Applied Clinical Trials
How the adoption of electronic clinical outcome assessment in trials can drive increased communication and patient reporting of events.
The use of electronic clinical outcome assessment (eCOA) represents a mechanism of capturing both patient and clinician reported outcomes digitally instead of on paper. The most common use of eCOA is for data capture in clinical trials. The evidence for obtaining improved data quality with digital systems over paper has grown substantially and as such, avenues for using eCOA in healthcare are being explored. eCOA captures data on handheld smartphones, tablets, browsers, interactive voice response systems, and patient’s own devices (bring-your-own-device, or BYOD), using secure systems that meet regulatory guidelines for electronic capture of clinical data. Consent for clinical trials details patient privacy, explains how the trial will be conducted, and confirms that the clinical site owns all clinical research data. The patient may authorize trial access to their lab, imaging, and electronic medical record (EMR) data for integration with their study data.
As adoption and the use of eCOA grows, additional learnings have provided a more complete understanding of how to use it effectively in order to derive the benefit of improved data quality. Herein, we will discuss the evidence of how the use of eCOA can promote increased communication between patients and clinical staff, increase patient reporting of events, and how tools such as training and patient engagement should be implemented to deliver maximal benefits from the use of technology. Collecting high quality data for clinical research requires a blend of clinical science and technology. Clinical science influences patient engagement behaviors with study design, collection schedules, predictive instruction, and assessment selection.
As more questions arise about improving patient engagement in clinical trials, many sponsors are finding that the answers may lie in the use of technology. Most pharmaceutical companies are considering methods for implementing novel technologies (e.g., activity trackers and mHealth devices) in their trials, in order to maintain better, more consistent interaction with study subjects. Many of these devices are still in proof-of-concept testing. Whether they will find their place in clinical research will be the decisions of global regulators. The US 21st Century Cures Act mandates that FDA regulate accessories based on their intended use, instead of based upon the parent device with which the accessories are associated.
What many sponsors may not realize is they already have access to regulatory-approved technology that can address current patient engagement challenges. Researchers will find that the use of eCOA not only improves data quality, but also offers the potential to improve patient engagement during clinical development.
The benefits of capturing high quality clinical trial data via eCOA have been widely recognized for more than a decade. Researchers have documented significant improvements in patient protocol compliance and data quality, a reduction of missing data and data “noise,” and, most importantly, increased study power with fewer patients.1
Here we review some of the well-established literature demonstrating how eCOA can also improve patient/clinician communication and candor vs. traditional paper-based COA, helping sponsors to keep patients better engaged during clinical development.
eCOA prompts and increases patient/clinician interactions and enables subjects to think through their symptoms prior to meeting with site staff. As a result, patients are more likely to bring up clinical events in discussions with the clinical site, since the eCOA completion prompts their memory of additional details. For example:
eCOA has been proven to increase patient candor. Patients are more likely to report more (and more severe) events electronically than on paper. This principle applies across a spectrum of indications and is generally applicable to patient-reported data. Patient reporting on diverse topics such as medication compliance and blood glucose levels are common examples.
Self-reported electronic data capture (EDC) enables increased patient candor in suicidal ideation and behavior. Patients are more likely to reveal a higher frequency and severity of symptoms than ascertained by site interviewers. These phenomena are also well documented for topics including sex, drug/alcohol abuse, obesity, HIV, and mental health.
There is considerable evidence that using eCOA instead of paper is a mechanism for achieving improved compliance with patient reported outcomes collection.13 In addition to providing greater accountability in reporting, electronic media is noted by patients in general as more engaging compared to paper. For example, patient preference for using eCOA technology over paper has been shown across therapeutic areas and demographics; whether a population is technologically savvy or not, there is universal preference for using eCOA over paper. This is noted in published studies such as in oncology,14,15,16 diabetes,17,18 headache,19 inflammation/arthritis,20,21,22 pain,23 respiratory,24,25 and gastrointestinal disorders.26
Programming a patient or clinician reported outcome assessment into a digital system reduces errors by avoiding errors in logic such as branching or scoring, but what technology alone cannot address is variability in patient and clinician understanding of how to complete the assessments. From a patient perspective, the total time spent on informed consent is the strongest predictor of patient comprehension in a clinical trial. Comprehension is maximized when consent takes at least 15 minutes.27 Studies show that training a patient on the instrument’s properties and clinical trial expectations is critical to reducing noise.28 And, regulatory guidances from the FDA and the European Medicines Agency (EMA) recommend training patients, caregivers, and site staff not only on the assessments but also on the EDC elements.29,30,31 Patients themselves strongly assert a need for training (see Figure 1 below). Over 95% of 437 patients who express an interest to participate in a clinical trial indicated that training is needed. In addition, caregiver variability32 and placebo effect33,34 are also noted to reduce data quality and can be similarly addressed with caregiver. Rater training for site staff conducting clinical interviews and assessments reduces inter- and intrarater variability and improves data quality.35,36,37
Didactic training, while useful, is not the most effective mechanism for sustained learning and improved rater reliability. Studies show that interactive training is an optimal mechanism for user engagement, improvement, and retention of learning.38,39,40 Interactive training-including video modules that reside on the same device as the eCOA assessment-represents a solution whereby training can always be accessible in an offline environment for the subject or site staff.
The use of technology to capture clinical trial data electronically, such as eCOA, can represent a change in behavior or practice for the subjects and site staff using it. This additional factor should be considered such that user interfaces are not only simple, but also engaging and motivate the desired behavior (compliance with patient and clinician reported outcome assessments). Clinical science and the use of patient engagement tools and strategies can provide evidentiary-based mechanisms for maximizing both data quality and quantity. Key factors to drive engagement and
compliance include a simplified study design and schedule, collection of key assessments only, minimized burden on subjects and sites, and the combination of useful trial information into a single location, such as the eCOA trial device. Tools such as alarms and reminders, graphics both static and interactive, progress bars during questionnaire completion, adaptive designs, on-device time estimates to patients of how long an assessment completion will take, appointment scheduling, educational information, training, and feedback on data/results during the trial all represent mechanisms by which user motivation and compliance with eCOA can be enhanced.
There is a wealth of evidence demonstrating the value of eCOA in fostering better communication and increasing candor between patients and clinical site staff, as well as in improving clinical outcomes. However, in use of technology, there are human elements that need to be considered regardless of the simplicity of the user interface. These aspects include the vital role for training and engagement strategies in parallel with the use of eCOA. There are aspects of obtaining high quality clinical trial data that are dependent on patients and site staff having a unified understanding of expectations and the following of a standard methodology for data capture.
This environment is markedly different from that of clinical care in many ways. For example, in clinical care if site staff are nurturing, encouraging and positive and there is a placebo effect, the impact of this behavior is very different than if this same behavior is replicated within a clinical trial where neutral behavior and accurate reporting are paramount to distinguishing placebo from treatment. Similarly, setting these expectations with subjects is also critical. Patients may feel obliged to report feeling better, when they are not, if it is not understood by the subject how important accurate reporting is to clinical trial outcomes.
Overall, combining science and technology can enable better patient-physician communication during a trial; sponsors will have the benefits of higher quality data collection, and tools/strategies such as training and patient engagement are key elements to achieving successful reporting of patient and clinical outcomes.
Susan M. Dallabrida, PhD, is Vice President, eCOA Clinical Science & Consulting, ERT; email: Susan.Dallabrida@ERT.com
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