1. AUDIT AND FOLLOW-UP IN CLINICAL STUDIES 1 DECEMBER 2007, ISTANBUL In a general sense, an audit may involve PersonnelOrganizationSystemProcessProjectProduct Financing and many other matters not listed hereunder.

2. AUDIT AND FOLLOW-UP IN CLINICAL STUDIES 1 DECEMBER 2007, ISTANBUL An audit should aim for an acceptable quality. Although acceptable quality is of a great significance, it is by no means perfect. Surely, what is under consideration here involves high-quality clinical studies. It should always be remembered that audits constitute a step towards high-quality clinical studies. An investigator who is aware that an audit will be performed will tend to generate higher quality data. However, the objective of the audit should be to encourage the investigator more when an acceptable quality is already available.

3. AUDIT AND FOLLOW-UP IN CLINICAL STUDIES 1 DECEMBER 2007, ISTANBUL As far as clinical studies are concerned, an audit serves to determine whether the study is conducted in compliance with the protocol, the standard operation procedures, ethical values and good clinical practice norms.

4. AUDIT AND FOLLOW-UP IN CLINICAL STUDIES 1 DECEMBER 2007, ISTANBUL In order to ensure that the audit is performed in a correct manner, the auditor should abide by a standard operation procedures which is previously agreed upon and duly sent to the investigator. It would be even more proper to indicate the said method in the audit report. In order to ensure that the audit is performed in a correct manner, the auditor should abide by a standard operation procedures which is previously agreed upon and duly sent to the investigator. It would be even more proper to indicate the said method in the audit report.

5. AUDIT AND FOLLOW-UP IN CLINICAL STUDIES 1 DECEMBER 2007, ISTANBUL In each case, observations and findings should be documented in an audit. The most correct and proper way of handling this is to keep the minutes of the closing meeting and to sign the said minutes as this procedure will serve to prevent many potential correspondences and discussions in the future. In each case, observations and findings should be documented in an audit. The most correct and proper way of handling this is to keep the minutes of the closing meeting and to sign the said minutes as this procedure will serve to prevent many potential correspondences and discussions in the future.

6. AUDIT AND FOLLOW-UP IN CLINICAL STUDIES 1 DECEMBER 2007, ISTANBUL Although the said minutes will not be considered as an audit report, it would serve as a guideline for the said report. There certainly will be matters to be considered in detail. These matters could be indicated with to be discussed in detail in the results report in the minutes. Although the said minutes will not be considered as an audit report, it would serve as a guideline for the said report. There certainly will be matters to be considered in detail. These matters could be indicated with to be discussed in detail in the results report in the minutes.

7. AUDIT AND FOLLOW-UP IN CLINICAL STUDIES 1 DECEMBER 2007, ISTANBUL The investigator is liable to promptly supply the documentation and instrumentation required during audits. However, the investigator will be entitled to cause an official report listing the submitted documentation to be kept. The auditor will be authorized to request copies of the said documentation as long as the documentation does not violate the volunteers right to keep their identities confidential. The investigator is liable to promptly supply the documentation and instrumentation required during audits. However, the investigator will be entitled to cause an official report listing the submitted documentation to be kept. The auditor will be authorized to request copies of the said documentation as long as the documentation does not violate the volunteers right to keep their identities confidential.

8. AUDIT AND FOLLOW-UP IN CLINICAL STUDIES 1 DECEMBER 2007, ISTANBUL From the investigators viewpoint, one of the most important problems is the possible availability of different legal regulations concerning the performance of the study. There is no doubt that the local legal regulations in force at the site where the study is conducted will be given primary importance. However, no complete harmonization has yet been achieved in spite of intensive efforts to this end. From the investigators viewpoint, one of the most important problems is the possible availability of different legal regulations concerning the performance of the study. There is no doubt that the local legal regulations in force at the site where the study is conducted will be given primary importance. However, no complete harmonization has yet been achieved in spite of intensive efforts to this end.

9. AUDIT AND FOLLOW-UP IN CLINICAL STUDIES 1 DECEMBER 2007, ISTANBUL Another problem faced by the investigator involves the contracted research organization. Although contracted research organizations play very important roles in many studies, it is always possible to be confronted with research organizations without any established standard working methods. Another problem faced by the investigator involves the contracted research organization. Although contracted research organizations play very important roles in many studies, it is always possible to be confronted with research organizations without any established standard working methods.

10. AUDIT AND FOLLOW-UP IN CLINICAL STUDIES 1 DECEMBER 2007, ISTANBUL One of the most significant problems encountered during audits is the investigators failure to abide by the protocol. The reason for this may either lie with the investigator who does not exactly comprehend the standard operation procedures or with the methods themselves which are not sufficiently clear and enforceable. One of the most significant problems encountered during audits is the investigators failure to abide by the protocol. The reason for this may either lie with the investigator who does not exactly comprehend the standard operation procedures or with the methods themselves which are not sufficiently clear and enforceable.

11. AUDIT AND FOLLOW-UP IN CLINICAL STUDIES 1 DECEMBER 2007, ISTANBUL With a particular emphasis on bio-equivalency studies, our clinic completed 620 bioequivalency, phase I and phase II trials since its establishment and went through 32 audits which resulted in certification. However, let us not forget that the said figures do not include audits performed during studies as well as the study close-out visits. With a particular emphasis on bio-equivalency studies, our clinic completed 620 bioequivalency, phase I and phase II trials since its establishment and went through 32 audits which resulted in certification. However, let us not forget that the said figures do not include audits performed during studies as well as the study close-out visits.

