AdvertoriAl

ADVERTORIAL22 Applied CliniCAl TriAlS December 2014

RBM Objectives, Design and Deployment: How Covance Transforms Risks into ReturnsAdam Baumgart, BSc, CPM, Director, Process Excellence & Process Lead, Risk-Based Monitoring, Clinical Development Services, Covance Inc.

Guidance released by FDA and

EMA in 2011 and 2013 has by

now generated an array of very

different risk-based monitoring

(RBM) approaches, tools and

systems. But a key question remains:

what makes an RBM implementation

effective, such that it helps meet regu-

lator expectations and transforms risks

into returns?

Covance has leveraged a decade’s

worth of experience implementing risk-

based approaches to create a unique,

end-to-end RBM enterprise solution,

powered by its own proprietary, state-

of-the-art analytics platform. This article

focuses on real life experiences from our

ongoing RBM implementation, including

the benefits of RBM and recommenda-

tions on how to implement RBM effi-

ciently by “keeping it simple.”

Keeping it SimpleOne of the guiding principles and objec-

tives of the Covance RBM implementa-

tion roll out is Simple Process & Organi-

zation. We have identified the following

key components to what “keeping it sim-

ple” looks like:

1. Roles and organizational structures

that are simple to understand and follow

2. Holistic, robust, end-to-end clinical

trial RBM systems and tools from the

Request-for-Proposal stage to the final

Clinical Study Report

3. Pilot studies to refine and develop

processes and test tools and to further

develop future roles and organizational

structures

1. Simple Roles & OrganizationAt first glance, it might appear easy to

inadvertently over-complicate RBM and

its implementation. For example, in the

traditional monitoring paradigm, the re-

sponsibility for data quality at the in-

vestigator site primarily rests with the

CRA. In risk-based approaches, however,

this responsibility becomes distributed

among the CRA, in-house CRAs, data

managers, statisticians, physicians, etc.

In this case, we have found the simple

approach is to take one role at a time

and examine and determine the extent

of change and then consolidate, train

and manage, before moving on to the

next impacted role.

New RBM RolesThe need for change in the RBM para-

digm doesn’t just impact processes, but

also the people side of the equation, as

we have found RBM requires new skill

sets and roles. One such role that Co-

vance has introduced is that of an RBM

Subject Matter Expert (SME). We have

trained a series of experienced Project

Managers as RBM SMEs, to proactively

guide study teams throughout the RBM

project lifecycle and make recommen-

dations based on study data. The RBM

SME works closely with study teams

from the proposal stage to study close,

focusing primarily on risk identification

and management. Each RBM SME has

oversight of a portfolio of studies and

helps transfer and apply best practices.

This new, specialized role has helped

us scale up RBM rapidly, and assimilate

knowledge and best practices to con-

tinuously enhance our RBM solution.

2. Robust Processes, Systemsand ToolsCovance has made significant invest-

ments to design simple, scalable RBM

processes. These processes have gener-

ated our system requirements which in

turn have resulted in easy-to-use sys-

tems and tools. Instead of rolling out

everything at once, we’ve deployed a

staged process, targeting the most im-

portant elements first. For example, the

definition of critical data and processes

is a significant element of the regulatory

guidance. Correspondingly, it is one of

the first RBM processes to be formalized

with a new SOP.

Continuously share the high level RBM processOur high level RBM process map has

11 simple to understand steps. We are

continuously using this visual to call at-

tention to the RBM roll out and how it

ADVERTORIAL

ADVERTORIAL

Applied CliniCAl TriAlS 23December 2014

impacts staff functions, and to refer the

staff back to the current RBM step that

the study they support is going through

at a given point in time. Also, the pro-

cess map is shared with RBM process

users on a continuous basis through our

intranet. This continuous use of the RBM

visuals, language and terminology has

in and of itself proven to be an effective

agent for change.

Maturing toolsets drive escalating adoptionOur experience shows that once risk fac-

tor visualizations and operational met-

ric dashboards are mature and widely

available, the study staff will proac-

tively adopt and advocate the use of

risk-based approaches and systems in

their studies. In addition, as the staff

increasingly realizes that RBM tools and

approaches can benefit their studies be-

cause of improved overall control and

proactively addressing risks, demand

escalates for implementation of the RBM

tools and process.

