Society for Clinical Trials, 37th Annual Meeting Leveraging online technology for purposes of remote monitoring throughout the protocol lifecycle Dee Blumberg, Donna Brown, Ashley Case, Kayla Daniels, Anne Hoehn, Oscar Moreno May 15, 2016 Society for Clinical Trials, 37th Annual Meeting Hello, I am going to be discussing reviewing informed consents using a remote review process. Before I begin – is there anyone that has used a remote review process for reviewing ICFs?

Remote Consent Monitoring Review of Informed Consent or other document through Electronic Data Capture (EDC) system Review ICF documents remotely Quicker reviews / ‘real time’ review Can be used for other regulatory document Identify errors more quickly Reduce number of reoccurring errors Increase productivity at site visits Review a percentage of regulatory documents and focus on other issues remainder of visit This remote review process can be used for ICF and other regulatory documents that are sensitive in nature and contain PHI Because this is a remote process, the review can happen much sooner than waiting for an on site visit which may occur 3 to 6 months after enrollment at the site has begun. This helps by reducing the number of ICFs that need to be reviewed at one time. Since it is ongoing process, we can review every day or every other day, rather than review several months worth of ICFs at one time. If we can review earlier, we can identify errors that are reoccurring and discuss with the site staff. Traditionally during onsite visits 100% of the ICFs were reviewed; however, with the remote review, 100% are reviewed remotely and only 10% are reviewed during the site visit. This allows the site monitor to focus on other issues

Possible drawbacks and solutions Uploading documents for the wrong participant Create a report that links participant name and participant ID Reviewing out of date / expired documents Create reports to identify important dates for each site Date of ICF approval Number of pages expected in ICF Responses/scores for quizzes Security Training Restrictions on access Restrictions within the system In our current study we were lucky that the study includes a Locator form, so we were able to create a report that is viewable only to the regulatory reviewer that links the ppt name and ppt id. For protocols that do not utilize the locator form, another method of identifying the ppt name vs ppt id will need to be determined In multi site protocols where each site has their own IRB it can be difficult to keep track of the different IRB requirements, the dates of approval and expiration and so on. We have created a report that the Regulatory Reviewer maintains that documents the most recent and up to date IRB information for each site. This way you can ensure that you reviewing the appropriate ICFs ICFs contain sensitive information and there is the very real security concern. We have addressed this by providing ample training for both the site staff and the regulatory reviewer. We have set up restrictions on access – only sites with IRB approval of the process can receive access and only site staff that have been trained. And lastly we have set up restrictions within our system.

IRB considerations Provide clear background Provide details on security Provide details on GCP and 21 CFR adherence With the current out current protocol that is using the remote consent process we provided a memo to each of the sites IRBs You can find an example of that memo in your binder Within the memo we provided clarity on the process, and why we felt it would be beneficial to implement. We additionally provided some of the details about the system security and clarified that we are GCP compliant and adhere to 21 CFR. All users will have a unique username and password and we have an audit trail that documents information that is entered. None of the IRBs where this was submitted had any questions or concerns about the process.

Processes Site: Reviewer: Follow-up: Page 1 is completed by site staff Page 2 is completed by site staff and document(s) uploaded Reviewer: Page 3 is completed by regulatory reviewer Follow-up: When Page 3 is saved, comments are emailed to designated staff and site staff that uploaded document Corrected document re-submitted by starting process over (new Page 1 and 2 completed; new Page 3 for review) The remote consent upload process consists of three forms. The first page is completed by site staff and is a ‘summary’ or checklist of the document(s) that they are uploading Page 1 is not reviewed by regulatory staff’ Page 2 is the form where the actual document is uploaded. Page 1 and page 2 have been separated because page 2 and the uploaded document are deleted from they system. Lastly, page 3 is completed by the regulatory reviewer. When the regulatory reviewer saves page 3 site staff who loaded the ICF will receive an email notification; I will discuss this in more detail in a few minutes. Whenever there is corrective action needed, the entire 3 page process begins again.

