ASN and FDA Form the Kidney Health Initiative

ASN and the U.S. Food and Drug Administration (FDA) have joined forces to form the Kidney Health Initiative (KHI). Established through a memorandum of understanding signed in September 2012, KHI’s mission is to “advance scientific understanding of the kidney health and patient safety implications of new and existing medical products and to foster development of therapies for diseases that affect the kidney by creating a collaborative environment in which FDA and the greater nephrology community can interact to optimize evaluation of drugs, devices, biologics, and food products.”

“KHI represents an exciting undertaking by ASN and FDA to bring about long-needed interactions between all of the different health care stakeholders responsible for developing, delivering, and monitoring care for patients with kidney disease,” said ASN President Bruce Molitoris, MD, FASN. “Bringing together the different, often fractured, components of the health care industry into interdisciplinary interactions will promote innovation, hasten translation, and improve the quality of patient care through new diagnostic and therapeutic advances. By catalyzing these developments, KHI will benefit stakeholders, including payers, but most importantly our patients.”

KHI has attracted attention from a diverse range of stakeholders in the kidney community, and at press time comprised nearly 20 member organizations. As KHI begins operations in 2013, how do stakeholders view its potential and what impact could KHI have on kidney research and patient safety?

KHI structure and scope

With up to 26 million Americans living with kidney disease, and given the disease’s serious health implications and economic burdens, KHI’s creation is timely. During his President’s Address at ASN Kidney Week 2012, Ronald Falk, MD, FASN, introduced KHI to the kidney community by stating that the ASN-FDA partnership would “help write a new and exciting chapter in our fight against kidney disease.” KHI seeks to address the lack of new medications for kidney disease and improve patient safety by facilitating dialogue, developing efficient trial designs, drafting white papers, and creating a transparent infrastructure to facilitate communication and collaboration among the greater kidney community and the FDA. To learn more about KHI’s mission and objectives, please visit http://www.asn-online.org/khi/KHI_Mission.pdf.

KHI is open to a wide variety of stakeholders, including patient and health professional organizations, pharmaceutical and biotechnology companies, device manufacturers, dialysis providers, foundations, research institutes, and U.S. and international government agencies. And because nephrologists collaborate with many other medical specialties, organizations representing these professionals (such as cardiovascular disease or diabetes) are eligible for KHI membership.

KHI’s public-private framework is a byproduct of FDA’s Critical Path Initiative (CPI), a blueprint to foster innovation in the development and evaluation of medical products. Other CPI partnerships include the Clinical Trials Transformation Initiative, the Medicare Device Innovation Consortium, and the Cardiac Safety Research Consortium (CSRC), which served as the template for KHI. A partnership between FDA and the Duke Clinical Research Institute, CSRC evaluates the cardiac safety profiles of new drugs and devices. Since 2006, CSRC has authored nine white papers, convened several think tanks, and created the CSRC ECG Warehouse—a database of electrocardiogram data that is an important resource for cardiac researchers.

Although similar to CSRC, KHI differs in its structure and scope. ASN will serve as an equal partner with FDA on the KHI board of directors, which is headed by two co-chairs—one each from ASN and FDA. The board will also include voting members from each branch of FDA, as well as non-voting members from other federal agencies, including the National Institutes of Health, Centers for Disease Control and Prevention, and the Centers for Medicare & Medicaid Services.

The inaugural KHI co-chairs are Prabir Roy-Chaudhury, MD, PhD, FASN, of the division of nephrology at the University of Cincinnati College of Medicine, and Patrick Archdeacon, MD, of the FDA’s Center for Drug Evaluation and Research.

Roy-Chaudhury views KHI as an opportunity to improve nephrology’s “orphan status” in the areas of randomized controlled clinical trials and bringing new therapeutics to market. “This requires having all of the stakeholders—physicians, patient advocacy groups, industry, and, critically, FDA—at the same table working together to open pathways for getting the right drug, biologic, or device to the right patient in the right way,” he said.

