1. INTRODUCTION

1.1 Purpose

The Syncrony EDC system facilitates the entry of site-specific eCRF data by providing reporting features, automated edit checks, and a query system for posting and resolving potential data discrepancies.

1.2 Audience

This operating manual should be followed by site personnel completing electronic case report forms (eCRFs) of a clinical study in the Syncrony EDC system.

1.3 Roles and Responsibilities

There are five default roles defined in the EDC system: Investigator, Study Manager, Data Manager, Monitor, and Research Coordinator. Each role involved in a clinical study has different responsibilities and uses different features offered by the EDC system. These roles are split into two categories: managers (the Data Manager, Study Manager, and Monitor roles) and site users (the Investigator and Research Coordinator roles). Managers can interact with the entire study, while site users can only interact with their assigned site. Your study may have custom roles created to meet other needs.

Each user has an associated role.

1.3.1 Managers and Monitors

A Data Manager has permission to:

- View, but not edit, subject data from all subjects
- Freeze and lock forms
- Raise and comment on queries on all subjects
- View and create reports (report creation not from within Syncrony)
- Export Data
- Print forms

A Monitor has permission to:

- View, but not edit, subject data from all subjects at assigned sites
- Freeze and Verify forms
- Raise and comment on queries on all subjects
- View reports
- Print forms

1.3.2 Investigator

An Investigator has permissions to:

- View and edit subject data from all subjects at their assigned sites
- Create new subjects at their assigned sites
- Comment on queries on all subjects at their assigned sites
- Sign off eCRF forms
- Mark Missing and NA statuses on single forms or all forms for a subject
- View reports
- Print forms

1.3.3 Research Coordinator

A Research Coordinator has permission to:

- View and edit subject data from all subjects at their assigned sites
- Create new subjects at their assigned sites
- Comment on queries on all subjects at their assigned sites
- Mark Missing and NA statuses on single forms or all forms for a subject
- View reports
- Print forms

2. SYSTEM DESCRIPTION

2.1 Key Features

The Syncrony EDC is a web app. It does not require the installation of any other software packages or dedicated hardware. It can be accessed using Google Chrome.

Syncrony complies with 21 CRF Part 11 and ICH Good Clinical Practice E6 (R1). Syntactx individually validates every study built on Syncrony.

2.1.1 Profile Information

All users have a Profile Information page, which they can access by clicking their name at the top right of any page. It is through the Profile Information page that users can Change Passwords.

2.1.2 Main Dashboard

The Main Dashboard includes the following features:

- Task Bar. The Task Bar on the left-hand side of the screen offers the ability to perform various role-based functions, including Adding Subjects, Viewing the Subject List, Viewing Queries, viewing Reports, Data Exports, and Printing. The Task Bar remains accessible across all sites and forms.
- Subject List. The Subject List overview table is for the study overall for managers, and for the assigned site for site users. It displays number of subjects, total # of queries, # of open queries, # of answered queries, # of open and answered queries, and # of closed queries. Managers can also use a dropdown menu to view statistics for single sites.
- Queries Chart. Displays the relative numbers of open, answered, and closed queries. Managers can see all queries; site users only see queries from their site.
- Profile Information. Clicking on your username (role) in the upper right hand corner will open the Profile Information page.
  
  From here users can view and switch roles (for users with multiple roles assigned to them), view assigned sites, and update their password.

2.1.3 Query List

The query list is a detailed list of queries raised about subjects in the study. It is available through the Queries dropdown menu on the Main Dashboard. The information visible in it varies by user role.

- Global features
  - All users can see:
    - Site
    - Subject Id
    - Query Id
    - Form and field of the subject data that the query is on
    - The initial comment of the query
    - User who created the query and their role
    - Date query was created
    - A clickable Comments button to load comments
    - How many days query is/was open
    - Status of Query (Open, Closed, Answered)
  - Investigators
    - See queries for all subjects at their assigned sites.
  - Research coordinators
    - See queries for all subjects at their assigned sites.
  - Data Managers and Monitors
    - See queries for all subjects in the entire study
    - Filter by site and role
    - Can close any open or answered queries

2.1.4 Print CRFs

The Print CRFs page provides case report forms in a printer-friendly format. It is reached through the Print CRFs button found in the Task Bar on the left side of your screen. On the Print CRFs page, there is a list of the study's forms that can be selected individually, or in bulk using the Select All button at the bottom of the page.

The Clear All button deselects all forms, while the Print Selected Forms button loads a print preview for all selected forms–the printing process can be finalized from this page. Selecting Annotate Datapoints will include each field's variable name in the printout, while Print Subject Answers will print any subject data that has been entered into form fields. NOTE: This option is limited to printing from within a site.

2.1.5 Subject Creation

Investigators and Research Coordinators, but not Managers, can add subjects to sites. The Add Subject button found in the Task Bar on the left side of your screen opens the Create New Subject page, where the user can add a subject to the appropriate site. The Create New Subject page also allows the addition of study-specific data points that aren’t covered in CRFs. This often includes information like birth date or initials.

