|By Tré LaRosa
Patient-Reported Outcomes: The Basics
Patient-reported outcomes (PROs) are clinical trial measures that capture the patient’s own perspective on how they feel. While they are commonly used in clinical trials, they are also used in the clinic as another measure to gauge a patient’s health over time. Crucially, one of the best assets of PROs is that they are reported outside of the interpretation of the clinicians or researchers, thereby offering an unobstructed and uninfluenced line of communication between patients and clinical results.
This is especially helpful because it provides an insight into the way patients — and not just individually but across the population — perceive their care and a given intervention that can corroborate or even contrast what might be expected based on other trial endpoints. Condition symptomatologies are often complex. How a certain symptom affects a person’s quality of life is not necessarily intuitive. Every person with the same condition has a different experience and likely perceives symptoms and adverse effects differently. To that end, if a quantitative measurement demonstrates an intervention has improved a given symptom, clinicians or researchers might assume that the patient will report improvement in their quality of life. But this isn’t a guarantee. Quality of life is a nebulous, sometimes counterintuitive concept influenced by a confluence of factors including environment, personal circumstances, even weekly fluctuations. Quality of life, then, is not just affected by a person’s diagnosis but by their presence in the world around and within them.
Alternatively, certain symptoms that clinical investigators have never experienced assume are negligent when evaluating overall quality of life could be profoundly impactful. Patient-reported outcomes exist in a liminal space in the clinical research world, functioning both complementarity and as a counter-balance to existing clinical research biases and offer patients more influence and a sense of agency in a world where patient autonomy and influence can be lacking. Even a sense of autonomy itself could prove to be a positive influence on quality of life. They give insight into the personal life of patients while also allowing patients more influence and control over their condition.
PROs can be any type of primary or secondary endpoint
No part of a clinical trial is non-essential, but endpoints are where the buck stops: Endpoints determine whether the intervention of interest works. (Though, it should be stated that even if the intervention doesn’t work, so long as the clinical trial is well-designed, researchers still learn something new, just as every “failed” experiment in science still provides valuable data.)
For clinical trials to advance through drug development and eventual United States Food and Drug Administration (FDA) approval process, trials must demonstrate safety and/or efficacy (depending on if it’s an early or later stage clinical trial) by reaching their endpoints. There are two main classifications of endpoints: Primary endpoints are generally the most prominent established endpoints used to measure the specific effects of an intervention on the disease. When designing any trial, there is a strategy in establishing primary endpoints — they have to effectively measure the intervention in respect to the condition, and will be the basis for the submission to the FDA if the sponsor intends to pursue regulatory approval.
Secondary endpoints are compelling, but they are less rigorous and regarded as secondary by-products of the investigation; to be confirmatory, they should be treated as statistically rigorous as primary endpoints.
Patient-Reported Outcomes: The Deeper Details
Design and Validation of Patient-Reported Outcome Measures
Patient-reported outcomes are measured through questionnaires called “instruments” or “patient-reported outcome measures” (PROM). Every question in a questionnaire has a specific purpose for being included and a well-designed PROM should include only as many questions as necessary to achieve its goal. Patient-reported outcome measures can be specific and focused, informing only a single “domain,” such as medication adherence in people with epilepsy. Or they can be more comprehensive and broad, measuring several domains of physical, mental, and social health. Of course, there are drawbacks and strengths for different PROMs and approaches. If a drug is expected to have a deep, widespread impact on a patient’s condition, researchers might use a multi-domain instrument like the Health-Related Quality of Life instead of multiple separate single-domain instruments. A drawback of using a multi-domain instrument can be that they are usually not as exhaustive for all the covered domains, limiting what can be learned about various aspects of health.
For PRO instruments to be useful, they must be proven to consistently and reliably measure what they intend to measure through a process known as “validation.” Otherwise, an instrument can’t be considered valid or reliable, which of course undermines its capacity to be effective and informative. To validate an instrument and ensure acceptability of use, researchers must invite patient participation during the development process. Before a PROM is ever designed, a need has to first be identified and refined. From there, researchers define what goes into the overarching concept that they’re intending to measure. For example, if researchers want to understand how well patients adhere to their medications, they would need to understand what goes into adherence, such as how burdensome the medication is to take or administer. From there, they develop the questionnaire, refine it through an iterative process, test it, validate it in the clinic, and finally publish the results. This process can be cumbersome, but to be a validated PROM, the process must be rigorous and supported by evidence.
Patient-reported outcomes are essential tools that provide complementary and necessary evidence for how patients perceive medications and their own condition. They give researchers far more evidence than would otherwise be provided and they are scientifically-validated to ensure they reliably and consistently measure the domains of interest.
What we haven’t covered is how PROs are effectively used in clinical trials, their impact, and how they actually inform current and future treatment. Please stay tuned for the next blog, where we’ll get into those details and discuss case studies of how PROs have been incredibly valuable in neurological clinical trials. We’ll even discuss how neurologists view PROs!