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.

Rapid Deployment of New Functionality in OpenClinica Using MirthConnect

In a previous article, we describe how we at Geneuity Clinical Research Services exploit OpenClinica’s new web services feature to automate the entry of lab data keyed to accession numbers.  Here, we describe more fully how and why we use MirthConnect.

Started in 2006, MirthConnect is an open source project sponsored by the Mirth Corporation of Irvine, CA.  It is middleware designed to transform, route and deliver data.  It supports HL7, X12, XML, DICOM, EDI, NCPDP and plain old delimited text.  It can route via MLLP, TCP/IP, HTTP, files, databases, S/FTP, Email, JMS, Web Services, PDF/RTF Documents and custom Java/JavaScript.  MirthConnect has been likened to a Swiss army knife and justifiably so.

Channels are the heart and soul of a MirthConnect installation.  A channel is user defined and has a source and a destination.  A source may be a flat file residing on a remote server or a web service call or a database query or even another channel—whatever you like, it doesn’t matter. A destination may be to write a PDF document, email somebody an attachment or enter data into a database.  Again, whatever!

To illustrate, say you want to poll a database and generate a weekly report.  No sweat! Using MirthConnect’s easy-to-use drag-and-drop template-based editor, define a channel with a database reader as a source, and a document writer as a destination, fill in details like user names, passwords and machine names, define which database fields you want to retrieve and how you want to display the data, and you’re done!  MirthConnect’s daemon handles the rest based on your channel’s configuration.

Once defined, a channel can be exported as XML for later import into another MirthConnect installation.  This is all done with the point and a click of a mouse.

At Geneuity, we use MirthConnect to get data in and out of OpenClinica.  Originally, we used custom JAVA code to do this.  But once we found MirthConnect, we quickly realized we were reinventing the wheel.  Why do that?

Here’s a concrete example.  Consider the very simple CRF from a mock OpenClinica installation shown in Figure 1.  It has three groups of items: accessioning, results and reportage.  When a specimen arrives at Geneuity, the lab tech looks up the patient and event pairing in the subject matrix as specified by the requisition and types into the CRF the accession number, the receipt date and any shipping deviations.  This is done by hand and is indicated as step 1 of Figure 2.

Then, as shown in step 2 of Figure 2, the tech tests the specimen at the testing platform.  In step 3, the platform spits out the data whereupon a collection of MirthConnect channels operating in tandem parses the results, transforms them into SOAP messages and sends them to the EventDataInsertEndpoint web service feature of OpenClinica for upload into the CRF fields designated ‘Assay date’ and ‘Analyte concentration’.

After the tech reviews the data and marks it complete, another collection of channels polls the database for results newly marked complete, generates and delivers PDF reports of the corresponding data (step 4) and then reports back to OpenClinica (step 5) via EventDataInsert the details of the reportage, including status, time and any errors (see the third and last item grouping labeled ‘REPORTAGE’ in Figure 1).

The scenario outlined above requires NO CUSTOM CODE beyond the channel configurations and these are encapsulated and standardized by design.  As such, you don’t need an army of coders on staff to develop and maintain them.

Both OpenClinica and MirthConnect are great as standalone products.  Linked together, however, they really sizzle.

Figure 1: A simple CRF from a mock OpenClinica installation
Figure 1: A simple CRF from a mock OpenClinica installation
Figure 2: This shows how the different item groupings in the CRF depicted in Figure 1 are populated.  Values for items under ACCESSIONING are entered manually by the lab tech.  Values for items under RESULTS are populated by the Mirth channels continuously listening for in-coming data from the clinical testing platform.  Values for items under REPORTAGE are populated by a distinct set of  Mirth channels responsible for polling and reporting newly completed results.
Figure 2: This shows how the different item groupings in the CRF depicted in Figure 1 are populated. Values for items under ACCESSIONING are entered manually by the lab tech. Values for items under RESULTS are populated by the Mirth channels continuously listening for in-coming data from the clinical testing platform. Values for items under REPORTAGE are populated by a distinct set of Mirth channels responsible for polling and reporting newly completed results.