EvidenceMatters
A P U B L I v
C A T I O id
N O F U N I T Ee
D B I O S nc
O U R C E C O R P O R A e
T I O N
Mat
M A Y 2 0 0 9 ter
V O L U M E X V I S S U E 2

Inside this Issue
F O C U S O N : Right Evidence – Right Audience – Right Time
Cover Story:
Evidence Generation Strategic Planning for
Evidence Generation
Strategic Planning
Optimal Product Positioning
UBC and the PACE Initiative ......... 2
By Teresa Wilcox, RPh, PhD, Senior Research Scientist, and Peter Marangos, BA, BS, Manager, Product Marketing
Upcoming Presentations .............. 3
In this turbulent global economy, fraught with increasing regulatory require-
UBC at ISPOR ............................... 4
ments and impending legislative changes, obtaining optimal product posi-
tioning and market uptake requires thoughtful planning and a fresh perspec-
F O C U S O N : Right Evidence –
tive. The crowded therapeutic marketplace has driven the need for product
Right Audience – Right Time
differentiation and comparative assessment, and formulary decision makers
Publication Plans ........................ 7
and payers are demanding greater quantities of evidence with an increasing
level of scientific rigor. For instance, the Centers for Medicare and Medicaid
Evidence Gathering in Support of
Services find that the available evidence that is evaluated for national cover-
Health Economic Evaluations ...... 9
age decisions is very seldom graded better than ‘fair’, and as result condi-
Pricing & Reimbursement at
tional coverage decisions and ‘coverage with evidence development’ have
Each Stage of Development ..... 12
become increasingly common.1
Drug Related Adverse Events ... 13
Identifying Subgroups of
Therefore, it is now more than ever critical that pharmaceutical and medical
Differential Responders ............ 14
device manufacturers seek to answer the tough questions that wil define
UBC’s Evidence-Based
product value. These questions may include:
Methodology Initiative .............. 16
Do you understand the unmet need in the marketplace, and are you
Label Strategies to Inform
leveraging the clinical endpoints and appropriate evidence to address it?
Drug Development ................... 17
What are the critical thresholds for evidence that must be met to enable
New Regulations and Expectations
decision making?
for Industry-Sponsored Medical
Are you aware of the competitive, regulatory, and reimbursement environments, both present
Publications ............................. 18
and future, and is your product development strategy designed accordingly?
FDA Issues Proposed Rule
on Pregnancy and Lactation
Do you understand the evidence-based value profile required by al relevant customer groups
Labeling ................................... 20
for optimal product positioning?
Effective Planning and Conduct
Do your product development/commercialization plans mitigate risk while also ensuring maxi-
of Data Monitoring Committee
mal market adoption?
Meetings .................................. 21
Although often complex and challenging in the face of resource limitations, effectively answering
News Briefs ............................... 23
these questions requires a comprehensive, multi-year, multi-dimensional strategy to document and
communicate evidence of product value. Establishing such an evidence generation strategic planning
Recent Presentations ................. 25
(EGS) methodology will facilitate coverage, reimbursement, and adoption by ensuring that the right
Recent Publications ................... 26
value-based evidence is communicated to the right audience at the right time.
Science Policy Corner ................ 28
The right Evidence…
to the right Audience…
EGS :
EGS :
Optimal
•
Evidence
Identify unmet need
Communication &
Product
Generation
Dissemination
• Determine & align value
(Payers, Regulatory, etc.)
Positioning
• Implementation plan
EGS : Or

