BUSINESS DEVELOPMENT IN CLINICAL RESEARCH

1. BUSINESS DEVELOPMENT IN CLINICAL RESEARCH • PATIENT RECRUITMENT & RETENTION • MARKET RESEARCH IN CLINICAL RESEARCH • PROJECT MANAGEMENT- CPM/ PERT • ROLE OF CRO/ SMO IN CLINICAL RESEARCH • OUT SOURCING CLINICAL RESEARCH • BUSINESS DEVELOPMENT IN CLINICAL RESEARCH • HIRING & RETAINING CLINICAL RESEARCH COORDINATORS (HR) • BASIC INFRSTRUCTURE: SPACE PLANNING/ SOPs & FINANCING

2. DESTINATION INDIA • Large & essentially treatment naïve patient pool • Low cost • Sufficiently good medical infrastructure & scientific pool • Availability of suitable subjects – a key component inspite of good funding, well designed, it may fail

3. PATIENT RECRUITEMENT AND RETENTION

4. TRIAL PROCESS • Phase I – a new drug or treatment for the first time in a small number of people (20-80), usually normal, healthy volunteers, (pharmacokinetic studies, bio-availability and bio-equivalence studies ) • to evaluate its safety, • determine a safe dosage range, and • identify side-effects • Phase II – • drug or treatment is administered to a larger group of people (100-300) to further assess its safety and effectiveness • Phase III - drug or treatment is administered to large groups of people (1,000-3,000) • to further determine effectiveness, • monitor side-effects, compare it to commonly used treatments, • and collect information that will allow safe use of the drug or treatment

5. The Phase IV – • performed after the drug or treatment has been authorised for medical prescription and has been marketed. • continue testing the drug or treatment to collect information on the effect in various populations and any side-effects associated to long-term use. • Patients are randomly assigned to the group receiving the new treatment (treatment group) or to the standard group (control group) to ensure the trial's impartiality.

6. further characterise the drug. • For HIV drugs, which are approved on the basis of surrogate markers (for example, CD4 counts, changes in viral load), these studies are intended to document the drug's clinical benefit. • If the drug shows no clinical benefit, the sponsor is required to voluntarily withdraw the drug from the market. • also enable sponsors to evaluate the drug in populations that may not have been well represented in the Phase III trials

7. PERSPECTIVES • Process of new drug delivery a time consuming & expensive process- 10-15 yrs/ $500-800m • Patient recruitment – 30% time consumed • Erstwhile – large hospitals where patient data available • Patient recruitment – key “bottle neck” in CTs

8. No. of patient required to undergo new drug trial gradually increasing • 5300 patients needed for each NDA • In US alone – 80,000 CTs undergoing (intense competition in US Europe • Attention towards Asia, Latin America and East Europe

10. COST OF DELAY • One study – “average cost of phase III CT - $4-20 m, minimum two P-III trials needed. • A moderate success drug – delay in P-III trial to cost $1.0 m per day • For a block buster drug - $ 4.0m

11. PRINCIPLES OF PATIENT RECRUITMENT • Reasons for joining CT – • to help advance knowledge of the disease in the interest of society/ • lack of available therapy/ • improved medical care • lack of health insurance, • advice from family physicians/ • financial reasons

12. Barriers to participation- • Risk of side effects • Concern about getting placebo • Centre too far away • Unable to find a trial • Not eligible • Inconvenient hours • Not enough information

13. Nature of patients’ concerns • What if I change my mind and decide to drop • Will I get a placebo or real drug? • What is in it for me? • Will I be taken advantage of? • What is in it for my doctor?

14. Motivation for patient to participate • Access to promising therapy • Access to greater medical expertise • Close individualised medical attention care • Emotional support • Some thing to do (break boredom) • Altruistic feeling

15. ETHICAL ISSUES • Confidentiality and personal Health Information • Advertising for CT patients- prior approval of IRB/ IEC • Undue influence • Vulnerable population- children/ mentally disabled/ elderly/ students/ employees of investigators (Legally acceptable representative)

16. METHODS OF RECRUITMENT • Essentials – scientific planning and budget during protocol design stage • Investigator database • Clinical referrals • Opt- out procedure • Opt-in procedure • Advertising • Mass media campaign- radio/ TV/ press release/ mass mailing/ bill boards/ public service announcements/ through call centres (24 hrs telesrvice)

17. CRITERIA FOR ADVERTISEMENT • Neither misleading nor coercive • No claims for proven safety/ effective/ superiority over others • Use of terms “new treatment” “new therapy”, “new drug” not permitted without explanation • Not to promise “free medical treatment”

