Good Clinical Research Start Up Activities Suzanne Pozsonyi SynCon International June 7 2013

1. Good Clinical Research Start Up
Activities
Suzanne Pozsonyi
SynCon International
June 7 2013
MedicReS Good Clinical Research CME
June 7-8 2013 | Istanbul Turkey

2. Agenda
• Study preparation activities
– Division of responsibilities : SPONSOR - CRO
• Concrete study set up activities
– Focus on activities usually dedicated to CRO

3. Clinical Trial Preparation
- Responsibility of Sponsor -
- Write Project Plan
- Write quality management system, SOPs, defining the
process for conducting the clinical trial
Writing clinical trial documents ( protocol, investigators brochure, patient
information , patient informed consent, case report form, local trial
agreements, financial disclosure forms, FDA 1572, etc.)
- Define Adverse Events process
- Prepare labeling

4. Clinical Trial Preparation
- Responsibility of Sponsor -
- Define the monitoring process/prepare monitoring manual
- Select and train monitor
- Qualify the indentified investigators and clinical trial sites
- Obtain clinical trial insurance *
- Prepare and submit documentations to ethics committees and
authorities*

5. Clinical Trial Preparation
- Usually by CRO -
1.Feasibility Study
2. Identification and Selection of Clinical Trial Sites/ Investigators
3.Pre-study Visits, Evaluation of Potential Sites
4.Contracting*
5.Prepare and submit documentations to ethics committees and
authorities*
6.Traning for the Clinical Trial *
7. Initiation visits

6. 1.Feasibility Study
-definition-
• Process of evaluating the possibility of
conducting a particular clinical program / trial
in a particular geographical area
• With the objective to achieve:
– optimum project completion of the target
– on time
– on budget

7. 1.Feasibility Study
Why, when, who, what,
• Globalization of clinical trials……go to various
regions…
–Local differences…….
• Results in various challenges
• To identify these challenges and address them

8. 1.Feasibility Study
Why, when, who, what,
HELPS SPONSOR TO KNOW :
• Which countries and sites can be selected
• Recruitment rate
• Quality of data that may be generated
• Infrastructure and facility present at site

9. 1.Feasibility Study
Why, when, who, what,
FROM FINANCIAL PERSPECTIVE:
• Clinical trial related costs:
– Labor costs
– Costs of laboratory, various examinations ( CT, MRI…)
– Costs of regulatory/EC approval
– Investment required for particular site for setting up basic
infrastructure like internet, separate computer , telephone
line, fax

10. 1.Feasibility Study
Why, when, who, what,
• To identify potential challenges before hand
thus before study start

11. 1.Feasibility Study
Why, when, who, what,
• Global or regional/ local level by study team
member
– Local affiliate of the sponsor
– CRO / service provider (consultant, patient
recruitment organisation , etc.)

12. 1.Feasibility Study
Why, when, who, what,
• Investigator’s interest in conducting the
proposed clinical trial
• Is the required patient pool available with
physician ?
• If yes, how many patient can be provided for
the clinical trial?

13. 1.Feasibility Study
Why, when, who, what,
• Is the disease under study relevant to the
patient population
• Is the study design acceptable
• What are the anticipated cultural, regulatory
and ethical challenges …….

14. 1.Feasibility Study
Why, when, who, what,
….……..
• To know the whether site is under the supervision of
IRB or IEC or not
• What are charges of IRB/IEC
• What is frequency of meeting of IRB/IEC
• How many days prior to meeting the documents are
needed to be submitted
• How many days after meeting is approval for clinical
trial granted helps to know time from IRB submission
to the approval date……..

