Clinical Research

Is it a New Paradigm?
Krathish Bopanna PhD, PhD, DSc
Chief Technology Officer
Manipal Acunova
Bangalore
 Overview of the Presentation

• Healthcare Players
• Drug Development Process
• Clinical Trials : Definition
• Players in Clinical Research
• Regulatory, Phases, Roles in Clinical Research
• Benefits & risks of Clinical research
• Regulations in Clinical research
• Thoughts to Consider
• Clinical Research Market
• CRO Market, revenues, job opportunities
• Summary
 Healthcare Industry Players

Insurance
Physician
Company

Patient
Care

Pharmaceutical
Hospital
Industry
 Drug Development Process

Target Validation
Proof of Concept Pre-clinical
Target Selection & lead
Clinical Trials Phase
optimization

Compound Proof of Concept

Selection 2 – 4 Years Outcome
(5,000 – 10,000) (250)

Drug Marketing
Clinical Phases I, II
Registration (Phase IV
III, IIIB*
FDA Approval Clinical Trials)
*Key variable guiding
development time
Marketing
(5) 4 – 7 Years Introduction
(1)
 Clinical Trials: What Are They?

• An organized research study designed to investigate

new methods of preventing, detecting, diagnosing, or
treating an illness or disease (such as cancer).
Clinical: Pertaining to humans (subjects volunteers, patients)
Research: The study of material & sources in order to establish facts
& reach new conclusions (analysis, enquiry, examination,
experimentation, exploration, fact-finding, inquiry, investigation,
probe, scrutiny, searching, study)

Source: Concise Oxford Dictionary

 The Players in Clinical
Research

Investigator
Sponsor Patient
Site

CRO IRB/IEC

SMO
 What is Involved in a Clinical
Trial?
File IND application Sites enroll patients

Develop protocol Patients cycle through study

Submit to FDA for comment or Capture: Adverse events, vital
no action signs, study drug adherence,
QOL questionnaires captured
Select investigational sites on Case Report Forms
based on # of patients
needed for the study
Patients exit study
Regulatory requirements for
each trial at each site Data collected and cleaned
•PI’s CV
•Financial disclosure forms Sites closed
•Informed consent
•IRB approval
Write study report

Initiate site(s) Add study to NDA

 Clinical Trials Process and
Associated Regulatory Process

Phase II
Pre-IND Meeting Phase Phase End of Phase II
IND Application I II Meeting

Phase III Drug

Phase File NDA
Pre-NDA Approval
IV
Meeting
 Phases of Clinical Trials

Category # of Participants Purpose

Phase I Less than 10 Tests how to administer a new therapy, exam, or

preventive option

Phase II 30-40 Test patients responses to a new therapy, exam, or

preventive option

Phase III 100-1000+ Compares new therapy exam or preventive option

to a standard one

Phase IV Varies For marketing purposes, to compare the

effectiveness of two therapies already on the
market or to study new uses of therapies
 Tasks Involved in Clinical
Trials

• Protocol development
• Volunteer recruitment
• Project Management
• Monitoring
• Data management
• Assurance of Drug safety
• Clinical statistics
• Medical writing
• Quality assurance
• Technology support
 Clinical Trials Benefits & Risks
Possible Benefits of Trials
• Having access to potentially more
effective therapies than those currently
available
• Receiving quality medical care from
leading physicians
• Being closely monitored for possible
negative effects
• Sometimes receiving treatment at a
reduced rate or free of charge
• Helping to further new research that may
result in significant medical advances
• For patients in cancer therapy trials
assigned to control groups, they still
receive the top standard therapy available
today
Possible Risks of Trials
• Patients may not receive the therapy
under investigation (may receive a
placebo – inactive pill – instead)
• The new therapy may not be more
effective than the standard, thoroughly
tested therapy
• In Phase I trails, not knowing the safety
consequences of the new therapy (risk is
less in Phase III trials)
• New therapy may have unexpected,
possibly severe side effects or may be
less effective than standard of care
• Insurance companies may not cover all
costs of clinical trials
 History Behind Regulations
of Clinical Trials

