Patient reported outcomes (PROs) play a key role in clinical trials. Both the US Food and Drug Administration (FDA) and ISOQOL describe a PRO as any health-status report coming directly from the patient, unfiltered by clinicians. PROs reveal outcomes that matter to patients, like pain levels, fatigue, and the ability to carry out normal activities.
Historically, PROs were secondary. However, regulators, researchers, and patients now see them as essential for designing and evaluating patient-centred interventions, shifting trials from “What does the drug do?” to “How does the treatment affect daily life for the patient?” This change means PROs are no longer optional but rather vital for showing the real-world impact of clinical interventions.
Regulators around the world are paying more attention to PROs since trials must reflect patient priorities and not just lab data.
In the US, the FDA’s 21st Century Cures Act encourages the use of patient experience data in drug development and regulatory decisions. This includes PROs, especially when they highlight symptoms, side effects or impacts that clinicians might overlook. As such, patient input is directly shaping treatment approval. We’re also seeing strong support for clearer PRO design and reporting. Two key tools helping with this are:
These tools help raise the bar for PRO use in trials, shifting PROs from an afterthought to a planned, meaningful part of the research to meet both patients and regulators expectations.
Clinical trials often focus on what can be measured in a lab such as tumour size, blood counts, survival time. However, relying on lab data alone can result in overlooking the patient experience. That’s where PROs add real value, giving a direct line to patients’ experiences.
They capture:
These insights help researchers and regulators see not just if a treatment works, but if it improves daily life. Let’s look at a few examples. In oncology, a cancer drug might shrink tumours but leave patients too fatigued to leave bed. PROs track that. In chronic pain, patients might report good days and bad days, something clinical scores often miss. Then, in haematology, bleeding episodes might be brief but distressing. PROs help capture how these affect daily confidence and safety. Without PROs, we risk missing the outcomes that matter most. PROs ensure trials reflect a patient-centred value.
Choosing the right PRO measures shapes the data you collect, and ultimately, the story you tell about patient experience. So, what makes a good PRO measure? Here are four key criteria:
Validity
Does the measure actually assess what it claims to? For example, a fatigue scale should reflect real tiredness, not just sleep habits.
Reliability
Does it give consistent results over time, when the patient’s condition hasn’t changed?
Responsiveness
Can it detect meaningful changes, whether patients are getting better or worse?
Burden
Is it short and simple enough for patients to complete, even when they’re unwell?
To help with selection, many trials now use item banks like PROMIS (Patient-Reported Outcomes Measurement Information System). These tools use Item Response Theory (IRT) to tailor questions to each patient, keeping surveys brief while still capturing detailed, accurate data.
Importantly, selecting or developing PRO instruments must involve the patients themselves. Frameworks like COMET (Core Outcome Measures in Effectiveness Trials) and COSMIN (Consensus-based Standards for the selection of health Measurement Instruments) help guide this process, ensuring outcomes are relevant, clear, and aligned with patient priorities.
Once you've chosen the right PRO measures, the next step is to collect them smoothly and consistently. Good administration keeps data reliable, and patients engaged.
PROs can be collected in two main ways:
Paper
Simple to use but prone to missing data, late entries and transcription errors.
Electronic PROs (ePROs)
Entered via tablets, phones or computers. These are more reliable, reducing errors, time-stamp entries, and enabling automatic follow-ups.
While ePROs are now widely used, they need planning. Not all patients are confident with technology and some may even lack internet access or prefer paper. Therefore, it’s important to offer support or alternatives when needed.
Site staff play a key role and should be trained to introduce PROs, respond to concerning scores (e.g. high pain), and handle technical issues.
Alert-management workflows are also essential for ensuring urgent symptoms aren’t missed. For example, high-risk responses can be flagged automatically and sent to a nurse, with steps for quick follow-up.
Real-time dashboards make it easier to track progress, showing who has completed their PROs, highlight missing data, and flag outliers or trends. These tools also support site-level oversight, allowing sponsors to identify which sites are on track, and where extra support may be needed.
Even the best-designed PRO measures are only useful if patients complete them. So, how do we make sure that happens consistently and across diverse sites? Research offers some clear answers.
