The Kidney Health Initiative is a public-private partnership founded in September 2012 by the American Society of Nephrology and the U.S. Food and Drug Administration.

Inaugural Review 2012-2014

Table of ContentsKidney Health Initiative Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

Governance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

Board of Directors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

Membership . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

Members of the Kidney Health Initiative . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

Events . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

Project and Workgroup Identification and Selection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

Pilot Projects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

1. Pharmacokinetics in Patients Receiving Continuous Renal Replacement Therapy (CRRT) . . . 14

2. Outcome Measures in Lupus Nephritis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

3. Promoting Kidney Health and Innovative Treatments for Kidney Disease -

Barriers and Potential Solutions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16

Member-Driven Projects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17

1. Clinical Trial Endpoints for Dialysis Vascular Access . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18

2. Workshop to Elucidate Role of Patient Preferences in Support of the Center for Devices and Radiological Health Regulatory Actions in Kidney Disease . . . . . . . . . . . . . . . 19

3. Data Standards in Diabetic Kidney Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20

4. Pragmatic Trials in Nephrology: Challenges & Opportunities . . . . . . . . . . . . . . . . . . . . . . . . . . 21

5. Advancing Technologies to Facilitate Remote Management of Patient Self-Care in Renal Replacement Therapy (RRT) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22

6. Regulatory Policies & Positions Affecting Device Approval in the United States: Tools to Assess the Process and Foster Device Development for Patients with Kidney Disease . . . . . . 23

More than 20 million Americans have kidney disease, and more than 600,000 Americans have kidney failure, also known as end-stage renal disease (ESRD)(1)(2). Despite these staggering statistics, the number of randomized clinical trials published in nephrology is lower than other specialties in internal medicine (Figure 1)(3). Kidney disease was the ninth leading cause of death in the United States in 2012, but little progress has been made to treat this disease in the past few decades(4).

Recognizing both the lack of clinical trials and the huge unmet clinical need in kidney disease, the American Society of Nephrology (ASN) and the US Food and Drug Administration (FDA) established the Kidney Health Initiative (KHI) in September 2012 under a Memorandum of Understanding. KHI is dedicated to improving patient safety and promoting the development of the best possible therapies for diseases that affect the kidneys and quality of life for millions of people around the globe.

There are many barriers to innovation in kidney disease. Some key obstacles are (a) an inadequate characterization of the pathogenesis of renal disease progression; (b) poorly defined molecular pathways and targets; (c) poorly characterized animal models of kidney disease; (d) the lack of well-defined clinical trial endpoints and timelines; and (e) a limited clinical trial infrastructure and supportive personnel. KHI seeks to identify and develop solutions that target the current stagnation within the realm of kidney disease research. These solutions include, but are not limited to, opportunities to elucidate clinical trial endpoints, to improve clinical trial design and execution, to discuss the use of patient registries, and to create avenues for closer collaboration with FDA and other stakeholders. Ideally, these solutions will advance awareness, and therefore funding, of kidney disease.

1 Centers for Disease Control and Prevention (CDC). National Chronic Kidney Disease Fact Sheet General Information and National Estimateson Chronic Kidney Disease in the United States, 2014. Atlanta, GA: US Department of Health and Human Services, Centers for Disease Control and Prevention; 2014. 2 U.S. Renal Data System, USRDS 2013 Annual Data Report: Atlas of Chronic Kidney Disease and End-Stage Renal Disease inthe United States, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 2013. 3 Palmer et al, AJKD 2011. Vol. 58, Issue 3, p. 335 4 Xu JQ, Kochanek KD, Murphy SL, Arias E. Mortality in the United States, 2012. NCHS data brief, no 168. Hyattsville, MD: National Center for Health Statistics. 2014.

The mission of KHI 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 Food and Drug Administration (FDA) and the greater nephrology community can interact to optimize evaluation of drugs, devices, biologics, and food products.”

Kidney Health Initiative Background

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The KHI Board of Directors is charged with advancing KHI’s mission by providing oversight of operations, recruiting and retaining members, as well as maintaining scientific oversight by soliciting, reviewing, and approving scientific project proposals; fostering communication; identifying opportunities for education; and building consensus.

The KHI Board of Directors is led by two co-chairs, one appointed by FDA and the other appointed by ASN. Currently, Patrick Archdeacon, MD, Medical Officer in the Center for Drug Evaluation and Research (CDER) serves as the FDA appointee, and Prabir Roy-Chaudhury, MD, PhD, FASN, Professor of Medicine at the University of Cincinnati, serves as the ASN appointee.

The inaugural KHI Board of Directors was selected from the Pioneer Members of KHI within five months of the initiative’s formation in September 2012. In March 2014, KHI expanded its Board of Directors, adding five additional seats to reflect the initiative’s growth in membership. The expansion allowed Pioneer Members (members that joined by December 31, 2013) to express their interest to serve. Members of the KHI Board of Directors serve renewable three-year terms, and the expansion of the board allowed KHI to begin to stagger the terms of its members.

