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1. WHITE PAPER
FOUR WAYS TO ACCELERATE CLINICAL
PORTFOLIO STRATEGY
JUNE 2013

2. TABLE OF CONTENTS
INTRODUCTION..............................................................1
LOOKING AT THE DRUG LIFECYCLE............................ 2
TRIAL TIMELINES .......................................................... 5
KEEPING ABREAST OF THE COMPETITIVE
ENVIRONMENT IN CLINICAL DEVELOPMENT.............7
ASSESSING DRUG SAFETY IN CLINICAL TRIALS ......10
SUMMARY......................................................................11
TIM MILLER
VP PRODUCT MANAGEMENT,
ANALYTICS
Tim Miller has worked within the
Thomson Reuters organization for 30
years, and specializes in the interface
between Science and IT. In his
current role Tim focuses on bioinformatics, cheminformatics,
semantic technologies, and text/data mining &visualisation,
specifically as they apply to the Pharma space. Tim holds
a bachelor’s degree in Chemistry from the University of
York and a bachelor’s degree in Law from the University of
London. He is a Chartered Chemist (Member of the Royal
Society of Chemistry) and a Chartered Information Technology
Professional (Member of the British Computer Society)
LARISSA COMIS-TIS
DIRECTOR, PRODUCT STRATEGY,
CLINICAL SOLUTIONS
Larissa has worked for more than a
decade in the healthcare industry
developing and implementing
strategies and launching products
focused on the needs of all industry stakeholders –
biopharmaceutical companies, payers, providers, and
patients. Her work has primarily been focused on clinical
trials informatics and technology, with a concentration
in oncology. She led one of the nation’s leading cancer
clinical trials matching services and databases, and has
developed and launched clinical informatics products for
the pharmaceutical and biotechnology industries. Prior to
her work in healthcare Larissa was director of international
operations at VerticalNet, one of the country’s first B2B
internet companies where she led the launch of sales and
operations of the company in several new markets including
London, Japan and South Africa. She has a master of
journalism from Temple University and a bachelor of arts from
William Smith College.

3. FOUR WAYS TO ACCELERATE CLINICAL PORTFOLIO STRATEGY 1
INTRODUCTION
The advances made in clinical research around targeted therapies have accelerated
quickly in the last decade. This has lead to the rapid expansion in the understanding
of many diseases, inherently increasing the complexity of clinical portfolio strategy
decisions and design. Additionally, the amount of clinical data and information is
expanding at the fastest rate in history.
Concurrently, the clinical R&D infrastructure is decentralizing and more and more
studies are being conducted in multiple countries. All of this is happening at a time
when payers around the world are putting downward pressure on pharmaceutical
and biotechnology companies, while regulatory bodies are insisting on real-world
evidence for new indications but not changing regulations to keep pace with the need
for this data.
Despite all of this rapid change, pharmaceutical and biotechnology companies are
still using many of the same clinical trials intelligence systems and products that they
have relied on for more than a decade. New technologies and human expertise can
make the volume of clinical trial information accessible and manageable, allowing for
more accurate predictions and better results.
Traditional methods of data and research conducted to aid in the R&D of new
treatments and therapies use a myriad of approaches that are often fragmented
and static. For instance, data from traditional sources have limitations of being
unstructured or built on a technology platform that doesn’t enable dynamic
visualizations and sophisticated searching. Visualization tools are available via long-
established clinical trials intelligence systems; however they are static representations
of data that must be re-created one by one when you want to drill down on the data or
view it in a different way, wasting time and money.
Additionally, there is no commercial way to connect those sources to each other or to
other research information and technology such as clinical trial benchmarking data
and advanced, dynamic analytics tools. This paper will explore four areas of clinical
trial design that can be accelerated through straightforward analytic approaches
leveraging advanced technology and the power of a global information business
keeping the information up to date in real time. These approaches were developed
over the course of year working hand-in-hand with the clinical development team of a
large pharmaceutical company.