Scoping reviews have helped identify what works. These reviews scan a wide range of studies, using clear inclusion criteria and structured searches across databases like PubMed, Embase and Cochrane. Common themes include the value of dedicated staff, simple technology, and patient-first thinking.
One proven approach is to appoint dedicated PRO coordinators at each site. These team members help patients with logins, troubleshoot issues, and follow up on missed entries. Training programmes for all site staff also help. When teams understand the “why” behind PROs, they’re more likely to support patients and ensure consistent collection.
Technology can do some of the heavy lifting with the use of automated reminders via the likes of text, email, or apps to reduce missed entries as well as offer an avenue for patients to report symptoms from the convenience of their home. Additionally, kiosks or tablets at the clinic can also make it easy for patients to complete PROs while they wait.
Ultimately, the key is to offer simple, flexible tools that work across age groups, languages and comfort levels with technology.
Perhaps the most important piece is thinking like a patient. What would make you more likely to fill in a health survey? Evidence suggests that opting for shorter questionnaires help reduce burden and fatigue, flexible timing better accommodates individual’s day-to-day responsibilities, and small incentives like travel vouchers or thank-you notes all come together to help encourage engagement. Ensuring that the material is clear and educational is also very important in reaping the outcomes you want.
Completion rates improve with support, not pressure. With the right systems and a patient-friendly mindset, trials can gather better data and give patients a smoother, more respectful experience.
Missing PRO data is common but manageable. The key is to plan ahead, understand the reasons for missingness, and use clear methods to handle it.
Missing data usually fall into four categories:
Instrument-Level
A question or domain was skipped (e.g. patient skipped the fatigue section).
Participant-Level
The entire questionnaire was missed (e.g. patient forgot or declined).
Centre-Level
A whole site didn’t collect PROs at all, often due to training gaps or local issues.
Staff-Level
A site team member failed to prompt or assist the patient, usually by mistake.
Knowing the type helps identify where things went wrong and how to prevent it next time.
Most missing data can be reduced by thinking ahead. In the protocol stage, it’s important to consider these factors:
Clear Scheduling
Align PRO assessments with clinic visits to avoid extra burden.
Staff Training
Make sure teams know when and how to collect PROs and why it matters.
Patient Onboarding
Explain early on how PROs fit into the trial and how the data are used.
Backup Plans
Allow for catch-up options if a visit is missed, such as remote or phone-based PRO entry.
Despite best efforts, some data will still go missing. That’s where auxiliary data and imputation help. Auxiliary data, such as visit dates, lab results, or clinician notes, can help understand or adjust for missing patterns. Statistical imputation, on the other hand, can estimate missing values based on what’s known. For example, if a patient missed one fatigue score but completed the others, the missing score can be reasonably predicted.
Therefore, it’s important to plan for this in the analysis stage. That way, your results stay as complete and credible as possible. Missing data doesn’t have to mean lost insight. With smart design and a bit of planning, you can protect data quality and keep the patient voice front and centre.
Traditionally, PROs were seen as passive data points, something to review after a trial ended. But today, electronic PRO systems (ePROs) now play an active role in improving care during a trial.
Studies show that patients who used ePROs to report symptoms in real time had fewer emergency visits, reported better symptom control, and showed improved survival rates in some cancer trials.
This is because symptoms like pain, nausea or anxiety don’t need to wait for clinic visits. When patients can report issues early, care teams can act sooner, adjusting treatment, offering support, or preventing complications.
ePROs also drive broader changes in care delivery. With real-time dashboards, clinicians can spot trends across patients or sites, prioritise high-risk individuals, and improve communication between and care teams.
Some systems even let patients track their own progress, turning the data into a tool for self-management. This shift from delayed data to live feedback loops is reshaping how trials operate. It's also nudging routine care to become more responsive, patient-focused, and digitally enabled.
So, PROs aren’t just about what we measure but are becoming part of how we care. When used in real time, they don’t just capture outcomes, they improve them.
To make that data meaningful and trustworthy we need clear plans for how it will be analysed and reported. This starts well before the trial begins.
