Stanford University Required Questions for the Protocol Application

Stanford University Required Questions for the Protocol Application

Research Compliance Office Medical

1. Describe steps taken to minimize the possibility of coercion or undue influence.

It will be explained to the subject that participation in the study is absolutely voluntary. Furthermore, it will be explained that participation will provide no direct benefit to him or her and that participation will be purely for the sake of better understanding atrial fibrillation.

2. Provide an assessment of the importance of the knowledge expected to result from this study.

Atrial fibrillation is the most common arrhythmia in adults, occurring in 1% of the population and is strongly associated with stroke and death. There is still a great deal about the pathophysiology that is not well understood and a better understanding of the familial contribution, be it genetic or otherwise, could in the future lead to new and better treatments or prevention.

3. If you have indicated “Other” as the study location, please provide the following information:

a. Name of the site,

b. Contact name for the site with phone number/email address,

c. Has the site granted permission for the research to be conducted?

d. Does the site have an IRB?

e. If yes, will that IRB approve the research?

N/A

RESOURCES

4. Will you have access to a population that will allow recruitment of the required number of participants? Please explain and justify.

Yes. There are plans to recruit 300 patients with atrial fibrillation, which comes to on average, about 3 patients per week over a 2 year period. There are approximately 30-40 ECGs performed per day at Stanford, of which, on average, 2-5 have atrial fibrillation. Our patient population will be selected from this pool. Controls will be selected at random from those patients who had ECGs but did not have atrial fibrillation. This includes a pool of approximately 30-40 patients per day.

5. Will you have sufficient time to conduct and complete the research?

Please explain the time required and justify.

Yes. I will be finishing my clinical training in cardiology by June and will dedicate 90% of my time to research. I will attend relevant coursework and will also have research meetings during the day, but the majority of my research time will be devoted to interviewing subjects and analysing data.

6. Will you have adequate numbers of qualified staff?

Please explain and justify the number and qualifications of your study staff.

Yes. Dr. Paul Wang, the director of the Electrophysiology division of cardiovascular medicine, will be my primary mentor and faculty sponsor. He is trained in the management of atrial fibrillation and has a great deal of experience in clinical trials. Dr. Larua Lazzeroni will be my co-sponsor. She is experienced in genetic epidemiology and has helped in the design of this study. Dr. Themistocles Assimes is a cardiovascular genetic epidemiologist who has also assisted in the design of the study and will continue to help with data analysis.

7. Will you have adequate facilities to conduct the study? Please explain and justify.

Yes. There will be minimal costs associated with the study. Most of the patients interviewed will be inpatients and interviews will take place at the bedside. There will be minimal costs, including stationary, as well as telephone bills that will be covered by support from grants. Office space and computer use will be supplied by the faculty sponsor, Dr. Paul Wang.

8. Will your process ensure that all persons assisting with the research are adequately informed about the protocol and their research related duties and functions?

Please describe the training you will provide to meet this requirement.

Yes. I will be performing the interviews and data collection. If another member of the team is asked to perform these interviews, I will have a meeting with them to review the protocol for interviewing the subjects. I have already met with the current members of the research team in order to review the protocol.

9. Will you have medical or psychological resources available that participants might require as a consequence of the research when applicable?

Please describe these resources.

Because this research protocol involves a survey and does not require intervention, the likelihood of the subjects needing medical or psychological resources as a consequence of the survey is minimal.

PRIVACY AND CONFIDENTIALITY

10. For minimal risk studies, have you considered waiving the signature requirement since the only record linking the subjects and the research would be the consent document and the principal risk would be the potential harm to privacy?...... YES NO

If you decide to do so, please remember that each participant must be asked whether he/she wants

documentation linking them with the research, and the participant’s wishes will govern.

(Common Rule 45 CFR 46.117(c))

Consent will be obtained, especially given that a review of the patients' medical records will be performed.

11. Please include a description of procedures for protecting the privacy interests of participants. Additionally, are the conditions affecting interaction with the participants and data collection adequate for the protection of privacy (for example, recording physical measurements of pre-teens in a school-setting, eliciting private medical or financial information in a quasi-public setting)?

The information solicited will be done in a private setting. After collecting the data, all survey sheets will be locked in a cabinet and any electronic information gathered will be secured with password protection.

12. Do personal identifiers (e.g., names, social security or medical record numbers) need to be recorded for potential participants during screening and recruitment and for actual participants?

Yes. Medical record numbers will be collected in order to help review the subject's medical records.

13. Will the private information you will be using be coded or be destroyed at some stage of the research?

Yes. After being gathered, the written information will be transferred to electronic database. The written information will be locked and, after data analysis, will be shredded. The electronic information will remain in a password-protected format until completion of the study. Once it is decided that no further analysis can be performed, which would be in approximately 10 years, the electronic information will be destroyed.

14. Will a code (e.g., number, letter, symbol replacing identifier) afford sufficient protection from deciphering? For instance, the use of initials or the last 4 digits of the social security number may not offer sufficient protection.

The medical record number will need to be collected in order to gather the information necessary from the medical record. Only those with access to the hospital computer system or medical records will be able to identify the patients involved.

15. Describe the steps you will take to ensure the security of the data or the codes linking information to an individual (including encryption, safe transmittal and storage, protection against loss, theft, or access by unauthorized persons).