4. 2 FOUR WAYS TO ACCELERATE CLINICAL PORTFOLIO STRATEGY
FOUR WAYS TO ACCELERATE CLINICAL
PORTFOLIO STRATEGY
The four scenarios below represent a more advanced way of accessing next-
generation clinical trials information and technology that could aid everyone involved
in clinical trials in the development and launch of new therapies.
1. LOOKING AT THE DRUG LIFECYCLE
Few drug candidates, fewer still in oncology, progress straightforwardly through the
classic Phase I, Phase II, Phase III cycle. Many have an interesting and checkered
history, being tried in different indications, picked up by different companies or
investigators, and succeeding or failing in each attempt.
Getting a view on the lifecycle of, for example, a competitor drug or in-licensing
candidate can answer important questions like:
• What was the rationale for the drug owner taking the drug into this indication?
• Was the drug ever tried in combinations, and did that affect the optimal dose?
• What happened to the drug after it was handed back to its originator?
APPROACH
To perform this kind of analysis requires data from different trials is comparable
on an “apples-to-apples” basis: at least the intervention and indication need to be
indexed to the same vocabulary. To answer the deeper questions you need to tie
the trial registry information about the protocol to the outcomes of the trial; so you
can understand why, for example, the owner chose to discontinue the drug in that
indication. Using the manually curated information in Cortellis for Clinical Trials
Intelligence, we are able to construct a view of all the trials for a given intervention.
We can then plot that as a PERT like view, and follow the drug chronologically
through its trial history. Behind the view we present detailed information on the trial
outcomes so questions about why the drug progressed or not can be answered.
RESULTS
Looking at the Novartis drug dovitinib, this initial view shows its progress through
different indications.
We’ve selected the Phase III renal cancer trial for further information in the details
panel. Drilling down into trials sponsored by the originator company, Chiron, and its
acquirer, Novartis, we can see a succession of Phase I trials in solid and advanced
solid tumors. The first Phase II trials started in 2009/2010 in breast, multiple
myeloma and transitional cell carcinoma. The first Phase III is in renal cancer at the
end of 2011. This is followed by new Phase II studies in HCC, endometrial cancer, GCC
& breast cancer.

5. FOUR WAYS TO ACCELERATE CLINICAL PORTFOLIO STRATEGY 3
Figure 1: Overall progress through different indications
Figure 2: Filtering to owner-sponsored trials

6. 4 FOUR WAYS TO ACCELERATE CLINICAL PORTFOLIO STRATEGY
Inverting the selection shows us who else are performing trials with this drug.
Figure 3: Investigator led trials
Selecting a single trial brings up details of the outcomes and reported adverse events.
Figure 4: Detailed outcomes for a trial
As can be seen, presenting the information in this way enables the user to interact
with the data, asking, and answering, questions that come to mind in looking at the
progression of the drug through trials without leaving the analysis.

7. FOUR WAYS TO ACCELERATE CLINICAL PORTFOLIO STRATEGY 5
2. DERIVING INSIGHTS FOR MORE ACCURATE TRIAL DURATION
PREDICTIONS THROUGH CURATED DATA
Clinical studies consume more than 70 percent of the time and over 90 percent of the
cost of bringing a drug to market. Getting the timing right is key to the success of a
clinical program. The trial needs to be long enough to provide statistically significant
results, but a trial that gets bogged down in recruitment or protocol amendment
increases costs. Delivering behind a competitor program could mean the commercial
and regulatory positioning of a candidate needs to be completely revised.
Teams engaged in clinical development need to have answers for questions like:
• What would the competitive landscape look like if this program was delayed by 6
months?
• Is the estimate I’ve given for executing this trial reasonable, given the performance
of other similar trials?
• Is a new trial of a drug in my indication likely to change the success factors for my
trial?
APPROACH
There are 2 questions here that can be applied to different areas of clinical trials
development and commercial operations: firstly, the race of competing drugs towards
registration, and secondly estimating trial durations. Both need to work on the same
data points. Those data points are the start and (estimated or real) end dates of trials
broken down by phase, indication, enrollment, etc.
For the first question we constructed a GANTT-like plot showing trials side-by-side.
To handle the cases where the trial has yet to complete we computed a projected
trial end date, constructed from the historical data on similar trials in the Cortellis
database. For the second question we used a standard “box-and-whiskers” plot
of the data from completed trials. This visualization highlights the spread of data
in the sample so you can get a sense of the variation. In addition to the Cortellis
content on published trial start and end dates, for this analysis we have added an
additional measure derived from anonymous, detailed trial information from our CMR
benchmarking database.
RESULTS
In this example we are looking at trials in Non-Hodgkin’s lymphoma. We have filtered
the focus to Phase II and Phase III trials, where the drug owner is sponsoring the trial
and adjusted the date filter to see trials currently in progress or recently completed.
Each bar on the chart represents a trial from start to finish date. Here we are showing
actual and projected end dates for the trials. Selecting a drug brings up further detail
on the trial, e.g. the status of the trial and biomarkers employed in the study. It’s easy
to see which trials are likely to end in the coming year or whenever your own trial is
due to complete.
In the following analysis we see the trial durations, in the same indication, for the
same phases and by the drug owner.

