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PPT

  1. 1. GU Advisory Panel Meeting Nocturnal Home Hemodialysis Carolyn Y. Neuland, Ph.D. Chief, Gastroenterology and Renal Devices Branch Division of Reproductive, Abdominal and Radiological Devices Office of Device Evaluation Center for Devices and Radiological Health June 8, 2005
  2. 2. Overview <ul><li>Introduction </li></ul><ul><li>Panel Update </li></ul><ul><li>Regulation of Hemodialysis Devices </li></ul><ul><li>Guidance Documents for Hemodialysis </li></ul><ul><li>Definition of Nocturnal Home Hemodialysis </li></ul><ul><li>Meeting Objectives </li></ul>
  3. 3. Linda Carr Consumer Safety Technician Jeffrey Cooper, D.V.M. Veterinarian / Panel Exec. Sec. Linda Dart, M.S. Biochemist Gema Gonzalez, M.S. Biomedical Engineer Irada Isayeva, Ph.D. Polymer Chemist Kristina Lauritsen, Ph.D. Tumor Biologist Barbara McCool, M.S.R.N. Nurse Consultant Joshua Nipper, M.E. Biomedical Engineer Kathleen Olvey Biologist Claudia Ruiz-Zacharek, M.D. Nephrologist Rebecca Stephenson Chemical Engineer Kellie Straughn Clerk Typist Richard Williams Mechanical Engineer
  4. 4. Panel Update
  5. 5. P020006 - Enteryx Procedure Kit Boston Scientific Corporation <ul><li>Description/Indication – solution injected into the LES for the treatment of GERD in patients who are responsive to pharmacologic therapy </li></ul><ul><li>Panel Meeting Date – January 17, 2003 </li></ul><ul><li>GU Panel Recommendation – Approval with Conditions </li></ul><ul><ul><li>Modified physician labeling </li></ul></ul><ul><ul><li>Modified patient labeling </li></ul></ul><ul><ul><li>Post market study with 36 months follow-up from the last injection </li></ul></ul>
  6. 6. <ul><li>Current Status – PMA approved </li></ul><ul><li>April 22, 2003 </li></ul><ul><li>Post-approval Study </li></ul><ul><ul><li>3 year post-implantation follow-up </li></ul></ul><ul><ul><li>Medical Device Reporting (MDR) </li></ul></ul>P020006 - Enteryx Procedure Kit Boston Scientific Corporation
  7. 7. Nocturnal Home Hemodialysis
  8. 8. Regulation of Hemodialysis Devices <ul><li>Class II Medical Devices </li></ul><ul><li>Risk Based classification </li></ul><ul><li>Moderate level of risk </li></ul><ul><li>Requirement for General Controls and Special Controls to ensure safety and effectiveness </li></ul><ul><li>510(k) - Premarket Notification </li></ul><ul><li>There are currently no devices cleared by FDA for Nocturnal Home Hemodialysis </li></ul>
  9. 9. Regulation of Hemodialysis Devices <ul><li>Establishes substantial equivalence (SE) to a legally marketed predicate device </li></ul><ul><li>As safe and as effective as predicate device </li></ul><ul><li>Performance data: </li></ul><ul><ul><li>Bench studies </li></ul></ul><ul><ul><li>Clinical studies (especially for Home Systems) </li></ul></ul>
  10. 10. Dialysis Devices <ul><li>Most are regulated as Class II devices </li></ul><ul><li>Primary classification regulations used: </li></ul><ul><ul><li>§876.5820 – Hemodialysis systems and accessories </li></ul></ul><ul><ul><ul><li>Conventional Dialyzers </li></ul></ul></ul><ul><ul><ul><li>Reuse of Conventional Dialyzers </li></ul></ul></ul><ul><ul><ul><li>Dialysis Delivery Systems and Tubing Sets </li></ul></ul></ul><ul><ul><ul><li>Hemodialysates </li></ul></ul></ul><ul><ul><li>§876.5860 – High permeability hemodialysis systems </li></ul></ul><ul><ul><ul><li>High Flux Dialyzers </li></ul></ul></ul><ul><ul><ul><li>Reuse of High Flux Dialyzers </li></ul></ul></ul><ul><ul><ul><li>Dialysis Systems with Ultrafiltration Controller </li></ul></ul></ul>
  11. 11. Dialysis Devices <ul><ul><li>§876. 5600 - Sorbent regenerated dialysate delivery system for hemodialysis </li></ul></ul><ul><ul><li>§876. 5665 - Water purification system for </li></ul></ul><ul><ul><li>hemodialysis </li></ul></ul><ul><ul><li>§876. 5540 - Blood access device and accessories </li></ul></ul><ul><ul><ul><ul><ul><li>Class III for implanted catheters </li></ul></ul></ul></ul></ul><ul><ul><li>§876.5630 - Peritoneal dialysis system and accessories </li></ul></ul>
  12. 12. Guidance Documents for Hemodialysis Devices <ul><li>Guidance for the Content of Premarket Notifications for Conventional and High Permeability Hemodialyzers – 1998 </li></ul><ul><li>Guidance for the Content of Premarket Notifications for Hemodialysis Delivery Systems – 1998 </li></ul><ul><li>Guidance for Hemodialyzer Reuse Labeling – 1995 </li></ul><ul><li>Guidance for the Content of Premarket Notifications for Water Purification Components and Systems for Hemodialysis – 1997 </li></ul>
  13. 13. Guidance Document <ul><li>“ Guidance documents are documents prepared for FDA staff, applicants/sponsors, and the public that describe the agency’s interpretation of or policy on a regulatory issue” </li></ul><ul><li>21 CFR §10.115 </li></ul>
  14. 14. Definition of Nocturnal Home Hemodialysis <ul><li>Nocturnal Home Hemodialysis (NHD) is a type of hemodialysis performed in the home by the patient, while the patient is asleep ( typically at night ), over a 6-10 hour period, using slower flow rates for blood and dialysate, and a treatment frequency of 5 to 7 days per week. </li></ul>
  15. 15. Nocturnal Home Hemodialysis Objectives of Meeting <ul><li>To discuss and provide recommendations on the clinical and scientific issues associated with hemodialysis device design, labeling, and training for Nocturnal Home Hemodialysis </li></ul><ul><li>To discuss and provide recommendations on clinical trial design to study Nocturnal Home Hemodialysis </li></ul><ul><li>To obtain scientific feedback which can be used to help in device evaluation decisions and may lead to the future development of a guidance document for Nocturnal Home Hemodialysis </li></ul>
