Adaptative designs Adaptative designs and sites.and sites.

Pierre Gervais Pierre Gervais

President, Q&T Research, SherbrookePresident, Q&T Research, Sherbrooke

President, AQRCPresident, AQRC

Discuss areas mostly affected with Discuss areas mostly affected with implementation of Adaptive Designs (AD)implementation of Adaptive Designs (AD)

1.1. Approach to the patients, Approach to the patients,

2.2. Remote data entryRemote data entry

3.3. Study material.Study material.

People People

ParticipantsParticipants

NursesNurses

PhysiciansPhysicians

SystemsSystems

ProjectsProjects

WorkWork

FinancesFinancesBudget & Cash flowBudget & Cash flow

These changes are applied over an already rapidly changing environment

What is changing ?

Actual load of pressure on sites to make changes.

NursesNurses

«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 sitei.e. managing a study vs managing a site

• CRO / Sponsor / Site management / PI / AuditorCRO / Sponsor / Site management / PI / Auditor

• Computer literateComputer literate

PPhysicianshysicians

Dedicated research timeDedicated research time Clinical research set up that is Clinical research set up that is

changing from ‘’amateur’’ to changing from ‘’amateur’’ to ‘’‘’professionalprofessional’’’’

Much more attractiveMuch more attractive ‘ ‘’Plan B’Plan B’’’’ More than 50% of physicians in More than 50% of physicians in

the US will do only 1 trial.the US will do only 1 trial. Lack of US Investigators in Lack of US Investigators in

’08-’09’08-’09 ? ?

ProjectsProjects

Made on time Made on time Increasing globalisationIncreasing 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$

Patients and populationPatients 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 generalNegative press in general Lack of knowledge of the population Lack of knowledge of the population

and the medical bodiesand the medical bodies

Erosion of patient trust in drugs and Erosion of patient trust in drugs and drug companiesdrug companies

Perception is often that:Perception is often that:

Drugs are Drugs are commodities.commodities.

Drug companies are Drug companies are commodity providers.commodity providers.

Only in North America ?Only in North America ?

4th Annual Forum on Patient Adherence, 4th Annual Forum on Patient Adherence, Compliance and Persistency Compliance and Persistency

November 29 - 30, 2007, Prague, Czech November 29 - 30, 2007, Prague, Czech RepublicRepublic

II. Are Patients Being Scared off Their II. Are Patients Being Scared off Their Medicines?Medicines?

Erosion of trust in clinical researchErosion of trust in clinical research

There is a need to There is a need to

Develop a sufficient level of Develop a sufficient level of confidence and support from the confidence and support from the community.community.• By investigative sitesBy investigative sites• By pharmaceutical sponsorsBy pharmaceutical sponsors

AD / Approach to the patientAD / Approach to the patient

Sites must be very careful when explaining Sites must be very careful when explaining the details of clinical research, the details of clinical research, experimentation, side effects, risks, etc to experimentation, side effects, risks, etc to patients. patients.

Adaptative designs make our jobs even Adaptative designs make our jobs even more challenging when we have to explain more challenging when we have to explain these complex designs and the risks of these complex designs and the risks of early treatment cessation are increased early treatment cessation are increased when designs are modified. when designs are modified.

AD / Data entryAD / Data entry

Sponsors must analyse early and Sponsors must analyse early and rapidlyrapidly

Data to be entered into the system Data to be entered into the system as it is generated by the siteas it is generated by the site

New role is allocated to the sites but New role is allocated to the sites but unfortunately very often without the unfortunately very often without the necessarily equivalent resourcesnecessarily equivalent resources• data entry peopledata entry people• or specific budget for RDEor specific budget for RDE

Actual managementActual management

Protocols of increasing complexityProtocols of increasing complexity More visitsMore visits More proceduresMore procedures More documentationMore 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, SAE reporting, Amendment (s…), data lock, data queries, deadlines, etcdata queries, deadlines, etc

More reluctant patientsMore reluctant patients

AD and managementAD and management

All the above, plusAll the above, plus Complex study medication packages Complex study medication packages Bulky laboratory boxesBulky laboratory boxes

• Space is becoming an issue for centersSpace is becoming an issue for centers More reluctant patientsMore reluctant patients

What’s next ?What’s next ?

Emergence of dedicated specialized Emergence of dedicated specialized in the conduct of trialsin the conduct of trials • An increasing challengeAn increasing challenge

Part time investigative sites will not Part time investigative sites will not find their place with complex design find their place with complex design and be left with much more simple and be left with much more simple trials, i.e. Phase IIIb and IVtrials, i.e. Phase IIIb and IV

What’s next ?What’s next ?

Many physicians may very well Many physicians may very well simply return to their clinic, a simply return to their clinic, a reaction that will further increase the reaction that will further increase the lack of investigative physicians. lack of investigative physicians.

More than 50% of US investigators will More than 50% of US investigators will complete a 1572 only once.complete a 1572 only once.

In conclusionIn conclusion

While the use of AD is increasing, While the use of AD is increasing, sites have to adapt their work sites have to adapt their work strategies and the skills of the strategies and the skills of the research staff. research staff.

… … and to carefully adapt with these and to carefully adapt with these changes while maintaining high changes while maintaining high standards for work ethics. standards for work ethics.