Source: http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm373750.htm?source=govdelivery
Timestamp: 2015-05-05 10:19:43
Document Index: 371690566

Matched Legal Cases: ['art 3', 'arts 50', 'art 56', 'art 50', 'art 812', 'art 812', 'art 812']

Design Considerations for Pivotal Clinical Investigations for Medical Devices - Guidance for Industry, Clinical Investigators, Institutional Review Boards and Food and Drug Administration Staff Quick Links: Skip to main page content
Cross-Center Final Guidance Office of Compliance Final Guidance Office of the Center Director Final Guidance Office of Communication and Education Final Guidance Office of Device Evaluation Final Guidance 2010 - 2014 Office of Device Evaluation Final Guidance 1998 - 2009 Office of Device Evaluation Final Guidance 1976 - 1997 Office of In Vitro Diagnostics and Radiological Health Final Guidance Office of Surveillance and Biometrics Final Guidance Office of Science and Engineering Laboratories Final Guidance Draft Guidance Radiation-Emitting Products Guidance Temporary Guidance Holding Withdrawn Guidance Design Considerations for Pivotal Clinical Investigations for Medical Devices - Guidance for Industry, Clinical Investigators, Institutional Review Boards and Food and Drug Administration Staff
(PDF - 340kb)Document issued on: November 7, 2013The draft of this document was issued on August 15, 2011.For questions regarding this document that relate to devices regulated by CDRH, contact Gregory Campbell, PhD at (301) 796-5750 or by email at greg.campbell@fda.hhs.gov, if desired. For questions regarding this document that relate to devices regulated by CBER, contact Stephen Ripley at 301-827-6210.U.S. Department of Health and Human ServicesFood and Drug AdministrationCenter for Devices and Radiological HealthCenter for Biologic Evaluation and ResearchPrefacePublic CommentWritten comments and suggestions may be submitted at any time for Agency consideration to the Division of Dockets Management, Food and Drug Administration, 5630 Fishers Lane, Room 1061, (HFA-305), Rockville, MD, 20852. Additional CopiesAdditional copies are available from the Internet. You may also send an e-mail request to dsmica@fda.hhs.gov to receive an electronic copy of the guidance or send a fax request to 301-847-8419 to receive a hard copy. Please use the document number 1776 to identify the guidance you are requesting.Additional copies of this guidance document are also available from:Center for Biologics Evaluation and Research (CBER), Office of Communication, Outreach and Development (HFM-40), 1401 Rockville Pike, Suite 200N, Rockville, MD 20852-1448,or by calling 1-800-835-4709 or 301-827-1800, or email ocod@fda.hhs.gov, or from the Internet at http://www.fda.gov/BiologicsBloodVaccines/ GuidanceComplianceRegulatoryInformation/Guidances/default.htm. Table of ContentsIntroductionScope 2.1 Types of Studies Addressed in this Guidance2.2 Types of Studies Not Addressed in this GuidanceRegulatory Framework for Level of Evidence and Study Design 3.1 The Statutory Standard for Approval of a PMA: Reasonable Assurance of Safety and Effectiveness3.2 Valid Scientific Evidence3.3 Benefit-Risk Assessment3.4 Clinical Study Level of Evidence and Regulation3.5 The Least Burdensome Concept and Principles of Study DesignTypes of Medical Devices 4.1 Types of Devices Based on Intended Use4.2 Special Considerations for Clinical Studies of DevicesThe Importance of Exploratory Studies in Pivotal Study Design Some Principles for the Choice of Clinical Study Design 6.1 Types of Studies6.2 General Considerations: Bias and Variability in Device Performance.6.3 Study Objectives6.4 Subject Selection6.6 Site Selection6.7 Comparative Study DesignsClinical Outcome Studies 7.1 Endpoints in Clinical Studies7.2 Intervention Assignment (Randomization) for Clinical Outcome Studies7.3 Blinding (Masking)7.4 Controls in Comparative Clinical Outcome Studies7.5 Placebo Effect and Other Phenomena7.6 Non-Comparative Clinical Outcome Studies7.7 Diagnostic Clinical Outcome Studies7.8 Advantages and Disadvantages of Some Clinical Outcome Studies7.9 Some Regulatory ConsiderationsDiagnostic Clinical Performance Studies 8.1 Consideration of Intended Use8.2 Clinical Reference Standard for the Target Condition8.3 Study Population for Evaluation of Diagnostic Performance8.4 Study Planning, Subject Selection and Specimen Collection8.5 Diagnostic Clinical Performance Comparison Studies8.6 Blinding (Masking) in Diagnostic Performance Studies8.7 Skill and Behavior of Persons Interacting with the Device (Total Test Concept)8.8 Common Types of Bias in Diagnostic Clinical Performance StudiesSustaining the Quality of Clinical Studies 9.1 Handling Clinical Data.9.2 Study Conduct9.3 Study Analysis9.4 Anticipating Changes to the Pivotal StudyThe Protocol GlossaryDesign Considerations for Pivotal Clinical Investigations for Medical Devices - Guidance for Industry, Clinical Investigators, and Food and Drug Administration StaffThis guidance represents the Food and Drug Administration's (FDA's) current thinking on this topic. It does not create or confer any rights for or on any person and does not operate to bind FDA or the public. You can use an alternative approach if the approach satisfies the requirements of the applicable statutes and regulations. If you want to discuss an alternative approach, contact the FDA staff responsible for implementing this guidance. If you cannot identify the appropriate FDA staff, call the appropriate number listed on the title page of this guidance. 