Risk Based Monitoring and Management · Risk Based Monitoring Exercise – in groups look at the specific items which the Grey Guide identifies as needing to be considered in drawing

Going Grey – Risk Based

Monitoring and Management

Jo Burmester

Director Global Operations PharmaSchool Ltd

Editor Journal of Clinical Research & GCP

Risk Based Monitoring and

Management

FDA Guidance

EMA Reflection paper

MHRA/MRC/DoH guidance

Grey Guide

FDA - RBM

FDA believes centralised monitoring more effective than on-site in some circumstances

Better overview of issues

Easier to see anomalies

Some issues to address:

– Communication with PI

– Informed consent review

– Access to site records

– SDV

FDA - RBM

Risk assessment

– Identify risks

– Analyse risks

– Determine controls necessary

Prioritise risks

– Likelihood

– Impact

– Detectability

FDA - RBM

Monitoring Plan – Factors to consider:

– Complexity of study design

– Types of study endpoints

– Clinical complexity of the study population

– Geography

– Relative experience of the investigator and of the sponsor with the investigator

– Electronic Data Capture

– Relative safety of IMP

– Stage of the study

– Quantity of data

FDA - RBM

Monitoring Plan – methods,

responsibilities and requirements

Include:

– Description of monitoring approaches

– Communication of monitoring results

– Management of noncompliance

– Ensuring quality monitoring

– Monitoring plan amendments

FDA - RBM

Triggers are critical

What are potential issues which might

lead to change of monitoring strategy?

FDA - RBM

Documenting Monitoring

– Date and individuals involved

– Summary of activities

– Any issues identified

– Actions taken or to be taken

FDA - RBM

It’s not just about monitoring

– Protocol and Case Report Form design

– Investigator training and communication

– Sponsor oversight of monitoring delegated

to a CRO

– Site Selection

EMA Reflection Paper on Risk

Based Monitoring and

Management

Adopted and published Sept 2013

Covers Risk Assessment and Control:

– Risk Assessment

• Identification

• Evaluation

– Risk Control

• Risk mitigation/acceptance

• Quality tolerance limits

– Risk Review and Reporting

EMA Reflection Paper

Refers to ICH Q9 – more detail on risk

assessment and management

generally

MRC/DH/MHRA Joint Project

Risk-adapted Approaches to the

Management of Clinical Trials of

Investigational Medicinal Products

Trials Classed as A, B or C

MHRA - Risk Adaptations

Guidance on adaptations possible (or

not!)

– Approvals

– Application content

– Labelling

– Safety Surveillance

– IMP Management

– Documentation

– GCP Inspections

MHRA - Risk Based

Monitoring and Management

Appendix 2

The purpose of this guidance is to

assist Investigators and Sponsors:

– Consider and identify the main

hazards inherent in a clinical trial

protocol

– Develop relevant risk-mitigation

plans

– Develop proportionate trial

management and monitoring plans.

MHRA - Risk Assessment

Two aspects to consider

A: Risks to participant safety associated with the

IMPs and other intervention(s) being tested

B: Other risks associated with the design and

methods of the trial, such as risks to:

- participants due to the clinical procedures

specified by the protocol

- participant rights related to consent and

protection of their data

- reliability of trial results.

MHRA - Monitoring Plan

Risk Assessment will inform

monitoring plan in terms of:

– Intensity

– Focus

– Methods

The Grey Guide

Risk Assessment recommended for all

clinical trials

Clearly documented – ideally as a a

separate document

Recommended prior to finalisation of

the protocol

The Grey Guide

People to involve in Risk Assessment

– Medic with understanding of

therapeutic area

– Pharmacist/toxicologist/pharmacolo

gist

– Statistician

– GCP expert

– Others as necessary

The Grey Guide

Aspects to consider:

– IMP requirements

– Country specific risks

– Investigator and site staff

experience

The Grey Guide

Examples on the GCP Forum page on

MHRA website

Ongoing review needed

Risk Based Monitoring

Exercise – in groups look at the specific

items which the Grey Guide identifies as

needing to be considered in drawing up

the monitoring plan. Think of a situation

which would lead you to a high intensity

of monitoring and one which you think

would allow for a lower intensity.

Risk Based Monitoring

Here to stay

More advice and guidance available

now

For commercial as well as non-

commercial