1. Adaptative designs and sites. Pierre Gervais Pierre Gervais President, Q&T Research, Sherbrooke President, AQRC

2. Discuss areas mostly affected with implementation of Adaptive Designs (AD) 1. Approach to the patients, 2. Remote data entry 3. Study material.

3. PeopleParticipantsNursesPhysicians SystemsProjectsWorkFinances Budget & Cash flow These changes are applied over an already rapidly changing environment What is changing ? Actual load of pressure on sites to make changes.

4. Nurses «Must have» qualities «Must have» qualities Caring personalityCaring personality Well integrated nursing and medical knowledgeWell integrated nursing and medical knowledge Organised and structured mind… but also flexibleOrganised and structured mind… but also flexible A «Make it Happen!» mentalityA «Make it Happen!» mentality A «Sixth Sense» for problemsA «Sixth Sense» for problems BilingualismBilingualism Understanding roles and responsibilitiesUnderstanding roles and responsibilities i.e. managing a study vs managing a site i.e. managing a study vs managing a site CRO / Sponsor / Site management / PI / AuditorCRO / Sponsor / Site management / PI / Auditor Computer literateComputer literate

5. Physicians Dedicated research time Dedicated research time Clinical research set up that is changing from amateur toprofessional Clinical research set up that is changing from amateur toprofessional Much more attractive Plan B Much more attractive Plan B More than 50% of physicians in the US will do only 1 trial. More than 50% of physicians in the US will do only 1 trial. Lack of US Investigators in 08- 09 ? Lack of US Investigators in 08- 09 ?

6. Projects Made on time Made on time Increasing globalisation Increasing globalisation Competitive pricing. Competitive pricing. One case in US = 1.0 $ One case in US = 1.0 $ In Canada = 0.87 $ In Canada = 0.87 $ In China = 0.18 $ In China = 0.18 $ In India = 0.27$ In India = 0.27$

7. Patients and population General population has a General population has a Negative opinion of drugsNegative opinion of drugs Perceived guinea pig activityPerceived guinea pig activity Lack of trustLack of trust Negative press in general Negative press in general Lack of knowledge of the population and the medical bodies Lack of knowledge of the population and the medical bodies

8. Erosion of patient trust in drugs and drug companies

9. Perception is often that: Drugs are commodities. Drugs are commodities. Drug companies are commodity providers. Drug companies are commodity providers.

10. Only in North America ? 4th Annual Forum on Patient Adherence, Compliance and Persistency November 29 - 30, 2007, Prague, Czech Republic II. Are Patients Being Scared off Their Medicines? II. Are Patients Being Scared off Their Medicines?

11. Erosion of trust in clinical research

12. There is a need to Develop a sufficient level of confidence and support from the community. Develop a sufficient level of confidence and support from the community. By investigative sitesBy investigative sites By pharmaceutical sponsorsBy pharmaceutical sponsors

13. AD / Approach to the patient Sites must be very careful when explaining the details of clinical research, experimentation, side effects, risks, etc to patients. Sites must be very careful when explaining the details of clinical research, experimentation, side effects, risks, etc to patients. Adaptative designs make our jobs even more challenging when we have to explain these complex designs and the risks of early treatment cessation are increased when designs are modified. Adaptative designs make our jobs even more challenging when we have to explain these complex designs and the risks of early treatment cessation are increased when designs are modified.

14. AD / Data entry Sponsors must analyse early and rapidly Sponsors must analyse early and rapidly Data to be entered into the system as it is generated by the site Data to be entered into the system as it is generated by the site New role is allocated to the sites but unfortunately very often without the necessarily equivalent resources New role is allocated to the sites but unfortunately very often without the necessarily equivalent resources data entry peopledata entry people or specific budget for RDEor specific budget for RDE

15. Actual management Protocols of increasing complexity Protocols of increasing complexity More visits More visits More procedures More procedures More documentation More documentation SOP, archive, study binder, …SOP, archive, study binder, … New roles, such as data entry (RDE) New roles, such as data entry (RDE) More hidden costs: More hidden costs: SAE reporting, Amendment (s…), data lock, data queries, deadlines, etcSAE reporting, Amendment (s…), data lock, data queries, deadlines, etc More reluctant patients More reluctant patients

16. AD and management All the above, plus All the above, plus Complex study medication packages Complex study medication packages Bulky laboratory boxes Bulky laboratory boxes Space is becoming an issue for centersSpace is becoming an issue for centers More reluctant patients More reluctant patients

17. Whats next ? Emergence of dedicated specialized in the conduct of trials Emergence of dedicated specialized in the conduct of trials An increasing challengeAn increasing challenge Part time investigative sites will not find their place with complex design and be left with much more simple trials, i.e. Phase IIIb and IV Part time investigative sites will not find their place with complex design and be left with much more simple trials, i.e. Phase IIIb and IV

18. Whats next ? Many physicians may very well simply return to their clinic, a reaction that will further increase the lack of investigative physicians. Many physicians may very well simply return to their clinic, a reaction that will further increase the lack of investigative physicians. More than 50% of US investigators will complete a 1572 only once. More than 50% of US investigators will complete a 1572 only once.

19. In conclusion While the use of AD is increasing, sites have to adapt their work strategies and the skills of the research staff. … and to carefully adapt with these changes while maintaining high standards for work ethics.