Set up in Electronic Data Capture System Form 1: Checklist for site As I mentioned the first page (please note that there is also a paper copy in your binder) asks specific questions about the information that the site staff is uploading. The first several questions are regarding ICF. Please note that in your paper copy, there are additional questions that are related to other regulatory documents that may be uploaded. So the staff member will review the information in the document that is being uploaded and answer the questions in page 1. This is a good review for the staff an may identify an error before the file is uploaded. For instance, Q1b asks when date written informed consent obtained – if they look at their ICF that is being uploaded to get the date, and they notice the date is missing, they can address this issue before uploading the consent. Once the questions are answered and the form saved, the site staff will move to page 2.

Set up in EDC system cont Form 2: Document upload form Page 2 is also completed by site staff We have provided an example for the staff of an acceptable file name for the uploaded ICF and we ask them to confirm in Q1 that there isn’t PHI in the file name. Then click upload file and upload the ICF It is important to note that once the file is uploaded, the ONLY person that can review this file is the regulatory reviewer. When that form is saved, the ICF is uploaded. For our current protocol we have set up a report that runs daily and provides a list of all the participants who documents uploaded and if they have been reviewed. Any uploads that have not been reviewed are highlighted in yellow to let our regulatory reviewer know that they require review.

Set up in EDC system cont Form 3: Regulatory Reviewer Page 3 of the remote upload process is for the regulatory review. The regulatory reviewer will go to Page 2 and view the uploaded document. It is important to note that this is a sensitive process that requires concentration and minimal distraction. So we try to choose a time where we have sufficient time to review without distractions, close email, shut the door, whatever is needed to be able to soley focus on the review. As I mentioned in the possible drawbacks, we want to ensure that the consent is uploaded for the correct person, so that is the first item that is reviewed. If NO is answered none of the subsequent questions are relevant and the reviewer will indicate this in the Reviewer comments and save page 3. If upload is for the correct ppt, the reviewer will look a the ICF and ensure all items are documented correctly. They will then answer the questions in Page 3. These questions are a check list for the reviewer to ensure that we look at all the required areas. Reviewer will answer YES to all questions that are done correctly. For example, was the appropriate version of ICF used – YES. If incorrect, reviewer will indicate NO and provide a comment in the specify field. ***CLICK*** At the end the reviewer will add all issues identified and corrective actions to the REVIEWER COMMENT field. When Page 3 is saved, the information in the reviewer comment field will then be emailed to the site staff that uploaded the ICF. Also, when page 3 is saved, the information including the uploaded document in page 2 is deleted. Also, page 3 is locked and the reviewer is no longer to make any updates.

Notifications Email notification for missing uploads Enrolled participant and missing upload at the end of the day, email is sent every 24 hours to site staff as a reminder. Email notification with regulatory reviewer comments Regulatory review form is saved -> comments and actions in the Reviewer Comment field sent in emailed notification to staff member who uploaded document(s) We have implemented several notifications to help site staff

User and Reviewer Training Demonstration Practicum Site practicum Reviewer Practicum User’s Guide - Site Clarification on “No” vs “N/A” User’s Guide and Procedures Document – Reviewer Key items to remember when reviewing Breakdown of each review Because this process involves the upload and review of sensitive information we have a comprehensive training process Both reviewer and site staff are given a demonstration of the process Regulatory reviewers should have at least one back-up for when they are out of the office and unable to review. For each protocol you will need to establish the timeline for when review of the uploaded consents are expected. For instance in our protocol they should be reviewed within 48 business hours so we have 2 back up reviewers. Back-up reviewer must go through the same training as primary reviewer

Helpful Tools Reports Participant Information ICF Document details With our process we have implemented some helpful tools. Examples of each of these helpful tools should be in your binder for review As I mentioned we are able to create a participant report to link the ppt ID and ppt first and last name We have the IRB requirements for each site.

Helpful Tools cont. Pending documents to review Reports continued Pending documents to review Completed and correct ICFs We currently have the Pending document to review report We are programming and will implement by the end of the month a report that provides a list of completed and informed ICFs

Helpful tools cont. Calendar – Reviewers and back-up reviewers

Demonstration Participant 1 – Submitted single ICF Multiple document regulatory review Within your binder I have included some documents where we can do a ‘mock’ review or two There are two ICFs submitted, one for Site A and one for Site B. Please take some time and review these and IRB summary report and see if you can identify any of the issues. 5 min Show completed ZC3 for each site Additionally, I have included in the binder a copy of our page 3 for regulatory reviewer when multiple documents are uploaded, for instances an ICF and a separate