ganization and Pr

oject Management
Evidence Matters.
…at the right Time
continued on page 6

---

2
U N I T E D B I O S O U R C E C O R P O R A T I O N
UBC and the PACE Initiative Recommend
Pragmatic Methods in Institute of Medicine Priority Setting
The American Recovery and Reinvestment Act of 2009
Priority 1: Invest in methodological innovation to improve
(H.R. 1, also referred to as the Stimulus Bil ) designated $1.1
the cost efficiency, timeliness, pragmatism and
bil ion dol ars for the purposes of exploring Comparative
usefulness of comparative effectiveness trials
Effectiveness Research (CER). Federal agencies are currently
to real-world health care decision makers.
launching efforts to respond to Congressional mandate and
Rationale:
prioritize research opportunities to utilize these funds.
a. Filling the comparative evidence gap requires both
observational and clinical trial research. The gulf (cost,
The Institute of Medicine (IOM), in particular, has been tasked
timeliness, standards of evidence, validity, and reliability)
with $1.5 mil ion to prepare a Report to Congress by June
between these two approaches is enormous. Today, much
30, 2009, in which it wil make “recommendations on the
attention, effort, and presumably funding is being made
national priorities for comparative effectiveness research to
to improve observational methods in an effort to fill the
be conducted or supported” using these new stimulus funds.
gap that exists in comparative medicine. However, there
On March 19-20, 2009, the IOM’s Committee on Compara-
is currently an insufficient investment under consid-
tive Effectiveness Research Priorities held a meeting during
eration to improve clinical trial methods. I would argue
which it heard from government stakeholders (March 19) and
that improving clinical trial methods is at least as important
public stakeholders (March 20). IOM also issued a question-
as improving observational methods.
naire requesting no more than three therapeutic area-specific
research priorities from each interested stakeholder.
b. Traditional clinical trial approaches:
1. Are highly burdensome to design and conduct;
During both meetings, there seemed to be a consensus that IOM
needed to consider priorities beyond intervention-intervention
2. Often contain stringent design rules resulting in
comparisons and consider system-wide improvements to
studying research rather than real-world scenarios;
maximize the
3. Are inflexible, not allowing for learning and adapting
benefit of evi-
as evidence is developed; and
dence develop-
“We need true transformational
4. Generate findings that may no longer be relevant by
ment. In particu-
thinking in clinical trial design or we
the time the trial is completed. For example, con-
lar, Dr. Carolyn
sider two prominent NIH-funded CER studies: the
Clancy, Director
risk wasting vast amounts of money
anti-hypertensive study “ALLHAT” ($135 mil ion over
of the Agency
answering the wrong questions, or
5 years) and the anti-psychotic study “CATIE” ($40
for Healthcare
million over 4 years). Neither resulted in significant
Research and
the right questions too late.”
changes in medical practice, and the findings from
Quality (AHRQ),
at least one (ALLHAT) is believed by many to have
emphasized the
led to largely irrelevant results due to changes in
need for IOM to
medical practice that occurred during the course
focus beyond a list of comparison projects, and focus instead
of the lengthy trial.
on resolving the “inherent tension between how much is the
framework and how much is the list.” Further, Dr. Clancy argued
c. To date, there is substantial interest and slowly growing
that the more IOM considers infrastructure needs, such as
experience in designing pragmatic clinical trials (PCTs) as
people, data, methods, and strategies, “the better off we
a solution to real-world evidence problems, but there has
will be.”
been insufficient investment in PCT methodology. A
pragmatic clinical trial differs from a randomized clinical
Dr. Bryan R. Luce, Senior Vice President for Science Policy
trial in that it allows real-world scenarios such as co-
at UBC, spoke to the Committee on Friday, April 20, and
morbidities, adherence issues, delivery variation, evolving
stressed the importance of developing innovative yet prag-
intervention strategy, etc., to be integrated into the design
matic methods to pursuing real-world comparative clinical
and expected outcome of a trial.
evidence: “We need true transformational thinking in
clinical trial design or we risk wasting vast amounts
Priority 2: Invest in Bayesian adaptive trial methods
of money answering the wrong questions, or the right
for application to “real-world” comparative
questions too late.”
effectiveness research.
Rationale:
In his statement submitted for the record, Dr. Luce outlined
two high priorities for comparative effectiveness, reproduced
a. Many comparative effectiveness research questions
here.
are, by their very nature, often best characterized as a

---

E V I D E N C E M A T T E R S • W W W . U N I T E D B I O S O U R C E . C O M
3
Bayesian problem in which prior evidence is weighed
All of the above are fundamentally Bayesian concepts and
together with new data to produce a better-informed deci-
may benefit from Bayesian approaches.
sion. For instance, we currently struggle with existing evi-
dence which is deemed useful but insufficient for decision
b. Bayesian adaptive trial methods have been shown to be
making (often the conclusion of systematic reviews from
feasible and acceptable in numerous Phase II pharmaceu-
AHRQ, for instance). The implicit challenge from the “insuf-
tical dosing studies and medical device registration trials,
ficient evidence” conclusion seems to be to incrementally
potential y leading to significant cost and time efficiencies.
add evidence for an informed decision. Beginning a trial or
None of these trials are applications in “real-world” condi-
research on the shoulders of established knowledge (often
tions. Many data and safety monitoring boards use essen-
referred to as the “prior”) is a Bayesian principle.
tial y Bayesian methods to ensure that trial participants
are not being exposed to undue risks during the course of
Also, the clinical question often relates to identifying the
a trial. Further, to our knowledge, no effort or investment
relative benefits and harms of alternative therapies (e.g.,
has yet been made, nor experience gained, in evaluating
for whom? when? how? under what conditions?). These
Bayesian adaptive techniques to “real-world” comparative
questions may best be answered by adapting a research
trial applications.
design during the course of a trial—an approach that
is general y considered inconsistent using predominant
Federal agencies will continue to align research priorities
classical methods of clinical trial design and analysis; for
and pursue opportunities in comparative effectiveness
example, adapting to the unique clinical circumstances
research, as we have seen with the National Institutes of
experienced within a Medicare population with various
Health’s recent Challenge Grant topics. UBC and the PACE
types of co-morbidities.
Initiative wil remain poised to contribute innovative ideas
Final y, health care decision makers think natural y in terms
on pragmatic real-world comparative trials.
of “probability”, inherently understanding uncertainty and
seeking to improve chances their decisions are correct.
For more information on PACE, please visit www.PACEInitiative.org.
19th European Congress of Clinical Microbiology
Upcoming Presentations
and Infectious Diseases (ECCMID)
May 16–May 19 2009, Helsinki, Finland
2009 Pediatric Academic Societies Annual
Meeting (PAS)
Poster Presentation
Cost-Effectiveness of Daptomycin in Hospitalized Patients
May 2–May 5 2009, Baltimore, MD, USA
with cSSTI Caused by Gram-Positive Organisms Muszbek N,
Poster Presentation
Gould IM, Brown RE, Balp MM
Reduction in Mortality Among High-Risk Preterm Infants
Receiving Palivizumab Prophylaxis: A Systematic Review and
American Psychiatric Association (APA)
Meta-Analysis Checchia PA, Nalysnyk L, Fernandes AW,
Annual Meeting 2009
Mahadevia PJ, Xu Y, Fahrbach K, Wel iver R
May 16–May 21 2009, San Francisco, CA, USA
American Thoracic Society International Conference
Workshop
May 15–May 20 2009, San Diego, CA, USA
The Use of Research Measures in Clinical Practice
Moderator: J Busner, PhD, Practice Leader, Specialty Clinical
Poster Presentations
Services, United BioSource Corp.
How Stable is Stable in COPD? An Analysis of Day-to-Day
EXACT Score Variability in Acute and Stable Patients with
MAGI’s 2009 Clinical Research Conference—East
COPD Leidy NK, Wilcox TK, Sethi S, Jones PW, EXACT-PRO
May 31–Jun 3 2009, Miami, FL, USA
Study Group
Oral Presentation
Patient Perceptions of COPD: Development of the COPD
Registry Study Budgets and Contracts
Assessment Test Harding G, Roberts L, Gavriel S, Murray L,
Speaker: G Morton, MBA, Senior Contracts Manager, United
Jones P, Berry P, Wiklund I, Leidy NK
BioSource Corp.
Psychometric Evaluation of the Asthma Control Test and Asthma
Alzheimer’s Association 2009 International Conference
Control Questionnaire in Patients with Moderate to Severe Asthma
Revicki D, Margolis MK, Rentz A, Sapra SJ
on Alzheimer’s Disease (ICAD)
Jul 11–Jul 16 2009, Vienna, Austria
Mini-Symposium
Poster Presentations
Chronic Obstructive Pulmonary Disease Exacerbation:
Mechanism and Management
Screening for Alzheimer’s Disease: Health Economic Projections
Chairs: S. Sethi, MD; J. A. Wedzicha, MD
of the Impact of Earlier Diagnosis and Treatment Getsios D,
Blume S, Ishak J, Maclaine G
Patterns of Recovery from Exacerbations of COPD: EXACT
Change Scores Days 1–14
Updated Cost-Effectiveness Projections for Donepezil in the
Oral Presenters: Wilcox TK, Leidy NK, Sethi S, Jones PW,
Treatment of Patients with Mild to Moderately Severe Alzheimer’s
EXACT-PRO Study Group
Disease in the UK Getsios D, Blume S, Ishak J, Maclaine G

