our eer eviewed guide to global clinical trials ... - sas.com · in-depth phone interview of 20...
TRANSCRIPT
E-BOOK
E-BOOK
YOUR PEER-REVIEWED GUIDE TO GLOBAL CLINICAL TRIALS MANAGEMENT appliedclinicaltrialsonline.com
CURRENT PERSPECTIVES
ON
RISK-BASED MONITORING
CO-SPONSORED WITH:
2 APPLIED CLINICAL TRIALS appliedclinicaltrialsonline.com
E-BOOK
E-BOOK
YOUR PEER-REVIEWED GUIDE TO GLOBAL CLINICAL TRIALS MANAGEMENT appliedclinicaltrialsonline.com
CURRENT PERSPECTIVES
ON
RISK-BASED MONITORING
CO-SPONSORED WITH:
TABLE OF CONTENTS
3 Why Risk-Based Monitoring?
Costs, patient quality, data quality factor
into monitoring decisions.
6 Risks, Signals, and Scoring
What determines risk and how are risk levels determined?
8 Technology Use to Achieve
Risk-Based Monitoring
Where is the technology for RBM exactly and
what should organizations be looking for? CO
VER
DES
IGN
: D
AN
WAR
D
O U R M I S S I O N
Applied Clinical Trials is the authoritative, peer-reviewed resource and thought leader for the global community that designs, initiates, manages, conducts, and monitors clinical trials. Industry professionals learn effective and efficient solutions to strategic and tactical challenges within the tightly regulated, highly competitive pharma ceutical environment.
IntroductionThe development of this eBook came on the heels of Applied Clinical Trials’ last successful eBook, titled Risk-Based Moni-
toring in Clinical Trials. This eBook, Current Perspectives on Risk-Based Monitoring, was developed in conjunction with
SAS, and is based largely on two projects: a custom research survey conducted by a third-party research firm using an
in-depth phone interview of 20 executives, culled from the Applied Clinical Trials audience database, regarding risk-based
monitoring usage and perceptions.
The second project was a December 2013 webcast titled Myths, Models and Momentum: Risk-Bssed Monitoring, which
featured three presentations from industry experts. Andrew Schafer, President, Industry Standard Research, presented
results on its survey and covered the high-level issues regarding risk-based monitoring. Mark Hronec, Director at PwC, pre-
sented on risk-based monitoring from a CRO and sponsor perspective, delving more into the models. Laurie Rose, Principal
Industry Consultant, Health & Life Sciences at SAS, then discussed using more integrated technologies that improve data
quality with less human intervention to gather and report the data information needed for a risk-based monitoring program.
Schafer also wrote a peer-reviewed article earlier this year that went into his research findings more in-depth, which
touched on the concerns and challenges executives have with risk-based monitoring. But in the end, he noted in the article,
“Survey results reinforced that traditional clinical monitoring will not go away. It can’t. Its scope is a critical component to
help ensure squeaky clean data and utmost patient safety.” Yet, according to study results, if sponsors and service provid-
ers are to relieve stubborn industry-wide financial pressures and meet growing industry demands, clinical monitoring must
begin to morph into more of a hybrid model—at least in the later phases of clinical trials. As one respondent aptly put it,
“There is a large area of opportunity to improve how clinical trials are conducted. Hopefully the combination of new tech-
nologies and alternative models can help to improve monitoring and data quality.”
And this eBook will address those concerns, how companies go about applying scores and rating signals in clinical trials,
and how technology is being used now, and how it is envisioned to be used more effectively in the future.
appliedclinicaltrialsonline.com APPLIED CLINICAL TRIALS 3
Why Risk-Based Monitoring?
Biopharmaceutical firms and CROs are feel-
ing the pressure to conduct what has been
touted as more cost effective, risk-based
monitoring of clinical trials. But there are
several roadblocks to using this technique:
• Complexity of managing international sites.
Monitoring multiple international sites is com-
plicated. According to the NIH, 261,000 clinical
studies were registered in August 2013; 44%
were non-US only. Over the average 7-12 year
period of a clinical trial, that means millions
spent on travel and site visits using traditional
monitoring practices.
