An Overview of Clinical Trial Registry - Trial

Transparency Requirements
Solutions to the meet global requirements for public data disclosure

Note about this presentation

This presentation is intended as an introduction to clinical

trial registration and results disclosure requirements.
Level: BEGINNER
This presentation is intended to provide an overview of
the evolution and current state of clinical trial registration
and results disclosure and regulatory requirements are
paraphrased using lay language for clearer
communication. However, the presentation should NOT
be considered a complete or authoritative source of
information.

April 15, 2010

ARMA Presentation

Agenda

A Brief History of Clinical Trial Transparency

Clinical Trial Transparency Requirements
The Challenges with Trial Transparency
The Cost of Compliance Survey Results
Solution Overview

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ARMA Presentation

.
.
.
.
.

A Brief History of Clinical Trial Transparency

Agenda

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ARMA Presentation

What is a Clinical Trial

A clinical trial evaluates new therapies to test whether they are

safe and effective
Clinical Trials are generally divided into four phases:

Phase I:
ranges

Initial safety investigation and evaluating dosage

Phase II:

Initial efficacy investigation and further safety

assessment

Phase III:
larger

Extensive exploration of efficacy and safety in a

population

Phase IV:
world

Post market evaluation of the drug in the real

And two main types :

Interventional: The investigators give the research subjects a

particular medicine or other intervention.

Observational: The investigators observe the subjects and measure

their outcomes. The researchers do not actively manage the
April 15, 2010
ARMA Presentation
experiment.

Have You Ever Participated in a Clinical

Trial?

April 15, 2010

ARMA Presentation

A Problem with Transparency

Trials repeated unnecessarily, adding to patient risk

TGN1412. In 2006, the drug caused catastrophic systemic organ

failure in the trial subjects. A similar study had been conducted in
1994 (March 2006)

Potential safety concerns or lack of efficacy not adequately

reported
Paxil Apparent suppression of unfavorable research (2004)
Vioxx Meta analysis published with safety concerns (November,
2004, The Lancet) and NEJM editorial (December, 2005)
Trasylol Negative results from a retrospective study initially
withheld (September 2006)
Avanida Meta analysis published with safety concerns (June,
2007, NEJM)

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ARMA Presentation

A Problem with Perception

In 2006, only 7% percent of Americans believe that statements

made by Pharmaceutical Companies are "generally honest and
trustworthy - Harris Poll Survey in July 2006

There was a perception that Life Sciences companies engage in

selective publication:
By not publishing Trials that dont support the desired efficacy
statements
By not including Trials that indicate undesired adverse events in
peer-review articles
By not conducting meta-analysis across trials looking for adverse
events with enough rigor

There was a perception that the FDA was too cozy with Life
Sciences companies

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ARMA Presentation

Timeline Mandatory Disclosure

Maine
Maine Law
Law
Enacted

FDAMA
FDAMA 113
113
(Mar 2002)
Registry
Registry Available
Available

FDAMA
FDAMA 113
113 1997
1997
(No Registry
Available)
1988
1988 Hope
Hope Act
Act
AIDS Study
Enrollment
Enrollment

198
0

Clinicaltrials.gov
Clinicaltrials.gov
implemented

199
0

200
0

200
1

200
2

200
3

200
4

Int.
Int. Legislation
Legislation
Israel

Maine Regulation

Int. Legislation
South Africa

FDA-AA
FDA-AA 2007
2007
Title VIII

Int.
Int. Legislation
Legislation
Italy

Multiple
Multiple States
States
introduce
introduce
Legislation
Legislation

200
5

200
6

200
7

Registration
Required
Required
Argentina, Brazil,
Czech
Czech Republic
Republic
(gov't
(gov't posts,
posts, like
like
EudraCT)
India, France, etc.

