Review of Research Involving Medical Devices: Webinar Questions and Answers

The IRB Review of Medical Device Research: Questions and Answers

In this follow-up to our webinar, Review of Research Involving Medical Devices, Quorum Review’s regulatory attorneys answer questions about the IRB review of medical device research that were submitted by attendees of the September broadcasts.


Q: Can you give example(s) of when an IRB would not allow a sponsor to charge for a device?

A: The IRB would only very rarely take action in regards to the cost of an investigational device due to 21 CFR 812.7, which prohibits the commercialization of an investigational device by charging participants a price greater than that is necessary to recover costs of manufacture, research, development, and handling. For additional information, please see Charging for Investigational Products – Information Sheet.

An IRB, however, may ask for additional rationale for the cost of the device if the cost is considered exceptionally high and the prospect of benefit is low or the participant has no available alternative therapies. In either circumstance, the IRB would be concerned that there could be the possibility of undue influence (therapeutic misconception) or coercion (lack of choices) and thereby an inability to obtain legally effective informed consent.

Q: How does an IRB decide who can present the risks/benefits of a complex device study (eg., physician or study coordinator?  What if the SC is not a medical professional?

A: The PI is ultimately responsible for ensuring that informed consent is obtained (see 21 CFR 812.100) and the general expectation is that the PI will ensure that the person(s) conducting informed consent is appropriately qualified to lead the discussion. This means they are able to explain the research, facilitate understanding by the participant, and answer any study related questions. This may or may not be a study physician, another study medical provider, or a study coordinator and it may be one person or several persons. That said, it would generally be expected that a study coordinator would not present a complex study involving significant medical risk without at least partial involvement of a medical provider (Iikely the PI), but not that a medical provider must lead the entire discussion.

Q: Are there specific guidelines related to consenting children or adolescents?  What is the age definition of child and adolescent?

A: There are no specific guidelines for assenting children or adolescents and instead each IRB develops its own standard. The Federal Regulations give IRB’s the authority to determine if assent is required based on capability and whether it must be documented. See 45 CFR 46.408 & 21 CFR 50.55.

Quorum Review typically requires written documented assent of minors ages seven to seventeen. Quorum Review also recommends use of a single assent form for this age range.

Q: If an investigator develops a home-grown device that will be inserted into the heart chamber during open-heart surgery to measure internal pressures, but there is no intent to diagnose, treat, cure mitigate a disease or affect the structure/function of the body (it will be used to assess different physiologic conditions to understand the pathologenesis of disease), is the research FDA-regulated?  In other words, they want to develop a device for future research on heart conditions, but it does not meet the definition of a medical device.  Does the IRB need to insist that this device is classified by the FDA?  Or can the IRB approve the study, noting that the device is not a medical device.

A: For this type of clinical investigation, it would be highly recommended to get a written statement from the FDA regarding the applicability of the investigational device exemption regulations (21 CFR 812). Even if you are correct that the device as used should not be considered as meeting the FDA’s definition of a medical device, most IRB’s would focus their attention on the device’s status as home-grown (not approved) and device’s use during open-heart surgery and find it to be significant risk (requires an IDE) or else require a formal FDA determination. A statement from the FDA either concurring with your view or else labeling the use as non-significant risk would remove the question from the IRB and would ensure a more efficient IRB review process.

For more information see the FDA’s guidance for IRB Responsibilities for Reviewing the Qualifications of Investigators, Adequacy of Research Sites, and the Determination of Whether an IND/IDE is Needed, which states in part “FDA is available to assist sponsors, investigators, and IRBs in making these determinations. Sponsors, clinical investigators, and IRBs who need assistance in making a risk determination for a medical device may also contact:

IDE Staff
Office of Device Evaluation
Center for Devices and
Radiological Health
Food and Drug Administration
10903 New Hampshire Avenue
Silver Spring, MD 20993-0002
(Tel) 301-796-5640

Based on the information provided, FDA will determine if a device study is SR, NSR, or exempt from the IDE requirements found in 21 CFR Part 812. If FDA makes the SR, NSR, or exempt determination for a study, the agency’s determination is final.

