Patients as Partners in Clinical Trial Development—What Are We Waiting For?

“I’m upset because no one has offered me a clinical trial. When I asked about a trial in clinic today, my nurse did not know what to say.”

—Nichole Jefferson

The climate of kidney drug and device development has certainly improved in the past two decades, from advances in trial design to higher numbers of trials being funded and conducted, as well as increased investment in kidney pipelines. But to fully realize the goal of the 2019 Advancing American Kidney Health executive order—reducing the number of Americans progressing to kidney failure by 25% by 2030—more collaborative work must be done. Although the efforts and results of past years can be itemized, it is often recognized that the least tangible change is in fact the one that is hardest to improve: culture change. Nephrology stakeholders must partner closer with the very people we are trying to positively impact—our kidney patients—to accelerate development of new and innovative therapies. Put simply, we need, or shall I boldly suggest that we demand, a culture shift in nephrology to view trial participation as an option for care.

When a patient is diagnosed with chronic kidney disease (CKD), nephrologists and care teams need to make the patient aware of the possibility of enrolling in a trial. Two informal surveys (one conducted by NephCure and the other by patient advocate Kevin Fowler) highlight that 69%–78% of CKD patient respondents noted that their physician never mentioned trial participation to them, but if the physician would take a few minutes to explain the potential benefits of a trial, that conversation would influence 73% of respondents to participate.

Vimal Derebail, MD, FASN, UNC Kidney Center


In the past, there may have been a supply issue. In 2000, there were only 5 nephrology trials registered on; however, by 2018, there was a 110-fold increase, to 544 trials (1). Specifically, the landscape for rare kidney diseases was dry in 2015, with only 2 primary hyperoxaluria (Ph)2 or -3 trials for focal segmental glomerulosclerosis (FSGS) and none for immunoglobulin A nephropathy (IgAN). Four years later, in 2019, the drought was over, with 24 Ph2 or -3 trials collectively for those 2 diseases, an increase of 92% (or more than an 11-fold increase) (NephCure). We have gone from famine to feast and have more CKD trials than ever to offer. We need to create the urgency and demand and promote a culture in which every CKD patient is offered the chance to participate in a study—whether interventional, an observational registry, or qualitative research. After a diagnosis of CKD, it should not be a matter of if they will participate in a study but rather, which one will best serve their needs.

In 2017, the International Society of Nephrology (ISN) Global Kidney Health Summit proposed a stretch goal of “30 by 30”: 30% of CKD patients should be involved in relevant clinical trials by 2030 (2). Thus, regardless of what hat you wear—patient or researcher or clinician—what will you do to get us to those goals?

“Happiness and fulfillment are so much more than a measurement from a blood test.… When the outcomes are prioritized with the patient in mind, patient satisfaction rockets.”

—Jonathan Haydek (CJASN 2019)

Not every patient can participate in a study, but many opportunities exist to solicit a patient’s disease insight in supporting study design, planning, and regulatory decision-making. Patients are the experts of their disease, so it is critical to engage their feedback on what should be measured and addressed in clinical studies. There are several mechanisms to obtain their insight. We need to make studies more relevant and patients more willing to participate in these studies. The following is a start, but by no means is the list complete.

Patient-Focused Drug Development (PFDD)

The PFDD is a framework enacted by the 21st Century Cures Act (2016) that mandated that the US Food and Drug Administration (FDA) engage patients in disease-specific public meetings to learn more about their disease. It falls under 1 of 4 titles, notably, the one dedicated to speeding up clinical development. The others are patient experience data (see below), as well as facilitating novel trial designs and real-world evidence. Collectively, the aim is to generate more data that can serve as evidence to help inform research.

To date, three externally led PFDDs have focused on CKD and have been cohosted by the National Kidney Foundation (NKF): Alport syndrome, complement 3 glomerulopathy (C3G), and IgAN. At the IgAN meeting, Norman Stockbridge, MD, PhD, FDA director of the Division of Cardiovascular and Renal Products, emphasized that the FDA staff was eager to hear from patients about their symptoms, limitation of current therapies, and willingness to undergo potential risks associated with trials investigating novel agents. Figure 1 shows one of the questions designed for audience response and one patient’s subsequent reaction.

Figure 1.