3. Pilot Studies and ImplementationIn theory, RBM can be deployed in any

clinical trial of any phase. Pragmatically,

Covance made a decision to begin the

rollout of RBM in Phase III studies as

they tend to involve a larger number

of patients, be longer in duration and

therefore more costly. Such a study pro-

file provides a greater opportunity for

quality improvements over time lead-

ing to higher potential cost efficiencies.

Phase I and II studies generally include

fewer patients and are shorter in dura-

tion so there may be less value from

changes in the monitoring strategy, and

the implementation of an RBM dash-

board may not be as cost effective as in

later phases.

At the same time, Covance continues

to meet with sponsors and evaluate the

RBM implementation in other phases.

It is clear that risks identified and expe-

rienced in Phase I and II studies inform

those in Phase III studies, therefore im-

plementing RBM in early phase studies

can potentially save even more time and

effort across the development program.

Accordingly, Covance will extend the

implementation of RBM to early phase

studies as well.

In addition, by cross-training staff

from our Phase IV and lifecycle man-

agement teams, we aim to use the best

principles of their more minimal, long

established approaches to help refine

RBM principles. Therefore approaches

from Phase IIIb and IV studies will be

used to provide ideas and inputs to fur-

ther develop RBM in Phase I-III.

RBM pilot studies – lessons learnedCovance has already piloted the RBM

processes in a number of clinical trials

and has gained useful experience across

several areas, for instance:

• Initial high level study risk assess-

ments have been carried out using

a tool similar to the TransCelerate

RACT. This tool has been deployed as

early as at the Request-for-Proposal

stage, providing study teams a head

start deploying key RBM approaches

in the event of a study award

• For over five years, Covance has been

using a Risk Management Register in

the planning stages to perform de-

tailed assessments of study operation

risk. With RBM, this Register is be-

ing enhanced to include clear, docu-

mented ownership of risk identifica-

tion and mitigation

Finally, based on positive pilot study

deployment experiences, Quality by De-

sign techniques such as the two exam-

ples above will be used in wider portfo-

lio level governance and will no longer

be limited only to studies considered

RBM trials.

In-flight RBM implementationThe increase in deployment of RBM ap-

proaches in new studies has prompted

a wave of interest in adopting RBM for

studies that are already in-flight. For

example, one of our Asia Pacific-based

clients and project teams approached

us to implement a risk dashboard in an

ongoing trial. Once launched, this dash-

board is expected to reduce the cost and

effort required to review risk factors that

the study team had been tracking manu-

ally. In addition, the RBM dashboard will

introduce a richer suite of risk indica-

tors and operational KPIs which in turn

enables the study team to better assess

patient safety and data quality.

Let the data do the talkingOne of the main tenets of the FDA and

EMA quality and risk guidance is cen-

tralized monitoring or centralized review

of data. These processes are proving a

challenge as they impact long-estab-

lished structures, processes and distrib-

uted data sources in clinical operations,

data management, statistical analysis

and medical monitoring. However, hav-

ing access to an experienced in-house

group of data scientists has helped over-

come this challenge: their experience in

visualizing clinical trial data and trends

has enabled the data to “do the talking”

in ways that simply didn’t exist before.

Further, implementation experiences

have taught us that the process of de-

signing trial data visualizations is an

evolution: end user feedback is dynami-

cally shaping and optimizing the visu-

alizations. This agile software develop-

ment approach has helped to convince

key clinical trial stakeholders, such as

clinical trial investigators, by being in-

clusive of their feedback and input.

For Covance, the RBM implementa-

tion journey is far from complete. We

hope the real life experiences shared

in this article including the application

of RBM processes into ongoing stud-

ies, the development of specialized risk

management roles, the selection of

which development phase to implement

RBM, and our lessons learned in “keep-

ing it simple” are of help and inspiration

– and indeed illustrative of how RBM

makes it possible to transform risks into

returns. Further examples including

RBM case studies and white papers are

available at www.covance.com/rbm.