You

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• Partners in Success

You nTEGRA, LLC
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• Faster Enrollment.

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Patients. Not Patience.
Time is money. Slow recruitment is costing us
both. Its time to trust the only recruiter
smart enough to guarantee fast enrollment. We
need patients, not patience.

• nTEGRATM

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Risk-Sharing Guarantee
"Using nTEGRA's promotional materials and
enrollment plan, we will deliver an agreed number
of screened referrals within your defined time
period at the lowest possible cost or we will pay
up to 100 of recruitment costs to complete
enrollment."
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nTEGRA Recruitment

• Founded in 1994
• 6 project FTEs / 50 feasibility media FTEs
• At least 20 studies in each of 18 therapeutic
  areas.
• Protocol review led by Joe Goddard, M.D., nTEGRA
  Medical Director.
• Affiliated with the Virginia Commonwealth
  University (VCU) Center for Drug Studies, and
  associated physicians.
• All strategies and tactics meet HIPAA
  requirements.
• Single Source inTEGRAted recruiter who may also
  work on a Consulting basis.

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Who is nTEGRA?

• Privately owned, founded November 1994
• Bill Ballas
• Joseph Goddard, M.D.
• Bill Barr, Pharm.D.
• Lea Ann Hansen, Pharm.D.
• Barry Dvorchik, Ph.D.
• Bob Levin
• Tom Sweeney

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Bill Ballas

• Bill possesses 23 years in healthcare marketing.
  While serving on the administrative faculty at
  the University of Virginias Neurological
  Institute (Charlottesville, Va.), he was
  responsible for the business development and
  recruitment functions for the universitys CRO
  (now privately owned as INC Research/San Diego,
  Calif.)
• Bill has provided subject recruitment, practice
  management, and communications and marketing
  consultations to more than 500 private
  Investigators, and another 150 radiologists,
  orthopedists, neurosurgeons and neurologists in
  academia. He has created and implemented
  advertising and public relations campaigns for a
  number of pharmaceutical and healthcare
  companies, including more than three dozen
  clinical studies, as well as for Warner Bros.,
  Columbia Pictures, Universal Studios and NASA.

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Joe Goddard, M.D.

• In 1980, Dr. Goddard received his Doctor of
  Medicine degree with Distinction
• from George Washington University in Washington,
  D.C., where he was also
• a member of the Alpha Omega Alpha Medical Honor
  Society. He completed
• his residency in Family Practice at the
  University of Tennessee Memorial
• Hospital in Knoxville, TN from 1980 to 1983, and
  was Chief Resident in 1982.
• His professional experience includes the Cherokee
  Mental Heath Center in
• Morristown, TN, Concord Medical Center (private
  practice) in Knoxville,
• Midlothian Family Private Practice in Richmond,
  VA, and from 1990-91 was
• Chairman of the Family Practice/Internal Medicine
  Department at Park West
• Hospital. He is a member of the Virginia Academy
  of Family Practice and the
• American Academy of Family Practice.
• Joe practices in the largest and oldest
  multi-specialty medical group in
• Virginia, established before the Civil War. They
  are also part of the largest
• privately held physician group in North America.
  Through Joe, considerable
• resources and clinical expertise are available to
  nTEGRA clients.

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Bob Levin

• Bob has over 30 years of marketing and market
  research
• experience in the pharmaceutical industry. As
  Director of Market
• Research for the A.H. Robins Company, he
  contributed to the
• success of brands such as Robitussin, Dimetapp,
  Chap Stick
• and Anacin through the employment of creative
  marketing
• strategies.
• Bob has also designed marketing campaigns for
  several
• consumer product brands that exceeded their
  business goals
• through the use of targeted, creative advertising
  strategies.
• At Ballas Levin, Bob serves as COO of our patient
  recruitment
• enterprise and provides market research and
  planning services
• to clients.
  
  

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Bill Barr, Pharm. D.

• Bill Barr holds both a Pharm. D. and a Ph.D. in
  Pharmaceutical Chemistry from the University of
  California at San Francisco. From 1972 to 2001,
  he was Professor and Chairman, Department of
  Pharmacy and Pharmaceutics at Virginia
  Commonwealth Universitys (VCU) School of
  Pharmacy. Since 1982, Bill has served, also, as
  Director of VCUs Center for Drug Studies.
• Bill has been Principal Investigator in more than
  90 clinical studies. He is a Fellow of the
  American Association of Pharmaceutical Scientists
  and the American College of Clinical Pharmacology.

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Lea Ann Hansen, Pharm. D.

• Lea Ann, an associate professor and oncology
  clinical specialist at Virginia Commonwealth
  University, performs protocol review and
  marketing communications consulting for nTEGRA.
• She has been an Investigator in more than 20
  oncology studies and currently serves as Chair of
  IRB Panel D at VCU.
• Lea Ann has been published extensively in
  national and international pharmacy and oncology
  journals, and has contributed chapters to several
  academic books. She is a member of the American
  Association of Colleges of Pharmacy, the American
  Society of Clinical Oncology, and the American
  Society of Health-System Pharmacists. She has
  presented research at almost 40 meetings, from
  the local to international level.

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Barry Dvorchik, Ph.D.

