An ePRO Case Study

What does the term “source” bring to mind for you? Paper files? A clinic’s EMR? Fair enough. Those are the typical formats of source data in clinical trials. But when you think about it, those records are a few removes from the true source: the patient.

Granted, most trials depend on a host of instruments and analyzers. No patient can self-report their own hemoglobin levels. But there are measures, such as quality of life, whose source really is the patient’s own experience. And for an industry whose raison d’être is enhancing (and sometimes saving) lives, we have a hard time obtaining those measures.

That’s not to say that patient-reported outcomes are a rarity in clinical trials. In fact they’re common. But so are obstacles to collecting them. Even today, with several ePRO solutions on offer, too many trials rely on patients to complete paper diaries. But paper records are prone loss or damage. Also, it’s virtually impossible to tell whether a patient made daily diary entries as instructed, or retrospectively wrote responses just prior to a study visit, raising data quality concerns. (Here’s a great analysis of “parking lot syndrome”.)

“Mochaccino with a side of ePRO” has to become the new normal for trials

ePRO is a big improvement on paper, but it doesn’t integrate seamlessly into a patient’s day to day life. Nearly all trials today using an electronic system for PROs provision dedicated devices to patients for this purpose. Patients need to be trained on how to use this device, recall that training at the relevant time, and make a habit of keeping the device on their person to stay current with reporting tasks. These systems also require patients to remember passwords and other access credentials. A step as apparently simple as downloading an app can be fraught with challenges: the patient must remember their app store login, locate the download area, have sufficient memory on their phone to house and run the app, ensure the app installs successfully, and ensure it remains installed, running, and updated.

All of the above examples are potential points of failure that can compromise the quality of real world data and increase trial costs. These myriad tasks and responsibilities unrelated to the data itself can place a significant burden on a volunteer patient, particularly one who is very sick.

OpenClinica Participate eliminates potential points of failure by:

  • providing an system that can be used on the patient’s own device(s),
  • eliminating the need to patient’s to remember login credentials, and
  • removing the complexities associated with apps.

This helps place the patient at the center of the research. And perhaps best of  all, OpenClinica Participate places the patient reported data into the master EDC database in real-time with zero additional effort.

The advantages of this approach aren’t just theoretical. OpenClinica and its partners have realized their benefits in more than 20 studies since the launch of OpenClinica Participate about a year and a half ago. In this post and future ones in this series, I’d like to share some short and informal case studies. I call this one:

On time, nearly every time

In a phase II study assessing the prophylaxis of a nasal powder in subjects challenged with rhinoviruses, subjects were asked to self-report symptoms at 27 time points over 12 days. On 7 of the days, self-reports were to be submitted in the morning, in the afternoon and at night. To help drive compliance with this rigorous self-reporting schedule, trial managers needed to engage their subjects and ensure their convenience. To do so, they tapped the ability of OpenClinica Participate to present clear, attractive eCRFs to patients right on their own mobile device or laptop. Data managers established rules that fixed the date of all future study events based on the date of enrollment. OpenClinica Participate automatically sent text messages and emails to each subject hours prior to a scheduled event, directing them to the relevant data capture form regardless of which of their devices they happened to be accessing at the time. (This is a best practice, with hours spent online per day continuing to grow around the world. And while a crowded “app” field may fragment populations – a Snapchat user is not necessarily an Instagram user – an email client and SMS messaging feature can almost always be found, and found running, on any web-enabled mobile device.)

In this case, success would mean the vast majority of study subjects not only entering their data, but doing so in real-time; that is, once in the morning, once in the afternoon, and once in the evening on each of those 7 critical days. And that’s just what happened.

Of the 115 subjects who completed at least one of the 27 ePRO forms, even just a basic intake form, 89 (77%) completed all of the 21 forms required in the morning, afternoon and evening of seven consecutive days, when timely reporting was most critical.

Of the 1,892 “3x daily” forms completed, the vast majority were completed in “real-time”:

Forms CompletedWithin 4 Hours
(of 6am, noon and 5pm
respectively)
% Within 4 Hours
Morning63059995.08%
Afternoon63161296.99%
Evening63160495.72%

“Bring your own device” may not be the final frontier in ensuring patient convenience. Passive monitoring by nearly invisible devices is already a reality. But the principle will never change: let technology do the work, so people can live their lives.