“KHI is a forum where FDA can be more responsive to the nephrology community,” said Archdeacon, “and we’re looking forward to hearing from KHI members about what they perceive are the important issues and priorities.”

KHI’s focus on bringing patients to the table distinguishes it from other CPI partnerships. “Having patients involved is absolutely critical,” said ASN co-chair Roy-Chaudhury. “They give KHI a different and much-needed perspective, because patients and patient advocacy groups often have the ability to quickly focus down on the key obstacles to better care, in a way that health care professionals may not be able to,” he added. The FDA co-chair Archdeacon agrees, noting “FDA, industry, and the entire nephrology community need to better understand the issues facing kidney patients, as experienced by the patients themselves. KHI will allow us to hear from the patients directly.”

In launching KHI, ASN and FDA personnel worked proactively to develop a strong and transparent policy regarding conflict of interest (COI) management and disclosure. KHI board members and working group participants are required to disclose and update COI disclosures for the duration of their involvement. Because some members will possess competitive interests, KHI has a clearly delineated plan for disclosing and managing COIs in the selection of, and participation in, KHI projects and activities, which is available at http://www.asn-online.org/khi/coi.aspx.

Stakeholder perspectives

Reaction among stakeholders in the kidney space to KHI’s creation has been uniformly positive. “I’m really excited to see this true collaboration between industry, practitioners, FDA, and patients—the end users who have the most important voice,” said Karen E. Ryals, executive director of the American Association of Kidney Patients. She views KHI as an opportunity to address patient safety issues, explore new avenues in treatment, and most important to improve communication not only between patients and kidney professionals but within care settings. “The kidney community can become segmented, but if we work in a collaborative spirit I believe a lot more will get done, which will benefit patients tremendously,” Ryals said.

“I believe those of us in industry are quite excited about KHI,” said Mark T. Houser, MD, of Abbott Laboratories. “From a drug development perspective, anything that improves dialogue and communication between the renal community, regulatory agencies, and industry is highly desirable, and should lead to advancements in the number of new therapeutics to treat patients with CKD. These interactions should help identify areas where the needs for new therapies are the greatest, and also provide additional clarity to industry regarding a regulatory path which always reduces risk in drug development. However, given that drug development is a global process it will clearly be important to include other global regulatory agencies as KHI matures.”

Archdeacon added there needs to be a perception that ideas developed at KHI can apply worldwide. “KHI has received a fair amount of interest from outside the United States, and I’m optimistic that KHI’s influence can extend beyond our borders,” he said.

Sharon A. Perlman, MD, of the American Society of Pediatric Nephrology (ASPN), said she is delighted with the mission and broad focus of KHI, adding that ASPN is especially interested in advocating for improved development of drugs and devices for treatment of children and adolescents with kidney disease. “Given the relatively small number of pediatric nephrology patients with any specific disorder, KHI’s objective to develop approaches to the systematic collection of retrospective or prospective data, as well as to establish data standards, offers an opportunity to maximize the information available from clinical trials conducted on these relatively small patient populations,” she said.

“As a KHI pioneer member, the American Society of Diagnostic and Interventional Nephrology (ASDIN) has an opportunity to collaborate with ASN and FDA to nurture novel therapeutics that meet patient care goals that all three entities share,” said Alexander S. Yevzlin, MD, ASDIN president-elect. Interventional nephrology focuses primarily on vascular access, and ASDIN would like to see improvements in the delivery of access care via novel therapeutic solutions and increased knowledge of vascular disease processes, he said.

Could KHI benefit FDA as well, in facilitating cross-talk among FDA’s different branches? Absolutely, said Archdeacon. Because of the wide range of products and breadth of diseases that impact the kidney, there are numerous FDA review divisions that regulate products affecting kidney health that may not regularly interact with one another. “Having a single forum where we’re able to talk about nephrology and ways to facilitate innovation and renal safety also provides a good opportunity for the FDA to facilitate intramural interaction,” he said.

