A significant risk device presents a potential for serious risk to the health, safety, or welfare of a subject. Significant risk devices may include implants, devices that support or sustain human life, and devices that are substantially important in diagnosing, curing, mitigating, or treating disease or in preventing impairment to human health, or have the potential to evoke collateral harm. Examples include sutures, cardiac pacemakers, hydrocephalus shunts, and orthopedic implants. The sponsor must demonstrate in the application that there is reason to believe that the risks to human subjects from the proposed investigation are outweighed by the anticipated benefits to subjects and the importance of the knowledge to be gained, that the investigation is scientifically sound, and that there is reason to believe that the device as proposed for use will be effective.
In order to conduct a significant risk device study, a sponsor must:
• submit a complete IDE application88 to FDA for review and obtain FDA approval of the IDE; submit the investigational plan89 and report of prior investigations90 to the IRB at each institution where the investigation is to be conducted for review and approval, and
• select qualified investigators, provide them with all necessary information on the investigational plan and report of prior investigations, and obtain signed investigator agreements from them.
Upon receipt of an IDE application, sponsors are notified in writing of the date that FDA received the original application and the IDE number assigned (receipt of supplements and amendments are not acknowledged). An IDE application is considered approved 30 days after it has been received by FDA, unless FDA otherwise informs the sponsor prior to 30 calendar days from the date of receipt, that the IDE is approved, approved with conditions, or disapproved. In cases of disapproval, a sponsor has the opportunity to respond to the deficiencies and/or to request a regulatory hearing under 21 CFR §16.
Once an IDE application is approved, the following requirements must be met in order to conduct the investigation in compliance with the IDE regulation: [9]
• Informed Consent—Each subject must be provided with and sign an informed consent form before being enrolled in the study. The Protection of Human Subjects regulation93 contains the requirements for obtaining informed consent.
• Monitoring—All investigations must be properly monitored94 to protect the human subjects and assure compliance with approved protocols.
• Prohibitions—Commercialization, promotion, and misrepresentation of an investigational device and prolongation of the study are prohibited.95
• Records and Reports—Sponsors and investigators are required to maintain specified records96 and make reports to investigators, IRBs, and FDA.