• Barry Dvorchik holds a B.S. in Pharmacy and a
  Ph.D. in Pharmacology. He was a member of the
  faculty (Obstetrics Gynecology, Pharmacology
  and Internal Medicine) at the Milton S. Hershey
  Medical Center of the Pennsylvania State
  University. He is a fellow and past president of
  the American College of Clinical Pharmacology,
  and is the author of more than 40 peer-reviewed
  articles.
• Barry has over 19 years experience in the
  pharmaceutical industry encompassing the
  development of small molecular weight compounds
  and macromolecules. He has developed and written
  INDs, NDAs, clinical protocols and investigator
  brochures, and completed 4 U.S. INDs, 2 Canadian
  INDs, and 1 UK phase I filing in two years.
  Barry also developed SOPs for phase I clinical
  research.
• Past positions include Senior Director,
  Metabolism, Analytical and Pharmacokinetics at
  Hybridon, Inc. V.P., Scientific Business
  Development at Bioclin, Inc. and Group Leader,
  Drug Metabolism with McNeil Pharmaceutical.

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Tom Sweeney

• Tom Sweeney has over 40 years experience in the
  Pharmaceutical and
• Biotech Industry. All of this experience has
  been associated with identifying
• market opportunities, creating and developing
  prescription and consumer
• product businesses for companies such as Pfizer,
  Upjohn, American Home
• Products, Warner Lambert, A.H. Robins Company,
  Pharmacia and
• CollaGenix Pharmaceuticals.
• Tom has intimate knowledge of pre- and post-NDA
  events associated with the
• marketing of prescription products to consumers
  and diagnosed patients
• using DTC or DTP techniques. He is a recognized
  leader in the field of
• marketing and advertising of many well-known OTC
  consumer and
• prescription brands to healthcare professionals
  and consumers. Among his
• successes are Pravachol, Nicotrol, Periostat,
  Pnu-Imune, Isoptin, Glucotrol,
• Vicodin, Rythmol, Centrum Vitamins, Robitussin
  Cough Medication, and
• Dimetapp Cold Medication, Boost, Excedrin, Bayer
  Aspirin and others.
• Tom is a graduate of Notre Dame University.

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nTEGRAs Higher Functions

• Analysis prior to/during protocol design
• Data collection leading to enrollment statistics
• Cost-efficient media buying, planning and
  tracking
• Speedy/cost-effective enrollment strategies
• nTEGRA is uniquely qualified to help select a
  patient population and clinical endpoints that
  are relevant to the pharmacologic activity of the
  compound and that will provide the best label
  positioning.
• Label positioning is important because a label is
  really a marketing claim. This is
  commercialization!

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Speed Tricks

• Spend promotional dollars on fewer sites
• Rather than 40 sites in 40 markets, do 40 in 20
  markets or less
• Savings result from start-up, monitoring, and
  marketing cost reductions
• Products get to market sooner and optimize
  opportunity costs
• nTEGRAs proprietary media system
• Site-centric / patient-focused
• Centrally managed recruitment programs
• Amortizes costs
• Allows good data capture
• Dont pay for competitors recruitment

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Speed Tricks

• Centrally managed recruitment programs
• Amortizes costs
• Allows good data capture
• Dont pay for competitors recruitment

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• Enrollment Trends/Concepts

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Emphasis on Enrollment

• Patient recruitment accounts for 22.4 of the
  clinical development timeline.
• Barnett International

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Challenges to Enrollment (1 of 8)

• Recruitment environment has fundamentally
  changed, requiring sponsors and CROs to change as
  well
• 50k60k trials in the US competition for
  evaluable patients has exploded!
• Rise in RD expenditures
• Number of compounds in pipelines
• More studies testing new compounds in special
  populations
• More complex and global nature of trials

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Challenges to Enrollment (2 of 8)

• Recruitment environment has fundamentally
  changed, requiring sponsors and CROs to change as
  well
• Number of subjects needed per NDA has grown from
  1,321 (1975) to 7,000 (2002)
• Six-fold increase in clinical trials from 2001 to
  2002
• Longer trials requiring more patients
• Sources DIA, CenterWatch, Applied Clinical
  Trials, nTEGRA

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Challenges to Enrollment (3 of 8)

• Recruitment environment has fundamentally
  changed sponsors must change, too.
• Shortage of experienced investigators
• 8 out of 9 investigators may overestimate their
  ability to recruit qualified patients for
  clinical trials.
• (PAREXEL, Pharmaceutical RD Statistical
  Source Book, 1999, p.56)
• Site Selection (1/3!)
• Growing of uninsured (44M / 6)
• Lack of emphasis on retention
• Poor consenting process, delivery, performance,
  etc.

