Claims-Based Pharmaceutical R&D

Time to Walk Backwards

Competitive Benchmarking of Clinical Development Programs to

Optimize Trial Designs and Clinical Operations
Sanjay Parikh, PhD
Director, Indegene Lifesystems

Claims-Based R&D Page 1 of 10


It’s time to bring the “market”
into the early stages of the
pharmaceutical R&D process
by working backwards from
the unmet market need
Claims-Based R&D
Over the last quarter of the twentieth century, medical research made substantial
advances in defining our understanding of diseases, their etiologies, and the
biochemical pathways through which they were mediated. Our understanding was
further augmented by human genome research. As the pathways of disease were
clearly identified, pharmaceutical research largely focused on a “lab to market”
approach, which involved identifying/synthesizing molecules that could mediate a
disease pathway, characterizing their various attributes, and then commercializing
them. In several cases, new molecules had characteristics that were marginally
different from others already on the market, and therefore, did not address any
unmet clinical need. Commercial success was often determined by the intensity of
the sales and marketing effort behind the product, which resulted in an “arms race”
(a battle for maximizing share of voice by investing in larger and larger sales
teams) and the emergence of “blockbusters.”
The last 10 years have seen a seismic shift in the dynamics of pharmaceutical
sales and marketing. The return on investment in sales force expansion is shrinking,
causing almost all major pharmaceutical companies to reduce their head counts.
Further, it is increasingly evident that the market and regulators are interested in
new therapies that address an unmet need rather than yet another product in an
existing class of molecules with little or no clinical or economic benefit.
Over the last few years, most of the innovations in pharmaceutical development
have been only incremental — for most indications, there are significant therapy
options available and it is unlikely that a radically better “wonder drug” will become
available soon. Consequently, a disproportionate amount of ongoing research and
development (R&D) effort has gone into products already in the market to expand
the spectrum of indications where they can be used. Figure 1 shows the number of
drugs approved by the US FDA over the years. The decline in approvals is a clear
indication of how difficult it will be for pharmaceutical companies to continue to show
revenue growth in future.
As they grapple with shrinking pipelines, stricter safety requirements of the
regulator, and spiraling costs to bring a product to market, pharmaceutical
companies need to ensure that their products genuinely fulfill an unmet market
need. Therefore, it is imperative that the R&D effort follow a “market to lab”
approach—one that reverses the conventional approach used over the last
few decades.
Number of drugs approved by US FDA
A systemic decline
40
35
30
25
20
15
10
5
0
2000 2001 2002 2003 2004 2005 2006 2007 2008
Figure 1. Number of drugs approved by US FDA: A systemic decline.
Adapted from the Wall Street Journal.
Page 2 of 10
 Aligning the Organization to the Goals of Clinical Development
Clinical R&D is a complicated process involving several steps and multiple
stakeholders, both internal and external, in a pharmaceutical organization. Over
the last 50 years, the journey of a product from laboratory to the market has not
only become more arduous and time-consuming, but also more risky. Furthermore,
since more and more clinical development plans (CDPs) include global, multicentric
clinical trials, their formulation and execution are broken into several sub-elements,
each of which have become the responsibility of different functional silos in
a pharmaceutical company. Consequently, clinical R&D at present involves
stakeholders from the strategic, marketing, sales, medical, R&D, clinical operations,
regulatory affairs, documentation, and health economics teams.

Given that the collective objective of all the teams involved in the CDP is to achieve
a desirable Target Product Profile (TPP) and therefore a superior product label,
pharmaceutical companies must ensure that all stakeholders are aligned and share
a common line of sight to the end objective. This is not always easy, but is a critical
All aspects of a well-designed challenge that must be overcome. Failure to do so runs the risk of a CDP not being
in step with current and future market needs, and oblivious to the competitive
Clinical Development Program scenario in the future.
revolve around the desired The essence of “claims-based R&D” lies in taking a backward “market to lab”
Target Product Profile approach so as to ensure that the CDP is designed to address specific unmet
market needs. It also involves the systematic benchmarking of a product’s CDP to
current and future competition while continuously evaluating scientific and market
threats and opportunities. It involves the integration of multiple inputs to develop
the CDP and then prospectively simulate the likely TPP of the product and a SWOT
analysis vis-à-vis its inline and pipeline competitors.