---

4
U N I T E D B I O S O U R C E C O R P O R A T I O N
ISPOR 14th Annual International Meeting
M A Y 1 6 – 2 0 , 2 0 0 9 , O R L A N D O , F L O R I D A , U S A
Short Courses
Educational Symposium
Saturday, May 16
S P o n S o R E d B y
Bayesian Analysis: Overview and Applications
United BioSource Corporation
Faculty: David Vanness, PhD, Research Scientist, United BioSource
Corp.; Christopher S. Hol enbeak, PhD, Assistant Prof., Surgery and
Monday, May 18 7:15am – 8:15am
Health Evaluation Sciences, Penn State College of Medicine
The Comparative Effectiveness Research
Saturday, May 16
Wave: Solving Surfing Techniques
Finding and Extracting Cost Data
Faculty: L. Clark Paramore, MSPH, Executive Director and Research
Moderator: Bryan R. Luce, PhD, MBA
Scientist, Center for Health Economics & Science Policy, United
Senior Vice President, Science Policy,
BioSource Corp.; Steve Blume, MA, Research Scientist, United
United BioSource Corporation
BioSource Corp.
Sunday, May 17
Whether we like it or not, the new evidence ‘wave’ includes
Bayesian Analysis: Advanced
comparative trials and with it comes the need to solve new
‘surfing’ techniques. The future comparative effectiveness
Faculty: David Vanness, PhD, Research Scientist, United BioSource
Corp.; Keith R. Abrams, PhD, Prof. of Medical Statistics, Dept. of Health
(CE) research agenda inevitably wil (and should!) include
Sciences, Univ. of Leicester; Christopher S. Hol enbeak, PhD, Assistant
comparative real-world (aka “pragmatic”) trials. Traditional
Prof., Surgery and Health Evaluation Sciences, Penn State College of
research designs are extremely expensive and lengthy
Medicine
making them not very practical. Further, there tends to be
Discrete Event Simulation for Economic Analyses
high uncertainty due to the nature of the messy real world.
Faculty: J. Jaime Caro, MDCM, FRCPC, FACP, Adjunct Prof. of
This session poses a Bayesian adaptive design approach
Medicine, Adjunct Prof. of Epidemiology and Biostatistics, McGill
as a possible solution to reduce uncertainty of findings,
Univ. and Sr. VP Health Economics, United BioSource Corp.; Jörgen
cost and time and features a series of working papers to
Möller, MSc, Mech. Eng., VP, Modeling, United BioSource Corp.
address four specific technical issues.
Getting to “Yes” (aka: When do we know (what is
the minimal threshold) when we have “just enough”
Issue Panels
evidence for a real-world (read, coverage decision
Monday, May 18, Session I
maker; clinical guideline committee) decision?
Bryan R. Luce, PhD, MBA
Models for Collaborative Development of Patient-Reported
Outcome Measures for Clinical Trials—Different Paths,
Senior Vice President, Science Policy
Same Destination?
United BioSource Corporation
Moderator: Asha Hareendran, PhD, Sr. Research Scientist, United
BioSource Corp.
Thresholds to Invest: Manufacturers’ Elasticities for
Sponsoring Real-World Comparative Trials (aka: Just
Panelists: Priti Jhingran, PhD, U.S. Health Outcomes Director,
how much does cost, time, risk need to be decreased
GlaxoSmithKline; Dennis A. Revicki, PhD, Sr. VP Health Outcomes
for a manufacturer to fund a CE trial of its product?)
Research & Scientific Director Center for Health Outcomes Research,
United BioSource Corp.
Anirban Basu, PhD
Assistant Professor, Hospital Medicine
What is the Role for Pragmatic Trials in Regulatory Approval?
Department of Medicine
Moderator: Penny Mohr, MA, VP Programs, Center for Medical
University of Chicago
Technology Policy
Panelists: Marc L. Berger, MD, VP Global Health Outcomes, Eli Lilly;
Building Off the Existing Evidence (aka: The world
Robert Temple, MD, Director Office of Drug Evaluation I, FDA, Center for
may be flat, but is the prior?)
Drug Evaluation and Research
David J. Vanness, PhD
Non-Presenting Authors: Rebecca Singer Cohen, MPP, Research
Research Scientist
Associate, United BioSource Corp.; Bryan R. Luce, PhD, MBA, Sr. VP
United BioSource Corporation
Science Policy, United BioSource Corp.
The Role of Dynamic Predictive Simulation in Guiding
Tuesday, May 19, Session II
the Pragmatic, Adaptive Trial
Use of the QALY for Economic Evaluation: Pragmatic Choice
J. Jaime Caro, MDCM, FRCPC, FACP
or Unjustified Evil?
Senior Vice President & Senior Research Scientist
Moderator: Louis Garrison, PhD, Prof. of Pharmacy, Dept. of Pharmacy,
Univ. of Washington
Health Economics
United BioSource Corporation
Panelists: Michael F. Drummond, DPhil, Prof. of Health Economics,
Univ. of York, Centre for Health Economics; J. Jaime Caro, MDCM,
FRCPC, FACP, Sr. VP Health Economics, United BioSource Corp.

