Risk Based Monitoring (RBM)

October 30, 2014

Matt Harris BA Shane Hernandez BS Kristen Evenson BA

Joy Frestedt PhD, CCTI, RAC, FRAPS 1

Disclosure

The presenters for today’s session have no relevant financial relationships with respect to this educational activity.

Matt Harris is the Senior Quality, Regulatory and Clinical Manager for Frestedt, Inc.

Shane Hernandez is an Executive/Project Assistant for Frestedt, Inc.

Kristen Evenson is a Technical Writing Specialist for Frestedt Inc.

Dr. Joy Frestedt is the Founder, President and CEO of Frestedt, Inc.

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Share Fair Learning Objectives

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Upon completion of this educational activity, you will be able to: !  Describe aspects of clinical research practice that

exemplify a broad range of contemporary concerns presented at The Share Fair

!  Review differing approaches to the clinical research collaborative process, from the viewpoints of Sponsors and of clinical facilities

!  Determine whether a technique applied by colleagues to a specific clinical research issue pertains to your research process

RBM Learning Objectives

After attending this session, the learner should be able to : !  Define RBM and Find the FDA Guidance on

RBM !  Describe Different types of monitoring !  Develop a RBM plan and Form !  Identify forms associated to RBM !  List items that do not need to be monitored by

appropriately Identifying critical data

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Biographies Matt Harris; Senior Clinical, Regulatory, Quality Manager !  Matt has previous experience working at Albert Einstein

College of Medicine as a research technician in a biomedical research laboratory and earned his bachelor’s degree in Biology from Augsburg College, Minneapolis.

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Shane Hernandez; Executive/Project Assistant

!  Shane brings experience in clinical research coordination and data support to the Frestedt team. Shane received his Bachelor of Science in Psychology at the University of Minnesota.

Kristen Evenson; Technical Writing Specialist !  Kristen has a Bachelor’s degree from the University of

Minnesota. She brings with her more than fifteen years of scientific experience covering a wide range of studies including cancer genetics and epigenetics, cell cycle regulation, and protein interactions.

Joy L. Frestedt, PhD, CCTI, RAC, FRAPS founded Frestedt Incorporated in 2008 and Alimentix, the Minnesota Diet Research Center in 2012. Dr. Frestedt has managed clinical, regulatory, and quality affairs for over 30 years in companies like Johnson and Johnson, Medtronic, Mayo Clinical Trial Services, AstraZeneca and Orphan Medical. Dr. Frestedt is among the “100 Most Inspiring People in the Life Sciences Industry” (PharmaVOICE, 2011) and the top 25 “Industry Leaders” (Minneapolis/St. Paul Business Journal, 2011).

What is RBM?

•  RBM is a monitoring approach to focus specifically on subject safety (risks) and critical data elements.

•  RBM is different from traditional monitoring approaches by not requiring 100% source document verification, saving the sponsor time and resources by not worrying about minor insignificant details.

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How is RBM different?

Risk Based Monitoring !  Ongoing e-data available !  Real-time, continuously analyzed data !  Removes individual interpretations of

data !  Focuses on most critical data elements !  More effective !  Conduct a risk assessment to ID risks

critical to the data and processes !  Monitoring to address important and

likely risks

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Traditional Monitoring !  Relies heavily on manual

tracking

!  Data from disparate areas

are not integrated

!  No alerts to prompt risk-

mitigating action

!  Lag time in response

!  Labor and resource intensive

RBM is acceptable

Rationale: •  To provide current recommendations for

monitoring practices. •  To encourage Sponsors to adopt a RBM

approach to improve oversight of clinical investigations

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http://www.fda.gov/downloads/Drugs/.../Guidances/UCM269919.p

Why was the guidance issued? !  Alternative Techniques Help

Monitors

!  Determine if additional actions are needed for subject safety (e.g., staff training, clarification of protocol requirements)

!  Facilitate continuous improvement in trial conduct oversight

!  National Institutes of Health and Medical Research Council sponsored trials started the use of RBM with success

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!  Problems Necessitating Change !  Regulations not specific

on proper monitoring procedures

!  Increased number of clinical trials

!  100% data verification is time consuming

!  Infrequent monitoring visits

!  Examples of Alternative Techniques !  Communication with

study staff

!  Review of site processes, procedures and records

!  Source data verification and corroboration

Developing RBM Plans A risk based monitoring plan should describe: !  Type of monitoring !  Frequency of monitoring visits

!  Risk analysis

A RBM should be approved by an IRB prior to any monitoring activities.

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RBM Plan Contents

!  A RBM should include: !  Purpose – Why is the plan needed?

!  Scope – What will be monitored? !  Definitions/Abbreviations – Define terms in plan

!  Description of Study – Briefly describe the study protocol.

!  Selection/Qualification of Monitor – What are the monitor’s qualifications?

!  Visit Schedule – How often will visits occur? !  Activities prior/during/after visit – What is the visit

agenda?

!  Activities at last visit – What are the closeout plans?

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Forms Associated With RBM Plans !  Checklists

!  Can be helpful to facilitate the monitoring visit and ensure everything in the plan has been checked

!  These will be brought to the visit to document everything that was monitored and any results

!  Letters !  The RBM plan should describe how results will

be communicated

!  Should be sent to IRB, Site and Sponsor after the visit and the study recommendations going forward, including any actions items

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What not to monitor as closely:

!  Data that doesn’t effect safety or efficacy endpoints, such as: !  Concomitant treatments

!  Routine lab test results

!  Product storage, when none is specified

!  Date of birth (if enrollment is for “adults”)

!  Demographic Characteristics

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Identify Critical Data and Processes

The scope of any RBM plan should be to identify information that if inaccurate, not performed or not performed correctly, could compromise subject safety or study results.

Critical data and processes may include:

!  Verify informed consent has been signed

!  Verify inclusion and exclusion criteria

!  Ensure Drug Accountability

!  Ensure protocol compliance (study endpoints, safety requirements, reporting of adverse events, subject withdrawals, trial integrity)

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Conclusions !  “Based on FDA’s inspection and review

experience, infrequent errors in non-critical data are unlikely to alter FDA’s conclusions about whether a product is safe and effective and whether participants’ safety was appropriately monitored.”-Oversight of Clinical Investigations- A Risk-Based Approach to Monitoring (http://www.fda.gov/downloads/Drugs/.../Guidances/UCM269919.p)

!  RBM can save time and resources by focusing effort on subject safety and not 100% Source Data Verification!

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What to monitor Quiz!

Circle the correct answers

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Inclusion criteria

Exclusion criteria

Routine

lab work

Adverse events

Subject withdrawal

Study endpoint

Contact Us!

Frestedt Incorporated Tel: 952-426-1747

Fax: 952-426-1757

info@frestedt.com

www.frestedt.com

Dr. Joy Frestedt

jf@frestedt.com

612-219-9982

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Your prescription for success!