Primer for Data Managers on 2013 FDA Guidance and ... … · ©© 20132014 BioClinica,BioClinica, Inc.Inc. – Proprietary– Proprietary andand ConfidentialConfidential 2 Primer

© 2013 BioClinica, Inc. – Proprietary and Confidential

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© 2014 BioClinica, Inc. – Proprietary and Confidential

Welcome to today’s BioClinica Webinar!

Primer for Data Managers on 2013 FDA Guidance and Regulations in an Age of eClinical Innovation

The webinar will begin at 11:00 am eastern time.

© 2013 BioClinica, Inc. – Proprietary and Confidential© 2014 BioClinica, Inc. – Proprietary and Confidential 2

Primer for Data Managers on 2013 FDA Guidance and Regulations in an Age of eClinical Innovation

• Today’s Star:• Jonathan Andrus

› Sr. Vice President, Operation› 2014 Chair, SCDM

• Your Host:• Chris Englerth

› Director of Marketing

HOUSEKEEPING• Submit questions to BioClinica Host

• Q&A at the end• Please keep your phone on mute!


Agenda

• Clinical trial changes Data Managers must know• Evolving regulations and their impact

› Part 11 Electronic Records and Signatures› Risk‐Based Monitoring› Electronic Source

• How the role is changing• Hot eClinical trends• Where to get help to keep current• Q&A



Clinical Trial Changes that You Should Know About• Be smart and laser focused with monitoringand data cleaning (Risk‐Based Monitoring)

• Get involved (TransCelerate, CTTI, etc.)• Stop transcribing (eSource Guidance)• Embrace data standards


Be Smart and Laser Focused

• Develop Quality Risk Mitigation Plans› Program Level› Project Level

• Transactional Tools› Allow for Risk Based SDV

• Analytical Tools› Create site, country, etc. quality profiles


Get Involved

• TransCelerate• CTTI• BioClinica User Group


TransCelerate

What initiatives are under way? • Risk‐Based Monitoring*• Therapeutic‐based data standards*• Shared Site Portals• Site Qualification and Training• Comparator Drugs


Risk Based Monitoring

• Several different approaches• Global regulators’ input• Although regulated, we ALL monitor differently• White paper published May 2013

› Project update issued 27Jan2014

• Piloting on 6+ studies across therapeutic indications and companies


White Paper

• Risk‐Based Monitoring Methodology• Considerations for determining risk recommended by TransCelerate:› Safety: Sites with serious unexpected SAEs, outlier sites in regard to non‐serious AEs and SAEs.

› Investigational Product: Compliance associated with study drug receipt, drug accountability, dispensing errors, and temperature excursions.

› Subject Recruitment: Outliers in screen failure rate or discontinuation rate.

› Protocol Compliance: Protocol deviations (major and minor)


White Paper (cont’d)

• Risk‐Based Monitoring Methodology• Considerations for determining risk recommended by TransCelerate:› Trends in Data: i.e., Abnormal data trends. › CRF Completion Statistics: i.e., Time to enter and approve data.

› Query Issues: e.g., Time to answer queries, number of re‐queried queries.

› Regulatory Documents: Number of documents not reviewed or received.

› Site Staffing: Site turnover rate.› Site Management: Facilities review of adequate storage of supplies and adherence with procedures.


White Paper (cont’d)

• Interesting Metrics• 7.8 % of all data queries are related to SDV • 2.4 % of queries are on critical data

• Jan. 2014 Update• SDV vs. SDR • How is the Risk Assessment Categorization Tool (RACT) actually performed?


Planning and Preparing

Risk Assessment Categorization Tool (RACT)• Determine risks to subject safety, data quality, and regulatory compliance

• Identify how and by which function(s) those risks will be managed

• Document risk mitigations in each of the functional plans comprising a study’s overall Integrated Quality Risk Management Plan (IQRMP) (i.e., Data Review Plan, Statistical Analytical Plan, Safety Plan)

ONCE THIS IS DONE…


Defining Critical Data and Processes

Defined at Program Level• Reassess at Protocol Level

Critical Data and Processes • Data supporting primary and key secondary endpoints• Data critical to subject safety• Processes that underpin subject safety and ethical treatment (e.g., scheduling extra visits/procedures in the event of significant clinical or laboratory findings)

• Processes that underpin data quality (blinding, etc.)


