1.2 User Story Narrative: FDA Spontaneous Triggered Event Reporting
This user story is based upon the ASTER Study 1 and seeks to extend the Newborn Metabolic
Screening use case to support automated adverse event reporting using electronic health record
(EHR) data to the US Food and Drug Administration (FDA). The user story assumes: (1)
automated laboratory reporting to the hospital EHR and state public health agency, and (2) the
hospital subscribes to FDA Really Simple Syndication (RSS) feeds, which provides important risk
communication and warnings about FDA regulated products.
High-Level Functional Description:
Laboratory test results and RSS feeds are used to help initiate a series of related healthcare,
case management and reporting activities for a newborn and its parents. However, follow up
laboratory and diagnostic testing reveals that the testing method (test kit) used by the contract
laboratory is defective, which requires reporting to FDA, and subsequent changes to the newborn
and mother’s health records. The hospital’s EHR and incident reporting systems are
programmed with a pre-defined set of criteria, or “triggers” that are used to prompt the healthcare
provider and hospital risk manager to take appropriate action to manage the health concern and
complete reporting requirements.
Detailed Narrative Description:
A hospital’s contract testing laboratory returns results from a recent newborn metabolic screening
panel. The result indicates that the infant has the rare genetic disorder, Isovaleric Acidemia (IVA).
The pediatrician contacts the mother and requests a follow up appointment within the next two
weeks so that additional diagnostic tests can be performed. In the interim, the pediatrician
advices the mother to start using a leucine-free infant formula and contact the state’s public
health agency to obtain more information about the disease, including available services, such as
listings for specialists, dieticians, medical foods and other therapies used to manage the disease.
The pediatrician also advises genetic testing for both parents.
The mother contacts her OB/GYN and primary care physician about the infant’s test results and
requests a referral for genetic testing for her and her husband. Activities over the next two weeks
include verification of the state’s receipt of the initial laboratory report, assignment of an IVA
services case manager, parental genetic testing, and a second newborn screening panel.
The mother returns to the pediatrician’s office to review all laboratory tests and activities. The
pediatrician informs her that the second panel was negative, and the mother also confirms
negative genetic testing results for the disease, per separate follow up with her primary care
physician. The pediatrician advises the mother to continue using the leucine-free formula and
that she should return in 4-6 weeks for another series of diagnostic tests and clinical follow up.
A few weeks later, the hospital’s risk manager contacts the pediatrician concerning an FDA RSS
product recall alert for a manufacturer’s Amino Acids and Acylcarnitines Tandem Mass
Spectrometry Test Kits, which product lot numbers are confirmed to be used by the contract
laboratory facility. The risk manager coordinates follow up discussions with the pediatrician,
primary care physician, OB/GYN, and test laboratories (genetic and newborn screening) to
consult on the case and determine next steps. The consensus opinion is that the IVA test kit
used for the initial screening produced a “false positive” result, and that all records for the infant
1
The ASTER study was conceived as a proof of concept for a new model of gathering EHR data and
reporting spontaneous adverse drug events (ADEs) to FDA:
http://asterstudy.com/index.php?option=com_content&view=article&id=10:aster-description
and mother should be updated to reflect the correction. The newborn screening test laboratory
facility sends a corrected laboratory report to the hospital and state public health agency. The
risk manager confirms that the corrected report contains information that meets FDA reporting
criteria for a device malfunction report. The risk manager initiates an incident report, which is
auto-populated with EHR patient/parent information, medical/birth history, laboratory tests, and
product information (e.g., list of all medications/treatments, including the defective test kit
information). A report is generated and sent electronically to FDA.
1.2.1 Goal
In order to keep effective medical products available on the market, the FDA relies on the
reporting of serious adverse events, product quality problems, product use errors or therapeutic
inequivalence/failure associated with the use of an FDA-regulated drug, biologic, medical device,
dietary supplement or cosmetic. FDA uses these data to maintain our safety surveillance of
these products, and reporting from healthcare providers and product manufacturers is a critical
action that prompts a modification in use or design of the product, improves its safety profile and
leads to increased patient safety.