• Resistance to business process change. Reg-
ulatory authorities are pushing risk-based moni-
toring, but companies are resisting the necessary
business process changes to make that happen.
Global regulatory authorities are suggesting the
move from 100% source data verification (SDV)
to a risk-based approach to monitoring, but there
is not enough evidence of success with this new
method to drive business process change.
• Variability according to clinical trial type.
Monitoring trials varies according to therapeutic
area, site selection, and trial stage. The bigger
and more complex the trial, the more likely the
failure rate.
Whether these roadblocks are myths or fact,
they remain perceptions uncovered in a group
of in-depth telephone interviews of 20 execu-
tives representing both CROs and sponsors,
conducted by SAS with Applied Clinical Trials, in
October 2013.
There are three central objectives in clinical
trials that pertain to risk-based monitoring: en-
suring patient safety throughout the trial, ob-
taining the highest quality data, and from a cost
perspective, conducting the trial at the lowest
cost without compromising patient safety and
data quality.
But what is risk-based monitoring? In Figure
2, which Mark Hronec, Director of PriceWater-
houseCoopers, shared during a December 2013
webinar sponsored by SAS and Applied Clinical Tri-
als titled “Myths, Models and Momentum: Risk-
Based Monitoring,” the four types of risk-based
monitoring strategies are described. The first is
around reduced monitoring, where organizations
conduct less than 100% source document veri-
fication (SDV). Targeted monitoring is based on
particular triggers that could happen during the
study that would trigger a site visit. Centralized
monitoring is using algorithms or predictive ana-
Costs, patient safety, and data quality factor into monitoring decisions.
Characteristics of Companies On-Site Monitoring Trials
Larger companies with larger budgets
Larger companies with rigid SOPs
Early phase trials
Small trials
Limited sites
Therapeutic area/High level of expertise
Trial plan established with CRO
Source: SAS, Applied Clinical Trials Risk-Based Monitoring, October 2013
4 APPLIED CLINICAL TRIALS appliedclinicaltrialsonline.com
lytics to determine the level and type
of monitoring that occurs in a trial.
And the final piece is remote moni-
toring, where monitoring is achieved
either off site and/or potentially in a
different country.
Taken together and implemented
holistically on a study or in a company,
the determination of which sites would
require an increase in monitoring re-
sources—or potentially decreases—is
based on the risk-based approach. By
focusing resources to the sites in need,
the risk-based approach then is in-
creasing the patient safety and data
quality coming from those sites, rather
than having those resources focused
on sites that do not necessarily need
the extra attention, explained Hronec.
Laurie Rose, Principal Industry Con-
sultant Health & Life Sciences at SAS,
agreed during the webinar, and stated
that another misconception is that
RBM means moving completely away
from onsite monitoring. “But in reality,
at least for the near future, it’s more a
matter of optimizing the activities of
monitoring where only essential on-
site visits are required, and then put-
ting technology in place for the more
advantageous, analytical monitoring
of data.”
According to the SAS research, re-
spondents believe that 30% of clini-
cal trial costs are attributed to on-site
monitoring. Reducing these costs, as
noted above, is a key driver for the in-
terest in risk-based monitoring.
However, behind the cost drivers,
there are challenges around the adop-
tion of risk-based strategies. While 80%
of the survey partcipants responded
that they do take a triggered or targeted
approach to risk-based monitoring, 80%
also said that they desired 100% SDV in
100% of trial participant records. Further, 55% said that they
use risk-based monitoring in their organizations and 80%
said centralized monitoring is attractive but slow on the up-
take in their organization.
These discussions, while not statistically high, are in-
dicative to the level of understanding of risk-based moni-
toring in the clinical trials industry. Basically, if your com-
pany is currently applying triggers or targets for site visit
requirements, your company is doing risk-based monitor-
ing, as per the PwC descriptive table.
And while these respondents also stated a 100% SDV
preference, that may not be the key to quality data. Rose
said, “Another area very common to traditional organiza-
tions where they have concerns is that if you move away
from 100% source data verification, then you might risk
patient safety and data integrity. But, in fact, there’s al-
Source: SAS, Applied Clinical Trials Risk-Based Monitoring, October 2013
Figure 1.