Quality and Risk Planning

Integrated Quality and Risk Management Plan (IQRMP)• Include clinical and medical risks identified at program level• Define actions for each function to proactively identify, assess,

and manage risk over the life of the clinical trial• Define the Critical Data identified by cross‐functional

representatives (e.g. elements that impact primary efficacy endpoint and critical safety parameters)

• Align associated quality management plans (including the Monitoring Plan) across identified risks and defined Critical Data and Processes to ensure cross‐functional teams focus on risks most important to subject safety, data quality and regulatory compliance

• Describe the process that each function will follow to review and revise the IQRMP over the life of the clinical trial


Monitoring Plans

Define Monitoring Methodologies• The plan is a living document that may change based on what is going on in the study

• On‐Site Monitoring› Based on the timing of study activities (SIV), workload (amount of SDV needed) and interventions to address issues or risks (targeted risk indicators).

• Off‐Site Monitoring› Reviewing data remotely and confirming data validation issues and responses to issues are being addressed in a correct and timely manner.

• Central Monitoring› Using aggregate data tools and technologies, looking for trends, outliers, data oddities, etc. Ability to apply risk‐based algorithms during the planning phase, with possibility of changing as data are collected.


What are the potential struggles?

• Service Providers• Fearful of being “blamed” for missing something

• Access to tools to help put Risk‐Based Monitoring in place• Finding risk areas• Correct and timely response• Limiting impact on monitors and other research professionals


TransCelerate and Data Standards

• Working with CDISC• Providing expertise and resources• Therapeutically considered• Includes both exchange and submission related standards

• CDISC sets the standard, TransCelerate moves it along faster(funding/people)


CDISC SHARE Initiative

Shared Health And Clinical Research Electronic Library• Repository for developing, integrating and accessing CDISC metadata standards in electronic format

• Help users find, understand and use rich metadata and controlled terminologies relevant to clinical studies more efficiently and consistently

• To improve integration and traceability of clinical data from protocol through analysis


CTTI

• 60+ member organizations• NIH, FDA, other Ministries of Health, industry (Sponsors and CROs), AROs, societies, etc.

• Identify and promote practices that increase quality and efficiency of clinical trials

• Turn clinical trials on their head!• Public‐private partnership between FDA and Duke


CTTI

Current Projects• Effective and efficient monitoring as a component of

quality**• Workshops on quality-by-design in clinical trials• Improving unexpected SAE reporting to IND

investigators • IND safety assessment and communication • Improving public interface of ClinicalTrials.gov for

use of aggregate data• Site metrics for study start-up• Use of central IRBs for multicenter clinical trials• CTTI recommendations


Effective and Efficient Monitoring as a Component of Quality

Survey Conducted• 65 respondents

(18 ARO/Gov.; 11 CRO; 36 Sponsor)• A wide variety of monitoring practices is used • Monitoring approach correlates with type of

organizational sponsor• Rationale for using a specific monitoring

approach does not appear to be evidence-based


Effective and Efficient Monitoring as a Component of Quality (continued)

Survey• On‐site monitoring

› Industry and CROs:80% or more

› ARO/gov’t. organizations: < 33%

• Despite availability of central data, 33% or fewer use centralized data monitoring to guide, target, or replace site visits

Our new workstation!


