On Rare Disease Day, PKD Foundation, IQVIA Highlight Patient Registry Gathering Quality-of-Life Data

Imagine if your kidneys ballooned from the size of a fist to a football, swelling with cysts that cause fatigue, chronic pain, and eventually renal failure. Until recently, there was no treatment for this condition, short of surgery to drain or remove the cysts.

This is polycystic kidney disease (PKD), a genetic condition that affects about 600,000 people in the United States and 12.4 million worldwide, according to the PKD Foundation. The more common type, autosomal dominant PKD (ADPKD), develops from a genetic mutation, although many are not diagnosed until their 30s or later. ADPKD is passed from parent to child and does not skip a generation, which means a person who has the disease is 50% likely to pass it to a child. About 50% of those who have PKD will have end-stage renal failure by age 50.

PKD’s debilitating effects, its fallout on families, and the relative lack of treatments all affect quality of life. (Tolvaptan was approved in 2018 to slow decline in rapidly progressing ADPKD, but dialysis remains the common management strategy; some receive a kidney transplant.) To develop better clinical trials and therapies for the disease, the PKD Foundation and the information technology company IQVIA are joining forces to highlight the ADPKD Registry, the first North American database to track patient-reported health-related quality of life (HRQOL) effects over time. The goal of the registry, which launched in 2019, is to better understand longitudinal disease progression, including symptoms, pain events, and access to care.

The PKD Foundation’s new CEO, Susan Bushnell, along with Elise Hoover, the foundation’s vice president of research programs, and David Voccola, senior director of Global Strategic Planning for IQVIA, spoke with The American Journal of Managed Care® for Rare Disease Day about the development of the ADPKD Registry and its role in creating better treatments for patients.

How did the PKD Foundation and IQVIA come together for this project? Bushnell said about IQVIA: “They've demonstrated expertise in keeping the data of patient communities private, secure, and confidential, which is highly important to us,” and “their growing technological expertise always contains an element of patient centricity.”

Voccola said the field of patient data is rapidly changing, and getting it right means realizing that technology “is really less than half the equation.”

“It's the vision of understanding how you can really emphasize the patient experience—and start to answer real questions that are rate limiters to advancing health care delivery and research. That was the mission that we were able to start supporting with the right technologies,” he said. But it starts with the vision, and understanding the PKD Foundation’s priorities, Voccola said.

Bushnell said the registry uses measures from existing validated tools: the ADPKD Pain and Discomfort Scale, which evaluates chronic dull kidney pain, acute severe kidney pain, and fullness/discomfort; and the ADPKD Impact Scale, which measures 14 different items. “This is important, because although we know that up to 60% of patients with ADPKD experience pain at some point, chronic pain has been found to be underreported to clinicians,” she said.

The partnership with IQVIA will allow the registry to match patient-reported data with patient records, including those of cyst ruptures and lab results, which occur as the disease progresses, Bushnell explained. Voccola said it’s been difficult until now to match patient-reported data with clinical data, but with new interoperability rules taking effect, this will become easier as patients participating in the registry release their electronic health records (EHRs).

“That’s going to allow us to start to match up those data directly from the EHRs,” he said. The nature of PKD means that it requires more information than the structure data of the EHR, so over time, the goal is to include key pieces such as genomic information and imaging—both crucial for understanding the PKD journey over time and keys to development of therapeutics and improving care delivery.

In the early going, he said, “We're going to be focused on the patient-reported data, and unlocking that patient-mediated data for the near future. There's so much rich information in that first step.”

Will family members share data, too? Bushnell and Voccola said yes, but the PKD Foundation is creating the flexibility to do this going forward, and not trying to do everything at once.

How does the foundation expect clinicians will use this data over time? Right now, Hoover said, “There’s a general lack of understanding of the health-related quality of life aspects of the disease. And clinical trials are not helping, because they’re also not including measures to understand pain, mobility issues, or fatigue as the primary outcome.”

Creating a longitudinal tool to track HRQOL measures over time will create “an observational study of sorts,” Hoover said, “that can really understand how the disease impacts an individual.”

Scientists and physicians who treat patients may learn more about how patients are affected before they are diagnosed and what happens once the kidneys start to fail. This will be new information for the most part, Hoover explained, because despite the strong genetic component of the disease, historically family members have not been encouraged to get genetic testing until symptoms appear. Before the Affordable Care Act, health insurers could deny coverage for a preexisting condition, and life insurance is still a problem, she said. Guidelines are changing, and this pattern could shift as new gene therapies are developed.

The registry will help overcome the current challenge many patients face—many are the only person with PKD in their community, so their nephrologist lacks a frame of reference for their symptoms. Until now, registry data of this type were limited to a clinical research site, Hoover said.

For patients, participation in the registry is collaborative. At enrollment, patients are asked to complete a core questionnaire that concerns their initial disease experience and also identifies whether they are eligible for a clinical trial (FALCON, a phase 3 study involving bardoxolone methyl, is still recruiting patients, and Regulus Therapeutics is enrolling 36 patients in a phase 1b study for an investigational therapy).

Every 3 months, patients receive a new module; questions will cover family history, diet, lifestyle, presence of liver cysts, and other factors. Some questions are repeated. At the same time, Hoover said, participants will receive information on how the PKD Foundation is using the data. Already, the PKD Foundation has presented research posters on data gleaned from the registry.

Do patients with PKD have concerns about joining the registry? Bushnell said the questions the foundation receives are similar to those regarding a clinical trial: Will data be kept safe and confidential?

“The trust of our community is very important to us,” she said. “We want them to trust us with their data and their personal family histories and experience with the disease. We want them to trust that we will make the data accessible to researchers in a way that protects their privacy, and we want to do it in a way that makes sure they know we’re listening to their voice and their priorities. IQVIA is key to fulfilling those promises for us.”