EMEA
EMEA
EudraCT
for
for Pediatric
Pediatric Trials
Trials

200
8

200
9

Mandatory disclosure includes trial registration and, under some laws, results posting
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ARMA Presentation

Voluntary and Mandatory Disclosure

Voluntary Disclosure

Disclosure Required

Africa
(Pan-African registry)
Australia
China
Cuba
Germany
Japan
Netherlands
(may be mandatory soon)
Sri Lanka
UK

April 15, 2010

ARMA Presentation

Argentina
Brazil
Czech Republic
France
India
Israel
Italy
South Africa
Taiwan
US FDAMA 113 (1997) and FDAAA
(2007)

Clinical Trial Transparency Requirements

Agenda

April 15, 2010

ARMA Presentation

Trial Registration in the US

Trials that DO require registration

Most Phase II , III and IV drug clinical trials

Sponsors may voluntarily register trials that do not
require registration by law

Trials that DO NOT require registration according to

FDAAA

Phase I Trials
Observational Studies

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ARMA Presentation

Trial Registration in the US

State of Maine Registration of Trials

The State of Maine has recently passed an amendment to their

disclosure law that additionally requires registration of
observational studies, as well as making most optional fields
mandatory.

Registration for device trials

Device trials have a slightly different definition for applicable

clinical trial.
Under FDAAA there is a special provision that allows delayed
public disclosure of registration information for trials for a novel
device.

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ARMA Presentation

Results Disclosure Status in the US

FDAAA

Disclosure of results required for a sub-set of registered clinical

trials. Results must be disclosed for all interventional trials of
FDA approved marketed products.

Note:
- It is possible that results disclosure will be required for unapproved
drugs by September 27, 2010 under FDAAA

Results Disclosure Maine

The State of Maine has recently passed an amendment to their

own trial disclosure law that requires disclosure of results for
observational trials and discontinued trials.

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ARMA Presentation

Deadlines: Results

FDAAA requires results not later than 12 months after:

The earlier of either the estimated or actual date of the last visit
of the last patient specifically for purposes of data collection for
the primary outcome of the trial
Within 30 days of receiving a marketing authorization for a new
drug
Note:
- Sponsor can apply for an extension in certain circumstances when
a trial is still ongoing with blinded data.

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ARMA Presentation

Elements that may be added in 2010

The expansion of FDAAA, mostly for trial results

disclosure, is under consideration by US lawmakers and
must be finalized by September 27, 2010.
Under consideration are:

Adding a summary of the trial and results in non-technical

language.
Adding a technical summary of the trial and results
Disclosing the full protocol or at least that information on the
protocol for the trial that may be necessary to help evaluate the
results of the trial.
Requiring results for unapproved products
Other categories as the HHS Secretary determines appropriate.

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ARMA Presentation

EU Clinical Trial Results Disclosure

Legal requirement

Disclose Results on EudraCT (EU Clinical Trials Database)

Applies to pediatric trials (for now)

All Pediatric trials conducted in the EU or if part of a PIP

For pediatric trials, results are to be disclosed within 6 months of
study completion for both unapproved and marketed products.
For adult trials, results are to be disclosed 1 year after study
completion.

Results to be made public sometime in early 2011

Note: EudraCT to make protocol registration data public

in Q3, 2010

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ARMA Presentation

The Challenges with Trial Transparency

Agenda

April 15, 2010

ARMA Presentation

Clinical Trial Registry Landscape

Areas

that influence disclosure

Legal

requirements and the registries

that support their regulations such as
FDAAA, Maine, EudraCT,
clinicaltrials.gov.
Policy Influences such as International
Committee of Medical Journal Editors
(ICMJE), WHO, WMA
Organizational SOPs and guidelines
Institutional Review Boards (IRB) and
Ethics Committees (EC)
These

four areas establish

Required

data (depth and breadth of

data)
Timing for submission and disclosure
The

requirements from these four may

not align with one another.
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ARMA Presentation

ORGANIZATIONAL SOP

ICMJE

REGULATORY

IRB & EC

Requests and interests from patient

advocacy groups and the media add further
disclosure pressures

Multiple Registries / Different Timelines

Register trial
before study
approval with
EudraCT, South
Africa, etc.

Study
Approved

Register
Study at
ClinicalTrials
.gov to
comply with
FDAAA,
Maine and
ICMJE
First Patient
Enrolled

Update Study
at
ClinicalTrials.g
ov

Open New Site

In US

Study

Update Study
at
EudraCT
Register Study
in local
country
Update Study
at
ClinicalTrials.g
ov

Open New Site

In EU

Submit
Results
at EudraCT
of
pediatric
trials
(expected
by early
2011)

Submit
Results to
ClinicalTrials.g
ov

Study
Complete
Primary
Completion
Date

and results data must be provided to multiple registries

Accurate and consistent data should be reported across
registries.
Registries may have different disclosure timeframes
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ARMA Presentation