15. 1.Feasibility Study
Why, when, who, what,
.…….
• Has the site faced any regulatory audit like USFDA
and if audited, is certificate of audit present?
• Was site suspended for any misconduct or fraud
during clinical trial?
• Will there be any ethical concerns while using
placebo arm ?
• Will there be any concerns re. a medical procedure
related to the trial ? ( ex. GI gastroscopy…)

16. 1.Feasibility Study
Why, when, who, what,
To know whether there are any suggestions from
investigators regarding any of following
• Protocol
• Inclusion/exclusion criteria
• Is there any safety concern for the patients of clinical trial
or any other safety concern like life threatening condition.
• Concomitant medications
• Overall conduct of clinical trial
• Will there be any safety issue or ethics committee concern
/ placebo arm
• Any other aspect

17. 1.Feasibility Study
Why, when, who, what,
• To know whether there are any competitive
trial running at investigator site that may
affect recruitment
• In case of competitive trial:
– next step is to find out whether inclusion and
exclusion criteria are same for the other trial as
proposed trial
• To know investigator’s and site staff ‘s
experience in ICH GCP trials

18. 1.Feasibility Study
Why, when, who, what,
• Has he worked previously with the same
sponsor - site performance can be evaluated
by sponsor by previous details of the site
• What is the overall commitment of potential
partners – patients, investigators, country
offices, service providers

19. 1.Feasibility Study
Why, when, who, what,
To know
• If laboratory facilities available
• Whether special investigation instrument like CT
scan, MRI scan , spirometer etc as required by trial is
present at site, or not
– At times sponsor provides investigator with some
instruments for conduct of clinical trial
• Overall patient load and clinical trial load of
investigator
– and to judge whether he shall be able to dedicate
appropriate time for conducting clinical trial

20. Relevant topics to feasibility
in ICH GCP E6
4.1 Investigator's Qualifications and Agreements
• 4.1.1 The investigator(s) should be qualified by education,
training, and experience to assume responsibility for the
proper conduct of the trial….
• 4.1.3 The investigator should be aware of, and should comply
with, GCP and the applicable regulatory requirements.
• 4.1.4 The investigator/institution should permit monitoring
and auditing by the sponsor, and inspection by the
appropriate regulatory authority(ies).

21. Relevant topics to feasibility
in ICH GCP E6
4.2 Adequate Resources
• 4.2.1 The investigator should be able to demonstrate
(e.g., based on retrospective data) a potential for
recruiting the required number of suitable subjects
within the agreed recruitment period.
• 4.2.2 The investigator should have sufficient time to
properly conduct and complete the trial within the
agreed trial period.

22. Relevant topics to feasibility
in ICH GCP E6
• 4.2.3 The investigator should have available an
adequate number of qualified staff and adequate
facilities for the foreseen duration of the trial to
conduct the trial properly and safely.

23. Sample feasibility form
• Cover letter
• Feasibility questionnaire
• Feasibility summary
– Include suggestions

24. Good feasibility questionnaire
indicators
• Adequate patient pool
• Experienced PI with ICH GCP knowledge
• Appropriate infrastructures available
• Presence of experienced staff
• Presence of IRB/IEC as per regulatory
requirement

25. 2.Identification of Selection
of Clinical Trial Sites/ Investigators
It is a process
• Usually as a result of a good feasibility
• Assessed during pre-study visits
• Evaluate ………..select………..

26. 3.Pre-study Visits,
Selection of Sites
Pre-study visits (PSVs), = Site Selection Visits (SSVs)
• Conducted at a potential study site
• To introduce the prospective investigator to the
study protocol and to familiarize the staff with
regulatory obligations and sponsor procedures.

27. • The visit provides an occasion for you to
assess the investigator's interest in and ability
to carry out the study
– this includes determining whether the potential
investigator has the time, facilities, equipment,
access to subjects, and staff necessary to conduct
the study
3.Pre-study Visits,
Selection of Sites

28. 3.Pre-study Visits,
Selection of Sites
Objectives are:
• Validate site claims made on Site Feasibility Questionnaire and
in previous discussions during site identification
• Evaluate condition of site
• Ensure that sponsor’s representatives have the opportunity to
tour the facilities, such as:
– Exam rooms for subject evaluation and treatment
– Laboratory area
– Any special testing areas
– Pharmacy (satellite pharmacy, if appropriate)
– Hospital unit
– Work areas for research staff
– Storage areas for study drug and supplies
– Monitoring or data entry area, if appropriate