---

E V I D E N C E M A T T E R S • W W W . U N I T E D B I O S O U R C E . C O M
5
Workshops
Tuesday, May 19, Poster Session II
Can Older, Chronically Ill Adults Use Electronic Diaries?
Monday, May 18, Session I
Compliance Rates in a Prospective Study of Patients
Innovations in Physiologic and Patient-Reported Data
with COPD
Capture: Implications for Streamlining Data Collection
Cates C, Roberts L, Eremenco S, Wilcox TK, Leidy NK
and Leveraging Access to Real-Time Data
Discussion Leaders: Sonya Eremenco, MA, ePRO Manager, United
Development of a Valuation Function for a Diabetes-
BioSource Corp.; Wilhelm Muehlhausen, DVM, Sr. Project Manager,
Specific Preference-Based Measure of Health Based
Cardinal Health Germany 234; Lionel Tarassenko, FREng, Prof.
on the Multi-Attribute Utility Theory
of Electrical Engineering, Univ. of Oxford, Institute of Biomedical
Sundaram M, Smith MJ, Revicki D, Miller LA, Madhavan SS
Engineering; Barbara Marino, PhD, RN, Director, Clinical Operations
Scientific Advisor, PHT Corp.
Glycemic Variability and Complications in Patients with
Diabetes Mellitus: Evidence from a Systematic Review
Tuesday, May 19, Session II
of the Literature
Uncertainty Around an Efficiency Frontier
Nalysnyk L, Hernandez-Medina M, Xavier N, Krishnarajah G
Discussion Leaders: J. Jaime Caro, MDCM, FRCPC, FACP, Sr. VP
Health Economics, United BioSource Corp.; Isao Kamae, MD, DrPH,
Saving Costs From Influenza Immunization Among Young
Prof., Keio Univ. Graduate School of Health Management; Charalabos-
Children—Live Attenuated Vs. Inactivated Influenza
Markos Dintsios, MA, MPH, Research Fellow, Institute for Quality and
Vaccination
Efficiency in Health Care (IQWiG), Pharmaceutical Products Evaluation
Rousculp MD, Quon P, Belshe RB, Woodward TC, Luce B,
Mahadevia PJ
Wednesday, May 20, Session III
Coping with the Validation Requirements of the FDA PRO
Wednesday, May 20, Poster Session III
Guidance: The Intersection of Science and Practice
Cost-Effectiveness of Screening and Treatment of
Discussion Leaders: William Lenderking, PhD, Sr. Research Leader,
Alzheimer‘s Disease with Donepezil in the United Kingdom
United BioSource Corp.; Elizabeth Merikle, PhD, Research Scientist,
Getsios D, Blume S, Ishak J, Maclaine G
United BioSource Corp.; Michelle Stewart, PhD, Director, Pfizer
Cost-Effectiveness Study in Patients with Mild to Moderately
Wednesday, May 20, Session V
Severe Alzheimer‘s Disease: Projected Benefits of Donepezil
Implementing E-PRO Measures in Clinical Trials: What
in the United Kingdom
Sponsors Need to Know
Getsios D, Blume S, Ishak J, Maclaine G
Discussion Leaders: Sonya Eremenco, MA, ePRO Manager, United
BioSource Corp.; Stephen Joel Coons, PhD, Prof., Univ. of Arizona,
Development of the Injection Pen Assessment Questionnaire
Pharmaceutical Sciences; Ari Gnanasakthy, MSc, Director, Health
(IPAQ) to Evaluate a New Device to Administer Human
Economics and Outcomes Research, Novartis Pharmaceuticals
Growth Hormone (HGH)
Etschmaier M, Kimel M, McCormack J, Hey-Hadavi J, Cara JF
Podium Presentation
Flushing Assessment Tool (FAST): Psychometric Properties
Monday, May 18, Podium Session II
of a New Measure Assessing Flushing Symptoms
Association of Cardiometabolic Risk Factors and Prevalent
Kawata AK, Thakkar R, Davidson MH, Punzi HA, Jiang P, Li D, Krause S,
Cardiovascular Events
Padley R, Revicki DA
Malone DC, Boudreau D, Nichols G, Raebel MA, Fishman P, Feldstein A,
Literature Review on the Global Cost of Multiple Sclerosis
Ben-Joseph R, Okamoto LJ
Birt JA, Duhig AM, Naci H, Fleurence RL
Poster Presentations
The Impact of Different Stages of Multiple Sclerosis on
Health Utilities: A Systematic Review of the Literature
Monday, May 18, Poster Session I
Naci H, Fleurence R, Birt J, Duhig AM
Clinical Outcomes and Patterns of Care in Patients with
The Prediction of Stroke and Mortality Outcomes in Patients
Chronic Liver Disease, Bridging Fibrosis and Cirrhosis:
with Atrial Fibrillation Maintaining Sinus Rhythm With and
Adaptable Methodologies for the Design, Implementation
Without Antiarrhythmic Drugs
and Conduct of Multi-National, Retrospective Chart
Review Studies
Xenakis JG, Quon P, Getsios D, White SA, Khaykin Y
Payne KA, Lordan N, Duran B, Ishak KJ, Grotzinger K
Urinary Urgency Intensity Rating in Relation to Symptom
Frequency, Bother, and Treatment Seeking: Results from
Development and Validation of an ePRO Template
EPILUTS in the US, UK and Sweden (SE)
Administered Via a Web-Based Interface
Thompson CL, Coyne KS, Sexton C, Kopp Z
Eremenco S, Coyne KS, Duran B, Leidy NK
U.S. Budget Impact of Increasing Aspirin Usage for Primary
Is the Health Utilities Index Valid and Responsive in
and Secondary Prevention of Cardiovascular Disease
Assessing Patients with Ankylosing Spondylitis?
Benedict A, Manson SC, Pan F, Wittrup-Jensen KU, Fendrick AM
Gooch K, Feeny DH, Wong R, Pangan A, Revicki D, van der Heijde D
Methods for Personalized Medicine: Factor Mixture Models
for Investigating Differential Response to Treatment
Stop by Booth #4 at the
Stull D, Wyrwich KW, Frueh FW
ISPOR Conference to meet the UBC staff
Off-Label Use of Oncology Drugs in a Community Oncology
and learn more about how UBC can
EMR Database
support your product needs.
Stephen R, Knopf K, Reynolds MW, Luo W, Fraeman K

