eCOA’s time has come. The market is currently estimated to be worth $2.3 billion, with projections showing it reaching nearly $5 billion by 2030. Despite this, paper still plays a prominent role for some clinical trials today.
At first glance, paper may seem simple and familiar, even economical. However, in today’s regulatory and operational environment, paper COAs are not a risk averse choice when held to the standards of what sponsors, CROs, and regulators are looking for trial data to prove.
Regulatory risk: can paper truly meet ALCOA standards?
Clinical trial data must meet ALCOA principles, meaning it must be Attributable, Legible, Contemporaneous, Original, and Accurate. Paper COAs inherently struggle to satisfy these standards. Handwritten entries lack embedded authentication safeguards, making attribution difficult to verify. Legibility becomes a variable, introducing interpretation disputes and transcription errors. The contemporaneous requirement is undermined when participants complete entries retrospectively, a practice often referred to as forward or back filling. Original documents can be lost, damaged, or altered, and manual transcription into electronic databases creates additional opportunities for human error.
The risks are not theoretical. A widely cited 2002 BMJ study found that 45 percent of participants forward-filled paper diaries at least once. That finding highlights a structural vulnerability in paper-based data collection. While the study is of age, it was conducted at a time when paper COA use was at its peak, and reflects its inherent issues.
- Reported Compliance: Based on what patients wrote in the diaries, compliance was 90%.
- Actual Compliance: Based on the electronic logs, actual compliance was only 11%.
- Hoarding Behavior: On 32% of study days, the diaries were not opened at all, yet patients later turned in diaries that were fully completed for those days (Stone et al., 2003). This indicated massive amounts of both back-filling (filling past days) and forward-filling (filling future days to "get it over with").
Electronic Clinical Outcome Assessments, or eCOA, are designed to address these weaknesses directly. Time stamps, audit trails, automated validation checks, and secure attribution mechanisms are built into the system. In an inspection-ready world, those safeguards are not enhancements, they are expectations.
Data integrity risk: variability, missingness, and bias
Every missing diary entry, illegible response, or delayed transcription introduces uncertainty. With paper workflows, those uncertainties accumulate. Sites must decipher handwriting, reconcile discrepancies, and issue queries long after the participant interaction occurred. The result is higher variability, more missing data, and increased potential for bias.
Electronic Patient-Reported Outcomes, or ePRO, have demonstrated measurable improvements in data precision. In one study conducted by Merck Research Laboratories, ePRO reduced standard deviation by 41 percent compared to paper methods. Lower variability strengthens statistical confidence and protects the integrity of endpoints.
Compliance risk: when patients are unsupervised
Unsupervised questionnaires and daily diaries are particularly vulnerable in paper-based studies. Participants may forget to record entries, complete multiple days at once, or inaccurately report timing. Without real-time oversight, these deviations often remain invisible until monitoring visits.
Electronic systems reduce these risks by design. Entries are time stamped, response windows can be controlled, and forward or back filling can be prevented. Automated reminders prompt participants at appropriate times, and sites can receive alerts when compliance falls below predefined thresholds. This allows intervention before noncompliance compromises the dataset.
In studies where diary data support primary endpoints, reliance on paper creates unnecessary exposure. If adherence drives outcome validity, then the collection method must actively protect adherence.
Safety risk: delayed awareness
Certain therapeutic areas demand immediate visibility into participant-reported data. Monitoring for Suicidal Ideation and Behavior, for example, requires real-time awareness. Electronic tools such as the self-reported or interviewer-rated Columbia Suicide Severity Rating Scale can generate alerts the moment a risk threshold is met.
Paper cannot provide that level of responsiveness. Information surfaces only when the document is reviewed, which may occur days or weeks later. In safety-critical contexts, delay is not neutral.
Operational risk: compounding inefficiencies
Paper COAs introduce friction across the trial lifecycle. Study packets must be printed, assembled, shipped, tracked, and archived, often for more than 15 years. Visual analog scales may require manual measurement. Complex ClinRO instruments, such as the Psoriasis Area Severity Index, demand careful calculation that is prone to human error. Each completed form must then be transcribed into an electronic database, verified, and reconciled.
These manual steps increase query volume, monitoring time, and the likelihood of delay. In large, multi-country studies, the burden multiplies. In rare disease trials, where every data point is critical, even minor loss or inconsistency can undermine interpretability.
Operational inefficiency eventually becomes timeline risk, and timeline risk becomes competitive risk.
Participant experience risk: not designing for today's norms
Participants today live in a digital ecosystem. They manage finances, communicate with providers, and access health records through smartphones and tablets. Asking them to rely on paper diaries introduces friction that feels out of step with modern expectations.
Well-designed eCOA platforms follow a quality-by-design philosophy. Tasks are released when needed, reducing overwhelm. Conditional branching logic ensures participants see only relevant questions, improving clarity and engagement. Real-time validation checks support data completeness at the point of entry. Notifications and reminders can be aligned with daily routines, reinforcing adherence in a way that feels integrated rather than intrusive.
Bring Your Own Device, or BYOD, models further reduce burden by allowing participants to use familiar personal devices. When participation feels intuitive, engagement improves. When engagement improves, data quality follows.
Ignoring participant expectations does not simply create inconvenience. It increases the likelihood of disengagement and missing data.
Strategic risk: inconsistency across development
Some sponsors consider paper in early-phase trials, assuming smaller studies carry lower exposure. However, shifting data capture methodologies between Phase I and later phases can introduce inconsistencies that complicate analysis and operations. Differences in collection methods may affect longitudinal comparisons, require retraining, and increase the complexity of technology migration mid-program.
Adopting eCOA early provides continuity and scalability. Consistency across phases reduces long-term vulnerability and supports a more cohesive development strategy.
Oncology/regulatory risk: the FDA has made the patient voice non-negotiable
For years, the FDA has been making one point crystal clear to sponsors and CROs, especially in oncology: the patient voice must be incorporated whenever possible.
Through the Patient-Focused Drug Development, or PFDD, initiative, reinforced by the 21st Century Cures Act, the FDA asks that patients provide their unique perspective on treatment effectiveness. Outcomes that truly matter, such as functioning, quality of life, and side effect burden, are often best measured directly from the patient without interpretation by clinicians.
The primary mechanism for capturing this voice is through Clinical Outcome Assessments, particularly Patient-Reported Outcomes, or PROs. Despite this clear direction, adoption has lagged. Between 2010 and 2020, only 9 of 108 FDA-approved oncology drugs, just 8.3 percent, included electronic patient-reported outcomes in their labeling. This gap represents not just missed opportunity, but mounting regulatory risk as expectations continue to evolve.
When could paper be considered?
There are limited situations in which paper may be reasonable, such as very small, short-duration Phase I studies conducted entirely on site, or trials with extremely infrequent questionnaire collection. Even in these cases, sponsors must weigh the cumulative regulatory, compliance, and inspection risks against perceived simplicity.
In most modern trials, paper is no longer the lower-risk option.
The real question in 2026
Paper may appear straightforward and familiar. However, in 2026, it concentrates preventable regulatory, scientific, safety, operational, and engagement risks into one fragile medium.
Simply put, in 2026, paper COAs are not “cheaper,” they’re riskier.