• Regulations often result in response to abuse of human research

subjects and concerns about the validity of data and conclusions
from clinical trials.
• The primary vehicles for human subject protection are IRBs and
informed consent.
• The Declaration of Helsinki and the Belmont Report are critical
documents for the protection of human subjects in research.
• The FDA, by means of PDUFA and FDAMA, has made significant
gains in speeding the process of making new drugs available for
patients who need them.
• Current problems with clinical trials and trial oversight may well lead
to increased regulation.
 Regulations for Clinical Trials

• The FDA regulations pertaining to clinical trials are found in 21 CFR

Parts 11, 50, 54, 56, 312 and 314.
• The ICH Guidelines for Good Clinical Practice should be followed in
clinical trials.
• The FDA publishes many guidelines and information sheets
pertaining to the appropriate conduct of clinical trials.
• Good clinical practices are the ethical and clinical standard for
designing, conducting, analyzing, monitoring and reporting on
clinical trials.
 Thoughts to Consider

Ë R&D Investment is high

Ë There is pressure on companies to perform
Ë The pipeline is exploding
Ë Sales growth is strong

Ë How do all these positive factors impact

employment in our industry?
 Clinical Research Market

Year Indian Indian Market Global Market

market (million $) [% of (million $)
(Rs. in cr.) global]
2003 315 70 [1.16 %] 5000 - 6000

2004 450 100 [1.11 %] 9,000

2005 810 180 [1.80 %] 10,000

2007 2700 600 [2.26% of US] 26,500 US + Rest

2010 4500 1,000 [2 %] 50,000

est McKinsey 2003

Assumption USD = Rs. 45
 3-Year Employment Growth
Global Pharmaceutical Industries

Growth rate
8%
6.0%
6%
4.2%
4%
2.0%
1.7% 1.5%
2%

0%
Asia Latin US Canada W. Europe
America

Source: PhRMA, CenterWatch analysis

 Allocation of R&D
Personnel by Function

49%
15% 8% 7% Discovery /
Regulatory 15% Other
Other Preclinical
Regulatory

23% 54% 29%

Clinical Discovery Clinical
/ Preclinical

Source: PhRMA, CenterWatch analysis

CRO Industry at a Glance

Source: SMA Report, 2003

CRO - Revenues

Source: SMA Report, 2003

CRO - Industry Analysis

Source: SMA Report, 2003

 Top 20 CROs in India

80.99

Overall 478.7

264.22

72.41

Stage 3 350

203
GR
CYREV
LYREV
225

Stage 2 52

16.3

80

Stage 1 72

40

Source: Data on File

 Staff Distribution in Indian
CROs

IT 7.9

Data Mgmt 14.83

Lab. Serv 22.68

Bus.Dev 4.06

Clin Ops 46.39

Corporate 18.9

0 10 20 30 40 50
Source: Data on File
 MNC Pharmacos in Clinical
Research

•Abbott, Mumbai • GSK, Glaxo SmithKline Pharmaceuticals

Ltd,Mumbai
•Chiron, Mumbai • Novartis International Clinical
Development Center, Mumbai
•Astra Zeneca Pharma India Ltd,
• Novartis Pharma, Mumbai
Bangalore • Roche,Mumbai
•AstraZeneca Foundation, Bangalore • Sandoz, Mumbai
•Aventis Pasteur, Delhi • Wyeth, Mumbai
• BMS, Mumbai
•Pfizer Ltd,Mumbai • Novo Nordisk, Bangalore
•Pfizer Biometrics, Mumbai • Lundbeck, Bangalore
• Eisai Pharmaceuticals, Mumbai
•Altana (Zydus), Mumbai
• LG Life Sciences, Delhi
•Lilly, Delhi • Bayer, Mumbai
•Boston Scientific, Delhi • GE, Delhi
• Johnson & Johnson, Jansenn Cilag,
Hospira, Delhi Mumbai,
•Merck ,Delhi • CordiBaxter, Delhi
• BD Biosciences, Delhi
•Sanofi Aventis Syntho Lab, Mumbai

These sponsors outsource work from the parent clinical development headquarters as
well as have a clinical development unit located in India. Several have entered 2003-05
and many more are setting up at brisk pace.
Synergy, 2005
 Indian Pharmacos in Clinical
Research