Complex Compliance Environment

Globally, there are many interest groups closely

monitoring clinical trials
Regulations and data requirements are frequently
changing and are not aligned internationally
Deadlines demand rapid integration of new requirements
Rules for disclosure are complex and often subject to
interpretation
Organizations may not have full control over what is
disclosed
Registration and results disclosure information remains
publicly available on clinicaltrials.gov indefinitely
(including the complete record of data changes)

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ARMA Presentation

Consequences for Non-Compliance

US

FDAAA
- $10,000 for first event
- $10,000 per day for every day late (if not corrected within
30 days)
- Public notice of failure in registry/results data bank
- Withholding remaining or future grant funding (where
applicable)
State of Maine
- Barred in Maine from advertising prescription drugs on
television, radio or in print
- Up to $10,000 per day

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ARMA Presentation

Consequences for Non-Compliance

International

No application possible without prior registration where trial

registration is mandated
Local IRB/ethics boards may deny approval, even in areas
where registration is voluntary

ICMJE

Unable to publish articles in peer-review journals that follow

the strict interpretation of the ICMJE rules.

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ARMA Presentation

Other Non-Compliance Risks

Violation of FDA labeling and advertising regulations

Violation of the False Claims Act
Violation of SEC rule prohibiting forward-looking
statements
Significant restitution payments to private insurance
companies
Damage to reputation, good will and brand equity
Company placed under consent decree
In the US, Sponsors must submit Form 3674 certifying
compliance, with criminal and civil penalties for
submitting a false certificate

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ARMA Presentation

The Cost of Compliance

Survey Results

Agenda

April 15, 2010

ARMA Presentation

Departments Responsible for Posting

Department Primarily Responsible for Registration
Clinical Operations
Regulatory Affairs
Clinical Sciences / Clinical R&D
Medical Writing
Medical Affairs
Clinical Communications and Standards
Department Primarily Responsible for Results
Regulatory Affairs
Clinical Operations
Biostatistics
Medical and Scientific Affairs
Publication
Clinical R&D
Medical Writing
Clinical Communications and Standards
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ARMA Presentation

Trial Disclosure - Stakeholders

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ARMA Presentation

Trial Transparency Time Allocation

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ARMA Presentation

Results Disclosure Time Allocation

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ARMA Presentation

Cost for a Typical Company

# of
Processes
per Month

Process

# of
Processes
per Year

General Administrative Tasks

Cost per
Year
$75,836.14

# of new trials registration

43

$27,441.82

# of site/location updates

23

273

$9,433.51

# of clinical trials registration updates (excl. site/location

updates)

15

180

$12,390.31

# of new trial results disclosures

31

$136,875.35

# of trial results disclosure updates

111

$117,114.81

# of ICH E3 study synopsis prepared

34

$35,780.29

Total Cost

$414,872.24

Number of
International
Registries
Additional Registries

April 15, 2010

# of additional Regs.

# of Months in 2010
with new registries

5
6
Total costs in 2010 with Additional Registries

ARMA Presentation

Cost per Year

$216,983.10
$631,855.34

Solution Overview

Agenda

April 15, 2010

ARMA Presentation

Common Data Sources

Clinical Trial Management System (CTMS)/Clinical Trial
Database or Trial Spreadsheet
Protocol/Clinical Study Report
Informed Consent Forms
Clinical Data Management System (CDMS) such as SAS
Pharmacovigilance System

April 15, 2010

ARMA Presentation

Common Requirements for a Solution

Centralized data capture and transformation for protocol

registration and results posting (automated to minimize
manual data entry, ensuring ensure data integrity)
Automated upload of protocol registration and results to
registries
A flexible platform that supports extension to international
registries
Mapping of common data elements across registry records
to maximize efficiency and guarantee consistency
Robust workflow for registration and results, including
disclosure assessment, review and approval workflows
Full audit trail & version control

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ARMA Presentation

Support for Data Standards

April 15, 2010

ARMA Presentation

Clinical Trial Design

Protocol Authoring
and Documentation

The BRIDG Model

c d Comprehens iv e Logica l Mode l

Design Concepts::Masking
+
+
+
+

l evel:
obj ectOfMaskin g (set):
pro cedureT oBreak:
unmaskTri ggerEve nt (set):

Protocol
Concepts::
Contr ol

Ha sSu bEl eme nts

AbstractActi vi ty
Perio d
De sign Conc epts ::El ement

Protoc ol Concepts::DesignCharacteristic

Name:
Author:
Version:
Created:
Updated:

