How ARIA Analyses Have Been Used by FDA

This page summarizes how select analyses conducted in Sentinel's Active Risk Identification and Analysis (ARIA) system have been used by FDA since Sentinel's official launch in February 2016. ARIA can contribute to FDA’s regulatory process in a variety of ways, such as contributing evidence to support a label change, respond to a Citizens Petition, or become part of an Advisory Committee deliberation. Information from ARIA can also provide evidence that alleviates concerns about a particular safety issue and might lead FDA to determine that no regulatory action is necessary based on the available information.

Each ARIA analysis listed below contributed in some material way to inform an important regulatory discussion or action. FDA makes decisions about drug safety issues based upon the totality of evidence. The listing of an ARIA analysis in the table means that Sentinel’s ARIA system was one important source of evidence considered.

 

Drug Name

Outcome Assessed

ARIA Analysis

Regulatory Determination / Use

Date Posted

Keppra (levetiracetam)

Anaphylaxis and angioedema

Level 1

Drug Safety Label Change, Warnings and Precautions

11/30/2017
Ketoconazole oral tablets

Drug use trends after safety label change and use in labeled indications

Level 1

Citizen Petition Response

12/4/2017

Antipsychotic agents (including haloperidol injection)

Ischemic and hemorrhagic stroke

Level 1, Level 2

Sentinel data was used to support decisions around potential labeling changes for antipsychotics and stroke risk. FDA decided that no action is necessary at this time, based on available information.

12/8/2017
Gadolinium-based contrast agents Exposure in pregnancy Level 1

Advisory Committee Presentation & FDA Drug Safety Communication

12/19/2017
TNF-alpha inhibitors Exposure in pregnancy Level 1

Drug Safety Label Change, Pregnancy and Lactation 

12/21/2017
None Respiratory syncytial virus associated illness (RSV-AI) Level 1

Epidemiological assessment of RSV-AI and patterns of health care utilization to help inform development of novel RSV therapeutics 

1/25/2018
Sinuva (mometasone furoate)

Cataracts and glaucoma

Level 1

Feasibility assessment of ARIA sufficiency to replace a sponsor postmarketing requirement (PMR) safety study

2/5/2018
Continuous or extended cycle oral contraceptives Venous thromboembolism Level 1, Level 2

FDA decided that no action is necessary at this time, based on available information.

3/5/2018
Multiple Drug utilization in pregnancy to evaluate enrollment in pregnancy registries compared with spontaneous reports  Prototype L1**

FDA is using these findings, in addition to input received from the 2014 FDA Public Meeting, to evaluate safety data collection in pregnant women

7/26/2018
Actemra (tocilizumab) Exposure in pregnancy Level 1

Provided information to evaluate reported difficulties in enrollment in ongoing pregnancy registry

8/7/2018

How Mini-Sentinel Analyses Have Been Used By FDA

Drug Name

Outcome Assessed

Analysis

Regulatory Determination / Use

Date Posted

Pradaxa (dabigatran etexilate)

Intracranial hemorrhage, gastrointestinal bleed

Level 1*

FDA decided that no action is necessary at this time, based on available information.

1/24/2018

Olmesartan medoximil

Intestinal sprue

Level 1*

Safety Labeling Change, Warnings and Precautions; Drug Safety Communication

  1/24/2018

Xarelto (rivaroxaban)

Intracranial hemorrhage, gastrointestinal bleed, and ischemic stroke

Level 3

FDA decided that no action is necessary at this time, based on available information.

1/24/2018

Second generation antipsychotic agents

Metabolic effects in children  (Type 2 diabetes, metabolic syndrome, weight gain)

Protocol-based assessment**

FDA decided that no new action on behalf of pediatrics is necessary at this time, based on available information.

2/2/2018

Onglyza (saxagliptin) and Januvia (sitagliptin)

Acute myocardial infarction

Protocol-based assessment**

Advisory Committee Presentation 

2/2/2018

Onglyza (saxagliptin) and Januvia (sitagliptin)

Hospitalized heart failure

Protocol-based assessment**

Advisory Committee Presentation 

2/2/2018

Intravenous iron products

Anaphylaxis

Protocol-based assessment

FDA decided that no action is necessary at this time, based on available information.

2/12/2018

*This query was performed using Mini-Sentinel’s Modular Program 3, the precursor to an ARIA L1 analysis.

**Complete results are contained in the associated publications and/or final written reports.