Patient reaction to question about current treatment reducing disease symptoms


An upcoming Voice of the Patient report will summarize the discussion and findings of the IgAN PFDD. Healthcare providers, patients, and caregivers also had the chance to attend the FSGS PFDD on August 28, 2020.

Patient Experience Data

This effort also falls under the 21st Century Cures Act and targets how to speed up clinical development. The first instance of a drug label incorporating a novel section, titled “Patient Experience,” occurred in late 2017. The drug label articulated how 77% of patients preferred the subcutaneous (SC) administration of Rituxan Hycela over the intravenous (IV) Rituximab infusion, primarily because it required less time. (These were lymphoma patients enrolled in the formulation study of the new SC injection.)

The first time a device received an expanded indication, based on a formal patient preference study, occurred for the home hemodialysis (HD) NxStage machine. Initially, this device had been approved in 2005 for use with a care partner at home and then received clearance for nocturnal dialysis in 2014. But, the FDA granted a label expansion for patients to use it at home without a care partner present, based on patients’ willingness and assessment of risk tolerance captured in the formal patient preference survey. The effect is liberating, as this label expansion increased the independence of patients to perform home dialysis. These examples underscore how patient feedback directly affects regulatory decision-making.

Courtesy IgAN patient-focused drug development meeting hosted by the NKF and IGA Nephropathy Foundation of America, August 2019


Standardized Outcomes in Nephrology (SONG)

These are global surveys that compare priorities of patients and caregivers with those of healthcare providers. One of the goals is to determine which outcomes should be routinely measured in future trials. SONG-HD highlighted how providers are biased toward outcomes of mortality, hospitalizations, and vascular access in contrast to patients who were more concerned with the ability to travel, dialysis-free time, and dialysis adequacy. Patients noted that their definition of dialysis adequacy was not the lab value dialyzer clearance of urea dialysis time/volume of distribution of urea (Kt/V; on which providers and payors focus) but rather, how they feel relative to receiving the amount of dialysis that is right for them. In other words: “Patients focus on living well with CKD rather than dying from it” (3). In the SONG-Glomerular Disease Workshop in 2019, patients prioritized developing cancer higher (#5) than the providers did (#8), once again displaying a discrepancy between those who manage disease and those who suffer from it.

Patient-Centered Outcomes Research Institute (PCORI)

This nonprofit, nongovernmental organization was authorized by Congress in 2010 with the mission of “promoting evidence-based information that comes from research guided by patients….” One recent joint PCORI/academic effort sought to identify barriers and generate solutions for cultivating a research-ready dialysis community by convening patients, dialysis staff, researchers, and dialysis organizations in a workshop (4). Some attendees also generated a video explaining research to target patient audiences (available at the University of North Carolina website, Patients and researchers may view the PCORI website to participate in PCORI-sponsored efforts in nephrology.

Workgroups to Identify Renal Endpoints

Several data-driven efforts have been underway to assess potential trial endpoints across many indications in CKD, resulting in at least 8 publications since 2014 (512). Two papers reflecting the inclusion of CKD patients in multi-stakeholder workgroups were published in 2018, recommending and defining trial endpoints for vascular access and HD catheters (6, 10). These papers were the output of workgroups from the Kidney Health Initiative (KHI), a public-private partnership between the American Society of Nephrology (ASN) and FDA, which has invited patients onto subsequent workgroups that define endpoints in other indications. The NKF has hosted 3 workshops since 2008, examining albuminuria, proteinuria, and glomerular filtration rate (GFR) decline and slope as endpoints. Notably, patients participated in the most recent one in 2018, which convened the FDA and European Medicines Agency with researchers and nephrologists.

Patients’ Reaction to Published Research

In January 2018, CJASN introduced a new editorial section, termed Patient Voice, where invited patients share their response to research published in the same issue. Additionally, the ISN Advancing Clinical Trials (ACT) initiative convened a Patient Engagement Workgroup. The initial effort will be to invite patients to provide perspectives on selected publications highlighted on the ISN Global Trial Focus website. These perspectives are important, as they should help guide research planning and areas of focus. We need to remember that without patient participation in these studies, there would be no data generated and no papers to publish. The following are the words of one patient but a sentiment echoed by many:

“Sponsors should acknowledge us with a thank you note and share study updates throughout and the study results at the end.”

—Janine Reed

Considering the large investment in time and emotional and physical energy that patients commit to research when agreeing to participate in a study, this is a small and easy-to-fulfill request.

