Clinical Research Is it a New Paradigm?

Transcription

1 Clinical Research Is it a New Paradigm? Krathish Bopanna PhD, PhD, DSc Chief Technology Officer Manipal Acunova Bangalore

2 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

3 Healthcare Industry Players Physician Insurance Company Patient Care Hospital Pharmaceutical Industry

4 Drug Development Process Target Selection Target Validation & lead optimization Proof of Concept Clinical Trials Pre-clinical Phase Compound Selection (5,000 10,000) 2 4 Years Proof of Concept Outcome (250) Clinical Phases I, II III, IIIB* Drug Registration FDA Approval Marketing (Phase IV Clinical Trials) *Key variable guiding development time (5) 4 7 Years (1) Marketing Introduction

5 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

6 The Players in Clinical Research Sponsor Investigator Site Patient CRO IRB/IEC SMO

7 What is Involved in a Clinical Trial? File IND application Sites enroll patients Develop protocol Submit to FDA for comment or no action Select investigational sites based on # of patients needed for the study Regulatory requirements for each trial at each site PI s CV Financial disclosure forms Informed consent IRB approval Patients cycle through study Capture: Adverse events, vital signs, study drug adherence, QOL questionnaires captured on Case Report Forms Patients exit study Data collected and cleaned Sites closed Write study report Initiate site(s) Add study to NDA

8 Clinical Trials Process and Associated Regulatory Process Pre-IND Meeting IND Application Phase I Phase II Phase II End of Phase II Meeting Phase III Pre-NDA Meeting Phase IV File NDA Drug Approval

9 Phases of Clinical Trials Category Phase I # of Participants Less than 10 Purpose Tests how to administer a new therapy, exam, or preventive option Phase II Test patients responses to a new therapy, exam, or preventive option Phase III 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

10 Protocol development Volunteer recruitment Project Management Monitoring Data management Assurance of Drug safety Clinical statistics Medical writing Quality assurance Technology support Tasks Involved in Clinical Trials

11 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

12 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.

13 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.

14 Thoughts to Consider R&D Investment is high There is pressure on companies to perform The pipeline is exploding Sales growth is strong How do all these positive factors impact employment in our industry?

15 Clinical Research Market Year Indian market (Rs. in cr.) Indian Market (million $) [% of global] Global Market (million $) [1.16 %] [1.11 %] 9, [1.80 %] 10, [2.26% of US] 26,500 US + Rest ,000 [2 %] 50,000 est McKinsey 2003 Assumption USD = Rs. 45

16 3-Year Employment Growth Global Pharmaceutical Industries Growth rate 8% 6% 4% 6.0% 4.2% 2% 2.0% 1.7% 1.5% 0% Asia Latin America US Canada W. Europe Source: PhRMA, CenterWatch analysis

17 Allocation of R&D Personnel by Function 15% Regulatory 8% Other 15% Regulatory 7% Other 49% Discovery / Preclinical 23% Clinical 54% Discovery / Preclinical 29% Clinical Source: PhRMA, CenterWatch analysis

