This guidance is to assist with understanding different types of research that require different levels of review.
Human Research - Is IRB Review Required?
Is IRB Review Required?
The first question one should consider when assessing the requirement for IRB review is whether the activity meets the regulatory definitions (DHHS and FDA) of human research. Anyone unsure about IRB review requirements and whether their proposed activity constitutes “human research” requiring IRB review should review the Is IRB Review Required? Guidance and contact the IRB office with any follow up questions. NOTE: This guidance was updated in November 2021.
The IRB staff will determine if the activity is human research upon submission of the Human Subjects Research Determination form. Click here to download the Human Subjects Research Determination Form. If an activity does not meet the regulatory definition of human research, the IRB will, upon request, issue a letter stating that the project does not require IRB review or approval.
For further information please contact:
- Stephanie Lesage email@example.com
- Patrick Landis firstname.lastname@example.org
- Christy Hullings email@example.com
Research Collecting Blood Samples (Volume limits and guidance)
IRB Review procedures for research involving blood sampling require careful assessment of sample collection methods and volume of collection. This assessment will inform whether the IRB may review a study via expedited mechanism as Minimal Risk or if convened review is required due to greater than minimal risk. Please Click Here to download specific guidance.
For further information please contact:
- Stephanie Lesage firstname.lastname@example.org
- Patrick Landis email@example.com
- Christy Hullings firstname.lastname@example.org
Research with Device Products
What is a device?
A device might be an instrument, apparatus, implement, machine, contrivance, implant, in-vitro diagnostic, lab developed test, in vitro reagent, assay, software application, algorithm, or other similar or related article or component, part, or accessory.
Research involving the use of device products requires a number of considerations, including:
- What type of device is being used?
- How is the device used on the submitted protocol?
- Is it being used according to the definition of a medical device?
- If used as a medical device, is it the subject of the investigation?
- Is the device marketed? If yes, is it being used on label or being used in an investigational manner?
- If the device is under investigation, is the protocol subject to IDE regulations?
- If the protocol is subject to IDE regulations, the study requires an IDE. The IRB must make a risk determination related to the device’s use on the protocol.
Click here for a visual representation of these considerations.
What is the FDA definition of a medical device?
A medical device is:
- Recognized in the official National Formulary or the United States Pharmacopoeia; OR
- Intended for use in the diagnosis, cure, mitigation, treatment or prevention of disease or other conditions; OR
- Intended to affect the structure or function of the body
- Does not achieve its primary intended purposes through chemical action within or on the body AND is not dependent upon being metabolized for the achievement of any of its primary intended purposes.
Is the protocol subject to IDE regulations?
Please click here for a detailed guidance on the applicability of IDE regulations entitled, Exemption from IDE Regulations Guidance.
If the protocol is not exempt from IDE regulations, what is the risk of the use of the device on the protocol?
Non-Significant Risk Protocol: Use of the device on the protocol does not meet the definition of significant risk below.
Significant Risk Protocol: Use of an investigational device that presents a potential for serious risk* to the health, safety or welfare of a subject due to its intended use AND is used:
- As an implant OR
- For supporting or sustaining human life OR
- Of substantial importance in diagnosing, curing, mitigating, or treating disease or otherwise preventing impairment of human health OR
- Presents some other serious risk to patient’s health, safety, or welfare
How is serious risk defined?
*Serious risk referenced above is defined as: any risk associated with the device that may adversely affect the health or safety of a participant that:
- Is life-threatening, or cause death, or
- Causes hospitalization, disability or permanent damage, congenital anomaly/birth defect, or
- Requires a medical / surgical intervention to prevent permanent impairment or damage, or
- Is any other serious medical event that may adversely affect the safety or welfare of subjects.
Devices that may be considered to present serious risk could include but are not limited to:
- A novel device with no predicate (a predicate is a medical device that may be legally marketed in the U.S. and is used as a point of comparison for new medical devices)
- A device used for an indication not previously evaluated by the research team, the FDA, or peer review, without medical and or scientific rational justifying the safety of the device(s)
NOTE: Risk determinations are not definitive and may change, should unanticipated adverse device effects occur, or evidence suggests that the risk of the device is greater or lower than originally anticipated.
