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Hotspots and Challenges in Medical Device Research

May 20th, 2016 by Robert Romanchuk, BSHS, CIP, CCRC, CCRP, IRB Vice Chair at Schulman IRB and Stephanie Pyle, Manager, Community and Communications at Schulman IRB

To help understand the unique challenges and best practices in conducting medical device clinical trials, it’s important to understand how medical device research is different from other research, as well as how things are the same.

The regulatory landscape for medical devices was developed side by side with regulations governing biopharmaceutical research, but each set of regulations grew out of different conditions. The following table outlines some of the key regulatory differences between device and drug studies. For further reading, FDA’s Device Advice site offers robust guidance and insights.

 IND (Drug)IDE (Device)
Start-Up1572 must be executed prior to study startCTA must be executed prior to device shipment
Start-UpCMS approval not requiredCMS approval must be granted prior to study start if CMS contractors will be billed
IRB ResponsibilitiesNo risk determination is made by IRB for IND studiesIRB must make risk determination before study can proceed—nonsignificant risk devices do not require an IDE (812.66)

Protocol may be submitted to the IRB before IDE approval is granted, but study may not begin until IDE is granted
(See FDA Information Sheet for more information)
Adverse Event DefinitionIND reports for “any untoward medical occurrence associated with the use of the drug, whether or not considered drug-related”
(312.32)
UADE (Unexpected Adverse Device Effects) means any serious adverse effect on health or safety or any life-threatening problem or death caused by, or associated with, a device, if that effect, problem, or death was not previously identified
(812.46)
AE Reporting-IND reports within 15 days
-Unexpected fatal or life-threatening adverse events within 7 days
UADEs reported to FDA and all reviewing IRBs within 10 days
Investigational ArticleDrug provided at no charge –pharmacy often manages receipt, storage and dispensingDevices often require purchase agreements and must be priced to avoid “commercial distribution,” e.g. charge only what will recover “costs of manufacture, research, development and handling”
(812.7)—pharmacy not involved in receipt, storage or dispensing.

Protocol and Study Design

Medical device protocols have some inherent differences from their biopharmaceutical brothers. Device research usually involves smaller participant populations, recruiting 100s of participants instead of biopharma’s typical 1000s. Instead of following biopharma’s customary Phases I-IV, medical device research uses:

  • Feasibility study – to evaluate safety
    • Usually involves participants with the device’s intended disease state, as most devices are applicable only to that particular disease state and difficult to evaluate in a healthy participant population
  • Pilot study – to evaluate effectiveness and optimize the protocol for use in the intended population
  • Pivotal study – to evaluate the device in the intended population
    • Pivotal studies usually have the largest enrollment numbers and greatest number of sites
  • Often employ “roll-ins” – allow the research practitioner to perfect the technique for implanting/using the device. Since surgical implantation is often involved, device studies require a skill level beyond what’s usually required to deliver an injection or administer a medication in biopharma research. Roll-ins help to ensure study procedures are performed consistently and lead to reliable study data.

Placebo controls can be problematic in device research, since many devices involve some kind of surgical intervention. There are some ways to use sham procedures as a sort of placebo. Historical controls or active comparator arms may be useful.

IRB Hotspots

The IRB must consider several particularly unique aspects of medical device study review.

  • Risk determination: The IRB is responsible for determining whether the device is significant or nonsignificant risk. Devices determined significant risk will require an IDE. The IRB’s risk determination may disagree with the sponsor. It falls to FDA to make the final risk determination. A significant risk device is:
    • Intended as an implant.
    • Used in supporting or sustaining human life.
    • Of substantial importance in diagnosing, curing, mitigating or treating disease, or otherwise prevents impairment of human health.
    • Otherwise presents potential for serious risk to health, safety or welfare of subject.
    • Previously nonsignificant risk or 510(k) exempt devices may be significant risk in the investigational application.
  • Must not confuse nonsignificant risk determination with “minimal risk” determination which is relevant in the enrollment of vulnerable populations.
  • Document decision-making process
  • Understand the difference between IDE regulations and HUD (humanitarian use device) regulations. Use of HUDs can be particularly challenging for IRBs, since HUDs are not technically research studies, though they do require IRB oversight.
  • Devices are not drugs—subjects must be informed of special aspects of device research, including:
    • Implants may be permanent. Subjects should understand how battery changes or device revisions will be covered and if explant is possible.
    • Approval: If the device is approved, what are the costs of maintenance? If the device is not approved, what options does the subject have?
    • Newer models may be developed over the course of the study. Subjects should understand their options.

There are many other unique elements of device research that we simply don’t have room for in this blog. For more on the differences between device research and biopharma research, view our recent webinar Meeting the Challenge of Device Studies. Schulman also offers Device Resources that may be helpful for those new to medical device clinical research.