---

6
U N I T E D B I O S O U R C E C O R P O R A T I O N
F O C U S O N : Right Evidence – Right Audience – Right Time
3. Identify and prioritize the evidence required to sup-
Evidence Generation Strategic
port the target value proposition, define the resources
Planning
needed, and outline a timeline for evidence generation.
continued from front page
4. Outline a publication plan and communication strategy
to ensure that the right evidence reaches the right
audience at the right time.
EGS is a results-oriented process to assure that available
data are ful y leveraged, new research projects are careful y
Opportunities for EGS Implementation
designed to build a unified body of evidence, and information
is effectively communicated to key decision-makers. EGS is
In order to effectively implement any EGS methodology,
most effective when a systematic, standardized, and repeat-
one must first understand the characteristics and target
able process is in place, and when properly implemented,
indications of the product and its place and progression
it wil result in efficient demonstration of product value.
through the development lifecycle. There are a number of
Typically, EGS will include the following four key steps:
opportunities for EGS implementation; however methods
may differ according to the needs of each product. General y
1. Identify, summarize, and evaluate the available evidence,
speaking, EGS may be applied to pharmaceutical, medical
the marketplace (i.e., standards of care, comparator
device, or diagnostic products spanning the entire product
treatments, key stakeholders etc.), and competitive
development life cycle.
challenges to identify evidence gaps and unmet need.
Early stage pre-clinical development: EGS as a
2. Determine the target value proposition that addresses
vehicle to set the stage for go/no-go due diligence
unmet need and describes (or demonstrates) product
decisions, prioritize information gathering on disease
value to internal stakeholders and external decision
burden and competitive landscape, and inform
makers.
clinical study design and implementation.
Product
Potential Challenge
EGS Opportunity
Early Stage—Preclinical Development
In Pre-clinical or
Enable go/no-go due diligence decisions
Phase I trials—very
little known about
Making an informed decision for allocat-
Prioritize information gathering on disease burden
the product and the
ing resources for further development
and competitive landscape
marketplace
Inform clinical study design and implementation
Mid-Phase Clinical Development — Successful Proof of Concept
New data/trials required for FDA, EMEA
Navigate competitive and regulatory hurdles
In Phase II or
or other regulatory agency—delaying
early Phase III—
submission and providing opportunity for
Define evidence generation tasks to position and
may have multiple
change in competitive landscape
support product for launch, U.S. or ex-U.S.
indications,
Leverage clinical trials and other studies in progress
submission dates,
Entering a crowded, competitive, and
Identify and establish payer/stakeholder audiences
target countries/
controversial market
and internal priorities for launch
markets, etc.
Obtaining optimal positioning and market
uptake when internal competitors exist
Approved and Marketed
Payer resistance if currently available
Define evidence generation tasks to ensure optimal
formulations or comparators are well
positioning and market uptake alongside other
Phase IIIb/IV, or
established and available at a low cost.
formulations and products in company portfolio
Phase III trials
underway for a
Underperforming product or competitor
Leverage body of existing evidence, and any clinical
new indication or
product
trials or studies in progress
formulation
Crowded marketplace; available generics
Integrate new evidence into current marketing
Effectively communicating improve-
strategy
ments in compliance and associated cost
Respond to competitive challenges and changing
savings
market dynamics