KHI would like to thank the Board of Directors for their service and leadership.

Governance

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Board of Directors

A liaison for the Center for Food Safety and Nutrition (CFSAN) at the FDA has been identified and will be involved as projects are identified. Current vacancies on the KHI Board of Directors include: the Agency for Healthcare Research and Quality (AHRQ), Center for Biologics and Research (CBER) at FDA, Centers for Medicare & Medicaid Services (CMS) and National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH). Filling these vacancies is a priority for KHI.

Matthew D. Breyer, MD, FASN (2015) Eli Lilly and Company

Dolph Chianchiano, JD, MPA (2016) National Kidney Foundation

Mark Costanzo (2016) Fresenius Medical Care North America

Ronald J. Falk, MD, FASN (2015) University of North Carolina

Michael Flessner, MD, PhD (2015) National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Nancy M. Gallagher, RN, CNN (2015) Nephrology Nursing Certification Commission

Stuart L. Goldstein, MD (2015) Cincinnati Children’s Hospital

Jula K. Inrig, MD, FASN (2015) Duke University, Quintiles Global Clinical Research Organization

Reshma Kewalramani, MD, FASN (2015) Amgen, Inc.

Alan S. Kliger, MD (2015) Yale University

Mahesh Krishnan, MD, MPH, MBA, FASN (2016) DaVita Healthcare Partners

Patrick Archdeacon, MDFDA

Prabir Roy-Chaudhury, MD, PhD, FASNAmerican Society of Nephrology

Kristine Kuus, PhD (2015) The Binding Site, Inc.

Celeste Castillo Lee (2015)Ann Arbor, MI & Vasculitis Foundation

Peter G. Linde, MD (2015)AbbVie, Inc.

Joe Muldoon (2016) FAST Biomedical, Inc.

Carolyn Y. Neuland, PhD (2015)Center for Devices and Radiological Health (CDRH), FDA

Meda E. Pavkov, MD, PhD (2015)Epidemiology and Statistic Branch (ESB), Centers for Disease Control (CDC)

Sam M. Pederson (2015) Seattle, WA & American Association of Kidney Patients

James A. Sloand, MD, FASN (2015)Baxter International Inc.

James P. Smith, MD, MS (2015)Center for Drug Evaluation and Research (CDER), FDA

Katherine R. Tuttle, MD, FASN, FACP (2016)University of Washington

Members (Term)

Co-Chairs

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One of KHI’s greatest strengths is its diverse and broad membership. KHI currently has nearly 70 members and includes all major stakeholders in the field of kidney disease: patient and health professional organizations, commercial entities (large pharmaceutical companies, device manufacturers, dialysis providers, and small start-ups), research institutions, and federal agencies. KHI is, in essence, a pre-competitive platform where the kidney community comes together to develop workshops, data standards, white papers, and other outputs that will facilitate the safe passage of drugs, devices, biologics, and food products into the kidney community. KHI members are involved in the selection and execution of a variety of projects: co-authoring white papers; collaborating to leverage previously conducted and ongoing clinical studies, research infrastructure, and databases; and promoting dialogue on kidney health pertaining to drug, device, biologics, as well as food product development, evaluation, and safety. KHI is dedicated to creating a process that facilitates collaboration and communication among the greater nephrology community and FDA. KHI members have access to the KHI web-based portal that collects member proposals, provides the opportunity to review proposals as they are submitted and provide comments that are constructive and enhance the submission.

KHI members are also invited to attend the Annual KHI Stakeholders Meeting held in the spring. This meeting fosters the dialogue, discussion and networking that is core to KHI’s mission and essential to developing KHI projects. If you are interested in learning more about the Annual KHI Stakeholders meeting or membership, please visit the KHI website at www.kidneyhealthinitiative.org. KHI thanks its nearly 70 members for their participation and contribution.

Membership

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Device Manufacturers:C.R. Bard, Inc.*Medtronic, Inc.*NxStage Medical Inc.*Puracath MedicalW. L. Gore & Associates*

Dialysis Providers:DaVita,Inc.*Dialysis Clinic, Inc. (DCI)*Fresenius Medical Care*Peace Health Dialysis Center*

Foundations:Institute Kidney Foundation of Delhi*JDRF International*NephCure Kidney International*PKD Foundation*Vasculitis Foundation*

