document

Human Subject Investigator

Guide

Updated July 2004

2

T A B L E O F C O N T E N T S

þ System Requirements

þ Log In

þ ID and Password

þ Help

þ Data Conversion Issues

þ The Investigator Role

þ Protocol Routing

þ Version, Status, User, Action

þ View Protocols

þ Open

þ Edit / Submit

þ Remove / Delete

þ Set Privileges

þ View Protocol Grant/Brochure

þ View / Print

þ Crystal Report

þ Letters / Protocol History

þ Contingency Memo or Letter of Determination

þ Renewal

þ Adverse Event

þ Amendment

þ Exception

þ Deviation

þ Exemption

þ Search

þ Create Protocol

þ Protocol Form

þ Submit a New Protocol

þ Reports

þ Appendix A: Version Table

þ Appendix B: Status Table

þ Appendix C: Action Table

BRAAN OVERVIEW The Biomedical Research and Assurance Network (BRAAN), an electronic system for submission and routing of protocols. BRAAN allows the protocol submission and review process to be more efficient since protocols are stored in a central database for easy retrieval. This allows protocols to be reviewed and processed by required personnel - all on-line from work, from home, or on the road. BRAAN is the online system for protocol creation, routing, signing, review, and tracking.

Before completing your research protocol, please read this entire manual and use the HRPO website as a source of information and a resource to help answer any questions you may have. The HRPO website can be found at the following link: http://medschool.umaryland.edu/orags/hrpo/

System Requirements You will need an up-to-date browser. For PC users, Internet Explorer 5.5 is supported but 6.0 or higher is preferred. Macintosh users running Mac OS 9 can use Netscape 6.2 higher. Those running Mac OS X should use Netscape 6.2 or higher or the recommended choice which is Apple's new browser: Safari 1.0. Bear in mind that Macintosh users will have sub-optimal quality when viewing certain contents whose formatting is critical such as Consent Forms and Meeting Minutes. There is no workaround to this issue at the moment. The HRPO suggests using a PC and Internet Explorer 6.0 to avoid problems.

Log In Access the system through the URL https://braan.umaryland.edu/ and use your email address and network password (if you have a @som.umaryland.edu email address) or assigned BRAAN password. To obtain a BRAAN password or to log into BRAAN for the first time, you will have to request access into the system by filling out the request form found at https://braan.umaryland.edu/esp1/interface/reqaccess.aspx or by going to the BRAAN log in screen found at https://braan.umaryland.edu/ and scroll down under the log in boxes and click on the hyperlink that says “click here to request access to BRAAN.” Once the form is completed and submitted it takes about 24-48 hours before your BRAAN password is emailed to you. BRAAN keeps a permanent record of who does what & when. Your login is your signature. It is a VIOLATION of UMB policy to work in BRAAN under anyone else's login or provide your login to another individual. Please make note: If the request form indicates that your EMPLID # is already in use, contact the School of Medicine (SOM) Help Desk at 410-706-3998 to have your password set up. Also, all BRAAN passwords expire after 90 days with no warning. When this happens an error message will appear indicating “bad password.” In order to get your password reset, please to contact the SOM Help Desk.

ID and Password

Log in using your email address and network password. If you don’t remember your password, contact the SOM Help Desk at 410-706-3998. They will create a new password for you.

Help - Once in the system, follow the first time user instructions carefully. If you have any questions on how to use the system, contact the BRAAN Administrator at [email protected] or the HRPO main office at 410-706-5037.

I N V E S T I G A T O R G U I D E

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S T E P - B Y - S T E P :

C O N V E R T A P R O T O C O L

þ Open workflow

þ Open approved protocol

þ Under What would you like to do?, select Amend

þ For Amendment reason select RIRS to BRAAN conversion

þ Click save icon

þ Under Go To Section, select Submit

þ Submit

Data Conversion Issues After the BRAAN system has been live for a year, all protocols that are still active will have been converted from the old paper system to the new BRAAN system. Any protocol that was closed, expired or exempt prior to September 15, 2003 (go live) will remain in the legacy database. Pending protocols will remain in the legacy database until they have completed their review process via the old paper system and are fully approved. Once they are approved they will be automatically imported into BRAAN. Anything not converted into BRAAN by 9/15/04 will be required to be resubmitted as a new study.

Only approved protocols were automatically imported into BRAAN from the old HRPO database. Since there is not a 1-to-1 correspondence between variables in the old IRB database and the new database (BRAAN), investigators will find their imported protocols are incomplete. Administrative data will have been imported into BRAAN (PI name, protocol title, etc.) but experimental descriptions and consent forms must be re-entered by the investigator. The system will not process incomplete protocols. Therefore, all existing protocols will have to be completed in BRAAN before they can be renewed or amended. You can report SAEs, deviations and exceptions on protocols that have been imported into the new system but have not yet been converted.

Putting the science of your study into BRAAN is easy. If you have an electronic version of your approved protocol, you can copy the data directly from that file and paste it into BRAAN.

You may choose to complete the conversion of an existing protocol into BRAAN immediately, or you may choose to wait until you need to amend or renew the protocol. For administrative purposes the process of converting will be considered a modification to the existing protocol, as some of the questions in BRAAN are different than those found in the RPN. Therefore, the IRB will need to re-review each conversion. When completing your “BRAAN Conversion,” either as an amendment or a renewal, enter the data EXACTLY as is appears in your currently approved protocol. If you wish to introduce any new changes, they must be clearly outlined in the description box within the amendment form or within the general summary of the renewal form.

Once a protocol is entered into the system, it never needs to be re-entered again, even for renewals. Allow sufficient time to convert your protocols before you try to renew or amend for the first time. The HRPO will make every effort to review and approve conversions as expediently as possible.

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The Investigator Role Investigative teams play a vital role in the protection of human subjects at the University of Maryland Baltimore. Investigators provide leadership for their team. Seasoned investigators are often relied upon as research experts by junior faculty and research coordinators.

Within BRAAN, the role “Investigator” refers to anyone on the investigative team, not just the PI. System users who have legitimate access to a research protocol will access that protocol via the “Investigator” role, regardless of their position on the research team. See “Set Privileges” section of this guide on how to add personal to a protocol with read/write or read only privileges .

As the individual responsible for the implementation of research, the principal investigator bears direct responsibility for ensuring the protection of every research subject. This responsibility starts with protocol design, which must minimize risks to subjects while maximizing research benefits. In addition, the principal investigator must ensure that all members of the research team always comply with the findings, determinations, and requirements of the IRB. The principal investigator must also ensure the adequacy of both the informed cons ent document and the informed consent process, regardless of which members of the research team are authorized to actually obtain and document consent.

Protocol Routing When you submit your protocol, it will route to the required signatory(s). Once you submit your protocol you do not have to do anything for it to move from the signatory(s) to the IRB. As soon as all signatures are gathered, your protocol will route to the Human Research Protections Office (HRPO) and the meeting date and IRB Analyst will automatically be assigned to your protocol. By looking at “View Protocols” under your Investigator role you can watch as the protocol moves from “Awaiting Signatures”, to “Submitted”, to either “In Review” (if minimal risk) or “Assigned to Committee” (if greater than minimal risk).

If your protocol meets the criteria for expedited review (protocol is minimal risk in nature), it does not have to be reviewed by the fully convened IRB and will be reviewed by the Executive Committee (EC). The EC is made up of the IRB Chair and Vice-Chairs. Therefore, the protocol will most likely be reviewed and approved before the meeting date it has been assigned. The review of your expedited protocol is then reported out in the minutes at a fully convened IRB meeting, ONLY if it has been fully approved before the meeting date in which it was assigned. If your expedited protocol is NOT fully approved before the meeting date, you will see the meeting date change to a future meeting date. The meeting date must be changed in BRAAN to avoid reporting unapproved protocols in the meeting minutes. Once your study is reviewed you will receive either an approval letter or a modification memo (EC questions or concerns) as soon as the review is complete.

If your protocol receives full board review, the protocol will be reviewed at the meeting date to which it has been assigned. You will receive either an approval letter or a modification memo (board has questions or concerns) after the conclusion of the convened IRB meeting.

****Please make note that the meeting date of protocols can be changed by the HRPO for one or more of the following reasons:

(1) Lack of expertise on the committee

(2) Committee member(s) conflict of interest

(3) Expedited protocol has not been fully approved before meeting date

(4) Outstanding Queries

(5) Incomplete Submissions


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Version, Status, User, Action Version/Status

There are a couple of terms that describe and define work passing through the BRAAN application. What an item is, is its version. Common versions include: Amendment, Renewal, and New. Where an item is, is its status. Common statuses include: Draft, Submitted, and Approved. Version and status interact as protocols move through the process and you will often see them listed together. For the full list of protocol versions and their definitions, see Appendix A. For the full list of protocol statuses and their definitions, see Appendix B.