12. AUDIT AND FOLLOW-UP IN CLINICAL STUDIES 1 DECEMBER 2007, ISTANBUL Audits performed in our clinic may be scrutinized in 3 groups: Audits performed in our clinic may be scrutinized in 3 groups: Legal authority (national and international) Legal authority (national and international) Sponsor audits Sponsor audits Contracted research organization audits Contracted research organization audits

13. AUDIT AND FOLLOW-UP IN CLINICAL STUDIES 1 DECEMBER 2007, ISTANBUL Audits are also divided into 3 groups by their purpose: Audits are also divided into 3 groups by their purpose: Audits performed on completed works, Audits performed on completed works, Audits performed on ongoing works, Audits performed on ongoing works, Audits performed on future planned works Audits performed on future planned works

14. AUDIT AND FOLLOW-UP IN CLINICAL STUDIES 1 DECEMBER 2007, ISTANBUL The distribution of audits conducted in our clinic is as follows. The distribution of audits conducted in our clinic is as follows. National health authority: 4 National health authority: 4 Foreign country health authority: 1 Foreign country health authority: 1 Contracted research organization: 18 Contracted research organization: 18 Sponsor: 9 Sponsor: 9

15. AUDIT AND FOLLOW-UP IN CLINICAL STUDIES 1 DECEMBER 2007, ISTANBUL With the exclusion of audits conducted by legal authorities, audits may be conducted by independent audit companies appointed by sponsors or contracted research organizations. Likewise, 6 of the audits conducted in our clinic were performed by such companies. With the exclusion of audits conducted by legal authorities, audits may be conducted by independent audit companies appointed by sponsors or contracted research organizations. Likewise, 6 of the audits conducted in our clinic were performed by such companies.

16. AUDIT AND FOLLOW-UP IN CLINICAL STUDIES 1 DECEMBER 2007, ISTANBUL From our own viewpoint, the most important problems encountered are as follows: From our own viewpoint, the most important problems encountered are as follows: To be a part of the state sector as a clinic To be a part of the state sector as a clinic Audits which sometimes last longer than required and which block out the investigators entire available time Audits which sometimes last longer than required and which block out the investigators entire available time Problems in explaining our standard working procedures Problems in explaining our standard working procedures Auditors reflecting their own problems on the audit process from time to time Auditors reflecting their own problems on the audit process from time to time Excessive delays in submitting the audit reports Excessive delays in submitting the audit reports

17. AUDIT AND FOLLOW-UP IN CLINICAL STUDIES 1 DECEMBER 2007, ISTANBUL To ensure a problem-free audit process: To ensure a problem-free audit process: Sub-investigators should be ready for all kinds of questions just as much as the investigator in charge, Sub-investigators should be ready for all kinds of questions just as much as the investigator in charge, All other personnel should embrace their roles in the study, All other personnel should embrace their roles in the study, Personnel employed by the clinic should keep immaculate notes about any issues concerning themselves, Personnel employed by the clinic should keep immaculate notes about any issues concerning themselves, There should be a good quality control system in place, There should be a good quality control system in place, There should certainly be an archiving system in very good working order. There should certainly be an archiving system in very good working order.

18. AUDIT AND FOLLOW-UP IN CLINICAL STUDIES 1 DECEMBER 2007, ISTANBUL To ensure a problem-free audit process: To ensure a problem-free audit process: The investigator should accept any criticism generated during the audit as part of the works nature, The investigator should accept any criticism generated during the audit as part of the works nature, No clinical study can ever be perfect, No clinical study can ever be perfect, Neither the investigator nor the clinic should not use futile efforts to make everything seem perfect, Neither the investigator nor the clinic should not use futile efforts to make everything seem perfect, Only the contents of the documentation will be considered valid and applicable during the audit, Only the contents of the documentation will be considered valid and applicable during the audit, As already mentioned, what is important is to attain acceptable quality. As already mentioned, what is important is to attain acceptable quality.

19. AUDIT AND FOLLOW-UP IN CLINICAL STUDIES 1 DECEMBER 2007, ISTANBUL IT SHOULD ALWAYS BE REMEMBERED THAT AUDITS SERVE TO IMPROVE THE QUALITY OF CLINICAL STUDIES. IT SHOULD ALWAYS BE REMEMBERED THAT AUDITS SERVE TO IMPROVE THE QUALITY OF CLINICAL STUDIES. NO CLINIC STUDY AUDIT IS EVER POSSIBLE WITHOUT ANY CRITICISM. IF THERE ARE NO ERRORS, NO CRITICISM WHATSOEVER; THEN I BELIEVE THAT THERE MUST UNDOUBTEDLY BE A PROBLEM. NO CLINIC STUDY AUDIT IS EVER POSSIBLE WITHOUT ANY CRITICISM. IF THERE ARE NO ERRORS, NO CRITICISM WHATSOEVER; THEN I BELIEVE THAT THERE MUST UNDOUBTEDLY BE A PROBLEM. IT IS ALWAYS POSSIBLE TO DO BETTER. IT IS ALWAYS POSSIBLE TO DO BETTER.