 

Our newest clients represent the future of research and care

New client relationships are exciting in any business. But they don’t get much more gratifying than the ones we’ve been fortunate to make. Looking back over the last six months of new client relationships, I’ve been struck with the emergence of some inspiring trends. A focus on personalized medicine. The willingness to take on looming problems in population health. The application of advanced computing and “big data” to challenges old and new. It’s been a potent reminder of the impact that our work here at OpenClinica makes possible.

Here is just a sample of the new partners that are energizing us:

The biotechnologists at miR Diagnostics specialize in the development of prognostic testing in cancer treatment. Their mission is to provide people diagnosed with cancer a deeper understanding their disease, and to help them make the safest, most informed treatment decisions possible. Using state of the art research, miR Diagnostics has developed cutting-edge, prognostic cancer testing systems that provide insight into tumor progression previously impossible to ascertain.

With Tools4Patient, too, medicine is personal. Tools4Patient develops companion diagnostics which contribute to the design of new treatment paradigms to improve outcomes and enhance quality of life for patients. Their first commercialized tool, Placebell, increases the sensitivity and power of clinical research results through improved Individual Placebo Response characterization.

From microbial pathogenesis to gene therapy, The Research Institute at Nationwide Children’s is claiming new frontiers on behalf of children from around the world. Add to that incredible mission a suite of stunning computational resources, and we knew we needed to work together.

Mercy Research, a centralized, multi-faceted research group within the Mercy health system, conducts more than 700 clinical studies at any given time. They’ve developed more than 40 innovating products and are now building one of the foremost teams for healthcare analytics. Suffice it to say, we’re proud to play our role in this enormous enterprise.

Malaria is responsible for more childhood mortality than any other single infectious agent. At Sanaria, through collaborations with renowned institutions like University of Tübingen, Germany, research is taking on a big aim: eradication through vaccination.  

Biolux Research develops technologies that enhance clinical outcomes and dramatically reduce treatment timelines in dentistry, implantology and orthodontics in a safe, effective and non-invasive approach. Learn how they’ve already succeeded with OrthoPulse®.

Again, these are only examples. In the space of a blog post, I can’t do justice to these missions, those of the new clients I didn’t mention, and the many we’ve been helping to advance for years. But I will be reporting our progress in making all these ventures like these as successful as they can be.

 

New eCRFs (Colleague Revelation Forms)

OpenClinica has welcomed several new team members over the last few months. We’ve collected some eCRFs (Collegue Revelation Forms) to introduce them!

Name: Paul Bowen
Title: Product Owner
Responsibility: I bridge the gap between our stakeholders and our engineering team to ensure that we build the features into OpenClinica that are needed most.
Background: Prior to joining OpenClinica, I spent ten years at Quintiles/Outcome Sciences developing an EDC platform for late phase studies. I also spent one year at Clinical Ink working on a patient engagement app.
What I love about research: I like being a part of something that is making people’s lives better in a significant way.
What I love about technology: Technology provides us with many new options to improve the way we do research. Working to figure out the best solutions is a fun part of this job.
What I love outside of work: When the weather is nice, my girlfriend and I like taking long walks with our dog. When it’s not as nice, we like watching sci-fi TV and movies.


Name:
 Bryan Farrow
Title: eClinical Catalyst
Responsibility: I’m the link between the data management community and OpenClinica. It’s my job to distribute news about our products and services to data managers who’ve been looking for solutions to industry-wide problems like integration and ease of use. Just as importantly, I bring unmet challenges back to our incredible team of developers and customer success professionals so that we can find a solution.
Background: Prior to joining OpenClinica, I spent five years at DrugDev, learning how just how much technology can affect the duration, cost and experience of running a trial. Prior to that, I was responsible for physician and patient communications at Boston Children’s Hospital.
What I love about research: The journey and the destination. Asking questions, devising ways to get an answer, and analyzing evidence are thrilling. With clinical research, we get to do all that with the aim of improving lives.
What I love about technology: For me, technology comes down to problem-solving. If you’re curious and persistent, you can always find a better way. And it’s so gratifying when you do.
What I love outside of work: My family above all. I love being a father to my two kids and a partner to my incredible wife. But when I need some “me time”, I usually reach for a book or journal dealing with philosophy. That was my major in college, and I’m still enamored with the power of logic and the gravity of big ethical and political questions.