1 IntroductionThis document is intended to provide guidance to those involved in designing clinical studies intended to support pre-market submissions for medical devices and FDA staff who review those submissions. Although the Agency has articulated policies related to design of studies intended to support specific device types, and a general policy of tailoring the evidentiary burden to the regulatory requirement, the Agency has not attempted to describe the different clinical study designs that may be appropriate to support a device pre-market submission, or to define how a sponsor should decide which pivotal clinical study design should be used to support a submission for a particular device. This guidance document describes different study design principles relevant to the development of medical device clinical studies that can be used to fulfill pre-market clinical data requirements. This guidance is not intended to provide a comprehensive tutorial on the best clinical and statistical practices for investigational medical device studies. Medical devices can undergo three general stages of clinical development. These stages may be extremely dependent on each other and doing a thorough evaluation in one stage can make the next stage much more straightforward. To begin, medical devices may undergo an exploratory clinical stage. In this stage, the limitations and advantages of the medical device are evaluated. This stage includes first-in-human studies and feasibility studies. The next stage, the pivotal stage, is used to develop the information necessary to evaluate the safety and effectiveness of the device for the identified intended use. It usually consists of one or more pivotal studies. Finally, devices undergo a post-market stage which can include an additional study or studies for better understanding of device safety, such as rare adverse events and long-term effectiveness. This guidance provides information on design issues related to pivotal clinical investigations and does not address the other stages in any detail.A medical device pivotal study is a definitive study in which evidence is gathered to support the safety and effectiveness evaluation of the medical device for its intended use. Evidence from one or more pivotal clinical studies generally serves as the primary basis for the determination of reasonable assurance of safety and effectiveness of the medical device of a pre-market approval application (PMA) and FDA’s overall benefit-risk determination. In some cases, a PMA may include multiple studies designed to answer different scientific questions.The focus of this guidance is providing recommendations to sponsors on how to design clinical investigations to support a PMA. However, sponsors who conduct clinical studies to support pre-market notification (510(k)) and de novo submissions may also rely on the principles in this guidance document.FDA's guidance documents, including this guidance, do not establish legally enforceable responsibilities. Instead, guidances describe the Agency's current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word should in Agency guidances means that something is suggested or recommended, but not required.2 ScopeThis guidance describes principles for the design of pre-market clinical studies1 that are pivotal in establishing the safety and effectiveness of a medical device. Practical issues and pitfalls in pivotal clinical study design are discussed, along with their effects on the conclusions that can be drawn from the studies concerning safety and effectiveness. The principles discussed in this guidance are intended to assist sponsors of marketing applications and investigators in designing studies adequate to provide a reasonable assurance of safety and effectiveness concerning a device.2.1 Types of Studies Addressed in this GuidanceDue to the range of intended uses and risks associated with medical devices and constraints in executing clinical studies, this guidance treats pivotal clinical studies in a general manner. It frames FDA’s recommendations in terms of two broad categories of medical devices:Therapeutic and aesthetic devicesDiagnostic devicesFrom this guidance, device developers can gain insight about important pivotal study design issues for devices in each of these categories. At the same time, communication with FDA review staff (e.g., through a pre-submission interaction) is often valuable in arriving at pivotal clinical study designs that are both practical and adequate.This guidance also includes principles that are applicable to the device-specific issues for combination products defined under 21 CFR Part 3 (e.g., device-drug products; device-biologic products). However, drug-specific or biologic-specific issues that may also be relevant for a combination product are not described in this guidance.This guidance is intended to complement other existing guidance, and is not intended to replace the policies described in other guidance documents. In cases where questions arise, consult the appropriate FDA review division directly or the Center for Devices and Radiological Health (CDRH) Division of Small Manufacturers, International and Consumer Assistance and Consumer Assistance or the Center for Biologics Evaluation and Research (CBER) Office of Communication, Outreach and Development (OCOD) depending on which Center is responsible for review of the device.2.2 Types of Studies Not Addressed in this GuidanceAlthough this guidance does not address the