common serious adverse event (sae)...

Project Overview & Outputs

Common Serious Adverse Event (SAE) Fields

Table of Contents

Initiative Highlights 3

Development Overview 6

Industry Landscape 7

Asset Overview 8

Industry Standard Creation 10

Stakeholder Engagement 14

Team Participation 15

Copyright ©2019 TransCelerate BioPharma Inc., All rights reserved.

What is a serious adverse event?To fully understand this initiative, it is important to understand what a serious adverse event is.

According to the FDA, an adverse event is any untoward medical occurrence associated with the use of drug in

humans, whether it is specifically drug related.1 An adverse event, therefore, can be any unfavorable or unintended sign,

symptom, or disease temporarily associated with the use of a product whether the event is related to the product itself.

The FDA considers an adverse event to be serious if it results in any of the following outcomes: death, a life-threatening

adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity orsubstantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect1. It is important

note that certain medical events may be considered serious when they jeopardize the patient or require medical

intervention to prevent one of the outcomes listed above.

3

Common SAE FieldsInitiative Highlights

What is the Common SAE Fields initiative?The Common SAE Fields initiative is a TransCelerate led project designed to increase the quality and comprehensiveness

of serious adverse event (SAE) reports. The project focused on assessment of the common core fields collected and

reported following a serious adverse event. Upon completion of this assessment, the team proposed a list of SAE fields

that would better support a complete clinical picture of a serious adverse event. The initiative’s ultimate objective is to

provide the deliverable to an industry standard-setting organization and work with that organization to facilitate the

promulgation of a standard for SAE data fields. The deliverable is intended to serve as the starting point for standard-setting work and such work very well may result in a standard that differs, perhaps markedly, from content contained in

this deliverable

TransCelerate sourced subject matter experts from a variety of disciplines to participate on this team. Specific disciplines

included medical review physicians, pharmacovigilance experts, clinical operations experts, and case reporting / data

management professionals.

Common

SAE Fields

Initiative

1National Cancer Institute. NCI Guidelines for Investigators: Adverse Event Reporting Requirements for DCTD (CTEP and CIP). 2018.


How did this team address this issue?

A comprehensive landscape assessment was conducted to understand the applicable current industry

regulations. Following the landscape assessment the team collected various SAE report collection forms.

A third-party consultant collected, blinded and aggregated all data fields into a master list. To arrive at

a common list of SAE fields, the team consolidated data fields based on commonality and relevance.

Following the completion of the core SAE fields list, the Common SAE Fields team passed on its work to

CDISC, a standard-setting body, to develop an industry standard. TransCelerate expects CDISC to

promulgate a standard that will achieve much greater consistency in the industry with regard to data

fields for SAE reporting, although CDISC’s ultimate standard may differ from the data fields identified by

TransCelerate.

4

Common SAE FieldsInitiative Highlights

What was the objective behind this initiative?

Throughout the industry, patient safety data collected during interventional clinical trials can

significantly differ. The resulting variation seen across Sponsors can create ambiguity for investigators.

All Sponsors are required to follow the same health authority reporting regulations. Therefore, an

opportunity exists to identify a set of core data fields for the purposes of serious adverse event (SAE)

reporting. TransCelerate sought to address this issue by launching the Common SAE Fields initiative and

working with an industry standards organization to facilitate standard-setting work on this topic.

Common

SAE Fields

Initiative

Copyright ©2019 TransCelerate BioPharma Inc., All rights reserved. 5

Inherent value-add by developing and adopting an industry standard around SAE data collection is expected across patients, sites, sponsors, and health

authorities.

Improves quality of case narratives

which ultimately improves signal

detection

Advances patient safety by allowing

for earlier knowledge of a drug’s benefit/risk

Improves efficiencies in SAE data collection and reporting processes

Addresses ambiguity in data reporting

for investigators

Improves initial report submissions by

reducing repetitive case versions & SUSAR reports

Optimizes data collection processes,

which, in turn, allows relevant case

information to become more apparent

Improves efficiencies in SAE reporting

operations

Advances the collection of quality data

Improves initial report submissions thereby reducing repetitive case versions

Patients

Investigators

Health Authorities

Sponsors

Common SAE FieldsImpact & Value


The Common SAE Fields Sprint was broken out into four phases: landscape assessments, asset development, handoff to CDISC, and industry awareness.

Phase 1: Current Landscape Phase 2: Asset Development Phase 3: Transition to CDISC Phase 4: External Engagement

In this phase, a

comprehensive landscape

assessment was conducted.

The intent was to understand

and ascertain the relevance

of specific industry guidance

and regulations.