Health Professional Organizations:Association for the Advancement of Medical Instrumentation (AAMI)*American College of Clinical Pharmacy- Nephrology Practice and Research Network (ACCP- PRN)*American Nephrology Nurses’ Association (ANNA)*American Society for Apheresis (ASFA)*American Society of Diagnostic & Interventional Nephrology (ASDIN)*American Society of Nephrology (ASN)*American Society of Pediatric Nephrology (ASPN)*American Society of Transplantation (AST)*European Renal Association – European Dialysis and Transplant Association (ERA-EDTA)*National Renal Administrators Association (NRAA)*Nephrology Nursing Certifications Commission (NNCC)*Renal Physicians Association (RPA)*Vascular Access Society of the Americas (VASA)*Vascular Access Society*

Patient Organizations:American Association of Kidney Patients (AAKP)*Dialysis Patient Citizens (DPC)*Home Dialyzors United*National Kidney Foundation (NKF)*Renal Support Network (RSN)*

Pharmaceutical & Biotechnology Companies:AbbVie, Inc.*Amgen, Inc. *Anthera Pharmaceuticals, Inc.*AstraZeneca*Baxter International, Inc.*The Binding Site*Boehringer Ingelheim*ChemoCentryx Inc. Clinical Metabolomics Inc. (d/b/a ClinMet)*Eli Lilly and Company*FAST BioMedical*Fibrotech Therapeutics Pty Ltd*Hospira, Inc.*Mallinckrodt Pharmaceuticals*MediBeacon, LLC*NephropathOPKO Health, Inc.*Otsuka America Pharmaceutical, Inc.*Pfizer, Inc.*Proteon Therapeutics, Inc.*Quintiles Global Clinical Research Organization*Reata Pharmaceuticals, Inc.*Relypsa, Inc.Rockwell Medical Inc.*Sanofi US Services Inc., A Sanofi Company*Thrasos Innovation, Inc.*Vascular Therapies*

Research Institutions:Arbor Research Collaborative for Health*Collaborative Study GroupDuke Clinical Research Institute (DCRI)*The George Institute*Karolinska Institutet*Kidney Research Institute at the University of Washington*University of Oxford- Clinical Trial Service Unit and Epidemiological Studies*The University of Tokyo Hospital*

Additional Partnership With:Center for Disease Control (CDC)Centers for Medicare & Medicaid Services (CMS) - vacantNational Institutes of Health (NIH)Veterans Health Administration (VHA)

Members of the Kidney Health Initiative

Kidney Health Initiative (KHI) is a public-private partnership founded in September 2012 by the American Society of Nephrology and the U.S. Food and Drug Administration.

As of October 2014

*Denotes Pioneer Members

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KHI brings together its members throughout the year to connect stakeholders across different fields, share ideas, collect feedback, and collaborate on new projects. KHI members are invited to attend the Annual KHI Stakeholders Meeting, held in the spring, and any event organized by KHI workgroups.

Annual KHI Stakeholders Meeting

Having held the First Annual KHI Stakeholders Meeting on September 11, 2013, the Second Annual KHI Stakeholders Meeting took place on June 11-12, 2014, in Bethesda, MD. Of the more than 100 participants at the Second Annual KHI Stakeholders Meeting, nearly one-third represented FDA and government agencies, one-third were affiliated with industry, and one-third represented patients and health professionals.

During the opening session, Mark McClellan, MD, PhD, provided his perspective on the intersection between incentives and innovation in the context of the unique infrastructures that have evolved around the management of kidney disease in the United States. Dr. McClellan serves as the senior fellow and director of the Health Care Innovation and Value Initiative at the Brookings Institution, and his presentation drew from his wealth of experience as former FDA Commissioner and former CMS Administrator.

Following Dr. McClellan’s presentation, much of the agenda was devoted to breakout sessions that allowed members to review current KHI projects and provide feedback to authors of project proposals in interactive and engaging presentations. To review the meeting’s entire agenda, please visit KHI’s meeting page online at www.kidneyhealthinitiative.org.

Workgroup Sponsored Events

The KHI Pharmacokinetics in Patients Receiving Continuous Renal Replacement Therapy (CRRT) workgroup held its open workshop titled “Standardized Pharmacokinetics Assessment in Patients Receiving Continuous Renal Replacement Therapy (CRRT)” on Tuesday, November 11, in Philadelphia, PA. Participants included nephrologists, pharmacologists, representatives from FDA and the pharmaceutical industry, and other stakeholders. The workshop reviewed and critiqued the recommendations on pragmatic study designs to generate pharmacokinetic data to guide drug dosing in patients receiving CRRT developed by the KHI workgroup and published in the Clinical Journal of the American Society of Nephrology (CJASN)(5). To review the workshop’s entire agenda, please visit the workgroup’s page online at www.kidneyhealthinitiative.org.

5 C J Am Soc Nephrol, 2014: doi: 10.2215/CJN.05630614

Events

KHI is excited to announce that the Third Annual KHI Stakeholders Meeting will take place May 20–21, 2015, at the Hyatt Regency in Bethesda, MD.

