Abstract
Occasional bursts of discovery and innovation have appeared during the otherwise stagnant past several decades of drug development in nephrology. Among other recent drug discoveries, the unexpected kidney benefits observed with sodium/glucose cotransporter 2 inhibitors may herald a renaissance of drug development in kidney disease. This recent progress highlights the need to further promote and stimulate research and development of promising therapies that may ameliorate the morbidity and mortality associated with kidney disease. To help identify and address barriers to drug development in nephrology, the Duke Clinical Research Institute convened a conference in April 2019 that included stakeholders from academia, industry, government agencies, and patient advocacy. From these discussions, several opportunities were identified to improve every stage of drug development for kidney disease from early discovery to implementation into practice. Key topics reviewed in this article are the utility of interconnected data and site research networks, surrogate end points, pragmatic and adaptive trial designs, the promising uses of real-world data, and methods to improve the generalizability of trial results and uptake of approved drugs for kidney-related diseases.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 842-850 |
| Number of pages | 9 |
| Journal | American Journal of Kidney Diseases |
| Volume | 76 |
| Issue number | 6 |
| DOIs | |
| State | Published - Dec 2020 |
Funding
Dr Edmonston reports consulting for Akebia. Dr Roe reports grant support from the American College of Cardiology, American Heart Association, AstraZeneca, Familial Hypercholesterolemia Association, Ferring Pharmaceuticals, Janssen Pharmaceuticals, Myokardia, Patient Centered Outcomes Research Institute, and Sanofi-Aventis; and consulting fees from Amgen, Ardea Biosciences, AstraZeneca, Eli Lilly & Co, Elsevier Publishers, Flatiron, Janssen Pharmaceuticals, Novo Nordisk, Pfizer, Regeneron, Roche-Genentech, Sanofi-Aventis, and Signal Path. Dr Block is an employee of Reata; has consulted for or received support from Kyowa Hakko Kirin, Amgen, Keryx, Akebia, OPKO, Vifor, CARA, AstraZeneca Inc, Mitsubishi, Kirin, Ardelyx, and Reata; is a director of Ardelyx, Inc; owns stock in Reata and Ardelyx, and his wife is an employee of US Renal Care. Mr Conway reports his relationships include but are not limited to the following: Member, Board of Directors, and Chair of Public Policy, American Association of Kidney Patients (occasional reimbursement for travel expenses); Patient Editor, Clinical Journal of the American Society of Nephrology (stipend); Member, Board of Directors, Kidney Health Initiative; Member, Kidney Committee, American Board of Internal Medicine (stipend); Co-Chair, Global Kidney Summit, a collaborative of AAKP & the George Washington University School of Medicine and Health Sciences; Chair, FDA Patient Engagement Advisory Committee; Member, External Expert Panel, Kidney Precision Medicine Project; Member, External Expert Panel, US Renal Data System, National Institute of Diabetes and Digestive and Kidney Diseases; Liaison, Healthcare Infection Control Practices Advisory Committee for the Centers for Disease Control and Prevention and US Department of Health and Human Services; Member, Peer Reviewed Medical Research Program, Congressionally Directed Medical Research Programs at the US Department of Defense (stipend); Speaker, Bayer (2019, speaker fee and travel). Dr Dember receives compensation from the NKF for serving as a Deputy Editor of the American Journal of Kidney Diseases and reports consulting fees from Merck, Cara Therapeutics, Proteon Therapeutics, and GlaxoSmithKline. Dr DiBattiste was a full-time employee of Janssen and shareholder in Johnson & Johnson at the time of this conference. Dr Greene reports personal consulting fees from Janssen Pharmaceuticals, DURECT Corp, and Pfizer Inc, and grant support from AstraZeneca Inc, CSL, and Boehringer Ingleheim. Dr Inker reports funding from the NIH, NKF, Retrophin, Omeros, Dialysis Clinics, Inc, and Reata Pharmaceuticals for research and contracts to Tufts Medical Center; and consulting agreements with Tricida and Omeros Corp. Dr Nkulikiyinka is a full-time employee and stock holder of Bayer AG. Dr Polidori is a full-time employee of Janssen Research & Development and a shareholder of Johnson & Johnson. Dr Roessig is a full-time employee of Bayer AG. Dr Tangri reports grants and personal fees from AstraZeneca Inc; personal fees from Otsuka Inc, Janssen, and Boehringer Ingelheim/Eli Lilly & Co; and grants, personal fees, and other from Tricida Inc. Dr Wyatt reports Academic Steering Committee membership for Allena Pharmaceuticals. Dr Chertow serves on the Board of Directors of Satellite Healthcare, a not-for-profit dialysis provider; has served or currently serves as an advisor or member of a clinical trial Steering Committee with Akebia, Amgen, Ardelyx, AstraZeneca, Baxter, CloudCath, Cricket, DiaMedica, DURECT Corp, Gilead, Outset, Reata, Sanifit, and Vertex; and has served or currently serves on Data Safety and Monitoring Boards with Angion, Bayer, and ReCor. Dr Wolf reports consulting for Akebia, Amag, Amgen, Ardelyx, Diasorin, Luitpold, and Pharmacosmos. All other authors declare that they have no relevant financial interests. Daniel L. Edmonston, MD, Matthew T. Roe, MD, MHS, Geoffrey Block, MD, Paul T. Conway, BA, Laura M. Dember, MD, Peter M. DiBattiste, MD, Tom Greene, PhD, Ali Hariri, MD, Lesley A. Inker, MD, Tamara Isakova, MD, MMSc, Maria E. Montez-Rath, PhD, Richard Nkulikiyinka, MD, David