***VERY IMPORTANT to note – To maintain appropriate chronology and timing of IRB approval, the system will not allow you to create more than one version of a protocol. As a result, if you have an amendment/renewal in draft or pending and you try to create another amendment or a renewal the “What would you like to do?” will not offer the option to amend, renew, or close the protocol. Once the pending amendment/renewal is either approved by the IRB or removed by the investigator the options to renew and amend will reappear in the “What would you like to do?” dropdown. To check and see if anything is outstanding on protocol go to Letters/Protocol History.

User

There are various user groups that access the BRAAN system. Many individuals will have multiple roles within BRAAN and will access protocols under different user roles, each of which will allow different access and privileges. Examples of different user groups include: Board Member, Investigator, and Reviewer.

Action

There are many actions that may be performed within BRAAN. Who can do what, to what, and under what conditions, is determined by your system administrator via an internal table called workflow. If you feel you need to be able to perform an action that is not currently listed for you under the “What Would You Like To Do?” dropdown list, please contact your system administrator to inquire whether or not this action is within the BRAAN capabilities. Examples of actions that may be performed within BRAAN include: submit, sign, amend, close, and approve. For a full list of all actions, across all user groups, see Appendix C.

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S T E P - B Y - S T E P : V I E W

P R O T O C O L S

þ Log in

þ Click the arrow next to Investigator to expand the task bar menu

þ Click View Protocol

View Protocols Selecting “View Protocols” from any of your roles, will display your “file room”. Your electronic file room is a listing of all protocols to which you have legitimate access. They are organized according to their status. For example, all protocols that are in draft status will be grouped together. Within this grouping, protocols for which you are the PI will be separated from protocols for which you are not the PI but have legitimate access, e.g. you are a collaborator.

You can view your protocols at any time. BRAAN will send an email notice to you when there are protocols upon which you need to act. Red stars ***** will appear next to a protocol to indicate that you must act on the protocol for it to proceed further in the review process. Once you act on the protocol, the PI will be required to re-submit for review and approval.

Other information displayed on the View Protocol page includes: version (new, renewal, amendment), adverse events, IRB meeting date, protocol expiration date, and whether the draft has been signed or is awaiting signatures.


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S T E P - B Y - S T E P : O P E N A

P R O T O C O L

þ Log in


þ Select View Protocol

þ Click the H number of the protocol to be opened

þ Demographics screen opens

þ Use “What Would You Like To Do” to navigate within or act upon the open protocol

Open Protocol You can open a protocol in two ways: (1) under the View Protocols screen, click on the hyperlink for the H number of the protocol you wish to open, or (2) select “Search” from your Investigator role options, in the left side menu bar, and enter the protocol number. All versions of that protocol will display. Click on the protocol number of the version you wish to open.

Protocol Demographics Screen

When you open a protocol, the first thing you see is the Protocol Demographic Screen. From here, you can see basic information on the study, and the action drop down menu, “What would you like to do?” The information displayed on the Protocol Demographics Screen changes as a protocol passes through the review process toward approval and eventual closure. The options under “What would you like to do?”, also changes based upon the status of the protocol, who is looking at the protocol and the status/version of the protocol.

What would you like to do?

All action items (see version, status, type, user, action section above) are listed under the “What would you like to do” dropdown list. Options under this list vary depending on the version/status of the protocol and who is accessing the protocol.

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Edit/Submit Protocols can only be edited when they are in draft or pending (with red stars) status. When an approved study is in need of revision or continuing review, a new version of the approved study is created, in draft status, for revision through an Amendment or a Renewal.

The PI is the only individual who can certify and submit a protocol for IRB review in BRAAN. To submit a protocol, the PI will open up the draft or pending protocol and select edit/submit protocol from “What would you like to do?” The PI will review the entire BRAAN submission, and then the PI will go to the “Certification/Submit for Approval” page within the BRAAN protocol, affirm to the attestations, and click the GO button found at the bottom of the page. The PI is the only individual who can access the GO button on their protocol. Clicking GO, attests to the statements on the page, signs the protocol, and sends it to the next stage of review. The PI assumes responsibility for all research personnel and certifies that they are appropriately trained and credentialed to perform study assignments. The next stage will be to the signatory if the study is new, and will be to the research office for all other submissions.


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Remove/Delete

Protocols can only be removed or deleted from consideration when in draft status or prior to being submitted to the HRPO for review. When a PI opens a draft protocol the only removal option available from “What would you like to do” will be the Remove/Delete option.

Once a protocol is in the review process it can be withdrawn from consideration by the PI. To withdraw a study while it is in the process of being reviewed, the PI would open the pending version of the study, and from “What would you like to do”, select Request for Withdrawal. When a PI opens a pending protocol the only removal option will be Request for Withdrawal.

When a study has been approved, the PI can request closure, but only if there are no outstanding issues to be resolved such as an adverse event that has not yet been reviewed and acknowledged. When a PI opens an approved version, assuming there are no outstanding issues, the only removal option under “What would you like to do” is Request Closure.

Thus, methods available to a PI for removing a study from use or consideration will change based upon where the protocol is at the time the PI decides to remove it.

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S E T T I N G P R I V I L E G E S

þ Log in





þ Under “What would you like to do” click Set Privileges

þ Click Go

Set Privileges “Set Privileges” allows anyone with read/write access to a protocol to determine who can access that protocol. There are two set privileges options when assigning someone access to a specific protocol: (1) read only or (2) read/write privileges. All personnel given privileges to a study will initially have only read access and this must be manually changed to read/write.

People with read/write privileges can edit, amend, renew, report SAE, report deviation, report an exception and request withdrawal or closure of the protocol. The only thing a person with read/write privileges can’t do is submit a new protocol, amendment or renewal; this can only be done by the PI.

Set Privileges is used to add the name of research personnel who need to read or edit the protocol. From the Set Privileges screen you also determine who will get e-mail notifications from BRAAN. Emails are sent as reminders. For example, prior to the expiration of a protocol, reminders are sent to renew the study. Emails are also sent when an action is needed from someone on the investigative team before the study can proceed through the review process.


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Protocol/Grant/Brochure The IRB will only review studies that have the full protocol, sponsor’s protocol, investigator’s brochure, or the human subject’s piece of the grant attached. If you do not have an electronic copy of these documents, the HRPO office will scan the paper copies into electronic format for you. Once you have the protocol, investigator’s brochure, or grant in electronic format you will need to attach it to your new protocol form in Section S: Attachments. If an attachment(s) is too big (>4.5 MB) to upload in section S, a copy of the attachment(s) can be put on a floppy or CD and delivered to the HRPO main office. The discs should be labeled with the protocol # H- along with the name and phone number of an individual for CD return. The HPRO will then attach the file(s) through the oracle database.

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V I E W / P R I N T

P R O T O C O L

þ Log in





þ Under “What would you like to do” click View Print Protocol

þ Click Go

þ Protocol output will display

þ Click on the paperclip symbol to view and print attachments

View/Print The BRAAN protocol is an electronic form used to create the protocol submission. The PI and members of the investigative team are the only individuals that can see and manipulate data on the input form (through an amendment or renewal). All roles in BRAAN have view/print only permission.

You can view the output document in two ways:

• Open the protocol. From the demographics screen, under “What would you like to do?” select View/Print Protocol.

• Under “What would you like to do?” select Letters/Protocol History and from under the Status History column, on the left hand side, you can choose which version of the protocol you wish to see. The current version is the first in the column. As you scan down that column you may see older versions of the protocol output.

When you have more than one version of a protocol available to you, you will see a compare button on the top left corner of the protocol. Clicking this will show you any differences between that version of the protocol and the previous version.

If there are attachments on this study, a paperclip icon will display in the left hand corner of the protocol. Click on the paperclip to view the attachment uploaded from section S. Also, in the top left hand corner of the protocol, you will see the protocol’s real time status, initial submission date, and approval period for that protocol version.


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Crystal Reports Consent forms will be displayed using Crystal Reports. The first time you open a consent form, you will be prompted to download an Active X component (Seagate software) from the internet onto your computer. When your system prompts you to download Crystal Reports for the first time, click “Yes”. Downloading Crystal Reports allows you to view your consent form in the format that you will use to consent a research subject. Once you have Crystal Reports on your machine you will not be prompted to download this again.