Comprehensive Logical Model

Fridsma
1.0
7/22/2005 2:53:51 PM
7/29/2005 2:33:32 PM

+
+
+
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+
+

Protoc ol
Conc epts::
Scope

Protocol
Conce pts ::
Configuration

synop si s:
type: test va lue domain = a ,d,f,g
summaryDescrip ti on :
summaryCode :
d etai led Method Descript ion :
d etai led Method Cod e:

Ch il dren: Se t
ep och Typ e: EpochT ype s

Ab stractActivit y

Clinical Trial
Registration

h asEl ements

hasSch edul ed Eve nts

De sign Conc epts::Pl annedTask

-

Protocol
Concepts::Bias

d ispl ayName : char[ ]

whoPerfo rms: i n t
se qu ence : in t
p rocDefID: PSM Cod edCon cep t
so urceTe xt: char[]

Sub jectEve nt

Protocol Conce pts ::StudyBac kground(w hy)

+
+
+
+
+
+
+
+
+
+
+

Design Conc epts::Arm

Des ign Conce pts::Protoc olEv ent

descri ptio n: PSMDe scri p ti on

su mm aryOfPrevio usFi nd i ngs: PSMDescripti on
su mm aryOfRisksAndBen efi ts: PSMDescri pti on
ju stifi catio nOfOb ject ives: PSMDescript ion
ju stifi catio nOfApproa ch: PSMDescri pti on
popul atio nDe scri ptio n: PSMDe scri p tion
ra ti onal eForE ndp oin ts: PSMDe scrip ti on
ra ti onal eForD esig n: PSMDe scri pti on
ra ti onal eForM asking : PSMDescri pti on
ra ti onal eForC ont rol: PSMDe scripti o n
ra ti onal eForA nal ysisApp roach: PSMDe scrip ti o n

hasEl em en ts
Protocol Conce pts ::StudyObli gation
+
+
+
+

t ype : ENUMERATED
d escri pti on: PSMDescriptio n
commission ingParty:
resp onsi bl eParty:

Des ign Concepts::

Random ization
+
+

Protocol Concepts::
Concurrency

pa ren t: AbstractActi vi ty
eventT yp e: Schedul edEven tTyp e
stu dyOffset: PSMInte rva l
stu dyDayOrTi me: char

nam eOfArm: char[]

pla nne dEn rol l men tPe rArm: char[]
ran dom ization Wei ghtForArn: int
associa tedSch edul es: Se t

ta sksPerfo rme dTh i sSched ule

taskAtEven t

hasOng oi ngEve nts

m ini mumBl o ckSize :

m axi mum Bl ockSi ze :
1..*
Ab stra ctActivi ty

+corre l ati veStudy 0.. *

Des ign Concepts::Eve ntTa sk

Busine ss Obj ects ::Study

Busine ss Obj ects ::

Clini calDeve lopme ntPlan
-_Deve lop me ntPl an

+
+
+
+
+
+

Bus ine ssObj e cts:

:Am endme nt

+pri maryStu dy 1

startDa te: Date

end Date: Date
typ e: PSM Cod edCon cept
pha se: PSMCodedCo nce pt
ran domi zedInd i cator: Text
Sub j ectTyp e: PSMCo dedCon cep t

h asArms

De sign Conc epts ::StudySchedule

lo calFaci li tyT ype : L ocal Facil ityTyp e

centra lFa cili ti tyT ype : Ce ntral Fa ci lit iyT yp e
eventID: OID
ta skID: OID
pu rpo ses: Se t

Pe riod s: Set
Ta sks: Se t
Ta skVi si ts: Se t
associ ated Arms: Set

h asUn sch edu led Events

Busine ssObje cts ::

Inte gra tedDev elopme ntPlan

Protocol Conce pts ::StudyObje cti v e(w ha t)

+
+
+
+

Subject Eve nt
Des ign Concepts::Unsche duledEv ent

BusinessObj ects::
Acti v itySchedule (the "how",
"w he re", "w hen", "w ho")

eve ntType: Un sch edu ledEventType

acti vityI D: OID

de scri ption : PSMDescripti on

descripti o n: PSMDe scri ptio n

in ten tCod e: SET ENUMERATED
obj ecti veTyp e: ENUM{Primary, Seconda ry,Anci ll ary}
id : PSMID

ha sPu rposes
execu tion mode

De sign Conce pts ::