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KHI advances its mission through a portfolio of innovative, collaborative, and member-driven projects. KHI has developed an inclusive and transparent project submission process where members submit project proposals via an online portal and obtain feedback from their peers through an open comment period.

Once the submission portal closes, proposals are reviewed by the KHI Board of Directors and evaluated based on the proposal’s ability to meet the KHI mission, make a lasting impact, and outline a deliverable that is feasible before endorsement as an official KHI project. Once a project is endorsed, multi-disciplinary workgroups are endorsed. The formation of workgroups is an open process by which an application to serve as a workgroup member is posted on the KHI website. When a workgroup is established and operational structure is finalized, deliverables are identified, a timeline is set, and work begins.

Project and Workgroup Identification and Selection

Call for Projects

Members Provide Comments

KHI Board Reviews and “Endorses” Appropriate Projects

Call for Workgroup Members

Project Implementation by Workgroup

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Pilot Projects To model activities that could be facilitated with the newly formed public-private partnership, KHI identified three pilot projects during its first six months of existence. Work began on these pilot projects in spring 2013.

Patient Care Issue: Patients in the intensive care unit often develop acute kidney injury (AKI) and require continuous renal replacement therapy (CRRT), a procedure that differs significantly from outpatient dialysis. While the rate of acute kidney injury in the United States has doubled during the last 10 years, less than 20% of the drugs used have been studied with regard to appropriate dosing for patients in intensive care units (ICUs) receiving CRRT(6)(7). As a result, clinicians and pharmacists often end up making best guesses in terms of dosages of life saving drugs in critically ill patients.

Challenge: The growing number of cases of AKI, increasing use of CRRT, and reliance on a large number of potentially life-saving medications in these critically ill patients necessitate a better understanding of basic pharmacokinetics in this setting. Standardized pharmacokinetics guided drug dosing studies during the pre-approval development process are urgently needed for drugs likely to be used in critically ill patients, and similar studies should be conducted on currently approved drugs commonly used in these patients.

KHI Solution: A KHI workgroup, including FDA staff, evaluated medication dosing during CRRT and prioritized drugs or classes of drugs to help generate key data to improve treatment for these critically ill patients. Based on this analysis, the workgroup recommended an appropriate design for future studies. The workgroup’s recommendations were published in the September 2014 issue of the Clinical Journal of the American Society of Nephrology(8). The workgroup organized an open workshop on November 11, 2014 titled “Standardized Pharmacokinetics Assessment in Patients Receiving Continuous Renal Replacement Therapy (CRRT).” To review the workshop’s entire agenda, please visit the workgroup’s page online at www.kidneyhealthinitiative.org.

6 Raymond K. Hsu, et al. Temporal Changes in Incidence of Dialysis-Requiring AKI. JASN January 2013 24: 37-42, doi:10.1681/ASN.2012080800 7 Clin Pharmacol Ther 2009;86:479 8 Thomas D. Nolin, et al. Pharmacokinetic Assessment in Patients Receiving Continuous RRT: Perspectives from the Kidney Health Initiative. CJASN 2014. doi:10.2215/CJN.05630614

Co-chairs

George R. Aronoff, MD, University of Louisville

Stuart Goldstein, MD, Cincinnati Children’s Hospital (KHI Board of Directors Member)

Thomas D. Nolin, PharmD, PhD, FASN, University of Pittsburgh

Members

Patrick Archdeacon, MD, Office of Medical Policy, Center for Drug Evaluation and Research (CDER), FDA (KHI Co-Chair)

John K. Leypoldt, MDBaxter International Inc.

William Fissell, MDVanderbilt University

Kellie Reynolds, PharmDOffice of Clinical Pharmacology (OCP), FDA

Michael Flessner, MD, PhD, National Institute of Diabetes and Digestive and Kidney Diseases (KHI Board of Directors Member)

Prabir Roy-Chaudhury, MD, PhD, FASNUniversity of Cincinnati (KHI Co-Chair)

Lokesh Jain, PhDOffice of Clinical Pharmacology (OCP), FDA

Jennifer Witcher, PhDEli Lilly and Company

Rajnikanth Madabushi, PhDOffice of Clinical Pharmacology (OCP), FDA

Lei Zhang, PhDOffice of Clinical Pharmacology (OCP), FDA

Rajnish Mehrotra, MD, FASNUniversity of Washington

Issam Zineh, PharmD, MPHOffice of Clinical Pharmacology (OCP), FDA

Shiew Mei Huang, PhD, FCPOffice of Clinical Pharmacology (OCP), FDA

1 Pharmacokinetics in Patients Receiving Continuous Renal Replacement Therapy (CRRT)

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Chair

Brad Rovin, MD, FACP, FASN, The Ohio State University

Members

Patrick Archdeacon, MD, Office of Medical Policy, Center for Drug Evaluation and Research (CDER), FDA (KHI Co-Chair)

