GCP of Devices
When an investigational device is given to or used with a subject, a record of the use of the device is provided to the sponsor by recording the use on the
Case report form (CRF)
Investigational Device Exemptions [IDE] (21 CFR 812)
Covers the procedures for the conduct of clinical studies with medical devices, including application, responsibilities of sponsors and investigators, labeling, records, and reports
Regular team meetings where all study team members have contact with principle investigator to review study progress is an example of
GCP
At which study visits can the site expect the sponsor to review subjects' signed informed consent forms?
Periodic and termination site visits
IRB Correspondence
Records communications between the investigator and the IRB to assure that regulatory requirements are met and that the subject's welfare and rights are protected
Investigator Agreement
Records that regulatory obligations are communicated and documented
Monitoring
the act of overseeing the progress of a clinical trial, and of ensuring that it is conducted, recorded, and reported in accordance with the protocol, standard operating procedures (SOPs), Good Clinical Practice (GCP), and the applicable regulatory requirement(s)
Class III Devices
the highest risk devices. General controls and special controls alone are not adequate to ensure their safety and effectiveness. These devices therefore require a stringent premarket approval application (PMA) to be filed before they can be sold in the U.S. They generally are devices that: Support or sustain life Are of substantial importance in preventing impairment of health Present a potential, unreasonable risk of injury or illness
Class I Devices
the lowest risk devices and are governed by general controls such as Establishment Registration, Device Listing, Compliance with Good Manufacturing Practice (GMP) regulation, labeling, and Medical Device Reporting (MDR) of death or serious injuries. Examples of Class I devices are surgical gloves and tongue depressors
Which of the following statements in a consent form is an example of language that appears to waive a subject's rights?
You must provide blood samples that will be kept in a "bank" for future research. Once you have provided these blood samples, you give up your rights to benefit from commercial development
Humanitarian Use Device (HUD)
a device that is intended to benefit patients in the treatment or diagnosis of a disease or condition affecting not more than 8,000 individuals in the U.S. per year.
Regulation
a law or code issued by an executive authority or regulatory agency of a government. Regulations have the force of law.
Investigators are required to report UADEs to the sponsor and the reviewing IRB within how many working days?
10 Working days
510(k) Clearance
A 510(k) clearance or premarket notification [(510(k)] submission is a route the FDA uses to approve a medical device. If the FDA agrees the new device is substantially equivalent to a legally marketed device for which a premarket approval (PMA) is not required, the manufacturer may market it immediately.
Which of the following informed consent statements is required for medical device studies conducted outside the U.S. (under ISO 14155:2011), but is not required for studies conducted in the U.S.?
A statement indicating that, upon subject's approval, the subject's personal physician will be informed of the subject's participation in the study shall be included
Protocol/CIP Amendments
All amendments to the protocol/CIP are available for review and to measure compliance with implementation and IRB approvals
Protocol/Clinical Investigation Plan (CIP)
All versions of the study protocol/CIP are present to assure the site used appropriate version(s) while conducting the trial
FDA approval of a Humanitarian Device Exemption (HDE) is based on all of the following criteria EXCEPT
Assurance of safety and effectiveness
The FDA requires retention of records related to a clinical trial of an investigational device for
At least two years after the investigational device's clearance/approval by the FDA or two years after the FDA is notified of the study termination
A cardiopulmonary bypass pump (used to pump blood during cardiac surgery) would be considered
Class III medical device
Dr. Smith is participating in a clinical trial of an investigational implanted device for epilepsy. He has a subject with intractable seizures who has not responded to approved therapy. He wants to enroll the subject in the clinical trial but notes that the subject does not meet inclusion criteria because she has undergone several excluded treatments. Which answer describes the best way for Dr. Smith to provide the device to the subject
Contact the device manufacturer to discuss the possibility of obtaining a treatment IDE for the subject
HUD Use
The FDA uses the term "use" to refer to the clinical use of a HUD according to its approved labeling and indications to treat or diagnose patients.
Which of the following statements is true regarding IRB approval of clinical use of a HUD in a healthcare facility?
