Adaptative designs and sites.

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

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

3. People Participants Nurses Physicians Systems Projects Work Finances Budget & Cash flow These changes are applied over an already rapidly changing environment Actual load of pressure on sites to make changes. What is changing?

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

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

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

7. Patients and population • General population has a • Negative opinion of drugs • Perceived guinea pig activity • Lack of trust • Negative press in general • 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. • 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?

11. Erosion of trust in clinical research

12. There is a need to • Develop a sufficient level of confidence and support from the community. • By investigative sites • By 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. • 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 • 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 • data entry people • or specific budget for RDE

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

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

17. What’s next ? • Emergence of dedicated specialized in the conduct of trials • An 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

18. What’s next ? • 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.

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.