Polidori, PhD, Lothar Roessig, MD, Navdeep Tangri, MD, PhD, Christina Wyatt, MD, Glenn M. Chertow, MD, MPH, and Myles Wolf, MD, MMSc. Funding support for the meeting was provided through registration fees from Akebia Therapeutics; Amgen; AstraZeneca; Bayer AG; Boehringer-Ingelheim International GmbH; Eli Lilly & Co; Janssen; Pfizer Inc; Reata Pharmaceuticals, Inc; Sanifit, Inc; and Sanofi. No government funds were used for this meeting. The meeting funders did not have a role in defining the content of this report. Dr Edmonston reports consulting for Akebia. Dr Roe reports grant support from the American College of Cardiology, American Heart Association, AstraZeneca, Familial Hypercholesterolemia Association, Ferring Pharmaceuticals, Janssen Pharmaceuticals, Myokardia, Patient Centered Outcomes Research Institute, and Sanofi-Aventis; and consulting fees from Amgen, Ardea Biosciences, AstraZeneca, Eli Lilly & Co, Elsevier Publishers, Flatiron, Janssen Pharmaceuticals, Novo Nordisk, Pfizer, Regeneron, Roche-Genentech, Sanofi-Aventis, and Signal Path. Dr Block is an employee of Reata; has consulted for or received support from Kyowa Hakko Kirin, Amgen, Keryx, Akebia, OPKO, Vifor, CARA, AstraZeneca Inc, Mitsubishi, Kirin, Ardelyx, and Reata; is a director of Ardelyx, Inc; owns stock in Reata and Ardelyx, and his wife is an employee of US Renal Care. Mr Conway reports his relationships include but are not limited to the following: Member, Board of Directors, and Chair of Public Policy, American Association of Kidney Patients (occasional reimbursement for travel expenses); Patient Editor, Clinical Journal of the American Society of Nephrology (stipend); Member, Board of Directors, Kidney Health Initiative; Member, Kidney Committee, American Board of Internal Medicine (stipend); Co-Chair, Global Kidney Summit, a collaborative of AAKP & the George Washington University School of Medicine and Health Sciences; Chair, FDA Patient Engagement Advisory Committee; Member, External Expert Panel, Kidney Precision Medicine Project; Member, External Expert Panel, US Renal Data System, National Institute of Diabetes and Digestive and Kidney Diseases; Liaison, Healthcare Infection Control Practices Advisory Committee for the Centers for Disease Control and Prevention and US Department of Health and Human Services; Member, Peer Reviewed Medical Research Program, Congressionally Directed Medical Research Programs at the US Department of Defense (stipend); Speaker, Bayer (2019, speaker fee and travel). Dr Dember receives compensation from the NKF for serving as a Deputy Editor of the American Journal of Kidney Diseases and reports consulting fees from Merck, Cara Therapeutics, Proteon Therapeutics, and GlaxoSmithKline. Dr DiBattiste was a full-time employee of Janssen and shareholder in Johnson & Johnson at the time of this conference. Dr Greene reports personal consulting fees from Janssen Pharmaceuticals, DURECT Corp, and Pfizer Inc, and grant support from AstraZeneca Inc, CSL, and Boehringer Ingleheim. Dr Inker reports funding from the NIH, NKF, Retrophin, Omeros, Dialysis Clinics, Inc, and Reata Pharmaceuticals for research and contracts to Tufts Medical Center; and consulting agreements with Tricida and Omeros Corp. Dr Nkulikiyinka is a full-time employee and stock holder of Bayer AG. Dr Polidori is a full-time employee of Janssen Research & Development and a shareholder of Johnson & Johnson. Dr Roessig is a full-time employee of Bayer AG. Dr Tangri reports grants and personal fees from AstraZeneca Inc; personal fees from Otsuka Inc, Janssen, and Boehringer Ingelheim/Eli Lilly & Co; and grants, personal fees, and other from Tricida Inc. Dr Wyatt reports Academic Steering Committee membership for Allena Pharmaceuticals. Dr Chertow serves on the Board of Directors of Satellite Healthcare, a not-for-profit dialysis provider; has served or currently serves as an advisor or member of a clinical trial Steering Committee with Akebia, Amgen, Ardelyx, AstraZeneca, Baxter, CloudCath, Cricket, DiaMedica, DURECT Corp, Gilead, Outset, Reata, Sanifit, and Vertex; and has served or currently serves on Data Safety and Monitoring Boards with Angion, Bayer, and ReCor. Dr Wolf reports consulting for Akebia, Amag, Amgen, Ardelyx, Diasorin, Luitpold, and Pharmacosmos. All other authors declare that they have no relevant financial interests. The authors thank Jennifer Gloc, BA, and Carolyn Moore Arias, MPH, for substantial contributions to the organization of the conference; and Peter Hoffmann, BA, for editorial contributions. Ms Gloc, Ms Arias, and Mr Hoffmann are all affiliated with the Duke Clinical Research Institute. Received February 10, 2020. Evaluated by 2 external peer reviewers, with editorial input from an Acting Editor-in-Chief (Editorial Board Member F. Perry Wilson, MD, MS). Accepted in revised form May 27, 2020. The involvement of an Acting Editor-in-Chief to handle the peer-review and decision-making processes was to comply with AJKD's procedures for potential conflicts of interest for editors, described in the Information for Authors & Journal Policies.
Keywords
- Drug development
- administrative data sets
- clinical investigation
- clinical trial design
- conference report
- data integration
- disease network
- drug discovery
- electronic health record (EHR)
- genetic determinants of disease
- health care innovation
- kidney disease end points
- nephrology research
- patient-centered endpoints (PCEs)
- post-approval trials
- post-marketing studies
- pragmatic trial
- real-world evidence
- surrogate end points
- therapeutic target
ASJC Scopus subject areas
- Nephrology