1. M ODULE E : INVESTIGATOR QUALIFICATION & SITE SELECTION Jane Fendl & Denise Thwing 14 Apr 2010 Version: Final 14-Apr-2010 1

2. O BJECTIVES Investigator Responsibilities in Clinical Research Identifying potential study sites & Investigators Contacting potential Investigators Selecting Investigators 2

3. R ESPONSIBILITIES OF THE I NVESTIGATOR IN C LINICAL R ESEARCH To conduct the investigation according to; Investigator statement Investigational plan Applicable regulations Protecting the rights, safety and welfare of subjects Control of drugs under investigation Obtain IRB/EC approval of the protocol Enroll the required number of qualified subjects Obtain informed consent from every subject 3

4. 4 Responsibilities of the Investigator in Clinical Research con’t Administer the test drug Observe and measure the effects of the study drug Record all pertinent data Evaluate & manage adverse events Comply with all procedures as required in the protocol Follow regulatory authority regulations & guidelines

5. N EEDS A SSESSMENT Total number of Investigators required Level of experience Preferred medical specialty Specialized facilities Number of subjects Preferred geographic location Expected expenditure per Investigator Qualifications of Investigator and staff 5

6. I DENTIFYING POTENTIAL STUDY SITES & I NVESTIGATORS Importance of Investigator Selection Ill-equipped, careless, dishonest or over extended Investigator compromised study data Compromised study data time repairing damage Time repairing damage delays in submission Delays in submission $$$$$$ 6

7. S TEPS TO P REPARE FOR I NITIAL C ONTACT 7  Primary CRA will prepare a telephone qualification document  Team will meet and CRA/Project Manager will train the team on the protocol and course of dialogue  CRA/Project Manager will train on preclinical development & disease  Procedures for maintaining confidentiality will be communicated  Verify Investigator is not on the FDA Disqualified/Restricted List http://www.fda.gov/ICECI/EnforcementActions/DisqualifiedRestrictedAssuranceList/ default.htm

8. SOURCES FOR POTENTIAL INVESTIGATORS Investigators from previous studies Medical and professional referrals Medical meetings, conferences, or scientific symposia Journals, magazines Literature searches Medline clinicaltrials.gov Association mailing lists American Medical Association, etc Marketing or sales representatives Employees/Consultants 8

9. I NITIAL C ONTACT 9  Develop list of potential Investigators  Contact is usually by phone, email or mail  Must be documented  The objective is:  Determine interest  Evaluation capacity  During the initial contact the study should be describe in broad non-specific terms:  Name and nature of test & comparative drugs  Objectives & diagnostic categories  Type & number of subjects  Length of study  Staff requirements

10. QUESTIONS FOR THE INVESTIGATOR 10 o Credentials o Clinical study experience o Medical training o Publications o Affiliations o Access to adequate number of subjects o Site and staff capability to conduct the study o Availability of IRB o Frequency of meetings

11. 11  A confidentiality agreement (CDA) is a legal agreement between at least two parties which outlines information the parties wish to share with one another for certain evaluation purposes, but wish to restrict from wider use and dissemination.  The parties agree not to disclose the non-public information covered by the agreement. CDAs are commonly executed when two parties are considering pursing a relationship together and need to understand the other’s processes, methods, or technology solely for the purpose of evaluating the potential for a future relationship.  CDAs are also valuable to protect the ability to patent an invention, something that can be compromised if a disclosure of the invention becomes public knowledge. These agreements can also be referred to as nondisclosure agreements (NDAs) or secrecy agreements. C ONFIDENTIALITY A GREEMENT

12. F OLLOW -U P C ONTACTS 12 Received CDA Disclosure additional information Description of medication Reasons for study Study design # and type of subjects Duration of treatment Special requirement Rationale for study Provide a study synopsis May provide Investigator’s Brochure and/or Protocol Confirm interest with Investigator Provide evaluation of Investigator to team Protocol dependent criteria Criteria desired in all Investigators Schedule a Pre-study Site Visit Follow-up Contact #1Follow-up Contact #2

13. NEW SITE FEASIBILITY QUESTIONNAIRE Review protocol/draft questionnaire PI experience Identify facility/ies PI will use Affiliation SMO/affiliated network Assess if site can work with a Central IRB Experience with study related equipment Assess contract timelines Adequate staff Enrollment capability/risks/challenges Competing studies? Expected number to screen/enroll/week 13

14. S ELECTION C RITERIA 14 Investigator training CV Publications GCP training Ability & experience Exp with study drug or similar drugs Exp with complex studies Reputation Evaluate through publications, presentations, symposia & medical societies Current diagnostics & therapies Access to subjects How will subjects be recruited # of competing studies Facilities & equipment Access to equipment Adequate space Recordkeeping Drug storage facilities Geographic & demographic concerns Characteristics of population Age, sex & race Convenient access Supports recruitment Enhances compliance with visits Other research sites in the area Time & cost factors Start date of study Rate of enrollment Length of study IRB approval time Staff Quality & size of staff Training, familiarity with study drug Turnover Research supervisor # of Study Coordinators Investigator Traits Investigator Accessibility

15. 15 COLLECTION OF REGULATORY DOCUMENTS DOCUMENTS Form 1572, signed and dated by PI CV PI, and any sub-investigators, signed dated and current within 2 years Current license PI/sub-Is Copy of IRB approval letter protocol and ICF Protocol signature page IRB approved ICF

16. C ONCLUSION Careful selection and screening ensures: Safe conduct of study Productive study Cost effective study Affects: Timeliness Quality of submission 16