Advertisement

Clinical Trials of Herpes Simplex Encephalitis: The Role of the Data Monitoring Committee

  • Richard J. Whitley

Abstract

Herpes simplex encephalitis (HSE) is the most frequent cause of focal necrotizing encephalitis, accounting for approximately 2,500 cases annually in the United States. Studies initiated in the early 1970s have continuously evaluated promising antiviral drugs for the treatment of this disease, utilizing randomized, blinded, controlled clinical trial designs. Fundamental to the early studies was the requirement for brain biopsy in order to establish a diagnosis of HSE unequivocally by isolation of herpes simplex virus (HSV) from brain tissue in cell culture. From the outset of these studies in 1973, Data Monitoring Committees (DMCs) were established by the program sponsor, the National Institute of Allergy and Infectious Diseases (NIAID), to assess clinical trial performance, data quality, and outcome. With several iterations over a period of 30 years, these DMCs have terminated one trial because of excessive drug toxicity and two trials because of significantly reduced mortality in recipients of an active therapeutic. These studies represented the first clinical trials sponsored by NIAID that utilized a DMC. The role of the DMC in the monitoring of these trials is described.

Keywords

Herpes Simplex West Nile Virus Brain Biopsy Herpes Simplex Encephalitis Case Study Approach 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Meyers HM Jr, Johnson RT, Crawford IP, Dascomb HE, Rogers NG. 1960. Central nervous system syndromes of “viral” etiology: A study of 713 cases. Am J Med 29:334–347.CrossRefGoogle Scholar
  2. 2.
    Longson M. The general nature of viral encephalitis in the United Kingdom. Viral Diseases of the Central Nervous System, pp. 19–31. Ellis LS. (ed.), 1984. Bailliere Tindall, London.Google Scholar
  3. 3.
    Whitley, RJ, Soong SJ, Hirsch MS, Karchmer AW, Dolin R, Galasso G, et al. 1981. Herpes simplex encephalitis:Vidarabine therapy and diagnostic problems. N Engl J Med 304:313–318.CrossRefGoogle Scholar
  4. 4.
    Whitley RJ, Soong SJ, Dolin R, Galasso GJ, Chien LT, Alford CA. 1977. Adenine arabinoside therapy of biopsy-proved herpes simplex encephalitis: National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study. N Engl J Med 297:289–294.CrossRefGoogle Scholar
  5. 5.
    Lerner AM, Bailey EJ. 1973. Concentrations of idoxuridine in serum, urine, and cerebrospinal fluid of patients with suspected diagnosis of herpesvirus hominis encephalitis. J Clin Invest 51:45–49.CrossRefGoogle Scholar
  6. 6.
    Lerner AM, Lauter CB, Nolan DC, Shippey MJ. 1972. Passive hemagglutinating antibodies in cerebrospinal fluids in herpes virus hominis encephalitis. Proc Soc Exp Biol Med 140:1460–1466.Google Scholar
  7. 7.
    Wilfert CM, Huang ES, Stagno S. 1982. Restriction endonuclease analysis of cytomegalovirus deoxyribonucleic acid as an epidemiologic tool. Pediatrics 70:717–721.Google Scholar
  8. 8.
    Wilfert CM, Lehrman SN, Katz SL. 1983. Enteroviruses and meningitis. Pediatr Infect Dis J 2:333–341.CrossRefGoogle Scholar
  9. 9.
    Boston Interhospital Virus Study Group and the NIAID Sponsored Cooperative Antiviral Clinical Study. Alford CA, Chien LT, Whitley R, et al. 1975. Failure of high dose 5-deoxyuridine in the therapy of herpes simplex virus encephalitis: Evidence of unacceptable toxicity. N Engl J Med 292:600–603.Google Scholar
  10. 10.
    O’Brien PC, Fleming TR. 1979. A multiple testing procedure for clinical trials. Biometrics 35:549–556.CrossRefGoogle Scholar
  11. 11.
    Whitley RJ, Alford CA, Hirsch MS, Schooley RT, Luby JP, Aoki FY, et al. 1986. Vidarabine versus acyclovir therapy of herpes simplex encephalitis. N Engl J Med 314:144–149, 1986.CrossRefGoogle Scholar
  12. 12.
    McCartney JJ. 1978. Encephalitis and ara-A: An ethical case study. Hastings Cent Rep 8:5–7.Google Scholar

Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • Richard J. Whitley
    • 1
  1. 1.Pediatrics, Microbiology, Medicine and NeurosurgeryUniversity of Alabama at BirminghamAlabama

Personalised recommendations