8. 6 FOUR WAYS TO ACCELERATE CLINICAL PORTFOLIO STRATEGY
Figure 1: Trial timelines in Non-Hodgkin’s Lymphoma
The analysis shows a reasonably close correlation of trials in the same indication and
phase and a good agreement between the Cortellis information, built from reports
in public documents, and the CMR benchmarks, built from granular information
deposited by Pharma companies themselves. There are some interesting outliers
in Phase III trials which can be further investigated by clicking the link into the trial
record on Cortellis.
Figure 2: Trial Durations in Non-Hodgkin’s Lymphoma
Using these visualizations derived from multiple sources ensures for instance that
timing of a commercial launch of a product is projected with the most up-to-date
clinical trials information and technology. Additionally it can be used to aid in
protocol development as enrollment for similar trials can be used to accurately
predict timelines of trial phases with the confidence that all information available is
being leveraged to do so.

9. FOUR WAYS TO ACCELERATE CLINICAL PORTFOLIO STRATEGY 7
3. KEEPING ABREAST OF THE COMPETITIVE ENVIRONMENT IN CLINICAL
DEVELOPMENT
It is easy to lose track of the broader picture when a clinical program is in progress
and get blindsided by external events. Questions that typically arise are:
• “Are there any new entrants in my disease, and are they employing novel
approaches?”
• “Have similar drugs, either in my disease or in other therapy areas, failed recently?
If so: why?”
• “Have any of my competitors altered their projection for starting or finishing a
clinical study?”
APPROACH
The classic visual metaphor in Pharma is the “development funnel” that provides a
snapshot the progress of drugs through the development pipeline. In a lot of cases
these funnel views are built manually by moving shapes around in presentation
software like Microsoft PowerPoint.
Thomson Reuters set out to build a version of this that is data-driven, i.e. the content
is built dynamically from the comprehensive drug development pipeline information
curated by us and managed on the Cortellis platform. Users can select an area of
interest: a competitor company, a disease or set of diseases or a mechanism of
action and get a dynamic view of the pipeline. The user can customize that view,
e.g. removing candidates from the view that they are not interested in or viewing by
different criteria, e.g. by company, drug or action.
Candidate progression can be tracked through trials across all indications and linked
back to the Cortellis platform for the full development profile on the drug.
RESULTS
In this example we are looking at the competitive environment in renal tumor
therapy. Using the filters in the analysis we have narrowed the focus to drugs in
development (from Discovery to Registration) and we have opted to look at the
landscape by small molecules vs. biologics, labeling by drug name. The view enables
a rapid appreciation of the current landscape, or you can focus on just those drugs
that have changed status in a given period, e.g. over the last year. The analysis image
can be exported for sharing with other team members: by email or as a presentation
graphic for example. Selecting any of the cells brings up a summary of the drug in the
details panel below and includes a link to the drug record in Cortellis. For a selected
drug, the development history chart shows the progression of the drug. This includes
passage through pipeline events in different countries for each organization working
with the drug.

10. 8 FOUR WAYS TO ACCELERATE CLINICAL PORTFOLIO STRATEGY
Figure 1: Charting the progression of a drug candidate in different indications
The view enables a rapid appreciation of the current landscape, or you can focus on
just those drugs that have changed status in a given period, e.g. over the last year.
The analysis image can be exported for sharing with other team members: by email or
as a presentation graphic for example. Selecting any of the cells brings up a summary
of the drug in the details panel below and includes a link to the drug record in
Cortellis. For a selected drug, the development history chart shows the progression of
the drug. This includes passage through pipeline events in different countries for each
organization working with the drug.

11. FOUR WAYS TO ACCELERATE CLINICAL PORTFOLIO STRATEGY 9
Figure 2: Snapshot of the development funnel for renal tumor drugs
Here we can see that BNC-105 completed phase I trials in solid tumors in 2008 and
is in Phase II trials for renal and ovary tumors currently. We can also see that the drug
has been studied in mesothelioma, in Australia starting March 2010. Linking through
to the development profile on Cortellis we find that preliminary results of the renal
tumor trial were reported recently:
Figure 3: Report on preliminary results of renal tumor trial
This approach demonstrates how a dynamic visualization of information about drug
pipeline events supports:
• A high level overview of the competitive environment
• Exploration of detail that enables the user to follow a train of thought through the
application