following kinds of studies, some principles discussed herein are applicable to many of them:Non-clinical studies (e.g., bench, animal or measurement studies and, for in vitro diagnostic devices, analytical validation studies);Studies intended to support Humanitarian Device Exemption (HDE) applications;2Pre-market feasibility clinical studies, or other pre-market clinical studies that are not part of the pivotal stage;Studies to establish the clinical validity of companion diagnostic devices (i.e., in vitro diagnostic tests that provide essential information for the safe and effective use of a corresponding therapeutic product). Clinical development programs for companion diagnostic devices are typically part of the clinical development programs of the corresponding therapeutic products;Post-market clinical studies. Though the need for post-market clinical studies might arise from interpretation of pre-market clinical results, post-market studies do not drive the initial determination of safety and effectiveness, and their design is not addressed in this guidance. However, the principles discussed in this guidance may be useful in designing such studies;Studies of products regulated by CBER that require an Investigational New Drug application and Biologics License Application, such as donor screening tests, are not included in the scope of the guidance.Although this guidance is developed primarily for clinical studies used to support PMAs, the recommendations of this guidance may also be used in designing clinical studies used to support some 510(k) and de novo submissions with clinical data when applicable.3 Regulatory Framework for Level of Evidence and Study DesignClinical studies of medical devices must conform to certain legal requirements. This section describes the:Regulatory framework applicable to the design of clinical studies that support pre-market submissions for medical devices;Statutory standard for approval of a PMA;Regulatory requirements that apply to clinical and other data used to meet the statutory standard for approval of a PMA;How FDA evaluates the data to assess the risks and benefits of a device;Basic information about Investigational Device Exemption (IDE) applications; andFDA’s current thinking on good regulatory practice as identified in the least burdensome concept.This guidance reflects the Agency’s consideration of standards for designing, conducting, recording, and reporting studies that involve the participation of human subjects. Related international documents include the “Declaration of Helsinki” and are further explained in the International Standards Organization (ISO) 14155:2011, Clinical investigation of medical devices for human subjects - Good clinical practice and through the International Conference on Harmonisation (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) E6 Good Clinical Practice: Consolidated Guidance. FDA regulations under 21 CFR Parts 50, 54, 56, and 812 articulate good clinical practice (GCP) requirements applicable to clinical investigations of medical devices. In addition, FDA guidance documents describe FDA's current thinking on GCP and the conduct of clinical studies.3 Compliance with GCP, as applicable to medical devices, protects the rights, safety, and well-being of human subjects, ensures appropriate scientific conduct of the clinical investigation and the credibility of the results, defines the responsibilities of the sponsor and the clinical investigator, and assists sponsors, investigators, institutional review boards (IRBs), other ethics committees, regulatory authorities, and other bodies involved in the development and review of medical devices.If a clinical investigation of a device is conducted in the United States it must comply with the applicable regulations found in 21 CFR Part 56 (IRBs), Part 50 (informed consent), and Part 812 (investigation device exemption (IDE)). If the clinical investigation of the device is conducted outside of the United States, submitted in support of a PMA, and conducted under an IDE, the study shall comply with 21 CFR Part 812. 21 CFR 814.15(a). If a clinical investigation of a device is conducted completely outside the United States and not conducted under an IDE, FDA will accept studies submitted in support of a PMA, if the data are valid and the investigator has conducted the studies in conformance with the “Declaration of Helsinki” or the laws and regulations of the country in which the research is conducted, whichever accords greater protection to the human subjects, in accordance with 21 CFR 814.15. A PMA based solely on foreign clinical data may be approved if the foreign data are applicable to the United States population and medical practice; the studies have been performed by clinical investigators of recognized competence; if an inspection is needed, FDA can validate the data through an on-site inspection or other appropriate means; and the application otherwise meets the criteria for approval. 