Effective and Efficient Monitoring as a Component of Quality (continued)

High Level Take-a-Ways • Move away from post-hoc monitoring and

toward better incorporation of quality in the design• No single monitoring approach is appropriate or necessary in

all circumstances• Tailor your monitoring approach to the needs of that given

trial, which may be a combination of several methods• Focus oversight on those errors most likely to adversely

affect trial quality› Not all data elements are equal› Checking every data point is misguided› Agree up front, develop prospective metrics to ensure quality

data


FDA’s Perspective

• Guidance for Industry: Oversight of Clinical Investigations: A Risk-Based Approach to Monitoring› Finalized August 2013

• Guidance for Industry: Electronic Source Data in Clinical Investigations› Finalized September 2013


GFI: Oversight – A Risk-Based Approach to Monitoring

• Sponsors are encouraged to use a variety of monitoring approaches

• Focus on the most important aspects of study conduct and reporting

• Assess risk attributes of your study and develop a customized monitoring plan

• Highly supported in the TransCelerate white paper


GFI: Electronic Source Data in Clinical InvestigationsAddresses:• Identification and specification of authorized source data

originators • Creation of data element identifiers to facilitate

examination of the audit trail by Sponsors, FDA, and other authorized parties

• Ways to capture source data into the eCRF using either manual or electronic methods

• Clinical investigator(s) responsibilities with respect to reviewing and retaining electronic data

• Use and description of computerized systems in clinical investigations


What does all of this mean to me as a CDM? (How is my role changing?)

• RBM White Paper from TransCelerate• What impact does it have on my DMP (reports/listings and other aggregate data review)?

• How should we coordinate data review with CRAs?

• What about possibly creating a joint Clinical Data Monitoring Plan that incorporates both data review and risk‐based monitoring?



• Effective and Efficient Monitoring as a Component of Quality • What do these new approaches to monitoring mean to the relationship between DMs and CRAs?

• Should there be considerations for our relationship documents (DMP, CMP)?



• Utilization of eClinical Tools• Configuring eClinical tools to enable a risk‐based approach to trial management

• Using reporting tools to help inform risk‐based decision‐making

• How should these tools be addressed/covered in your governing documents? (DMP, CMP, etc.)


Hot eClinical Trends

• Complex study designs• Direct entry of data• Interest in risk‐based methodologies


Complex Study Designs

• Taking advantage of the full features and capabilities of eClinical systems for dynamic data collection

• Text messages, warnings and emails• Flexible risk based functionality based on configurable settings


Direct Entry of Data

• Eliminating transcription from paper• Direct entry into eCRFs as protocol assessments are

carried out• As indicated in FDA guidance on eSource

• Use of Apps on tablets slates, iPads, etc. for data collection at sites



Interest in Risk-Based Methods

• Automated• Proactive• Off‐site/centralized• Integrated• Data‐driven decisions• Partial, guided SDV


How is this different from the past?

• More emphasis is being placed on using study data to proactively inform actions of other research players:› i.e., what to focus on; which sites are doing well.

• Data analytics and smart monitoring are encouraged, by industry groups and the FDA –This is monumental!


How has BioClinica responded?

• Involved in review/comment on FDA guidance documents relating to eSource and risk‐based monitoring, including direct conversations with FDA author

• Implemented a risk‐based approach to planning and management of SDV in our Express EDC platform

World Class EDC


How has BioClinica responded?

• Extensive experience in the use of our EDC platform and associated electronic case report forms as electronic source

• Direct capture of patient data without transcription in both the US and abroad

• Form optimization based on CDASH and an approach to limited free text entry


Where can you go tokeep current?• SCDM Conference (20th Anniversary!) • Regulatory panels• Roundtables• Sessions – beginner and advanced• Where have we been and where are we going?• Get ready to be certified!


Where can you go to keep current?

• www.scdm.org• Get Certified• Download the GCDMP• Get involved with a task force, committee, etc.

• Write a chapter for the GCDMP


Where can you go to keep current?

• www.bioclinica.com• Blogs• Webinars• White Papers

A complimentary event for BioClinica Customerswww.bioclinica.com/user‐conference


Summary

• Keep on top of the activities of these groups!• Understand what these white papers, guidances and decision documents mean your organization and its data management approach

• Ask your technology providers what is offered to support risk‐based approaches and eSource

• Get involved with the change!› Task forces, committees, white papers, etc.


© 2013 BioClinica, Inc. – Proprietary and Confidential© 2014 BioClinica, Inc. – Proprietary and Confidential

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