Meggan Mackay, MD, MS, Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System Foundation

Maria Dall’Era, MDUniversity of California, San Francisco

Prabir Roy-Chaudhury, MD, PhD, FASNUniversity of Cincinnati (KHI Co-Chair)

Kenneth Kalunian, MDUniversity of California, San Diego

Laura StraubImmune Tolerance Network

Larissa Lapteva, MD, MHSCenter for Drug Evaluation and Research (CDER), FDA

Sarah Yim, MDCenter for Drug Evaluation and Research (CDER), FDA

Additional Support Provided By

Amrutha Baskaran, MD, MSCR, Post-Doctoral Scholar, University of California, San Diego

Martin L Lesser, PhD, EMT-CC, Director and Investigator, Biostatistics Unit, Feinstein Institute for Medical Research

Joanna Stein, PhD, Biostatistician Feinstein Institute for Medical Research

2 Outcome Measures in Lupus Nephritis

Patient Care Issue: Approximately 1.5 million Americans have systemic lupus erythematosus, and up to 60% of those patients may develop lupus nephritis, an inflammation of the kidney that can lead to chronic kidney disease (CKD) or end-stage renal disease (ESRD)(9)(10).

Challenge: Clinical trial endpoints measure success or failure of therapies being tested. Unfortunately, no well-defined endpoints exist for lupus nephritis. Without clear endpoints, researchers and industry face challenges developing new therapies for the disease. This is an important barrier to innovative drug development in this field.

KHI Solution: A KHI workgroup (in partnership with the Lupus Nephritis Trial Network) is analyzing existing data to test for clear, valid endpoints for lupus nephritis trials. The workgroup contacted pharmaceutical companies that have completed trials in lupus nephritis to discuss the inclusion of their data in this project. Recognizing the value of including physicians treating these patients, the workgroup recruited more than 10 global cohort sites to participate in the project. The project has an opportunity to aggregate up to 1,000 patients for further analysis by the end of 2014. Upon completion of the data analysis, the workgroup will recommend a core set of outcome measures, biomarkers, surrogate markers, and clearly defined terms that should be incorporated into all future lupus nephritis trials. Developing these measures will make it much more feasible for companies to invest in the research necessary to improve treatments for patients with this serious disease.

9 Lawrence RC, et al. for the National Arthritis Data Workgroup. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States: part II. Arthritis Rheum. 2008;58:26–35. 10 Lee YH, et al. Induction and Maintenance Therapy for Lupus Nephritis: A Systematic Review and Meta-Analysis. Lupus. 2010;19703-710.

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Members

Patrick Archdeacon, MD, Office of Medical Policy, Center for Drug Evaluation and Research (CDER), FDA (KHI Co-Chair)

Carolyn Y. Neuland, PhD, Center for Devices and Radiological Health (CDRH), FDA (KHI Board of Directors Member)

Matthew D. Breyer, MD, FASN, Eli Lilly and Company (KHI Board of Directors Member)

Prabir Roy-Chaudhury, MD, PhD, FASN, University of Cincinnati (KHI Co-Chair)

Ronald J. Falk, MD, FASN, University of North Carolina Chapel Hill (KHI Board of Directors Member)

James A. Sloand, MD, FASN, Baxter International Inc. (KHI Board of Directors Member)

Jula Inrig, MD, FASN, Quintiles Global Clinical Research Organization (KHI Board of Directors Member)

Kimberly Smith, MD, MS, Center for Drug Evaluation and Research (CDER), FDA and formerly Center for Medicare and Medicaid Services

Reshma Kewalramani, MD, FASN, Amgen, Inc. (KHI Board of Directors Member)

Jennifer Snook, PharmD, Chicago, IL

Celeste Castillo Lee, Ann Arbor, MI and The Vasculitis Foundation (KHI Board of Directors Member)

Chair

Peter Linde, MD, FASN, AbbVie Inc. (KHI Board of Directors Member)

3 Promoting Kidney Health and Innovative Treatments for Kidney Disease - Barriers and Potential Solutions

Patient Care Issue: More than 20 million Americans have CKD and more than 600,000 Americans have kidney failure or ESRD(11)(12). Too few new products treating or preventing kidney disease have appeared on the market as companies and researchers face a variety of barriers to the innovation of new therapies in the kidney community.

Challenge: Barriers exist in the discovery phase of development, in developing new therapeutics, and in establishing the evidence base for clinical practice. These obstacles include a lack of infrastructure, uncertain regulatory landscape, lack of universally accepted clinical trial endpoints, and payer and reimbursement challenges.

KHI Solution: A workgroup comprised of KHI members from patient groups, health professional organizations, industry, and representatives from FDA are examining, defining, and explaining the major barriers to innovation in kidney health. In a future white paper, the workgroup will define the major barriers to innovation in kidney health, and identify potential solutions to those barriers. This project is expected to help frame the strategic priorities that will stimulate innovation in kidney disease.