Once you see the printer friendly version of the consent form output, you are in Crystal Reports. To navigate from page to page in Crystal Reports, use the arrow keys in the Crystal window. To print the report, also use the buttons in the Crystal window. Do not use your browser buttons. The export button will not save an electronic version of a consent form. In order to save your consent form electronically, you will need to buy adobe writer, which allows you to save the consent form as a PDF. You cannot change the information displayed in the report, it is merely a representation of data in the database. To exit the report, click the X icon.

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S T E P - B Y - S T E P : V I E W

L E T T E R S / P R O T O C O L

H I S T O R Y

þ Log in





þ Under “What would you like to do” click Letters/Protocol History

þ Click Go

þ History and all related documents will display

þ Click on any of them to open

Letters/Protocol History Letters/Protocol History is considered to be the protocol binder or filing cabinet for your protocol. From the Letters/Protocol History page you can view/print the protocol, view/print any letters associated with past or current versions of the protocol, view/print consent forms and view the entire history of the protocol.

To view the letters (documents) and history of a protocol, open the protocol and under “What would you like to do?” select Letters/Protocol History. On the history page, there are four columns which chronicle the life of a protocol including status history, who acted upon the protocol, when they acted upon the protocol and all related documents.

Documents available from the history page include all past, current, and draft versions of the research protocol and consent form(s), all communication between the research team and the IRB, and all memos and letters related to the research.

Auditors will use the Letters/Protocol History page often because this is your complete study file. All people with legitimate access to the study will have the same electronic file available. As such, there will no longer be the possibility of lost or misfiled documents, or of the investigative team and the IRB office having different file histories on a study.

This page eliminates the need to phone the HRPO to inquire about the status of a protocol or transaction.


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R E S P O N D T O

C O N T I N G E N C Y M E M O

þ Log in




þ Demographics screen opens with contingency issues in a text box

þ Respond to the contingency issues in the text box

þ Under “What would you like to do” click Edit/Submit Protocol, make changes to the study

þ From last page of the protocol, submit to the research office

Letter of Determination Once a protocol is reviewed by the EC or IRB, most PIs will either receive an approval letter or a letter of determination (mod memo) that outlines the board’s prescriptive concerns or comments regarding the protocol.

If a letter of determination has been transmitted through BRAAN, your protocol will have red stars next to the H number in the View Protocol list. The status of the protocol will change to Board Mods Required. You will receive an email notice that the memo is available, and you can view the memo from the letters/protocol history screen.

Once all issues are addressed by the investigative team, the protocol is resubmitted to the research office. The response is reviewed and most protocols are then approved. In some instances, the IRB may send to the investigative team a second letter of determination requesting further clarification of issues. Once approved, the approval letter is available to the PI via the Letters/Protocol History page.

Note that BRAAN system uses different terminology than we have used in the past. The letter of determination is called a “Modification Memo”.

Continued onto pg.16

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How Do I Know When I Have a Contingency?

When the IRB has reviewed your protocol and issued a contingency letter, you will receive an email notice telling you that the board has reviewed it and there are issues that you need to resolve. The email will state “board mods required” and the status of the protocol will be “approved with mods.”

The protocol will be listed in your view protocol display with red stars next to the protocol number. If no manual changes have been made to the set privileges then the PI only, by default, will receive email notices.

How Do I View the Contingency Issues?

There are two ways to view the IRB’s contingency issues. First, by opening the protocol, you will see the board’s issues listed on the demographics page in a modifiable text box.

Second, to see (and print if needed) the contingency issues on official letterhead, from the demographics page, select Letters/Protocol History, from “What would you like to do”, select “Modification Memo” of the most current protocol version.

How Do I Respond to the Contingency Issues?

From the demographics page, look at the issues noted in the modifiable text box. Under each numbered item, enter your response to the board. BRAAN will create a response memo for you. In addition to addressing all issues raised, you must open the actual protocol (now with an open input form again) by selecting Edit/Submit Protocol, from “What would you like to do”.

Example –

(1) Please revise the consent form to indicate only the risks related to the participation in this research study.

Response – Section Q has been revised accordingly.

Make any changes necessary. Ensure that the changes made to the protocol and the responses to the memo coincide and that all changes that need to be made are completed. Then, the PI will need to go to the last page of the protocol, Certification/Submit for approval, and submit by clicking GO.

This submission is the same procedure used when the protocol was initially submitted, except that the protocol does not re-route for scientific review signatures. A thorough response to the IRB’s contingency memo will speed up review and approval of the study.


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S T E P - B Y - S T E P : R E N E W

þ Log in





þ Under “What would you like to do” click Renew

þ Click Go

þ Complete the renewal form and submit

Renewal When you submit a renewal you are actually submitting a copy of your currently approved protocol along with the answers to renewal form questions. In addition, BRAAN will create and submit to the IRB a synopsis report of all adverse events, amendments, deviations and exceptions that have occurred on the protocol.

When your study is 90 days prior to expiration, you will receive an email reminder notice and the option to renew will appear under the “What would you like to do” dropdown list. You will receive a second notice 60 days prior to expiration (if you have not yet started the renewal process). After that point, you will receive a daily email reminder until the renewal process is started or protocol closure is requested.


Why Does the Second Reminder Notice Go Out Every Day?

EXPIRED RESEARCH PROTOCOLS (NOT RENEWED BEFORE THEIR APPROVAL PERIOD ENDS) ARE OUT OF COMPLIANCE WITH FEDERAL REGULATIONS AND INSTITUTIONAL POLICY. Continuing research activities when a protocol has expired is a violation and is not permitted except to avert immediate hazard to the subject(s). Therefore, in order to protect our research subjects, the institution, and investigative teams, we have initiated this reminder mechanism. Using a daily reminder notice on protocols within 60 days of expiring, for which no renewal has been started has been an effective tool to significantly reduce the number of protocols expiring.

How Do I Start the Renewal Process?

To start the renewal process, open the study and under “What would you like to do”, select Renew. That’s it.

You can complete the renewal form now or you may simply save and close the draft renewal for completion at a later point in time. Please make note – at this point the email reminders will stop. This means that it is the PI’s responsibility to submit the renewal to the HRPO with sufficient time for the IRB to review and approve it before its expiration date. The HRPO requires submitting the renewal minimally 30 days before the expiration date and suggest 45 days to ensure approval before the expiration date.

What Happens If My Protocol Expires?

If an active study expires, BRAAN will place the study into a delinquent status called system closure. The protocol will move into closed status and have a yellow box around it to indicate that it expired. At this point, you will have to either renew the study or close the study ASAP. If you have not started the renewal process (created a draft renewal) and your study expires, you will have to submit a brand new study for review in order to continue conducting your research. Once you renew the protocol the system will show the protocol in approved status and closed status, as it keeps a history of everything that has happened to the protocol.

PI’s with delinquent protocols are subject to sanctions, which may include having privileges to submit new IRB protocols revoked.

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Renewal: Form

The Renewal Form documents subject recruitment in detail including statistics on: gender, total number of subjects enrolled, ethnic identity, and institution where recruited. Investigators must address questions regarding: study monitoring, recruitment status, any new information on the topic of study that might affect a subject’s willingness to continue participating, general summary of work to date, and a risk to benefit ratio reassessment. All questions asked on the renewal form MUST be answered completely. If all questions are not answered adequately, the renewal may be returned to the PI without IRB review.

When the study is submitted, BRAAN will generate a summary of all adverse events and all amendments reported on that protocol for the board to review. The PI is the only individual with privileges to submit a renewal for review.

What Happens to my Approved Version When I Submit a Renewal:

Once you have completed the renewal form, use the “Go to section” icon at the top of the protocol form and proceed to the Review for Completion /Submit section of the protocol. Submit to the HRPO. Renewals do not route for Department signature.

You will note that your currently approved protocol version remains in the “Approved” menu, and the renewal version appears in the “Pending Approval” menu. Once approved, the renewal becomes the current “Approved” protocol.


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A D V E R S E E V E N T S

þ Log in





þ Under “What would you like to do” click Report Adverse Event

þ Click Go

þ Complete the adverse event form and submit

Adverse Events The HRPO policy on SAE’s can be found at http://medschool.umaryland.edu/orags/hrpo/saevents.asp

Internal SAEs

Any serious adverse event associated with the use of the investigational product/procedure, which occurs to a study subject enrolled via a UMB-IRB informed consent form (Internal SAE), must be reported to the IRB within 48 hours of the event.

Internal adverse events that are not serious, but are unexpected and associated with the use of the investigational product/procedure, must be reported to the IRB within 15 working days of the event.

External SAEs

A serious, unexpected adverse event associated with the use of the investigational product/procedure, which occurred at another site (i.e., subject enrolled by non-UMB investigator; External SAE), must be reported to the IRB within five (5) days of the UMB investigator’s receipt of the report.

