PMID- 30915153
OWN - NLM
STAT- MEDLINE
DCOM- 20190904
LR  - 20200225
IS  - 1748-6718 (Electronic)
IS  - 1748-670X (Print)
IS  - 1748-670X (Linking)
VI  - 2019
DP  - 2019
TI  - Likelihood-Ratio-Test Methods for Drug Safety Signal Detection from Multiple 
      Clinical Datasets.
PG  - 1526290
LID - 10.1155/2019/1526290 [doi]
LID - 1526290
AB  - Pre- and postmarket drug safety evaluations usually include an integrated summary 
      of results obtained using data from multiple studies related to a drug of 
      interest. This paper proposes three approaches based on the likelihood ratio test 
      (LRT), called the LRT methods, for drug safety signal detection from large 
      observational databases with multiple studies, with focus on identifying signals 
      of adverse events (AEs) from many AEs associated with a particular drug or 
      inversely for signals of drugs associated with a particular AE. The methods 
      discussed include simple pooled LRT method and its variations such as the 
      weighted LRT that incorporates the total drug exposure information by study. The 
      power and type-I error of the LRT methods are evaluated in a simulation study 
      with varying heterogeneity across studies. For illustration purpose, these 
      methods are applied to Proton Pump Inhibitors (PPIs) data with 6 studies for the 
      effect of concomitant use of PPIs in treating patients with osteoporosis and to 
      Lipiodol (a contrast agent) data with 13 studies for evaluating that drug's 
      safety profiles.
FAU - Huang, Lan
AU  - Huang L
AUID- ORCID: 0000-0003-2290-7466
AD  - Mathematical Statistician in the Division of Biostatistics, Office of Clinical 
      Evidence and Analysis, CDRH, FDA, Silver Spring, MD 20993, USA.
FAU - Zalkikar, Jyoti
AU  - Zalkikar J
AUID- ORCID: 0000-0002-6212-8793
AD  - Mathematical Statistician in the Division of Biometrics I, Office of 
      Biostatistics, OTS, CDER, FDA, Silver Spring, MD 20993, USA.
FAU - Tiwari, Ram
AU  - Tiwari R
AD  - Division Director in the Division of Biostatistics, Office of Clinical Evidence 
      and Analysis, CDRH, FDA, Silver Spring, MD 20993, USA.
LA  - eng
PT  - Journal Article
DEP - 20190219
PL  - United States
TA  - Comput Math Methods Med
JT  - Computational and mathematical methods in medicine
JID - 101277751
RN  - 0 (Proton Pump Inhibitors)
RN  - 8008-53-5 (Ethiodized Oil)
SB  - IM
MH  - Algorithms
MH  - Computer Simulation
MH  - *Data Interpretation, Statistical
MH  - Databases, Factual
MH  - *Drug-Related Side Effects and Adverse Reactions
MH  - Ethiodized Oil/pharmacology
MH  - Humans
MH  - *Likelihood Functions
MH  - Medical Informatics/*methods
MH  - Models, Statistical
MH  - Osteoporosis/drug therapy
MH  - Patient Safety
MH  - Product Surveillance, Postmarketing/statistics & numerical data
MH  - Proton Pump Inhibitors/pharmacology
MH  - Reproducibility of Results
MH  - Risk
MH  - Software
PMC - PMC6399568
EDAT- 2019/03/28 06:00
MHDA- 2019/09/05 06:00
PMCR- 2019/02/19
CRDT- 2019/03/28 06:00
PHST- 2018/09/28 00:00 [received]
PHST- 2018/12/07 00:00 [revised]
PHST- 2019/01/21 00:00 [accepted]
PHST- 2019/03/28 06:00 [entrez]
PHST- 2019/03/28 06:00 [pubmed]
PHST- 2019/09/05 06:00 [medline]
PHST- 2019/02/19 00:00 [pmc-release]
AID - 10.1155/2019/1526290 [doi]
PST - epublish
SO  - Comput Math Methods Med. 2019 Feb 19;2019:1526290. doi: 10.1155/2019/1526290. 
      eCollection 2019.