  16. 16. Nocturnal Home Hemodialysis <ul><li>Overview of Conventional </li></ul><ul><li>Hemodialysis System </li></ul><ul><li>Joshua Nipper – Biomedical Engineer </li></ul><ul><li>Gastroenterology and Renal Devices Branch </li></ul>
  17. 17. Overview of Conventional Hemodialysis Delivery Devices Joshua C. Nipper, M.E. Biomedical Engineer Gastroenterology and Renal Devices Branch Division of Reproductive, Abdominal and Radiological Devices Office of Device Evaluation Center for Devices and Radiological Health June 8, 2005
  18. 18. Overview <ul><li>Conventional Hemodialysis (HD) Systems </li></ul><ul><ul><li>A “standard” device </li></ul></ul><ul><ul><li>Monitored parameters </li></ul></ul><ul><ul><li>Alarms </li></ul></ul><ul><li>Accessory Devices </li></ul><ul><ul><li>Water treatment systems </li></ul></ul><ul><ul><li>Hemodialysis blood tubing </li></ul></ul><ul><ul><li>Remote monitoring systems </li></ul></ul><ul><ul><li>Blood access devices </li></ul></ul>
  19. 19. Disclaimer <ul><li>Any examples in this presentation are not intended as an endorsement or criticism of any specific technology, device or company </li></ul><ul><li>No devices are currently cleared for nocturnal home hemodialysis </li></ul>
  20. 20. Hemodialysis Delivery Systems <ul><li>Classified under two different sections of the Code of Federal Regulations (CFR): </li></ul><ul><ul><li>21 CFR §876.5820 for a low permeability system </li></ul></ul><ul><ul><li>21 CFR §876.5860 for a high permeability system (ultrafiltration controller) </li></ul></ul><ul><li>Suggestions for the content of a 510(k) submission found in the FDA guidance document: “Guidance for the Content of Premarket Notifications for Hemodialysis Delivery System” </li></ul>
  21. 21. Air Detector Blood Leak Detector PT PT = Pressure Transducer PT Venous clamp Anticoagulant Blood from Patient Blood return to Patient Dialysate In Dialysate / UF Out (green / yellow) Informational Display A “Standard” HD Delivery System PT Mixing System Conductivity Meter Water, Acid Concentrate, Bicarbonate Concentrate In Pre-mixed or sorbent regenerated dialysate Saline Drip Chamber
  22. 22. Solute Transfer & Ultrafiltration C blood > C Dialysate P blood ≈ P Dialysate C blood > C Dialysate P blood > P Dialysate Blood Dialysate
  23. 23. Monitored HD Parameters <ul><li>Blood and dialysate flow rates (pump speed) </li></ul><ul><li>Pressure </li></ul><ul><ul><li>Arterial </li></ul></ul><ul><ul><li>Venous </li></ul></ul><ul><ul><li>Dialysate </li></ul></ul><ul><ul><li>Waste / Dialysate Out </li></ul></ul><ul><ul><li>Transmembrane Pressure (TMP) </li></ul></ul><ul><li>Patient fluid removed (UF) </li></ul><ul><li>Temperature </li></ul>
  24. 24. HD Alarms <ul><li>Typically come in two varieties: </li></ul>CAUTION WARNING
  25. 25. Standard HD Alarms <ul><li>Temperature </li></ul><ul><li>Blood leak </li></ul><ul><li>Flow rates </li></ul><ul><li>Pressure </li></ul><ul><ul><li>Arterial </li></ul></ul><ul><ul><li>Venous </li></ul></ul><ul><ul><li>Transmembrane Pressure (TMP) </li></ul></ul><ul><ul><li>Dialysate </li></ul></ul><ul><ul><li>Waste / Dialysate Out </li></ul></ul><ul><li>Excessive UF </li></ul><ul><li>Air embolism </li></ul><ul><li>Conductivity / pH </li></ul><ul><li>Water quality </li></ul><ul><li>System alarms </li></ul><ul><li>Vascular access disconnection – venous pressure? </li></ul>
  26. 26. Accessory Devices <ul><li>Water Treatment Systems </li></ul><ul><li>HD Blood Tubing </li></ul><ul><li>Remote Monitoring Systems </li></ul><ul><li>Blood Access Devices </li></ul>
  27. 27. Water Treatment Systems <ul><li>Classified under 21 CFR §876.5665 </li></ul><ul><li>Guidance for The Content of Premarket Notifications for Water Purification Components and Systems for Hemodialysis </li></ul><ul><li>Converts potable water to purified water meeting the requirements of the Association for the Advancement for Medical Instrumentation (AAMI) RD:62 standard </li></ul><ul><li>Can be designed for multiple patients, or can be single patient </li></ul>
  28. 28. Water Treatment Systems Reverse Osmosis Deionization Carbon Filters Worker / Polisher Water Out Data Out Water In Ultrafilter Pre-treatment
  29. 29. Blood Tubing <ul><li>Serves as basic conduit for blood </li></ul><ul><li>Contains a “blood pump” segment </li></ul><ul><li>Can have multiple connection points </li></ul><ul><ul><li>Patient access (arterial & venous) </li></ul></ul><ul><ul><li>Pressure transducers with transducer protectors </li></ul></ul><ul><ul><li>Air detectors </li></ul></ul><ul><ul><li>Roller / peristaltic blood pump </li></ul></ul>
  30. 30. Blood Tubing <ul><li>Can be “cassette” based, which limits the number of user connections needed </li></ul><ul><li>Kinked tubing can cause hemolysis, which can lead to death </li></ul>
  31. 31. Remote Monitoring Systems <ul><li>Can be used for data transmission </li></ul><ul><li>Connect HD machine to Internet via modem or broadband connection </li></ul><ul><li>Can transmit real time alarms, and/or completed treatment data </li></ul><ul><li>FDA labels current systems are contraindicated as the sole method of monitoring a patient during hemodialysis </li></ul>
