a. Purpose of the Clinical Trial. This section describes broad study goals, as well as specific aims of the investigation. A background and rationale for conducting the study is generally helpful for the FDA to understand the broader purpose and determine risk/bene – fits of the investigation. The background information may include earlier studies conducted with similar devices and technologies, relevant clinical data from literature, and how it applies to the proposed investigation. It is also helpful to provide in this section an overview of the study design that clearly lays out how the study will be conducted and what procedures will be used to determine efficacy and safety.
b. Clinical Protocol. The clinical protocol should provide details on how the subjects will be screened; what the inclusion/exclusion criteria for the study are; at what point the subjects will be enrolled; what evaluations will be conducted before initiating the treatments (baseline evaluation); provide details of the treatments, including procedure, number of treatment visits, and duration of the treatment phase; details for the follow-up phase including, the duration of the follow-up period, number and frequency of visits should be provided.
The study protocol should also define the efficacy and safety measures. Depending on the type of study (research, pilot, or pivotal) the primary and secondary end-points may need to be prospectively defined, that is, what quantitative measure will determine whether the treatment has achieved an effective outcome? Details of the analytical procedures for any objective measures should be provided. The type of subjective measures, for example, subjective questionnaires administered to patients and their usefulness in assessing efficacy and safety should be discussed.
A statistical analysis plan for the data, justification for choosing the sample size, and the randomization scheme should be presented. The details of the statistical plan again will be determined by the development phase of the study. A pivotal study requires a detailed statistical plan, whereas the research-type studies that are primarily designed to gain initial learning that would help modify and set the device parameters may not require a detailed statistical plan.
Risk analysis: This section should clearly identify risk to the patients, and risk management. A detailed description of risks and anticipated adverse events (AEs) should be provided. The risks identified may be theoretically based on the device parameters, mechanism of action, and the known tissue interaction of the emitted energy, or the risks may be based on earlier investigations presented in literature or conducted internally. For example, potential risks for a laser device may include eye injury, pain and discomfort to subjects during treatments, and dermal effects such as erythema, edema, blistering, crusting, and pigmentary changes.
A risk-benefit analysis may be presented, especially if significant AEs are anticipated. For laser and IPL devices, laser parameters and any built-in device features that can affect safety should be described. Procedures for recording and reporting AEs and unanticipated adverse device effects (UADE) should be clearly defined.
c. Device Description. This section provides a detailed description of the device that will be used in treatments. For example, a laser device may consists of a base unit connected to the hand piece that may either directly come in contact with the skin, or may emit laser energy directed at the skin surface for treatment. There may also be a chiller unit that is part of the device components to keep the laser from overheating, or to cool the skin surface during treatments. The laser parameters, including the wavelength, power, pulse width, and frequency, beam-spot size, calculated energy density or fluence on skin should be described. If a secondary skin-cooling method is used, such as contact surface cooling with chilled sapphire tip, cold air spray, cooling gels, or other cooling methods at pre-, post-, and during treatments these should be listed as part of the device description. Additional information may include calibration methods, verification of key laser parameters at certain interval, and cleaning and sanitation procedures.
d. Monitoring Procedures. Sponsor should select qualified individuals to monitor the study. The person or the CRO contracted to monitor the study should be identified. The monitor should be familiar with the investigational device, the clinical protocol, and the informed consent document. It is the monitor’s responsibility to ensure that the investigation is conducted in accordance with the approved investigational plan, the investigator’s agreement, requirements under the IDE regulations, and any conditions imposed by the IRB or FDA. The monitor also ensures that the reported data are consistent with the recorded source document data and that the rights of the subjects are being protected as per informed consent.
e. Labeling.106 An investigational device must carry a label identifying it as such: “CAUTION—Investigational Device. Limited by law to investigational use.” The label or other labeling shall describe all relevant contraindications, hazards, adverse effects, interfering substances, warnings, and precautions such as “DANGER”; “LASER RADIATION”; “DIRECT EXPOSURE TO BEAM”. The label cannot represent that the device is safe or effective for the purposes for which it is being investigated.
f. Consent Material. Before initiating any clinical investigation, informed consent must be obtained. It is a process by which the subjects entering the study must voluntarily confirm their willingness to participate in a particular clinical study, after having been informed all aspects of the study relevant to the subject’s decision to participate. A typical consent of document provides information on the principal investigator, the investigational site, the purpose of the study, study details as to the procedures that will be performed before (baseline), during (treatment phase) and after (follow-up) light-based treatments, the time commitment and the number of visits for each phase, risks, and discomforts of the treatments, benefits and alternative treatments, maintenance of confidentiality, and remuneration for participation in the study. The clinical investigator or his or her designee describes the relevant study details to the patients. The informed consent is signed and dated and a copy provided to the subject.
g. IRB Information. The clinical protocol should provide information on the IRB that will be used to obtain approval of the study protocol and the informed consent documents.