Humanitarian Use Devices (HUDs): Review of FDA Guidance and UMCIRB Procedures to Ensure Proper Use and Billing of HUDs

1. Humanitarian Use Devices (HUDs): Review of FDA Guidance and UMCIRB Procedures to Ensure Proper Use and Billing of HUDs Thursday, May 17, 2007 ECU/PCMH Study Coordinators Lunch and Learn Series Joan A. Kavuru, J.D. Brody School of Medicine Director of Compliance ECU HIPAA Privacy Officer

2. Overview • Humanitarian Use Device (HUD): Background • HUD Defined • Humanitarian Device Exemption (HDE) • Process for granting HDE • Role of the IRB • Investigator Responsibilities • Off-Label Use of HUD: Compassionate Use and Emergency Use • Billing for HUDs

3. Humanitarian Use Device: Background • Approval process for “regular” investigational devices long and expensive • Disincentive for manufacturers to invest much time or resources into devices that cannot be mass marketed • Congress enacted laws allowing for shorter, less burdensome approval process for “orphan” devices – i.e. those that will be used to treat or diagnose diseases or conditions affecting less than 4,000 individuals per year in the United States

4. HUD: Defined • HUD is a medical device intended to benefit patients in the diagnosis and/or treatment of a disease or condition that affects or is manifested in fewer than 4,000 patients per year in the United States • HUD designation is performed by the FDA Office of Orphan Products Development

5. Humanitarian Device Exemption (HDE) • HDE designation performed by FDA Office of Device Evaluation (75 days to review) • An “approved” HDE allows for marketing of the HUD • Must be no “comparable device” available on the market, or if a comparable device is available: • It is under an approved HDE application; or • Under an approved Investigational Device Exemption (IDE)

6. Humanitarian Device Exemption (HDE) • The “comparable device” need not be identical to the device submitted under the HDE application. In determining whether a comparable device exists, FDA considers: • Device’s intended use and technological characteristics • Patient population to be treated or diagnosed with device • Whether the device meets the needs of the identified patient population • Charge for device cannot exceed the costs of research and development, fabrication, and distribution • If charge is greater than $250, must obtain independent opinion from certified public accountant.

7. HDE (cont’d) • Different “effectiveness” standards for HDEs as compared to “regular” pre-market approval (PMA) pathway • HDE approval is based on demonstrating reasonable assurance of safety and probable benefit whereas PMA approval is based on demonstrating reasonable assurance of safety and effectiveness. • Probable benefit may be demonstrated by literature and may not require submission of any clinical data.

8. HDE (cont’d) • Since first HDE approval in 1997, 40 additional HDEs have been granted. Examples: • First totally implanted permanent artificial heart (Abiomed, Inc.) • Assay for monitoring peptides in rare cancer • Wingspan Stent System for intracranial atherosclerotic disease • LVAD for peds patients • JOSTENT Coronary stent graft for use in treatment of coronary artery perforations • VOCARE Bladder System for patients with spinal cord lesions to allow for urination and reduce post-void residuals. • See all at FDA website:http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfHDE/HDEInformation.cfm

9. Role of the IRB for Use of HUD • IRB is required to approve use of HUD by a provider in a facility except in emergency situations (discussed later) • IRB is required to perform both initial and continuing review; initial review cannot be expedited but continuing review can be expedited unless determined otherwise by IRB • IRB has discretion with respect to terms of approval: • Can approve as to use of device in general; • Use of the device for groups of patients meeting certain criteria; • Use of the device under a treatment protocol

10. Role of the IRB for Use of HUD • IRB may specify limitations on the use of the device based upon one or more measures of disease progression, prior use and failure of any alternative treatment modalities, reporting requirements to the IRB or IRB Chair, appropriate follow-up precautions and evaluations, or any other criteria it determines to be appropriate. • HDE holder has ultimate responsibility for ensuring that the HUD is not administered to or implanted in a patient prior to obtaining IRB approval at a facility. 61 Fed. Reg. 33231 (June 26, 1996)

11. Provider Responsibilities for Use of HUD • Must obtain IRB approval for use of HUD • Report serious adverse events immediately to sponsor and UMCIRB • Submit report to FDA no later than 10 working days after you become aware of information, from any source, that reasonably suggests that a device has or may have caused or contributed to the serious injury or death of a patient of your facility; must also submit to device manufacturer

12. Provider Responsibilities for Use of HUD • Must use device according to label specifications (exceptions for emergency use and compassionate use but additional requirements apply) • Informed Consent • Regulations do not require informed consent but UMCIRB has discretion to require consent document. • Best if patient provides written consent and is fully informed about HUD and potential risks and alternative treatments; remember - efficacy has not been formally tested for HUDs

13. Emergency Use of HUDs • In general, HUDs may only be used strictly according to labeled indications • Exception for emergency use in which case HUD may be used off-label. • Same requirements as emergency use of IDEs • Emergency use defined by FDA: • The patient has a life-threatening condition that needs immediate treatment; • No generally acceptable alternative treatment for the condition exists; and • Because of the immediate need to use the device, there is no time to use existing procedures to get FDA approval for the use.

14. Emergency Use of HUDs (cont’d) • UMCIRB definition “life threatening:” Diseases or conditions where the likelihood of death is high unless the course of the disease is interrupted, and diseases or conditions with potentially fatal outcomes, where the end point of clinical trial analysis is survival. The criteria for life-threatening does not require the condition to be immediately life-threatening or to immediately result in death. Rather, the subjects must be in a life-threatening situation requiring intervention before review at a convened meeting of the UMCIRB is feasible.

15. Emergency Use of HUDs (cont’d) • FDA (and usually the sponsor as well) recommends that certain patient protection measures be followed, including the following: • Informed consent from the patient or a legal representative; • Clearance from the institution as specified by its policies; • Concurrence of the IRB chairperson; • An independent assessment from an uninvolved physician; and • Authorization from the HDE holder.

16. Emergency Use of HUDs (cont’d) • Following the emergency use, the provider should: • Immediately notify sponsor (HDE holder) • Provide sponsor with a follow-up report on the patient’s condition and information regarding the patient protectionmeasures that were followed.

17. Compassionate Use of HUDs • Off-label use of HUD is also permitted if characterized as a “compassionate use” • Physician should provide HDE holder with the following: • Description of patient’s condition • Circumstances necessitating use • Discussion of why alternative therapies or diagnostics are unsatisfactory • Information to address patient protection measures – sponsor may require similar steps as in emergency use (i.e., independent assessment, concurrence of IRB chairperson, institutional clearance, informed consent).

18. Compassionate Use of HUDs (cont’d) • In turn, HDE holder submits this information to the FDA to obtain FDA approval for compassionate use. • FDA will review in “the most expeditious manner possible” and issue a letter to HDE holder. • Close follow-up monitoring should occur with patient.

19. Billing for Humanitarian Use Devices • Charge no more than approved by FDA in HDE application • Our carrier (CIGNA) does not address payment for HUDs but a different carrier has advised facilities to produce the following to the carrier related to HUDs: • Information to payor including HDE number, description of clinical situations where you plan to use it, proof of IRB approval. • Theoretically claim should not be denied as investigational or experimental because HUD is not an investigational device; however best if can obtain preapproval from payor.

20. Thank you! Joan A. Kavuru, J.D., R.N. The Brody School of Medicine Director of Compliance ECU HIPAA Privacy Officer (252) 744-5200 kavuruj@ecu.edu