 Additional FDA contacts for questions about medical devices include:

  • DICE@fda.hhs.gov – Division of Industry and Consumer Education
  • Manufacturer’s assistance: 800-638-2041
  • Questions about whether a product is subject to IDE regulations: call 301-796-5640 

Q: When a commercial device is used in research in the population for which the device is intended, but the researcher plans to use a slightly different surgical procedure for putting the device in place does it require an IDE?

A: Your question is highly dependent on the specific device at issue and whether its approved indication covers how it is surgically place (cemented versus non-cemented) and so unfortunately we are not able to provide a specific answer.

 However, the use of an approved medical device in a clinical investigation is exempt from the IDE regulations if the device is being used or investigated in accordance with its FDA approved indications. See 21 CFR 812.2(c)(2). Any analysis of whether an IDE may be required should start with the approved indication and if questions remain a consult with the FDA should be sought. If the FDA makes a determination that the use of the device is exempt, the agency’s determination is final and IRB’s are resolved of this obligation.

 For more information see the FDA’s guidance for IRB Responsibilities for Reviewing the Qualifications of Investigators, Adequacy of Research Sites, and the Determination of Whether an IND/IDE is Needed,

 FDA contacts for questions about medical devices include:

  • DICE@fda.hhs.gov – Division of Industry and Consumer Education
  • Manufacturer’s assistance: 800-638-2041
  • Questions about whether a product is subject to IDE regulations: call 301-796-5640

Q: If class I in Europe device can it be used in US FDA study?  What about outside labeling?

A: If a device maintains a certain status in another country or countries, that status does not by default extend to the US. Thus, if a device is considered Class I in Europe, that does not necessarily mean it would be considered Class I in the US (although it is possible it could ultimately be classified in Europe and the US as Class I). If used in a clinical investigation in the US, the device would still have to meet all the standard FDA requirements for clinical investigations of devices regardless if used within or outside its European labeling.

Q: Didn’t see “Mobile Medical Devices” called out as a “special consideration” but I really hope they’re also covered!

A: Unfortunately we did not have time to cover Mobile Medical Devices in this webinar. Here are a couple good reference materials for Mobile Medical Devices for the US:


Q: I just got a question yesterday from a study team “Once a user downloads the app and begins generating data, we’re interested in potentially analyzing their paradata (e.g. How many times they clicked on a particular link, how often they logged in to the app, etc.) for use in research.” Would love some ideas that are developing …

A: We would have to know more of the specifics of the scenario you begin to describe to provide any guidance, but it sounds like you are referring to the regulation of analyzing data in relation to mobile medical devices. Here are a couple reference materials for Mobile Medical Devices from the FDA, which is the best resource for what must be kept in mind for doing this type of research (assuming your question is for the US):

Q: If you had some new, unapproved *type* of blood glucose monitor in consideration w/ some new *type* of insulin, would the former be a “companion device”?

A: It is certainly possible the blood glucose monitor could be considered a “companion device”. Whether the blood glucose monitor would be considered a “companion device” would ultimately be up to the FDA’s assessment of the study, devices, and insulin at play. Quorum recommends you consult with the FDA if you have any questions about how they intend to regulate a device in this particular scenario.

Q: Can you talk about what kinds of documentation the IRB should request when reviewing studies that include MR-PET scanners, MRI, etc?  What about hybrid devices?  What do we need to know?

A: Any clinical investigation of a device submitted to review at an IRB should provide clear documentation regarding the regulatory status of the device (IDE number, request for nonsignificant risk (NSR) determination, etc.). This would include clinical investigations of MR-PET scanners, MRIs, etc. The submission also should include any necessary supporting information needed to support the IRB’s review – such as device manuals, correspondence from FDA (if requested/required by the IRB), protocol, consent forms, and any other forms and documents required by the IRB or needing review. At Quorum, a standard device study submission should include 1. The device study submission form (F-019) – this document informs the Board of the device status and you can request any determinations needed, such as a nonsignificant risk (NSR) determination; 2. The device manual; and 3. All other standard submission documents (protocol, consent form, other submission forms). You should contact Quorum if you have any questions about unique issues related to your particular submissions.