  32. 32. Blood Access Devices <ul><li>Long-term, cuffed HD Catheters </li></ul><ul><ul><li>Single or double lumen </li></ul></ul><ul><ul><li>Contain luer locks meeting ISO standards for connection to blood tubing </li></ul></ul><ul><li>Arterio-Venous (AV) Grafts </li></ul><ul><ul><li>Implanted prosthesis designed to bypass sections of native vessels </li></ul></ul><ul><li>AV Fistulas </li></ul><ul><ul><li>Surgical procedure, not a device regulated by FDA </li></ul></ul><ul><ul><li>Fistula needles are medical devices, and contain the same luer locks as catheters </li></ul></ul>
  33. 33. Nocturnal Home Hemodialysis Michael Mendelson, D.D.S., M.S. Biomedical Engineer, Director Health Promotion Officer Human Factors Science and Engineering Branch
  34. 34. Michael Mendelson, D.D.S., M.S. Biomedical Engineer, Director Health Promotion Officer Human Factors Science and Engineering Branch Division of Device User Programs Office of Communication, Education, and Radiation Control Center for Devices and Radiological Health June 8, 2005 Human Factors and Nocturnal Home Hemodialysis
  35. 35. Topics <ul><li>Introduction to human factors (HF) </li></ul><ul><li>Magnitude of medical error-caused adverse incidents </li></ul><ul><li>HF methods </li></ul><ul><li>Nocturnal Home Hemodialysis (NHD) challenges and observations </li></ul><ul><li>Human Factors Branch recommendations for premarket submissions </li></ul>
  36. 36. General Definition of Human Factors <ul><li>Human Factors discovers and applies information about human behavior , abilities, limitations , and other characteristics to the design of tools, machines, systems, tasks, jobs and environments for productive, safe, comfortable, and effective human use. * </li></ul><ul><li>-- Alphonse Chapanis, 1985 </li></ul><ul><ul><ul><ul><li>*Sanders & McCormick, Human Factors in Engineering </li></ul></ul></ul></ul><ul><ul><ul><ul><li>and Design., McGraw-Hill, Inc., 1987; p 5 </li></ul></ul></ul></ul>
  37. 37. General Definition of Error <ul><li>Human error is an inappropriate or undesirable human decision or behavior that reduces, or has the potential for reducing, effectiveness, safety, or system performance. * </li></ul><ul><ul><li>* Sanders & McCormick, Human Factors in Engineering </li></ul></ul><ul><ul><li>and Design., McGraw-Hill, Inc., 1987; p 607 </li></ul></ul>
  38. 38. Magnitude of the Problem of Medical Error Errors during hospital treatment result in 120,000 deaths each year – roughly equivalent to a jumbo jet’s crashing each day . (Leape, Harvard School of Public Health) At least 44,000 people,and perhaps as many as 98,000 people,die in hospitals each year as a result of medical errors that could have been prevented …( To Err is Human: Building a Safer Health System ; Institute of Medicine / National Academy of Sciences, 1999) Photo courtesy of Boeing
  39. 39. Design of Hemodialysis Systems Requires Human Factors Engineering Process <ul><li>The Quality System Regulation: HF implied in </li></ul><ul><li>Design Controls Section (21 CFR 820.30) </li></ul><ul><li>Manufacturer </li></ul><ul><li>Must address the intended use </li></ul><ul><li>Must address the needs of the user and patient </li></ul><ul><li>Shall include testing under actual or simulated use conditions </li></ul><ul><li>HF required at Input phase (design needs), Output phase (compare user needs <===> device design), and Validation Phase (realistic “use” study) </li></ul>
  40. 40. Safe & effective Unsafe or ineffective (Use Error) <ul><li>Use Environment </li></ul><ul><li>Light, Noise </li></ul><ul><li>Distraction </li></ul><ul><li>Motion/Vibration </li></ul><ul><li>Device User </li></ul><ul><li>Knowledge </li></ul><ul><li>Abilities </li></ul><ul><li>Expectations </li></ul><ul><li>Limitations </li></ul><ul><li>Device </li></ul><ul><li>Operational requirements, procedures </li></ul><ul><li>Device complexity </li></ul><ul><li>Specific user interface characteristics </li></ul>Use Device Use Human Factors Considerations
  41. 41. Increased Patient Safety through USABILITY of the Use Interface <ul><li>Intuitive operation </li></ul><ul><li>Clear displays </li></ul><ul><li>Safe and simple-to-use controls </li></ul><ul><li>Positive and safe connections </li></ul><ul><li>Effective alarms </li></ul><ul><li>Clear and effective labeling </li></ul><ul><li>Safe and simple installation, repair, maintenance, and disposal </li></ul>
  42. 42. Two Key Human Factors Messages <ul><li>A poorly designed device use interface can needlessly permit and even induce error </li></ul><ul><li>Warnings and instructions in the operating manual (and even on the device) may help but they can not OVERCOME a flawed design </li></ul>
  43. 43. Important Principles of Good Design* <ul><li>Make things visible </li></ul><ul><li>Communicate clearly </li></ul><ul><li>Provide correct and natural mappings </li></ul><ul><li>Don’t be arbitrary, be consistent </li></ul><ul><li>Simplify tasks </li></ul><ul><li>Use appropriate constraints </li></ul><ul><li>Design for error </li></ul><ul><li>*modified from The Design of Everyday Things , Donald Norman </li></ul>
  44. 44. Make Things Visible: This PCA pump fails. Obradovich and Woods (1996)
  45. 45. Obradovich and Woods (1996)
  46. 46. Important Principles of Good Design* <ul><li>Make things visible </li></ul><ul><li>Communicate clearly: e.g., mode / system status </li></ul><ul><li>Provide correct and natural mappings </li></ul><ul><li>Don’t be arbitrary, be consistent </li></ul><ul><li>Simplify tasks </li></ul><ul><li>Use appropriate constraints </li></ul><ul><li>Design for error </li></ul><ul><li>*modified from The Design of Everyday Things , Donald Norman </li></ul>