External adverse events that are:

• serious and unexpected but not associated with the investigational product/procedure

• serious, expected, and associated with the investigational product/procedure

• serious and expected but not associated with the investigational product/procedure

are to be reported to the IRB, in tabulation or summary form, with the study annual progress report and renewal request.

Adverse events may be reported on approved or closed versions in BRAAN. You can submit multiple adverse event forms for review simultaneously or even if an amendment or another transaction is pending. You can attach one file (<2 MB) to an adverse event form.

To report an adverse event, open the protocol. From “What would you like to do?”, select “Report an Adverse Event”. Complete the AE form, select “Send to HRPO/ORS”, and hit GO to report the event. The summary should include type or nature of the event, a full description of the activities leading to the event, intervention/actions taken in response to the event, and current status of the subject. The PI should also justify NOT changing the consent form. Anyone on the research team with read/write privileges can submit an SAE.

Some adverse events are reviewed by the full IRB. IRB acknowledgements of adverse event reports are available from the “What would you like to do?” Search Adverse Events.

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A M E N D M E N T S

þ Log in





þ Under “What would you like to do” click Amend

þ Click Go

þ Complete the amendment form and submit

Amendments All protocol modifications are referred to in BRAAN as Amendments.

Federal regulations require that all revisions be approved by the IRB prior to their implementation. Revisions that increase the risk of research participation MUST be approved by the full IRB committee.

All amendments that qualify for expedited review according to the Code of Federal Regulations are automatically considered for that review path. The IRB reserves the right to review via full board any amendment it deems in need of this level of review.

When you process an amendment you are actually modifying a copy of the currently approved version of the research. Due to the way BRAAN controls protocol versions, only one amendment can be processed at a time. For the same reason, you cannot process an amendment and a renewal at the same time.

When an amendment is approved, the approved version is archived and the amended version becomes the new currently approved version. You can amend an approved protocol at any time as long as there is no other amendment or renewal already under review.

To amend: open the approved protocol, select “Amend” from “What Would You Like To Do?”, provide a detailed description of the proposed amendment(s). Proposed amendment(s) lacking sufficient detail may be returned to the PI without IRB review for completion. Once the amendment has been adequately described, make any necessary changes in the BRAAN protocol and/or consent form, and submit from the last page as you did when you initially submitted the study.

A careful list and justification of the changes will speed up review and approval.

To help the IRB review protocol amendments other than pure administrative, the amendment form should:

1. State what was formerly done and what is being proposed. 2. Provide the rationale for the change. 3. State what impact the change has on patient safety, (i.e. either positive or negative or no impact). 4. State whether the change has an impact on the scientific integrity of the study, (i.e. decreases or increases or no impact).

If necessary, due to space limitation on the Amendment Form, this information can be provided in a separate document as an attachment.

Make the described changes to the BRAAN protocol and/or consent form and submit it to HRPO for review. The PI is the only individual who can submit an amendment.



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E X C E P T I O N S

þ Log in





þ Under “What would you like to do” click Request an Exception

þ Click Go

þ Complete the exception form and submit

Exceptions An exception is an anticipated departure from approved protocol procedures requested by the investigator and are usually specific to an individual subject. Exceptions are also approved by the sponsor.

The exception form includes a description of the requested exception and its justification, whether the exception could affect subject safety, and whether the sponsor is already aware of the exception request. ALL of this information is required to be completed before submitting to HRPO for review.

Anyone on the research team with read/write privileges can submit an exception.

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D E V I A T I O N S

þ Log in





þ Under “What would you like to do” click Report a Deviation

þ Click Go

þ Complete the deviation form and submit

Deviations

A deviation is a departure from the IRB approved protocol.

The IRB recognizes that deviations to approved IRB protocols may occur. It is the responsibility of the Principal Investigator to notify the IRB of all protocol deviations that (1) exposed subjects to potential increased risk or that (2) compromised the integrity of the entire study. Such deviations must be reported within 5 working days after the deviation or exception becomes known. The PI should provide an explanation of the circumstances that led to the deviation, a description of the steps taken to address the problems resulting from the deviation, the impact of the deviation on the research subject(s), and a plan for assuring that similar deviations will not occur in the future.

Anyone on the research team with read/write privileges can submit a deviation.


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E X E M P T I O N S

þ Log in


þ Select Create Protocol

þ Choose Human

þ Enter the title

þ Copy existing protocol, if applicable

þ Complete the form

þ Submit

Exemptions

The determination that a protocol is exempt from IRB oversight is the responsibility of the IRB. As such, all protocols that you think may be exempt from IRB review must be entered into BRAAN. When completing a BRAAN protocol in which you feel may be exempt, you should skip over section B1 and in section B2 select the category under which you feel the study is to be exempted.

For guidance and resources regarding exemptions, please go to:

http://medschool.umaryland.edu/orags/hrpo/exemptrequest.asp

Complete the required fields within the BRAAN new protocol application and submit the study. If the study is exempt the IRB will send to you an Exemption Letter. This letter will be generated by BRAAN and will be available to you from the Letters/Protocol History page.

If the protocol is not exempt or if the IRB has questions for you, you will receive a modification memo from the board, outlining issues to be resolved.

Please make note - on exempt studies: no continuing review is required and no adverse events can be reported. Once the IRB determines that a study is exempt and the protocol is flagged as exempt.

If you are considering changing anything on the exempt protocol that may affect the studies exempt classification, please notify the IRB before proceeding with the change.

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T I P S T O S E A R C H F O R

A P R O T O C O L

þ Log in

þ Click Search under Investigator on the left task bar.

þ When entering a protocol number do not include H-.

þ When entering a Person (PI, Administrative Contact, Co-Investigator), enter the name in the following syntax: “Last Name, First Name”. You must enter at least 3 letters. Then hit the TAB key, click

another field, or hit the icon.

þ When entering a title, you can enter keywords that may be in the title.

þ Select a status or leave the default to all

þ Click go

þ Select the version of the resulting protocol you wish to view

Search for a Protocol You have the ability to find protocols of all versions and statuses for which you have read or read/write access via the search function. You can search for a study version by: number, title, personnel, and status.

When you get results from a search, you will see all versions of that study. For example, if a study has much activity and has been open for a couple of years, a search might net a couple of archived versions, one active and approved version, and a draft amendment version. Click on the H number of the version that you need.

The search function is the easiest way to find a study when you do high volume research.


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C R E A T E A N E W

P R O T O C O L

þ Log in


þ Select Create Protocol

þ Choose Human

þ Enter the title

þ Copy existing protocol, if applicable

þ Complete the form

þ Submit

Create a New Protocol Protocols are created, routed, signed, reviewed, and approved online. The initial step occurs when the PI creates an initial draft of a protocol. In BRAAN, the PI is the ONLY individual who can create and submit a protocol. As the PI, you may copy an approved version of a related existing protocol to make the creation process faster. Coping from an approved version of an existing protocol will populate all of the fields of the BRAAN protocol with the information from the approved version. Anyone with read/write privileges can then revise the fields accordingly.

Minimal qualifications to be a PI on a research study at UMB are = 51% compensation with the status of Assistant Professor or above. Exceptions to this policy are granted by the Senior Associate Dean for Research and Graduate Studies through the Department Chair.

The new protocol application is detailed and contains the science of the study in addition to the basic demographic data and typical IRB questions. The human subject’s portion of the grant, investigators brochure, or sponsor’s protocol should be submitted through BRAAN in electronic format. Sponsors will usually release a protocol in electronic format if you call and let them know upfront that the UMB IRB will require an electronic version. If you do not have an electronic copy of these documents, the HRPO office will scan the paper copies into electronic format for you.

BRAAN contains certain fields that must be completed before your protocol can be submitted and reviewed. In many cases this information is required by federal agencies. The REQUIRED sections are highlighted in red. The sections outlined in blue are not required UNLESS they are applicable to your research study. Required fields are different for protocols that are being considered for exempt review. The Review for Completeness feature will check that all of these fields have been completed before the protocol is submitted to HRPO. Many fields contain pull down lists of choices to facilitate completion.

A successful submission requires a complete and through response to all sections of the BRAAN protocol. Reach each section carefully and respond to every item within each section.

BRAAN also creates the consent form for you and will include all required institutional language. See section Q under the Protocol Form section.

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Navigate the Form

Navigate through the form using the “Go to Section” icon on the top of each page. Each section of the form opens independently so save your work in one section before moving to another section.

indicates a searchable field. For instance, if you want to change the department field, type in the name of the department and hit the <TAB> key. BRAAN will fill in the data if you typed in a unique name or open a search result screen to allow you to select between choices. If you get the search result screen, click on your choice. BRAAN will then automatically fill in the data for you and return you to the protocol form.