The clinician obtains initial IRB approval and ensures continuing review approval by the IRB
Sponsor
The entity that takes responsibility for and initiates a clinical investigation. The sponsor can be any legal entity, including a company, an academic organization, or an individual. Note: the sponsor is often but not always the entity that funds the clinical research
The investigator's financial interests with the device manufacturer (sponsor) or to the outcome of the clinical investigation is reported directly to the U.S. FDA by
The sponsor
Who is responsible for making the initial risk determination for a device being used in a study?
The sponsor-investigator
The U.S. FDA regulations require that
The subject (or the subject's LAR) must receive a copy of the informed consent form
Investigators are required to report unanticipated adverse device effects (UADE)
To the FDA within ten working days
Informed Consent Form (ICF)
Verifies that all versions of the ICF used to enroll subjects indicate the effective dates, necessary elements of informed consent were included, and the approved versions of the form were appropriately used
Institutional Review Board (IRB)
defined by FDA at 21 CFR 56.102(g) (Institutional Review Boards 2019) as "any board, committee, or other group formally designated by an institution to review, to approve the initiation of, and to conduct periodic review of, biomedical research involving human subjects. The primary purpose of such review is to assure the protection of the rights and welfare of the human subjects."
Institutional Review Boards (21 CFR 56)
Covers the procedures and responsibilities for IRBs that approve clinical investigational protocols
Medical Device Reporting (21 CFR 803)
Covers reporting of adverse events (AEs) for approved medical devices (and HUDs)
Financial Disclosure by Clinical Investigators (21 CFR 54)
Covers the disclosure of possible financial conflicts of interest by clinical investigators
Premarket Approval of Devices (21 CFR 814)
Covers the procedure for obtaining approval to market certain devices and HDEs
Premarket Notification Procedures (21 CFR 807, Subpart E)
Covers the procedure for obtaining clearance to market certain devices
Design Controls of the Quality System Regulation (21 CFR 820, Subpart C)
Details requirements to ensure that specified design requirements are met
Which of the following is an example of how the principle of beneficence can be applied to a study employing human subjects?
Determining that the study has maximized potential benefits and minimized potential risks of harm to subjects
Which of the following is an important component of device accountability?
Device shipping and disposition records
Significant Risk
Device studies that are those that involve a SR device. Examples of SR devices include: sutures, cardiac pacemakers, hydrocephalus shunts, and orthopedic implants.
Nonsignificant Risk (NSR)
Device studies that involve a device that does not pose a significant risk to subjects. Examples of NSR devices include: most daily-wear contact lenses and lens solutions, ultrasonic dental scalers, and temporary urinary catheters.
Non-significant Risk (NSR) Device
Device that does not pose a significant risk of harm to subjects. Examples include most daily-wear contact lenses and lens solutions, ultrasonic dental scalers, and temporary urinary catheters
Significant Risk (SR) Device
Device that poses a significant risk of harm to the health, welfare, or safety of the subject. These include devices that are implanted, devices that support or sustain human life, and devices that are very important in diagnosing, curing, mitigating, or treating disease or preventing impairment to human health (21 CFR 812.3). Examples include sutures, cardiac pacemakers, hydrocephalus shunts, and orthopedic implants.
A 46-year-old man is currently enrolled in a study of a device used to control lower extremity edema through the use of alternating pressure on the legs. The FDA recently approved a device after determining that it is safe and effective for lower extremity edema. In fact, the data show that this new approved device is the most effective for treating this condition. The investigator should do which of the following?
Discuss the new information with the subject including pros and cons of both the investigational device and the commercially available device, then allow the subject to decide whether to withdraw from the research so he can use the new device
When must the investigator update the IRB about the progress of a trial?
During the conduct of the study and at termination
The overall goal of monitoring, audits, and inspection activities is to
Ensure the protection of human research subjects, compliance, and data integrity
The three main objectives of the pre-study visits are: (1) determine the investigator's interest in conducting the study; (2) determine whether the investigator will be able to meet the recruitment goals; and
Evaluate the facility and the staff to determine whether they have the capacity to successfully conduct the trial
All of the following regulatory requirements apply to an investigation of a HUD consistent with the HDE approved indication(s), EXCEPT
Investigational Device Exemption requirements
Humanitarian Use Device (HUD) Investigational Use
FDA uses this term to refer to a clinical investigation designed to collect safety and effectiveness data
Which of the following is not a common deficiency noted during FDA inspections
Failure to maintain a subject recruitment log
Best practices for social and behavioral research based on Good Clinical Practice (GCP) include which item below?