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Challenges to Enrollment (4 of 8)

• Recruitment environment has fundamentally
  changed, requiring sponsors and CROs to change as
  well.
• Recruiter cant translate protocol into
  enrollment timeline or understand sites
• Media buys must focus on RF and GI, not number
  of ads
• DR, ROS, Print, and Interactive advertising are
  slow modalities
• Excessively strict Inclusion/Exclusion criteria
• Sponsors
• Inadequately funding site advertising
• Giving recruitment responsibilities to CROs/sites
• Mistakenly adding sites in new markets to spur
  enrollment

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Challenges to Enrollment (5 of 8)

• Doctors often fail to pass on to patients the
  fruits of any discoveries even when researchers
  parlay basic science into "best practices." (WSJ,
  9/26/03)
•  Examples
• Doctors are failing to give long-acting
  medications to asthmatics who use short-acting
  ones a lot.
• They're not giving anti-platelet therapy to
  stroke patients.
• They're not urging patients with lower-back pain
  out of bed.
• 76 of diabetics aren't getting routine
  hemoglobin screening (Rand, as reported in New
  England Journal of Medicine, Summer 2003)
• Only 45 of heart-attack patients are on
  beta-blockers (Rand, as reported to New England
  Journal of Medicine, Summer 2003)

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Challenges to Enrollment (6 of 8)

• Many physicians do not like being told that
  science knows best, and that the way they've
  always done things is second-rate.  
•    Sidney Smith, M.D., professor of medicine,
  University of North Carolina, Chapel
  Hill, former President, American Heart
  Association

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Challenges to Enrollment (7 of 8)

• Why the disconnect?
• Doctors don't believe clinical trials apply to
  their patients.
• Ex mid-1990s spinal fusion study reported by
  Agency for Healthcare Research and Quality
• Others take a "show-me" attitude.
• Treatment effects are often small, such
  as reducing future risk of heart attack by 25.
• Individual physicians typically have too few
  patients with any one illness, or don't
  follow patients long enough to detect such
  benefits.

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Challenges to Enrollment (8 of 8)

• Why the disconnect?
• Treating patients according to guidelines takes
  time that doctors often don't have.
• Treating to guidelines requires a team approach
  that some group practices, let alone solo
  practitioners, can manage.
• Lack of information technology prevents doctors
  form electronically recording patient information
  and matching it to best-practices guidelines. 
• "A lot of bad medicine is being paid for."
• Helen Darling, Washington Business
  Group on Health

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Who Participates in Clinical Trials?

• 60 million Americans have severe, chronic
  illnesses, yet less than 3.6m (10) have
  participated in a clinical trial.
• The typical study participant is somewhat older
  and has a somewhat lower household income and
  education level than the general population. 50
  men, 50 women.
• With the exception of those with the most
  life-threatening or severe illnesses, patients do
  not consider clinical research a treatment
  option.
• In 1995, 1/3 of surveyed patients said they
  self-referred into a clinical trial. Today that
  number is 75.
• Non-whites may still be statistically under
  represented .
• 1993 NIH Revitalization Act (to encourage women
  and minority participation) and FDA Gender
  Guidelines.

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Why Dropouts Occur

• Placebo
• Lack of Study Drug Efficacy
• Length of Study (short studies fewer drop outs)
• Study Logistics (transportation, limited clinic
  hours, etc.)
• Protocol Design (must factor patient
  considerations when created)
• Non-Communicative Coordinators (leads to weak
  relationship w/ patients)
• New Paradigm Participation is a patient choice,
  not an obligation.

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Dropouts

• Dropout rates are variable due to many factors,
  but rates of 15 to 40 are common.
• When significant attrition occurs, the remaining
  data may no longer be representative of the
  original population, and significant biases may
  be introduced that affect study findings.
• Dropout rates correspond to specific therapeutic
  areas.
• The more severe, rare or life threatening the
  indication, the higher the retention rate.

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nTEGRA Industry Firsts

• nTEGRA leads the way
• First recruiter to share financial risk of
  enrollment
• First to offer patient recruitment to
  commercialization
• Patentable Feasibility Methodology
• Pre-negotiated TV and Radio costs in 140 TV
  markets
• Tracking/posting of TV, Radio buys/performance
• Real-time call center tracking, warm transfers,
  etc.
• Site PotentialTM A program to improve site
  techniques for recruiting and retaining patients

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Points of Distinction (1 of 2)

• We are the only recruiter to share enrollment
  risk
• Single-Source Recruiter
• Proprietary Media System
• Guaranteed Placement, not Direct Response or ROS
• Post Radio Television
• Lowest Possible Enrollment Costs
• Site-centric w/centralized Call Center
  Advertising

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Points of Distinction (2 of 2)

• Commercialization
• A thread woven into all of your clinical
  activities
• A component of all your companys service
  offerings worldwide
• Business strategy focused on Investigators and
  Patients
• Site PotentialTM training for sites (proprietary
  retention/enrollment accelerator program)
• Interactive ICF (Informed Consent Form)
• Interactive subject satisfaction survey
• Turning patient recruitment into a profit center

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Turning Patient Enrollment Into A Profit Center

• Profit Forumula
• Saved Days X Projected Recruitment Profit
  
• Daily Net Budget
  Contribution
• Profit
• 14 X 100,000 200,000
  1,200,000

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Therapeutic Experience

• Asthma Allergy Nephrology Cardiology Neuro
  logy
• Dermatology Obstetrics/Gynecology
• Endocrinology Oncology
• Fertility Ophthalmology
• Gastroenterology Psychiatry
• Hematology Pulmonary
• Infectious Diseases Rheumatology
• Musculoskeletal Urology

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Study Experience

• Hypertension Genital Herpes
• Diabetes Smallpox (vaccine)
• DDD Overactive Bladder
• Stroke Acne
• Parkinsons Psoriasis
• Alzheimers Rosacea
• Antiemetic AECB
• Cachexia Asthma
• Prostate Cancer COPD
• HRT Uterine Fibroid
• Polycystic Ovary Syndrome

