Status: Final

Organizations: U.S. Food and Drug Administration, Center for Devices and Radiological Health

Date: January 2000

Target Audience: Makers of spinal devices who wish to apply to the FDA for an Investigational Device Exemption (IDE)

Laws and Regulations Referenced:
21 CFR 25: Describes the FDA’s considerations relating to environmental impact
21 CFR 50: Describes how human subjects are to be protected in clinical trials
21 CFR 56: Describes the role of institutional review boards
21 CFR 58: Describes good laboratory practices studies that are not conducted on humans
21 CFR 801: Describes the labeling requirements for medical devices
21 CFR 812: Outlines the requirements of an IDE application
21 CFR 860: Explains how device classification is determined based on safety and effectiveness data

Definitions:
Investigational Device Exemption (IDE): The FDA grants device makers the ability to test their new devices in humans by approving an IDE.

Spinal system: A complete spinal implant including all parts.

Component: An individual part of a spinal system.

Background:
The latest spinal devices are designed in different ways than older devices. They may use new materials and pose greater risks along with potentially new benefits to patients. Before a new device can be tested in humans, the device maker must apply to the FDA for an IDE. The IDE includes all details of how the clinical studies will be conducted and how the results will be interpreted. This guidance outlines the FDA’s areas of concern specific to IDEs for spinal devices.

Summary:
Before testing a new spinal device in humans, the device maker must show that the new product appears to be reasonably safe. They may do this by:

(1) Citing scientific articles describing clinical trials conducted in other countries or on similar devices or components

(2) Providing the results of animal testing to show that the material will likely be safe in the human spine, will stabilize the spine as intended, and will promote or prevent fusion, depending on the intended use

(3) Providing the results of mechanical testing showing the device withstands certain weights (static testing) and repetitive motions (fatigue testing)

After establishing preliminary safety, the device maker describes the details of the human studies they plan to conduct. The applicant states the goals of the study and proposes a study design. The preferred design is a randomized control trial, in which one group of patients (control group) is given a standard treatment and a similar group (experimental group) is given the new treatment and the outcomes compared.

The IDE application should outline the factors that will determine whether a patient is eligible for the study. Patients may be included if they are within a specific age range, have a certain condition affecting a specific area of the spine, and are deemed likely to adhere to the follow-up schedule. Patients may be excluded if they have other diseases that could affect results, if they have had previous surgeries, are pregnant, or are deemed unlikely to follow up.

The number of patients to be included in the study should ensure that results are statistically meaningful. Patients should be followed for at least 2 years. The FDA recommends that patients be evaluated at the start of the study (before surgery), and 2 weeks, 3 months, 6 months, 1 year, and 2 years following surgery.

There are many ways to determine the success of a new spinal implant. The FDA notes that the outcomes should be both statistically and clinically meaningful. This means that there should be a measurable (objective) improvement in range of motion and/or anatomical measurements of the spine, as well as a patient-reported (subjective) improvement in pain and functionality.

Safety of the implant should be evaluated by documenting any repeat surgeries or adverse events during the follow-up period, and testing for any neurological problems that did not exist prior to surgery.

The IDE application must also describe how statistical methods will be used to analyze the study results. This explanation should include how the sample size was determined, and how trends in the data will be detected.

Finally, the IDE must include proposed labeling for the device. The package label, the information contained inside the package, and the manual describing the surgical technique for implanting the device must all clearly state that the product is an investigational device.

Rationale:
Spinal systems are complex medical devices that can pose serious risks that are unique to their design and their uses in the spine. The FDA must evaluate the safety and effectiveness of these devices in humans before approving them for widespread use. Device makers must create a lengthy and complex IDE application that addresses the FDA’s concerns specific to these devices. This guidance outlines those areas of concern to help device makers produce a complete IDE application.

Resulting Recommendations:

·Device makers should consult the FDA early in the development of proposed human testing of their devices.

·Devices should be shown likely to be safe in the human spine through evidence in the scientific literature, animal testing, and mechanical testing.

·The proposed clinical study should have a clear hypothesis and objective.

·The proposed clinical study should include enough patients to make it statistically relevant.

·Study participants should be randomly assigned to either a control group or the testing group.

·Patient inclusion and exclusion criteria should be defined in the IDE application.

·Patients should be followed up for at least 2 years.

·Effectiveness of the device should be determined by both objective measurements and reports of patient satisfaction, including improvements in pain and function.

·Safety should be evaluated by analyzing adverse events, reoperations, and neurological problems.

·Planned statistical analyses should be described in the IDE application.

·The IDE application should include proposed package labeling, informational insert, and surgeon instructions, all of which should identify the device as investigational.

Impact:
By explaining the FDA’s main areas of concern relating to the safety and efficacy of spinal devices, this guidance should shorten the time to ultimate device approval by helping device makers submit a successful IDE application on their first attempt.