Name: Brittany Stark
Title: Project Manager
Responsibility: I direct client projects involving the implementation of clinical trials using OpenClinica software. I oversee the planning, build, testing, and delivery of client projects on time, within scope and budget.
Background: Prior to joining OpenClinica, I spent 4 years in the Cancer Clinical Trials Office at Beth Israel Deaconess Medical Center, working with phase 0-IV clinical trials in oncology. During this time, I gained experience as a Clinical Research Coordinator, Regulatory Affairs Specialist and later Clinical Trials Staff Educator. Prior to this, I spent over 4 years working in academia at the University of Kentucky (in a Human Behavioral Pharmacology and Clinical Psychology Lab) and later at the University of Maine (teaching SPSS as part of a Research Methods and Designs Course Lab).
What I love about research: The potential to advance our understanding of the world we live in and change lives for the better.

Name: Chris White
Title: Customer Success Team Lead
Responsibility: I direct client projects involving the implementation of clinical trials using OpenClinica software. I oversee the planning, build, testing, and delivery of client projects on time, within scope and budget.
Background: Prior to joining OpenClinica, I spent two years in the consulting industry working with many different types of software. Prior to that, I spent 14 years creating positive customer experiences with two successful start-ups, helping to build their client focused operations.
What I love about research: There is still part of me that is the seven-year-old Calvin (from Calvin and Hobbes), always asking questions, wanting to know and understand the wide world around me.

 

 

What prevents you from doing (more) ePRO?

Patient-reported outcomes give us insights that no clinical assessment, imaging study and lab report can. For subjective measures, such as mood or energy level, there’s often no other source. But common methods of collecting PRO, from paper diaries to provisioned devices, pose real barriers. We want to know which ones you’ve faced. Tell us by completing the form below. We have more to say on the topic, but we want to start with your experiences!

Calculating ROI for ePRO

I recently delivered a webinar titled “Getting Started with eCOA/ePRO,” in which roughly a third of attendees polled cited expense as the number one reason that has prevented them from adopting an ePRO solution. So what does ePRO really cost? Is it worth it? Here I strive to provide a basic, high-level framework for thinking about the return on investment ROI of eCOA vs. paper.

Let’s start by taking a look at the costs that are unique to each approach.

Paper

In a traditional paper based model, you are incurring costs that stem from printing, mailing, data entry, and data cleaning. These are all expenses than can be estimated with a fair degree of accuracy, with the cost of data entry being the most significant of these. To estimate the cost of data entry, see how long it takes to key in a subject completed paper casebook, multiply this by your cost of labor (don’t forget to include overhead!).

ePRO

The cost side for ePRO is similarly straightforward, but the expense elements are different. You’re either building an ePRO system (which will almost carry a highly unpredictable cost) of buying one (much more predictable cost). Assuming you’re buying, here are the costs you may expect to incur:

· License
· Hosting
· Training and support
· Professional services (e.g. study configuration)
· Devices

You should evaluate whether your study and selected ePRO system will allow for patients to use their own devices, or if you will need to provision devices (or some mix thereof). The cost of provisioning devices, especially for a global study can be significant—in addition to the costs of the devices themselves, you will need to consider the costs of data plans, and logistics associated with supporting the devices. I’m a big fan of BYOD (bring your own device) but, depending on the study, it may not be feasible to utilize while maintaining scientific validity of data collected.

Once you’ve mapped out your costs of each route, you can begin to weigh these against the benefits of going eCOA.

cropped-istock_000037068804.jpg

Paper vs. eCOA

When you boil it down, people employ ePRO/eCOA to maximize data quality, increase productivity, and/or enable new capabilities that help answer their research questions. ePRO is e-source, so you don’t have worry about administering a paper data entry process. Depending on the study, the cost savings from this alone might justify ePRO.

