IDE Guidance Memorandum #D89-1
This guidance was written prior to the February 27, 1997 implementation of FDA’s Good Guidance Practices, GGP’s. It does not create or confer rights for or on any person and does not operate to bind FDA or the public. An alternative approach may be used if such approach satisfies the requirements of the applicable statute, regulations, or both. This guidance will be updated in the next revision to include the standard elements of GGP’s.
May 17, 1989 Review of IDEs for Feasibility Studies The attached guidance details the purpose and procedure for the review of IDE applications for feasibility studies involving limited numbers of human subjects. It was developed through review of a citizen petition submitted to the agency requesting amending the IDE regulation to provide for such studies, by review of ODE's procedures in reviewing early-phase studies, and from input from ODE Division Directors and other staff. The concepts and procedures outlined in the guidance should be implemented immediately. Attachment
ATTACHMENT GUIDANCE ON THE REVIEW OF INVESTIGATIONAL DEVICE EXEMPTIONS (IDE) APPLICATIONS FOR FEASIBILITY STUDIES INTRODUCTION On November 21, 1984, the American Society for Artificial Internal Organs (ASARIO) submitted a citizen petition requesting FDA to amend the investigational device exemptions (IDE) regulation to allow limited clinical investigations of significant risk devices to be subject to less than the full IDE requirements. FDA may not be able to accept the petition in its entirety but recognizes the importance of providing flexibility in the review of IDE applications for feasibility studies, as long as the subjects' safety and welfare are ensured. While CDRH has been exercising its discretion in the review and approval of feasibility studies, it has become apparent that this procedure needs to be formalized in order to be consistently applied by the reviewing divisions and to advise the research clinical community of these procedures. It is relatively easy for a sponsor to identify a feasibility study by merely pointing out that the study involves a new device or a new technology and will involve only a few human subjects. It is much more difficult to establish the criteria for relief from specific requirements of IDE regulation while assuring that patients are not placed at unreasonable risk. Relief can only be granted on a case-by-case basis, and continual assessment and analysis of the review of feasibility studies is essential to developing more concise guidance. This guidance document outlines principles which should be considered when reviewing IDE applications for feasibility studies. It is expected that application of these principles will facilitate the review and approval of feasibility studies, to the extent consistent with research subjects' safety and welfare and within ethical standards. THE CONCEPT OF FEASIBILITY STUDIES In a developmental process, a device is designed to meet a clinical need and testing begins in the laboratory using animal and/or bench methodology. Once the design and operating parameters have been subject to adequate preclinical tests, the developer may wish to conduct an initial limited study in humans to confirm the design and operating specifications before beginning an extensive clinical trial. The initial study may indicate that minor or major changes in the device or its manufacture are necessary before proceeding. It may also indicate that the device does not meet expectations and it will be terminated. The performance of the device in the limited study serves to establish the parameters for the larger clinical study, such as sample size and indices of measurement. Inherent in the utility of the limited study is the importance of maintaining sufficient flexibility for the researcher to make adjustments in the device, its manufacture or the investigational plan in the early stages of clinical testing without the need for repeated prior FDA approval. REVIEWER GUIDANCE 1. APPLICABILITY This guidance applies to limited clinical investigations of significant risk medical devices which are intended to provide data on the device's feasibility for diagnostic or therapeutic clinical use. IDE applications subject to the guidance are those which are identified by the sponsor as feasibility studies and which demonstrate that they meet the general considerations applicable to such studies as note below. A feasibility study may also be identified as phase 1 studies, pilot studies, prototype studies, introductory trials or feasibility studies, or which is characterized as a feasibility study from the objectives of the investigational plan. 2. INTERACTIONS WITH SPONSORS FDA encourages early and continued interactions with device innovators and potential IDE sponsor to establish a rapport which will expedite the review process. Device technology is advancing rapidly and FDA must develop and nurture lines of communication in order to anticipate problems, training needs and other resources necessary to review applications. The sponsor or researcher gains by being able to plan an acceptable preclinical and clinical approach to product development. The sponsor and reviewer should also explore possible waivers that could be granted. 