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Cost-Effective Approach to Managing Laboratory Reference Ranges for Local Laboratories in Clinical Research

  • Vadim TantsyuraEmail author
  • Imogene Grimes
  • Jules Mitchel
  • Sergiy Sirichenko
  • Jim Crowe
  • Deborah Viola
Drug Information

Abstract

The use of a single central laboratory with universal references ranges is not always a viable option in clinical studies; examples are oncology studies where a rapid turnaround of clinical laboratory results is critical. However, the complexities associated with multiple sites, multiple laboratories, and multiple age and sex groups can lead to logistical nightmares across clinical trials and make handling laboratory data one of the most challenging, labor-intensive, and time-consuming tasks for clinical data managers, especially where different laboratories are used for the same patient. Also, evidence suggests that the reference ranges (RRs) used by the local laboratories often create a false sense of precision that is not always supported by science. Managing time-specific, demographic-specific, and site-specific RRs requires significant investment in time and labor. As a result, an alternative approach to management of local laboratory RRs that uses “standard” (sometimes called “published”) ranges has been growing in popularity over the past several years. This article attempts to compare the pros and cons of this approach relative to the historic ways of handling local laboratory RRs. Scientific, operational, and economic perspectives are also presented.

Keywords

reference ranges normal ranges clinical trials clinical data management cost-effectiveness 

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References

  1. 1.
    Karvanen J. The statistical basis of laboratory data normalization. Drug Information Journal. 2003;37:101–107. https://doi.org/dij.sagepub.com/content/37/1/101.full.pdf+html.CrossRefGoogle Scholar
  2. 2.
    Thompson WL, Brunelle RL, Wilson MG. Performance and interpretation of laboratory tests. Quoted by: Cato A, Sutton L, Cato A III. Clinical Drug Trials and Tribulation. 2nd ed. New York, NY: Marcel Dekker; 2002. Drugs and the Pharmaceutical Sciences.Google Scholar
  3. 3.
    Wallach JB. Interpretation of Diagnostic Tests. 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2000.Google Scholar
  4. 4.
    Haag MDM, Kelly JR, Ho A, Seccombe DW. A study to examine the accuracy of potassium measurements in clinical laboratories across Canada. Clin Biochem. 2000;33(6):449–456. https://doi.org/www.ceqal.com/files/data/Publications/Methods/Accuracy%20of%20Potassium%20Measurements%20in%20Canada%202001.pdf.CrossRefGoogle Scholar
  5. 5.
    Dutta A, Saha C, Johnson CS, Chalasani N. Variability in the upper limit of normal for serum alanine aminotransferase levels: a statewide study. Hepatol. 2009;50:1957–1962. https://doi.org/onlinelibrary.wiley.com/doi/10.1002/hep.23200/pdf.CrossRefGoogle Scholar
  6. 6.
    Ruvuna F, Flores D, Mikrut B, De La Garza K, Fong S. Generalized lab norms for standardizing data from multiple laboratories. Drug Information Journal. 2003;35:61–79.CrossRefGoogle Scholar
  7. 7.
    Solberg HE, Stamm D. International Federation Of Clinical Chemistry (IFCC) Scientific Division, expert panel on theory of reference values approved recommendation on the theory of reference values, part 4. Control of analytical variation in the production, transfer and application of reference values prepared for publication. Eur J Clin Chem Clin Biochem. 1991;29:531–535. https://doi.org/edoc.hu-berlin.de/oa/degruyter/cclm.1991.29.8.531.pdf.PubMedGoogle Scholar
  8. 8.
    Henny J, Petitclerc C, Fuentes-Arderiu X, et al. Need for revisiting the concept of reference values. Clin Chem Lab Med. 2000;38:589–595. Quoted by: Hyltoft-Petersen P. A review of the Clinical Chemistry and Laboratory Medicine special issue on reference values (vol. 42, n. 7, 2004). https://doi.org/www.westgard.com/the-latest-on-reference-values-and-reference-intervals.htm#interpretlimits.CrossRefGoogle Scholar
  9. 9.
    Hyltoft-Petersen P. A review of the Clinical Chemistry and Laboratory Medicine special issue on reference values (vol. 42, n. 7, 2004). https://doi.org/www.westgard.com/the-latest-on-reference-values-and-reference-intervals.htm#interpretlimits.
  10. 10.
    Grimes I, Kidd M. Memo to file included in Map to NDA. Confidential source. 1997.Google Scholar
  11. 11.
    Henderson L. Oncology clinical trials, keys to approval. Appl Clin Trials Online. https://doi.org/www.appliedclinicaltrialsonline.com/appliedclinicaltrials/article/articleDetail.jsp?id=730568. Published July 1, 2011.
  12. 12.
    Congressional Budget Office. Research and development in the pharmaceutical industry. 2006. https://doi.org/www.cbo.gov/ftpdocs/76xx/doc7615/10-02-DrugR-D.pdf.
  13. 13.
    Kaitin KI. Deconstructing the drug development process: the new face of innovation. Clin Pharmacol Ther. 2010;87:356–361.CrossRefGoogle Scholar
  14. 14.
    Chuang-Stein C. Laboratory data in clinical trials: a statistician’s perspective. Drug Information Journal. 1998;19:167–177. Quoted by: Ruvuna F, Flores D, Mikrut B, De La Garza K, Fong S. Generalized lab norms for standardizing data from multiple laboratories. Drug Information Journal. 2003;35:61–79.Google Scholar
  15. 15.
    Chuang-Stein C. Summarizing laboratory data with different reference ranges in multicenter clinical trials. Drug Information Journal. 1992;26:77–84. Quoted by: Ruvuna F, Flores D, Mikrut B, De La Garza K, Fong S. Generalized lab norms for standardizing data from multiple laboratories. Drug Information Journal. 2003;35:61–79.CrossRefGoogle Scholar
  16. 16.
    Kratz A, Ferraro M, Sluss PM, Lewandrowski KB. Laboratory reference values. N Engl J Med. 1998;339:1063–1072.CrossRefGoogle Scholar
  17. 17.
  18. 18.
    FDA. Guidance for industry: drug-induced liver injury: premarketing clinical evaluation, July 2009. https://doi.org/www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM174090.pdf
  19. 19.
    FDA. Guidance for industry: development and use of risk minimization action plans, March 2005. https://doi.org/www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM126830.pdf
  20. 20.
    FDA. Guidance for industry: oversight of clinical investigations—a risk-based approach to monitoring, draft guidance, August 2011. https://doi.org/www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM269919.pdf

Copyright information

© Drug Information Association, Inc 2012

Authors and Affiliations

  • Vadim Tantsyura
    • 1
    Email author
  • Imogene Grimes
    • 2
  • Jules Mitchel
    • 3
  • Sergiy Sirichenko
    • 4
  • Jim Crowe
    • 5
  • Deborah Viola
    • 6
  1. 1.Vadim TantsyuraDanburyUSA
  2. 2.Otsuka Pharmaceutical CompanyRockvilleUSA
  3. 3.Target Health IncNew YorkUSA
  4. 4.Pinacle21/OpenCDISCBedminsterUSA
  5. 5.JT Crowe ConsultingRichmondUSA
  6. 6.New York Medical CollegeValhallaUSA

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