There are some additional benefits ePRO offers over paper that may be harder to quantify, but nonetheless  very real. For example, there are clear data quality benefits to ePRO. The electronic system can ensure a minimum standard of data quality through edit checks and enforced data structures. ePRO data will always be cleaner than the same data captured on paper.

Benefits and Motivations for eCOA

 

The use of an ePRO system also allows you to know for sure when the data were recorded. For instance, patients can be reminded automatically when their diaries are overdue, and you now only have much stronger assurances that data were collected at the appropriate time (vs paper), you can also more easily monitor the study progress.

Bypassing manual data entry and having the system provide notifications to subjects to ensure data are captured in a timely way might allow for faster and better in-study decision making and even may accelerate study closeout. Also, an increasing amount of evidence exists that mobile-based messaging and communication strategies help increase patient engagement and treatment adherence. And of course, not having to deal with a stack of paper during a site visit might allow the clinician’s interaction with the patient to be higher quality.

Quantifying the benefits of all of these things can be tough, but start with those which are most quantifiable and see if those items alone these alone provide a compelling ROI (from my experience they often do).  Then the less tangible benefits become gravy to the ROI argument.  When modeling costs over time and a pay-back period, keep in mind that ePRO will typically carry a higher upfront cost than paper, with the cost saving benefits realized downstream over time. With today’s technologies, even most smaller studies should be able to realize a positive payback.

Naturally, there may be additional ROI factors to consider which are specific to your situation. If you have particular thoughts, questions, or experiences on this topic I encourage you to add a comment to this post.

A Look at the 2014 OpenClinica Conference Program – An Ecosystem of Innovation

The program for OC14 (the 2014 OpenClinica Global Conference) has been posted–what a line-up! Having been involved in each of the past 5 OC conferences, I can say that this one has a lot new and useful things to offer.  Many in the OpenClinica community are not aware of all the useful innovations produced by our community scattered throughout the globe. The theme of the conference is “An Ecosystem of Innovation,” and OC14 will help to communicate a number of the innovations available to you and show you how you can take advantage of them for your own work.

OC14 is a unique opportunity to enhance your capabilities and skills with OpenClinica in an information-packed 2 days, June 22-23 in Boston. Early bird deadline registration is May 2nd.

Here are some of the things you can do at OC14:

Interactive demonstrations:

  • OpenClinica Monitoring Platform
  • Converting OpenClinica Datasets to SDTM
  • DynaOCreports: A web-based reporting tool for OpenClinica
  • Medical Coding for OpenClinica EDC
  • OpenClinica-CTMS Integration with Clinical Conductor
  • New Features Playground
  • OpenClinica ePRO Mobile & OpenClinica ePRO Web
  • A Tour of Developer Resources
  • elluminate: Aggregate and Standardize Your Clinical Data
  • OpenClinica Enterprise Edition
  • Randomization in OpenClinica with RANDI2

Informative sessions, featuring innovative OC extensions, case studies, best practices, and more:

  • Lessons Learned from Integrating OpenClinica with Other IT Systems
  • Using OpenClinica for Risk-Based Monitoring and Monitoring Reports
  • Developer Meet-Up Report
  • Data Preparation, Delivery and Analysis: The Emerging Value of CDISC Data Standards in the New Era of Data Transparency
  • OpenClinica Extensions: From Nano to Macro
  • Importing Lab Normal Values: A Case Study
  • Risk-Based Monitoring with OpenClinica, add-ons and REST
  • con•nec•tiv•i•ty: Using Open Source APIs to Redefine the eClinical Ecosystem
  • OpenClinica in an Integrated Translational Environment
  • Maximizing your OpenClinica ROI with Community Engagement
  • EDC Methods in Studies Conducted in Western Kenya
  • Simplifying ODM with JSON
  • Expanding OC the Ecosystem

Workshops (in-depth, hands-on instruction in focused areas):

  • Rules for Advanced Users (includes new Rules-based calendaring features)
  • Best Practices for Building Studies
  • Meeting GCP and 21 CFR Part 11 Requirements with OpenClinica
  • Internationalizing OpenClinica
  • IT Primer for Setting-up and Running OpenClinica

In addition to the above, you can:

  • Connect with the developer community at a special OpenClinica Developers Meet-up.
  • Roll up your sleeves, relax, and enjoy the summer sun at a classic New England clam bake.
  • Get certified with 4-day OpenClinica Central User Training course while you are in Boston.