---

E V I D E N C E M A T T E R S • W W W . U N I T E D B I O S O U R C E . C O M
7
Mid-phase clinical development (successful proof
When implemented properly, EGS provides a comprehen-
of concept): EGS to define evidence generation tasks,
sive, multi-year strategy, across the product life-cycle, to
external decision maker and internal stakeholder audi-
document and communicate evidence of product value.
ences, as well as competitive and regulatory hurdles.
This systematic approach al ows for thoughtful planning of
evidence generation and associated resource al ocation to
Marketed products: EGS to leverage or expand
optimize product positioning. In others words, EGS provides
upon existing evidence, revitalize an underperforming
the ability to generate the right value-based evidence, for
product (increase market uptake), or respond to new
the right audience, at the right time.
competitive chal enges, new information, or changing
market dynamics.
For more information, please contact
Teresa.Wilcox@unitedbiosource.com.
The Value of EGS
References
Using EGS to deliver the right evidence to the right audience
1Neumann PJ, Kamae MS, and Palmer JA. Medicare’s National
at the right time empowers evidence-based coverage deci-
Coverage Decisions for Technologies, 1999-2007. Health
Affairs 2008; 27(6):1620-1631.
sions that foster optimal product positioning. The design of
a comprehensive evidence generation strategy enables one
to understand and adapt to the changing world economy,
health care legislation, and regulatory and reimbursement
Publications Plans Change over
policies, and thereby anticipate competitive challenges
Time and with Mounting Evidence-
and changes in market dynamics.
Based data
Using EGS to establish clear priorities and focus maxi-
mizes efficiency of product development by eliminating
By Cara Coffey, Business Planning, and Dan Donovan,
Senior Vice President of Strategy and Market Development
redundancy and streamlining efforts across internal groups,
optimizing resource allocation, and providing opportunities
Historically, the output of traditional publications efforts pre-
to leverage planned studies and available resources. EGS
dominantly consisted of documents reporting on some of the
also facilitates decision making for early stage products in
data generated from a compound’s clinical trial program and
development.
perhaps documents describing the therapeutic landscape in
Considerations for Effective Implementation of EGS
which the compound resides in the marketplace. In recent
years, however, the types of articles that are considered in
The key elements required to create a valuable evidence
a publications plan have expanded as a result of increased
generation plan (EGP) are senior scientific expertise, a
legislation concerning the timing of when clinical trials must
proven approach, solutions-oriented, communication-
be registered and their data reported,1 as wel as increased
focused recommendations, and an emphasis on the evi-
legislative requirements for studies supporting the safety
dence. Scientific expertise should include both therapeutic
and efficacy of pre- and post-approval drugs and devices.2
and methodology expertise (e.g., epidemiology, modeling,
In addition to publications plans built around the clinical tri-
patient-reported outcome [PRO] development), and should
als program, the data generated from its associated health
consider the established understanding of regulatory agen-
economics, outcomes research, and Phase IV observational
cies as wel as formulary decision makers and payers. Any
studies are contributing to an expanding array of product-
truly valuable EGP wil succeed in aligning internal teams
specific literature. In essence, they are amounting to
and ensure that all groups are communicating and leveraging
evidence generation and communication plans.
the work that others are doing. Transparent working relation-
ships with vendors (e.g., partnership is desirable in lieu of
Building Today’s Plan
standard contract service), and strict adherence to timelines
and deadlines are also critical elements.
Broadly, the evidence communication plan usual y spans
three main stages of a product’s lifecycle:
Once completed, an EGP should emphasize the ability
Pre-launch
to demonstrate effectiveness, manage safety risks, and
document product value. In order to accomplish this, it is
Peri-launch
imperative that evidence development recommendations are
not solely driven by capabilities or available resources, but
Post-launch
instead are solution-oriented, evidence-driven, communica-
tion-focused, and effectively aligned with messages
and audiences.
continued on page 8