  47. 47. Important Principles of Good Design* <ul><li>Make things visible </li></ul><ul><li>Communicate clearly </li></ul><ul><li>Provide correct and natural mappings: “What is this switch for?” </li></ul><ul><li>Don’t be arbitrary, be consistent </li></ul><ul><li>Simplify tasks </li></ul><ul><li>Use appropriate constraints </li></ul><ul><li>Design for error </li></ul><ul><li>*modified from The Design of Everyday Things , Donald Norman </li></ul>
  48. 48. Important Principles of Good Design* <ul><li>Make things visible </li></ul><ul><li>Communicate clearly </li></ul><ul><li>Provide correct and natural mappings </li></ul><ul><li>Don’t be arbitrary, be consistent: </li></ul><ul><li>e.g., valve conventions </li></ul><ul><li>Simplify tasks </li></ul><ul><li>Use appropriate constraints </li></ul><ul><li>Design for error </li></ul><ul><li>*modified from The Design of Everyday Things , Donald Norman </li></ul>
  49. 49. Important Principles of Good Design* <ul><li>Make things visible </li></ul><ul><li>Communicate clearly </li></ul><ul><li>Provide correct and natural mappings </li></ul><ul><li>Don’t be arbitrary, be consistent </li></ul><ul><li>Simplify tasks: e.g., reduce </li></ul><ul><li>programming steps </li></ul><ul><li>Use appropriate constraints </li></ul><ul><li>Design for error </li></ul><ul><li>* modified from The Design of Everyday Things , Donald Norman </li></ul>
  50. 50. Use Appropriate Constraints FDA, Dec. 28, 1993 SAFE Lead Wires with Protected Pins and Correct Connections UNSAFE Lead Wires with Unprotected Pins and Incorrect Connections Protected Pins Protected Pins Electrode Lead Wires Patient Cable Power Cord Monitor Use only lead wires that have protected pins. Protected pins can not accidentally be plugged into power cords or electrical outlets. From Patient Unprotected Pins From Patient Unprotected Pins Power Cord or Extension Cord
  51. 51. Important Principles of Good Design* <ul><li>Make things visible </li></ul><ul><li>Communicate clearly </li></ul><ul><li>Provide correct and natural mappings </li></ul><ul><li>Don’t be arbitrary, be consistent </li></ul><ul><li>Simplify tasks </li></ul><ul><li>Use appropriate constraints </li></ul><ul><li>Design for error: e.g., require confirmation of critical actions </li></ul><ul><li>*modified from The Design of Everyday Things , Donald Norman </li></ul>
  52. 52. Human Factors: Critical in NHD <ul><li>Users </li></ul><ul><li>Lack of on-site staff and supplies </li></ul><ul><li>Variable level of education </li></ul><ul><li>Medically compromised: vision, touch, memory </li></ul><ul><li>Language and cultural diversity </li></ul><ul><li>Healthy-patient selection responsible for home safety level* </li></ul><ul><li>Environment </li></ul><ul><li>Family responsibilities, children, pets </li></ul><ul><li>Stress </li></ul><ul><li>Physical (placement, voltage/grounding, temperature, humidity, dust, water quality) </li></ul><ul><li>* D’Amico&Bazzi, Home Hemodialysis , in Replaplacement of Renal Function by Dialysis, 1989, page 694 </li></ul>
  53. 53. Clinical Incidents: Potential Nocturnal Home Issues? <ul><li>Hazards always exist: </li></ul><ul><li>For 3 fault codes which indicate need for manual adjustment of transmembrane pressure (TMP) => not actually controllable. Recall. Solution: labeling * </li></ul><ul><li>If unit plugged into receptacle without ground fault circuit interrupter (GFCI) – with certain other conditions => overheating. Recall. Solution: labeling * </li></ul>*ECRI Healthcare Product Comparison System, Sept. 2004; p 10 (HDA A5092, A5624)
  54. 54. NHD User Needs <ul><li>Simplify setup: minimize requirements for strict hygiene where possible. </li></ul><ul><li>Minimize burden on training. Consider periodic retraining. </li></ul><ul><li>Minimize dependence on bulky labeling. Use: </li></ul><ul><ul><li>On-screen help/voice prompts (“Wizards”) </li></ul></ul><ul><ul><li>Quick Guides (laminated cards, “cheat </li></ul></ul><ul><ul><li>sheets”) </li></ul></ul>
  55. 55. NHD User Needs (continued) <ul><li>Monitor supplies and preparation of prescribed dialysate </li></ul><ul><li>Ensure simple set up operation, and adjustment </li></ul><ul><li>Ensure safety of consumables </li></ul><ul><li>Need for priming blood lines, knowing symptoms of air embolism, how to respond </li></ul>
  56. 56. NHD User Needs (continued) <ul><li>Potential interrupted treatment: Ability to detect and respond? </li></ul><ul><li>Allow flexible installation – various viewing angles </li></ul><ul><li>Allow for physical impairment (ESRD co-morbidities) </li></ul><ul><li>Consider touch screen and no cryptic error codes </li></ul>
  57. 57. NHD User Needs (continued) <ul><li>Consider “progressive disclosure” of information– for range of user abilities and wants. </li></ul><ul><li>Facilitate detection of bleeding: enuresis pads, moisture detectors, effective needle dislodgement alarm (single needle?). </li></ul><ul><li>Patient abilities may be lowest at start of session. </li></ul>
  58. 58. NHD User Needs (continued) <ul><li>Consider tricky power-interruption scenarios (error-codes, default settings) </li></ul><ul><li>Design in virtual “guardrails” </li></ul><ul><li>Allow for compromised nocturnal response to alarms </li></ul>
  59. 59. Human Factors Engineering Process (HFE) <ul><li>Start integrating HFE at concept phase (beginning of design) </li></ul><ul><ul><li>User needs designed in </li></ul></ul><ul><ul><li>Early HF design changes fast , economical, and effective </li></ul></ul><ul><ul><li>Fewer “slapped-on” warnings and bulky manuals </li></ul></ul><ul><ul><li>User acceptance and product life increased </li></ul></ul><ul><li>Usability (HF) study at Validation phase demonstrates: low risk of dangerous use error where and when device is used by typical users (usually a simulation). </li></ul><ul><li>Clinical trials demonstrate: safety and effectiveness where and when used exactly as directed. </li></ul>
