OpenClinica 3.1 (project “Amethyst”) Preview

The next major milestone for OpenClinica (project code-named “Amethyst”) will be OpenClinica version 3.1. While this release contains roughly 85 tweaks, fixes, and enhancements, this post describes some of the more significant enhancements that will be included (check out the Amethyst project roadmap page for a full list—note: openclinica.org login required).

New features in OpenClinica 3.1 will include:

  • Dynamic Items in CRFs
  • Audit Log and Discrepancy Note Data with ODM Exports
  • Assignment of Failed Validation Check Discrepancy Notes
  • Relative Paths for Item OIDs in Rules
  • Discrepancy Note Flag Colors in the CRF
  • Modularization
  • Multiple Site Level Users Allowed Access to an Event CRF
  • Simple Conditions

Dynamic Items in CRFs

OpenClinica 3.1 will support Showing and Hiding of CRF Items using both the CRF template and a Rules file. When a user enters data and saves a CRF section, data fields may be shown or hidden based on value(s) that user provided in one or more other fields on that form. This capability is also commonly referred to as “skip patterns.” A simple example would be a CRF question asking if the patient is male or female. If the value provided is female, a pregnancy related question could then be displayed to the user entering data and all questions associated with males could be hidden from view.

Audit Log and Discrepancy Note Data with ODM Exports

Audit Log data and Discrepancy Note data for a subject will be available in the ODM data extract format with OpenClinica extensions. This will allow the user to have all of the clinical data, audit log data, and discrepancy note data in a single data file.

Assignment of Failed Validation Check Discrepancy Notes

Currently, OpenClinica supports assignment and workflows around only the Query type of Discrepancy Note. OpenClinica’s “assignment” capability will be expanded to also include the Failed Validation Check type of Discrepancy Note. For Failed Validation Checks, the first note in the Discrepancy Note thread will not be assigned, but Data Managers, Study Directors and Monitors will be allowed to assign the thread to a user for review/resolution. OpenClinica will also restrict the Clinical Research Coordinators and Investigators (both site-level users) from setting the status of Failed Validation Checks to Closed.

Relative Paths for Item OIDs in Rules

A new enhancement to Rules authoring will allow the Rule creator to write one Rule Assignment for a particular CRF Item, and have the Rule execute wherever that Item’s OID is used throughout all of the study events. This increases the “portability” of rules, allowing the user to write one Rule, and have it apply multiple times rather than having to author multiple Rules and multiple Rule Assignments.

As an example, a Rule Assignment would need to contain the following path in OpenClinica 3.0.x:

SE_OBSERVAT[ALL].F_GROU.IG_GROU_GROUP_1[ALL].I_GROU_TC_ADV_PRIMARY_05

If the CRF was used in multiple events, the creator of the Rule file would have to specify the path to the other event as well.

In 3.1, all the user has to do is write:

I_GROU_TC_ADV_PRIMARY_05

and the Rules will be executed wherever that Item shows up in the study.

Discrepancy Note Flag Colors in the CRF

OpenClinica 3.1 will include additional Discrepancy Note flag colors that correspond to the various statuses of a particular thread. Currently in OpenClinica, if a Discrepancy Note thread exists, the flag will always display in a red color regardless of the Discrepancy Note status. In 3.1, the color of the flag will be reflect the “most severe” status of any thread that is on a particular item (more than one thread may exist for any item). For example, if there is a Closed thread and an Updated thread on one item, the color of the flag will be yellow representing the Updated status. If there is just a Closed thread, the color of the flag will be black. To support people who are color blind or shade blind (like myself) there will be a roll over when you put your mouse on the flag, showing you the number of threads and each of their statuses when Viewing a CRF.

Modularization & New Web Services

Modularization is defined as a software design technique that increases the extent to which software is composed from separate parts, called modules. Conceptually, modules represent a separation of concerns, and improve maintainability by enforcing logical boundaries between components.

What this means for OpenClinica is we have started to separate the application into multiple pieces. In version 3.1, we have modularized the web application from the web services functionality. This will allow new web services to be developed on separate release timelines from the main web application, facilitating the system’s extensibility.