StudyActivityRe f

Sche dule d S ub Act ivitie s

0 ..*
-source
ob j ective

Pr otoc ol Conc epts::StudyDocum ent

+
+
+
+
+
+
+
+
+
+
+
+

Busi nes sObj ec ts::

ProtocolDoc ument

effe ctiveEn dDate: DATET IME

version :
aut hor: SET
effe ctiveStartDate : DATETIM E
ID: SET PSM ID
documentID:
type: ENUMERATED = fo rma l pl us n on.. .
descrip ti on: PSMDescri pt ion
title :
stat us: PSMSt atus
con fi de nti a li tyCode: PSMCo ded Con cep t
busine ssProce ssMo de: PSMBusin essProcessMod e

1..*

Protoc ol Conc epts ::Outcome

1..* -

BusinessObj ects ::
Clinic alStudyRe por t

descrip tion : BRIDGDe scri pti on

ran ki ng : O utco me Ran k
associa tedObj e ctive: Set
ana l yti cMe tho ds: Set
asMeasuredBy: Se t
out comeVa ri ab le:
thre sho l d:

Defin ed By

t ype :

co mp lete: b ool
va lue : Value
ti mestamp: t ime stamp
i temOID:

Defin ed By

+
+
+
+

tran saction Type:

ODM ItemDa ta
Design Conc epts::
Dia gnostic Image

Ba sic Types::RIM Activ ityRel ationship

+
+
+
+
+
+
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+

subj ectID: in t

Bas icTypes ::StudyVar iable

-

ODM:ItemData
De sign Conc epts ::
Trea tme ntConfi rmed

Sta tistical Conce pts::Sta tisti cal ConceptAre a

+
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Entitie s and Roles::Orga niza tion

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+

instant iati on Type: ENUM {Pl acehold er, Actual }

id: SET <PSMID>
1
name: stri ng
cod e: PSMCo dedCon cep t
qua nti ty: i nt
descrip ti on: PSMDescri pt ion
sta tusCode: BRIDGStatus
1
exi sten ceT i me : BRIDGIn terval
riskCod e: PSMCo dedCon cep t
han dli ngCode : PSMCod edConcept
con tactInforma tion : SET <PSMCont actAddr>

* +
+
+
+
+
+
+
+
+

Entities and Roles::Activ ityRoleRe lations hip

i d:
code: PSM CodedConcept
n ame:
statu s:
e ffe ctive Sta rtDa te:
e ffe ctive End Da te:
g eo graphi cAdd ress:
e lectroni cCo mmAd dr:
certi fi ca te/li cen seText:

+
+
+
+
+
* +
+
+
+
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+

ge ogra phi cAd dre ss:

el e ctro nicCommAddr:
standa rdIn dustryClassCod e:
1

birthTi me:
sex:
de ceasedI nd: boo lea n
de ceasedT i me :
mu l tip l eBi rthIn d: boo l ea n
mu l tip l eBi rthO rde rNu mbe r: i nt
org anDono rInd : b ool ean

Entitie s a nd Role s::

Ma nufacturedMa teria l

+
+
+
+
+
#

-source
a ctivi ty

+
-

BasicTypes::ActActRelation

si gni fi canceLe vel : do ubl e

lowerReje cti o nRe gion : i nt
upperRej ecti o nRegi on: i nt
testSta ti sti c:
compa ri so nType: Anal yt icCo mp arisonT ype s
associ atedSum ma ryVaria bles:

hasAnal ysisSets

de scri ption : BRIDGDescriptio n

rel atio nQu ali fier: BRIDGCod edConcept
mo de: PSMBusin essProcessMod e
eff ecti veT i me : BRIDG Interva l
pri orityNumbe r: NUMBER
ne gati onRul e : Ab stra ctRule
de tail : char
sou rce Act: Ab stractActivi ty
de stAct: Abst ractActivi ty
seq ue nce: i n t

