Data Standards in Clinical Trials, A Regulatory Perspective

CDISC Interchange October 24-26, 2012

Dr. Janet Woodcock Center Director Center for Drug Evaluation and Research U.S. Food and Drug Administration (FDA)

October 24 , 2012

It’s A Difficult Road To A New Medicine

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Clinical Trials Suffer High Failure Rates – Costly in Time and $$

Rate of Attrition for Drugs Entering Each Phase

Kola I, and Landis J. Can the pharmaceutical industry reduce attrition

rates? Nature Rev. Drug Discov. 3:711-715, 2004.

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Efficient, Consistent Review Is Challenging

Priority

Review

43% of effort in a review is spent on data management and primary analysis

In fiscal 2012, CDER received about 1280 study datasets per week, up to 10GB in size

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CDER’s Vision –

A standards based end-to-end fully electronic receipt, review, and dissemination environment that aids us in our mission to make safe and effective drugs available to the US Public

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Standards Are Key

Great Baltimore Fire of 1904

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How Will Clinical Content Standards Help?

• Improve efficiency of drug review

• Establish “common language” for disease and therapeutic areas through information models, concepts and controlled terminologies

• Facilitate use of sophisticated analytic tools

• Enable data sharing and data pooling

• Enhance the ability to perform complex analyses

• Build a foundation for broader benefits in clinical research, premarket analysis and safety signal detection

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Example: OMOP Common Framework

Common Data Model

MedDRAMedDRA

MedDRAMedDRA

Low-level Terms

(Level 1)

Preferred Terms

(Level 2)

MedDRAMedDRA

MedDRAMedDRA

MedDRAMedDRA

High Level Terms

(Level 3)

High Level Group Terms

(Level 4)

MedDRAMedDRASystem Organ Class

(Level 5)

Existing

De Novo

Mapping

Derived

Source codes ICD-9-CMICD-9-CM

Low-level concepts

(Level 1)

Higher-level

classifications

(Level 2)

ReadReadSNOMED-CTSNOMED-CT

SNOMED-CTSNOMED-CT

OxmisOxmis

Top-level

classification

(Level 3)SNOMED-CTSNOMED-CT

SNOMED-CTSNOMED-CT

MedDRAMedDRA

MedDRAMedDRA

Low-level Terms

(Level 1)

Preferred Terms

(Level 2)

MedDRAMedDRA

MedDRAMedDRA

MedDRAMedDRA

High Level Terms

(Level 3)

High Level Group Terms

(Level 4)

MedDRAMedDRASystem Organ Class

(Level 5)

Existing

De Novo

Mapping

Derived

Existing

De Novo

MappingExisting

De Novo

Mapping

Derived

Source codes ICD-9-CMICD-9-CM

Low-level concepts

(Level 1)

Higher-level

classifications

(Level 2)

ReadReadSNOMED-CTSNOMED-CT

SNOMED-CTSNOMED-CT

OxmisOxmis

Top-level

classification

(Level 3)SNOMED-CTSNOMED-CT

SNOMED-CTSNOMED-CT

NDF-RTNDF-RT

RxNormRxNorm

NDCNDCGPIGPI MultumMultum

Existing

De Novo

MappingExisting

De Novo

Mapping

HCPCS*HCPCS*

Derived

CPT-4*CPT-4*

Source codes

Low-level drugs

(Level 1)

Ingredients

(Level 2)

Classifications

(Level 3)

RxNormRxNorm

Top-level concepts

(Level 4) NDF-RTNDF-RT

ICD-9-Proc*ICD-9-Proc*

Standardized Terminologies

Accommodating Disparate Observational Data Sources

Drugs

Conditions

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Example: RxNorm – Standardized Terminology Enables OMOP Research Beyond translation to enabling structured analytics

NDC Thomson

GPI GE

VA Product VA

Multum PHS

Multilex GPRD

GPPC

NDF-RT

FDB

RxNorm Clinical drug

Branded drug

Ingredient Form

Strength

Characterization tools

Queries

Database benchmarking

Comparison of analytical methods

HOI definitions

Drug class definition

Ingredient-based eras

Indication based methods

Disparate Sources

Drug Codes

Normalized to RxNorm

Enabling Standardized Tools and Methods

Quality control

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New Regulation

Supports the Solution

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FDA Safety and Innovation Act (FDASIA)

• Reauthorizes the fifth instance of Prescription Drug User Fee Act (PDUFA V)

• Authorizes the new Generic Drug User Fee Act and Biosimilars User Fee Act

• FDASIA Section 1136: – Allows FDA to require standardized fully electronic

submissions related to marketing applications

• Phased-in through guidance to industry according to an agreed timetable

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PDUFA V - Section XII

• Clinical Terminology Standards: Using a public process that allows for stakeholder input, FDA shall develop standardized clinical data terminology through open standards development organizations with the goal of completing clinical data terminology and detailed implementation guides by FY 2017.

– FDA shall develop a project plan for distinct therapeutic indications, prioritizing clinical terminology standards development within and across review divisions. FDA shall publish a proposed project plan for stakeholder review and comment by June 30, 2013. FDA shall update and publish its project plan annually.

ELECTRONIC SUBMISSIONS AND STANDARDIZATION OF DRUG APPLICATION DATA

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Many Activities In This Area

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Examples of CDER Public-Private Partnerships

Biomarker Consortium (BC)

International Serious Adverse

Events Consortium (iSAEC)

Pediatric Anesthesia

Safety Initiative (PASI)

Analgesic Clinical Trial Translations, Innovations,

Opportunities, and Networks (ACTTION) Initiative

Cardiac Safety Research

Consortium (CSRC)

Critical Path Institute (CPath)

Coalition Against

Major Diseases

Consortium (CAMD)

Patient Reported

Outcomes

Consortium (PRO)

Predictive Safety

Testing Consortium

(PSTC)

Polycystic Kidney Disease

Consortium (PKD) Critical Path to TB Drug

Regimens Consortium (CPTR)

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And Now CFAST

CDISC and Critical Path Institute Partnership

• Objective – Accelerate clinical research and medical product development by facilitating the creation and maintenance of data standards, tools, and methods for conducting research in therapeutic areas important to public health

• First Challenge – To progress content standards in therapeutic areas as identified by the aggressive PDUFA commitment to develop standards over the next 5 years

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Closing thoughts…

• This area is rapidly evolving – data overload

• Standards are critical to facilitate both regulatory review and regulatory research

• Collaborations are critical – we can’t get there alone

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Thank You

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