Saving

In order to be FDA compliant with Title 21 CFR 11 the system will time you out after being inactive for 60 minutes. Inactive means that you have not hit the save button within the last 60 minutes. After 40 minutes of being inactive BRAAN will warn you that you have been logged in for 40 minutes, but have not saved. Hit Save ASAP. If BRAAN logs you out and you have not hit save within 60 minutes ALL of your information will be lost. Each time you hit the save, next, and the back buttons your 60 minutes will start over.

Logging Out

To properly log out of the BRAAN protocol click on the orange close button within the application and log out using the “log out” button on the tool bar to the left.

DO NOT click on the X in the upper right hand corner of the screen. Clicking on the close button within the BRAAN application will provide a prompt to the investigator to say changes before closing. Clicking on the X in the upper right hand corner will not provide this prompt and your change will NOT be saved and the protocol will be locked. BRAAN does not recognize closure through the X button. The only way to unlock a protocol is to have the person, who locked it:

• Log in • Open the protocol like they are going to edit/submit it • Hit save • “Close” out of the protocol properly by using the close button within the

BRAAN application • Log out of BRAAN properly using the log out button.

Enter Data - BRAAN will auto populate section A2 of a newly drafted protocol, the name and demographic information of the PI for the protocol.

If you are not the PI, but still need access to the protocol either for read or read/write privileges, you will have to contact the PI to have him/her add you to the protocol under the Set Privileges section.

You do not have to complete the form in one sitting. If you exit the form before sending to HRPO, BRAAN will save the protocol as a draft. You and/or anyone to whom you have given read/write privileges will be able to access the protocol.

Edit a Saved Draft - You can Edit or Remove a protocol any time prior to submitting it to HRPO. Protocols returned to you for revisions by the committee (Board Modifications Required), can also be edited. When a protocol is under the Draft or Pending section, from “What would you like to do?” select Edit/Submit Protocol / GO. You can edit and save as many times as you would like. The protocol will remain in draft or pending until the PI submits it.


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Protocol Form The ‘Go to Section’ icon at the top of each page allows you to jump through the protocol sections without having to proceed sequentially through the application.

Section Aa: Title and PI

Section A1 - The Protocol Title – There should be no spelling errors

Section A2 - The PI – The PI’s current contact information and correct School, Department, Division and Center should be listed here. If the PI is not associated with a Center choose NONE. If the Division is incorrect for the PI the system will not let you submit a new protocol for signatures. A message indicating that no signatory has been assigned to the protocol will appear. If you receive this message, change the PI’s Division and hit SAVE.

If the PI has any kind of financial interest in the study, s/he is required to complete the Economic Disclosure Form and submit it via campus mail to HRPO – HSF I Rm. 146

****Make Note – If the contact information in BRAAN is incorrect or you need to update your BRAAN account, contact the SOM help desk at 410-706-3998 for assistance.

Section A3 - The PI’s administrative contact – This should be the primary contact person for the study outside the PI. Same as above regarding the economic interest.

****Make Note – Adding someone to this section will automatically provide her/him with read/write privileges to the protocol. Removing someone from this section will automatically delete their privileges.

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Section Ab: General Information

Section A4 – Research Team – All members of the protocol team should be listed in this section. Do not add the PI or the administrative contact to this section or you will receive an error message. Adding someone to this section DOES NOT provide them with read/write privileges. Deleting someone from this section will delete their privileges if previously set. Same as above regarding economic interest.

Section A5 – Funding Sources – You can choose more than one if applicable. The protocol # text box should contain the industry sponsor’s protocol # NOT the IRB #. If your protocol is industry sponsored a copy of the Industry Sponsored Billing Form must be attached in section S. The form can be found at:

http://medschool.umaryland.edu/orags/hrpo/newproject.asp

Section A6a – Institution(s) Where Recruitment or Other Work Will be Performed – This section indicates where study subject are recruited and where study visits occur, i.e. where patients are seen for the study. More than one institution may be selected by using the control key on your keyboard. Selecting the VAMHCS as a site will automatically generate the consent form on the 10-1086.

Section A6b – Research Conducted Outside the US – Complete this section as indicated.


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Section B: Review Path Determination

Section B1 – Review Path Determination - Includes questions taken directly from the Code of Federal Regulations and is used to automatically determine if the study meets the criteria for expedited review or full board review. This determination is the PI’s initial attempt at what s/he considers as review type. The IRB can disagree and request the review type be changed.

****Make Note – Selecting the first bullet “Emergency Situation” indicates that you are requesting the one time use of a test article, investigational drug/device. This option should not be selected if you are in jeopardy of losing funding.

Section B2 – Exempt from UMB IRB Review – Research that is exempt from IRB review is defined in the regulations and presented in this section. If you choose NO or N/A for all of section B1, and choose one of the categories for exemption the system will consider your protocol for exempt review.

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Section C: Justification

Section C – Justification - This section includes background information (i.e. pharmacology, pre-clinical data, results of clinical studies conducted to date and relevant literature summaries), a review of disease process under investigation, and the rationale that justifies conducting the research being proposed.


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Section D: Purpose

Section D – Purpose and Objectives - This section should contain the primary and secondary objectives and/or hypotheses for the research study. There should be clarity and consistency between the full protocol, the BRAAN protocol and the consent document regarding the purpose of the study.

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Section E: Protocol Risk/Subjects

Section E1 – Risk Category - This section is the basis for determining the level of monitoring appropriate for the study. Level I = Minimal Risk; Level II = Low Risk; Level III = Moderate Risk; Level IV = High Risk. The assigned level of risk should be appropriate for the research being proposed. The IRB can disagree with the investigator’s perception of risk categorization and request it be changed.

Section E2 – Subjects –

Gender, Age, Race/Ethnicity

If the study is going to compare different subgroups of the population that is being enrolled, the PI should justify his/her enrollment plan (section F1) and outline the statistical analysis plan (section G). The number of subjects enrolled and the proposed statistical analysis should have enough power to differentiate between the identified subgroups.

***Make Note - The Age # found in parentheses is not your “specific” inclusion criteria. The inclusion criteria will be delineated in section F1. The age in this section is to make you aware of how Maryland state differentiates between infants, children, adolescents, adults and elderly.

Primary Language – The consent form should be written in English and put in section Q. If a foreign language consent form is required, it should be attached in section S as a word document along with a certified translation of the English consent into the required language.

Vulnerable Populations – If you are using a federally defined group of vulnerable subjects, the “Additional elements of informed consent” as stated in 12 CFR 50.25(b) are mandatory and should be incorporated into the consent form. Also, provide the committee with a plan to reduce their risks.

If you are not using a federally defined group of vulnerable subjects, (i.e. students/employees), provide the committee with a plan to reduce their risks.


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Section F: Design/Procedure

Section F1 – Design – The study design should match the purpose of the study.

Phase I – Initial tests of safety in humans, usually in normal, healthy volunteers. These studies usually include a limited number of subjects (~20). Risk category is usually High.

Phase II - Initial testes of efficacy for the disease/condition under investigation, in relatively small populations of patients (~50). Some studies may include health volunteers. Risk category is usually Moderate or High.

Phase III – These are usually multi-center, randomized, double-blind studies that compare an investigational product to the standard of care in large numbers of patients (~100/site, thousands worldwide). Some Phase III studies may be placebo-controlled. Risk category is usually Moderate or High.

Phase IV – These studies are conducted with FDA approved drug(s) or device(s). They may be marketing studies to determine consumer acceptance of the product, economic impact studies of the drug or device, and long term safety studies. Risk category is usually Low or Moderate.

Pilot – Preliminary study to generate a hypothesis and determine if conducting a larger study is feasible, e.g. to determine if there are enough individuals with the condition to be studied. Risk level will correspond with type of research.

Text box (1) – Research design should be appropriat e to meet the study objectives. Text box (2) - Inclusion/Exclusion Criteria – This should consist of a numbered list of the criteria. The inclusion/exclusion criteria should match the full protocol.

Section F2 – Data and Safety Monitoring – All studies require safety monitoring. The UMB IRB has developed four risk categories that apply to the studies – minimal, low, moderate and high. Three levels of safety monitoring apply to these four categories of risk – Protocol Safety Officer, Internal Data and Safety Monitoring Board (DSMB) and External DSMB. Any minimal risk study that utilizes the General Clinical Research Center (GCRC) must have a monitoring plan, but otherwise, minimal risk studies are not required to have a detailed monitoring plan other than PI review. Low, Moderate, and High risk studies MUST have a detailed Data and Safety Monitoring Plan (DSMP).