Guidance for informed consent procedures
Ms. Reynolds was admitted to the hospital with a heart attack. She undergoes an emergency cardiac catheterization, and the cardiologist determines that she needs a cardiac stent placed immediately. However, the artery requiring the stent is very small and tortuous, and the only available suitable stent is labeled "investigational." The cardiologist decides that Ms. Reynolds is in a life-threatening situation due to her evolving myocardial infarction and use of the investigational stent offers Ms. Reynolds the best chance for surviving the event without further damage to her heart. Ms. Reynolds is sedated and she came to the hospital alone. The cardiologist successfully uses the investigational stent to treat Ms. Reynolds' cardiac artery. What should the cardiologist do?
He must report to the sponsor and the IRB within five (5) working days that he used the investigational stent without first obtaining informed consent
An investigation to collect data on a new indication of a significant risk HUD requires
IRB approval and an Investigational Device Exemption (IDE)
A clinician may use a HUD without IRB approval
If the clinician determines that approval from an IRB cannot be obtained in time to prevent serious harm or death to a patient
Unless the IRB or privacy board waives the requirement, HIPAA requires the patient's authorization for the use and disclosure of protected health information (PHI)
If the use or disclosure of PHI is for the purpose of a clinical investigation with a HUD
Where is information on storage requirements for the investigational product usually found?
In the study protocol/CIP
Which of the following best describes the three elements of informed consent according to the Belmont Report's principles?
Information, comprehension, voluntariness
Who has ultimate responsibility for an investigational device at the site?
Investigator
For studies conducted outside of the U.S., the device risk analysis and assessment are described in the
Investigator's Brochure (IB)
Dr. Smith decides he will no longer participate in ABC Company's clinical trial. Two (2) subjects were enrolled at his site but all follow-up is complete and subjects are no longer coming to his site for study-related visits. The main consideration for Dr. Smith is
Maintaining clinical trial records for two years after the device is granted marketing approval or for at least two years after the study is terminated and the FDA is notified
Dr. Jones is participating in a clinical trial sponsored by ABBA Device Company. Dr. Smith submitted the required documents for IRB approval and the IRB required significant changes to the consent document. Dr. Smith should
Notify the sponsor of the IRB's requirements before using the revised consent document
During continuing review of a clinical trial, the reviewing IRB for Dr. Smith terminated approval of the study after determining that the risks of conducting the study outweighed potential benefits. Dr. Smith is required to:
Notify the sponsor of the IRB's termination of approval of the clinical trial
The two-step process of obtaining an FDA marketing approval for a HUD includes
Obtaining a HUD designation then submitting a Humanitarian Device Exemption (HDE) to the FDA
According to both U.S. regulations and international standards, the sponsor is required to do what?
Only ship the investigational device to qualified investigators participating in the investigation
Which of the following best describes when the majority of case report form (CRF) data are verified against source record information?
Periodic site visits
Which monitoring visit would not include an inventory of investigational devices?
