Analytical and Bioanalytical Chemistry

, Volume 385, Issue 5, pp 975–981 | Cite as

Testing equivalence between two laboratories or two methods using paired-sample analysis and interval hypothesis testing

  • Shixia Feng
  • Qiwei Liang
  • Robin D. Kinser
  • Kirk Newland
  • Rudolf Guilbaud
Technical Note


A modified interval hypothesis testing procedure based on paired-sample analysis is described, as well as its application in testing equivalence between two bioanalytical laboratories or two methods. This testing procedure has the advantage of reducing the risk of wrongly concluding equivalence when in fact two laboratories or two methods are not equivalent. The advantage of using paired-sample analysis is that the test is less confounded by the intersample variability than unpaired-sample analysis when incurred biological samples with a wide range of concentrations are included in the experiments. Practical aspects including experimental design, sample size calculation and power estimation are also discussed through examples.


Equivalence Interval hypothesis testing Paired-sample analysis Bioanalysis Comparability 



The authors would like to thank Drs. Hans Roethig and Mohamadi Sarkar for helpful discussion and suggestions.


  1. 1.
    Shah VP, Midha KK, Findlay JW, Hill HM, Hulse JD, McGilveray IJ, McKay G, Miller KJ, Patnaik RN, Powell ML, Tonelli A, Viswanathan CT, Yacobi A (2000) Pharm Res 17:1551–1557 (also see FDA/CDER (2001) Guidance for industry bioanalytical method validation (online document). FDA/CDER, Rockville, MD, see, last accessed 24th April 2006)
  2. 2.
    Kuselman I (2006) Accred Qual Assur 10:466–470CrossRefGoogle Scholar
  3. 3.
    EURACHEM/CITAC (2003) Traceability in chemical measurement: A guide to achieving comparable results in chemical measurement (online document). EURACHEM/CITAC, Budapest, Hungary (see http://www/, last accessed 24th April 2006)
  4. 4.
    Youden WJ, Steiner EH (1975) Statistical manual of the Association of Official Analytical Chemists. AOAC, Washington, DCGoogle Scholar
  5. 5.
    Miller JN, Miller JC (2000) (eds) Statistics and chemometrics for analytical chemistry, 4th edn. Prentice Hall, New YorkGoogle Scholar
  6. 6.
    Schuirmann DJ (1987) J Pharmacokinet Biop 15:657–680Google Scholar
  7. 7.
    Hartmann C, Smeyersverbeke J, Penninckx W, Vanderheyden Y, Vankeerberghen P, Massart DL (1995) Anal Chem 67:4491–4499Google Scholar
  8. 8.
    Boogaard PJ, van Sittert NJ (1995) Occup Environ Med 52:611–620CrossRefGoogle Scholar
  9. 9.
    Boogaard PJ, van Sittert NJ (1996) Environ Health Perspect 104 (Suppl 6):1151–1157CrossRefGoogle Scholar
  10. 10.
    Diletti E, Hauschke D, Steinijans VW (1991) Int J Clin Pharmacol Ther Toxicol 29:1–8Google Scholar
  11. 11.
    Phillips KF (1990) J Pharmacokinet Biop 18:137–144Google Scholar
  12. 12.
    Chow SC, Liu JP (eds) (1999) Design and analysis of bioavailability and bioequivalence studies, 2nd edn. Marcel Dekker, New YorkGoogle Scholar
  13. 13.
    Liu JP, Chow SC (1992) J Pharmacokinet Biop 20:101–104Google Scholar
  14. 14.
    Locke CS (1984) J Pharmacokinet Biop 12:649–655Google Scholar
  15. 15.
    Richter SJ, Richter C (2002) Qual Eng 14:375–380Google Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Shixia Feng
    • 1
  • Qiwei Liang
    • 1
  • Robin D. Kinser
    • 1
  • Kirk Newland
    • 2
  • Rudolf Guilbaud
    • 3
  1. 1.Philip Morris USAResearch CenterRichmondUSA
  2. 2.MDS Pharma ServicesLincolnUSA
  3. 3.MDS Pharma ServicesSt. Laurent (Montreal)Canada

Personalised recommendations