11 Centers for Disease Control and Prevention (CDC). National Chronic Kidney Disease Fact Sheet: General Information and National Estimates on Chronic Kidney Disease in the United States, 2014. Atlanta, GA: US Department of Health and Human Services, Centers for Disease Control and Prevention; 2014. 12 U.S. Renal Data System, USRDS 2013 Annual Data Report: Atlas of Chronic Kidney Disease and End-Stage Renal Disease in the United States, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 2013.

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Member-Driven Projects Beginning in September 2013, after the three pilot projects were well underway, KHI members submitted their ideas for projects that could be administered through this public-private partnership. As of October 2014, KHI has endorsed six projects submitted via the project submission process.

Patient Care Issue: Hemodialysis vascular access has been called the “lifeline” for patients on hemodialysis. Unfortunately, due to the many problems associated with dialysis vascular access (stenosis, thrombosis, infection), it is also the “Achilles Heel” of hemodialysis. Specifically, more than 50% of arteriovenous fistulae (AVF) are unsuitable for hemodialysis four to five months following creation; the primary patency of arteriovenous grafts (AVG) has been reported to be as low as 23% at one year; and only 9% of tunneled dialysis catheters (TDCs) are still functional at one year(13)(14)(15).

Challenge: Despite the magnitude of this clinical problem, there are currently no truly effective therapies for dialysis vascular access dysfunction. An important barrier to the development of safe and effective therapies could be the lack of consensus as to the "right" clinical trial endpoints for this condition.

KHI Solution: This project brought together the diverse stakeholders in this area (patients, health professionals, industry, dialysis organizations, and federal agencies) to clarify appropriate trial endpoints for vascular access trials best suited to inform clinical, regulatory, and coverage decisions, in those circumstances where clinical data is required to support the decisions.

At an organizational level, it is important for this project to be operationally nimble but also very inclusive. Ideally, each stakeholder must participate. Therefore, the workgroup is comprised of a small core group that will allow for quick operational decisions as well as a larger steering committee with international advisers which will allow for the voices of all the stakeholders in this area to be heard.

13 Dember LM, et al. Effect of clopidogrel on early failure of arteriovenous fistulas for hemodialysis: a randomized controlled trial. JAMA 2008;299:2164-71. 14 Dixon BS, et al. Effect of dipyridamole plus aspirin on hemodialysis graft patency. N Engl J Med 2009;360:2191-201 15 Hodges TC, et al. Longitudinal comparison of dialysis access methods: risk factors for failure. J Vasc Surg 1997;26:1009-19.

Co-chairs

Haimanot Wasse, MD, MPH, FASN, Northwestern University

Surendra Shenoy, MD, PhD, Washington University School of Medicine, Barnes Jewish Hospital

Core Committee

Paul Chandeysson, MDCenter for Devices and Radiological Health (CDRH), FDA

Douglas M. Silverstein, MDCenter for Devices and Radiological Health (CDRH), FDA

Laura M. Dember, MDHospital of the University of Pennsylvania

Aliza Thompson, MDCenter for Drug Evaluation and Research (CDER), FDA

Prabir Roy-Chaudhury, MD, PhD, FASN, University of Cincinnati (KHI Co-Chair)

Jack Work, MD, Asheville, NC

Steering Committee

Michael Allon, MDUniversity of Alabama at Birmingham

Paul KravitzNxStage Medical Inc.

Lynda K. Ball, CNN, Everett, WA (Liaison for the American Nephrology Nurses’ Association)

Mahesh Krishnan, MD, MPH, MBA, FASNDaVita Healthcare Partners (KHI Board of Directors Member)

Deborah J. Brouwer-Maier, RN, CNNFresenius Medical Care

Jeffery Lawson, MD, PhDDuke University

Steven K. Burke, MDProteon Therapeutics

Charmaine E. Lok, MDUniversity Health Network-Toronto General Hospital

Deepa H. Chand, MD, FASN, Rush University Medical Center (Liaison for the American Society of Pediatric Nephrology)

Gordon McLennan, MDCleveland Clinic (Liaison for the Society of Interventional Radiology)

Dirk M. Hentschel, MD, FASN, Brigham and Women’s Hospital (Liaison for the Vascular Access of Society of the Americas)

Ronald L. Pisoni, PhDArbor Research Collaborative for Health

Thomas S. Huber, MD, PhDUniversity of Florida (Liaison for the Society for Vascular Surgery)

Aris Q. Urbanes, MDLifeline Vascular Access

Alethia Karkanis, BSN, MSN-CRMW.L. Gore & Associates

International Advisers

Eric S. Chemla, MD St. George’s Healthcare NHS Trust, United Kingdom

Kevan Polkinghorne, PhD, MBChBMonash University, Australia

Maurizio Gallieni, MD, FASN, A.O. Ospedale San Carlo Borromeo, Italy (Liaison for Vascular Access Society)