Source: PriceWaterhouseCoopers (PwC), August 2013
Figure 2.
No
Yes
Risk-based monitoring
Reduced monitoring
Targetedmonitoring
Centralizedmonitoring
Remotemonitoring
Data-driven oversight is tailored to the speci�c studyrisk areas, and the monitoring approaches arecontinuously updated via robust data analysis.
Monitoring at less than 100% SDV depending on studyand site risk
Monitoring based on triggers and predeterminedassessments across sites
Transfer of monitoring activities to low-cost countries,reducing the need for high-cost resources
• Algorithm-based study risk assessment following customized parameters for each study• Automated and nonautomated intervention based on statistical data review
Do You Use Risk-Based Monitoring in Your Organization?
Four Strategies of Risk-Based Monitoring
appliedclinicaltrialsonline.com APPLIED CLINICAL TRIALS 5
ready evidence from studies by Clinical Trial Transforma-
tion Initiative, other organizations are showing significant
impact by reducing SDV.” She also notes that there are im-
provements in data quality and in capturing patient safety
signals using EDC and through leveraging central statisti-
cal monitoring.
From its survey at Industry Standards Research, Andrew
Schafer, President, reported in the webcast that there are
factors hindering risk-based monitoring. However, they are
not related to the models, but rather related to the industry
and sponsor-based reasons. These reasons include a lack
of strong regulatory guidance; models being too new and
unproven; general corporate inertia; being risk averse; and
averse to trying new techniques.
Behind the CostsThat being said, cost was found to be the major driver for
conducting risk-based monitoring studies, according to
ISR’s research. In the webinar panel discussion regard-
ing costs, Rose said, “A lot of costs [are] from the clinical
research associates, whether it’s travel or training. And
sometimes with high turnover rates, retraining or having
to re-recruit and retrain. So with a more central remote
modeling, there are some upfront investments; and there
are going to be business process changes within the orga-
nization. There are very likely going to be some software
investments so that they are better improving the data
capture at the site.”
Rose said these upfront costs, however, will also lead to
a cost reduction over time, by having better upfront iden-
tification of risk and trial performance expectations. “That
can reduce a lot of the costs in the operations along the
way. Things like faster recognition of patient safety, and
protocol compliance, and data integrity issues, all of those
will allow for some optimization of the trial.” Hronec men-
tioned, many companies are doing pilots and still trying to
figure risk-based monitoring out. Which includes exactly
where they will get cost savings to then build that into the
organization. He said, “Right now it’s in the early stages;
but over the next several years, we’ll be able to see those
savings throughout the studies.”
Schafer concluded by saying that the momentum of risk-
based monitoring is at a fairly good clip within the organi-
zations they surveyed. Comparing to other studies that ISR
has conducted, the momentum with risk-based monitoring
is higher and more favorable than ePRO technology adop-
tion, or even adaptive trial design. Schafer said, “Risk-based
monitoring isn’t going anywhere and seems to be going to
increase in momentum within the sponsor organizations.”
As revealed by the SAS research, companies are at differ-
ent stages of development for risk-based monitoring. Com-
panies realize they need to have more efficiently executed
trials and risk-based monitoring can help them get there.
With streamlined clinical trial operations, a more pa-
tient-centric approach is enabled. Patient data contains
enormous amounts of information. “We have to change the
way patients are being treated within the system so we can
design protocols that will actually fit the patient,” said an
executive director of a CRO.
When that happens, clinical trials will be truly adap-
tive. They will go beyond collecting data to meet a spe-
cific endpoint. Instead, studies will have quality inherent
in their design, their execution will be optimized, and
they will drive the development of successful new thera-
pies. The risks are simply too great for not doing risk-
based monitoring.