  60. 60. Human Factors Recommendations/Conclusion <ul><li>Assume significant patient/user and environmental compromises. </li></ul><ul><li>Minimize burden on training and paper instructions. </li></ul><ul><li>Ensure comprehensive patient/user support from manufacturer or value-added retailer. </li></ul><ul><li>Encourage postmarket feedback from users. </li></ul><ul><li>Design to protect user/patient from error. </li></ul>
  61. 61. Nocturnal Home Hemodialysis Claudia C. Ruiz-Zacharek, M.D. Medical Officer / Nephrologist Gastroenterology and Renal Devices Branch
  62. 62. Nocturnal Home Hemodialysis Claudia C. Ruiz-Zacharek, M.D. Medical Officer / Nephrologist Gastroenterology and Renal Devices Branch Division of Reproductive, Abdominal and Radiological Devices Office of Device Evaluation Center for Devices and Radiological Health June 8, 2005
  63. 63. Nocturnal Home Hemodialysis Devices <ul><li>Optimal device design for actual use conditions </li></ul><ul><li>Adequate labeling to minimize error </li></ul><ul><li>Appropriate training for successful treatments </li></ul><ul><li>Risk analysis to minimize unforeseen problems </li></ul><ul><li>Clinical study design to demonstrate safety and effectiveness </li></ul>
  64. 64. Overview <ul><li>Background Information </li></ul><ul><li>Nocturnal Home Hemodialysis </li></ul><ul><li>Clinical Studies </li></ul>
  65. 65. Overview <ul><li>Background Information </li></ul><ul><li>Nocturnal Home Hemodialysis </li></ul><ul><li>Clinical Studies </li></ul>
  66. 66. Background Information <ul><li>Demographics </li></ul><ul><li>Review of the literature </li></ul><ul><li>Definitions and nomenclature </li></ul>
  67. 67. Background Information <ul><li>Conventional Hemodialysis </li></ul><ul><ul><ul><li>Typically in-center, 4 hours, 3 X week </li></ul></ul></ul><ul><ul><ul><li>Medical personnel </li></ul></ul></ul><ul><ul><ul><li>Patient has a passive role during treatment </li></ul></ul></ul><ul><li>Nocturnal Home Hemodialysis </li></ul><ul><ul><ul><li>Performed at home, typically at night, and while the patient sleeps </li></ul></ul></ul><ul><ul><ul><li>Absence of medical personnel </li></ul></ul></ul><ul><ul><ul><li>Patient is the performer of the treatment </li></ul></ul></ul>
  68. 68. Definitions and Nomenclature <ul><li>Nocturnal Hemodialysis (NHD) </li></ul><ul><ul><li>Nightly Hemodialysis </li></ul></ul><ul><ul><li>Nocturnal Home Hemodialysis </li></ul></ul><ul><ul><li>Long nocturnal hemodialysis </li></ul></ul><ul><ul><li>Slow nocturnal hemodialysis </li></ul></ul><ul><li>In-center nocturnal hemodialysis </li></ul><ul><li>Daily hemodialysis </li></ul>
  69. 69. Definitions and Nomenclature <ul><li>Nocturnal Home Hemodialysis </li></ul><ul><li>Performed at home by patient </li></ul><ul><li>Absence of medical personnel </li></ul><ul><li>Frequency has reportedly ranged from 5-7 nights a week </li></ul><ul><li>Length is 6-10 hours per night </li></ul>
  70. 70. Definitions and Nomenclature <ul><li>Nocturnal Home Hemodialysis </li></ul><ul><li>Blood flows (QB) 200-300 ml/min </li></ul><ul><li>Dialysate flows (QD) usually ~300 ml/min, up to 800 ml/min* </li></ul><ul><li>* Pierratos, A. Nephrol Dial Transplant 1999; 14:2835-2840 </li></ul>
  71. 71. Data from the United States Renal Data System (USRDS) <ul><li>Prevalence of patients on hemodialysis in the United States, 2002: 281,594 </li></ul><ul><li>0.3% (843) home hemodialysis patients </li></ul><ul><li>115 NHD patients in 13 centers in North America* </li></ul><ul><ul><li>* Lockridge, et al., Adv Ren Replace Ther 2001; 8(4):250-256. </li></ul></ul>
  72. 72. Population Comparison <ul><li>Lockridge et al. </li></ul><ul><li>Diabetic nephropathy* 14% </li></ul><ul><li>Hypertension 18% </li></ul><ul><li>Glomerulonephropathy 11% </li></ul><ul><li>Polycystic Kidney 9% </li></ul><ul><ul><li>* Lockridge, et al., Adv Ren Replace Ther 2001 </li></ul></ul><ul><li>US Demographics (USRDS) </li></ul><ul><li>Diabetic nephropathy 45% </li></ul><ul><li>Hypertension 28% </li></ul><ul><li>Glomerulonephropathy 8% </li></ul><ul><li>Polycystic Kidney 2.3% </li></ul>
  73. 73. Background Information – Review of the Literature 37 Prospective Pierratos, 1999 16 Prospective Agar, 2003 9 Case control Chan, 2003 18 Prospective Alloati, 2002 12 Retrospective Van Biesen, 2003 23 (total), 22 matched controls Prospective, observational London Daily/Nocturnal Dialysis Study, 2003 # Patients Design Study
  74. 74. Background Information – Review of the Literature No significant improvement Improved control Improved Pierratos,1999 Increased epoetin & iron Improved control Improved Agar, 2003 Improved Chan, 2003 No significant improvement Improved control Improved Alloati, 2002 No significant improvement Improved control Improved London Daily/Nocturnal Dialysis Study, 2003 Anemia Calcium - Phosphorus Blood pressure Study
  75. 75. Background Information – Review of the Literature <ul><li>No fluid or dietary restrictions </li></ul><ul><li>Improved sleep patterns </li></ul>Reduction of sleep apnea Pierratos, 1999 Agar, 2003 Improved serum albumin Van Biesen, 2003 Improved control reduction of number and severity of dialysis symptoms London Daily/Nocturnal Dialysis Study, 2003 Reported Outcome Study