All phsycial data will remain locked in a cabinet in the electrophysiology department. The electronic database will be stored under password protection in a locked room in the electrophysiology department. Any transfer of this data will be done using high levels of encryption.

16. For this study, is it feasible to either not collect (e.g., anonymous data) or remove identifiers, substitute a code for identifiers, or separate identifiable portions of data from survey instruments?

It will be possible to remove all identifying data from the data collection records except the medical record number, which will be needed to call and review the subject's medical records as part of the study.

17. How will you dispose of electronic and paper documents containing private information?

Paper documents will be shredded. Electronic documents will be erased from the hard drive with software specifically designed to remove all traces of the information from the hard drive using a multiple write-rewrite method.

18. How will you educate research staff about (and impress on them) the importance of confidentiality, including being conscious of their communication, both verbally and in writing, in such situations as workplace conversation, insurance billing, lost or misplaced papers, and unsecured electronic documents?

I will meet with each member of the research staff individually to explain that all identifying information about the subjects must remain confidential. They are not to speak of any subject in public or in any place where their conversation could be overheard. All physical documents must be treated carefully and, as soon as the data has been entered into a database, should remain locked. I will also emphasize the importance of storing all electronic material in a password-protected computer and that computer should be logged out whenever not in use. I will also explain that no subject information is to leave the hospital grounds, in order to minimize possiblitiy of loss or leakage of data.

19. Describe how you will maintain research records in a secure manner (e.g., locked file cabinet), or use additional and more elaborate security (e.g., statistical techniques, encrypting electronic data) for research involving sensitive information.

20. Describe the planned procedures for protecting against or minimizing risks, including risks to confidentiality.

As previously mentioned, all data will be secured either in locked cabinets or under a password-protected electronic format. To minimize the risks of breaching this confidentiality, the keys to the cabinets will be carried only by the research staff and the passwords for the electronic data will be known only by those who will be actively involved in entering data or analysing data.

IND / IDE QUESTIONS

21. If the drug that is undergoing investigation is lawfully marketed as a prescription drug product, please confirm that the investigation is not intended to support a significant change in the advertising for the product.

N/A

22. Either submit a Security and Controlled Access Plan below or as an attachment that includes a description of the procedures that will be followed to prevent the investigational device from being used by a person other than the investigator and to prevent the investigational device from being used in someone other than a research participant.

N/A

23. Will the investigational drug/ biologic be maintained and dispensed by a pharmacy or through an outpatient clinic monitored by a pharmacy?...... YES NO

If “yes”, provide the name of the pharmacy.

If “no”, either submit a Security and Controlled Access Plan below or as an attachment that includes a description of the procedures that will be followed to prevent the investigational drug from being used

by a person other than the investigator and to prevent the investigational drug from being used in someone other than a research participant.

N/A

24. Submit documentation supporting the IND/IDE number other than the investigator’s brochure (e.g., letter from the FDA, letter from the sponsor, or sponsor’s protocol documenting the IND/IDE number).

N/A

25. Are you the holder of the IND or IDE?...... YES NO

If “yes”, have you fulfilled the requirements described in policies and procedures (e.g., auditing, reporting

or training)?

N/A

INFORMED CONSENT QUESTIONS

26. a. For VA research, list the people whom you have formally delegated the responsibility to obtain informed consent and indicate that this person has appropriate training to perform this activity.

N/A

b. Respond to the questions concerning consent and provide more detail for any question that might raise an issue under the circumstances of your protocol:

1. Will legally effective informed consent be obtained from the participant or the participant’s legally authorized representative or both? If LAR, is it clear who can serve as a LAR?

2. Will the circumstances of the consent process provide the prospective participant or their representative sufficient opportunity to consider whether to participate?

3. Will the circumstances of the consent process minimize the possibility of coercion or undue influence?

4. Will the information being communicated to the participant or the representative during the consent process exclude any exculpatory language through which the participant or the representative is made to waive or appear to waive the participant’s legal rights, or release or appear to release the investigator, the sponsor, the institution, or its agents from liability for negligence (e.g. I give up any property rights I may have in bodily fluids or tissue samples obtained in the course of the research)?

Legally effective informed consent will not be obtained. In order to avoid coercion or undue influence, the subject of the study will be explained that participation in the study is completely voluntary. They will be explained that they will not directly benefit from participation of the study, there is no monetary compensation and that their participation will not influence their medical care, for better or for worse, in any way. These explanations should provide sufficient opportunity for the participant to consider whether to participate. The consent will not include any language which will make the subject waive any of the participant's legal rights, will not release the investigator or the sponsor or the institution or its agents from liability or negligence.

MULTI-SITE STUDIES

27. Is this a multi-site study?...... YES NO

a. If “yes”, are you the lead investigator for this study?...... YES NO

b. Is Stanford the coordinating site for this study?...... YES NO

28. If you are the lead investigator for this multi-site study, what is your role in coordinating the participating sites?

N/A

29. Since Stanford is the coordinating site for this study, please describe what procedures are in place for routine communication with the other participating sites. Additionally, please explain how you will document these routine communications with the participating sites (e.g., telephone conferences, planned meetings, email communications, etc.).

N/A

30. Since Stanford is the coordinating site, explain how you will manage the communication of adverse outcomes, unexpected problems involving risk to participants or others, protocol modifications or interim findings.