Abstract
The number of clinical trials conducted simultaneously in the USA and outside of the US (OUS) for medical device development has been increasing over the last decade. However, the presence of inherent regional differences in treatment effects poses a great challenge to the US regulatory agency’s decision making. In this chapter, we propose a two-tier procedure for analyzing data from such trials for the US regulatory agency’s decision making, allowing treatment effects to vary from region to region. We differentiate direct evidence from supporting evidence while using both to exemplify the advantage of such trials for the US regulatory agency’s decision making. The contribution of the supporting evidence can be adjusted according to the expectation of the magnitude of regional differences and the statutory requirements in the USA. Examples are presented to illustrate the design and analysis based on our proposed procedure. Using the proposed two-tier procedure with an upfront explicit decision tree can increase the predictability and transparency of the regulatory decision making.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Binkowitz B (2010) Highlights from the PhRMA MRCT Key Issue Team & DIA MRCT Workshop. Presented at: the 4th Seattle Symposium in Biostatistics: Clinical Trials. Seattle, WA, 20–23 November
Campbell G (2008) Statistics in the world of medical devices: the contrast with pharmaceuticals. J Biopharm Stat 18:4–19
Chen J, Quan H, Binkowitz B et al (2010) Assessing consistent treatment effect in a multi-regional clinical trial: a systematic review. Pharm Stat 9:242–253
Chen J, Quan H, Gallo P et al (2012) An adaptive strategy for assessing regional consistency in multiregional clinical trials. Clin Trials 9:330–339
CE Mark (2012) http://eur-lex.europa.eu/LexUriServ/site/en/consleg/1993/L/01993L0042-41220031120-en.pdf. Accessed 22 Oct 2012
FADASIA (2014) http://www.gpo.gov/fdsys/pkg/BILLS-112s3187enr/pdf/BILLS-112s3187enr.pdf. Accessed 3 Feb 2014
Food, Drug and Cosmetic Act (FD & C Act) (2012) www.fda.gov/RegulatoryInformation/Legislation/FederalFoodDrugandCosmeticActFDCAct/FDCActChapterVDrugsandDevices/ucm110188.htm. Accessed 25 May 2012
Guidance on the Collection of Race and Ethnicity Data in Clinical Trials (2012) http://www.fda.gov/RegulatoryInformation/Guidances/ucm126340.htm. Accessed 22 Oct 2012
Hung HMJ, Wang S-J, O’Neill RT (2010) Consideration of regional difference in design and analysis of multi-regional trials. Pharm Stat 9:173–178
International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. Q & A for the ICH E5 guideline on ethnic factors in the acceptability of foreign data (2012) www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E5_R1/Q_As/E5_Q_As__R5_.pdf. Accessed 25 May 2012
Lu N, Nair R, Xu Y (2011)Decision rules and associated sample size planning for regional approval utilizing multi-regional clinical trials. Presented at: the 4th Annual FDA/MTLI Medical Device and IVD Statistical Issues Workshop, National Harbor, MD, 13-14 April, 2011
Quan H, Chen J, Gallo P et al (2010) Assessment of consistency of treatment effects in multiregional clinical trials. Drug Inf J 44:617–632
Rothwell P (2005) External validity of randomized controlled trials: to whom do the results of this trial apply?. Lancet 365:82–93
Tanaka Y (2010) Statistical considerations in multi-regional clinical trials. Presented at: the Biopharmaceutical Applied Statistics Symposium XVII, Hilton Head, SC, 5–9 November, 2010
Tsou H-H, Chow S-C, Lan KKG et al (2010) Proposals of statistical consideration to evaluation of results for a specific region in multi-regional trials—Asian perspective. Pharm Stat 9:201–206
Disclaimer
No official support or endorsement by the Food and Drug Administration of this article is intended or should be inferred.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2015 Springer International Publishing Switzerland
About this paper
Cite this paper
Lu, N., Xu, Y., Gray, G. (2015). A Two-Tier Procedure for Designing and Analyzing Medical Device Trials Conducted in US and OUS Regions for Regulatory Decision Making. In: Chen, Z., Liu, A., Qu, Y., Tang, L., Ting, N., Tsong, Y. (eds) Applied Statistics in Biomedicine and Clinical Trials Design. ICSA Book Series in Statistics. Springer, Cham. https://doi.org/10.1007/978-3-319-12694-4_16
Download citation
DOI: https://doi.org/10.1007/978-3-319-12694-4_16
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-12693-7
Online ISBN: 978-3-319-12694-4
eBook Packages: Mathematics and StatisticsMathematics and Statistics (R0)