This user story raises awareness for the need for accurate newborn screening methods, and is
based upon the complementary activities of the FDA Office of Orphan Products Development
(OOPD) and the Center for Devices and Radiological Health (CDRH). OOPD’s mission is to
advance the evaluation and development of products (drugs, biologics, devices, or medical foods)
that demonstrate promise for the diagnosis and/or treatment of rare diseases or conditions. In
fulfilling that task, OOPD evaluates scientific and clinical data submissions from sponsors
(product manufacturers) to identify and designate products as promising for rare disease and to
further advance scientific development of such promising medical products. CDRH manages the
Medical Products Safety Network (MEDSUN) and the Manufacturer and User Facility Device
Experience Database (MAUDE). Collectively, these systems help protect and promote public
health by assuring the safety, effectiveness, and quality of medical devices, assuring the safety of
radiation-emitting products, fostering innovation, and providing the public with accurate, sciencebased information about the products they oversee throughout the total product life cycle.
1.2.2 Description of Data Reporting Events, Actors and Triggers
All States and Washington, DC have newborn screening programs. These programs help
integrate genetics into public health and population health by supporting state newborn screening
programs, genetic education programs and health information technology initiatives that work to
link families, consumers and providers.2
For the purposes of this user story:
The minimum event triggers are: 1) receipt of confirmed “negative” test rests, and 2) risk
manager’s discovery of a potential AE. The initial data collection occurs within 24 hours at the
birthing center/hospital. The attending pediatrician obtains a blood sample (heel-stick) from the
infant and completes the appropriate forms and sends the sample to the hospital’s contract
testing laboratory for a NBS (newborn screening) analysis. NBS results are used to help verify
the overall health status of the infant, and work to reduce morbidity and mortality in newborns and
children who have or are at risk for heritable disorders. The accuracy and reliability of approved
test methods, procedures and devices used for diagnosing rare diseases is a critical first step in
US HHS Health Resources and Services Administration’s Maternal and Child Health, Newborn Screening
webpage: http://mchb.hrsa.gov/programs/newbornscreening/index.html
2
mitigating risk or harm by insuring that newborns obtain the immediate and appropriate
healthcare required to manage the disease.
Since this user story is an extension of the Newborn Metabolic Screening use case, we expect
that there is a combination of paper-based and electronic data sources. For example, some
diagnostic laboratories have the ability to receive orders electronically (e.g., request for
service/test) sample tracking and linking (samples sent via mail/courier to electronic orders, which
help pre-populate the lab system), or one-way communication to a state/local public health entity
(agency or registry). Or, conversely, the entire process is paper-based and begins with the
receipt of the NBS screening form and sample.
Furthermore, because the user story is leveraging preexisting work efforts (Newborn Screening
and Electronic Laboratory Reporting), it is expected that the common data elements or content of
the “base record or report”, that is, patient demographics, parent information, medical history, etc.
would already exist in the EHR or other format (albeit that the formats may not be immediately
interchangeable or interoperable). The frequency of reporting is considered ad hoc – that is,
there is no predefined interval for when an adverse event report is required. The end-to-end
processing of the report is dependent upon the initial criteria or trigger used initiate other
programs or processes that would extract relevant data from the EHR and render it in such a way
that a human (physician, risk managers, etc.) could review the data and append additional
information prior to release to FDA. Once FDA receives the report (via FDA’ Electronic
Submissions Gateway), the report can be validated and immediately parsed into the appropriate
database for immediate review and follow up. Current reports are paper-based and are often
incomplete or have data quality issues. For example, a “dump” of patient laboratory data that is
not relevant to the adverse event and/or therapy dates. Automated reporting will help reduce
manual data entry costs (healthcare provider and FDA), ease reporting burden and facilitate
timely reporting of serious adverse events.