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Clients

• 3M
• Acambis
• Allergan
• Amtrak
• Astra Merck
• Bayer
• BioConferences International
• Bioglan Pharm, Inc.
• ColleGenix Pharmaceuticals
• Commonwealth Biotechnologies
• Covalent Group
• DynPort
• Eye Care Centers of America
• Fleet Pharmaceuticals
• Insmed Inc.
• Kendle International
• Mead Johnson Nutritionals

• Merck
• National Heath Council
• Niche Pharmaceuticals
• Novartis
• Pfizer
• Pharmacia
• PBM Products, Inc.
• PhARMA
• PPD
• Searle
• SpineCore
• SRA Life Sciences Stiefel Laboratories
• Triton Consumer Products
• UCB Pharma, Inc.
• United Network for Organ Sharing (UNOS)
• Wyeth

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Client Brands

• Bayer Aspirin
• Boost
• Centrum Vitamins
• ChapStick
• Comet
• Cutex
• Denorex
• Dimetapp
• Dilaudid
• Excedrin
• Eye Care Centers of America
• Flexall
• Glucotrol
• Gold Bond Powder
• Grecian Formula
• Isoptin
• Just For Men
• Kaopectate
• Lortab

• Navane
• Nicotrol
• Ore Ida
• Pamprin
• Periostat
• Phisoderm
• Pnu-Immune
• Pravachol
• Progaine
• Rogaine
• Q-tex
• Robitussin
• Rythmol
• Scalpicin
• Seneguan
• Slim Fast
• Spic n Span
• Vagisil
• Vicodin

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Services (1 of 5)

• Feasibility Planning
• Primary and Secondary Market Research
• Media Research, Planning, and Buying
• Patient Recruitment Database (20 million)
• Protocol Review
• Site Identification
• Project Management

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Services (2 of 5)

• Comprehensive, Full-Service, In-House Advertising
  Support
• Advertising Creative and Production
• All media types including Web
• Media Research Placement and Analysis
• Public and Community Relations
• Site Staffing

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Services (3 of 5)

• Call Center
• Warm transfers
• Block book/online appointment scheduling
• Real time tracking
• Telephone staffing support at sites
• M.D./nurse home screening visits
• Clinic Visit Reminder Cards/Phone Calls
• Site PotentialTM training program

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Services (4 of 5)

• Scientific
• Effective and efficient design and implementation
  of clinical pharmacology and pharmacokinetic
  clinical studies
• Writing of reports and regulatory documents
• Review of clinical study reports and NDA
  technical data sections

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Services (5 of 5)

• Regulatory
• Strategic planning for INDs and Marketing
  Applications for the US and Europe
• Preparation of IND Applications and Drug Master
  Files (both US and European)
• Preparation of FDA meeting packages and
  attendance at FDA meetings
• Electronic NDA/CTD submissions in conjunction
  with another company

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Advertising Samples

• Television Samples

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Advertising Samples

• Radio Samples

• High Blood Pressure
• PCOS
• SpF 100

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• Our Process

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Its Smart to Hire nTEGRA Early

• Our feasibility process reduces enrollment time
  and costs
• Limited IRB costs (if using a central IRB to
  review all materials with the initial regulatory
  package)
• Minimizes overall study time and costs
• Making sure clients dont refer patients to a
  competitors study.
• Feasibility and Implementation SOPs available
  upon request.

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Feasibility Planning

• Should be used for developing
• A protocol
• Post-marketing studies seeking expanded
  indications
• A product
• A portfolio of products

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Feasibility Process
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Research Tools (1 of 6)

• Demographics
• Psychographics
• Socioeconomics
• Prevalence/Incidence
• Qualitative Research

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Research Tools (2 of 6)

• Qualitative Research answers questions such as
• What kinds of compounds most likely fit the
  treatment needs of the various types of targeted
  patients?
• What investigational compounds are competing with
  our study?
• What are clinicians opinions about your drug,
  study, etc.

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Research Tools (3 of 6)

• nTEGRA maintains one of the most extensive
  research libraries in the industry. Our
  state-of-the-art research services are part of
  our compensation package for existing clients and
  can be utilized for outside project work.
• Our research library is comprised of data from
  sources to which we subscribe on a monthly or ad
  hoc basis, and are augmented by our in-house
  primary and secondary research capabilities.

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Research Tools (4 of 6)

• Our major research tools and available data
  include
• National and worldwide data regarding therapeutic
  product use by indication, physician specialty as
  well as geography. Includes office-based versus
  hospital use, and segmented by physician. Data
  is available in terms of prescriptions and dollar
  value on a payer basis.
• Disease Prevalence/Incidence of population by
  ICD-9 codes
• Contact info. for 20 million individuals with
  self-reported medical conditions comprised of
  surveys, 95 of hospital discharges, 100 of
  Medicare claims (INPT and OUTPT), 100 payer data
  in 26 states, client submitted payer data (UB-92)
  level.
• Public UB-92 data from 23 states through 2002.
• Local estimates of ICD-9 and CPT-4 procedures,
  Emergency Department visits.
• Local demand for physicians and visits along with
  physician supply information.