29. 3.Pre-study Visits,
Selection of Sites
• Review essential study documents
– Protocol
– Source Docs
– Patient Information (PIF ) & Informed Consent Form ( ICF)
• Discuss patient recruitment strategies
– advertising campaigns
– home care study nurses
– patient transportation
• Provide training

30. Notes
Investigators claim:
Protocols are often developed without real world input from experienced
clinician investigator and coordinators.
• 5.6.2 Before entering an agreement with an investigator/institution to conduct a trial, the
sponsor should provide the investigator(s)/institution(s) with the protocol and an up-to-date
Investigator’s Brochure, and should provide sufficient time for the investigator/institution to
review the protocol and the information provided.
• In the US and Europe, protocols to support drug registration are developed by the study
sponsor with input from outside experts, investigators and regulatory agencies.
• In Japan, protocols to support drug registration are often developed by the investigator with
input form the study sponsor, outside experts and the regulatory agency.
• “Investigator Initiated” studies
• Written and developed by investigators requesting financial support
• Usually Phase IV studies
• Almost never a pivotal registration study

31. 4. Contract
ICH GCP E7 ..1.7 Contract:
A written, dated, and signed agreement
between two or more involved parties that
sets out any arrangements on delegation and
distribution of tasks and obligations and, if
appropriate, on financial matters. The
protocol may serve as the basis of a contract.

32. Challenges
• Various country differences
• Governing law and language
– Sponsors’s country of origin vs. Investigator
country of origin
• Contract with PI only/investigator only vs
with each staff member
• Difference between investigator fees in
various countries
• Various institutional ( hospital ) regulations
• Length of obtaining investigators contract

33. 5.Prepare and submit documentations
to ethics committees and authorities*
• Site / study staff selected
• Agreements are in place
• All study related documentation is available
( inc. translations, pts recruitment materials, …INSURANCE..)
Submit to Ethics Committees and Authorities
Parallel or consequent *

34. 6. & 7. Training
–Investigator Meeting – Initiation visit
• ICH GCP 8.2.20, the sponsor of a clinical study must
carry out a trial initiation visit or training to ensure
the principal investigator understand the study
procedures of the protocol, his/her duties, among
other things.
• The study initiation visit is usually conducted after
the site has been selected by the sponsor to
participate in study conduct, but just before the site
starts enrolling patients for the study.

35. 6.Traning for the Clinical Trial
- Investigators Meeting -
• Review protocol and procedures
• Get better acquainted with the sponsor and other
investigators
• Answer outstanding questions
• Generate enthusiasm for the trial and for recruitment
• Identify / fine tune further potential problems …. how
to support pts recruitment……( pts transportation, etc. )
• May serve as the initiation visit

36. 6.Traning for the Clinical Trial
- Investigators Meeting – c’td
• Study Coordinators and sub-investigators
should also attend the meeting
• Sponsor participants include the medical
expert, biostatistician, CRAs, and CRO
personnel
• Investigators meeting can be organized ,
prepared and led ( jointly with sponsor ) by
CRO
• Key Opinion Leader / Medical expert – to hold
scientific presentation

37. 7. Initiation visits
Some of the activities that may be discussed during this
visit:
• Study protocol (study objectives, purpose, endpoints)
• Reporting AEs and SAEs
• Investigational drugs (storage, dispensing, destruction,
accountability)
• Inclusion/Exclusion criteria of protocol
• Patient Enrollment
• CRF completion and error correction
• Randomization procedures, including breaking the blind
• Protocol compliance and deviation issues

38. Conclusion
• Well defined process
• Good planning is needed
• On going process
• Good communication between parties , and
adaption to local situation is needed
• Be flexible ( reasonably ) to change….even during
the study