1.2.3 Data
FDA considers the content of the MedWatch (MW) Form 3500 and 3500A as the minimum
required dataset, and represents an historic, unstructured reporting format. Note that FDA has
implemented the HL7 Individual Case Safety Report Release 1 standard for electronic medical
device reporting based upon the content of the MW 3500A. However, the maximum dataset
(which includes the use of controlled terminology and the capture of structured data) is the
ISO/HL7 27953-1 V3 message specification. This specification is a multi-part standard, where
Part 1 is an overall framework for AE reporting for a variety of FDA-regulated products. Part 2 is
a conformance profile for human pharmaceuticals reporting, and covers the content of the
International Conference on Harmonisation’s E2B(R3) reporting guideline: “Electronic
Transmission of Individual Case Safety Reports (ICSR) Implementation Guide, Data Elements
and Message Specification3.
For the purposes of this user story, the following high-level information domains are included in
the data exchange – note that this is NOT an exhaustive list:
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3
Patient Demographics:
o Age, date of birth or patient age group
o Sex/Gender
o Weight
o Height
o Race
Associated Person Information
ICH E2B(R3) Public Consultation Information: http://estri.ich.org/new-icsr/index.htm
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o Parent or Sibling
Medical History (Patient and Associated Person)
Medications History, including concomitant medications (therapy dates and duration)
Relevant Laboratory/Procedure Information (including relevant dates and results)
Product Information
o Name or ingredients
o Product identifiers (e.g., NDC or UDI)
o Manufacturer
o Dosage Form, Route of Administration and Approach Site
o Product strength and dose amount
Adverse Event and Actions Taken
AE/Patient narrative (describing the event, actions taken, patient status, etc.)
Report Sender Information (organization name, contact party, etc,)
Primary source reporter (person that discovered the event and/or healthcare provider)
1.2.4 Other information
FDA has been very active in various international Standards Development Groups (SDOs),
involved in harmonizing adverse event, product problem and patient safety reporting standards
that can be considered as part of this user story:

HL7 Patient Safety: Provided leadership and sponsorship of the HL7 Individual Case
Safety Report (ICSR) V3 messaging standard. ICSR Release 1 – HL7 Normative and
ANSI standard 2005 (adopted for FDA CDRH Electronic Medical Device Reporting
(eMDR) program in 2006), ICSR Release 2 (aka ISO/HL7 27853): Completed HL7
balloting and ISO Final Draft International Standard ballot October 2011. Final
publication expected early 2012. FDA’s Center for Veterinary Medicine is an early
adopter of the standard (December 2010)

International Conference on Harmonisation (ICH): Common content guideline,
terminology and exchange format in use since 1997. Current ICH E2B standard is used
for expedited and clinical trial pharmacovilance reporting between global regulatory
authorities, pharmaceutical industry and the World Health Organization. ICH parties will
adopt ISO 27953-2, which is a conformance profile for 27953-1

Global Harmonization Task Force (GHTF): Common set of data elements and
terminologies for exchange of medical device reports (referred internally as N87
guideline). Current exchange format unique to GHTF; however, data elements (as of
2008) were harmonized with ISO/HL7 27953-1.

IHE Drug Safety Content (DSC) Profile: DSC describes the content and format to be
used within the Pre-population Data transaction described within the Retrieve Form for
Data Capture (RFD) Integration Profile. The purpose of this profile is to support a
standard set of data in CCD format which the Form Filler provides for use in reporting
adverse events as it relates to Drug Safety. In addition this profile will reference the ability
to convert this output into the ICH E2B(R3) standard
.
1.3 Stakeholder Commitment
There is significant stakeholder interest in using the ISO/HL7 ICSR 27953 standard. It has
already been adopted for global veterinary product surveillance and will replace the existing ICH
E2B(M) specification. Currently, reporting by healthcare providers to product manufacturers is a
manual process, that is, reports are usually phoned into a hotline or sent to a manufacturersponsored product registry. Companies are manually translating and/or data entering information
that is then transformed again so that it can be sent to FDA. Consistent data exchange and use
of common terminology will facilitate interoperability and data sharing across the product lifecycle:
clinical trials, use of products within the market, and patient safety/efficacy experience feedback
(via active or passive surveillance methods).
1.4 Contact Information:
Lise Stevens, Data Standards Project Manager
Bioinformatics Support Staff
FDA Center for Biologics Evaluation and Research
Lise.Stevens@fda.hhs.gov
(301) 827-2743