protocol representation model in the real worldprotocol representation model in the real world...

Optimizing Clinical Trials: Concept to Conclusion™ © 2012 Medidata Solutions, Inc. § 1

Optimizing Clinical Trials: Concept to Conclusion™

Protocol Representation Model in the Real World

Joshua Pines Senior Manager, Medidata Solutions


Agenda

•  Introduction

• Challenges

• Opportunities

• Application


Brief Intro - The Theory Behind PRM!


The PRM and BRIDG Relationship

• PRM is a domain analysis model

• PRM is a collection of BRIDG Classes

• Protocol Representation Sub Domain View + Additional Classes

4


Why Use BRIDG?

• Protocol ID = Protocol ID = Protocol ID

• Whatever the implementation, we can be assured that “Protocol ID” is semantically the same across the entire study lifecycle

• BRIDG ensures it is technically the same as well

5


But People Think it’s Not That Simple


Challenges – A Reality Check!

7


PRM is a Scary-Sounding Acronym


Analysis Model vs. Implementation


Document-Centric Thinking Abounds

“My protocol standards will be different than

yours so how can there be an ‘industry

standard’?”


Opportunities for PRM

11


There is More Complexity and Data

• Studies are increasingly longer and more complex1

•  49% higher procedure frequency •  74% longer studies •  270% longer CRFs •  6.5% more unique procedures

• 15-30% of data not used in NDA2

• 24% of procedures are non-core3 •  Contributing 18% of per patient procedure budget

1 Tufts Center for the Study of Drug Development: Assessing the impact of protocol design changes on clinical trial performance,

2 Tufts Center for Drug Development: Assessing the down stream impact of protocol design complexity

3 Tufts Center for Drug Development: 2012 Protocol Study


Which is Driving Up Protocol Amendments

Getz, Zuckerman, Cropp, Hindle , Krauss. Measuring the Incidence, Causes and Repercussions of Protocol Amendments. Drug information Journal. 2011 45(3); 265 - 275

13

*Analysis of those protocols with at least one amendment Note: All values are means

•  69% of all protocols have at least one amendment

•  46% of all amendments occur BEFORE first patient first dose

•  34% are considered “somewhat” or “completely’” avoidable

•  Adds 61-days and cost $450,000+ to implement each amendment


Application of PRM

14


Results

•  Simplified protocols •  Reduced number of procedures and CPP •  Reduced effort on downstream systems •  Minimized cleaning and analysis of excess data

•  Avoid amendments/rework •  Reductions in cycle times •  Minimized duplicate entry

•  Shift from CDM to information management •  Increased quality, consistency of clinical info •  Align objectives, endpoints and procedures

A New Approach to Study Design Strategy/Goal

•  Line of sight from strategy to plan to study design •  Parallel development of Protocol, RAP, eCRF, CSR •  Leverage industry benchmarks

Modular Authoring

Tem

plat

es a

nd R

euse

Feas

ibilit

y As

sess

men

tRe

view/

App

rova

l/ Di

strib

utio

nAu

thor

ing

Plan

ning

& s

tudy

des

ign

CIL

Medidata Designer

Enter study id

1

Trigger: CIL ‘wants to’

1

Study Information Skeleton Created

Automatic

Medidata Designer2, 3

Grow study information in Design environment

8Medidata Designer

CIL / EST2,3,4,5,6,7

Medidata Designer

Select delivery template(s)

9CIL / EST

9

8,9 10Automatic

Medidata Designer

Populate study information from Design env

Medidata Designer

CIL / EST11

Develop WORD content within Design env

9

Templates include:- CSP- Protocol- RAP- eT&E- CSR focus document / shell- Disclosure summary (tbd)

12CIL / EST

12

Upload deliverables to eDX for review

eDX

eDX

Approval of deliverables

Governance

eDX

13

15

12

Review of deliverables

Internal / External

14

17

IMMS

CIL / EST

PIER

16CIL / EST

Upload approved deliverables to PIER

16

15

Upload approved deliverables to IMMS

Conduct Protocol Specific Feasibility

??

Regional Medical Director

Or does this input to WORD content?

Do we need Inc/Exc flow into eDX in order to perform

feasibility analysis (ref SB)? Or is this just manual

reference?

Draft

Final

Internal functionality not mapped: review, report, ppt

Internal references utilised in growing the information but not mapped:

- Reference content- Standard procedures

- Indicative costs

What is captured here?- new content or

- content that cannot go into design environment

IR interface for tables/listing & graphs – where?

Would details for adaptive trials have to be added here?

Trigger:1, Want wider input2, Develop WORD

content

Trigger??