The Process of Developing a CDP

The process of claims-based R&D is iterative since it attempts to temper the desire
to develop an “ideal” product with scientific and operational feasibility. Figure 2
illustrates the process of claims-based R&D.

Customer Clinical
insights trial
design

Ideal Real CLINICAL

Scientific target target
insights Prioritization DEVELOPMENT
product product PLAN
profile profile

Clinical
Competitor
insights Continuous Benchmarking of CDP to Competition operations
plan

Figure 2. A Schematic Overview of Claims-Based R&D

Claims-Based R&D Page 3 of 10

 With the ever-growing volume of information and data available in the secondary
domain, it is now possible to pursue claims-based R&D to a far greater level of
granularity than before. It also enables TPP simulation on a near real-time basis as
pivotal information becomes available.

Customer Insights
In an earlier era of pharmaceutical development, unmet market needs were
determined almost exclusively from the opinions of physicians and medical key
opinion leaders (KOLs). In the modern era, however, there has been a significant
shift in the level of influence exerted by different stakeholders (customers) on the
patterns of pharmaceutical consumption. These stakeholders (customers) include
the patient, the payor, and the regulator.

While pursuing claims-based R&D, it is critical to ensure that the insights and
opinions of all the key stakeholders (customers) are accurately captured so
that the product(s) developed can genuinely claim to deliver a clinical and/or
economic benefit.

These insights are most often captured through primary research and intelligence
initiatives, which include engagement with physician groups, patient and caregiver
groups, insurance agencies, etc. However, such initiatives can be effectively
complemented by research of secondary sources of information such as online
patient discussions boards and transcripts of regulatory proceedings.

Scientific Insights
The volume of scientific research has been growing at an astounding rate.
A search on www.pubmed.com (the online index of the National Library of Medicine)
reveals that approximately 725,000 articles were published over the last year alone.
Journal articles and congress presentations constitute a wealth of information about
cutting-edge scientific developments.

A thorough analysis of such publications and academic congresses is critical at the

time of developing a CDP and simulating the TPP because:

99 It serves as an advanced warning system about novel scientific

developments that could threaten to make obsolete a particular product

99 It could reveal alternate approaches to addressing the unmet clinical need

at an early stage, and therefore throw up opportunities for partnerships or
ideas for development

