With the industry-wide push towards patient-centricity, electronic clinical outcome assessments (eCOAs) have become a more widely used strategy to streamline patient data collection, provide real-time access to data for review and monitoring, enhance patient engagement, and improve the integrity and accuracy of clinical studies. While many companies have chosen to partner with eCOA vendors to provide electronic devices for use in a clinical study, other sponsors are exploring “bring your own device (BYOD)” strategies to save costs and start-up time. Rho answers some commonly asked questions about eCOAs.

Q: What is an eCOA?
A: Using technology such as smartphones, tablets, or computers to allow patients, health care professionals, or caregivers to directly report outcomes from clinical trials.

Q: What are some examples of eCOA assessments and devices?
A: There are a variety of electronically captured assessments, including patient reported outcomes (PROs), clinician-reported and health-care professional assessments (ClinROs), observer reported outcomes (ObsROs), and patient performance outcomes administered by health-care professionals (PerfOs). The main methods for collection of eCOA data include computers, smartphones, and tablets, as well as telephone systems.

Q: What is the difference between those eCOA assessments?
A:  The differences in the eCOA assessments mentioned above are:

• Patient Reported Outcomes (PRO) – A report on the status of a patient’s health condition that comes directly from the patient. For example, asking a patient, on scale of 1-10, what is your level of pain today.
• Clinical Reported Outcomes (ClinRO) – When a health-care professional observes the patient and records the clinical data. In this scenario, the health-care professional often provides his/her interpretation of a patient’s observable behavior of physical signs. For example, a Parkinson’s disease patient may be unable to report through ePRO. Instead, the clinician would report that patient’s clinical outcomes.
• Observer Reported Outcomes – When clinical data is reported by an observer that is not a health-care professional, such as a parent or caretaker. This data does not include a medical judgement or interpretation. In this case, the patient typically cannot respond themselves. This is often the case when studying infants or patients that are mentally impaired.
• Performance Outcomes (PerfO) – Data that is generated when a patient performs a tasks according to instructions provided by a health-care professional. For example, performing memory recall or other cognitive testing.

Q: What are some considerations when deciding if an eCOA is right for your clinical trial or program?
A: There are 2 critical factors to consider before embarking on this path:

1. Need – Is there a need to collect clinical outcome data from a person and is there a benefit to collect this data electronically? For a given clinical outcome or assessment tool is there a benefit to the study collecting the data directly from the patient? For certain endpoints eCOA data is more appropriate than for others. If the study objective is to understand the subjective impact of a product on the patient or health-care community, a well-designed eCOA can be a valuable tool to capture this information. These data can tell you specific information about your product and help inform the labeling language that will be included in the package insert of your marketed product. The eCOA device can be configured to require daily or weekly data entry and real-time review by site personnel prior to the next scheduled clinic visit. Additionally, the eCOA system can send out alerts and reminders to patients (to ensure data is entered in a timely manner) and to health-care personnel (to ensure timely review and verification of data and subsequent follow-up with patients as needed).

2. Cost/ benefit of eCOA vs paper – Many studies still use paper methods to collect clinical outcome data, and there are cases when it may make more sense to achieve your study objectives through paper rather than electronic methods (e.g., Phase 1 studies with limited subjects). However, several types of clinical outcome data can be collected more efficiently, at lower cost, and at higher quality with electronic approaches (e.g., diary data or daily pain scores). From an efficiency standpoint, data can be entered directly into a device and integrated.

Q: What are some considerations during the planning phase?
A: Studies that include eCOA for data collection require additional time and planning to ensure successful implementation. eCOA instruments often require additional validation (such as equivalence testing), licensing, translation, vendor management, user acceptance testing, and training for both patients and site personnel.

Q: Where does the FDA stand on the use of eCOAs?
A: FDA has encouraged the use of PROs to capture certain data endpoints, such as pain intensity, from a patient population who can respond themselves. Recent regulatory agency guidance has encouraged the use of eCOAs to evaluate clinical outcome data. The fifth authorization of the Prescription Drug User Fee Act (PDUFA V), which was enacted in 2012 as part of the Food and Drug Administration Safety and Innovation Act (FDASIA), included a commitment by the FDA to more systematically obtain patient input on certain diseases and their treatments. FDA holds COAs to the same regulatory and scientific standards as other measures used in clinical trials. To support these efforts, the FDA has developed an extensive Clinical Outcome Assessment Qualification Program, which is designed to review and assess the design, validity, and reliability of a COA for a particular use in a clinical study.

Q: How is the integrity and accuracy of the data maintained when using an eCOA?
A: For the cases where an instrument was developed for paper-based collection or an instrument is collected using multiple modes, it may be necessary to test for equivalence and additional validation. This regulatory expectation is often required (especially for primary and secondary endpoints) to ensure that the electronic version of the instrument is still valid and data collected with mixed modes are comparable. The qualification of an eCOA often requires input from patients and/or health-care professionals to evaluate the effectiveness of the assessment. This input is necessary for the regulatory agency to determine whether the eCOA can accurately measure what it’s supposed to measure (validity) and to demonstrate that it can measure the outcome dependably (i.e. that the measure is reliable). Make sure the eCOA supports your intended labeling claims because the instrument will be evaluated in relation to the intended use in the targeted patient population.

Q: Is there any research supporting the effectiveness of eCOAs?
A: At this time, there are no reliable metrics on the ROI of eCOA. Some claim that the use of eCOAs can result in higher quality data, less monitoring, and greater patient engagement, including compliance in eCOA trials being 90% compared to 30% for non eCOA trial and a more than 50% savings when data is entered via eCOA instead of on paper. While there is anecdotal evidence to support these numbers, there have been no studies done to officially verify them.

Q: What are some of the caveats of using an eCOA?
A: The data is subject to more bias than other objective measures, so it’s critical to take steps to reduce bias as much as possible. Examples of ways to reduce bias include single- or double-blind clinical trial designs, wherein the patient or assessor is not aware of the assigned treatment, and building in a control arm (e.g., placebo or active comparator) to compare eCOA outcome data across treatment groups. Any downsides to using the electronic data collection methods tend to be associated with the costs and time to implement the system at the beginning of the clinical study.

Q: How do we determine which eCOA is best for data collection in our clinical trial?
A: The most effective choice depends on the protocol design, the length of data collection, what intervals data will be collected at, the type of data, the study phase, the patient population, the instrument being used, and whether the measure is a primary safety or efficacy endpoint. Making your eCOA selection based on those criteria will help ensure that you’re choosing the most appropriate device for your clinical trial.

Q: What value does a CRO bring in working with eCOAs?
A: A CRO well-versed in best practices around eCOAs should be able to advise and support you on the following:

• Determine endpoints where eCOA data is appropriate
• Determine the cost/benefit of electronic versus paper data capture
• Determine the best mode of electronic data capture
• Recommend eCOA vendors when appropriate
• Perform equivalence analysis
• Facilitate discussions with regulatory authorities
• Manage the entire process of eCOA implementation

Rho can partner with sponsors to develop and implement their eCOA strategy and manage the entire process to ensure successful eCOA implementation.