The HRPO has standard forms found on our website at: http://medschool.umaryland.edu/orags/hrpo/qualitymanagement.asp or within this section of BRAAN this is a hyperlink that you can click on to get to the forms. The monitoring plan should be described in section F2 or attached in section S.

Section F3 – Procedures – Describe all the procedures the subject will undergo as a participant in the study, including but not limited to: pre-study screening tests and evaluations, randomization and/or blinding procedures, on-study clinical evaluations, tests and interventions, safety management, subject withdrawal criteria, and study termination criteria. This section should be consistent with the full protocol and consent form.

Section F4 - Study Schedule - Instructions for creating a study schedule are found within BRAAN. ALL research proposals, other than studies exempt from IRB review, require a study schedule. The study schedule should be consistent with section F3, the full protocol and the consent form.

If you have problems creating a study schedule within BRAAN, please attach a word document of your study schedule in section S.

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Section G: Sample Size/Data Analysis

Section G1 – Sample Size – Number of subjects anticipated to be enrolled in the study should be listed in the local and worldwide boxes. Both “local” and “worldwide” boxes need to be completed. Local = the number being enrolled at this site and Worldwide = the number being enrolled total at other sites (multi-center). If your study is a single site study the number of subjects being enrolled locally should equal the number of subjects being enrolled worldwide.

Text box (1) – Rationale/Justification for the sample size. For example, how this sample size will be sufficient to address the objectives of the study. The number of subjects being screened should be listed in this text box, NOT included in the local and worldwide boxes.

Section G2 – Data Analysis – Discuss data handling, reporting and storage.

Efficacy – describe the efficacy variables, the primary and secondary endpoints, and the analytic plan.

Safety – describe how safety will be measured and what analyses will be performed.


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Section H: Potential Risk/Discomforts

Section H – Potential Risks and Discomforts - Delineate the risk associated with participation in this research study. There should be a description of the measures that will be taken to minimize the risks. The risks should be consistent with the full protocol and should be outlined in the Risks/Discomforts section of the consent form.

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Section I: Potential Benefits

Section I – Potential Benefits –

Text box (1) – Describe potential benefits to the subject. If there are no potential benefits to the individual subject, it should be stated.

Text box (2) – Describe potential benefits to society. If no benefits to society are expected, this should be stated, and justification for conducting the research should be provided.

Text box (3) – Discuss the Risk/Benefit ratio. Do anticipated benefits outweigh potential risks? Are the potential risks to the participant too great for the study to be undertaken? If not, justify why not with adequate rationale.

Do not overstate the benefits to participation and payment for participation is NOT a benefit.


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Section J: Consent Procedures

Section J1 – Consent Procedures

Anyone who is recruiting or obtaining consent should have the proper training to do so, i.e. CITI training – www.citiprogram.com and on campus training offered by CCT and/or HRPO.

Text box (1) – Include the list of people who will be involved in recruiting subjects for the study. More than one person may be listed. Titles may also be indicated instead of names, i.e. PI, CO-PI, CRC.

Text box (2) – Describe the process of how initial consent will be obtained and documented, as well as ongoing consent throughout the study. Describe any special provisions that will be made, if applicable (i.e. subject is not competent/able to provide consent at the time of enrollment, but at some point during the study, recovers sufficiently to provide consent). Include a description of any instruments/tools used to document competency. Describe procedures for ongoing consent or how a review/discussion of the consent will happen with the subjects in the future. Discuss who will be obtaining consent and what the setting will be.

Section J2 – Waiver of Consent

Health Insurance Portability and Accountability (HIPAA) regulations state that either an authorization (consent) to access Protected Health Information (PHI) or a waiver of consent (authorization) is required for any research. Three situations in which a waiver of consent may be required include:

(1) Consent waiver – A waiver of consent regulations 45 CFR 46.116 and 21 CFR 50.20, 25 is necessary to conduct research.

(2) Privacy waiver – the objectives of the study cannot be met without having access to PHI

(3) Partial privacy wavier – recruitment for the study cannot be done without having access to PHI

If you answer yes to any of the check boxes in this section, all text boxes relating to justification for requesting the waiver, in this section are required to be completed.

If you are requesting an exemption, this section can be skipped. If you are requesting expedited review this section must be addressed.

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Section K: Confidentiality

Section K1 – Confidentiality - The questions in this section are used to gather information about the privacy and confidentiality of the research data. For example, where the research data will be kept and secured, who will have access to the data, and other potential confidentiality issues related to the study.

Certificates of Confidentiality are issued by the National Institutes of Health (NIH) to protect identifiable research information from forced disclosure. They allow the investigator and others who have access to research records to refuse to disclose identifying information on research participants in any civil, criminal, administrative, legislative, or other proceeding, whether at the federal, state, or local level. Certificates of Confidentiality may be granted for studies collecting information that if disclosed could have adverse consequences for subjects or damage their financial standing, employability, insurability, or reputation. By protecting researchers and institutions from being compelled to disclose information that would identify research subjects, Certificates of Confidentiality help achieve the research objectives and promote participation in studies by assuring confidentiality and privacy to participants. For more information, see link below

http://grants2.nih.gov/grants/policy/coc/index.htm

Section K2 – HIPAA – If the investigator plans on using a subject’s protected health information (PHI), a HIPAA authorization form is required. The HIPAA authorization form can be downloaded by clicking on the hyperlink in BRAAN or can be found on the HRPO website at:

http://medschool.umaryland.edu/orags/hrpo/hipaa.asp

The form should then be attached in section S of the BRAAN protocol for IRB review.


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Section L: Cost/Payment

Section L – Cost/Payment – Answer all of the questions presented in this section. List the total dollar amount paid to the subject (for completion of the study) in the box, and describe the payment distribution plan. List any costs the subject will incur as a result of participating in the study, and describe the payment plan to be followed in the event the subject withdraws or is withdrawn from the study prior to completion. Will the subject receive full or prorated payment if s/he withdraws from the study due to an adverse event?

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Section M: EHS/Genetics

Section M1 – Environmental Health & Safety (EHS) – If your protocol involves radiation, please contact EHS to determine whether or not your protocol requires review and approval by the Radiation and Safety Committee.

http://www.ehs.umaryland.edu/

If your protocol requires review by the Radiation Safety Committee, click the check box and put in the EHS # text box PENDING, to inform the IRB that you have submitted your proposal for Radiation Safety approval. If you have already obtained Radiation Safety approval, click on the check box, put the EHS # in the text box and attach a copy of the Radiation Safety approval letter in section S.

Please make note – Once you have received Radiation Safety approval the approval letter should be attached in section S and the IRB should be made aware via an amendment. Also, the consent form should also have language in the risks/discomforts section regarding the risks of the radiation. This language should be provided by EHS.

Section M2 – Genetics – If your protocol involves genetics please answer all of the questions in this section. The consent form should include a section with spaces for the subject to indicate (by signature or initials) his/her consent, or refusal to consent, to the future use of his/her biological samples. For example:

“I agree to allow my samples to be used for research purpose in the future.”

_________YES _________NO

Additionally, include a statement concerning the subject’s right to withdraw consent, with pertinent contact information, and the circumstances under which s/he may be able to withdraw consent (i.e. if the samples have already been analyzed).


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Section N: Sample Collection

Section N – Sample Collection - This section is collapsed unless you are collecting sample(s) for RESEARCH purposes. If you are collecting sample(s) for RESEARCH purposes, click on the + sign to Add New Samples. This opens up a list of questions that apply to sample collection. Choose the Sample type that will be collected from the drop down menu, and then answer the questions below it with regard to that specific sample. Multiple sample types can be entered by clicking on the + sign again.

The investigator should describe each sample collected for RESEARCH purposes, and the specific reason the sample is being collected, i.e. genetic testing. If more than one sample is being collected, the PI can copy and paste from one sample to the next, or from another protocol(s), and modify as necessary. The source of the research samples should be specified (i.e. directly from the subject, from samples obtained previously from the subject, from an outside source such as a blood bank, etc.) and included in this section. Some of the information in this section may be relevant to obtaining consent from a potential research subject and should be addressed in the consent form.

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Section O: Drug Studies

Section O1 – Drug Studies - This section asks questions about ANY drugs involved in the study. All four questions, including those related to placebo use, should be addressed. If applicable, the Investigator Brochure, Package Insert, and/or Investigational Drug Information Sheet should be attached in section S.

Section O2 – Indicate Drugs to be Used -

Text box (1) – List the agents (biologics, drugs) being used in the study. The Source of the drug(s) supplies and storage conditions of the drug(s) should be specified. If the study is being conducting under an IND, the IND # should be indicated in this section. If the study is NOT being conducted under an IND, the justification/rationale for this must be clear and adequate. How does the research affect RISK to the subject?

