Clinical Trials

❘❙❚■ Chapter 14 | Noninferiority Trials• ensuring that the trial is well monitored• ensuring that the results of the two analysis populations (PP and ITT)do not conflictThe choice of δ is critically important, and needs to be prespecified and justifiedwhen designing the trial. Although the choice of δ is dependent on the indicationand available regulatory guidance, sound clinical judgment is always required.References1. International Conference on Harmonisation of Technical Requirements for Registrationof Pharmaceuticals for Human Use. ICH Harmonised Tripartite Guideline: StatisticalPrinciples For Clinical Trials E9. Recommended for Adoption at Step 4 of the ICH Processon 5 February 1998 by the ICH Steering Committee. Available from:www.ich.org/MediaServer.jser?@_ID=485&@_MODE=GLB. Accessed May 6, 2005.2. File TM Jr, Lode H, Kurz H, et al. Double-blind, randomized study of the efficacy and safety oforal pharmacokinetically enhanced amoxicillin-clavulanate (2000/125 milligrams) versus those ofamoxicillin-clavulanate (875/125 milligrams), both given twice daily for 7 days, in treatment ofbacterial community-acquired pneumonia in adults. Antimicrob Agents Chemother 2004;48:3323–31.3. Committee for Proprietary Medicinal Products. Points to Consider on the Choice of Non-Inferiority Margin. Efficacy Working Party, EMEA. Draft released for consultation, February 2004.Available from: www.emea.eu.int/pdfs/human/ewp/215899en.pdf. Accessed June 10, 2004.4. Garau J. Treatment of drug-resistant pneumococcal pneumonia. Lancet Infect Dis 2002;2:404–15.5. Committee for Proprietary Medicinal Products. Note for guidance on evaluation of medicinalproducts indicated for treatment of bacterial infections. Efficacy Working Party, Note forGuidance, European Commission. Draft 1996. Available at www.emea.eu.int/pdfs/human/ewp/055895en.pdf. Accessed June 14, 2004.6. Snapinn SM. Noninferiority trials. Curr Control Trials Cardiovasc Med 2000;1:19–21.7. Makuch R, Simon R. Sample size requirements for evaluating a conservative therapy.Cancer Treatment Reports 1978;62:1037–40.8. Farrington CP, Manning G. Test statistics and sample size formulae for comparative binomial trialswith null hypothesis of non-zero risk difference or non-unity relative risk. Stat Med 1990;9:1447–54.9. Hauck WW, Anderson S. Some issues in the design and analysis of equivalence trials.Drug Inf J 1999;33:109–18.10. Jones B, Jarvis P, Lewis JA, et al. Trials to assess equivalence: the importance of rigorous methods.BMJ 1996;313:36–9.140