Here is the full program. Looking forward to seeing you in June!

– Ben

6 Days Left to Contribute to OC14!

That’s right–there are only 6 days left to submit proposals for participation in the 2014 OpenClinica Conference, June 22-23 in Boston. This is a unique opportunity to present at the premier OpenClinica event headlined by luminary Dr. Eric Perakslis, Executive Director of the Harvard Center for Biomedical Informatics and former Chief Information Officer at the U.S. FDA. Share your knowledge and experience, learn from others, and build valuable relationships.

Here are 4 ways to participate:

  • Presenting a session at OC14 is a great way to share your OpenClinica work and experience. Format can be lecture, panel discussion, or other creative idea.
  • Showing a demo can be a great way to get show your OpenClinica related technology in a hands-on way while obtaining direct feedback
  • Leading a workshop gives you a chance to take a deep dive into subject matter you have mastered.
  • Or, join as an attendee to soak it all in!

Learn more and submit your proposal at www.oc14.org. Deadline for submissions is March 31st.

Introducing OC14: Call for Content

Save the date for the 2014 OpenClinica Global Conference: June 22-23 at the Exchange Conference Center on Boston’s historic waterfront.Image

Planning is well underway. We are pleased to have as our keynote speaker, Dr. Eric Perakslis, Executive Director at the Harvard Center for Biomedical Informatics and former CIO of the U.S. FDA.

Do you want to present at OC14?

Presentation proposals are being accepted now through March 31st.

Spend some quality time learning with the best and brightest in the OpenClinica Community, while meeting new (and old) friends.

Early bird registration is now through May 2nd.

More at www.oc14.org.

– Ben Baumann

Synchronizing OpenClinica Instances: Another Option for Using OpenClinica in Disconnected Settings

While tablet software maker Mi-Co is showcasing an integration of their Mi-Forms tablet-based forms software with OpenClinica that can be used in “offline” settings, elsewhere within the OpenClinica community, Raymond Omollo and Michael Ochieng have developed a separate option for using OpenClinica in settings without internet connectivity. Their method synchronizes multiple locally deployed instances of OpenClinica with a central OpenClinica database. Michael and Raymond recently presented their work at the OC13 conference. You can access their presentation slides here to see how they address key issues such as synchronization, back-ups, encryption, and user training.

Synchronization Flow Chart
Synchronization Flow Chart

While working for Drugs for Neglected Diseases initiative (DNDi), Michael and Raymond devised this approach for a WHO study of Buruli ulcers in West Africa (Ghana and Benin). The study, which is ongoing as of the date of this post, is a randomized controlled trial comparing the efficacy of 8 weeks treatment with clarithromycin and rifampicin versus streptomycin and rifampicin. It involves 430 subjects across 5 sites. The participating sites have limited or unstable internet connectivity, so a solution is needed that provided timely, auditable, and quality data entry given this constraint. A positive byproduct is enhancing the capacity of these disconnected sites to utilize EDC.

As they say, necessity is the mother of invention. And open source makes it easier for people to believe that what is necessary can in fact be accomplished. Kudos to Raymond and Michael for devising a solution that works for them. Perhaps it may work for others as well.  If you’d like to access the source code and documentation for their work, you can download these from the OpenClinica Tools and Tips page (scroll to bottom).  You can reach Raymond and Michael on the OpenClinica Developers mailing list: developers@openclinica.org.

– Ben Bauman

More About DNDi

Headquarted in Geneva, DNDi is a global organization that develops safe, effective, and affordable treatments for neglected diseases. The neglected diseases that DNDi tackles afflict many of the world’s poorest people (Malaria, Leishmaniasis, Chagas disease, Sleeping Sickness, Paediatric HIV, Filaria). DNDi’s goal to develop 11 to 13 new treatments by 2018. More at www.dndi.org.