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Research Tools (5 of 6)

• Past and projected discharges and days by DRG and
  ICD-9.
• Local estimates and 5-year forecasts of
  population.
• Local cancer incidence and heart prevalence
  estimates.
• Segments US population on demographic and
  psychographic bases (i.e., likely to participate
  in a clinical study.)
• U.S. Census Bureau
• State Departments of Health Statistics
• A.C. Nielsen Local and national broadcast and
  cable audience measurement.

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Research Tools (6 of 6)

• MRI Measures product usage and media habits of
  25,000 consumers.
• StrADegy Online media intelligence system
  measuring your competitors advertising in
  easy-to-read formats, including share of dollars,
  GRPs, and impressions for more than 750,000 call
  center phone numbers/brands.
• IMS A PC-based media planning tool for
  demographic and geographic product user profiles,
  market-sensitive TV and radio research and
  frequency analysis, magazine optimization
  schedules and media mix analyses.
• Tapscan PC software system for
  pre/post-analysis of Spot Broadcast and Cable TV
  proposals. Also reach and frequencies for up to
  20 demographics.
• Radar Measures National Network Radio audiences
  for 15 major radio networks and 13 standard
  age/sex categories.

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Protocol Obligation

• Factors Influencing Enrollment/Retention
• Demographics
• A narrow patient population reduces variability
  increases statistical power.
• Narrow studies can use fewer patients since
  they have less variability than the general
  population. Stand. Dev. are smaller and the n is
  reduced.
• Narrow studies make enrollment difficult if I/E
  criteria are restrictive.
• A broad population helps prevent restrictive
  labeling

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Length of Study

• The more chronic the disease, the longer duration
  patients will tolerate

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Choice of Control Groups

• A placebo group makes recruitment more difficult.
• Patients like knowing they can take a rescue med
  if they dont get relief if the rescue med is
  more potent than that being tested.
• Positive controls that are well known and trusted
  encourage participation.

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I/E Criteria

• Use as broad an age range as possible (unless
  condition being studied is restricted to a
  certain age group).

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Degree of Disease

• Patients with mild diseases are more willing to
  participate in a clinical trial than those with
  severe or life threatening diseases.
• Patients are very willing to enroll if no
  treatment currently exists.

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Concomitant IllnessesAnd Medical Exclusions

• Many trials omit severe concomitant illnesses so
  as to avoid biasing the apparent side effect
  profile of the study drug. However, taken to
  extremes, these exclusion criteria deter
  enrollment.
• Helps enrollment IF the protocol broadly allows
  exposure to previous meds, but with an
  appropriate washout period
• It is reasonable to exclude concomitant meds
  which influence the efficacy endpoints of the
  trial since these may lead to ambiguous results.
  
• However, it is good for enrollment if the
  protocol allows concomitant meds which have
  little or no impact on the efficacy measures.
• Recruitment of patients with chronic disease that
  is sub-optimally managed can be very challenging

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Procedures Performed

• Procedures do not inhibit enrollment if they are
  part of current standard of care
• Blood Draws and Invasive Diagnostic Procedures
  curb enrollment

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How Does nTEGRAAchieve Faster Enrollment?

• nTEGRAs
• Patentable feasibility process
• Proprietary media buying system
• Risk-sharing
• Site PotentialTM retention program
• InForm interactive informed consent

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How Does nTEGRAAchieve Faster Enrollment?

• Empowers sponsors to be more Investigator- and
  Patient-centered
• Improves collaboration/information sharing among
  all teams involved in trials
• Helps your company improve profits from ways it
  serves or could serve stakeholders
• Using nTEGRAs and your informatics, we identify
  new services to offer sponsors

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Speed Metrics-Example Rescue Mission
Source Eli Lilly
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Speed Metrics-Diabetes, Phase I
66
Speed Metrics-Diabetes, Phase II
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Speed Metrics-Hypertension, Phase III
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Speed Metrics-PCOS, Phase II
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Media

• Television
• Broadcast TV Spot, Direct Response, Network,
  and Syndicated
• Cable TV Local and National
• Radio
• Local, National, and Syndicated
• Print
• Newspapers, Consumer, Business, Professional, and
  Trade
• Direct Mail
• Out of Home
• Internet

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Television

• Proprietary Buying System
• Actual Cost Comparison
• Guaranteed Placement, not Direct Response or ROS

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New York City-Example-

• Traditional Buy (A35) nTEGRA Buy (A35)
• WNBC (ER, February, 2002) WABC, WCBS, WNBC,
  WPIX, WNYW, WWOR
• 1 Spot Thursday 10pm - 11pm 111 Spots Mon-Sun,
  6am - 2am
• Cost 78,000 Cost 78,000
• Day -.- Day 33
• Fringe -.- Fringe 44
• Prime 100.00 Prime 23
• HH Rtg 21 HH Rtg 505
• Adults 25-54(000) 1,687 Adults
  24-54(000) 23,145
• Frequency 1.0 Frequency 6.5

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Media Mix Comparison Report
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Radio

• Proprietary Buying System
• Actual Cost Comparison
• Weekly monitoring of buys
• We are the only agency to post radio, and we do
  so weekly

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Actual Spot Radio CPMs

• Washington, DC
• Traditional Buy (A25-54) nTEGRA Buy (A25-54)
• WTOP-FM WHUR-FM, WOL-AM,
• WARW-FM
• 75 spots 5A-12M 12am-5am 62 spots 530am-12mid
• Cost 7,500 Cost 7,340
• Demo GRPs 21.4 Demo GRPs 50.5
• Demo CPP 350 Demo CPP 145.35
• Reach 7.6 Reach 17.0
• Frequency 3.0 Frequency 2.9
• 3 reach 4.5 3 Reach 9.4