Unsure about risk of the device? Sponsors or sponsor-investigators can submit a Study Risk Determination Q Submission to the FDA.
- See the FDA Guidance: Requests for Feedback on Medical Device Submissions
- The only required documents consist of: Cover letter, device description, and protocol. A full IDE application is NOT required.
- FDA will determine whether the protocol qualifies for exemption and issue a determination letter. If the protocol is not exempt, FDA will provide a risk determination.
What is required by the IRB if my protocol is not exempt from IDE regulations?
- The Devices in Research form must be submitted along with your other submission materials that documents the device risk [non-significant risk (NSR) or significant risk (SR)] determination and the associated rationale for your determination. The staff may also ask for the submission of this form if an exemption determination needs to be made by the IRB. The form is available for download online here: https://irb.upenn.edu/forms.
- A standalone protocol. HSERA may not serve as the IRB protocol for these types of studies. The following template should be utilized: Protocol Template- Clinical Trial which is available for download online here: https://irb.upenn.edu/forms.
- A Device Investigational Plan. The following guidance explains the required parts of a Device Investigational Plan. - New as of 8/2020
Guidance on Requirements for Abbreviated IDE Holders from the PSOM Office of Clinical Research
For additional assistance, please contact: Jessica Yoos or the Penn Medicine Office of Clinical Research, Sponsor Support Unit.
Research with Drug Products
What is a drug product?
A drug product might be a drug, biologic, vaccine, cosmetic product, food, food additive, dietary supplement, or generally recognized as safe (GRAS) product.
What is the FDA definition of a drug?
- Intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animal; OR
- Intended to affect the structure or any function of the body of man or other animals (other than food); OR
- Recognized in the official US Pharmacopoeia, official Homoeopathic Pharmacopoeia of the United States, or official National Formulary
A drug product achieves its primary intended purposes through chemical action within or on the body AND is dependent upon being metabolized for the achievement of any of its primary intended purposes.
When is the use of a drug product considered to be an investigation?
Any use of a drug product, except use of a marketed drug in the course of standard medical practice is considered to be an experiment, according to FDA regulations. Likewise, any experiment in which a drug is administered or dispensed to, or used involving, one or more human subjects is considered by the FDA to be a "clinical investigation." Clinical investigations are considered to be subject to FDA regulations.
Is the protocol subject to IND regulations (i.e., is IND application to the FDA required?)
It must be assessed whether the clinical investigation meets the criteria for exemption from IND regulations.
- What is the type of product being used? There are different exemption criteria depending on the type of product (e.g., drug versus dietary supplement).
- Is the product approved by FDA or marketed in some way? (NOTE: Unapproved drugs are never exempt from IND regulations).
An unapproved product can be administered for treatment purposes under the FDA’s expanded access program, if certain criteria are met. For more information, please see: https://irb.upenn.edu/how-submit-penn-irb/expanded-access-and-humanitarian-use.
Investigators at Penn are not permitted to self-determine exemption from IND regulations. The following entities may determine whether a protocol is IND exempt:
- IRB: Submit the Research with Drugs form
- Penn Medicine Office of Clinical Research Sponsor Support Unit (SSU): Penn Medicine principal investigators only; all product types
- Penn Medicine Department of Radiology: Investigations using imaging agents (including Gadolinium)
- Penn Medicine RRSC: Investigations using Nuclear Medicine Agents (radiopharmaceuticals)
How do I submit an IND Application the FDA?
FDA Guidance: Sponsor-Investigator held Investigational New Drug (IND) Applications.
For further assistance: please visit the Office of Clinical Research for additional information.
Guidance for Student Researchers
The IRB has developed a brief guidance document for students conducting research. The IRB asks students to review this guidance and subsequently reach out to IRB staff with any follow up questions not addressed in the guidance. Student Guidance Manual: Submitting to the Penn IRB
- When should I start the IRB process?
- Step 1: Determining whether your study requires IRB review
- Step 2: Completing any required trainings
- Step 3: Drafting your IRB application & Associated Study Documents
- Step 4: Completing any revisions from your advisor and/or department chair
- Step 5: The Initial IRB Review Process
- Step 6: Completing any revisions required by the IRB
- Step 7: IRB review and approval of your responses
- Step 8 (if applicable): Obtaining other supplemental approvals
- Frequently Asked Questions
- Who to Contact?