Comments / Edits

Comments / Edits

‘Approved’ / FPAData Input and Output

1.Study id’s 2. Medium term study design (OneCDP)3. Study Master Data (MDM)4. Library of approved standard content (eProtocol) {All studies, Asset, study level}5. Legacy information (IMMS)6. Standard procedures (within system from MDR?)7. Indicative costs (eProtocol)8. Study information 9. Document Template Library10. Study information from design environment in template11. Additional information captured in WORD in design environment12. Draft deliverable13. Review deliverable14. Final ‘Approvable’ Deliverable15. Approved Deliverable16. Published Deliverable17 Archived Deliverable18. eDocument Metadata

2

15,16Technical Authoring Team

Store & Manage Deliverable Metadata

Medidata Designer9

Technical Authoring Team

6

??

eProtocol, IMMS


Metadata Search of Ref Content for Reuse

9

eProtocol

18

2

Define Deliverables Templates


Copy Existing Deliverables Content: ??

??

??

Scope:Start = medium term study design onwardsEnd = approval, publishing & archiving of all study deliverables; deliverable metadata to facilitate re-use

eSignature or workflow transfer

to IMMS


Objectives

Endpoints

Schedule

What We Mean by Structured Design

80% protocol standard, design is buried as unstructured text


Structured Design Streamlines

Simplifies and Expedites Facilitative Review and Design Challenge

Study Outline

• Structured Design

• Import CDP (TPP/Label)

Protocol Challenge

• Provide Design Line of Sight

• Incorporate Industry Metrics & Benchmarks

Document Authoring

• Author based on study design

• Incorporate Standard Content


And Facilitates Reuse

PRM


"Within Study" Re-Use Instances

% Re-Use

Study 1 As-Is Transformed Total

Stats plan 13 1.5% 1.6% 3.1%

CSR Introduction & Methodology sections 37 4% 39% 43%

CSR Synopsis 22 17% 82% 99%

CTR Summary 22 1% 91% 92%

Ct.gov ----- 1% 99% 100%

CSR Study Results in text tables2 ----- 0% 100% 100%

"Within Study" Re-Use Instances

% Re-Use

Study 2 As-Is Transformed Total

CSR Introduction & Methodology sections 41 2% 66% 67%

CSR Synopsis 13 5% 93% 98%

CTR Summary 16 19% 76% 95%

"Across Program" Re-Use Instances

% Re-Use

Study x to Study y As-Is Transformed Total

Protocol to Protocol 73 23%3 24% 47%3

Stats plan to stats plan 29 3% 27% 30%

Which Can Enable Better Analysis

© 2011 Medidata Solutions, Inc. – Proprietary and Confidential © 2012 Medidata Solutions, Inc. § 20 Optimizing Clinical Trials: Concept to Conclusion TM

And Comparisons Across Designs

Complexity - Study Work Effort Sponsor 80.57 Industry 36.05

Total Procedures 254.27 Industry 117.25

Unique Procedures 31.69 Industry 21.27

Total Study Visits 10.94 Industry 8.58

Patients per site 15.40 Industry 9.63

Cost Per Patient $13,810 Industry $8,083

Benefit Per Study (Potential) Sponsor spend compared to Industry Avg/study $69,205 Avg of individual study details

Clinical Study Analysis (ANTI-INFECTIVE) Sponsor vs Industry Median (indications, phase and year)

Analysis includes 32 sponsor studies

Sponsor

Sponsor

Sponsor

Sponsor

Sponsor

224% higher

217% higher

149% higher

128% higher

160% higher

171% higher


Some Real-Life PRM Benefits

*24 studies across phases II – IV

Prior to data-centric process improvements

After data-centric process improvements

§ Avg. Protocol Amendments: 1.94 § Sites w/zero enrollment: 14% § Median recruitment cycle: 68 weeks

§ Avg. Protocol Amendments: 1.54 § Sites w/zero enrollment: 10% § Median recruitment cycle: 38 weeks

§ Handoffs in review process: 312 § Authoring & Review Cycle Time: 268 Days

§ Authoring & Review Effort: 57.5 Days

§ Process value added time: 48.7%

§ Handoffs in review process: 78 § Authoring & Review Cycle Time: 99 Days

§ Authoring & Review Effort: 39.5 Days

§ Process value added time: 84%


Summary


PRM Can Drastically Influence Study Design

• Significant process change involved in adoption

• Real business value can be demonstrated

• Opportunities •  Influence trial cost and complexity •  Drive reuse and efficiency •  Interface with other standards

• Analytics and business intelligence


Learn More

• CDISC.org

•  Forthcoming PRM Toolkit Wizard

• November 1 webinar with Jeff Abolafia, Rho

• MDSOL.com


Questions Thank you! Joshua Pines [email protected] Twitter: @JoshPines LinkedIn: JoshPines

protocol representation model in the real worldprotocol representation model in the real world...

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