12. 10 FOUR WAYS TO ACCELERATE CLINICAL PORTFOLIO STRATEGY
4. ASSESSING DRUG SAFETY IN CLINICAL TRIALS
One of the key differentiators in bringing a drug to market is its safety profile. The
regulatory and public focus on adverse events is growing. Understanding the safety
landscape around a class of drugs or comparing the safety profiles of competing
drug candidates is an imperative. The most reliable source of safety data is adverse
events reported in clinical trials which are typically disclosed in journal articles and
presentations at meetings. The challenge is to aggregate the information across
multiple trials, for multiple interventions so that you can assess the entire landscape
– rather than searching for results trial by trial.
Questions that typically arise are:
• Is the safety data on my drug sufficiently better than the current gold standard to
warrant approval?
• Why is my competitor continuing with this drug candidate when reports of its
efficacy aren’t very encouraging?
• What adverse events are reported in the literature for a particular intervention or
class of drugs?
APPROACH
In this case, a heat map approach can present aggregated information in a way that
easily identifies areas of interest or concern. To drive this type of analysis, we leverage
powerful ontologies from Thomson Reuters Cortellis™. These allow you to select
drugs for comparison by their mechanism of action or disease, or individually by their
trade, approved name, chemical, or lab-code identifiers.
Adverse events are reported by their Cortellis indication terms and grouped into
MEDDRA classes so you can see, for example, whether Drug A’s side effects are
mostly cardiovascular while Drug B’s are mostly gastrointestinal. The intensity of
the heat map can be toggled between number of patients affected, percentage of
patients, or numbers of trials in which the adverse event has been reported. Users
can then drill down into the details of individual trials, summarized from the original
paper or meeting presentation.

13. FOUR WAYS TO ACCELERATE CLINICAL PORTFOLIO STRATEGY 11
Figure 1: Thomson Reuters clinical safety visualization comparing side effects of two drugs
Details of the trial(s) in which the adverse event was reported appear on selecting
one of the cells in the heat map. In this case we have selected the GI bleeding adverse
event (colored blue). In the details panel below are key facts about the trial plus a
manually curated abstract of the adverse events including more detail than can be
presented in the image. There are also embedded links to Cortellis and to the trial
registry. This approach reduces the need to search for safety results trial-by-trial.
RESULTS
In this example (Figure 1) we compare 2 VEGF inhibitors. The side-by-side comparison
shows the percent affected aggregated over the trials in the Cortellis database
presented as a gradient from green (low) to red (high). Grey cells indicate where the
trial reports the adverse event but doesn’t give numbers affected. The adverse events
are grouped by MEDDRA classes, which makes it easy to see that the adverse events
of the first drug are chiefly rash and diarrhea; whereas those of the second drug are
emesis, nausea, and fatigue.
SUMMARY
Traditional methods of clinical trials information gathering are no longer suited to the
increased pace and complexity of discovery. Real-time visualization tools, extensive
analytics capabilities driven off of expansive global data and information are crucial
to successfully executing clinical strategies, research and development. Data about
clinical trials is published and updated around the world and the clock. Decisions
that clinical trialists make must leverage the most complete and accurate information
and have it presented in a way that enables them to ask new questions based on the
information presented.

14. About Clinical Solutions from Thomson Reuters
Thomson Reuters Life Sciences offers a range of information, tools, and services
relating to clinical trials.
Cortellis Clinical Trials Intelligence
The most powerful resource to accelerate a wide variety of strategic clinical
development decisions. Covering drugs, medical devices and biomarkers, Cortellis
Clinical Trials Intelligence is built on globally focused technology, including: robust
searching, alerting, exporting, analytics/ visualizations, customer information
integration and an application programming interface (API). Cortellis Clinical Trials
Intelligence also integrates with other best in class content from Thomson Reuters.
Professional Services – Clinical
Our Life Sciences Professional Services team provides customized solutions that
leverage our unique blend of content, technology, and expertise
• Clinical trial design - patient stratification techniques, recommended endpoints
• Clinical trial planning – site selection and future disease landscaping and
epidemiology
• Strategic decision making – entering or exiting disease area decision support,
R&D organizational consulting
• Custom Analytics & Visualizations – to drive strategic decision making around
drug safety, trial timelines, and competitive trials
About Thomson Reuters
Thomson Reuters is the leading source of intelligent information for professionals
around the world. Our customers are knowledge workers in key sectors of the global
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fields that are vital to developed and emerging economies such as law, financial
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Our knowledge and information is essential for drug companies to discover new
drugs and get them to market faster, for researchers to find relevant papers and
know what’s newly published in their subject, and for businesses to optimize their
intellectual property and find competitive intelligence.
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