2.1.6 Subject List

The subject list is a detailed list of queries raised about subjects in the study. It is available through the subject List button on the Main Dashboard. The information visible in it varies by user role.

- All users can see:
  - Site number, subject ID, and Subject Status or each subject they have access to
  - Subject Statuses are:
    - Complete:
    - Incomplete. Not all forms are marked as complete
  - Open queries. Someone has added one or more unanswered questions about this subject
- Investigators
  - Can see all subjects assigned to them, but not all subjects at their site
  - See queries for all subjects at their site
  - Filter by address
- Research coordinators
  - See queries for all subjects at their site.
  - Filter by address and investigator
- Managers
  - See queries for all subjects in the entire study
  - Filter by site, address, role, user who created the query, and investigator associated with the subject of the query
  - Can close any open or answered queries

2.1.7 Form Status

Different user roles have different permissions to alter the status of forms.

- Investigators can mark each field, or an entire form, as “Signed.”
- Managers can make each field, or entire forms, with the following statuses:
  - Verified (Only the Monitor role)
  - Frozen. This status prevents any user from editing the marked fields.
  - Locked. This status prevents any user from editing the marked fields. (Only the Data Manager role)

2.1.8 Edit Checks

Syntactx can customize fields to accept or reject incorrect inputs:

Check Type	Details
Required	If no value entered for required field, user is alerted that field is required
Range	If input value is outside of specified range, alert pops up showing minimum and maximum values
Valid Answer	If value is anything besides the specified “valid answer”, user is alerted with message Ex: Entering “Yes” for an exclusion criterion
Relative Time	If time value input is before or equal to a reference time point, user is alerted with message
Relative Date	If date value input is before or equal to a reference date point, user is alerted with message
Time Format	If a time is input does not fall between 00:00 and 24:00, user is alerted with message

2.1.9 Audit Trail

Every field containing subject data has an “audit button” next to it. When clicked, this audit button brings up the following information for every change that has been saved in that field:

- The value that was saved
- The reason that value was changed
- The date and time of the change
- The user who made the change
- Any queries that have been raised on that field, and the corresponding answers and closing
- Any status changes, such as Verified, Frozen, Locked, NA, and Signed

2.1.10 Queries

- All users can:
  - Add comments to open queries
  - Check if a field has open queries, answered queries, or closed queries, via color coded statuses.
- Data Managers and Monitors can:
  - Open queries
  - See queries for all subjects in the entire study
  - Can close any open or answered queries
  - Filter by site, address, role, user who created the query, and investigator associated with the subject of the query
    To open a query, highlight the field and click the Open Query

2.1.11 Form Editing & Saving

- Investigators and Research Coordinators can:
  - Edit data point values
  - Save forms
  - Can (and must) give a reason for change whenever save a change to a data point. Change Reasons are applied via the dropdown list found in the far-right column of the Confirm Save popup.
- Managers can:
  - Alter field and form status
  - Save forms

2.1.12 Adding and Deleting Subforms

- Investigators and Research Coordinators can add and delete repeating subforms as needed. To add a subform, click the Add button found at the top of the subform's section (this can be where the subform is placed in the study).
- To delete a subform added in error, click the gear icon at the top of the form and select 'enable subform deletion'. Click delete at the bottom of the subform in question, then click delete again to confirm. Note that the subform numbering will remain in place. For example, if you delete Subform 2, subforms 3 and on will retain their original number designation.

2.1.14 Data Exports

Data Managers have permission to export forms from all subjects in the study. This is done by clicking the Data Export button in the task bar.

- Exporting case-report forms creates a report including subject number, site number, and all data points from the form
- Exporting repeating report forms creates a report including subject number, site number, form number, and all data points from the repeating form
- Once desired forms are selected, clicking the Export Selected Forms button will initiate the export

2.1.15 Reports

Monitors, Managers and Investigators have permission to run standard reports for all subjects in the study. This is done by clicking the Reports button in the task bar.

- Each tab on the reports page provides different information, including Enrollment, Form Status, and Query Status. The Variable Dictionary tab offers a means to match variables with their fields.

2.2 Environment

The Syncrony EDC is built to run on Chrome.

2.3 System Operations

Normal system operations in the Syncrony EDC include adding subjects; filling out and saving forms; creating and commenting on queries; and locking, freezing, and signing off on forms.

3. PRODUCT INSTALLATION

3.1 First-Time Users

You will receive a user account email providing your study URL; user ID; and temporary password. EDC access procedures and the corresponding documentation should be determined as per the sponsor’s SOPs.

For first time log in, access your EDC study in your web browser using the URL provided (a unique URL per study), and enter the user ID and Password you received in the email.

You can reset forgotten passwords by clicking on ‘Forgot Password’. Enter your email address and click on ‘Recover Account.’ You will receive a temporary password within a few minutes.

3.2 Access Controls

The administrator of the EDC system defines and manages user access. The administrator will be responsible for releasing the study EDC system into production, and for any updates in testing environments.