Miguel C. Riella, MD, PhDCatholic University of Parana, Brazil

Will G. Herrington, MBBS, Clinical Trials Service Unit & Epidemiological Studies Unit (CTSU), University of Oxford, United Kingdom

Jan Todoir, MD, PhDUniversity Hospital Maastricht, Netherlands

Clinical Trial Endpoints for Dialysis Vascular Access1

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Co-chairs

Dolph Chianchiano, JD, MPA, National Kidney Foundation (KHI Board of Directors Member)

Frank Hurst, MD, Center for Devices and Radiological Health (CDRH), FDA

Members

Terri BonadioFresenius Medical Care

Celeste Castillo Lee, Ann Arbor, MI (Liaison for the Vasculitis Foundation) (KHI Board of Directors Member)

Deborah J. Brouwer-Maier, RN, CNNFresenius Medical Care

Carolyn Y. Neuland, PhD, Center for Devices and Radiological Health (CDRH), FDA (KHI Board of Directors Member)

Diana Clynes, Tampa, FL (Liaison for the American Association of Kidney Patients)

Lillian Pryor, MSN, RN, CNN, Jersey City, NJ (Liaison for the American Nephrology Nurses’ Association)

Maria Ferris, MD, MPH, PhD, University of North Carolina Chapel Hill (Liaison for the American Society of Pediatric Nephrologists)

Bradley Roynon, RACBaxter International Inc.

Jennifer E. Flythe, MD, MPHUniversity of North Carolina Chapel Hill

Melissa Threlkeld, MHA, FACHEAustin, TX

Martin Ho, MSCenter for Devices and Radiological Health (CDRH), FDA

Linda Upchurch, MBA, MHANxStage Medical, Inc.

Workshop to Elucidate Role of Patient Preferences in Support of the Center for Devices and Radiological Health Regulatory Actions in Kidney Disease

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Patient Care Issue: Although patients are the final consumer, they rarely have an opportunity to influence products that come to market. The success of a new product is based on many factors, including the usability by patients. Finding appropriate and fulfilling ways for patients to participate in the development of new products is a vital goal.

Challenge: The Center for Devices and Radiological Health (CDRH) at FDA has emphasized the importance of incorporating patient preferences for risk over benefit into product development programs and into regulatory decision making. However, the relevant stakeholders (patients, health professionals, industry, and federal agencies) have an imperfect understanding of best practices for creating the tools to capture and analyze data related to patient preferences.

KHI Solution: KHI has formed a workgroup that is planning a series of webinars and a workshop where patient organizations, health care professionals, device manufacturers, and regulators can come together to discuss the barriers and solutions to developing the necessary tools to facilitate the incorporation of patient preferences into product development and regulatory decision making for medical products in kidney disease.

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Patient Care Issue: Nearly one-half of patients with CKD, approximately 10 million Americans, have diabetes mellitus(16). Diabetes accounted for 44% of new cases of kidney failure in 2007(17). In diabetic kidney disease (also called diabetic nephropathy); cells and blood vessels in the kidneys are damaged, affecting the organs’ ability to filter out waste. The progression from initial kidney injury due to diabetes, to diabetic kidney disease, to ERSD severely affects patients’ quality of life, and is responsible for a very significant morbidity and economic cost for the diabetes and kidney communities.

Challenge: There is a lack of consensus for not only clinical trial endpoints in this area, but also for established standards for clinical research data collection, in order to support the acquisition, exchange, and comparisons of future trials.

KHI Solution: In coordination with the Clinical Data Interchange Standards Consortium (CDISC), Coalition for Accelerating Standards and Therapies (CFAST), FDA, and TransCelerate BioPharma, Inc., KHI is assembling a workgroup to help define appropriate standards in the therapeutic area of diabetic kidney disease. KHI’s specific role is to provide the clinical and medical expertise to this broader team.

KHI Workgroup: The KHI Board of Directors liaison is Jula K. Inrig, MD, FASN. A complete listing of the workgroup can be found on the KHI website, www.kidneyhealthinitiative.org.

16 Michelle A. Roett, et al. Diabetic Nephropathy - The Family Physician’s Role. Am Fam Physician. 2012 May 1;85(9):883-889. 17 United States Renal Data System. USRDS 2007 Annual Data Report. Bethesda, MD: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, U.S. Department of Health and Human Services; 2007

3 Data Standards in Diabetic Kidney Disease

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4 Pragmatic Trials in Nephrology: Challenges & Opportunities

Patient Care Issue: Defining the benefit of a therapy in routine clinical experience is an important opportunity for kidney disease. There are almost 400,000 hemodialysis patients in the United States(18). This patient population has a mortality rate approaching 50% at three years from the start of hemodialysis, incurring Medicare expenditures in excess of $24 billion annually(18).