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Actual Spot Radio CPMs

• Dallas, TX
• Traditional Buy (A35) nTEGRA Buy (A35)
• KSCS-Radio (1 Country Format) KSCS-Radio (1
  Country Format)
• 15 spots Wed-Sat 10am-8pm 41 Spots Mon-Sun
  530am to 8pm 12mid-6am
• Cost 3,975 Cost 3,965
• GRPs 12.3 GRPs 31.3
• Gross Impressions 271,800 Gross
  Impressions 708,200
• CPP 323 CPP 127
• CPM 14.62 CPM 5.60
• Reach 7.4 Reach 12.1
• Frequency 1.6 Frequency 2.4

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nTEGRAs CPMs vs. Spot Network (W18)

• FY nTEGRA SPOT NETWORK
• 1997 3.62 10.06 9.77
• 1998 4.24 10.20 10.51
• 1999 4.32 11.14 10.95
• 2000 4.52 13.60 11.54
• 2001 4.36 13.02 11.74

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• Newspaper and Magazine
• Actual Cost Comparison

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New York City-Example-

• Traditional Buy
• New York Times, Full Page, BW 137,000
• New York Times, Full Page, BW 10 page Freq.
  Discount
• 123,300
• New York Post, Full Page, BW 27,800
• New York Post, Full Page, BW
• 10 page Freq. Discount
• 25,000

• nTEGRA Buy
• New York Times, Full Page, BW 120,500
• New York Times, Full Page, BW10 page Freq.
  Discount
• 86,300
• New York Post, Full Page, BW
• 24,500
• New York Post, Full Page, BW
• 10 page Freq. Discount
• 17,500

79
nTEGRA Print Cost Comparison Actual Schedule

• 4C Pages
• Redbook 4x Harpers Bazaar 3x
• Womans Day 4x Allure 3x
• Glamour 3x New Woman 3x
• Seventeen 3x Vogue 3x
• Elle 3x Mademoiselle 2x
• Rate Card 2,435,760
• Client Cost 1,146,600

80

• Results and Metrics
• Liars, damn liars and people who use
  statistics.
• When enrollment lags, adding sites is not a
  remedy.
• Use centralized advertising/call center early.
• A rescue mission is the biggest mistake a sponsor
  can make.

81
Actual Costs per Enrolled Patient

• Phase II PCOS
• 45 sites/2weeks/2500 rp/60 per enrolled patient
• Phase II Type II Diabetes
• 40 sites/2 weeks/ 1200 rp/186 per enrolled
  patient
• Phase I Type II Diabetes
• 1 site/2 weeks/53 rp/982 per enrolled patient
• Phase III Hypertension
• 18 sites/2 days (1 week)/350 rp/214 per
  enrolled patient

82

• Commercialization
• Preparing for Market Leadership
• Designing studies around how the final labeling
  should appear

The nTEGRA Way
83
Industry Trends The Case for Commercialization

• 65 billion spent on RD in 2000
• 12 compounded annual growth rate
• Development cycles have lengthened from 8 years
  in 1960s to about 9 years today
• 34 billion a year spent on trials in 2000
• 10 to 15 annual growth rate

84
The Case for Commercialization

• Each year sponsors initiate 100 new drug trials
• Worldwide there are more than 15,000 trials
  underway today
• Number of trials will grow dramatically due to
  new technologies
• High throughput screening
• Genomics
• Molecular modeling

85
The Case for Commercialization

• About 400 drugs will advance to Phase 3 trials by
  2005
• At the same time, the number of potential
  Investigators and Patients is flat/shrinking
• The increase in trials without corresponding
  increase in Investigators and Patients has made
  recruitment problematic

86
The Case for Commercialization

• Increased complexity of trials
• Average number of studies per NDA has grown from
  30 to 75 in the past 25 years
• Number of pages per NDA has grown from 38,000 to
  over 100,000 in this same period
• Number of subjects needed for each NDA has grown
  from 1,321 to 4,237 (mid-1990s)
• Fewer potential patients for each NDA due to more
  targeted RD
• Sponsors increasingly recruit internationally
  works both ways!

87
The Case for Commercialization

• Strengthening relationships with Investigators
  and Patients expedites trials by
• Improving the quality of data
• Reducing the chance for errors
• Improving data turnaround
• Speeding payments to Investigators and Patients

88
The Case for Commercialization

• Helps solve Investigator recruitment
• Identifying and signing experienced Investigators
  is competitive
• Investigator retention is also difficult
• 1/3 of Investigators never do a second trial
  this represents a huge loss of investment time
  and money

89
The Case for Commercialization

• Builds stronger more personal relationships with
  Investigators
• Provides Investigators with convenient and
  immediate access to the information they need
• Provides Investigators with access to data when
  and where they want (protocol help/InForm,
  stocking supplies, payment process, etc.)
• Loyalty can give sponsors a huge competitive edge
• Site PotentialTM

90
The Case for Commercialization

• Establishes strong relationships with Patients
• Helps ensure the trial experiences is a
  satisfying one (Site PotentialTM and other means)
• Improves adherence and retention (Site
  PotentialTM and other means)
• Enables patient questions to be answered
  competently, consistently, and quickly (InForm,
  other means)