99 It presents the successes and failures of competitive development

programs, thereby sparing a lot of unnecessary effort and investment

99 It is a good source to unveil new information about the epidemiology of a

disease and therefore the size of the addressable market opportunity

Claims-Based R&D Page 4 of 10


Analysis of the clinical trials
of the competition leads to a
reasonably accurate appreciation
of its strategic intent
Claims-Based R&D
Competitor Insights
Ultimately, pharmaceutical R&D needs to be viewed in the context of competition
because of the underlying commercial objectives associated with the process.
Consequently, an understanding of the development, licensing, and marketing
strategies of the competition constitutes a critical input into the development
of the CDP.
It is important to note that competition needs to be viewed not merely in today’s
context but also in context of what lies ahead. Therefore, it is recommended that any
CDP and its derived TPP be benchmarked to the claims and positioning strategies of
competitive products already in the market as well as the likely claims and strategies
of pipeline products.
Fortunately, substantial amount of information about clinical trials—completed and
ongoing—is available in the public domain through sources such as product labels
and clinical trial registries. The main source for clinical trial information is www.
clinicaltrials.gov (the official site of the US FDA), which contains several essential
details about all registered clinical trials.
Although the information is accessible through sources such as the ones cited
above, it is essential to note that deriving insights, simulating competitive claims,
etc., is an exercise that requires substantial human expertise.
The Ideal Target Product Profile
As a first step of an iterative process to design a CDP, it is recommended to
build an “ideal TPP.” To do this, one would need to integrate the various insights
and inferences described above and evolve a TPP that would address all the
unmet needs of the market while also yielding superior marketing claims across all
product attributes.
Therefore, an “ideal TPP” would represent best-in-class performance for efficacy,
safety (ideally, would result in no adverse effects), tolerability, convenience, drug and
food interactions, and perhaps, even cost. In addition, the “ideal TPP” would cover a
wider patient population than all competitors.
The Real Target Product Profile
Much as we may aspire for an “ideal TPP,” it is necessary to recognize that in
the real world, we cannot get every product attribute we desire. Therefore, we must
modify the “ideal TPP” by prioritizing the attributes and claims that the CDP must
focus on and compromising on others to arrive at the “real TPP.” This can be done
by classifying the product attributes in the “ideal TPP” as either essential
or desirable.
The essential features of the TPP would represent a set of product attributes
that represent either superiority over competing products or, at the very least,
noninferiority to competing products. Without these features, the product would enjoy
no unique selling point when launched.
The desirable features of the TPP would represent additional product attributes
that could enhance the product’s marketability. These additional attributes could
include some side indications, tolerability improvement, application for specific
subpopulations, or even improved product stability. They all represent features that
are not absolutely mandatory for commercial success but would certainly amplify the
claim of superiority. Figure 3 illustrates at a conceptual level how an “ideal TPP” will
be modified to a “real TPP.”
Page 5 of 10
 Ideal TPP Real TPP

Parameters “Best Case Scenario” Parameters “Base Case Scenario”

The drug is used in all cases The drug is used in xyz indication
Indications and Usage Indications and Usage
of xyz indication with cde criteria

XY strength, administered Y strength, administered before

Dosage and Administration Dosage and Administration
irrespective of meals orally meals orally

Dosage Forms and Strengths Tablets Dosage Forms and Strengths Tablets

Contraindications No contraindication Contraindications Contraindicated in abc

Warnings and Precautions No warnings Warnings and Precautions xyz

Adverse events such as xyz were

Adverse Reactions Minimal adverse events Adverse Reactions
reported

Drug Interactions No drug interaction Drug Interactions Excretion increased with drug b

Caution must be used in African

Use in Specific Populations Use similar in all populations Use in Specific Populations
Americans

Drug not prone for abuse and

Drug Abuse and Dependence Drug Abuse and Dependence Has potential drug dependence
dependence

Overdose causes potential adverse

Overdosage Has a high therapeutic window Overdosage
effects

Summary of the clinical pharmacology Summary of the clinical pharmacology

Clinical Pharmacology Clinical Pharmacology
and actions of the drug in humans and actions of the drug in humans

Carcinogenesis observed in rat

Nonclinical Toxicology No long-term carcinogenic potential Nonclinical Toxicology
at high doses

How Supplied/Storage and How Supplied/Storage and

As specified in the product label As specified in the product label
Handling Handling

Include information for prescribers to Include information for prescribers to

Patient Counseling Informa-
Patient Counseling Information convey to patients the use of the drug convey to patients the use of the drug
tion
safely and effectively safely and effectively

Figure 3. Modification of an Ideal TPP to be more Realistic Clinical Trial Design

The medical and clinical development groups must design clinical trials for the product
to achieve the “real TPP” described previously. For this, it is advisable for the clinical
development group to carry out extensive and detailed clinical trial analytics on the CDPs
of competitive products to help derive appropriate trial parameters such as inclusion and
exclusion criteria, primary and secondary endpoints, and patient populations. Such an
approach helps ensure that the results obtained from the clinical trials will allow “apples to
apples” comparisons between the product and its competitors.