• Bharat Biotech, Hyderabad •Biocon,Bangalore

•Bharat Serum,Mumbai
•Cadila Pharmaceuticals, Ahmedabad
• Cadila Pharmaceuticals •Intas Pharmaceuticals Ltd.
•Cipla,Mumbai Ahmedabad
• Emcure, Pune •Glenmark Pharmaceuticals Ltd.
• Fulford IndiaMumbai •Himalaya Drugs ,Bangalore
• Indus Biotherapeutics,Ahmedabad
•Lupin Ltd. Pune
• IPCA, Mumbai
• Shreya Biotech,Pune •Nicholas Piramal,Mumbai
• Shantha Biotechnics Pvt. Ltd. Hyderabad •Panacea Biotech,Delhi
• Sun Pharma, Mumbai •Ranbaxy Research Laboratories Delhi
•Torrent Pharmaceutical Ltd, Gandhi nagar, •Ranbaxy Research Laboratories,
•USV Ltd. Mumbai Gurgaon

•Wockhardt, Mumbai •Serum Institute of India, Pune

•Zydus Cadilla, Ahmedabad •Torrent,Ahmedabad

Synergy, 2005
 Business Challenges

Stage 3

Improve Patient Recruitment

Quality & Delivery Time
Competition
Stage 2 Retention of Human capital
Regulatory Issues
IPR Issues

Stage 1

0 2 4

Source: Data on File

 CRO (Clinical Research
Organizations)

• CROs provide product development services to the pharmaceutical,

biotechnology, and medical device industries allowing their clients to
manage product development efforts more efficiently & cost-
effectively.

• CROs employ some 100,000 professionals around the world.

• CRO market size is estimated at $12 billion and growing. Revenue

is increasing at an annual rate of 14-16 %.

Source: Center Watch Estimates, World Contract Research Organizations Markets, Frost & Sullivan,2003
PARAXEL’s Pharmaceutical R&D Statistical Sourcebook 2003/2004
 CRO Industry
Facts & Figures

• According to an independent analyst, clinical trials

conducted by CROs are completed at an average of
30% more quickly than those conducted in-house. This
results in an average time-saving of some 4-5 months
translating to $120 million to $150 million in increased
revenue potential.

• This is based on market expectation that an average

product generates $1 million in revenues every day.

Source: PARAXEL’s Pharmaceutical R&D Statistical Sourcebook 2004/2005

Jobs!

ICRI, 2005
 Key Qualifications Sought

Experience
59%
Organizational
Skills
2%

Computer Skills
2%

Degree
16%

Communication Skills Flexibility

4% Work Ethic Attitude 4%
2% 11%

Source: CenterWatch Survey

 Demands on Position

Increased Use No Change

Increased of Technologies
Qualifications 5%
6% Increased Workload
Required 45%
7%
Accomplish
in less time
9%

Other
10%

Increased Studies
18%

Source: ACRP Outlook

 Changes in Roles & Responsibilities
During Past 3 Years

0% 20% 40% 60% 80% 100%

Significantly changed
66.7%
roles & responsibilities

Changed employer 48.6%

N = 1771
Received a promotion 46.6%

Relocation 14.4%

Source: ACRP Outlook

 Salaries by Function

CRA I CRA II CRA III

INR 80

40
INR 40 32
30
23
20 20
15 15
12

INR 0
2003 2004 2005
Source: Data on File
 Salaries by Function

CDM Project Managers QA / Regulatory

INR 100

70
60
50 50
INR 50
40
35 35
25
20

INR 0
2003 2004 2005
Source: Data on File
 Technologies & Clinical Trials

Percent of Total
Currently Use Often Will Use Often in 2 years
100%

80%

60% 58%
60% 52%
45%
40%

16% 17%
20% 14%
5%

0%
Electronic CRF RDE Internet-based Clinical Electronic Medical
Data Management Records
Source: ACRP Outlook,
Business Process Flow

Source : Data on File

 Employment Facts &
Trends

Ë Wages are up; Productivity is rising; Inflation is in

check
Ë Living in a new economy
Ë powered by technology
Ë fueled by information
Ë driven by knowledge
Ë a new century with new opportunities

Source: Futurework- Bureau of Labor Statistics

 Summary

Ë Industry is in flux
Ë More trials
Ë More speed
Ë More burnout
Ë Jobs and roles are changing
Ë 2/3 have had recent major role changes
Ë 1/2 have recently changed jobs
Ë Pace will only accelerate
Ë Blurring of roles, end of road warrior?