21 CFR 814.15(d). The sponsor must be able to show that the foreign clinical data are adequate to support approval of the device in the United States, under applicable standards. Section 569B of the Federal Food, Drug, and Cosmetic Act (FD&C Act or the Act). We encourage you to meet with FDA in a Pre-Submission meeting if you intend to seek approval based on foreign data, or based on a combination of foreign and U.S. data. 3.1 The Statutory Standard for Approval of a PMA: Reasonable Assurance of Safety and EffectivenessAs indicated by Sections 513(a)(1)(C) of the FD&C Act, a PMA must provide reasonable assurance of safety and effectiveness of the device. FD&C Act Section 513(a)(2) states: [T]he safety and effectiveness of a device are to be determined---(A) with respect to the persons for whose use the device is represented or intended,(B) with respect to the conditions of use prescribed, recommended, or suggested in the labeling of the device, and(C) weighing any probable benefit to health from the use of the device against any probable risk of injury or illness from such use.In addition, FDA has, through regulation, interpreted the statutory standard for approval of a PMA as follows:21 CFR 860.7(d)(1). There is reasonable assurance that a device is safe when it can be determined, based upon valid scientific evidence, that the probable benefits to health from use of the device for its intended uses and conditions of use, when accompanied by adequate directions and warnings against unsafe use, outweigh any probable risks. The valid scientific evidence used to determine the safety of a device shall adequately demonstrate the absence of unreasonable risk of illness or injury associated with the use of the device for its intended uses and conditions of use.21 CFR 860.7(e)(1). There is reasonable assurance that a device is effective when it can be determined, based upon valid scientific evidence, that in a significant portion of the target population, the use of the device for its intended uses and conditions of use, when accompanied by adequate directions for use and warnings against unsafe use, will provide clinically significant results.These statutory and regulatory provisions specify that a finding of reasonable assurance of safety and effectiveness must be supported by data relevant to the target population, and evaluated in light of the device labeling. Further, a determination of whether the standard of approval for a PMA has been met is based on balancing probable benefit to health with probable risk. 3.2 Valid Scientific EvidenceThe regulations state that the safety and effectiveness of a device will be determined on the basis of valid scientific evidence. 21 CFR 860.7(c)(1). Valid scientific evidence is defined through regulation as follows:21 CFR 860.7(c)(2) Valid scientific evidence is evidence from well-controlled investigations, partially controlled studies, studies and objective trials without matched controls, well-documented case histories conducted by qualified experts, and reports of significant human experience with a marketed device, from which it can fairly and responsibly be concluded by qualified experts that there is reasonable assurance of the safety and effectiveness of a device under its conditions of use. The evidence required may vary according to the characteristics of the device, its conditions of use, the existence and adequacy of warnings and other restrictions, and the extent of experience with its use. Isolated case reports, random experience, reports lacking sufficient details to permit scientific evaluation, and unsubstantiated opinions are not regarded as valid scientific evidence to show safety or effectiveness. Such information may be considered, however, in identifying a device the safety and effectiveness of which is questionable.FDA regulations also consider which types of evidence support reasonable assurance of safety and effectiveness:21 CFR 860.7(d)(2) Among the types of evidence that may be required, when appropriate, to determine that there is reasonable assurance that a device is safe are investigations using laboratory animals, investigations involving human subjects, and nonclinical investigations including in vitro studies.21 CFR 860.7(e)(2) The valid scientific evidence used to determine the effectiveness of a device shall consist principally of well-controlled investigations, as defined in [21 CFR 860.7](f), unless [FDA] authorizes reliance upon other valid scientific evidence which [FDA] has determined is sufficient evidence from which to determine the effectiveness of a device, even in the absence of well-controlled investigations. [FDA] may make such a determination where the requirement of well-controlled investigations in [21 CFR 860.7](f) is not reasonably applicable to the device.Thus, one key principle evident in 21 CFR 860.7 is that evidence of effectiveness of a medical device must generally be obtained from well-controlled studies (as described in 21 CFR 860.7(f)). However, the regulations provide FDA with some flexibility regarding its determination of the type of evidence that may be considered valid scientific evidence to demonstrate the safety of a medical device. FDA believes that in most cases, clinical data will be necessary to demonstrate effectiveness for a device being reviewed in an original PMA. Sections 6, 7, and 8 of this guidance provide some principles to help sponsors determine an appropriate study design. The results of the study must provide sufficient evidence for FDA to make a determination of reasonable assurance of safety and effectiveness, as defined in the regulations above. Based on pre-submission discussions with the sponsor, FDA may determine that alternative study designs can yield appropriate data on which the Agency can make a determination of safety and effectiveness.Even with a well-planned design, the study may not yield the results expected or necessary to demonstrate safety and effectiveness. The sponsor may need to reassess its goals for the medical device and conduct additional studies to obtain evidence necessary to demonstrate safety and effectiveness. 