The number of decentralized clinical trials is on the rise—and along with it, concerns about maintaining the quality of data collected and incorporating the voice of patients are increasing. Electronically collected clinical outcome assessments (eCOAs) and patient-reported outcomes (ePROs) can be useful tools if executed effectively.
To learn more about how eCOA and ePRO technology can be implemented in trial environments, Outsourcing-Pharma checked in with Florence Mowlem, director of eCOA at Medable.
OSP: Please share an overview of collecting data from patients in clinical trials—what technologies traditionally are used, and what are the issues with these tools/techniques?
FM: We are seeing a strong push to focus on incorporating the patient voice in drug development, as evidenced by the patient-focused drug development (PFDD) FDA guidance series that have recently come out. It’s really positive to see the drug development industry and regulators recognizing the importance of patient-reported outcomes (PROs) in medical product development and measuring concepts that matter to the patient. If we don’t, we can miss a real opportunity to build a well-rounded understanding of the value (benefit and risk) of a treatment and the more far-reaching benefits it can offer.
This means, for instance, that we are challenging the assumption that extension to life is the most beneficial outcome. In fact, if this extension is with a poor quality of life compared to a shorter survival period with a greater quality of life, this may be preferred by those who actually live with these conditions.
To capture the PROs measure, we have seen the progression from paper-and-pen to electronic data capture (ePRO) using apps or web-based solutions on provisioned devices, to enabling participants to use their own device – known as BYOD (bring your own device). The app for data capture can be downloaded directly onto their own smartphone or tablet, or they can access the PRO questionnaires via a web link, meaning participants don’t have to carry around a second device. Additionally, we are seeing trials incorporate wearables and sensors to capture data in a more continuous and passive manner to try and reduce the patient burden from too many ePROs and potentially offer an additional objective measure.
However, despite seeing an increasing interest in wearables and sensors for capturing data, it is important to consider that PROs provide participants the chance to have their voices heard and feel they are advocating for themselves, so I do not think we should necessarily view wearables and sensors as replacing PROs; rather, they can complement them.
OSP: How can eCOA offerings help improve and streamline the process?
FM: Clinical outcome assessments (COAs) include not only reports from patients (PROs), but also clinicians (ClinROs), observers (ObsROs), and from standardized performance tasks (PerfOs) – put an ‘e’ in front and it refers to capturing them electronically as compared to paper.
Electronic data capture can enhance the participant experience in clinical trials, and also the site experience - we mustn’t forget this. eCOA technologies offer efficiency in data capture, with the ability to capture real-time actionable data and drive completeness due to the controls that can be implemented, as well as ensure user authenticity and timely completion. This all serves to improve and streamline the process of data capture in clinical trials.
It’s important that we work with all the stakeholders involved in clinical trials who will touch the technologies and manage tech adoption in a way that isn’t overwhelming to users, whether they are patients, caregivers, or site teams. We need to introduce the tech into the clinical trial workflow in a thoughtful way and remember there are real people at the other end of the technologies we are providing, with other priorities besides learning new system after new system - we can’t forget that in all that we do.
At Medable, we have a patient and caregiver network, as well as a site network whose members provide detailed feedback on our platform and technologies. We capture their input in the development and implementation of Medable products and ensure we are solving the right problems for these various stakeholders. As an industry, we need to work closely with sponsors and the study teams running the trials as we set up systems like eCOA to ensure we are adding value to the process and not making it more cumbersome.
OSP: What advantages does combining eCOA with telehealth technology offer?
FM: In the traditional, brick-and-mortar clinical trial model, participants attend research sites for all study visits, which can be burdensome and potentially reduce diversity due to accessibility challenges (e.g., travel, length of visits, childcare, time away from work). The COVID-19 pandemic, which meant many participants could no longer attend site visits, really advanced the adoption of telehealth in clinical trials. Subsequently, this highlighted the value to be gained from remote assessments via telehealth solutions, and the demand for integrating this into trials has remained.