+
+
+

p roperty rel ati onQu ali fi er() : PSMCod edConcept

p roperty so urceAct() : AbstractActi vi ty
p roperty de stAct() : AbstractActivity

cl ini calJusti fica tion : T EXT

kind OfActRe lati on

AbstractActivity

ki ndOfAnal ysis

BasicTypes:: RIMActi vi ty

ki ndOfAnal ysis

businessPro cessMo de: PSMBusin essProcessMod e

cod e: PSMCo dedCon cep t
derivati onExpressio n: TEXT
stat us: PSM Co ded Concep t
+Te rmi natin gActivi ty 1 ..*
ava il ab i lityTime: Ti mingSpeci ficati on
prio ri tyCode: PSMCodedConcep t
con fi de nti a li tyCode: PSMCod edCon cep t
rep eatNum ber: ran ge OfIntege rs
+EndEven t 1
inte rruptibl eInd icator: BOOLEAN
uncerta i ntyCod e: Cod edConcept
+Sta rtEvent 1
rea sonCode : P SM Cod edConcept

-_Stat isti calA nal ysisSet

Sta tisti cal Concepts::

Sta tistical As sumption

Statistica l Conc epts ::Hypothes is

*
Pr otocol Concepts::StudyObj ec tiv e Relationship
+

typ e: PSMCoded Con cep t

+
-

statement: PSMDe scrip ti on

asso ciatedObj ecti ve:
cl ini call ySig ni fi can tDi ff: ch ar

Abstract Acti vity

-_Hypot hesis
*
hasAna lyse s

Bas icType s::

Abstr actRule

descripti on: PSMDescri pti on

Statis tical Conce pts ::Analys is

+
+
+
+
#
#

de scri pti o n: PSMDe scri ption

an alysisT ype : Se t{Anal ysisT ype s}
an alysisRol e:
ra ti on aleForAnal ysisApp roach: PSMDe scri p tion
associ ated Strateg y:
associ ated Hypoth ese s:

h asChil d Ana l yse s

hasStrate gy

i sExclusi ve: boo l

ru n() : bo ol

hasAssump ti o ns

ha sMo de l

Statistic al Concepts::Stati stic alM ode l

+
#
-

de scrip ti on : P SMDescri ption

ou tputSta tistic: StudyVariab le
co mpu tati ons: Se t
assumpti o ns: Set

i mp lements

Imple me nts

i mple me nts

ha sCo mpu tati ons

Entitie s a nd Role s::Dev ice

-

+
-

Stati stic al Concepts::

Sa mpleSi zeCalc ulation
+

+First Acti vity 1..*

strai n:
gend erStatu sCo de:

de scri ptio n: cha r

subgroup Vari abl e: Stud yDa tum
seque nce : i n t

hasAna l yse s

Entities a nd Rol es::

NonPer sonLiv i ngEntity
+
-

de scrip ti o n: PSMDescri p tion

sco peT yp e: Anal ysi sScopeT ype s

ha sCri teria

-sou rce
acti
vi ty acti vi ty
+target

+
+
+
+
+
+
+
+
+
+
+

co nfid ential it yCo de:

Entities a nd Roles::
Acce ss

Enti ties and Roles::Pe rson

ODM:It em De f
Des ign Concepts::
PlannedObs erv ation

Stati stic al Conc epts::

Sta tisticalAna lysis Se t

ha sAn alysi sSe ts

e val uabl eSu bj e ctDefin ition : char

i ntentTo Tre atPopu lati on: cha r
cli ni cal l yMe ani ngfu lDi ffere nce : char
p roceduresForM issin gData: ch ar
statSoftware : ch ar
methodForMi ni mi zi ngBi as: ch ar
subj ectRepl ace men tStrateg y: cha r
rand And Stra tificatio nProce dures: char

Statis tical Conce pts ::Hypothes isTe st

j obCode : PSMCod edConcept

OPr otoc olStruc ture ::

Elec tronicSystem

l otNumb erT ext: stri ng

e xpi ratio nTi me :
stab il ityT im e:

OID: lon g
Name : char
u nitOfMe asureID: O ID
m inValid :
m axVali d:
co ntro l le dName: ENUM