The SAS survey also found the legion of respondents strictly adhering to the final FDA Guidance Oversight of Clinical Investigations —A Risk-Based Approach to Monitoring issued in August 2013. However, they also noted they find the guidance lacking in detail or insight into cutting edge technologies. Rose noted during the webinar that RBM is not required by regulators. What is required is the monitoring of the progress and conduct of the trial. Rose said, “The risk-based approach is being suggested as a way to become more efficient in clinical trial operations. And like in other areas, regula-tors are encouraging innovation with technology and analytics to help improve these processes.”
A Note on Regulation
Upfront costs, however, will also lead to a cost reduction over time, by having better upfront identification of risk and trial performance expectations.
6 APPLIED CLINICAL TRIALS appliedclinicaltrialsonline.com
Risks, Signals, and Scoring
Whichever risk-based monitoring type a
company uses for data-driven oversight,
a set of metrics, signals and levels of
scoring risk is necessary to determine
the monitoring plan. According to the
SAS custom research project, many metrics and
signals were used to identify, track, and under-
stand the impact of trial characteristics. The
most significant of these were identified as que-
ries being issued at particular sites, EDC discrep-
ancies, patient risk, and regulatory risk.
Then the respondents identified measures or
signals that would be used during an on-going
trial to adjust or respond to the performance of
a risk-based monitoring plan. These included
work level readjustment, missed data points, data
quality, data quantity, and number of queries.
Across the board, the SAS research respon-
dents determined what would trigger a site-
monitoring visit. These included: sites reporting
a problematic issue with the trial; a centrally
identified problematic trend in reporting; com-
plexity of the trial; delayed recruitment; adverse
events; case report forms needing to be moni-
tored/not being filed for new enrollees; lack
of communication by site; increases in enroll-
ment; and on-site monitor reporting need for
increased future monitoring. One director at a
CRO noted, “We don’t have a formal process to
initiate a site visit. When the monitor is seeing
issues and questions coming from a site and we
start seeing a gap in training or issues that oc-
cur repeatedly.”
The SAS research also concluded that when
serious things go wrong with a trial, such as an
adverse event or an incident report is filed, it is
easy for the respondents to identify issues; how-
ever, unanticipated and less obvious situations
can happen throughout the trial and put it at
risk. These events should be identified as real-
time as possible so that changes can be made
as quickly as possible to help respondents stay
on top of these issues.
Mark Hronec, Director of PriceWaterhouse-
Coopers, noted during a December 2013 webinar
sponsored by SAS and Applied Clinical Trials titled
“Myths, Models and Momentum: Risk-Based
Monitoring,” this exact situation. He termed
them traditional and non-traditional risk factors.
What determines risk, and how are risk levels determined?
Source: SAS, Applied Clinical Trials Risk-Based Monitoring, October 2013
Figure 1.
Dynamic site-monitoring
Static site-monitoring
Site Monitoring Schedules
appliedclinicaltrialsonline.com APPLIED CLINICAL TRIALS 7
Along the traditional were those previously mentioned—
recruitment rates, protocol deviations, serious adverse
events, the drug safety profile or the site location or expe-
rience at the site. However, those non-traditional risks that
could be identified and leveraged using real-time “big data”
predictors included average patient visit window deviation,
the number of visits the site has per day, the number of
inclusion or exclusion criteria, and the length of the in-
formed consent form, among others.
Hronec also said that the traditional and non-traditional
risk factors are further framed under three categories—pro-
tocol risk, study site risk, and dynamic risk.
For example, protocol risks include the therapeutic area,
drug safety profiles, etc. But also aspects around the number
of inclusion/exclusion criteria, the number of procedural vis-
its, etc., can be made to complete this profile of protocol risk.
For the sites, the number of universities per square mile
near the site, the physician density, etc. can be examined.
And for the dynamic risks, the number of visits per day can
be a potential risk indicator.
Looking at these non-traditional factors, the potential
relationships can help inform the riskiness of the site, the
protocol, and then the overall study.
Many questions in the webinar were centered on risk-
determinations. Laurie Rose, Principal Industry Consultant,
Health & Life Sciences at SAS, recommended using histori-
cal data, information on past site performance; country and
regional information and statistics; sites that perform bet-
ter with recruitment, enrollment, and actual study startup.