3.3 Installation

The EDC System requires a computer with an internet connection and a web browser. It does not require installing any files on your computer.

3.4 Configuration

The EDC is customized for the needs of each study. Different studies will involve different forms. Each study can be accessed at https://syncronyedc.com.

The following aspects of a study can be customized:

Forms
Data points
Edit checks
Workflow (i.e. which users have access to signoff, freeze, and lock)

4. SYSTEM USAGE

4.1 Instructions

The user can navigate throughout the EDC system by using the buttons on the left of the screen. The Home button is used to get back to the main menu from an eCRF page.

4.1.1 Add subject

As an Investigator or Research Coordinator, you can add new subjects into the eCRF. Click on the Add Subject button from the Task Bar on the left side of your screen. Enter the requested subject information into the appropriate fields, then click on the Create button. You are automatically redirected to the new subject.

4.2 Completion and navigation of the eCRF forms

Navigate from one eCRF page to another in Syncrony EDC by clicking navigation tabs. You can use the browser Back and Forward buttons to navigate to the previous and next pages. Navigation tabs are sequentially arranged from left to right in a folder style. Click a tab to display the corresponding eCRF page.

4.2.1 Data completion

The heart of the Syncrony EDC system is the forms used for data entry. Each tab contains one or more forms which in turn contain one or more fields.

Users can switch between tabs, create extra forms (for repeating forms, such as adverse event reports), and enter data in fields.

Fields come in several varieties:

- Radio buttons, in which the user selects one of two or more options.
- Checkboxes, in which the user selects any number of options.
- Dropdown menus, in which the user selects one of two or more options.
- Textboxes, in which the user can enter both text and numbers directly.
- Texatareas function like textboxes but offer a user-expandable area for making longer entries, such as narratives.
- Number boxes can contain only numbers. Numeric boxes can have their values increased or decreased with up and down arrows or keyboard arrow keys, and often have limits on the range of values they will accept.
- Date fields, which bring up a calendar when clicked. Clicking a date on the calendar selects it. Arrows at the top of the pop-up calendar allow the user to navigate between months and/or years. Certain date fields ("Stingdate") allow for entries of unknown days, months, or years. Unknowns will appear as UNK, e.g. UNK-OCT-2017.
- Time fields, which accept time-of-day entries in a 24-hour format (e.g. 13:00, not 1:00 PM).

Site users can edit saved data. All changes and prior versions are automatically recorded in each field’s audit trail.

The Syncrony EDC System saves form data when users click the Save button on the appropriate page. SYNCRONY DOES NOT AUTOSAVE DATA; users should save data on a given page or tab before switching to a different page or tab.

4.2.2 Query generation

Manager users can open and close queries on particular fields in a form. All users can add comments to queries. Site users should use comments to answer questions managers raise. A manager should close a query once the issue that prompted the query has been resolved.

The query system can be customized with stock responses, which users can click to save time when the situation only needs a generic comment. “Data entry error” and “Corrected” are common choices.

4.2.3 Sign a subject, folder or eCRF form

When instructed to by your Monitor, the Investigator will need to sign off on the forms. Click the Sign buttons next to fields to sign them. Some studies have a Sign All button at the top of the page, which lets you sign off on every field on the page at once.

To record your electronic signature, be sure to save after signing.

4.2.4 Freeze and lock data

The Freeze and Lock checkboxes allow users to prevent data on forms from being changed.

Monitors and Data Managers can freeze and unfreeze forms. Only Data Managers can lock and unlock forms.

5. SYSTEM MANAGEMENT

5.1 Change Management

To report a bug, email support@syncronyedc.com.

For features and updates to variables that go beyond or alter the initial requirements, the Project Sponsor should contact Syntactx to fill out a Change Request Form. Once details are agreed upon, Syntactx will initiate a new development and validation cycle based on the extent of the changes.

5.2 Configuration Management

Syntactx and the Project Sponsor develop study-specific User Requirement Specifications at the start of a project. Syntactx then translates the URS into Functional Specifications, a more detailed documentation of how the software should behave. Once the Project Sponsor approves the FS, Syntactx collects signatures to approve the specifications and begin project-specific programming.

The Syntactx development team creates and validates project-specific eCRF modules in a test environment.

6. BACKUP AND RECOVERY

The Syncrony system has several, redundant backups. It is hosted on multiple cloud locations on different continents via Azure, and on Syntactx’s private servers. The Azure servers back up Syncrony every 15 minutes. In the event of an Azure failure, Syncrony can be used from the Syntactx servers, which back up daily. The databases that store subject data have backups internally, on Azure, and on Amazon Web Services. Even in the event of a failure that made the app temporarily unavailable, subject data would not be lost.

7. REGULATORY REQUIREMENTS

The Syntactx EDC system has been developed and validated to comply with 21 CFR 11.10(a), to ensure accuracy, reliability, consistent intended performance, and the ability to discern invalid or altered records, and with nd ICH Good Clinical Practice E6 (R1).

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