieburtz K. Science and ethics of sham surgery: a survey of Parkinson disease clinical researchers. Arch Neurol. 2005;62(9):1357–60.PubMedCrossRefGoogle Scholar
  54. 54.
    Wennberg JE. An apple a day? N Engl J Med. 1994;331:815; author reply 6.PubMedGoogle Scholar
  55. 55.
    The AMIS Study Group. The aspirin myocardial infarction study: final results. The Aspirin Myocardial Infarction Study research group. Circulation. 1980;62:79–84.Google Scholar
  56. 56.
    Harlow SD, Linet MS. Agreement between questionnaire data and medical records. The evidence for accuracy of recall. Am J Epidemiol. 1989;129:233–48.PubMedGoogle Scholar
  57. 57.
    St Sauver JL, Hagen PT, Cha SS, Bagniewski SM, Mandrekar JN, Curoe AM, et al. Agreement between patient reports of cardiovascular disease and patient medical records. Mayo Clin Proc. 2008;80:203–10. http://dx.doi.org/10.4065/80.2.203.
  58. 58.
    Bolland MJ, Barber A, Doughty RN, Grey A, Gamble G, Reid IR. Differences between self-reported and verified adverse cardiovascular events in a randomised clinical trial. BMJ Open. 2013;3:1–6. PMC3612743.Google Scholar
  59. 59.
    The FDA’s poor oversight of postmarketing studies. (Editorial). The Lancet. 2009;374:1568. doi:  10.1016/S0140-6736(09)61932-2.
  60. 60.
    Strain EC, Stitzer ML, Bigelow GE. Early treatment time course of depressive symptoms in opiate addicts. J Nerv Ment Dis. 1991;179:215–21.PubMedCrossRefGoogle Scholar
  61. 61.
    Hesse M. The Beck Depression Inventory in patients undergoing opiate agonist maintenance treatment. Br J Clin Psychol. 2006;45:417–25.PubMedCrossRefGoogle Scholar
  62. 62.
    21 CFR Part 310 section 502(a) of the Food and Drug Administration Modernization Act of 1997, 21 U.S.C. 352(a).Google Scholar
  63. 63.
    Baylor-Henry M, Drezin N. Regulation of prescription drug promotion: direct-to consumer advertising. Clin Ther. 1998;20(C):C86–95.PubMedCrossRefGoogle Scholar
  64. 64.
    Section 502(n) of the Food Drug and Cosmetics Act, and Title 21 Code of Federal Regulations, 202.1(1) (1).Google Scholar
  65. 65.
    Kessler DA, Pines WL. The federal regulation of prescription drug advertising and promotion. JAMA. 1990;264:2409–15.PubMedCrossRefGoogle Scholar
  66. 66.
    21 CFR Part 310 section 502(a) of the Food and Drug Administration Modernization Act of 1997 (Modernization Act)., 21 U.S.C. 352 (n).Google Scholar
  67. 67.
    Rounsaville BJ, Weissman MM, Crits-Christoph K, Wilber C, Kleber H. Diagnosis and symptoms of depression in opiate addicts. Course and relationship to treatment outcome. Arch Gen Psychiatry. 1982;39:151–6.PubMedCrossRefGoogle Scholar
  68. 68.
    Section 502 (n) of the Food Drug and Cosmetics Act, and Title 21 Code of Federal Regulations, 202.1.Google Scholar
  69. 69.
    Chen LY, Crum RM, Martins SS, Kaufmann CN, Strain EC, Mojtabai R. Service use and barriers to mental health care among adults with major depression and comorbid substance dependence. Psychiatr Serv. 2013;64:863–70. doi: 10.1176/appi.ps.201200289.PubMedCrossRefGoogle Scholar
  70. 70.
    Woodcock J. Statement by Janet Woodcock, MSD Director, Center of Drug Evaluation and Research. US Drug Administration. Department of Health and Human Services; 2003.Google Scholar
  71. 71.
    Gahart MT, Duhamel LM, Dievler A, Price R. Examining the FDA’s oversight of direct to consumer advertising. Health Aff (Millwood). 2003;Suppl Web Exclusives:W3–120–3. doi:  10.1377/hlthaff.w3.120.
  72. 72.
    Waxman HA. Ensuring that consumers receive appropriate information from drug ads: What is the FDA’s role? Health Aff (Millwood). 2004;Suppl Web Exclusives:W4–256–8. doi:  10.1377/hlthaff.w4.256.
  73. 73.
    Waxman RHA. Letter from Rep. Henry A. Waxman to the Honorable Tommy G. Thompson. 2002. Available from: www.oversight.house.gov/story.asp?ID=441. Cited 1 June 2007.
  74. 74.
    Salas M, Martin M, Pisu M, McCall E, Zuluaga A, Glasser SP. Analysis of US food and drug administration warning letters: false promotional claims relating to prescription and over-the-counter medications. Pharm Med. 2008;22:119–25.CrossRefGoogle Scholar
  75. 75.
    Food and Drug Administration. Available from: www.fda.gov/opacom/backgrounders/miles.html. Cited 10 June 2010.
  76. 76.
    Radley DC, Finkelstein SN, Stafford RS. Off-label prescribing among office-based physicians. Arch Intern Med. 2006;166:1021–6.PubMedCrossRefGoogle Scholar
  77. 77.
    Wittich CM, Burkle CM, Lanier WL. Ten common questions (and their answers) about off-label drug use. Mayo Clin Proc. 2012;87:982–90. PMC3538391.PubMedCentralPubMedCrossRefGoogle Scholar
  78. 78.
    Accreditation Council for Continuing Medical Education Website. Available from: www.accme.org/education. Accessed 17 Feb 2013.

Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  • Stephen P. Glasser
    • 1
    Email author
  • Carol M. Ashton
    • 2
  • Nelda P. Wray
    • 2
  1. 1.Division of Preventive MedicineUniversity of Alabama at BirminghamBirminghamUSA
  2. 2.Department of Surgery, Center for Outcomes ResearchHouston Methodist Hospital Research InstituteHoustonUSA

Personalised recommendations