  76. 76. Overview <ul><li>Background Information </li></ul><ul><li>Nocturnal Home Hemodialysis </li></ul><ul><li>Clinical Studies </li></ul>
  77. 77. Nocturnal Home Hemodialysis <ul><li>Device Design and Components </li></ul><ul><li>Human Factors Issues </li></ul><ul><li>Water Quality </li></ul><ul><li>Use of a Partner and Remote Monitoring </li></ul><ul><li>Vascular Access and Extracorporeal Circuit Connections </li></ul><ul><li>Labeling </li></ul><ul><li>Lay-User Training </li></ul>
  78. 78. Nocturnal Home Hemodialysis <ul><li>Conventional Hemodialysis </li></ul><ul><ul><li>Patient is passive recipient </li></ul></ul><ul><ul><li>Troubleshooting by medical personnel </li></ul></ul><ul><li>Nocturnal Home Hemodialysis </li></ul><ul><ul><li>Patient’s active role </li></ul></ul><ul><ul><li>Presumably asleep </li></ul></ul><ul><ul><li>Need to troubleshoot </li></ul></ul>
  79. 79. Nocturnal Home Hemodialysis <ul><li>Human Factors Issues </li></ul><ul><li>User- friendly </li></ul><ul><li>Use device successfully while minimizing use error </li></ul><ul><li>Minimal dependance on labeling and training </li></ul>
  80. 80. Nocturnal Home Hemodialysis <ul><li>Considerations for device design : </li></ul><ul><li>Redundancy </li></ul><ul><li>Adequacy of alarms </li></ul><ul><ul><li>Loudness </li></ul></ul><ul><ul><li>Sensitivity </li></ul></ul><ul><ul><li>Ease of understanding and correction </li></ul></ul><ul><li>Additional safety alarms </li></ul>
  81. 81. Nocturnal Home Hemodialysis <ul><li>Water Quality concerns </li></ul><ul><li>Conventional Hemodialysis: </li></ul><ul><li>360 L/week </li></ul><ul><li>Nocturnal Hemodialysis: </li></ul><ul><li>648 L-1080 L/week </li></ul><ul><li>Standard water quality for hemodialysis vs higher standards </li></ul><ul><ul><li>Total viable microbial count <200 CFU/mL </li></ul></ul><ul><ul><li>Endotoxin concentration < 2 EU/mL </li></ul></ul>
  82. 82. Nocturnal Home Hemodialysis <ul><li>Water Quality concerns </li></ul><ul><li>Types of water treatment systems </li></ul><ul><ul><li>Reverse osmosis (RO) </li></ul></ul><ul><ul><li>Deionization (DI) </li></ul></ul><ul><ul><li>Combination </li></ul></ul><ul><li>Water source </li></ul><ul><ul><li>Municipal water suppliers </li></ul></ul><ul><ul><li>Well water </li></ul></ul>
  83. 83. Nocturnal Home Hemodialysis <ul><li>Monitoring </li></ul><ul><li>Without a partner* </li></ul><ul><ul><li>59 patients, prospective study </li></ul></ul><ul><li>In-center hemodialysis – constant monitoring </li></ul><ul><li>Home hemodialysis </li></ul><ul><li>* Raija, et al., Experiences on Home Hemodialysis without an Assistant . Hemodialysis International 2003; 7(1):73-104. </li></ul>
  84. 84. Nocturnal Home Hemodialysis <ul><li>Monitoring </li></ul><ul><li>“ Monitoring is essential for the initial 3 months of nocturnal HD therapy until the HD team is convinced the patient is stable and compliant.” </li></ul><ul><ul><li>* The London Daily/Nocturnal Hemodialysis Study . AJKD, 2003 </li></ul></ul>
  85. 85. Nocturnal Home Hemodialysis <ul><li>Vascular access </li></ul><ul><ul><li>Long-term cuffed catheter </li></ul></ul><ul><ul><li>Synthetic graft </li></ul></ul><ul><ul><li>Arteriovenous fistula </li></ul></ul>
  86. 86. Nocturnal Home Hemodialysis <ul><li>Vascular access </li></ul><ul><ul><li>Long-term cuffed catheter </li></ul></ul><ul><ul><li>Synthetic graft </li></ul></ul><ul><ul><li>Arteriovenous fistula </li></ul></ul><ul><ul><ul><li>Observational study; 24 patients in daily dialysis; follow up 3.6 years* </li></ul></ul></ul><ul><ul><li>* Quintaliani, et al., Survival of vascular access during daily and three times a week hemodialysis. Clin Nephrol 2000; 53:372-377. </li></ul></ul>
  87. 87. Nocturnal Home Hemodialysis <ul><li>Vascular access location </li></ul><ul><li>Connection to the device </li></ul><ul><li>Self cannulation </li></ul><ul><li>Locking devices </li></ul><ul><li>Fluid detection alarms </li></ul><ul><li>Moisture sensors </li></ul><ul><li>Single vs dual needle technique </li></ul>
  88. 88. Nocturnal Home Hemodialysis <ul><li>Labeling </li></ul><ul><li>Operator’s Manual </li></ul><ul><ul><li>Warnings </li></ul></ul><ul><ul><li>Precautions </li></ul></ul><ul><ul><li>Device specifications </li></ul></ul><ul><ul><li>Instructions for maintenance </li></ul></ul><ul><ul><li>Cleaning and disinfection </li></ul></ul>
  89. 89. Labeling <ul><li>Physician’s Instructions for Use </li></ul><ul><li>The manual that accompanies a medical device </li></ul><ul><li>It should also include relevant data from clinical studies and instructions for using and caring for the device </li></ul>
  90. 90. Labeling <ul><li>Patient’s Instructions for Use </li></ul><ul><li>The manual that accompanies a medical device </li></ul><ul><li>It should also include relevant data from clinical studies and instructions for using and caring for the device </li></ul><ul><li>Written for a person with no medical training </li></ul>
  91. 91. Nocturnal Home Hemodialysis <ul><li>Training </li></ul><ul><li>Teaching provided by the manufacturer </li></ul><ul><li>Medical expert to train the lay user </li></ul><ul><li>Lay user to successfully use the device </li></ul>
  92. 92. Nocturnal Home Hemodialysis <ul><li>Lay user training </li></ul><ul><li>Conduct safe and effective NHD treatments </li></ul><ul><li>Length of training reported to be approx 2-8 weeks* φ </li></ul><ul><li>* Agar, et al., Hemodialysis International 2003; 7(4):278-289. </li></ul><ul><li>Φ Leitch, et al., Am J Kidney Dis 2003; 42(1):S56-60 . </li></ul>