Statis tical Conc epts ::AnalysisSetCrite rion

Entitie s a nd Role s::Patie nt

Enti ties and Roles ::Employee

+

form Cod e:

g eograph i cAddress:
marital Statu sCo de:
e ducatio nLe velCod e:
raceCode :
d isab ili tyCode:
l i ving Arra ng eme ntCdoe:
e lectroni cCo mmAddr:
rel igi ousAffi l i atio nCode:
e thni cGroup Cod e:

hasHypotheses

re lati onshipCode: PSMCod edConcept

se que nceNu mber: NUMBER
n ega tion Indi cator: BOOLEAN
ti me: Ti min gSp ecifi cat ion
conta ctMedi umCode : PSMCod edConce pt
ta rge tRo leAware nessCo de: PSMCo ded Co nce pt
si gna ture Cod e: PSMCo ded Con cep t
si gna ture : P SMDescri pt ion
sl otReservati onIndi cator: BOOL EAN
su bst iti onCon dit ionCode : PSMCod edCo ncept
i d : PSMID
status: PSMCod edConcept
1.. *

Entitie s and
Roles::Materia l

Entities and Roles ::Li v ingEntity

+
+
+
+
-

+
+
+
+

Business Obj ec ts::

Statistical Ana lysisPlan

Entities and Roles::Role

ki nd OfActivityRel ation

resta tes Obje ctive

*
Entities and Rol es::Entity

gpsText:
mob ileI nd: bo olea n
add r:
dire cti onsT ext:
position Text:

role InAnal ysis: Rol eIn An al ysisTypes

re latio nsh ipCode : PSMCod edConcept

se quence Numbe r: NUMBER
pauseCrit erio n:
ch eckpoin tCo de:
sp li tCode :
jo inCo de:
negati onI ndi ca to r: BOOLEAN
co nju nctio nCode :

1..*

Entiti es a nd Roles::Place

ODM:ItemDef
Des ign Concepts::
Pl annedInterv ention

ki ndOf

abstract
Des ign
Conce pts ::
Study ActivityDe f

ODM:Ite mData
Des ign Concepts::
Subje ctDatum
-

type:
d escripti on: PSMDe scri ptio n
versi on:
ID: SET PSMID

Entities and Roles ::

Study

+
-

Abst ractActi vi ty

i sKi nd Of

Ba sic Types::Ana lysisVa riableInst

associ ate dVa riab le
ODM ItemDa ta
Design Conc epts::Obs erv ation
Busine ssO bj e cts ::
Communica tionRec ord

+targ et 0..*

i sBase l ine : bo ole an

pu rposeType: Pu rposeType
associa ted Outcome:

Busi nes sObjec ts::

SupplementalMate rial

+so urce 1
Entitie s a nd
Roles ::
Rese archProgra m

BasicType s::StudyDa tum

Design Conc epts ::Ev entTas kPurpose

a s Measured By

man ufa cturerModel Na me:

software Name:
l oca lRe moteCo ntro lSta teCode :
alertLevelCode :
l astCali brati onT ime:
+IsCon tai ned In

+contai ns 1
OProtocolStr ucture::
Res ponsibilityAss ignment

1. .* +targ
+soetActi
urceActivi
vi ty ty 1

i mp lementa tio nCla ss

Design Conc epts::
Te mporalRul e

Statistical Conce pts::

Se quentia lAnalysisStra tegy
+
+
+
+

al ph aSp end ing Fun cti on :

timin gFuncti on:
anal ysis:
tri alAdju stmentRul e:

Ab stractActi vi ty

imp l em en tatio nCl ass

BusinessObj ects::
Busines sRule

i mpl eme nta ti onCl ass

Desi gn Concepts::
Clinica lDe cisi on

Statistic al Conc epts::Computa tion

-

descripti on: PSMDescri pti on

al gorithm: cha r
input: Abst ractStat isticalParam ete r
output: Ab stractSta tist ical Para me ter

+passedT
+ge nerates
o
0 ..*
OProtocolStructure::
Ac tiv i tyDeriv edData

hasSche dul es

Plans::Protocol/Plan

Business Obj ects ::

SiteSubj ectManagementPr oje ctPl an

1..*

OStudy Des ign and Data Coll ection::

O BRIDGDeriv a tionExpres sion

Bas icTypes ::BRIDG Interv a l

Bas icTypes ::BRIDGBusine ssProc ess Mode
+

mod eVal ue : ENUM {Pl an, Execu te}

startT ime : ti mestamp

e ndT ime : tim estamp

+
+
+
+

Busi nes sObj ec ts::