Moving research forward

What will KHI’s role be in the promotion and advancement of kidney research? Molitoris believes “KHI represents an opportunity to delineate the clinical aspects and quality measures that will be used to evaluate drugs, devices, biologics, and food products. This will help researchers—whether academics or industry, basic or clinical—target specific undertakings thereby facilitating development and delivery of new diagnostic and therapeutic advances. Once a specific disease aspect is identified as being a therapeutic end point, then efforts to hasten and approve diagnostic capabilities will ensue so as to provide the best possible mechanism of quantifying the clinical end point, which will also help define therapeutic strategies,” he added.

One of the challenges of developing new therapies for kidney disease hinges on the difficulty in designing a trial in nephrology, said Archdeacon. “Compared to other therapeutic areas, the time required for kidney disease to manifest and have a clinical impact in the patient can be extremely long, which makes it more challenging to study.”

“KHI also levels the playing fields for smaller companies and therefore will be an engine of innovation as it brings together the entire health care industry, including the FDA, to unite behind specific ideas, targets, and quality measures,” said Molitoris. “Hopefully everyone in the ‘room’ will understand and appreciate that we all have a stake in the process, and will keep patient health and well-being at the forefront of all decision-making processes.”

One of KHI’s objectives is the systematic collection of retrospective or prospective data, such as registries and/or global databases, and establishment of data standards, which could be of great benefit to researchers.

“The development of databases and registries are expensive undertakings, and the cost-value relationship has been debated within the kidney community, especially at NIH, for quite some time,” said Molitoris. “However, I think it is safe to say that if KHI can help facilitate the development of these two processes it will be an important step forward in helping to delineate the natural history of the disease processes, successful therapies, and how to individualize therapy so as to achieve the best outcomes while minimizing adverse effects.”

Arriving at a challenging fiscal time for medical research, how could KHI influence the environment for kidney research funding?

“If KHI can help create consensus among all the stakeholders on the best practices for studying kidney disease, I think we can expect that whatever resources that are put into that sphere will produce more output,” said Archdeacon, adding “if we can make it more feasible and more attractive to study kidney health then it’s reasonable to expect that we may see an increase in the resources dedicated to it.”

A focus on safety

KHI’s focus on patient safety should be of great value to the kidney community, said Abbott’s Houser. “Active surveillance of adverse drug reactions, maintenance of patient registries, studies of biomarkers that might predict adverse outcomes and/or response to therapeutics are all areas that can be explored as part of KHI.”

Roy-Chaudhury adds that KHI can establish standard guidelines for the assessment of renal toxicity of new products across the entire spectrum of disease. “It’s critically important that nephrologists be involved, whether with industry or FDA, and if the correct steps to rule out renal toxicity are identified, the review process can be accelerated because compounds could be vetted beforehand. In the area of patient safety, the scope and impact of KHI can extend well beyond the renal space.”

The next steps for KHI

KHI will appoint board members in 2013 who will be charged with reviewing candidate projects and activities, with the eye toward selecting one or two key projects that could be completed in a short timeframe, said Archdeacon. Roy-Chaudhury believes that the initial project(s) should be enablers of future, larger projects, for example, endpoints for clinical trials. “It would be wonderful to have one set of endpoints for clinical trials in a particular area of nephrology (vascular access or transplantation for example) that everybody—physician groups, FDA, and industry—all agree on.”

How can ASN members become involved in KHI? “ASN members will play an important role in setting the course for the near term with regard to important undertakings for KHI,” said Molitoris. “In addition to serving on the board of directors, ASN members will be involved in subcommittees and working subgroups developing the informational material and approaches necessary to answer specific project questions.”

Roy-Chaudhury also sees KHI as a venue for ASN members to “channel their wealth of knowledge to facilitate the bench-to-bedside development of novel drugs, devices, and biologics, and also to provide direction, substance, and prestige to KHI.”

To learn more about KHI and how your organization can join, please visit http://www.asn-online.org/khi/, or contact the project director for KHI, Melissa West, at mwest@asn-online.org.

January 2013 (Vol. 5, Number 1)