Text box (2) – Describe how the PI and the institution are complying with the Federal regulations. Assistance is available from the HRPO on the web at http://medschool.umaryland.edu/orags/hrpo/ or by telephone at 410-706-5037.


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Section P: Device Studies

Section P – Device Studies - This section asks questions about the risk of any device involved in the study. All questions should be answered if the study involves a device. If the study is being conducted under the HUD/IDE regulations then the sponsor and HUD/IDE # should be specified. If the study is NOT being conducted under the HUD/IDE regulations, then justification/rationale for this must be clear and adequate. How does the research affect RISK to the subject? What are the risks if the device malfunctions? If the device is implanted into the subject, will it be explanted at the end of the study? If so, what are the procedures, risks, and benefits of explanation? If the device will not be removed from the subject, what are the long-term risks and benefits of the implant?

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Section Q: Consent Form

Section Q – Consent Form(s) – By selecting YES to the question “Is a consent form (CF) required for this protocol?” and hitting the save button, the system will automatically generate the CF template for you to follow when completing your CF(s). To add more than one CF, click on the + Add New Consent Form link and hit Save. The system will automatically generate another CF template BELOW the initial CF.

Consent form description - The purpose of this section is to distinguish between different CF’s used for the study, i.e. patients, controls, assent, etc. This section is NOT meant for typing in the title of the study (the system automatically does that for you). Some investigators use this section to list the names and contact information of the research team.

Background – This section should include background information related to the disease process under investigation and the general rationale for the study. An explanation of why the subject is being asked to participate in the study is included in this section. Please make note – BRAAN automatically inserts the sponsor(s) of the study in this section.

Purpose – This section should include information on why this study is being conducted – the purpose.

Procedures – This section should specifically outline the procedures the participant will undergo by participating in the study. Below is the guidance that BRAAN provides on what should be included in this section and this should be adhered to:

Procedures should include, but not be limited to: The overall design of the study, including methods and probability of assignment, randomization, controls and placebos; Procedures to be performed, including frequency and follow-up; Clarification of procedures/test articles that are investigational or included solely for research purposes and those that are standard clinical care; Medication or other intervention (including placebos) to be administered and the method, dose, and frequency of administration; Number, frequency and duration of visits; Specimens to be collected, including frequency and size/amount; Specify both blood drawn each time and total amount of all drawings in teaspoons (5cc = 5 ml = 1tsp); samples taken for safety monitoring of research subjects should be described here; If specimens taken will be used for any purpose other than as required for the study protocol, disclose the intended use; Specific requirements of the research subject, including post-treatment follow-up, diary cards, questionnaires, etc.

Potential Risk/Discomforts – This section should delineate the risks of the RESEARCH, including severity and frequency of anticipated adverse events (use words such as mild, moderate, severe, rare, occasional, frequent, likely, most likely, common, less common – not percentages). It may be appropriate to include a statement that participation in the study may involve risks that are currently unknown or unforeseen. NO CF should include a statement that “no risks are involved with participation in this study,” even in the case of minimal risk studies.

Potential Benefits – This section specifies the benefits, if any, of participating in the study. These benefits could be (1) none (2) to the patient (3) to society and (4) to both the patient and society. DO NOT OVERSTATE THE BENEFITS.

Alternatives – Unless the study includes ONLY healthy volunteers, there are alternatives treatments, other than not participating in the study. Describe the alternatives – what is the available standard of care (SOC)? What other investigational studies are available to the patient .

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Section Q: Consent Form – Cont’d

Subject Costs/Payments – If the default language is not appropriate for your study, the investigative team can delete it. Be sure to delineate all costs to participants, i.e. parking. Payments to participants and the plan for distribution of payment (i.e. prorating, payment at each visit, payment upon termination) should be specified.

Subjects’ Rights – This section includes the right to withdraw, the confidentiality statement, and the medical injury statement. The boilerplate language for this section is automatically inserted into the CF and is only visible through the print/view option (printer icon) of the CF. The investigative team should review the boilerplate language prior to developing the CF so as not to duplicate information.

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Section R: Advertisements

You can add as different types of advertisements in this section. Include the exact language for the advertisement in the text box. This is the language the IRB will review. Attach copies of your recruitment flyers, posters, etc. in section S, so that the IRB can determine if the it is balanced. The exact language is approved with the protocol submission and must be used for all advertisements, i.e. posters, flyers, etc. Use of any other language is a violation of the IRB approved protocol and federal regulations, and could be grounds for suspension.

Advertisements should not overstate the benefits, overemphasize the payment, or have misleading text. There should be no claims of safety, efficacy, equivalency or superiority in the ad.


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Section S: Attachments

This section allows for attachments of the full protocol, investigator’s brochure, full grant for federally funded protocols, questionnaires, recruitment flyers, etc. Any document that the IRB needs in order to adequately review your protocol should be attached in section S. An unlimited number of attachments can go into this section, but the maximum size of any one attachment is 4.5 megabytes.

If an attachment(s) is too big (>4.5 MB) to upload in section S, a copy of the attachment(s) can be put on a floppy or CD and delivered to the HRPO main office. The discs should be labeled with the protocol # H- along with the name and phone number of who to return the disc to. The HPRO will then attach the file(s) through the oracle database.

There are two different ways to view attachments in BRAAN:

(1) To view attachments uploaded through section S – open “What would you like to do?” and select View/Print Protocol. When the protocol opens you will see a paperclip icon in the upper left hand corner. Click on the paperclip to view your attachments found in section S.

(2) To view attachments uploaded by the HRPO through the oracle database – open “What would you like to do?” and select “Sponsor’s Protocol / Grant / Brochure”. The attachment will display. From the demographics page of any study, you can see if the full protocol is attached.

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Submit a New Protocol

Review for Completeness

The system can review the document for completeness. Only the PI has the button to send the protocol forward for signatures.

To send a protocol to HRPO for committee review, select “Review for Completeness” from the Go To Section. Click the “Review” icon. BRAAN will revi ew the document for completeness and will produce a list of items needing attention before it will submit the protocol to HRPO.

Use the “Go To Section” to return to sections requiring attention, make the necessary changes and continue to Review for Completeness until your protocol is ready to submit to HRPO.

Once your protocol is ready to be submitted you can use the “Go to Section” to go to the “Certification/Submit for Approval” page of the application. You will then need to click on the “GO” button at the bottom of the screen.


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Certify A Protocol

The last page of the form contains statements of certification from the PI. When the PI submits the protocol they are “signing” these statements and the content of the protocol.

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Submit A Protocol

After completing the protocol form, from the last page of the protocol, click “GO” to either submit the protocol for signatures or to the HRPO. Remember, only the PI can submit – this serves as your electronic signature. The protocol will move from your Draft menu, to the Pending menu and will be listed as Submitted once the signatory signs off on it.

If the signatory or HRPO has any questions about the protocol, you may receive an email, from the system, indicating the protocol has been returned to you along with a description of the reasons why. The protocol will also appear with reds stars in your View protocols sections, just in case you did not receive the email. When the protocol is ready for re-review, the PI will need to re-submit.

Once a protocol has been signed off on and is “submitted” to the HRPO for review, an IRB Analyst will be automatically assigned to your protocol and will stay with the protocol as long as it is active. The IRB Analyst is for your protocol can be found on the demographic page. For protocol specific questions you should contact the IRB Analyst assigned to your protocol by phone at 410-706-5037 or via email at [email protected].


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Reports Reports exist within the BRAAN system. They are user / role specific. With the Investigator role, you can view, print, and export the following reports: Closing Report and Protocol History Report).

Closing Report creates a table of human or human protocols that are due to expire within the number of days you indicate.

Protocol History Report (all) creates a table of the history of all protocols with which you are associated and displays their versions, statuses, and dates.

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Submit A Protocol

After completing the protocol form, from the last page of the protocol, click “GO” to either submit the protocol for signatures or to the HRPO. Remember, only the PI can submit – this serves as your electronic signature. The protocol will move from your Draft menu, to the Pending menu and will be listed as Submitted once the signatory signs off on it.

If the signatory or HRPO has any questions about the protocol, you may receive an email, from the system, indicating the protocol has been returned to you along with a description of the reasons why. The protocol will also appear with reds stars in your View protocols sections, just in case you did not receive the email. When the protocol is ready for re-review, the PI will need to re-submit.

Once a protocol has been signed off on and is “submitted” to the HRPO for review, an IRB Analyst will be automatically assigned to your protocol and will stay with the protocol as long as it is active. The IRB Analyst is for your protocol can be found on the demographic page. For protocol specific questions you should contact the IRB Analyst assigned to your protocol by phone at 410-706-5037 or via email at [email protected].