  93. 93. Nocturnal Home Hemodialysis <ul><li>Lay-user training </li></ul><ul><li>Appropriate use of the hemodialysis device </li></ul><ul><li>Interpretation and use of safety features, accessories and hemodialysis treatment itself </li></ul><ul><li>Test to confirm the adequacy of the training </li></ul>
  94. 94. Nocturnal Home Hemodialysis <ul><li>Risk Analysis </li></ul><ul><li>Inadvertent disconnections </li></ul><ul><li>Blood loss from increased frequency of treatments </li></ul><ul><li>Potential increased rate of vascular access infection </li></ul><ul><li>Psychological effects </li></ul>
  95. 95. Overview <ul><li>Background Information </li></ul><ul><li>Nocturnal Home Hemodialysis </li></ul><ul><li>Clinical Studies </li></ul>
  96. 96. Clinical Studies <ul><li>Purpose </li></ul><ul><li>Patient selection </li></ul><ul><li>Study design </li></ul>
  97. 97. Clinical Studies <ul><li>Purpose </li></ul><ul><li>To demonstrate the safety and effectiveness of the NHD devices under actual use conditions </li></ul><ul><li>Not intended to evaluate the long term morbidity and mortality of NHD as a therapeutic modality compared to conventional hemodialysis </li></ul>
  98. 98. Clinical Studies <ul><li>FDA concerns : </li></ul><ul><li>Patient selection for trial </li></ul><ul><li>Patient selection for marketing </li></ul><ul><li>Patient performs the entire treatment </li></ul><ul><li>Patient must wake up to attend the alarms </li></ul>
  99. 99. Clinical Studies <ul><li>Reported patient selection : </li></ul><ul><ul><li>Agar, et al., Nocturnal Hemodialysis in Australia. Hemodialysis International 2003; 7(4):278-289. </li></ul></ul><ul><ul><li>Alloatti, et al., Long Nocturnal Dialysis. Blood Purif 2002; 20:525-530. </li></ul></ul><ul><ul><li>Covic, et al., Long-hours home haemodialysis – the best renal replacement therapy method? Q J Med 1999; 92:251-260. </li></ul></ul>
  100. 100. Clinical Studies <ul><li>Reported patient selection : </li></ul><ul><ul><li>Agar, et al., Nocturnal Hemodialysis in Australia. Hemodialysis International 2003; 7(4):278-289. </li></ul></ul><ul><ul><ul><li>16 patients, prospective </li></ul></ul></ul><ul><ul><ul><li>Clinically stable > 3 mo in HD </li></ul></ul></ul><ul><ul><ul><li>Psychologically sound </li></ul></ul></ul><ul><ul><ul><li>Technically adept </li></ul></ul></ul><ul><ul><ul><li>Stable and supportive home </li></ul></ul></ul><ul><ul><ul><li>Compliant </li></ul></ul></ul>
  101. 101. Clinical Studies <ul><li>Reported patient selection : </li></ul><ul><ul><li>Alloatti, et al., Long Nocturnal Dialysis. Blood Purif 2002; 20:525-530. </li></ul></ul><ul><ul><ul><li>18 patients, nonrandomized, prospective </li></ul></ul></ul><ul><ul><ul><li>Glomerulonephritis (7) </li></ul></ul></ul><ul><ul><ul><li>Tubulointerstitial (4) </li></ul></ul></ul><ul><ul><ul><li>Nephroangiosclerosis (3) </li></ul></ul></ul><ul><ul><ul><li>Diabetic nephropathy (1) </li></ul></ul></ul><ul><ul><ul><li>Vasculitis (1) </li></ul></ul></ul><ul><ul><ul><li>Other (2) </li></ul></ul></ul>
  102. 102. Clinical Studies <ul><li>Reported patient selection : </li></ul><ul><ul><li>Covic, et al., Long-hours home haemodialysis – the best renal replacement therapy method? </li></ul></ul><ul><ul><li>Q J Med 1999; 92:251-260. </li></ul></ul><ul><ul><ul><li>286 UK patients; retrospective, observational study </li></ul></ul></ul><ul><ul><ul><li>Initially excluded older and frailer patients </li></ul></ul></ul><ul><ul><ul><li>Excluded patients with diabetes, cardiac failure, and multiple myeloma </li></ul></ul></ul><ul><ul><ul><li>Currently 33% diabetic patients </li></ul></ul></ul>
  103. 103. Clinical Studies <ul><li>Patient selection criteria : </li></ul><ul><li>Availability of a partner </li></ul><ul><li>Patient's compliance </li></ul><ul><li>Psychological well being </li></ul><ul><li>Home environment (Medicare) </li></ul><ul><ul><li>Water supply </li></ul></ul><ul><ul><li>Sewage </li></ul></ul><ul><ul><li>Electricity </li></ul></ul><ul><ul><li>Space </li></ul></ul><ul><ul><li>Social interaction </li></ul></ul>
  104. 104. Clinical Studies <ul><li>Study design discussion : </li></ul><ul><li>Clinical endpoints </li></ul><ul><ul><li>Effectiveness </li></ul></ul><ul><ul><li>Safety / Adverse Events </li></ul></ul><ul><li>Control group </li></ul><ul><ul><li>Randomized vs patient as own control </li></ul></ul><ul><li>Length of follow-up </li></ul><ul><li>Sample size </li></ul>
  105. 105. Clinical Studies <ul><li>Treatment related issues to be considered : </li></ul><ul><li>Dialysate composition and additives </li></ul><ul><li>Administration of anticoagulation </li></ul><ul><li>Choice of dialyzer </li></ul><ul><li>Type of monitoring </li></ul><ul><li>Vascular access </li></ul><ul><li>Dialyzer reuse </li></ul>
  106. 106. Conclusions <ul><li>Nocturnal Home Hemodialysis Devices </li></ul><ul><li>Optimal device design for actual use conditions </li></ul><ul><li>Adequate labeling to minimize error </li></ul><ul><li>Appropriate training for successful treatments </li></ul><ul><li>Risk analysis to minimize unforeseen problems </li></ul><ul><li>Clinical study design to demonstrate safety and effectiveness </li></ul>