Claims-Based R&D Page 6 of 10

 Fortunately, these clinical trial designs are readily available in the public domain.
However, substantial analytical effort is required to extract the parameters of
interest, homogenize the terminology across all clinical trials, and compare one trial
against another. The numbers of clinical trials that must be analyzed vary depending
on the therapy area and indication. However, for most large therapy areas, the
numbers run into hundreds or even a few thousands of clinical trials.
The analysis of such large numbers requires investment in human resources,
but this investment pays for itself because of the value it adds to the process of
developing the CDP. Knowledge of the distribution of endpoints, recruitment criteria,
and patient populations of competitive products can help design clinical trials that
enable head-to-head comparisons of the product with other products. Figure 4
shows some typical outputs from a detailed clinical trial analytics exercise on a
benchmark competitor. It highlights the most frequently used trial endpoints and
patient segments on which the drug is being investigated.

Endpoint Distributions for Benchmark Competitor

across Trials across Phases
7

6
6

5 5 5
Number of Trials

3 3
3

22 2 22 2 2 2
2

1 1 111 11 1 11 1 1 11 111 1 1
1

0
Phase II Phase II/III Phase III Phase IV

Safety/Tolerability Condition-A1/Condition-A2/Condition-A3
Chemical-A Use and/or Chemical-A Consumption Chemical-A Dependence and Withdrawal Symptoms
Adverse Events #-day point prevalence of non-action-A
Craving for action-A/Craving for chemical-A Chemical-A used per day
Psychophysiology/Neuropsychological evaluation Action-A Behaviour and Psychology

Patient Segment Distributions for Benchmark

Competitor across Trials across Phases
11 10
10
9 9
Number of Trials

8
7 6
6
5
5
4
3
3 2 2
2 1 1 1 1
1
0
Phase II Phase II/III Phase III Phase IV

Current/Active Action-A Doers Action-A Doers with Disorder-A

Chemical-A Dependant Subjects Action-A Doers with Disorder-B

Figure 4.
(A) Benchmark distributions for benchmark competitor across trial phases.
(B) Patient segment distributions for benchmark competitor across trial phases.

Claims-Based R&D Page 7 of 10

 It is also possible to analyze the results of clinical trials of competitive products
wherever available. These results point to the successes and failures of similar
products and CDPs.

At the time of developing the clinical trial design, it is possible that the clinical
development group may identify constraints that preclude the achieving of the
“real TPP” in its entirety. In such cases, the “real TPP” may have to be revised
after arriving at a consensus among all stakeholders such as marketing, clinical
development, medical affairs, and regulatory affairs teams.

Clinical Operations Plan

While the clinical trial design is the critical determinant of whether the product will
achieve its desired best in class position, the clinical operations plan focuses on the
timelines and logistics of the trial execution and therefore determines whether the
product can be launched within a reasonable timeframe—one that offers enough
time to earn a reasonable return on the investment in R&D.

In a crowded marketplace, there is tremendous competition between competitive

CDPs to recruit similar patients. It is well established that speeding up the
recruitment process yields a disproportionate return due to the extra duration earned
between the date of launch and patent expiry.

Knowledge and intelligence of investigators and global clinical trial sites in the
specific therapy area of interest can contribute tremendously toward the acceleration
of the patient recruitment process. Such information can be obtained through a
detailed analysis of information available in the secondary domain, that is, through
clinical trial registries and publications. However, this information ought to be refined
through primary research, wherein additional data about the sites of interest such as
productivity, resources, and costs are collected.

The model described in this paper for developing the CDP for a product is
necessarily iterative. The structure is designed to ensure that the development of the
CDP incorporates all relevant information and intelligence available so that the final
result stacks the odds in favor of obtaining a superior TPP to that of the competition.

Methodology of Research
For each of the boxes in the CDP development model in Figure 2, there are
substantial volumes of information available in the public domain. However, the
task of searching out the relevant information, analyzing it, and deriving the
necessary insight requires an approach that leverages the power of technology
along with the ability to apply the expertise of a rapidly scalable pool of medical and
pharmacology professionals.

