Patient-reported outcomes

Patient-reported outcomes

Patient-reported outcomes (PROs) are measurements of a patient’s health status, quality of life, or symptoms directly reported by the patient, without interpretation by clinicians or researchers. In randomized controlled trials (RCTs), PROs play a vital role in capturing the impact of interventions from the patient’s perspective, complementing clinical or laboratory outcomes.

Importance of PROs in RCTs

PROs provide unique insights into how patients experience illness, treatment effects, and overall well-being. Including PROs in RCTs supports more patient-centered research and enhances the interpretability of results for clinicians, regulators, and health system decision-makers.

Some of the key reasons to include PROs in trials include:

• Capturing the patient perspective: PROs assess outcomes that matter most to patients, such as symptom relief, functional ability, and emotional well-being.
• Supporting clinical and policy decisions: Regulatory bodies like the FDA and EMA encourage PRO use in clinical trials to inform benefit-risk evaluations.
• Assessing quality of life (QoL): PROs are especially useful in chronic, palliative, or life-limiting conditions where overall well-being is a primary concern.
• Evaluating symptom burden: PROs help quantify symptoms such as pain, fatigue, and depression that may not be fully captured by clinical tests.

Types of PROs in RCTs

Several categories of PROs are used depending on the trial’s objectives:

• Health-Related Quality of Life (HRQoL): Multidimensional assessments of physical, emotional, and social health (e.g., SF-36, EQ-5D).
• Symptom severity and burden: Measures specific symptoms such as pain or nausea (e.g., Numeric Pain Rating Scale).
• Functional status: Evaluates ability to perform daily tasks (e.g., Barthel Index).
• Treatment satisfaction: Assesses how satisfied participants are with their care or intervention.
• Adherence and compliance: Captures self-reported medication-taking behavior (e.g., Morisky Medication Adherence Scale).

Design Considerations for Using PROs

Instrument Selection: Choose validated and reliable tools appropriate to the population and research question. For example, PROMIS instruments or the EORTC QLQ-C30 are widely used in cancer trials.

Timing of Assessments: PROs should be collected at predefined points (e.g., baseline, during treatment, follow-up). Researchers should balance comprehensive data collection with the risk of burdening participants.

Bias Reduction: PROs can be subject to recall and reporting bias. Standardized administration—such as through electronic PROs (ePROs)—and blinding of assessors can reduce this risk.

Handling Missing Data: PRO data can be prone to loss, especially in longer trials. Strategies such as frequent reminders, electronic capture, and imputation techniques help reduce and manage missing data.

Analysis and Interpretation of PROs

PRO data should be analyzed using appropriate statistical and clinical frameworks:

• Descriptive analysis summarizes average scores and response distributions.
• Comparative analysis evaluates differences between groups, often using mixed-effects models to account for repeated measures.
• Clinically meaningful differences are essential for interpretation. Thresholds such as the Minimal Clinically Important Difference (MCID) help contextualize results.
• Longitudinal analysis assesses how PROs evolve over time and how they correlate with baseline health or treatment effects.

Challenges in Using PROs

Despite their importance, PROs present some challenges:

• Subjectivity and variability: Different patients may perceive or report symptoms in different ways.
• Response bias: Factors like social desirability or recall can influence responses.
• Missing data: Dropout or nonresponse can undermine data quality and lead to biased estimates.
• Regulatory compliance: PROs intended for regulatory submission must meet strict standards for validation, administration, and analysis.

Examples of RCTs Using PROs

• Cancer trials: The EORTC QLQ-C30 is widely used to assess quality of life in oncology.
• Pain trials: The Brief Pain Inventory (BPI) evaluates pain intensity and interference with function.
• Mental health trials: Tools like the PHQ-9 and GAD-7 are used to monitor symptoms of depression and anxiety.

Conclusion

Patient-reported outcomes are an essential element of modern clinical trials. They provide a direct view into patients' experiences, help assess the full impact of interventions, and support more informed decision-making. When rigorously selected, collected, and analyzed, PROs significantly enhance the relevance, transparency, and patient-centeredness of RCT findings.

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See also:

• Trial outcomes
• Quality of life measures

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Bibliography

1. Patrick DL, Burke LB, Gwaltney CJ, et al. Content validity—establishing and reporting the evidence in newly developed patient-reported outcomes (PRO) instruments for medical product evaluation: ISPOR PRO Good Research Practices Task Force report: part 1. Value in Health. 2011;14(8):967–977.
2. FDA. Guidance for Industry: Patient-Reported Outcome Measures – Use in Medical Product Development to Support Labeling Claims. U.S. Food and Drug Administration; 2009. Available from: https://www.fda.gov
3. Calvert M, Blazeby J, Altman DG, Revicki DA, Moher D, Brundage MD; for the CONSORT PRO Group. Reporting of patient-reported outcomes in randomized trials: the CONSORT PRO extension. JAMA. 2013;309(8):814–822.
4. Brundage M, Blazeby J, Revicki D, et al. Patient-reported outcomes in randomized clinical trials: development of ISOQOL reporting standards. Quality of Life Research. 2013;22(6):1161–1175.
5. Weldring T, Smith SM. Patient-reported outcomes (PROs) and patient-reported outcome measures (PROMs). Health Services Insights. 2013;6:61–68.

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Adapted for educational use. Please cite relevant trial methodology sources when using this material in research or teaching.