  107. 107. References <ul><li>United States Renal Data System (USRDS) www.usrds.org </li></ul><ul><li>Lockridge RS, Spencer M, Craft V, Pipkin M, Campbell D, McPhatter L, Albert J, Anderson H, Jennings F, and Barger T. Nocturnal Home Hemodialysis in North America. Adv Ren Replace Ther 2001; 8(4):250-256. </li></ul><ul><li>Pierratos, A. Nocturnal home haemodialysis: an update on a 5-year experience. Nephrol Dial Transplant 1999; 14:2835-2840 </li></ul><ul><li>Mehrabian S, Morgan D, Schlaeper C, Kortas C, and Lindsay RM. Equipment and water treatment considerations for the provision of quotidian home hemodialysis. Am J Kidney Dis 2003; 42:S66-S70. </li></ul><ul><li>Raija M, Riitta MK, Meeri K, and Eero H. Experiences on Home Hemodialysis without an Assistant. Hemodialysis International 2003; 7(1):73-104. </li></ul>
  108. 108. References <ul><li>Heidenheim AP, Leitch R, Kortas C and Lindsay RM. Patient Monitoring in the London Daily/Nocturnal Hemodialysis Study. Am J Kidney Dis 2003; 42:S61-S65. </li></ul><ul><li>Quintaliani G, Buoncristiani U, Fagugli R, Kuluiranu H, Ciao G, Rondini L, Lowenthal DT, and Reboldi G. Survival of vascular access during daily and three times a week hemodialysis. Clin Nephrol 2000; 53:372-377. </li></ul><ul><li>Agar JWM, Somerville CA, Dwyer KM, Simmonds RE, Boddington JM, and Waldron CM. Nocturnal Hemodialysis in Australia. Hemodialysis International 2003; 7(4):278-289. </li></ul><ul><li>Leitch R, Ouwendyk M, Ferguson E, Clement L, Peters K, Heidenheim AP, and Lindsay RM. Nursing Issues Related to Patient Selection, Vascular Access, and Education in Quotidian Hemodialysis. Am J Kidney Dis 2003; 42(1):S56-60. </li></ul>
  109. 109. References <ul><li>Alloatti S, Molino A, Manes M, Bonfant G, and Pellu V. Long Nocturnal Dialysis. Blood Purif 2002; 20:525-530. </li></ul><ul><li>Covic A, Goldsmith DJA, Venning MC, and Ackrill P. Long-hours home haemodialysis – the best renal replacement therapy method? Q J Med 1999; 92:251-260. </li></ul><ul><li>The following articles have not been cited in the above discussion of NHD, but may provide additional information. Copies of these may also be found in Appendix F. </li></ul><ul><li>Chan CT, Hanly P, Gabor J, Picton P, Pierratos A, and Floras JS. Nocturnal Hemodialysis Lowers Heart Rate during Sleep and Normalizes Its Parasympathetic and Sympathetic Modulation. Hemodialysis International 2003; 7(1):73-104. </li></ul>
  110. 110. References <ul><li>Faratro R and Chan CT. Nocturnal Hemodialysis Improves Productivity of End-Stage Renal Failure Patients. Hemodialysis International, 2003; 7(1):73-104. </li></ul><ul><li>Francoeur R and Digiambatista A. Technical Considerations for Short Daily Home Hemodialysis and Nocturnal Home Hemodialysis. Adv Ren Replace Ther 2001; 8(4):268-272. </li></ul><ul><li>Heidenheim AP, Muirhead N, Moist L, and Lindsay RM. Patient Quality of Life on Quotidian Hemodialysis. Am J Kidney Dis 2003; 42:S36-S41. </li></ul><ul><li>Kjellstrand CM and Ing T. Daily Hemodialysis: History and Revival of a Superior Dialysis Method. ASAIO Journal 1998; 117-122. </li></ul><ul><li>Kjellstrand CM and Blagg CR. Differences in Dialysis Practice are the Main Reasons for the High Mortality Rate in the United States compared to Japan. Hemodialysis International 2003; 7(1):67-71. </li></ul>
  111. 111. References <ul><li>Kroeker A, Clark WF, Heidenheim AP, Kuenzig L, Leitch R, Meyette M, Muirhead N, Ryan H, Welch R, White S, and Lindsay RM. An Operating Cost Comparison Between Conventional and Home Quotidian Hemodialysis. Am J Kidney Dis 2003; 42:S49-S55. </li></ul><ul><li>Lindsay RM, Leitch R, Heidenheim AP, and Kortas C. The London Daily/Nocturnal Hemodialysis Study – Study Design, Morbidity, and Mortality Results. Am J Kidney Dis 2003; 42(1):S5-S12. </li></ul><ul><li>Lindsay RM, Alhejaili F, Nesrallah G, Leitch R, Clement L, Heidenheim AP, and Kortas C. Calcium and Phosphate Balance with Quotidian Hemodialysis. Am J Kidney Dis 2003; 42, S1:S24-29. </li></ul><ul><li>Nesrallah G, Suri R, Moist L, Kortas C, and Lindsay RM. Volume Control and Blood Pressure Management in Patients Undergoing Quotidian Hemodialysis. Am J Kidney Dis 2003; 42:S13-17. </li></ul>
  112. 112. References <ul><li>Pierratos A. Daily nocturnal home hemodialysis. Kidney International 2004; 65:1975-1986. </li></ul><ul><li>Pierratos A. Quotidian Hemodialysis: Is it the Solution to the Problem? Seminars in Dialysis 2004; 17(2):77-78. </li></ul><ul><li>Radford MG, Shultman DS, Pasour AG, Cobb AM, and Chandler JT. An Incenter Nocturnal Hemodialysis Program – Three Years Experience. Hemodialysis International 2003; 7(1):73-104. </li></ul><ul><li>Rao M, Muirhead N, Klarenbach S, Moist L, and Lindsay RM. Management of Anemia with Quotidian Hemodialysis. Am J Kidney Dis 2003; 42:S18-S23. </li></ul>
  113. 113. References <ul><li>Spanner E, Suri R, Heidenheim AP, and Lindsay RM. The Impact of Quotidian Hemodialysis on Nutrition. Am J Kidney Dis 2003; 42(1):S30-S35. </li></ul><ul><li>Suri R, Depner TA, Blake PG, Heidenheim AP, and Lindsay RM. Adequacy of Quotidian Hemodialysis. Am J Kidney Dis 2003; 42:S42-S48. </li></ul><ul><li>Van Biesen W, Veys N, Vanholder R, and Lameire N. Effect of Long Nocturnal Dialysis on Nutritional Status and Blood Pressure Control. Hemodialysis International, 2003; 7(1):73-104. </li></ul><ul><li>Weick-Brady M. Medical Devices: Going Home. FDLI Update 2003; September/October: 23-24, 29-30. </li></ul>
  114. 114. References <ul><li>Weinger MB, Foreword to Designing Usability into Medical Products </li></ul><ul><li>Woods JD, Port FK, Stannard D, Blagg CR, and Held PJ. Comparison of mortality with home hemodialysis and center hemodialysis: A national study. Kidney International, 1996; 49:1464-1470. </li></ul><ul><li>Young BA, Hynes J, and McComb T. Home Hemodialysis: Associations with Modality Failure. Hemodialysis International, 2003; 7:73-104. </li></ul>

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