91
When is Commercialization Necessary?

• Pre-clinical (SRA, CBI, Insmed)
• Phase I
• Phase II to IV
• Post-approval

92
Pre-Clinical

• Strategic Market Planning
• Media/Investor Relations
• Advertising Trade Show/Journal

93
Phase I

• Subject Recruitment
• Strategic Market Planning
• Media/Investor Relations
• Advertising Trade Show/Journal

94
Phase II-IV and Post-Approval

• Subject Recruitment
• Strategic Market Planning

95
What is Commercialization?

• A thread woven into all of your service
  offerings worldwide
• Business strategy focused on Investigators,
  Patients and Managed Care.
• Combines Sponsors CRU with a commercialization
  perspective
• Combines Sponsors common data repository (CDR)
  with nTEGRAs expertise
• A commercialization orientation beginning in the
  pre-clinical phase maximizes the market potential
  of agents, compounds, and devices.

96
What is Commercialization?

• Some of the brands we have helped to succeed
  include
• Pravachol Robitussin
• Seneguan Dimetapp
• Dilaudid Excedrin
• Rythmol Nicotrol
• Navane Glucotrol
• Pnu-immune

97
Commercialization

• nTEGRA is uniquely qualified to construct a
  Commercialization Plan.
• nTEGRA is staffed by marketers who have held
  senior industry positions in companies such as
  Wyeth Pharmaceuticals and Bozell Healthcare.
• The Commercialization Road Map developed by
  nTEGRA is based on decades of clinical
  development and marketing experience.

98
Benefits

• Quicker to market
• Accelerated subject recruitment
• Patient enrollment becomes a profit center
• Collect/Sell clinical data and expertise,
  marketing and communications data and services to
  sponsors
• Initiating new clinical studies
• Developing new compounds/devices, or marketing
  existing ones
• nTEGRA has substantial data
• Self-liquidating, separate corp., etc.

99
Road Map

• The nTEGRA Commercialization Road Map reads
• Characterize the Marketplace
• Perform Analysis and Conceptualization
• Develop Customized Marketing Strategies and
  Tactics
• Create Market and Market Introduction Plans

100
Road Map

• Step One
• Characterize the marketplace
• Demographics
• Patients
• Health professionals
• Incidence and trends of the indication
• Competitive Product overview
• Category brands currently marketed
• Indications/contra-indications by brand
• Strengths and weaknesses
• Marketing strategies employed
• Impact/quality of detailing/Sales Departments
• Communication characteristics

101
Road Map
(Step One Continued)

• What marketing strategies, tactics are
  successful which are less effective
• Managed Care
• Identification of factors that influence the
  decision process

102
Road Map
(Step One Continued)

• The competitive pipeline
• Whats in development
• Phase II
• Phase III
• Phase IV
• Overview of relevant corporate product
  development alliances
• Strengths and weaknesses of client
  marketing/sales capabilities

103
Create a Market Mosaic

• Use Primary and Secondary market research to
  construct a mosaic of the market from the
  perspective of
• Patient/customer
• Health professional
• Competition
• Managed care

104
Construct a Mosaic of the Market from

• Incidence and demographics of indication
• Geographic regions of interest for indication
• Indications/contraindications
• Promotional methodologies

105
Competitive Market Modeling

• Use primary and secondary market research to
  determine drivers
• Capture competitive and noncompetitive category
  marketing strategies
• Set marketing goals and objectives
• Assess outcomes

106
Competitive Market Modeling

• Assess marketing and communications capabilities
• Focus groups
• Peer group assessment
• Test marketing

107
Competitive Market Modeling

• Identify clients marketing strengths (SWOT)
• Establish timelines and milestones

108
Implementation

• Implement strategies and tactics
• Track sales and marketing goals
• Adjust

109
Road Map

• Step Two
• Analysis and Conceptualization
• Objective is to coalesce data from Step One and
  hypothesize marketing strategies and tactics
• Analysis of data
• Produces a macro-marketplace where the
  competitive landscape is characterized
• Conceptualization and testing of alternative
  market strategies based upon the identification
  of market gaps and tactical opportunities
• Utilizes both Primary and Secondary Market
  Research

110
Road Map

• Step Three
• Strategies and Tactics
• Managed Care Strategies
• Push-Based
• Pricing/distribution
• Pull-Based
• Identification of pull tactics to create patient
  demand
• Advertising
• Symposia
• Stimulate use by key physicians
• Development of Marketing Strategies

111
Road Map
(Step Three Continued)

• Health Professional Tactics
• Personal approach
• Detailing
• Symposia
• Journal articles

112
Road Map
(Step Three Continued)

• Health Professional Tactics
• DTP Communication
• Print
• Broadcast
• Symposia
• Peer groups
• Web site
• Mailing
• Detail aids

113
Road Map
(Step Three Continued)

• Patient/Consumer Strategy
• DTC Advertising
• Television Advertising
• Radio Advertising
• Newspaper
• Specialty/Health Magazines
• Web site informational Resource
• Product information
• Physician offices locations
• Public Relations
• Support groups