“[With those data, you are] using a predictive model rather
than just summarizing and putting them all together. Using
a predictive model can help determine a better set of ex-
pectations of what might come in the future.”
Rose also noted other predictive data would include in-
formation within the same therapeutic area or other similar
compounds from past studies and using that understanding
in future studies. Where data is available, the analysis will be
helpful in preparing for the next study.
Who actually determines risk assessment in the organiza-
tion? According to the experts on the webinar, risk should
be determined in a cross-departmental way that includes
the physician, clinical operations lead, a statistician, data
manager, etc. Hronec said, “It depends on whether or not
the organization is doing this as a point-by-point solution,
in which case you would mostly have that centralized within
the study team. But if the organization wanted to take this
on holistically, then you really look at how do we categorize
the risk levels of allergy studies versus oncology studies?
And with those types of conversations, those need to be
escalated within the organization and include drug safety
representatives as well.”
Another point that Rose brought up is risk “re-use” in stud-
ies. Risks will not be the same for every trial, but a number
of studies will have similar rules and certain set thresholds.
“There might be some of those that are common and can be
used each time, but there will be others that will be specific
to the protocol or to the therapeutic area that the medical
personnel need to have influence on how those might change
from study to study.”
The upfront understanding and measuring of risk to suit-
ably determine the monitoring plan, as well as early discus-
sion with regulatory authorities about the monitoring plan,
can impact timelines. Andrew Schafer, President of Industry
Standard Research, noted in the webinar, “If you have not
really planned ahead, it can elongate study startup and, in
fact, the entire study timeline.” He continued, “From our
respondents, most people believe that that upfront time
is worth it to conduct the risk-based monitoring study; but
you just have to account for it.”
Source: SAS, Applied Clinical Trials Risk-Based Monitoring, October 2013
Figure 2.
0 10 20 30 40 50 60 70 80 90 100
No
Yes
Do You Use Triggers and Risks to Determine a Site Monitoring Visit?
Source: SAS, Applied Clinical Trials webcast, December 2013 www.appliedclinicaltrialsonline.com/monitoring
Figure 3.
0 5 10 15 20 25 30
(during study) Early signaling of site compliance to the protocol, GCP compliance
(during study) Early signaling of study risks and trends, potential protocol adjustments can be identi�ed
(during study) Early signaling of under-reporting
(pre-study start) Identify parts of the protocol according to their risk pro�le and implement mitigation strategies
(pre-study start) Identify sites with quality risks and implement mitigation strategies
19.4%
25%
0.9%
25%
29.6%
Of the Following Benefits from RBM Technology, Which is the Most Important?
See how leading firms are optimizing
risk-based monitoring.
AnalyticsIf risk-based monitoring is the silver bullet to more quickly developing safe and effective products at lower costs, how are life science organizations approaching this critical need? Learn about the barriers and rewards to risk-based monitoring, get suggestions for moving forward, and see what the ideal system looks like.
SAS and all other SAS Institute Inc. product or service names are registered trademarks or trademarks of SAS Institute Inc. in the USA and other countries. ® indicates USA registration. Other brand and product names are trademarks of their respective companies. © 2014 SAS Institute Inc. All rights reserved. S119211US.0114
Read the report
8 APPLIED CLINICAL TRIALS appliedclinicaltrialsonline.com
Technology Used to Achieve Risk-Based Monitoring
A SAS custom research project determined
that organizations currently using risk-
based monitoring are receiving benefits,
and are focused on at least meeting or
exceeding the benefits of on-site visits.
These organizations intend to continue imple-
menting innovative, technologically savvy, risk-
based monitoring plans that will allow them to
cut costs, improve quality, and meet regulatory
requirements while putting patient safety first.
The respondents also said they hope to
achieve the following benefits in that exercise:
identifying what is key in data collection/inte-
gration; the ability to focus resources on high-
est-need sites; reduction in site fatigue; empow-
ering adaptive studies; better patient outcomes;
and increasing understanding and integration of
global data.