When we talk about combining eCOA with telehealth, we are primarily referring to clinical reported outcome (ClinRO) assessments. PROs have been completed remotely for many years and do not require interpretation from anyone else, whereas ClinROs encompass interaction between the participant and clinician, and on occasion a caregiver during the assessment.
Whilst conducting this activity via telehealth can offer the potential to reduce the described burdens, it’s important to note that ClinROs are all different and so we cannot adopt a one-size-fits-all approach as some may not be suitable for remote administration. More research is needed here to understand if the data obtained is comparable to face-to-face administration and to ensure accurate assessment – or perhaps we can find alternative methods to measure these outcomes. But, where it is appropriate, it represents another opportunity to move some trial activities away from the site and reduce some burden for the participants (their caregivers, if applicable) and sites.
OSP: Please tell us about PROs, including what some concerns might be about the timely, accurate collection of such info from patients, and how ePRO can help address those concerns.
FM: Data quality and integrity are at the heart of data capture in clinical trials. Electronic data capture provides a robust way to collect data from participants and meets the principles of ALCOA++ which ensures data integrity and includes its contemporaneous and accurate collection.
On paper, there is a lack of ability to ensure that the data is being captured at the right time, in line with that specified in the protocol; however, with electronic capture, the data is date and time stamped so we know exactly when ePROs were completed, also enabling real-time oversight. You can also ensure greater accuracy of the data, for example by programming specified limits on data entry to stop out-of-range responses and ensure that all questions are answered to reduce missing data.
A recent review of patient-reported outcomes labeling for oncology drugs approved found that both the FDA and European Medicines Agency (EMA) identified missing PRO data as problematic for the interpretation of efficacy, which demonstrates the value offered by ePRO. This is especially pertinent when PROs are being used as primary or secondary endpoints in a study.
The digitalized nature of the measurement can also reduce patient burden (e.g., receiving alerts rather than having to independently remember to complete questionnaires, or not having to return the paper copies to the site due to automatic upload of data), as well as the burden on trial staff who are not having to enter data manually into a data management system.
OSP: You mention that eCOA can help trial teams gain real-time oversight of collected information. Why is this helpful?
FM: Increasingly, we are seeing eCOAs being used as primary and secondary endpoints and for capturing data more frequently outside of the clinic environment to enable more real-time monitoring of a participant’s health status. Early insight can help rectify problems earlier. For example, as compared to paper methods, these technologies can be configured based on specific study parameters to automatically alert site teams when participants have a drop in compliance with their ePRO assessments or if they report certain symptoms, facilitating follow-up with the participant to remedy any problems.
OSP: How can Medable help study professionals incorporate eCOA tools into their operation?
FM: We recognize the importance of a seamless patient and site experience and strive to optimize this through our platform and suite of solutions that, together, span the entire trial lifecycle to increase the success of clinical trials and get the treatment to the patients who need it, faster. Those at Medable have a wealth of experience, with knowledge of industry best practices as well as the regulatory environment that we operate in, who can work closely with those conducting clinical trials to support the incorporation of eCOA into their trial.
OSP: Do you have anything to add?
FM: Most of us in the clinical trials industry know that we operate within a very conservative model, for good reason – but we also need to enable ‘controlled’ flexibility in our approaches where possible to foster patient centricity and optionality. Across the many therapeutic areas, while we desire a level of standardization in the approach to data capture, we also want to ensure the solution is right for the specific target population.
We also need to be careful with semantics around digital data capture. For example, when we talk about decentralized clinical trials (DCT), we may scare off participants, sites, and sponsors, as there is a misconception that DCT means a siteless trial and that it is an all-or-nothing approach. This is in fact not the case, DCT refers to moving certain activities away from a central site – such as PRO completion – and trying to provide a flexible clinical trial environment with optionality built into the design to enable more democratized participation in research, and technology-enabled trials can really facilitate this.
Flexibility is so important, but in a thoughtful and considered way with the right safeguards around that flexibility. A one-size-fits-all approach is not always applicable.