Q: If a physical modification to a HUD doesn’t change the indication for use, should it be seen as a new device?

A: A physical modification to an HUD could be considered a new device by the FDA even if the indication for use does not change. It is recommended that you consult the FDA regarding your HUD to assess if the modifications change the status of the HUD and what requirements may apply as a result of the modifications.

Q: In the US, if a device is Class I, 510(k), or PMA, does the IRB still need to document in the minutes whether the device is SR or NSR?

A: An IRB is solely required to make a determination of SR or NSR for an investigational medical device study (see Information Sheet Guidance For IRBs, Clinical Investigators, and Sponsors Significant Risk and Nonsignificant Risk Medical Device Studies, http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM126418.pdf). This determination is not required for studies that are exempt from the IDE regulations (e.g., where a device is approved or cleared and used in accordance with its approved/cleared indication). The decision of what needs to be documented in IRB meeting minutes depends on the IRB procedures. As a best practice, it is best to document the device status in the study for all device studies. However, documentation of SR or NSR determination is only required for investigational medical device studies as noted in the above-referenced guidance document.

In the US, if a 510(k) device is used in a study, but it’s not being used within the approved indication, could the FDA help the researcher determine whether the device is SR (needs an  IDE) or NSR?  OR should the IRB just err on the side of a SR finding and require the researcher obtain an IDE.

The answer is outlined in the guidance document Guidance for IRBs, Clinical Investigators, and Sponsors: IRB Responsibilities for Reviewing the Qualifications of Investigators, Adequacy of Research Sites, and the Determination of Whether an IND/IDE is Needed.  This guidance indicates the sponsor should determine whether submission of an IDE application is required, which must be reviewed by the IRB. Additionally:

FDA is available to assist sponsors, investigators, and IRBs in making these determinations. For information on how to request such assistance, please see the guidance Procedures for Handling Inquiries Regarding the Need for an Investigational Device Exemptions Application for Research Involving Medical Devices.  Sponsors, clinical investigators, and IRBs who need assistance in making a risk determination for a medical device may also contact:

IDE Staff
Office of Device Evaluation
Center for Devices and
Radiological Health
Food and Drug Administration
10903 New Hampshire Avenue
Silver Spring, MD 20993-0002
(Tel) 301-796-5640

Q: How do you determine whether a device is just being used in a study (like an approved MRI device, a device that makes a dental mold, a CT scanner) vs. a study device? Is there a rule of thumb for this?

A: Under 21 CFR 812.2(c), a legally marketed device (i.e. a cleared or approved device) may be used in a clinical investigation (as defined in 21 CFR 56.102(c)) if used in accordance with its labeling. If the IRB is uncertain regarding the regulatory status of a device, the IRB should request additional information/documentation. However, studies of a cleared device for a new use must comply with the human subject protection, IRB, and IDE regulations. Additional information may be obtained by reviewing Information Sheet Guidance for IRBs, Clinical Investigators, and Sponsors: Frequently Asked Questions About Medical Devices .

Q: Do you have any tips/tricks for looking up device information on the FDA website? Sometimes the manufacturer is not the same as the company now marketing the device, sometimes the device name is not listed exactly the same way, etc.

A: We agree that the FDA website can be difficult to navigate, but don’t have any specific tips. In our experience, we typically request the 510(K) number or PMA number, company information, and device trade name. Additionally, many IRBs request documentation of the 510(k) clearance or PMA approval at initial review.

Q: Could you please speak to the IRBs responsibility if an investigator is testing the benefit of a software program (for example one that utilizes game type activities) to see if it improves cognitive functioning when the investigator is not the manufacture of the software.  Does it matter for a device if there is no intent to utilize the study to lead to marketing of the software?

A: We refer you to this FDA presentation for more information on specific considerations in software device research.

 

Tags: ,