Pre-study site visit
Manufacturers can show that a device to be marketed is substantially equivalent to a marketed product that was on the market prior to 28 May 1976, by submitting a
Premarket Notification
OHRP is an oversight body primarily concerned with
Protection of human research subjects
Investigator Curriculum Vitae (CV)
Provides evidence of the investigator's qualifications to conduct the study. CVs of subinvestigators and other staff may also be required
IRB Membership List/Roster
Provides information on the IRB members to assess compliance with 21 CFR 56
Protection of Human Subjects (21 CFR 50)
Provides the requirements and general elements of informed consent
Subject 417 is a subject in a study of an implantable device that is programmed to deliver narcotic pain medication to his lumbar spine. Subject 417's wife calls the research site and reports that subject has become increasingly lethargic. She brings him in for evaluation and the research nurse discovers that the pump was not programmed correctly and was delivering ten times the expected dose of narcotic. The nurse reprograms the pump and immediately reports the error to the investigator. After taking care of the medical needs of the subject, the investigator must:
Report this event to the IRB as an unanticipated problem involving risks to subjects or others and to the sponsor as a protocol violation
At visit 3, Subject 411, a subject in a clinical trial of a pacemaker with an implantable cardioverter-defibrillator (ICD) was noted to have a malfunctioning of the ICD sensing system resulting in frequent ICD discharges (shocks). Subject 411 was admitted to the hospital to have the ICD removed and replaced. The investigator should
Report this event to the sponsor and the IRB within ten working days as an UADE
Which of the following lists the three principles included in the Belmont Report?
Respect for persons, beneficence, justice
If the FDA investigator issues a Form FDA 483 after an inspection, the clinical investigator should
Respond in writing to the FDA within 15 business days
When the FDA conducts an inspection, the investigators will
Review regulatory records
An IRB determines that a clinical trial of an investigational device is a non-significant risk trial. Which of the following best describes a distinguishing characteristic of a non-significant risk trial?
Sponsor can initiate the study at the organization without first submitting an IDE to the FDA
Clinicians using a HUD to treat or diagnose patients are responsible for
Submitting medical device reports to the HDE holder
Humanitarian Device Exemption (HDE) Holder
The HDE Holder is the entity that obtains the approval of a HDE from the FDA and may be a manufacturer, sponsor, firm, or an individual.
An investigator, with the concurrence of another physician, believes that a subject must receive an experimental heart valve to save the patient's life. They have determined that no other alternative exists that will provide an equal or better chance of saving the subject's life. The subject is unconscious and there is no LAR available. FDA regulations at 21 CFR 50.23 and 50.24 provide exceptions to the requirement for informed consent. What other conditions must be met?
There is insufficient time to obtain consent and the IRB is informed of the use of the investigational product without informed consent within five (5) working days of the event
In the U.S., investigators must report unanticipated adverse device effects (UADEs)
To the sponsor and the IRB within ten days after becoming aware of the event
Dr. Jones is participating in a study of an investigational extended wear contact lens. He notes that Subject 316 has developed significant redness and severe pain in her left eye. The protocol requires subjects to wear the lenses for seventy-two (72) hours without removing them. Dr. Jones instructs Subject 316 to remove the lens from her left eye. Dr. Jones should initially report this event:
To the sponsor and the reviewing IRB within five (5) working days
Dr. Henry is participating in a clinical trial of an investigational device. Dr. Henry delegated device accountability to the clinical research coordinator and trained the coordinator on the records that must be maintained. A new shipment of devices arrives at Dr. Henry's site in the morning and a nurse from the organization's operating room contacts Dr. Henry's site and tells the nurse that a device is needed in the operating room for a surgery planned that afternoon. Neither Dr. Henry nor the coordinator is at the site. The nurse should
Try to contact the research coordinator and Dr. Henry so the shipment of devices can be opened, the accountability log can be completed, and the devices can be properly dispensed
A sponsor-investigator in the U.S. wants to assess the safety and effectiveness of a new device that can help control patients' appetite. The device is implanted in the chest during an outpatient procedure and has wires that stimulate a nerve to decrease the feeling of hunger. The sponsor-investigator assessed the device as significant risk. Does the device need an IDE?
Yes, the device does need an IDE because the device is assessed by the sponsor-investigator as significant risk
Blinded Trial
a trial divided into more than one experimental group where subjects are not told which group they are assigned. For example, subjects in one group might receive Device A and subjects in another group might receive Device B, and none of the subjects are told which of the devices they have received
Randomized Trial
a trial in which subjects are randomly (by chance) assigned to one of two or more arms of a clinical trial. Occasionally placebos (or "sham" controls and procedures) are utilized, but this is obviously more difficult in device trials than in drug trials
Humanitarian Device Exemption (HDE)
an application that is similar to a premarket approval (PMA) application, but for which the manufacturer does not need to provide evidence of efficacy. HDEs are subject to restrictions on profitability and can only be used in a facility after an IRB has approved their use in that facility, except in certain emergencies.
