The post-pandemic clinical trial landscape has paved way for the integration of technology, data analytics, and digitization to facilitate all aspects of trial management from patient identification and recruitment to data collection and statistical analysis

1. What is eCOA and ePRO?
The post-pandemic clinical trial landscape has paved way for the
integration of technology, data analytics, and digitization to facilitate all
aspects of trial management from patient identification and recruitment to
data collection and statistical analysis. Decentralized, site-less, and virtual
trials are becoming increasingly popular based on their several advantages
such as:
● Improved patient recruitment: the ability to reach out and recruit
patients that are geographically distant from the trial location thereby
increasing patient diversity and number
● Increased patient retention and compliance: reduced need to
travel and reminders to fill in outcomes information through SMS or
e-mail reminders
● Reduces site maintenance and staff costs due to their virtual nature

2. ● Increased data quality as information is entered in a timely manner
which allows for continuous and real-time monitoring of efficacy and
safety events
● The ability for seamless progress of the trial independent of global
issues and travel restrictions
In addition to the shift from physical to virtual approaches to clinical trials,
another aspect of trials that is evolving is ‘patient-centricity’. Patient-centric
approaches involve considering both the convenience of patients such as
their travel time and loss in productivity that may be incurred due to travel
to trial sites as well as their feedback that can help guide trial management
and safety monitoring. Perspectives from patients regarding the drug or
medical device can support physician preferences and payer
reimbursement issues and help regulators make more sound and robust
approval decisions. Patient feedback also forms part of real-world data
(RWD) and real-world evidence (RWE) through the processing of data
obtained from patient registries, patient surveys, and questionnaires. Thus,
the amalgamation of patient-centricity and technology has led to the use of
information obtained directly from patients for making decisions on the
safety and efficacy of experimental drugs and medical devices in clinical
trials.
Clinical outcome assessments (COA) and electronic
COA (eCOA)
The United States Food and Drug Administration (FDA) defines a clinical
outcome assessment (COA) as a measure that describes or reflects how a
patient feels, functions or survives. There are various types of COAs
depending on the person reporting the patient’s symptoms, but the
fundamental focus is on the patient's health status (Figure 1). The various
types of COAs are as follows:
● Patient-reported outcome (PRO) measure:

3. Measurement based on a report comes directly from the patient/study
subject about the status of the patient’s health condition without any
amendment or interpretation by a clinician or anyone else.
● Observer-reported outcome (ObsRO) measure:
Measurement is based on a report of observable signs, events, or
behaviors related to a patient’s health condition by someone other than the
patient or health professional such as a parent, caregiver, or someone who
observes the patient in daily life.
● Clinician-reported outcome (ClinRO) measure:
Measurement is based on a report that comes from a trained healthcare
professional after observation of a patient’s health condition through the
interpretation of observable signs, behaviors, or other manifestations
related to the disease or condition.
Performance outcome (PerfO) measures: measurement based on
standardized task(s) actively undertaken by a patient according to a set of
instructions.

4. Figure 1. Types of Clinical Outcome Assessment (COA)
Initially, most COAs were paper-based wherein the data entered by the
patient, caregiver, or clinician on paper forms were transcribed manually
onto electronic databases. This caused several errors in data transfer,
issues with data security, and inaccurate information as the data was not
usually entered by the patients at the time of occurrence of
signs/symptoms. The advent of technology, improved availability and
accessibility to the internet, and increased patient comfort with the use of
mobile technology have led to the uptake of electronic COAs in clinical
trials. An eCOA is a digital version of a COA and is used to measure the
efficacy and safety of health interventions. Various technologies such as
mobile devices (smartphones, tablets), computers, and interactive voice
response systems (IVRS) are deployed to capture information about a
patient’s health status and can be in the form of ePRO, eObsRO, eClinRO,
and ePerfO. Advantages of COAs include:

5. ● Time-savings as they eliminate the steps associated with transferring
information entered on paper records to databases which are often
error-prone
● Improved patient compliance through patient alerts and reminders
● Improved data quality as the data is entered by the patients in a
timely manner and not just at the end of the trial or before a visit
● Data completeness through mandatory fields and validation checks
that allows for more thorough and complete data capture
● Allows for real-time data capture and monitoring of adverse events
● Improved regulatory compliance
Patient-reported (PRO) measures and electronic
Patient-reported Outcome (ePRO)
Patient feedback and experience with healthcare interventions are
important as they form an integral part of RWE which is being looked upon
by regulators as an essential component of data that aims to monitor the
safety and efficacy of treatments. There are various types of PROs that
refer to different endpoints (Figure 2).
Figure 2. Various measures by PROs

6. PRO instruments include patient diaries and validated questionnaires that
are used to capture data directly from patients and can be in the form of
ePROs. PRO measures are usually developed with input from various
stakeholders such as clinicians and psychometric experts to ensure that
the questions address issues in an objective manner without any bias.
Electronic patient-reported outcome (ePRO) measures allow data to be
entered directly by patients in an electronic format. Like other eCOAs,
ePROs also have certain distinct advantages over traditional PRO
measures such as:
● Real-time data capture which is particularly important in case of pain
symptoms and safety events that require immediate attention
● Better patient adherence because of easy-to-fill questionnaires that
allow for data entry at the time of occurrence
● Improved patient convenience as data can be collected from
technologies such as smartwatches and is transmitted directly to
research teams without any change in the patient’s daily activities
There are different types of ePROs such as:
● Electronic questionnaires that periodically assess patients’ health
status at predetermined times set by the clinical trial protocol on
tablets, computers, and mobile devices
● Patient diaries or activity logs that involve data entry by the patient at
any time convenient to them which can help detect safety issues as
soon as they occur
● Fitness and health trackers that automatically record data without any
intervention from the patient
● Ecological momentary assessment (EMA) assesses a patient’s
experiences, behaviors, and moods as they occur in real-time
Thus, technological advances combined with the COVID-19
pandemic have increased the uptake of eCOAs and ePROs to

7. capture patient data that can help make better and more robust
decisions about newer treatments. Despite the obvious advantages of
these patient-centric and remote assessments, it is essential for the
sponsor and clinical trial team to determine the type of outcome that
is necessary for a particular trial and choose a suitable measure to
capture this. Furthermore, it is also extremely important to use a
validated measure and ensure that the platform for data collection
whether it be a smartphone, tablet, or computer can be suitably
integrated with the eCOA system. It is the hope that eCOA will help
reduce patient burden and improve the patient's experience by
eliminating tedious paper-based data collection methods.
References
● Clinical Outcome Assessment (COA): Frequently Asked Questions |
FDA
● Patient-reported outcomes: A new era in clinical research – PMC
(nih.gov)
● The importance of patient-reported outcomes in clinical trials and
strategies for future optimization – PMC (nih.gov)
● Why Aren’t All Pro/Coa Clinical Trials Using Electronic Data
Collection To Optimize Data Integrity And Patient Experience? –
Value in Health (valueinhealthjournal.com)