---

8
U N I T E D B I O S O U R C E C O R P O R A T I O N
F O C U S O N : Right Evidence – Right Audience – Right Time
begin to create an understanding of a new therapeutic agent,
Publications Plans Change
journal articles may be written that explore its pharmacoki-
continued from page 7
netic profile and mechanism of action. Abstracts and ensuing
publications may be developed that provide baseline
and study design information about the clinical
trial or trials under way. Additional y, in support of
evidence generation, pharmacoeconomic models
are developed and conveyed in congress abstracts
and journal articles increasingly during this crucial
first stage as proof of value (improving quality of life,
impact of enhanced safety profile, etc.) becomes
increasingly important.
Peri-Launch: Evidence Release
The availability of adequate product information
around and at the time a new compound is launched
is essential so physicians can make appropriate pre-
scribing decisions. Product usage will be impacted
by the availability and quality of published articles,
particularly in communication vehicles focused on
early prescribers, or adopters, of the drug or device
(e.g., specialty journals). Such articles may explain
Figure 1. General plan approach.
the product’s profile compared to competitors.
Usually, papers at this stage disclose and discuss—
first at congresses and then in medical journals—
The communication requirements differ in each of these
the key primary endpoint results and findings of the
stages, resulting in the need for different types of documents
clinical trial program. More and more often during launch,
within and across each stage (Figure 1).
pharmaco economic models and outcomes assessments are
being tested, and subsequently reported in publications.
Pre-Launch: Establishing the Evidence Rationale
In the preclinical and clinical testing phases leading up to
In tandem to the preparation of papers reporting the
filing, which can take more than a decade to complete, an
primary trial results, other educational activities may take
intermittent release of publications usually aims to establish
place that are directed by the scientific publications effort,
the rationale for the ensuing availability of the new com-
such as symposia and round table meetings at scientific
pound or device. These journal articles are often directed
congresses. Published proceedings and summaries resulting
at thought leaders or specialists in the therapeutic area
from these activities can support the core clinical trial-
because they have the greatest interest in developing com-
driven manuscripts.
pounds, are experts in the scientific area, and wil likely be
the first to need to know about the products so they in turn
Post-Launch: Accumulation of Evidence
can help educate other health care professionals and may
After a product is launched, its evidence generation require-
choose to prescribe the products to their patients in the early
ments are far from met. This is the period when the recep-
days after launch. The nature of the publications may be a
tion of the foregoing information in the marketplace can be
broad systematic review or a detailed examination of the
assessed as it relates to the market’s reaction to the new
general disease area, and they may discuss the limitations of
drug, to changes in the marketplace, or to expectations of
current therapeutic options while beginning to release per-
the drug’s performance. The continued stream of clinical y
tinent product information to begin the education process.
relevant publication evidence can be extended to include
These review articles also assist the medical community by
late-adopting prescribers. At minimum, papers wil need to
summarizing key findings from the existing medical litera-
be developed that continue to disclose critical data, includ-
ture, providing focus to relevant issues, and communicating
ing secondary endpoint results, and keep the health care
information to a wider audience, as is often necessary. To
community adequately informed.

---

E V I D E N C E M A T T E R S • W W W . U N I T E D B I O S O U R C E . C O M
9
These days, in the years after launch, the body of eviden-
Evidence Gathering In Support of
tial data associated with a new compound or device will
only increase (Figure 2). Post-approval surveil ance studies,
Health Economic Evaluations
long-term health economic and outcomes research analy-
By Krista Payne, Director, Health Care Data Capture
ses, and observational studies—in addition to the continued
company-sponsored clinical trial program and independent
The Right Evidence
investigator studies—al contribute to the growing body
Data from randomized control ed clinical trials (RCTs) remain
of patients exposed to the drug and to the continuous
the gold standard of evidence for treatment efficacy due to
development of publications designed to educate health
their high internal validity.1,2 The same cannot be said, how-
care providers and payers about the safety, efficacy, and
ever, regarding RCT data and the effectiveness of interven-
overall use of the new product.
tions, for example, real-world outcomes such as medication
adherence and health care resource utilization.3,4
In the trial environment, the ability to estimate
efficacy accurately is enhanced by requiring physi-
cians to comply with strict study protocols with
clearly defined assessment, treatment and proce-
dure schedules. Subject eligibility criteria, informed
consent, and participation in study visits have also
been shown to favor efficacy outcomes because
the appropriate use of medications, monitoring
and other required interventions is enhanced.5
These trial features are detrimental to the study
of effectiveness, however, because they artificial y
alter the treatment context to increase the accu-
racy of efficacy estimates. For example, in relation
to outcomes such as health care utilization, RCT
protocol driven site visits can alter the usual pat-
tern of care. As a convenience to study subjects,
medical management of the underlying disease can
Figure 2. Evidence-based medicine publication flow.
be provided during the study visit. As well, other
underlying health conditions requiring a medical
intervention can be identified as a result of diagnostic tests
and procedures which would not otherwise be performed
Thus, publications plans may be more accurately
unless the patient were participating in a study.6 A naturalistic
defined as evidence communication plans. Regardless
study design aims to minimize these kinds of phenomena
of the nomenclature, for completeness, a plan can be
to permit the evaluation of real-world physician and patient
considered in three, albeit complex, main stages and
behaviors and outcomes. Properly implemented, a naturalis-
the dissemination of information should be considered in
tic design can minimize the impact of the Hawthorne Effect,
alignment with the requirements and needs of each stage
which is the tendency of people to act atypically when they
to provide a complete communication continuum and for
know they are being observed.
enhanced educational value.
Generally, health economic analyses will require effective-
For more information, please contact
Cara.Coffey@UBC-EnvisionGroup.com or
ness and other real-world outcomes data for the populations
Dan.Donovan@UBC-EnvisionGroup.com.
and sub-groups of interest. Data from an RCT may stil be
used in health economic models to characterize the clinical
References
efficacy and safety profiles of one treatment compared to
1 Food and Drug Administration Amendments Act of 2007. The
another, but naturalistic data are essential to properly model
Library of Congress Web site. http://thomas.loc.gov Accessed
March 26, 2009.
the potential impact of an intervention in the usual care envi-
ronment. While trial data are usually abundant, there is often
2 Food and Drug Administration Revitalization Act: Enhancing
Drug Safety and Innovation Act of 2007. The Library of
a paucity of the latter. If by chance observational data are
Congress Web site. http://thomas.loc.gov Accessed
available, they are seldom for the sub-groups of interest that
March 26, 2009.
continued on page 10