3. GENERAL CONSIDERATION FOR ORIGINAL AND SUPPLEMENTAL IDEs Original IDEs: IDE applications for feasibility studies will vary in scope but typically will include one investigator at one site with a limited number of subjects, usually ten or less. Data from the feasibility study will not be considered as pivotal evidence of safety and effectiveness but rather as a basis to finalize and confirm the device design and determine its potential for further development. FDA will continue to require that an IDE application for a feasibility study address all the elements of an IDE application unless a waiver is approved. Generally, reviewers should focus their attention upon the device's potential risk to subjects. Additional concerns, e.g., a rigorous examination of the investigational plan, may be delayed until the next phase of development where the study is designed to determine the device's safety and effectiveness. The IDE regulation provides that an application may include anticipated changes to a device during the course of an investigation. For a feasibility study, FDA and the sponsor may employ this provision to qualify a range of device changes and testing parameters that can be undertaken by the sponsor without the need for further FDA approval. Supplemental IDEs: The IDE regulation provide that changes affecting the scientific soundness or the rights, safety and welfare of subjects need to be submitted to FDA for approval prior to implementation. IRB approval is also required when the changes affect the rights, safety and welfare of subjects. FDA and sponsors should use these criteria to the maximum extent possible to limit the type of changes needed to be submitted as supplements. It is the sponsor's responsibility to determine whether a change meets the criteria. All changes, whether major or minor or whether submitted as a supplement, should be described in progress reports, end-of-study reports and in request for expansion of the investigation. 4. SPECIFIC IDE REQUIREMENTS AND CONSIDERATIONS An IDE application for a feasibility study must address all the elements required by the IDE regulation unless a waiver is granted for a specific element. Elements that are not relevant may be indicated as "not applicable." Summary information, in lieu of full reports, is acceptable provided that the summary is sufficiently detailed and comprehensive to permit knowledgeable evaluation of the data. Preclinical Studies: It is the sponsor's, responsibility to define and conduct adequate tests to establish the lack of unreasonable risk and the expected performance of a device prior to clinical use. A limited trial may represent the initial introduction of a device into a human population, therefore, FDA must be assured that a sufficient battery of tests have been completed. It is the prerogative of the sponsor to indicate whether some preclinical tests (e.g., chronic toxicity) are not essential to early clinical studies and will be initiated only if the device will undergo further clinical study. Investigational Plan: The sponsor must include a thorough risk analysis which describes the risks to the subject, how they will be minimized and a justification that they are reasonable in relation to the expected benefits. The scope and duration of limited studies will vary, but in general, are less ambitious than full clinical studies which provide the pivotal evidence of safety and effectiveness. The investigational plan should have a valid scientific objective and reasonable study protocol. Disapprovals should be limited to situations where there are critical safety-related concerns. Other deficiencies can be corrected or clarified under a conditional approval decision. Manufacturing and Control Data: In some developmental programs which lead to feasibility studies, FDA recognizes that traditional manufacturing information may not exist. As noted above, often devices do not proceed to further development if the early studies do not prove satisfactory and so only pilot manufacturing processes may be used. It is incumbent upon the sponsor to establish a reasonable process of design, manufacture, quality control and testing and to indicate to FDA in an IDE application where other standard procedures are unnecessary or premature. FDA should tailor its deficiencies to the circumstances that exist and the stage of development. Expanded clinical studies that may follow early studies may require additional assurances regarding manufacture and quality control as the numbers of devices to be distributed increase. The conditional approval decision should be employed as much as possible. Informed Consent: Attention should be paid to the informed consent's description of the nature of the study, i.e., explanation of the purpose of the research, and indication that the subject is one of the first exposed to the device. Other IDE Application Requirements: All other aspects of IDE application for feasibility studies, including investigator agreement, IRB information, sales information, environmental impact statements and labeling should be evaluated under a conditional approval decision unless there are extentuating circumstances. ANALYSIS OF FEASIBILITY STUDIES ODE will conduct an analysis of the types of IDE applications being submitted for feasibility studies. The purpose of this analysis is to determine whether the guidance is providing sufficient direction to reviewers and flexibility to researchers. It will also further establish the nature and extent of feasibility studies. The IDE Staff will collect the following information in their analysis: device type; objectives of the study; study design; number of investigators and sites; study sample size; duration of study; conclusions of the study; use of the data; percent of device types progressing to expanded trials; time to approval of studies and percent of approvals; percent of applications accepted without additional information; and waivers granted. SUMMARY The reviewer should remain cognizant of the following principles when examining IDE applications for feasibility studies: o Focus the review on the risk/benefit ratio and place less emphasis on the scientific thoroughness o Open and maintain lines of communication with researchers and sponsors to forestall problems o Employ maximum flexibility, where appropriate o Use conditional approval decisions to the fullest extent when deficiencies exist o Consult with the Program Operation Staff (POS) on application of the guidance when necessary