PMID- 21178990
OWN - NLM
STAT- MEDLINE
DCOM- 20110228
LR  - 20191210
IS  - 1532-6535 (Electronic)
IS  - 0009-9236 (Linking)
VI  - 89
IP  - 2
DP  - 2011 Feb
TI  - Application of the BRAT framework to case studies: observations and insights.
PG  - 217-24
LID - 10.1038/clpt.2010.280 [doi]
AB  - The BRAT Framework is a set of flexible processes and tools that provides a 
      structured approach to pharmaceutical benefit-risk decision making in drug 
      development and post approval settings. A work in progress, it consists of six 
      steps that produce representations of key tradeoffs, with appropriate 
      documentation of the rationale for decisions and the assumptions made in their 
      development. This article describes insights, gained from case studies, into the 
      Framework's performance in a variety of constructed benefit-risk scenarios, 
      focusing on a hypothetical example of a triptan for migraine. The scenarios 
      described illustrate the challenges inherent in arriving at many of the 
      regulatory decisions, including obtaining data for matching populations for all 
      outcomes, finding data of consistent quality, addressing correlated outcomes 
      (e.g., elevated liver function tests and hepatitis rates), dealing with rare but 
      serious adverse events (AEs), and understanding and making decisions based on 
      information for many outcomes simultaneously. The Framework provides a structure 
      for organizing, interpreting, and communicating relevant information, including 
      heterogeneity in results and the quality and level of uncertainty of data, in 
      order to facilitate benefit-risk decisions.
FAU - Levitan, B S
AU  - Levitan BS
AD  - Department of Epidemiology, Johnson & Johnson Pharmaceutical Research & 
      Development, LLC, Titusville, New Jersey, USA. blevitan@its.jnj.com
FAU - Andrews, E B
AU  - Andrews EB
FAU - Gilsenan, A
AU  - Gilsenan A
FAU - Ferguson, J
AU  - Ferguson J
FAU - Noel, R A
AU  - Noel RA
FAU - Coplan, P M
AU  - Coplan PM
FAU - Mussen, F
AU  - Mussen F
LA  - eng
PT  - Journal Article
DEP - 20101222
PL  - United States
TA  - Clin Pharmacol Ther
JT  - Clinical pharmacology and therapeutics
JID - 0372741
RN  - 0 (Tryptamines)
SB  - IM
MH  - Decision Making
MH  - Drug Discovery
MH  - *Drug Industry
MH  - Humans
MH  - Migraine Disorders/*drug therapy
MH  - Outcome Assessment, Health Care
MH  - *Risk Assessment
MH  - Tryptamines/adverse effects/*therapeutic use
EDAT- 2010/12/24 06:00
MHDA- 2011/03/01 06:00
CRDT- 2010/12/24 06:00
PHST- 2010/12/24 06:00 [entrez]
PHST- 2010/12/24 06:00 [pubmed]
PHST- 2011/03/01 06:00 [medline]
AID - clpt2010280 [pii]
AID - 10.1038/clpt.2010.280 [doi]
PST - ppublish
SO  - Clin Pharmacol Ther. 2011 Feb;89(2):217-24. doi: 10.1038/clpt.2010.280. Epub 2010 
      Dec 22.