In addition, a secondary

objective of this phase was to

assess whether or not deriving

a list of common SAE fields

was feasible, given the

variability seen across sponsor

companies.

The results of the landscape

assessment were incorporated

into the common SAE fields list

as supporting documentation.

Following the landscape

assessment, three separate

assets were developed:

Common Core SAE Fields List

List of common core SAE Fields

necessary to obtain a

complete picture of a SAE.

Communications Packet

Documentation surrounding

the project, providing detail

into what was accomplished

CDISC Transition Plan

Documentation detailing the

transition of assets and work

from TransCelerate to CDISC

Upon completion of the three

assets, TransCelerate transitioned

the Common Core SAE fields list

to CDISC to create an industry

standard pertaining to data

collection at the onset of a SAE.

Developing an industry standard

typically is expected to takes

around 12 – 18 months to

complete.

Some of the members from the

TransCelerate initiative will be

working within CDISC to support

CDISC’s standards development

process by acting as Serious

Adverse Event and Safety

Operations SMES during the

standards setting process.

As with any TransCelerate

project, engaging with

industry stakeholders is

paramount to any project.

Connecting with the industry

helps foster new ideas and

growth.

In this case, TransCelerate will

showcase its work from the

Common SAE fields sprint via

the following methods:

- Attending industry

conferences

- Presenting at industry

symposiums

- Obtaining health authority

feedback via CDISC

- Connecting with CROs

Common SAE FieldsProject Phases


Regulatory

Considerations

MedWatch

CIOMS

ICH E2A/E2B

CDASH

MedWatch is the FDA’s safety information and

adverse event reporting program. It provides

guidance for industry and investigator safety

reporting requirements, specifically for INDs and

BA/BE studies.

See also: FDA Form 3500A

The Council for International Organizations of

Medical Sciences (CIOMS)was established by

WHO and UNESCO. It eleases health research

guidance including ethics, medical product

development, and safety.

See also: CIOMS Safety Form

The International Council for Harmonization of

Technical Requirements for Pharmaceuticals for

Human Use (ICH) developed guidelines (E2A & E2B)

to standardize data elements for transmission and

reporting of individual case safety reports.

See also: E2A Guidelines, E2B Guidelines

Clinical Data Acquisition Standards Harmonization

(CDASH) is a functional standard setting body

created by CDISC. It focuses on developing standards

around data collection during the SAE reporting

process.

See also: CDASH SAE Supplement v1.1

In order to ensure developing a core list of SAE fields would be pertinent and valuable, specific industry guidance and regulations were leveraged as a basis.

Common SAE FieldsCurrent Industry Guidance

7Current Landscape Asset Development Transition to CDISC Stakeholder Engagement


Common SAE FieldsAsset Development

The Common SAE Fields team used a multi-phase approach to aggregate its core list of common SAE fields. The methodology is described below.

8

4. Common SAE Fields List1. Data Field Aggregation

+

+

3. Grouping & Validation

By the numbers By the numbers By the numbers By the numbers

24 separate forms 2 separate lists 2 separate lists 1 master list

131 sections of data 73 sections of data 13 sections of data 9 sections of data

1238 total fields 833 unique fields 237 unique fields 133 unique fields

2. Commonality Assessment

Current Landscape Asset Development Transition to CDISC Stakeholder Engagement


The final list of common SAE fields yielded 135 unique fields across 9 categories of data. Category detail and additional details are listed below.

Supporting Documentation

- Field Description

- Existing CDASH Mapping

- E2B R3 Mapping

- CIOMS Mapping

- MedWatch Mapping

Common

SAE Fields

List

Protocol &

Investigator

Subject

Demographics

Relevant Medical

History

Medication

Information

Relevant Diagnostics

& Labs

Serious Adverse Event

Attributes

SAE Criteria –

Death Supplemental

SAE Criteria –

Hospitalization

Supplemental

Pregnancy Data

12 unique fields

9 unique fields

6 unique fields

44 unique fields

7unique fields

12 unique fields

5 unique fields

3 unique fields

35 unique fields

Common SAE FieldsAsset Development



Common SAE FieldsWhat is CDISC?

CDISC is a global, open, multi-disciplinary, vendor-neutral, non-profit

Standards Development Organization (SDO) founded in 1997. CDISC

collaborates with industry, regulators, NPOs and academia to develop

and maintain data standards. It also supports and facilitates standards

development teams to create open, free standards. CDISC

foundational standards include:

What does CDISC do?