18 CRO Industry at a Glance Source: SMA Report, 2003

19 CRO - Revenues Source: SMA Report, 2003

20 CRO - Industry Analysis Source: SMA Report, 2003

21 Top 20 CROs in India Overall Stage GR CYREV LYREV Stage Stage Source: Data on File

22 Staff Distribution in Indian CROs IT 7.9 Data Mgmt Lab. Serv Bus.Dev 4.06 Clin Ops Corporate Source: Data on File

23 MNC Pharmacos in Clinical Research Abbott, Mumbai Chiron, Mumbai Astra Zeneca Pharma India Ltd, Bangalore AstraZeneca Foundation, Bangalore Aventis Pasteur, Delhi Pfizer Ltd,Mumbai Pfizer Biometrics, Mumbai Altana (Zydus), Mumbai Lilly, Delhi Boston Scientific, Delhi Hospira, Delhi Merck,Delhi Sanofi Aventis Syntho Lab, Mumbai GSK, Glaxo SmithKline Pharmaceuticals Ltd,Mumbai Novartis International Clinical Development Center, Mumbai Novartis Pharma, Mumbai Roche,Mumbai Sandoz, Mumbai Wyeth, Mumbai BMS, Mumbai Novo Nordisk, Bangalore Lundbeck, Bangalore Eisai Pharmaceuticals, Mumbai LG Life Sciences, Delhi Bayer, Mumbai GE, Delhi Johnson & Johnson, Jansenn Cilag, Mumbai, CordiBaxter, Delhi BD Biosciences, Delhi These sponsors outsource work from the parent clinical development headquarters as well as have a clinical development unit located in India. Several have entered and many more are setting up at brisk pace. Synergy, 2005

24 Indian Pharmacos in Clinical Research Bharat Biotech, Hyderabad Bharat Serum,Mumbai Cadila Pharmaceuticals Cipla,Mumbai Emcure, Pune Fulford IndiaMumbai Indus Biotherapeutics,Ahmedabad IPCA, Mumbai Shreya Biotech,Pune Shantha Biotechnics Pvt. Ltd. Hyderabad Sun Pharma, Mumbai Torrent Pharmaceutical Ltd, Gandhi nagar, USV Ltd. Mumbai Wockhardt, Mumbai Zydus Cadilla, Ahmedabad Biocon,Bangalore Cadila Pharmaceuticals, Ahmedabad Intas Pharmaceuticals Ltd. Ahmedabad Glenmark Pharmaceuticals Ltd. Himalaya Drugs,Bangalore Lupin Ltd. Pune Nicholas Piramal,Mumbai Panacea Biotech,Delhi Ranbaxy Research Laboratories Delhi Ranbaxy Research Laboratories, Gurgaon Serum Institute of India, Pune Torrent,Ahmedabad Synergy, 2005

25 Business Challenges Stage 3 Stage 2 Improve Patient Recruitment Quality & Delivery Time Competition Retention of Human capital Regulatory Issues IPR Issues Stage Source: Data on File

26 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 & costeffectively. 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 %. Source: Center Watch Estimates, World Contract Research Organizations Markets, Frost & Sullivan,2003 PARAXEL s Pharmaceutical R&D Statistical Sourcebook 2003/2004

27 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

28 Jobs! ICRI, 2005

29 Key Qualifications Sought Organizational Skills 2% Experience 59% Computer Skills 2% Degree 16% Communication Skills 4% Work Ethic 2% Attitude 11% Flexibility 4% Source: CenterWatch Survey

30 Demands on Position Increased Qualifications Required 7% Increased Use of Technologies 6% No Change 5% Increased Workload 45% Accomplish in less time 9% Other 10% Increased Studies 18% Source: ACRP Outlook

31 Changes in Roles & Responsibilities During Past 3 Years 0% 20% 40% 60% 80% 100% Significantly changed roles & responsibilities 66.7% Changed employer 48.6% Received a promotion 46.6% N = 1771 Relocation 14.4% Source: ACRP Outlook

32 Salaries by Function INR 80 CRA I CRA II CRA III INR INR Source: Data on File

33 Salaries by Function INR 100 CDM Project Managers QA / Regulatory INR INR Source: Data on File

34 Technologies & Clinical Trials Percent of Total 100% Currently Use Often Will Use Often in 2 years 80% 60% 60% 58% 45% 52% 40% 20% 14% 16% 5% 17% 0% Electronic CRF RDE Internet-based Clinical Data Management Electronic Medical Records Source: ACRP Outlook,

35 Business Process Flow Source : Data on File

36 Employment Facts & Trends Wages are up; Productivity is rising; Inflation is in check Living in a new economy powered by technology fueled by information driven by knowledge a new century with new opportunities Source: Futurework- Bureau of Labor Statistics

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