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News Page / Log in Screen The HRPO will post important information regarding education and training sessions, conferences, BRAAN glitches, new research requirements, contact information, system downtime(s), office closures, etc. Please make sure to read the BRAAN news page at least once a week for important updates. All information posted on the BRAAN news page is archived for reference in the future. The archived BRAAN news can be found at:

http://medschool.umaryland.edu/orags/hrpo/braan_news.asp

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Appendix A: Version Table

There are a couple of terms that describe and define work passing through the BRAAN application. What an item is, is its version. Where an item is, is its status. Version and status interact as protocols move through the process and you will often see them listed together. Common versions include: amendment, renewal, and new. Common statuses include: draft, submitted, and approved.

Version: Definition:

Amendment Version of a study that is different from the currently approved version. Revisions have been made to the Protocol and/or Consent Form.

Approved with modifications

Version of a study that has been reviewed by the IRB and will be approved once minor issues have been addressed by the PI, resubmitted, and the response approved by the IRB.

Approved with modifications/ amendment

Version of a study that is different from the currently approved version (revisions were made by the PI). It has been reviewed by the IRB, and will be approved once minor issues have been addressed by the PI.

Approved with modifications/ renewal

Version of a protocol that is undergoing or will undergo continuing review and, upon approval, will become the approved/active version of the protocol. It has been reviewed, and will be approved once minor issues have been addressed by the PI.

Approved with modifications/ Deferred

Version of the protocol that was reviewed by the IRB and requires major modifications. The protocol will need to be re-reviewed by the convened IRB if greater than minimal risk.

Approved with modifications/ deferred/renewal

Continuing review version of the protocol that was reviewed by the IRB and requires major modifications. The continuing review will need to be re-reviewed by the convened IRB if greater than minimal risk.

Approved with modifications/ deferred/ amendment

Amendment version of the protocol that was reviewed by the IRB and requires major modifications. The amendment will need to be re-reviewed by the convened IRB if greater than minimal risk.

New Latest, most recent version of any piece of work.

Renewal Version of a protocol that will undergo continuing review and will become the active version upon approval.

Deferred Version of a protocol that was reviewed by the IRB and the PI received significant issues, to which they must respond for further consideration. Response to issues must be reviewed at a convened IRB meeting if greater than minimal risk.

Deferred/ amendment

Amendment version of a protocol that was reviewed and the PI received significant issues, to which they must respond for further consideration. Response to issues must be reviewed at a convened IRB meeting if greater than minimal risk.

Deferred/renewal Continuing review version of a protocol that was reviewed and the PI received significant issues, to which they must respond for further consideration. Response to issues must be reviewed at a convened IRB meeting if greater than minimal risk.


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Appendix B: Status Table

Status: Definition: Business Rules/Notes:

Administrative modifications required

A submitted protocol has been returned to the investigator by the HRPO prior to being assigned to the IRB for review. This is done when the HRPO staff completes their pre-review of the application and finds an issue(s) that they feel needs correction/completion prior to being routed for IRB review.

The protocol is returned to the PI in pending status so they can make changes on the application form and resubmit. The resubmission does not re-route for signatures.

Approved A study has successfully completed the review process and is active.

Must be re-reviewed at intervals no greater than 365 days.

Archived A study or version of a protocol that is no longer being drafted, reviewed, or utilized.

Archived studies are always accessible. You can report adverse events on archived/closed studies. Closed studies are archived. Non-active versions of any study, even approved, are archived.

Assigned to committee

A study is receiving review by the fully convened IRB and has been assigned to board members for that review.

Always means “Full Board Review”.

Awaiting signature

A protocol has been submitted by the PI, routed to those in the signatory path according to the UMB’s business rules, and will be submitted to the IRB only after all signatories have signed.

Will route simultaneously. Last required signature will send protocol to the HRPO for consideration.

Board modifications required

The IRB has reviewed the protocol and has questions/issues the PI must address before the protocol can be approved.

The PI must respond to the board modifications, make changes in the BRAAN protocol and or consent form (if requested by the board) and resubmit the protocol for further consideration.

Closed Protocol that represents a study that is no longer active.

When all versions of the protocol have been archived the protocol is closed. Protocols can be closed by the PI or by the system if they do not receive continuing review prior to their expiration date.

Disapproved A protocol that the IRB considers to be unethical as submitted.

Only the fully convened IRB can disapprove a study.

Draft A protocol or version of a protocol that is being drafted, modified, revised, and has not yet been submitted to either the IRB office or the signatories.

There is no time limit regarding how long a protocol can stay in draft status. Only the investigative team knows of protocols that are in draft. Other system users do not have view access to protocols in this status.

Exempt A protocol that does not require IRB review according to the criteria outlined in 45 CRF 46. Exempt status is determined by the IRB, not the PI; therefore, a submission through BRAAN is required.

Exempt protocols are in a closed status once they are approved, but the closed version of the exempt protocol is maintained in the system for data tracking purposes.

In Review A study is receiving expedited review and has been assigned to the EC for that review.

Always means “Expedited”

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Request closure Closure has been requested by the PI, on an approved study.

You can report AEs on closed studies. Closed studies cannot be reactivated, but they can be copied by the PI when creating a new protocol.

Request withdrawal

Withdrawal of the transaction (protocol/amendment/renewal/AE) has been requested by the PI, on what is being considered/ reviewed by the IRB, but has not yet been approved.

Once a piece of work has been withdrawn it can not then be reconsidered.

Resubmitted for signature

Protocol was resubmitted by the PI through the signature path after having been returned unsigned and then corrected.

Resubmitted for signature studies are re-routed to all people in the signatory path, not just the signatory that had an issue.

Returned unsigned

Signatory considered some aspect of the protocol to have scientific review issues and returned the protocol to the PI for correction before signing and sending the protocol to the HRPO.

PI must revision their submission in order to resubmit. Issues and responses are documented. When a returned unsigned protocol is resubmitted it will reroute to all signatories.

Submitted A new piece of work has been sent to the HRPO for consideration.

The IRB Analyst assigned to the protocol will pre-review protocol and triage (return to PI, send to EC, send to board) the protocol accordingly.

Suspended An active protocol has been temporarily put on hold. Protocols are usually reactivated after remediation. Suspension can be for any length of time.

Withdrawn A protocol/amendment/renewal/AE that is being considered/ reviewed, but has not yet been approved, has been removed from all further consideration. Like closed but on a transaction that has not yet received approval.

Once a piece of work has been withdrawn it can not then be reconsidered.


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Appendix C: Action Table

There are many actions that be performed within the BRAAN system. Who can do what, to what, and under what conditions, is determined by your system administrator via an internal table called workflow. If you feel you need to be able to perform an action that is not currently listed for you under the “What Would You Like to Do?” dropdown list, please contact your system administrator. Please make note – The options under the “What would you like to do? will change depending on where your protocol is in the review process.

Actions: Definition: Also called:

Request Closure Opens the final report form for someone on the investigative team, with read/write privileges, to complete and submit for approval.

Opens Closure form

Report Adverse Event (AE) Opens the AE form for someone on the investigative team with, read/write privileges, to complete and submit for review and acknowledgement.

Opens AE form

Amend Protocol Opens the Amendment form for someone on the investigative team, with read/write privileges, to complete and the PI is responsible for submitting to HRPO.

Opens amendment form

Report Deviation Opens the deviation form for someone on the investigative team, with read/write privileges, to complete and submit for review and acknowledgement.

Opens deviation form

Request Exception Opens the exception form for someone on the investigative team, with read/write privileges, to complete and submit for review and acknowledgement.

Opens exception form

Remove/Delete protocol Deletes any transaction (new/amendment/renewal/AE, etc.) that is in draft status.

Deletes protocol

Edit/Submit protocol Opens the BRAAN Protocol form for someone on the investigative team, with read/write privileges, to complete (edit) and the PI is responsible for submitting to HRPO.

Edit or Submit protocol

Renew protocol Opens the Renewal form for someone on the investigative team, with read/write privileges, to complete and the PI is responsible for submitting to HRPO.

Opens Continuing Review form

Request withdraw Allows PI to remove a transaction from HRPO consideration.

Withdraws protocol

Search adverse events Opens AE report generator to allow investigative team to run a report on AE’s for a specific protocol.

Creates a report of all or a specific criteria of AE’s

Set privileges Determines what level of access someone will have to a specific study.

Provides read/write or read/only access to a specific protocol.

View protocol deviations Opens a report on all deviations for that protocol View deviation report

View protocol exceptions Opens a report on all exceptions for that protocol View exception report

document

Documents

braan log

protocol protocol form

braan passwords

research protocol

protocol submission

assurance network braan

protocol creation

action table braan overview