CDISCClinical Data Interchange

Standards Consortium

SEND: Standard for Exchange of Nonclinical Data

PRM: Protocol Representation Model

CDASH: Clinical Data Acquisition Standards Harmonization

SDTM: Study Data Tabulation Model

ADaM: Analysis Data Model

QRS: Questionnaires, Ratings and Scales



CDASH, the foundational CDISC standard for data collection,

establishes a standard way to collect data consistently across studies

and sponsors. Additionally, harmonized data collection formats and

structures provide clear traceability of submission data into the Study

Data Tabulation Model (SDTM), delivering more transparency to

regulators and others who conduct data review.

What does CDASH do?

Data Consistency

Ensures precise, accurate

data is collected from

investigators / CROs.

Traceability to SDTM

Provides continuity

between data capture,

data management and

analysis

Data Format & Structure

Provides guidelines for how

data should be organized at

point of data capture

Regulatory Transparency

Allows for transparency into

the end-to-end lifecycle of

data from inception to

delivery

CDASHClinical Data Acquisition

Standards Harmonization

11

Common SAE FieldsWhat is CDASH?



Planning Data Collection Data Tabulation Study Reporting

Pre-Clinical Protocol Case Report Form Data Capture Data Mgmt Analysis Reporting Archiving

Therapeutic Area User Guides

Controlled Terminology (CT)

Operational Data Model (ODM), Define-XML, SDM-XML, Dataset-XML

SEND PRM CDASH SDTM ADaM

CDISC StandardR&D Study Phase Data Lifecycle

CDISC’s functional standards exist at various time points within the lifecycle of a data point. The below table highlights where CDASH resides within the

CDISC landscape.

Sta

nd

ard

Sta

nd

ard

Life

cyc

le

12

Common SAE FieldsCDISC Landscape



As planned, TransCelerate’s Common SAE Fields team transitioned its work to CDISC’s CDASH SAE Standard team who has proceeded with development of

an industry standard surrounding SAE data collection. Eventually, this SAE standard will serve as an update to the existing CDASH SAE Supplement v1.1.

TransCelerateCommon SAE Fields Team

Subject Matter ExpertsSpecific members of the

Common SAE Fields team will

participate on CDASH’s SAE

Standard Team to serve as

SAE Subject Matter Experts

Project AssetsThe Common SAE Fields team

also transitioned two assets that

will serve as guidelines for

developing this industry

standard:

- Common Core SAE Fields List

- Industry Regulations Mapping

CDASH SAE Standards Team

Standard DevelopmentUpon receipt of assets from

TransCelerate, CDASH’s SAE

Standards team proceeded

with work to create an industry

standard surrounding SAE

reporting.

Standard MaintenanceAs with any CDISC foundational

standard, CDISC will continue to

maintain and update the SAE

standard as new industry

guidance and regulations are

released.

- CDASH SAE Standard

Sta

nd

ard

De

ve

lop

me

nt

Pro

ce

ss

Complete Asset Development

Transition Assets

Begin Standard Development

Complete Public Review of

Standard

Finalize Standard & Prepare for

Release

Release Standard to Industry

Maintain Standard

TransCelerate6 Months

TransCelerate/CDISC1 Month

CDISC3 Months

CDISC2 Months

CDISC3 Months

CDISC1 Month

CDISC

Standard Development Details

13

Common SAE FieldsStandard Development Process



Common SAE FieldsStakeholder Engagement

Sponsors

Conference Presentations

- SCOPE 2020

- DIA Europe 2020

- DIA Annual 2020

Investigators / CROs

- SCRS Global Summit

- Investigator Value Survey

Standard-Setting Bodies

- Collaboration with CDISC

to Create Industry

Standard

As with many TransCelerate initiatives, sharing assets and discussing best practices with industry stakeholders is cornerstone. In addition to transitioning

assets to CDISC to create an industry standard, the Common SAE Fields team continues to engage with the following stakeholders to promote awareness

and collaboration throughout the industry.



Common SAE FieldsTeam Participation

TransCelerate would like to thank the following individuals for their hard work and dedication to this project.

Aileen NollAstellas

Brian DragusAbbvie

Claudia SchafferEMD Serono

Corinne HanotinSanofi

Deb SollodAllergan

Karen OuttenMerck

Kim RiveraPfizer

Maria Claudia BecerraMerck

Marie FasehunAllergan

Mike WardEli Lilly

Michelle BorrelliJ&J

Nancy PyrnAbbvie

Nik PembleJ&J

Norman HuangAllergan

Shelia TedderUCB

Simon TurnerAstraZeneca

Tara BarkerGSK

Vibeke MeriumNovo Nordisk

Vicki ReesJ&J

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