As was observed in the previous articles in
this eBook, upfront technology costs will be
necessary, and the need to pull data into pre-
dictive tools is key to the risk-based monitoring
profile. But what technologies are companies
currently using to achieve risk-based monitor-
ing? According to the SAS research, many were
using proprietary applications, EDC platforms,
CTMS, and IVRS; and many sponsor organiza-
tions were looking to rely on their CRO systems
for these needs. And from the custom research,
it appears that CROs are ahead of biopharma
companies in using technology, while smaller
biopharma companies lack the resources to
keep up. “We do remote monitoring via EDC,”
said the data operations leader of one CRO. An-
other firm reported it mixes hard copy and elec-
tronic reports. “We have regular reporting from
the CRO, after a dosing schedule and interim re-
ports and final reports. We use both electronic
and hard copy to evauate and review,” said the
CEO of a biopharmaceutical company.
“We establish the site in advance, and I re-
view the sites and audit the sites in person,” re-
sponded the CEO of a biopharmaceutical com-
pany. “Then we do the study. It is fixed once we
establish this.” In a separate survey by Applied
Where is the technology for RBM and how do companies get to next stage predictive analytics?
Source: SAS, Applied Clinical Trials Risk-Based Monitoring, October 2013
Figure 1.
No
Yes
Are You Considering a Centralized Monitoring Strategy?
appliedclinicaltrialsonline.com APPLIED CLINICAL TRIALS 9
Clinical Trials, conducted in October
2013, 36% of the respondents said they
are looking to purchase technology to
support risk-based monitoring within
the next two years.
Centralized MonitoringCentralized monitoring is one risk-
based monitoring strategy that is
benefitted by a healthy dose of tech-
nology investment. The majority of re-
spondents in the SAS custom research
project said that while they want to
increase centralized monitoring, they
don’t have strategic plans in place to
take them there. Instead, they are still
relying on static schedules for on-site
monitoring. But using technology for
centralized, risk-based monitoring and
predictive analytics, as defined by reg-
ulatory guidelines, is well documented
in the industry.
While the respondents of the SAS
research project noted a lack of speci-
ficity in the FDA Guidance, the docu-
ments does state: “FDA encourages
greater use of centralized monitoring
practices, where appropriate, than has been the case his-
torically, with correspondingly less emphasis on on-site
monitoring.” Again, not specific what types of electronic
systems should be used, however, the FDA recommends
that sponsors who plan to incorporate centralized moni-
toring, “should ensure that the processes and expecta-
tions for site record keeping, data entry, and reporting
are well-defined and ensure timely access to clinical trial
data and supporting documentation.”
While firms would like to move toward technologically-
driven, centralized risk-based monitoring; they are only
taking baby steps. “Risk-based is the only way,” said the
clinical development group leader of a CRO. And the chief
scientific officer of a CRO added: “Everybody is going to
go risk-based with less frequent monitoring. Due to tech-
nology, the information is available in most systems.”
What Technology for RBM?The key for risk-based monitoring, from an information
management perspective, is to bring together both clini-
cal data from past studies, as well as the operational data,
especially site performance, to use in assessing risk for new
studies, said Laurie Rose Principal Industry Consultant,
Health & Life Sciences at SAS, during a webinar sponsored
by SAS and Applied Clinical Trials titled Myths, Models and
Momentum: Risk-Based Monitoring. “Those historical data
sources enable views of the past studies that can be ana-
lyzed to help set a baseline for what to expect in similar new
studies. Once the new study is established, incoming data is
also prepared for views and risk analysis by country or thera-
peutic area, site, investigator, CRA, or any other preferred
hierarchy.”
But where is the technology for RBM exactly and what
should organizations be looking for? Rose said that one
myth is that there’s really no proven RBM technology.
While she conceded it may not be a complete myth, she
did note a number of pilots where results are being pub-
lished, including a joint project in the UK by the Medical
Research Council, Department of Health, and the Medi-
cines in Healthcare Regulatory Agency, published in 2011.
In addition, the TransCelerate BioPharma consortium of
19 pharmaceutical companies that have been sharing and
presenting best practices on a number of initiatives, in-
cluding Risk-Based Monitoring. Said Rose, “TransCelerate
as a whole has been sharing methodology and analytical
Source: SAS, Applied Clinical Trials webcast, December 2013 www.appliedclinicaltrialsonline.com/monitoring
Figure 2.