18. INCLUSION IN ADVERTISEMENT • Name of research facility • Purpose of research & eligibility criteria • Time commitment and remuneration, if any • Contact person for more information • Word “RESEARCH” should appear • Monetary compensation only as inducement

19. MARKETING ESSENTIALS • Marketing research • Market segmentation • Target marketing – particular section of society • 4 Ps – product specification / place/ price (what it will cost to patients)/ promotional activities (campaigns/ appointing recruitment agencies) • Differentiation • Positioning

20. ESSENTIAL OF RECRUITMENT MATERIALS • Neither misleading nor coercive to patients • No claims to believe that the treatment is proven safe and effective/ equivalent or superior to other treatments • The terms “New treatment”/ “New medication”/ “New Drug” not to be used without explanation- avoid misleading terms “receive new treatments”/ receive new therapy” • Do not promise free medical treatment- when intent is only not to charge patients for taking part in the study

21. 1st P- PRODUCT SPECIFICATION • Therapeutic indication of drug – • patients with limited options (cancer/ rare diseases); • patients not satisfied with current form of treatment & accept alternatives; • conditions in which patient is hesitant to share with doctors (sexual dysfunction/ urinary incontinence)

22. 2nd P- PRICE • What it will cost to the patient • Time • Inconvenience of travel • Leave from current job • Cost of any complications

23. 3rd P- PLACE • Facility of investigator – • CRO/ SMO/ Hospital/ Pharmaceutical company

24. 4th P- PROMOTION • Advertisement • Community based - Medical Camps • Referrals • Call centres • Web based- clinicaltrial.gov has appx 87000 trials in 170 countries/ companies’ web sites/ online partnership with search engines/ customised web sites – posting prequalified questionnaire and prescreen subjects online

25. CALL CENTRES • First point of contact for patients • Obtain health information data through telephone screen • Rapidly processing and filtering data to spread the recruitment over several sites • Identify appropriate modality of advertisement working – • giving first appointment • Limitations – intensive trg to operators/ language specialist for multinational/ unable to handle large traffic/ data confidentiality

26. DIFFICULTIES IN PATIENT RECRUITMENT • No strategic thinking to include recruitment in early stages of development- during protocol design. • Very narrow definition of inclusion/ exclusion criteria • Inadequate budget • Unrealistic time line • Lack of basic knowledge in recruitment in Investigator • Lack of dedicated staff • Own data inadequate • Negative publicity from media • Staggering costs involved in delays in recruitment

27. RECRUITMENT METRICS • Measurement of recruitment process • Accountability- complete tracking of all points of contacts (from prescreening call- first visit- recruitment- enrollment- retention- linking with referrals • Recruitment funnel – pre screening numbers : final enrollment • -

28. RECRUITMENT FUNNEL 1000 patients identified Fail to meet criteria - 250 Consent process - 100 Prescreening - 400 250 randomised EVALUABLE PATIENTS - 100 Drop-out - 150

29. STEPS IN RECRUITMENT PROCESS • IDENTIFY • APPROACH- information sheet- risk & benefits • INFORMED CONSENT & SCREEN- history & med exam & investigations • ASSESS • ENROLL - RECRUIT

30. APPROACH TO RECRUITMENT • Strategic planning- at protocol design stage/ monitoring of recruitment strategies • Budgeting- 10-15 % of total budget of study / appx $ 500 m spent per year by sponsors/ must in initial planning stage for correct appreciation of expenses • Monitoring & tracking • Metrics • Training – • by sponsor to investigator sites • By investigator to its staff

31. RETENTION OF STUDY OBJECTS – the patients • Harder than recruiting • Equals in Management – CRM for customer retention • Dropout rates- appx 25% ; very high rates make study invalid • Factors to be considered • Patient profile – correct selection – demography/ personal attributes/ education/ personality compatible with remaining compliant • Key influence – reasons for participating • Barriers to participation • Motivators for participation

32. REASONS FOR DROPOUT • Lack of efficacy • Adverse reaction • Tool long a study duration • Need for invasive procedures • Unfriendly staff at site • Time constraints • Lack of transportation • Protocol too complex and difficult to follow

33. RETENTION TECHNIQUES & TOOLS • How valued they feel? • How well are they treated at every touch point? • Personal attention & treatment from everyone • Queries to be answered • Well informed • Regimen aids • Well compensated for time & travel • Sense of commitment & sense of belonging • Newsletter/ appointment reminders/ follow up calls/ educational material/ appreciation items at intervals

34. RECENT ADVANCES • Professional recruitment providers • Increased use of Market Research • Informatics • Centralised recruiting • Development of Metrics – “Leaky pipe analysis”