NKF’s Patient Network

This will be the first of its kind CKD Patient Registry in the United States where patients can register and enter their health data. This information will be linked to electronic medical records where possible. Among the aims of the registry will be to collect patient-reported insights on their CKD, facilitate patient-centered trial designs, and expand patient participation in trials. There is also the potential for post-trial surveillance so that patient data can be continuously captured even after the trial ends. Providers across the spectrum who touch CKD patients (i.e., primary care, diabetologists, cardiologists, and nephrologists) should promote enthusiasm for this registry (planned launch, fall 2020) and encourage patients to sign up so its benefits can be fully realized.

“The trial didn’t go great for me, but it was enriching to contribute something back, and my experience gives some value, since the drug will be tested in other kidney diseases too.”

—Jesse Morales

Please don’t hesitate to promote the voices of the rising chorus of CKD patients who have been waiting long enough. Explore ways to seize a culture change in catalyzing nephrology to be more research ready, whether through participation in a trial or any one of the current efforts that employ patients’ insights to ultimately improve our goal in finding more therapies. Change starts with grass-roots efforts that can be as simple as wearing buttons on white coats of study staff to encourage patients to “Ask me about a clinical study” and empower patients to serve as peer mentors to other patients by sharing their research-related experience to encourage others. Whether or not you act as an investigator, start the discussion in your clinic today. Inject a sense of urgency about the importance of clinical research into your discussions with patients, because in the words of my research colleagues: “Patients can’t wait, and neither should we.”


I would like to thank the many patients who have taken the time to share their journey and thoughts with me, which include many who are not directly quoted here but have opened my eyes to issues I would not have otherwise recognized.



Mustafa R, et al Clinical trials in nephrology: An updated systematic review of Kidney Week 2019; FR-PO1199.


Levin A, et al Global kidney health 2017 and beyond: A roadmap for closing gaps in care, research, and policy. Lancet 2017; 390:1888–1917. doi: 10.1016/S0140-6736(17)30788-2


Evangelidis N, et al Developing a set of core outcomes for trials in hemodialysis: An international Delphi survey. Am J Kidney Dis 2017; 70:464–475. doi: 10.1053/j.ajkd.2016.11.029


Flythe JE, et al Cultivating a research-ready dialysis community. J Am Soc Nephrol 2019; 30:375–380. doi: 10.1681/ASN.2018101059


Thompson A, et al Complete and partial remission as surrogate end points in membranous nephropathy. J Am Soc Nephrol 2015; 26:2930–2937. doi: 10.1681/ASN.2015010091


Allon M, et al Recommended clinical trial end points for dialysis catheters. Clin J Am Soc Nephrol 2018; 13:495–500. doi: 10.2215/CJN.12011116


Smith KA, et al Addressing the need for clinical trial end points in autosomal dominant polycystic kidney disease: A report from the Polycystic Kidney Disease Outcomes Consortium (PKDOC). Am J Kidney Dis 2019; 73:533–541. doi: 10.1053/j.ajkd.2018.11.001


Levey AS, et al Change in albuminuria and GFR as end points for clinical trials in early stages of CKD: A scientific workshop sponsored by the National Kidney Foundation in collaboration with the US Food and Drug Administration and European Medicines Agency. Am J Kidney Dis 2020; 75:84–104. doi: 10.1053/j.ajkd.2019.06.009


Levey AS, et al GFR decline as an end point for clinical trials in CKD: A scientific workshop sponsored by the National Kidney Foundation and the US Food and Drug Administration. Am J Kidney Dis 2014; 64:P821–P835. doi: 10.1053/j.ajkd.2014.07.030


Beathard GA, et al Definitions and end points for interventional studies for arteriovenous dialysis access. Clin J Am Soc Nephrol 2018; 13:501–512. doi: 10.2215/CJN.11531116


Mackay M, et al Establishing surrogate kidney end points for lupus nephritis clinical trials: Development and validation of a novel approach to predict future kidney outcomes. Arthritis Rheumatol 2019; 71:411–419. doi: 10.1002/art.40724


Thompson A, et al Proteinuria reduction as a surrogate end point in trials of IgA nephropathy. Clin J Am Soc Nephrol 2019; 14:469–481. doi: 10.2215/CJN.08600718

October-November 2020 (Vol. 12, Number 10 & 11)