A recent AJKD Narrative Review by Nair and Wilson focuses on patient-reported outcomes (PROs) in nephrology research. This topic, which won the 2018 NephMadness, is of increasing relevance and importance in clinical trials. AJKD Social Media Editor, Timothy Yau @Maximal_Change (AJKDBlog), had a chance to interview first author, Devika Nair @devimol (DN), on leveraging patient-reported outcomes for person-centered kidney disease care.

AJKDBlog: Before we jump into the specifics of this article, would you please define patient-reported outcome measures, and give some real-life clinical examples in patients with kidney disease?

DN: A patient-reported outcome (PRO) is a patient’s perception of his or her functional well-being or health status. Examples are wide-ranging and can include perceptions of mood, physical fatigue, sexual function, pain, life goals, etc. Patient-reported outcome measures (PROMs) are the tools (usually questionnaires or interviews) that we use to measure these PROs. In this article, we focused on PROMs and not patient-reported experience measures (PREMs), which describe a patient’s experience of care in a health system. Confused yet? The key is that each of these seek to uncover a patient’s feelings and beliefs without input from a clinician or other party and can provide deeper insight into a patient’s illness experience.

AJKDBlog: Many times, the rigor of studies in nephrology are driven by the 3 Ds: death, dialysis, or doubling of SCr. I’ve been in journal clubs where trials looking at lupus or vasculitis were defined by improvement in QoL scores, and many clinicians debated whether an improvement in, for example, the SLEDAI lupus score is actually meaningful. How would you respond to someone who believes this score is not as meaningful as a more traditionally “hard” outcome?

DN: This question comes up a lot, and it’s important to note that adding PROMs to clinical trials, where appropriate, does not mean that the other outcomes should or would be deemphasized. But as prior work has shown, some patients may place certain PROMs over “hard” outcomes such as survival. Ultimately, it’s the patient who is suffering from the disease process, so shouldn’t the patient play a role in deciding what outcomes an intervention should target?

Not all trials would benefit from adding PROMs to their design, but in studies of interventions that may affect a patient’s physical or emotional symptoms, adding a validated PROM could strengthen analytic rigor and improve clinical validity. Some PROMs can be subject to recall bias (such as in the case of studies of dietary intake) or affected by a social desirability bias (such as in the case of reports of educational achievement or income), but PROMs related to a patient’s symptoms and emotions have been shown to be valid, reliable, and responsive.

AJKDBlog: On that topic, another thing that many clinicians struggle with is knowing whether a PROM is valid and reliable. If a PROM is applicable to an individual patient, how are they tested for validity/reliability?

DN: Briefly, validity is the extent to which a PROM measures what it intends to measure. Content validity is assessed qualitatively with interviews of participants and quantitatively through certain statistical techniques (factor analyses, structural equation modeling) that compare the PROM to other related measures.

Reliability is the extent to which a PROM is free from measurement error. This requires internal consistency (how well the scale items of a PROM reflect a single, underlying dimension) and reproducibility (the PROM produces the same results when administered to the participants after a certain amount of time).

AJKDBlog: Can you share how PROMs are being increasingly recognized by major groups such as the FDA and KDIGO? How have other specialties outside of nephrology started using PROMs in clinical research?

DN: Studies in cardiology (namely, those related to patients with heart failure) have included health-related quality of life as a key outcome and more recently, measured angina burden in patients. But perhaps because oncologists often interface with palliative care specialists (whose main focus is to preserve quality of life and reduce symptom burden), PROMs have been incorporated into numerous randomized clinical trials in oncology. This is particularly relevant to trials related to cancer survivorship.

The Center for Devices and Radiological Health (CDRH) at the FDA is interested in incorporating PROMs into risk-benefit assessments and medical device labeling to measure device efficacy, maintain device safety, and facilitate shared decision-making related to device usage. The opportunities are endless, but encouragingly, the nephrology community continues to make strides this area. A very recent KDIGO controversies conference described the development of a PROM related to patients’ symptoms and experiences related to blood pressure and volume management on hemodialysis.

AJKDBlog: A nice example included in this Narrative Review is the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT). Most readers are familiar that in this trial of diabetic non-dialysis CKD patients, no difference was observed in the rate of primary composite outcome of cardiovascular morbidity or mortality in those randomized to darbepoetin vs placebo. How would the PROM score in the secondary analysis be used to guide a patient decision?

DN: In a prespecified analysis of the TREAT trial, patients who received darbepoetin alfa experienced clinically-meaningful improvements in perceptions of fatigue. The KDIGO guidelines for anemia management in chronic kidney disease states that for some patients, ESA therapy may be individualized to target improvements in health-related quality of life as opposed to achieving strict hemoglobin control. For certain patients, such as those who opt for conservative management or who are otherwise informed of the risks of therapy, the benefits of ESA therapy may outweigh its risks. These studies and recommendations highlight the role PROMs can play in helping providers align with their patients’ goals, values, and treatment preferences.

AJKDBlog: Box 1 nicely summarizes considerations to implement PROMs into patient-centered kidney care. What are some of the more pressing challenges to develop and implement these?

Box 1 from Nair and Wilson, AJKD © National Kidney Foundation.

DN: Challenges in PROM development include ensuring that the measure is contextualized within a disease process. A hemodialysis patient’s perceptions of fatigue may differ greatly from those of a patient who recently received a kidney transplant.

As far as implementation, a challenge will be interoperability between patient devices that PROMs are collected on and electronic medical records (EMRs). Most existing EMRs are not designed to seamlessly integrate PROMs into a patient’s care plan. This does not need to be complicated. For instance, a PROM collected at intake that briefly inquires about support at home may flag a provider to ask more probing questions during the visit about a patient’s emotional well-being.

PROMs need not correlate perfectly with biologic markers to be considered valuable, but collecting PROMs alongside clinical and laboratory data may provide a more comprehensive picture of a patient’s overall health. Linking these PROMs to downstream clinical outcomes can generate additional evidence to support PROM-targeted interventions.

Importantly, PROMs should be collected from a wide spectrum of patients, including those of lower socioeconomic strata who may otherwise lack routine access to care. What’s the point of a PROM if it only represents the experiences of a select group of patients? Patients must also remain informed of how the additional time spent in filling out PROM questionnaires translates to a meaningful changes in their care plan. These are difficult but worthy challenges to overcome and can make patient care truly person-centered.

AJKDBlog: Thank you so much for taking the time to do this interview!

To view Nair and Wilson (subscription required), please visit AJKD.org. 

Title: Patient-Reported Outcome Measures for Adults With Kidney Disease: Current Measures, Ongoing Initiatives, and Future Opportunities for Incorporation Into Patient-Centered Kidney Care
Authors: Devika Nair and F. Perry Wilson
DOI: 10.1053/j.ajkd.2019.05.025