Organizations that are moving toward claims-based R&D need to set up technology
infrastructure and platforms to integrate the huge volume of information available so
that multiple functions and stakeholders involved in the clinical development process
can share benchmarked data, knowledge, and insights in a seamless fashion.

Although technology development is often a one-time exercise, the ability to tap into
a large talent pool poses a challenge in the United States and the Western Europe.
Not only are the resources (medical doctors, life science experts, etc.) too expensive,
but they are also part of a restricted pool. These factors together make it less
attractive to develop a large-scale clinical trial analytics function in the United States
or the Western Europe.

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 The challenge of accessing a scalable and cost-effective pool of human experts
is increasingly being addressed through a hybrid off-shoring model of knowledge-
intensive services where on-site expertise is integrated with a global delivery model.
Offshore destinations such as India are rapidly acquiring a reputation of being able
to build large, cost-effective centers of excellence to deliver knowledge-intensive
services to the pharmaceutical industry such as medical writing and communications,
medical information management, training services, health economics, and scientific
competitive intelligence.

Some early movers in the pharmaceutical industry have already embarked on

large volume offshoring of clinical trial analytics and secondary scientific research
to help simulate the TPPs of competitive products, and thereby assist in the
development of CDPs.

Offshore resources permit
high-volume clinical trial
benchmarking to support
claims-based R&D
Given the pressure on clinical R&D to deliver the “best in class” or “first in class”
products, the concept of claims-based R&D will become increasingly standardized
and ubiquitous. Since the benefits of claims-based R&D are palpable, pharmaceuti-
cal companies would like to extend this methodology across all its therapy areas and
pipeline products. The requirements for highly qualified experts are therefore likely to
multiply in future and will be best addressed by offshore service providers in lower-
cost destinations such as India.

About the author - Sanjay Parikh, PhD

Sanjay has more than 15 years of experience in the global health care industry. At Indegene, he is responsible for the
company’s European business. Sanjay earned a BTech in Electrical Engineering from Indian Institute of Technology
(IIT) Bombay, a Masters in Biomedical Engineering from Case Western Reserve University, and a PhD in Biomedical
Engineering from The Johns Hopkins University School of Medicine. Prior to joining Indegene, he was with Antfactory, a
$200 million British VC firm responsible for the health care portfolio. Sanjay has successfully founded and run a medical
diagnostics company in India.

Write to us at bd@indegene.com to know more about claims–based R&D

Claims-Based R&D Page 9 of 10

About Indegene
Indegene is a scientific partner to life science companies to enhance the commercialization and marketing success of their products

Overview

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Indegene’s suite of scientific content, media, and technology
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and help clients reach out to key stakeholders with greater impact
Scientific Competitive Intelligence Services
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Indegene’s proprietary solutions cover a range of critical
unmet client needs
TrialPedia – a revolutionary Clinical Trial Benchmarking
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surveillance system
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Management Solutions
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Indegene’s scientific competitive intelligence services combine the speed, breadth, and depth of our research with the rich pharmaceutical and medi-
cal expertise of our team of analysts to provide valuable insights to our clients.
Some of the key insights we generate are-

• Status and Potential of Novel Products • Emerging trends in the design of CDPs • Gauging potential risks through an
and Technologies • TPP Assessment and Benchmarking ongoing trial
• Assessment of Unmet Market Needs • Launch Timeline Analysis • Identifying reference trials for bench
• Pipeline and Competitor Landscaping marking
• Identification and profiling of specific
• Clinical Trial Analytics clinical investigators and trial site • Identifying most appropriate end
points to select
In addition to providing a wide array of scientific competitive intelligence services, Indegene has developed TrialPedia, an innovative and unique
platform for analyzing and benchmarking competitive clinical trial data as well as clinical development programs. TrialPedia offers multiple search
and display functionalities for analysis of over 10,000 trials, and reduces the search time to less than 5% of that consumed by traditional means.

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