Every regulatory submission involves uncertainty. The question is how much, and what the sponsor did before that moment to reduce it.
Patient-reported outcomes, when designed for the right indication, captured at the right frequency, and implemented faithfully by sites, give regulators something concrete to work with during benefit-risk evaluation. In most studies, they are not the primary endpoint. They work as a tailwind: supporting evidence that helps a benefit-risk decision feel less opaque to the people reviewing it.
That framing came from Ari Gnanasakthy, a PRO and regulatory expert at RTI Health Solutions with four decades of experience in outcomes measurement. He joined Derk Arts, CEO of Castor, and Lisa Charlton, CPO at Castor, for a webinar examining where PRO strategy works, where it fails, and what sponsors can do about it before the submission clock starts.
What the session covered
The right therapeutic area changes everything
PRO strategy is not a universal prescription. Ari was direct about this: dermatology, chronic pain, rare disease, and GI conditions are areas where patient-reported data directly shapes how regulators evaluate benefit and risk. Cardiovascular and certain oncology contexts are a different story.
“Patient experience data are very important because… it just helps regulators sort of minimize their uncertainty. And there are studies where it may not help.”
Ari Gnanasakthy, RTI Health Solutions
The corollary is that adding PRO instruments to a study where they do not belong produces noise, not evidence. More measurement is not better measurement.
The frequency trap in data capture
During the session, Ari cited upcoming research showing that biweekly ePRO capture achieved a 94% completion rate in an oncology cohort. Weekly capture, which intuitively feels more thorough, dropped to roughly 60%. “Almost useless,” he said of the weekly data.
Patient burden is a data quality decision, not an implementation footnote. Lisa added that timing within the day matters too. A diary for sleep disturbance belongs in morning assessments. A diabetes management diary belongs around fasting periods. These are protocol design questions. Making them late, during the build phase, means they reflect operational convenience rather than patient behavior.
The implementation gap that takes years to surface
The most persistent failure mode in clinical trial PRO strategy is not the design itself. It is the distance between whoever defines the COA strategy and whoever activates it at sites. Consultants write the plan. Operations teams implement it. Training materials often do not reach sites in time, or in a format sites can actually use.
“Strategy just doesn’t stop with defining the COAs for the protocol. It stretches all the way through implementation and training and activating the sites in order to help align with those strategic decisions and support the primary and secondary endpoints to remove the uncertainty.”
Lisa Charlton, CPO at Castor
Derk noted that this gap is nearly invisible by design. The feedback loop between PRO investment at study start and regulatory outcome at submission is measured in years, not months. The people who made the original strategy decisions have often moved on by the time the data arrives. When PRO data comes in with too much missing to be meaningful, the eCOA vendor typically absorbs the blame for a failure that happened upstream.
What’s in the full recording
The session runs just under 50 minutes. Several specific exchanges only exist in the full recording:
- Ari’s analysis of FDA review documents in oncology over a five-year window, examining which types of patient-reported safety and tolerability data entered product labels and which did not 21:10
- A question from attendees on how payers and HTA bodies weigh patient experience data differently from regulators, and Ari’s answer on why that distinction matters for sponsors designing multi-stakeholder evidence strategies 43:15
- Derk and Lisa on the institutional knowledge problem: why sponsors rarely build on past PRO success when the feedback loop spans an entire development cycle 37:00
- Ari on what sponsors owe patients after the trial ends: why PRO data is too often analyzed but never published back to the people who provided it, and what the field needs to do differently 47:30
The on-demand recording is available now. If you are designing a study in a PRO-critical indication, or working through a submission where patient experience data is part of the benefit-risk story, the conversation with Ari is unusually specific about what makes regulators more comfortable and what creates uncertainty instead. Built for clinical operations leaders, outcomes scientists, and regulatory strategists who want the operational reality, not just the framework.
Frequently asked questions
Which therapeutic areas benefit most from PRO data in regulatory submissions?
Therapeutic areas where symptoms and functional impact are central to benefit-risk evaluation benefit most, including dermatology, chronic pain, rare disease, GI conditions, and neurology or mental health. In cardiovascular disease or certain infectious disease studies, patient-reported outcomes tend to be exploratory rather than central to the regulatory decision. The key question is whether patient experience data directly informs how regulators evaluate benefit. If yes, PRO investment is worth building into the protocol from the start, not added as a secondary consideration after the primary endpoints are locked.
How does PRO data capture frequency affect completion rates in clinical trials?
Capture frequency has a more significant impact on data quality than most sponsors anticipate. Research Ari cited during the webinar found that biweekly PRO capture achieved 94% completion in an oncology study, while weekly capture dropped to roughly 60%. Higher frequency places more burden on patients and reduces adherence, which can make the dataset too incomplete to support a regulatory claim. The right frequency depends on the indication, the type of measure, and the patient population, and should be determined as part of the protocol strategy, not during eCOA configuration.
What causes patient-reported outcome strategies to fail during implementation?
The most common cause is the gap between the team that defines the COA strategy and the team that implements it at sites. Strategic decisions are often made by consultants or clinical leads who are no longer involved by the time site activation happens. Operations teams fill in the gaps, shortcuts accumulate, and training materials frequently do not reach sites in a usable format. By the time poor-quality PRO data arrives at regulatory review, it is too late to correct it. The feedback loop between PRO strategy decisions and submission outcomes spans four or more years, making it difficult for sponsors to build institutional knowledge from past failures.