The analysis of PRO data should follow a pre-specified statistical plan, just like any other clinical outcome. This includes defining which endpoints will be analysed, what comparisons will be made, and how missing data will be handled.
The SISAQOL group provides helpful guidance here. It recommends methods that respect the timing and nature of PRO data (often repeated over time), support valid comparisons between arms, and account for missing data without bias.
If PROs relate to adverse events (AEs) such as fatigue, pain or nausea, these should be included in the safety monitoring framework, with clear definitions and thresholds for concern.
Once the analysis is done, reporting should be clear, complete and easy to interpret. The CONSORT-PRO extension outlines what to include in trial publications. This covers PRO objectives, methods of administration, timing of assessments, how the results were analysed, and how missing data were addressed.
Clear, visual displays also make a big difference in making results accessible. Some great examples include line charts showing symptom trends over time, bar graphs comparing quality-of-life scores between groups, and heatmaps or icon-based visuals for patient-friendly summaries.
PRO data deserves the same rigour as any other trial outcome. With clear analysis plans, recognised standards, and honest reporting, we can turn patient voices into findings that shape real-world care.
As PROs become more digital and data-driven, prioritising inclusivity is vital. Technology can improve patient input, but only if all patients can access and understand it.
Not every patient has the same tools or skills to complete electronic PROs. Common barriers include limited access to devices or internet, low health literacy which can make questions difficult to understand, and language barriers, especially in multi-country or diverse local settings.
To tackle this, trials should offer alternatives (paper, phone interviews, kiosks), translated instruments, and plain language material and visual aids to aid better understanding.
Training for staff is also key. When site teams understand these challenges, they can confidently guide patients through them.
Looking ahead, new tools are offering exciting ways to collect more meaningful, real-time data. These include
These advances bring real promise. But they must be rolled out with equity in mind, tested across diverse patient groups. The future of PROs is smarter and more connected. But if we want it to be fair and meaningful, we need to design with accessibility, inclusivity and empathy from the start.
Bringing PROs into a clinical trial doesn’t have to be overwhelming. With the right structure, it becomes a manageable and rewarding process. Here’s a clear five-step roadmap to integrate PROs effectively.
Start by defining the PRO objectives. What exactly do you want to learn from patients? It could be symptoms, treatment side effects, daily functioning, or emotional wellbeing. These should align with the trial’s overall goals and be meaningful to both patients and regulators.
Next, select the right PRO measures. Choose validated tools that match your study population and objectives. Make sure they’re reliable, valid, responsive, and low burden. Consider using item banks like PROMIS and involve patients in the selection process wherever possible.
Now design your PRO strategy into the protocol. This includes mode of delivery, assessment timing, staff training and workflows for administration and alerts, and patient-facing materials and onboarding. This step helps ensure smooth day-to-day data collection and patient engagement.
During the trial, monitor PRO activity in real time. Use dashboards to track completion rates, identify missing or delayed entries, and respond to alerts or safety signals. Monitoring helps keep both the data and patient care on track.
Finally, report your PRO findings transparently. Use the CONSORT-PRO checklist to guide publication. Include how PROs were collected, analysed and handled, especially if there was missing data. Use clear visuals so the findings are accessible to all audiences.
With this roadmap, PROs become more than a tick-box but rather a core part of how trials are designed, delivered, and understood. It’s a practical way to elevate the patient voice and make trials more meaningful for everyone involved.
PROs are no longer a ‘nice to have’ but rather a key part of good clinical research. From choosing the right measures to reporting results clearly, every stage offers a chance to bring the patient voice into focus. When PROs are planned carefully and used well, they do more than collect data. They help us understand how patients feel, what they struggle with, and what truly matters in their care.
So, whether you’re just starting out or refining your approach, keep PROs front and centre. Doing so will not only improve your study, it will also help ensure that research leads to real, patient-centred impact.
Quanticate's clinical data management team offer streamlined ePRO deployment, PROMIS/IRT-tailored measures and SPIRIT-PRO & CONSORT-PRO compliance, backed by expert monitoring, and real-time dashboards. Ready to amplify patient voice, prove real-world impact, and accelerate regulatory approval? Submit an RFI today.