In addition, we are release some web services with 3.1, (these were contributed by Colton Smith of Geneuity and openXdata):

  • CRF Data Import
  • Retrieve a list of studies
  • Retrieve a list of events and their CRFs
  • Retrieve a list of subjects and their events

Multiple Site Level Users Accessing an Event CRF

OpenClinica 3.1 will allow different site level users access to an Event CRF, even if they are not the conceptual “owner” of that CRF. In prior versions of OpenClinica, once a user began data entry in a CRF, the system prevented other users from adding information or data to the CRF until it had been marked complete. The new feature will allow a second user to continue entering data before the CRF is marked complete.

This change to OpenClinica will also help facilitate the ease of recording adverse events in a separate CRF. A user will not have to mark it complete in order for another user to provide additional adverse events that have occurred for a particular subject. In addition, this new functionality will prevent users from accessing an Event CRF if another user already has the form open. In this case, the second user will receive a message saying that the form is currently being accessed by another user.

Simple Conditions

In addition to the Dynamics capabilities that will be part of 3.1, we have added a feature called Simple Conditions. This feature is similar to Dynamics in many ways, but can be implemented through the CRF Template directly rather than writing a separately Rules XML document.

With Simple Conditions, a person creating an OpenClinica CRF will have the ability to designate Items as “hidden” from the data entry person’s view until a particular option is chosen for another CRF Item. The data entry person will not have to click “save” on the form–instead, as soon as the option is selected, this hidden field will be shown in real time.An example of the type of use case this feature targets, is a CRF question with two fields, one for “race” and the other for “comments” (which is hidden). If the data entry person selects the value of “other” for the race field, the hidden comments field will be display underneath.

Akaza Research is excited about bringing OpenClinica 3.1 to the community! Your comments and feedback are appreciated. Please check back in next week or so for an update on our timelines for Alphas, Betas and a Production release.

Trial Sponsors and Their Contract Labs: Better Collaboration via OpenClinica

At Geneuity Clinical Research Services, we do lab tests for trial sponsors. As readers of this blog know, we use OpenClinica internally as an LIS (laboratory information system), but as more and more drug companies and CRO’s adopt OpenClinica we foresee the day when we will be using their installations as our LIS, not ours.  A common platform will eliminate lots of duplicated effort and will allow for real-time transparency and better collaboration.  But it will also require sponsors to design their CRF’s with their contracting laboratories in mind.  In this article, we describe how this could be done.

First, consider specimen collection and tracking.  Normally, trial sponsors don’t consider doing this within the context of OpenClinica.  But they should.  Let’s say a specimen accidentally thaws in transit between the collection site and the contract lab.  Shouldn’t that fact be summarily recorded in the same context as the resulting lab test whose value may ultimately be reported to the FDA?  I should say so.

So, can OpenClinica be configured to do this? Yes and easily. A separate CRF dedicated to specimen collection could be designed and assigned to each event.  Alternatively, a specimen section could be added to already existing CRF’s.  Either way, fields for such things like accession number and specimen type could then be included.  These would be filled in by site personnel responsible for specimen collection.  Additional fields like ‘shipping deviations’ and ‘laboratory receipt date’ could also be included and would be filled in by lab personnel upon specimen delivery to the testing lab.  When it comes time for data analysis, the sponsor can use OpenClinica’s data export capabilities to exclude or include those lab results with shipping deviations and to investigate the consequences.

Other important aspects of specimen collection include printing labels to barcode samples and generating an attendant paper manifest (know as a requisition) against which labs can check incoming shipments of specimens.  OpenClinica can’t do such things currently.  It would require a whole new software module, but lots of added value could be achieved if one were written.  For instance, one can envision that after accessioning a specimen, site personnel could print a corresponding requisition from the same application window.  Also, imagine the time savings if lab personnel could conveniently print barcode labels after receiving a specimen and recording its receipt date and shipping deviations (if any).  And because the paper requisitions would be generated within the context of OpenClinica, subsequent source data verification by lab personnel could be expedited using QR-encoded URL’s that drill-down into the patient-event matrix. For more on this, see here.