Ra ndomizationAssignment

OStudy Des ign and Data Coll ection::OBRIDGTra nsition

Basic Types::BRIDGID
+
+
+

so urce: T ext
ve rsio n: Text
va lue : T ext

+
+

criterion: RULE
e ven tName: TEXT

+
+
+
+

name: T EXT
val ue:
controlle dName : PSMCod edConcept
busi nessPro cessMo de: PSMBu sine ssProce ssMode

co de: TEXT
co deSyst em:
co deSyst emName: TEXT
co deSyst emVersion: NUMBER
d ispla yName: T EXT
o ri gin alT ext: TEXT
transl atio n: SET {PSMCode dConce pt}

+
+
+

Business Obj ects::

EnrollmentRe cord

rand omi zati onCode:

subje ctID:
a ssig nmentDate Tim e:

Business Obj ects::Guide

Busine ssObj e cts ::

FinalRandom iza tionAss ignment
Busine ssObj ects ::
Wa iv er

Pr otoc ol Concepts::Cons tra int

OStudy Design a nd Data Collection::
OEncounterDefinitionLis t--???
Ba sic Type s::BRIDGStatus
+
+
+

effect iveEndDate:
effect iveStart Date:
statusVal ue:

Ba sicTypes::BRIDGContactAddr

abstractio n
+
+
+

typ e: PSMCoded Concep t

effectiveT ime: BRIDGInterva l
usa ge: PSMC ode dCo nce pt

Protocol Conce pts::

Eligibil ityCriter ion

l istOfDat aCo llecti onInstrument s:

Protocol Concepts::
Varianc e

Protocol Concepts::
Ex clus ionCriterion

Bus ine ssObje cts:

:Protocol Rev iew
+
+

April 15, 2010

1 1..*
Busi nes sObj ec ts::Inv e sti gatorRe cruitme ntPlan
Busines sObj ec ts::
Clinica lTri alMater ialPlans

Bus ine ssObj e cts ::

Da taMonitoringComm itte ePl an
Busine ssObj e cts ::Bi ospecimenPla n

Bus ine ssObj e cts ::

Da taM ana gementPla n

Ba sicType s::BRIDGAnalysis Variabl e

BasicTypes ::BRIDGCodedConcept
-

Structured
Statistical Analysis

Busines sObj ec ts:

:
RegulatoryRecord

typ e: ENUM{transformatio n, sel ecti o n}

rul e: T EXT
i d: PSMID
na me: TEXT

1
Busine ssObj e cts ::
SiteStudyMa nagementProj ectPlan
BusinessObj e cts ::
SponsorStudyMa nagementProj ectPlan

da te:
re sult:

Protocol Concepts::
Mil estone

Protocol activities and

Safety monitoring (AE)
Eligibility
Determination

ARMA Presentation

Business Obj ects ::

Adv erseEv e ntPlan

Bus ine ssObj e cts ::

Subj ectRec ruitme ntPlan

Business Obj ects ::Assa yProcedure s

BusinessObj ects::
Conti nge ncyPla n

Business Obj ects::SafetyMonitoringPlan

From Douglas B. Fridsma, MD, PhD

Structured Content Management

Non-Clinical

Phase I-III

Phase IV

Submission Planning

IND

Protocols Analysis
Data Sets
toxicology
pharmacokinetics

Registries and Journals

Study Planning
& Management
Study
Concepts

Protocol
Authoring &
Collaboration
Objective
Stat Plan
CRF
Schedule
Amendments

Annual

Site
Management

Clinical Data
Management

Safety

CM&C

IRB Approvals

Data collection
Randomization
CRF Edit checks
Site queries

AE/SAE Case
Management

Product
manufacture
Route

USPI/SPL

1572 Forms

Data Sets
Interim Final

Expedited
Reporting

Control of
Excipients
Procedures\
validation

Promotional &
Ads

CVs

DMC
Collaboration

Aggregate
Reporting
PSUR ASR

Control of
Product
procedures
batch analysis

Investigator
Brochure

Budget
Funding &
Tacking

Enrollment /
Consent

Protocol
Disclosures &
CSR Publication

Monitoring

April 15, 2010

NDA

ARMA Presentation

Labeling &
Commercial

Key Questions Companies Face

How will they deal with non-US registries? and

differing US states?
How will they keep up with rapidly evolving
requirements
How do they ensure disclosure consistency globally?
Where does the data exist inside their organization?
What validation requirements do they have?
What are the Best Disclosure Practices?
Can they support an audit of their registry and results
disclosure process?
Will they consider SaaS solutions
Is business process outsourcing an option for them?
April 15, 2010

ARMA Presentation