114
Road Map
(Step Three Continued)

• Communication Strategies
• Identification of a compelling message
• Alternative communication platforms developed
  using market research techniques
• Primary market research
• Quantitative market research to verify
  communication values
• Production
• Media Plan created
• Media buying based upon nTEGRA efficiencies

115
Road Map

• Step Four
• Comprehensive Market Plan created based upon
• A comprehensive understanding of the Marketplace
• The Marketing Target
• Tested strategies and tactics

116
Road Map
(Step Four Continued)

• Market Introduction
• Execute the nTEGRA Plan
• Validate operations via Market Tracking
• Syndicated tracking
• National
• Regional
• Customized tracking
• Prescriber-based
• Patient-based

117
Road Map
(Step Four Continued)

• Follow up and adjust under-performing strategies
  and tactics, such as
• Communications
• Message comprehension
• Reach and Frequency
• Professional reaction
• Patient reaction

118
Commercialization Helps Enrollment

• Strengthens relationships between
• Investigators, Patients, and Sponsors

119
Commercialization Leads To Faster Enrollment

• Focuses on building strong relationships with
  Investigators and Subjects to shorten the
  enrollment.
• It updates the paper-intensive methods of the
  past and electronic means of today.
• Facilitates communication and understanding, and
  decision-making to provide consistent high
  quality and cost effective services to your
  internal and external stakeholders.

120
How Will Commercialization Enhance Your
Profitability?

• Today, 27 of study time is devoted to enrollment
• Faster enrollment means getting to market faster
• Drive down trial time and costs especially
  during subject enrollment
• Streamlines administrative processes and costs
  (planning and reporting)
• Improves Investigator and Patient satisfaction
  and loyalty
• Benefits your global enterprise

121
How Does Commercialization Begin?

• Must start with a Commercialization Officer,
  Department/nTEGRA
• It can start today without your informatics or
  a common data repository (CDR)
• It can start today with your informatics or CDR

122
What is a Common Data Repository (CDR)?

• Where data exists that can be accessed by various
  functional groups
• Functional groups must share/leverage the
  information to improve service to stakeholders
• Stakeholders are Investigators, Patients,
  sponsors and other staff at your company

123
What is a CDR?

• Where data are managed to define/track critical
  processes and timelines
• Your staff provide personalized service to
  stakeholders
• Should contain a database of Solutions to
  quickly solve problems

124
What is a CDR?

• Should house data on Investigators
• Therapeutic experience
• Board Certifications
• FDA standing
• Should feature personal portals for
  Investigators
• Include software tools to help in trials
• Check on payment (builds loyalty/retention)
• Enterprise branding concepts

125
What is a CDR?

• Means to increase CRA and Manager productivity
  through
• Automation of repetitive tasks
• Sharing data in real time
• More informed decision-making
• Pre-screen potential candidates through the web
  (use branching logic)
• Track advertising
• Monitor accrual by site

126
A CDR Aids Enrollment/Retention

• Improve retention by planning of subject visits
• Improve adherence with specialized tools (Site
  PotentialTM and other means)

127
Customer Data Repository

• Investigators and Web and Email Clinical
• Prescribers Sponsor
• Clinical
• Call Center Study Team
• Field (CRAs, PMs)
• Medical Affairs
• Vendors
• Sales Reps,
• medical liason

128
Customer Data Repository

• CRAs Web and Email Sponsor
• Sales and Clinical
• Marketing Subjects
• Call Center
• Information Investigators, Site Field
  Coordinators
• Medical Affairs
• Vendors

129
CDR Benefits

• Facilitates planning, budgeting, and tracking of
  all trial-related tasks in real time
• Track actual vs. planned progress
• Speeds accrual
• Helps get to market in minimal time

130
Investigator/Site Management

• Investigator
• Site Personnel Tracking
• Document tracking
• Should allow Investigators to maintain both
  private and shared notes

131
Investigator Patient Recruitment

• Should track Investigator qualifications
• Support Investigator recruitment through the web,
  email, and mail
• Support Patient recruitment through the web,
  e-mail, and mail

132
Trial Status Reporting

• Call Center utilization/volume (real time)
• Advertising schedules (real time)
• Enrollment Rate (real time)

133
Study Management

• Support site visit scheduling
• Protocol updating
• Enforce adherence to protocols
• Site PotentialTM
• InForm

134
CRA Productivity Tools

• Automate Simplify
• Site initiation, monitoring, evaluation, and
  visits
• Entering and tracking open issues and follow-up
  items
• Communication through auto-correspondence, mail
  merge, email blast, and quick searches

135
Payment

• Create, monitor, and track trial-related payment
  activities
• Allows Investigators to determine payment status
• Should integrate easily with existing back office
  payment systems

136
References

• Carol Alcasey, PPD
• 616.682.9096
• Bill Jacobsen, Ph.D., Wyeth
• 610.902.1200
• Wendy Christiansen, Clinical Manager, EBI
• 800.526.2579
• Teresa Joshi, Allergan Inc.
• 714.246.5893
• Bill Cerullo, SpineCore
• 610.952.2647
• Polly Jackson, Ingenix Pharma Services
• 919.677.8540

137
Lets get started now.
138
nTEGRATM Subject Recruitment to
Commercialization.SM

• 4900 Augusta Avenue, Suite 104
• Richmond, VA 23230
• 804.358.2314
• 866.436.2362
• www.n-tegra.com
• ballas1_at_erols.com