Specimen tracking is just part of the story when it comes to sponsors and their contract labs.  Getting lab data from the laboratory testing platform into OpenClinica is another.  Recently during OpenClinica’s March 22 Global Conference in Bethesda, Akaza Research and Geneuity did a live demonstration of how this can be achieved using a set of MirthConnect channels. A batch of raw lab data keyed only to accession numbers was sent from Geneuity’s corporate headquarters in Maryville, TN to a remote OpenClinica installation hosted at Akaza’s Waltham, MA facility where it was inserted into the database programmatically via an awaiting web service. The insertion was streamlined, secure and seamless.  When setting up a trial, sponsors should think about the lessons this demo provides and consider distributing already configured and validated MirthConnect channels to their contract labs.  In this way, sponsors can control how their data is treated and understand every detail of its electronic provenance. And because MirthConnect can be configured to store its history, the trial’s audit trail can be extended upstream to the data’s very source.
Finally, consider invoicing.  Contract labs have to be paid when they do a test.  Monthly invoicing reports could be generated from OpenClinica by configuring an appropriate ‘data set’ and having it execute at the end of each month using the application’s new built-in quartz scheduler.  In this way, billing would be a snap and everybody would be on the same page.

In summary, how can trial sponsors configure OpenClinica to collaborate better with their contract labs? Do the following, keeping the workflow shown in Figure 1 in mind:

1.    Include a specimen accessioning CRF for each event.  Educate your collection-site people and your lab people as to who is responsible for which fields.  Use OpenClinica’s internal messaging system to remind people of their roles when the study is actually underway.
2.    Exploit OpenClinica’s web services framework to enable batch uploads of laboratory data.
3.    Configure and validate MirthConnect channels to get the lab results from the source data files to your OpenClinica installation.
4.    Distribute these channels to your lab contractors and educate them on their use.
5.    Configure OpenClinica to automatically generate monthly data sets for billing purposes.

The bottom-line: OpenClinica is infinitely configurable and sponsors should start doing so with their lab contractors in mind.  The result will mean both better collaboration and lower costs.

Figure 1: A specimen is collected from a subject on site. The on-site data manager logs into OpenClinica and accessions the sample and prints an accompanying hard-copy requisition. The sample is then shipped to the contracting laboratory where lab personnel log into OpenClinica and indicate they have received the sample. Specimens are then tested in batch and the results are then uploaded en masse into the sponsor's installation of OpenClinica using a thoroughly vetted, validated and auditable MirthConnect channeling system.

OpenClinica 3.0 Features Preview: Part III

Welcome to the 3rd and final installment of the OpenClinica 3.0 features preview!  This post covers the new Web Services interface that is part of 3.0 and the job scheduler that can be used to automate Data Import and Data Export jobs.

OpenClinica 3.0 allows for programmatic interaction with external applications to reduce manual data entry and facilitate real-time data interchange with other systems.  The OpenClinica web services interface uses a SOAP-based API to allow the registering of a subject and scheduling of an event for a study subject.

OpenClinica provides a WSDL (Web Service Definition Language) that defines a structured format which allows OpenClinica to accept “messages” from an external system. For example, an EHR system could register subjects for a study in OpenClinica without direct human intervention. At the same time, the EHR could also be programmatically scheduling study events for these subjects. More information about the OpenClinica API can be found on the OpenClinica developer wiki.

An early reference implementation conducted by clinical lab Geneuity used the API to create a web service which inserts data programmatically into OpenClinica CRFs directly from laboratory devices. See the post by Geneuity’s Colton Smith below.

Another major productivity tool in 3.0 is the introduction of a Job Scheduler for automating bulk data import and export.  With this feature users can define a job that will generate an export at a specified time interval.  The Jobs Scheduler can also be configured to regularly scan a specific location for CDISC ODM files and run data imports when a new file is available. This feature can be particularly helpful in automating routing functions, such as the incorporation of lab data into OpenClinica from an external system.  The lab data does need to be in a valid CDISC ODM format (this can be accomplished via another great open source tool called Mirth), but it does save a person from entering data in two applications separately.

At time of this post, OpenClinica 3.0 is currently released as a beta3, but the production ready application is soon to follow. The application is passing through the highly rigorous strictures of our quality system (think Navy Seals training for software) and the output will be fully validated and ready of use in roughly a month. Needless to say, I, and everyone else here at Akaza is very excited to be so close to releasing 3.0. It is already quite clear that this release will have a momentous, positive impact on the community.