---

10
U N I T E D B I O S O U R C E C O R P O R A T I O N
F O C U S O N : Right Evidence – Right Audience – Right Time
designs are sometimes referred to as natural,9 or quasi-
Evidence Gathering In Support of
experimental.10 While not completely void of the Hawthorne
Health Economic Evaluations
Effect, with a carefully conceived design, data remain very
useful as inputs to analyses of real-world outcomes.11
continued from page 9
Detailed guidelines and checklists for the reporting of
observational studies have helped to streamline and
align with those studied in the trials. Adding further to the
standardize the dissemination of study results.12
need for tailored, naturalistic data collection is the evolution
of modeling techniques which permit the use of more refined
Hybrid retrospective and prospective study designs can also
real-world distributions of population characteristics and
be extremely useful.13 Using this approach, a retrospective
outcomes.7 While it may be evident that observational data
review of charts is paired with one or more study visits to
are necessary, the optimal design to address the research
obtain clinical and disease history information in addition
questions is likely not obvious.
to clinical, resource utilization and quality of life data. Study
outcomes can be tailored to match measures included in
The Right Design
clinical trials permitting a “mapping” of real-world outcomes
Administrative database and medical chart review studies
to clinical trial efficacy data—a critical link in most health
are examples of retrospective studies, which use exist-
economic models.
ing data that have been collected for reasons other than
research. Both designs are naturalistic and avoid the
When site-based data col ection is prohibitive, survey
Hawthorne
methods may be employed. Surveys of patients or provid-
Effect, which
ers using innovative data capture methods, such as IVRS or
Database analyses offer many
is an appealing
web-based methodologies, can be implemented to gather
advantages over chart review
characteris-
data in support of health economic analyses. Standardized
studies, primarily because they are
tic. Database
resource use questionnaires designed for multi-national use
more time and cost efficient and still
analyses offer
are ideal y suited to this mode of data col ection and can
many advan-
provide researchers with very rich datasets gathered in very
provide useful, disease-specific data
tages over
little time.
describing patterns of usual care.
chart review
Selecting the ‘right’ design requires consideration of both
Chart review studies, although more
studies, primar-
scientific and practical factors and an open and col aborative
challenging to implement, contain
ily because
approach between researchers and study sponsors. Real-
important usual care data…
they are more
world data col ection outside of the clinical trial environment
time and cost
and other clinical outcomes not
offers many chal enges, but also offers important research
efficient and
opportunities.
usually available in databases.
stil provide
useful, disease-
The Right Approach
specific data describing patterns of usual care. Chart review
studies, although more challenging to implement, contain
Researchers aiming to col ect effectiveness data to evaluate
important usual care data such as physician and nursing
the burden of a disease or to populate a health economic
evaluation may find the following considerations helpful:
notes, ambulatory and emergency room reports, consulta-
tions, admission and discharge documentation, laboratory
Health economics and outcomes research planning
and diagnostic testing reports, and other clinical outcomes
should be initiated as early as possible in the product
not usual y available in databases. In the European context,
life cycle so that data gathering needs and opportuni-
chart review designs8 may be implemented more frequently
ties can be delineated well in advance.
simply because suitable administrative databases are less
common than in North America.
A wel structured economic model, with clearly
defined parameters and data requirements, can be
Observational prospective studies are another source of
a useful framework to guide real-world evidence
effectiveness data. They are designed to include a broad
gathering activities.
range of subjects typical of those found in actual practice,
and to minimize the Hawthorne Effect by limiting intru-
Opportunities for col ecting health economic data
sion into usual care. When subjects are randomized, these
alongside clinical trials, despite lower external

---

Document Outline

• EvidenceMatters Cover Page
  • Evidence Generation Strategic Planning for Optimal Product Positioning
• UBC and the PACE Initiative Recommend Pragmatic Methods in Institute of Medicine Priority Setting
• Upcoming Presentations
• ISPOR 14th Annual International Meeting
• Publications Plans Change Over Time and with Mounting Evidence-Based Data
• Evidence Gathering In Support of Health Economic Evaluations
• Pricing & Reimbursement Consideration at Each Stage of Development
• Drug Related Adverse EventsSearches for Published Reports
• Identifying Subgroups of Differential Responders: Implications for Personalized Health Care
• UBCĐs Evidence-Based Methodology Initiative: Working to Establishing Guidelines to Assist in the Accuracy of Subjective Measurements in Clinical Trials
• Label Strategies to Inform Drug Development
• Crossroads and Crosshairs: New Regulations and Expectations for Industry-Sponsored Medical Publications
• FDA Issues Proposed Rule on Pregnancy and Lactation Labeling
• Effective Planning and Conduct of Data Monitoring Committee Meetings
• News Briefs
  • Ingela Wiklund, PhD, Joins UBCs European Staff
  • Robert M.A. Thwaites, MA, MCom, Joins UBC as Senior Executive Director, Europe
  • SAS Book Wins Award
  • Promotions Announced
  • New Outcomes Research Journal Established
  • Staff Appointments
  • UBC Accredited as Medidata Rave Ready Partner
  • UBC Announces New Office in the United Kingdom
• Recent Presentations
• The Critical Path Institute
• Recent Publications
• Science Policy Corner
• Click here for archived issues

---