Social Media Guidance
Government Funded Research
Studies that are funded by the following governmental departments have additional regulations for study teams and PI's to be aware of:
These checklists have been developed to assist research teams conducting research that is subject to these additional regulations.
Greater Than Minimal Risk Research which Excludes Pregnancy
The IRB has developed this document to assist researchers in addressing the many components that the IRB routinely looks for when pregnancy is an exclusion criteria in greater than minimal risk research. Before submitting for initial approval of a study that qualifies - research teams should review this document to ensure the protocol, HSERA application and informed consent forms include all of the appropriate information and plans that are needed in relation to:
- Providing an appropriate rationale for the exclusion
- Outlining the plan for pregnancy testing
- Describing contraception requirements
- Establishing a plan for an incidental pregnancy
Guidance for Using MTurk for Research Purposes
This guidance has been developed to ensure that the ethical principles of respect for persons, beneficence, and justice are being upheld for research involving MTurk Research participants.
What is MTurk?
Amazon Mechanical Turk (aka MTurk) is an online marketplace that matches “workers” with available work from various “requesters.” This work generally “requires human intelligence.” Many researchers have been utilizing MTurk to access a large heterogeneous population of participants for research studies. The MTurk site is designed for matching people with work and submitting payments to workers. It is not designed to facilitate the protection of human subjects in research studies.
Informed Consent Document/Language Guidance
- Clearly state what the task involves (e.g., writing, watching videos, survey, etc.)
- If there is any screening process to qualify for the study, please include this information in the consent language. This includes any “attention checks” within surveys.
Deception or Incomplete Disclosure (i.e. not stating the full study purpose or not including all the research elements/procedures so as to not bias participant responses)
- If deception or incomplete disclosure about any element of the research is occurring, the consent language must include statement informing the participant of the deception or incomplete disclosure.
- Debrief language should also be drafted that informs the participant about what was originally omitted, and this should be submitted to the IRB for review
Reasons for Failure or Rejection: Many MTurk workers take their rejection rates seriously. This rejection rate dictates what HITs they can take, which determines how much money the individual makes. This affects some participants’ livelihoods and they have no way to reverse rejections from their accounts.
- Given this, researchers should include a statement in the informed consent about instances in which participants may fail to qualify or might be rejected for a task (e.g., failed attention checks).
Confidentiality: Recent research shows that MTurk worker IDs can easily be linked to individuals Amazon profiles including individuals wish lists and previous product reviews. It is recommended that worker IDs not be collected unless out of necessity (e.g., to debrief participants). If there is any need to collect MTurk worker IDs:
- Ensure that the consent language describes this, the reason for their collection, and confidentiality measures in place (e.g., worker IDs will be deleted after being used and not linked to survey data)
Time Commitment: State the time required to complete the task(s)
- Please clearly detail the amount of compensation, and if applicable, any bonuses. Please consider that certain higher order tasks, such as writing, elicit higher compensation. In essence, the compensation should be commensurate to the complexity of the task.
- If there is a screening process, state whether participants will be compensated for the time it takes to complete this.
- Please provide an estimate of how long it will take for the researcher to approve their HIT (i.e. – how long it takes for the participant to receive payment).
Contact Information: Include the full name of the researcher, the researcher’s email or phone number, and the Penn IRB’s contact information.
HSERA Application Guidance
Research Design: The HSERA application should detail the full research design of the project including:
- Any incomplete disclosures or deception being utilized
- Any plans for screening or “attention checks” that may cause a worker to be rejected. Potential financial Risks to the participant due to rejection should be considered when applicable, including any plans to minimize this.
Confidentiality: If there is any need to collect MTurk worker IDs:
- Ensure that HSERA describes the collection MTurk worker IDs, the reason for their collection (e.g., debriefing), and confidentiality measures in place
- It is recommended that worker IDs be deleted after being used and not be linked to survey data, especially if the data collected is sensitive in any way.
HIT Description Guidance
- The researchers name and Penn affiliation should be listed in the Requester information or in the description of the HIT.
- Please ensure that the first page of an online survey includes the consent language.
- If there is debriefing language, it should be included at the end of the survey.
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