3.3 Benefit-Risk AssessmentFDA considers a number of factors when making benefit-risk determinations during the pre-market review process. FDA considers the factors within the intended use of the device, including the target population.4Under Section 513(a) of the FD&C Act FDA determines whether PMA applications provide a “reasonable assurance of safety and effectiveness” by “weighing any probable benefit to health from the use of the device against any probable risk of injury or illness from such use,” among other relevant factors. 21 CFR 860.7(b)(3) states that, in determining the safety and effectiveness of a device, FDA must weigh “the probable benefit to health from the use of the device against any probable injury or illness from such use.” FDA relies on valid scientific evidence to determine whether there is reasonable assurance that the device is safe and effective. 21 CFR 860.7(c)(1). There is reasonable assurance that the device is safe when it can be determined, based on valid scientific evidence, that the probable benefits outweigh any probably risks. 21 CFR 860.7(d)(1). There is a reasonable assurance of effectiveness when it can be determined, based on valid scientific evidence, that the user of the device for its intended use will provide clinically significant results. 21 CFR 860.7(e)(1).There are a number of factors that FDA considers when weighing the probable benefits and risks of medical devices. The FDA has issued guidance explaining the factors FDA considers when making benefit-risk determinations during the premarket approval process in “Guidance for Industry and Food and Drug Administration Staff; Factors to Consider When Making Benefit-Risk Determinations in Medical Device Premarket Approval and De Novo Classifications” (2012).5 After a thorough review of the data, FDA’s evaluation of a device’s probable benefits and risks, along with other factors, is intended to ensure that there are reasonable assurances of safety and effectiveness. Factors that FDA takes into account when considering the extent of probable benefit(s) include:the type of benefit(s),the magnitude of the benefit(s),the probability of the patient experiencing one or more benefits, andthe duration of effect(s).Factors that FDA takes into account when considering the extent of probable risk(s) or harm(s) include:the severity, types, number, and rates of harmful events associated with the use of the device,the probability of a harmful event,the duration of harmful events, andthe risk from false-positive or false-negative results for diagnostic devices.These factors should be considered during clinical trial design and conduct to ensure that the appropriate information is collected in the study to make these benefit-risk determinations at the time of the marketing application. Manufacturers are encouraged to frame their clinical study protocol in a benefit-risk framework.3.4 Clinical Study Level of Evidence and RegulationThe regulations under 21 CFR Part 812 describe when approval of an IDE application is required prior to the initiation of the clinical study. A sponsor or sponsor’s IRB (with or without consultation to FDA) must first determine if the proposed investigation is of a device that is a significant risk device or a non-significant risk device, although ultimately FDA is the final arbiter in this determination. See 21 CFR 812.2(b). If the study is with a significant risk device, the sponsor must submit an IDE to FDA for approval prior to commencing the study. Id.If the study is with a non-significant risk device, the study is considered to have an approved IDE when the sponsor obtains IRB approval of the investigation after presenting the reviewing IRB with a brief explanation of why the device is not a significant risk device, and maintains such approval and compliance with the abbreviated IDE regulations under 812.2(b). Id. In these situations an IDE application to FDA is not required unless FDA has notified a sponsor under 812.20(a) that approval of an application is required. Id. In any case, the scientific rigor necessary for a clinical study and the robustness of evidence that need to be collected are not dependent on whether an IDE is required in order to initiate the study. Further, the rigor and robustness should not be influenced by the categorization of the clinical study as a study of a significant risk device, non-significant risk device, or device exempt from the IDE regulation. FDA encourages sponsors seeking guidance from FDA on the appropriate study design to support a potential pre-market submission to interact with FDA on key elements of a protocol through the Pre-Submission process in advance of finalizing the protocol. Even for studies that do not require IDE approval, FDA encourages submission of the draft protocol in a Pre-Submission to obtain FDA feedback prior to initiation of the study.3.5 The Least Burdensome Concept and Principles of Study DesignIn considering appropriate clinical study designs, FDA is also guided by the principle that the evidentiary burden must be commensurate with the appropriate regulatory and scientific requirements. This principle is reflected in two statutory provisions that apply to clinical and non-clinical data requirements for PMAs and 510(k) submissions. The following two provisions are referred to as the ‘least burdensome provisions.’ Section 513(a)(3)(D) of the Act provides, in relevant part, that:(ii) Any clinical data, including one or more well-controlled investigations, specified in writing by the Secretary for demonstrating a reasonable assurance of device effectiveness shall be specified as a result of a determination by the Secretary that such data are necessary to establish device effectiveness. The Secretary shall consider, in consultation with the applicant, the least burdensome appropriate means of evaluating device effectiveness that would have a reasonable likelihood of resulting in approval.(iii) For purposes of clause (ii), the term “necessary” means the minimum required information that would support a determination by the Secretary that an application provides reasonable assurance of the effectiveness of a device.(iv) Nothing in this subparagraph shall alter the criteria for evaluating an application for premarket approval of a device.Similarly, Section 513(i)(1)(D) the Act, provides:(i) Whenever the Secretary requests information to demonstrate that devices with differing technological characteristics are substantially equivalent, the Secretary shall only request information that is necessary to making substantial equivalence determinations. In making such a request, the Secretary shall consider the least burdensome means of demonstrating substantial equivalence and request information accordingly.(ii) For purposes of clause (i), the term “necessary” means the minimum required information that would support a determination of substantial equivalence between a new device and a predicate device.(iii) Nothing in this subparagraph shall alter the standard for determining substantial equivalence. The FDA has issued guidance explaining how it intends to apply the least burdensome provisions in “The Least Burdensome Provisions of the FDA Modernization Act of 1997: Concept and Principles; Final Guidance for FDA and Industry” (2002) (The Least Burdensome Guidance). The Least Burdensome Guidance interprets “least burdensome” to mean a successful means of addressing a pre-market issue that involves the most appropriate investment of time, effort, and resources on the part of industry and the FDA. The guidance specifies that the least burdensome provisions do not affect the statutory pre-market review standards for devices, a principle affirmed by amendments added to the least burdensome provisions by the Food and Drug Administration Safety and Innovation Act of 2012.6 The guidance specifies further that for purposes of clinical study design, the FDA and industry should consider alternatives to randomized, clinical studies when potential bias associated with alternative controls can be minimized. The principles of study design discussed in this guidance are consistent with the principles discussed in the Least Burdensome Guidance, and expand upon them by discussing the considerations that may affect the level of evidence necessary to meet the standard for pre-market approval or clearance. 3.6 Approval of an Investigational Device ExemptionThe principles discussed in this guidance are intended to assist sponsors of marketing applications and investigators in designing studies adequate to provide data to demonstrate a reasonable assurance of safety and effectiveness concerning a device. Following these principles and tailoring the design of a pivotal clinical study to the premarket review standard for devices may streamline the approval process by avoiding requests from FDA reviewers for additional information, re-analyses of data, or entirely new pivotal studies. However, FDA will not disapprove an IDE because the investigation is inadequate to support a marketing application. Section 520(g)(4)(C) of the FD&C Act, as amended by section 601 of FDASIA provides that FDA shall not disapprove an [IDE] because:the investigation may not support a substantial equivalence or de novo classification determination or approval of a device;the investigation may not meet a requirement, including a data requirement, relating to the approval or clearance of a device; oran additional or different investigation may be necessary to support clearance or approval of the device.Thus, approval of an IDE does not necessarily indicate that FDA believes the study is adequate to support approval of a marketing application.The focus of this guidance is on the set of principles of clinical study design that will help provide a reasonable assurance of safety and effectiveness for a device, rather than on requirements for approval of an IDE. 4 Types of Medical DevicesThis document applies to two broad categories of medical devices based on intended use: (1) therapeutic and aesthetic devices and (2) diagnostic devices. Whether a device is intended for use as a therapeutic, aesthetic or diagnostic device depends on the indications for use statement in a device’s label. These types of devices are described in this section, along with characteristics unique to each type of device that should be considered when designing a pivotal clinical study. This guidance does not cover every type of device in every setting. 4.1 Types of Devices Based on Intended UseTherapeutic and Aesthetic DevicesTherapeutic devices are generally intended for use in the treatment of a specific condition or disease. Aesthetic devices are intended to provide a desired change in visual appearance through physical modification of bodily structure.Diagnostic DevicesIn this guidance, diagnostic devices are described broadly as devices that provide results that are used alone or with other information to help a