Risk Identi�cation & Assessment
Study Data
RiskBusinessRules
Risk /PredictiveModeling
Assess &Score
Monitor &Report
Risk Identification and Assessment
“Everybody is going to go risk-based with less frequent monitoring. Due to technology, the information is available in most systems.”
10 APPLIED CLINICAL TRIALS appliedclinicaltrialsonline.com
techniques that leverage technology to innovate these
processes.”
The TransCelerate methodology does not suggest spe-
cific technologies or solutions that are offered by tech-
nology vendors in its current paper. It does list a Systems
Requirements and Preferred System Attributes, under
categories including Planning, Data Capture, Data Ag-
gregation, Analytics, Reporting and Visualization, and
Miscellaneous.
But for Analytics, TransCelerate says that those pre-
ferred system attributes include the following abilities:
• apply analytics to aggregated data (virtually or
actual) in order to identify outliers, trends
• apply thresholds relative to outliers; pre-
fer dynamic threshold definition
• indicate potential quality risk
• automated reporting
Rose described the components that SAS believes will
take shape in risk-based monitoring technology decisions
and strategies in the near future. “The technology ap-
proach starts with information management. It is the criti-
cal first step that pulls together essential data sources and
provides a view across sites, investigators, countries, mon-
itors, and patients. And then using analytics to assess the
risk elements of the trial and managing those risks, those
will make up core components for moving to a more risk-
based approach and having the ability to mitigate risks
that are discovered through this more central approach to
monitoring.”
It is in the analytical exercise that additional factors
from historical data would be leveraged--from what did
happen—to look more into the future for what is the po-
tential of something happening. Said Rose, “A particular
area that it’s going to be useful in is with adverse events
or serious adverse events where a predictive model is go-
ing to spot a trend where adverse events might only be
showing up in a couple of sites, not all sites. But in those
unique sites that have some outliers, there might be simi-
lar characteristics of the types of patients; and you’re just
not going to find that in the traditional monitoring where
you’re looking at that data one site at a time. But when you
have the ability to look all the way across, use more pre-
dictive models to look at trends, then you can start seeing
things like safety signals with patients much sooner.”
Data Aggregation in PracticeThe processes that need to take place after the data
sources are identified are filtering and aggregating to de-
termine which data elements make sense to use in assess-
ing the risk, and automating the data collection and the
refresh process, explained Rose. “Depending on the stage
of the trial or even the type of the study, that refresh and
update of the data might vary from near-real time updates
to daily, weekly, or monthly summaries. The data can also
be refreshed in a way that can support cumulative analysis,
as well as just a snapshot as both of those may help re-
flect different types of risk.”
During the webinar presentation and the Q&A, the inher-
ent challenge of disparate data sources was noted, as well
as preparing the data for advanced analytics, which drives
the risk assessment and the scoring process.
The audience wondered how industry could manage
the aggregation of data when multiple providers are being
utilized in outsourced functional service provider models.
Rose admitted that it is a challenge, but that it would be
true with any data aggregation issues with different pro-
viders and different systems, and it was not specific to
risk-based monitoring technologies.
However, Rose advised that a plan for that aggregation
of that data be in place, especially on the provider’s side.
“For a sponsor who might have multiple providers, from a
pure data integration and from a technological perspec-
tive, there are information management systems available
that can gather data from any type of a data source and
bring that together. I know from a clinical data perspective,
it would be very helpful to have CDISC standard formatted
data, which most of the EDC systems are using.”
Not minimizing the challenge, Rose said how orga-
nizations are going to bring the data together and what
data they will use to run that monitoring process from a
more centralized approach, is something that needs to
be determined when making their risk management plans.
She noted, “Innovative technology will enable improved
processes for collecting and analyzing data centrally,
across an entire study, so that both central risk monitor-
ing groups and on-site monitors will have improved insight
into clinical studies.”
During the presentation and the Q&A, the inherent challenge of disparate data sources was noted, as well as preparing the data for advanced analytics.