Investigator
an individual who actually conducts a clinical investigation, i.e., under whose immediate direction the test article is administered or dispensed to, or used involving, a subject, or, in the event of an investigation conducted by a team of individuals, is the responsible leader of that team
Sponsor-Investigator
an individual who both initiates and conducts the clinical investigation and under whose immediate direction the investigational device is being administered, used, or dispensed. The sponsor-investigator assumes all of the responsibilities of the sponsor as well as all the responsibilities of an investigator as outlined in the regulations
Device
an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including a component part or accessory, which is: recognized in the official National Formulary, the United States Pharmacopoeia, or any supplement to them, intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease in humans or other animals, or intended to affect the structure or any function of the body of humans or other animals and which does not achieve any of its primary intended purposes through chemical action within or on the body of man or other animals and is not dependent upon being metabolized for the achievement of any of its primary intended purposes. The term 'device' does not include software functions excluded pursuant to section 360j(o) of this title
Contract Research Organization (CRO)
an organization that provides support to sponsors of clinical trials that choose to outsource some or all of its services on a contract-basis. Sponsors can delegate all or part of the sponsor's trial duties to the CRO
Unanticipated Adverse Device Effect (UADE)
any serious adverse effect on health or safety or any life-threatening problem or death caused by, or associated with, a device if that effect, problem, or death was not previously identified in nature, severity, or degree of incidence in the investigational plan or application (including a supplementary plan or application), or any other unanticipated serious problem associated with a device that relates to the rights, safety, or welfare of subjects
Premarket Approval (PMA)
any type of premarket approval application used to obtain FDA approval of certain types of medical devices. It is the most stringent application for medical devices. The FDA approves a PMA if it determines that the application contains sufficient valid scientific evidence to provide reasonable assurance that the device is safe and effective for its intended use(s).
Medical Device
dentified as any instrument, apparatus, implement, machine, appliance, implant, software, material, or other similar or related article:Intended by the manufacturer to be used, alone or in combination, for human beings for one or more of the specific purpose(s) of:Diagnosis, prevention, monitoring, treatment, or alleviation of disease;Diagnosis, monitoring, treatment, alleviation of, or compensation for, an injury;Investigation, replacement, modification, or support of the anatomy or of a physiological process;Supporting or sustaining life;Control of conception;Disinfection of medical devices; andWhich does not achieve its primary intended action in or on the human body by pharmacological, immunological, or metabolic means, but which may be assisted in its intended function by such means (ISO 14155:2011)
Study-oriented Inspections
directed toward review of study data supporting a pending marketing application, such as PMAs. Although the primary objective of this type of inspection is to verify data submitted to the FDA, all other study-related practices are also audited, such as protection of human research subjects and compliance with regulations. The FDA typically inspects the top enrolling sites and randomly picks ten percent of the remaining sites for inspection.
Investigator-Oriented Inspections
focused on the specific clinical investigator conducting the trial. Typically, this occurs when there are complaints of known or suspected misconduct (such as fraud, falsification, or data fabrication)
Investigator
individual who actually conducts a clinical investigation (that is, under whose immediate direction the test article is administered or dispensed to, or used involving, a subject, or, in the event of an investigation conducted by a team of individuals, is the responsible leader of that team)
Class II Devices
moderate risk devices and are subject to both general controls and special controls such as specific FDA performance standards, post-market surveillance, or special control guidance to ensure their safety and effectiveness. Examples of Class II devices are flexible laryngoscopes and surgical drills
Double-Blind Study
neither the investigators nor the subjects know which intervention the subjects are receiving until the trial is complete. This study design is meant to reduce bias and the potential for factors not related to the intervention to influence the study results (NCI 2019)
Investigational Device Exemption (IDE)
refers to the regulations under 21 CFR 812 that apply to clinical investigations. An approved IDE means that the IRB (and FDA for significant risk [SR] devices) has approved the sponsor's study application as meeting the requirements under 21 CFR 812 (Investigational Device Exemptions 2014).