The TiME Trial is a large pragmatic clinical trial that is being conducted through the NIH Health Care Systems Research Collaboratory, a Common Fund initiative that aims to integrate clinical trials into healthcare delivery. The objective of the trial is to determine whether dialysis facility implementation of a hemodialysis session duration of at least 4.25 hours for incident patients improves clinical outcomes and quality of life.

Challenge: Few randomized clinical trials, however, have been conducted in this setting due to various perceived barriers – including FDA regulations related to data collection, lack of clarity around best practices for ensuring human subject protections, and cumbersome CMS requirements related to billing for patients involved in research.

KHI Solution: KHI is supporting a workgroup comprised of TiME Trial investigators. The goal of the project is to provide the kidney community with information about the potential use of pragmatic trials to answer important clinical questions. In addition, the workgroup will recommend solutions to operational, regulatory, and business issues that may hinder routine conduct of clinical trials embedded in the provision of clinical care.

KHI Workgroup: This workgroup is being led by Laura M. Dember, MD and KHI Board of Director liaison, Michael F. Flessner, MD, PhD. A complete listing of the workgroup can be found on the KHI website, www.kidneyhealthinitiative.org.

18 U.S. Renal Data System, USRDS 2013 Annual Data Report: Atlas of Chronic Kidney Disease and End-Stage Renal Disease in the United States, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 2013.

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5 Advancing Technologies to Facilitate Remote Management of Patient Self-Care in Renal Replacement Therapy (RRT)

Patient Care Issue: Digital and mobile-based technologies present new and possibly better disease management options for patients and healthcare professionals. These technologies hold the potential of improving outcomes through individualized patient-centered education, remote communication and data exchange, in-home clinical guidance, prescription/treatment adherence or changes, and a rapid alert system for health professionals. This responsiveness empowers patients and family care providers and has the potential to increase the number of patients receiving home-based therapies.

Challenge: There is uncertainty regarding the approval of advanced medical devices, accessories, software, and mobile medical applications for consumer use. Reimbursement policies vary significantly across Medicaid, Medicare, and commercial insurance. This regulatory and payer misalignment and the knowledge gap is hindering patient access to technologies and services that have potential to improve outcomes for patients on home based therapies.

KHI Solution: KHI is currently assembling a workgroup that is tasked with addressing the state of remote monitoring wireless health/telemedicine technology that can be utilized to treat patients with kidney disease, assessing the potential clinical and economic value, and both the need and potential pathways. This information will be used to address key regulatory, legal, legislative, and reimbursement barriers affecting the adoption and usage of such technologies. The workgroup will develop a white paper and present their findings in an associated stakeholder symposium.

KHI Workgroup: The KHI Board of Directors liaison is James A. Sloand, MD, FASN. A complete listing of the workgroup can be found on the KHI website, www.kidneyhealthinitiative.org.

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6Regulatory Policies & Positions Affecting Device Approval in the United States: Tools to Assess the Process and Foster Device Development for Patients with Kidney Disease

Patient Care Issue: There have been few innovative therapies marketed for patients with CKD or ESRD during the last decade. In contrast, a number of new therapies have been approved and marketed outside of the United States.

Challenge: It is essential that device manufacturers and other stakeholders have optimal information regarding the standards and requirements for approval of clinical trial protocols and market approval for drugs and devices at FDA.

KHI Solution: KHI is assembling a workgroup that will define and study a few broad categories of devices that have been marketed outside of the United States. The workgroup will determine the value of these devices in patient care, ascertain pathways to expedite approvals in the United States (if felt to be appropriate), and then summarize their findings in a white paper.

KHI Workgroup: This workgroup is being led by Stephen R. Ash, MD, FACP, and Douglas M. Silverstein, MD. The KHI Board of Director liaison is Carolyn Y. Neuland, PhD. A complete listing of the workgroup can be found on the KHI website, www.kidneyhealthinitiative.org.

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Kidney Health Initiative1510 H Street NW

Suite 800Washington, DC 20005

khi@asn-online.orgwww.kidneyhealthinitiative.org

Co-Chairs

Patrick Archdeacon, MDMedical Officer, Office of Medical PolicyCenter for Drug Evaluation and Research (CDER)Food and Drug Administration (FDA)Email: Patrick.archdeacon@fda.hhs.gov

Prabir Roy-Chaudhury, MD, PhD, FASNProfessor of MedicineDivision of Nephrology University of Cincinnati College of MedicineEmail: roychap@ucmail.uc.edu

Staff

Melissa WestProject DirectorKidney Health InitiativePhone: 202-740-7891Email: mwest@asn-online.org

Ryan MurrayProject AssociateKidney Health InitiativePhone: 202-400-2485Email: rmurray@asn-online.org