1. 1 US Investigator Meeting DIAS-4, Chicago, July 2011 Informed Consent

2. US Investigator Meeting DIAS-4, Chicago, July 2011 2 Informed Consent No investigator may involve a human being as a subject in research… unless the investigator has obtained the legally effective informed consent of the subject or the subjects legally authorized representative

3. US Investigator Meeting DIAS-4, Chicago, July 2011 3 Informed Consent Is the key to respecting autonomy Provides a reasonable assurance that the subject has not been deceived or coerced Subject must receive verbal information on the trial Subject must receive written Subject Information Sheet / Informed Consent Form Must be personally signed, dated and timed prior to any study related activities

4. US Investigator Meeting DIAS-4, Chicago, July 2011 4 Who is responsible? PI can choose to delegate the verbal information part of the informed consent process to a sub-investigator or study nurse The delegation of the task needs to be documented on the signature and delegation list

5. US Investigator Meeting DIAS-4, Chicago, July 2011 5 Compliance with local requirements Use current, IRB approved version of ICF Written approval from IRBs on the informed consent form and any other written patient-related information must to be obtained prior to study start at the site HIPAA language/ Bill of Rights may be stand alone documents or part of the ICF per local IRB preference Any revised ICF should receive IRBs approval prior to use

6. US Investigator Meeting DIAS-4, Chicago, July 2011 6 When to obtain? GCP 4.8.8 Prior to a subjects participation in the trial the written informed consent form should be signed and personally dated by the subject or by the subjects legally acceptable representative, and by the person who conducted the informed consent discussion. Baseline Prior to initiating any study-related, non-standard procedure Should be signed, dated and timed

7. US Investigator Meeting DIAS-4, Chicago, July 2011 7 Emergency situations GCP 4.8.15 When prior consent of the subject is not possible, and the subjects legally acceptable representative is not available, enrolment of the subject should require measures descried in the protocol with documented approval by the IRB

8. US Investigator Meeting DIAS-4, Chicago, July 2011 8 Study Specific Consent Procedure Consent by.. A.Patient or legal representative B.Oral consent by patient, written consent by impartial witness C.Consent by relative/spouse, on behalf of patient unable to understand D.Declaration of 2 physicians, 1 independent of study With approval of local IRBs!

9. US Investigator Meeting DIAS-4, Chicago, July 2011 9 B: Consent by impartial witness The subject is able to understand The subject is able to give consent but not in writing An impartial witness attends the entire informed consent process and reads the ICF and any other written info

10. US Investigator Meeting DIAS-4, Chicago, July 2011 10 Impartial witness By signing the ICF the impartial witness attests that: – The info was accurately explained to and apparently understood by the subject/legal acceptable representative – Consent was freely given by subject/legel acceptable representative Re-consent by subject has to be obtained to confirm oral consent once capable of doing so

11. US Investigator Meeting DIAS-4, Chicago, July 2011 11 C: Consent by proxy The subject is not able to understand A proxy (a relative) is available to express the assumed will of the subject, and signs the consent form Consent by subject has to be obtained to confirm consent given by the person once capable of doing so

12. US Investigator Meeting DIAS-4, Chicago, July 2011 12 D: Declaration by two physicians The subject is not able to understand No proxy is available Consent by subject has to be obtained once capable of doing so

13. US Investigator Meeting DIAS-4, Chicago, July 2011 13 Forms Informed Consent Form A to D Re-Consent Form B to D Subject Information Sheet (where applicable)

14. US Investigator Meeting DIAS-4, Chicago, July 2011 14 Filing of ICF The original signed consent form must be kept and filed by the investigator in the I-TMF A copy of the signed consent form must be given to the patient

15. US Investigator Meeting DIAS-4, Chicago, July 2011 15 Assessment of biomarkers Consent obtained via the informed consent form on the assessment of biomarkers I agree that spare serum/plasma remaining after ensuring the mandatory central analyses may be used for assessment of biomarkers (e.g. MMP-9) or other unforeseen measurements to ensure quality of study data. Such analyses will not involve genetic testing. YES__NO__ Genetic testing will not be involved

16. US Investigator Meeting DIAS-4, Chicago, July 2011 16 eCRF – Informed Consent

17. US Investigator Meeting DIAS-4, Chicago, July 2011 17 eCRF – Re-Consent

18. US Investigator Meeting DIAS-4, Chicago, July 2011 18 Summary Informed Consent is a process by which a subject voluntarily confirms his or her willingness to participate in a particular trial National laws must always be adhered. This type of study must specifically address how an individuals capacity to give informed consent will be determined The Investigator is primarily responsible for the ethics and performing correct procedure

19. US Investigator Meeting DIAS-4, Chicago, July 2011 19 Questions