UConn Health’s HSPP Reaccreditation from the

Association for Accreditation of Human Research Protection Program (AAHRPP)

 

On March 27-28, 2024, UConn Health Human Subjects Protection Program (HSPP) underwent a Site Visit evaluation as part of the process of reaccreditation by the Association for Accreditation of Human Research Protection Programs (AAHRPP).  After the HSPP responds to the Site Visit report the application will be reviewed by the AAHRPP Council in June 2024.  This process required team work from many stakeholders. The Director of the Human Subjects Protection Program and the Associate Vice President for Research Integrity & Compliance extend their gratitude to the faculty, staff, IRB members and members of the Scientific Review and Conflicts of Interest Committees, Office of Clinical and Translational Research Services, Sponsored Program Services, Research Pharmacy and Research Safety, and many others who committed their time to the Site Visit and who ensure that we have an outstanding human subjects program every day.

 

 

FDA Regulated Research

Overview of Human Subjects Research with Devices

 

The U.S. Food and Drug Administration (FDA) regulates drugs, biologics, and devices used in the diagnosis, mitigation, treatment, or prevention of diseases.

 Investigators who will be conducting clinical investigations in which the purpose of the study is to obtain data about a medical device (e.g., data on its safety and effectiveness), should become familiar with the information provided below to determine whether: (a) the device is exempt from an investigational device application (IDE), (b) the device fulfills the requirements for an abbreviated IDE, or (c) the device needs an IDE issued by the FDA.

Investigators should only think about these determinations when research participants of a clinical investigation will become part of the group in which a medical device will be used or part of the control group, and the device is the object of the investigation/research study.

Unless the sponsor of the device has made the determination that the device is exempt from the requirements of Part 812.2 (c), the study may be conducted under an abbreviated IDE or the investigator must submit an IDE application to FDA. See Table 1 below.

An investigational device exemption (IDE) is a regulatory status granted by the FDA that allows researchers to conduct clinical investigations on medical devices that have not yet received FDA approval. However, not all device studies are required to submit an IDE application to the FDA.  If a device is determined to be a non-significant device (NSR) in concurrence with the IRB, then an IDE is not necessary.

An IRB may determine that a device is a non-significant device because it does not meet the definition for a significant risk device (SR) (see definition of SR below) and does not present a potential for serious risk to the health, safety, or welfare of participants.

The sections below explains when and how an investigator makes a determination that a device could be used in a clinical investigation under an abbreviated IDE or under an Investigational Device Exemption (IDE).

Abbreviated Investigational Device Exemption

The sponsor makes the initial determination of SR or NSR for the device. However, it is important to note the IRB will make the final determination for NSR devices. If the research study is investigator initiated, then the investigator is also acting as the sponsor.

NSR device studies may not require submission to the FDA providing they comply with the abbreviated requirements of the regulations described in the IRB Policy 2011-021.0.pdf – Investigational Device Studies 

The FDA considers an investigation of a non-significant risk device to have an approved IDE (Abbreviated Investigational Device Exemption) when an IRB concurs with the initial non-significant risk determination of the sponsor or investigator and approves the study. See Table 1 below.

 

Investigational Device Exemption (IDE)

If either the investigator or the IRB has made a determination that the device is a significant risk device an IDE application is to be submitted to the FDA.

To obtain an IDE approval by the FDA, the sponsor or manufacturer of the device must properly fill out an IDE application. This application should be submitted proposing a human clinical researcher to study an unapproved significant risk device or a cleared or approved device for use other than its approved indication or intent.

The application should provide information about the investigational device, including its design, manufacturing process, and intended use. A clinical investigational protocol that outlines study objectives, methodology, patient population, and end points should also be included.  In addition, the sponsor must demonstrate in the application that there is reason to believe that the risks to human subjects from the proposed investigation are outweighed by the anticipated benefits to subjects, the importance of the knowledge to be gained, that the investigation is scientifically sound, and that there is reason to believe that the device as proposed for use will be effective.

An IDE application can be considered approved 30 days after it has been reviewed by the FDA, unless otherwise indicated. The FDA may inform the sponsor of approval, approval with conditions, or disapproval prior to 30 calendar days from the date of receipt.

Once FDA approval is granted, and the IRB has approved the study the sponsor and/or investigator may proceed with the clinical investigation. See Table 1 below.

The FDA grants permission so a device that otherwise would be required to comply with a performance standard or to have premarket approval can be shipped lawfully for the purpose of conducting investigations of that device. This FDA permission is evidenced by the assignment of an IDE number.

Additional Points to Consider About Research Studies with Medical Devices

• Studies of SR Devices require review of the convened IRB.
• NSR device studies generally will require full board review but may be approved through the expedited review procedure if the study falls within a designated approvable category and is minimal risk.
• IRB approval must be obtained before any clinical investigation can begin, and for studies with a SR Device, both FDA and IRB approval must be obtained before any subject can be enrolled.

 

Definitions-

 Clinical investigation means any experiment that involves a test article and one or more human subjects and that either is subject to requirements for prior submission to the Food and Drug Administration under section 505(i) or 520(g) of the act, or is not subject to requirements for prior submission to the Food and Drug Administration under these sections of the act, but the results of which are intended to be submitted later to, or held for inspection by, the Food and Drug Administration as part of an application for a research or marketing permit. The term does not include experiments that are subject to the provisions of part 58 of this chapter, regarding nonclinical laboratory studies.

Significant Risk (SR) Device: A device that presents a potential for serious risk to the health, safety, or welfare of a subject and 1) is intended as an implant, or 2) is used in supporting or sustaining human life, or 3) is of substantial importance in diagnosing, curing, mitigating or treating a disease, or otherwise prevents impairment of human health, or 4) otherwise presents a potential for serious risk to the health, safety, or welfare of a subject.          

 

     Table 1

	Categories of Research Studies with Medical Devices
	IDE Exempt	Non-Significant Risk (NSR)	Significant Risk (SR)
Risk	Lowest Level of  Risk	Low Risk	High risk
FDA Approval	Exempt from 21 CFR Part 812	Must comply with an Abbreviated Investigational Device Exemption in 21 CFR Part 812.2 (b)	Must follow ALL IDE Regulations in 21 CFR Part 812-Investigational Device Exemption (IDE) Application
IRB Review Approval	YES	YES	YES

 

Resources for investigators:
ReGARDD – Regulatory Guidance for Academic Research of Drugs and Devices

Device Advice: Comprehensive Regulatory Assistance | FDA

 

UConn Health IRB Forms and Polices Revisions

&

Educational Resources

 

 

The following forms have been updated:

• Instructions for Requesting Reliance Upon Advarra IRB.docx(2/13/2024, updated contacts at Advarra and consent template injury language section)
• Request for UConn Health as a Recruitment Site -Without Engagement(*new form as of 3/20/24)

 

The following policy has been updated:

• 2011-008.2.pdf– Informed Consent – Waivers and Alterations (1/22/2024) (including the FDA final rule that allows IRBs to approve an informed consent procedure that does not include or that alters certain informed consent elements, or to waive the requirement to obtain informed consent, for certain minimal risk clinical investigations).

The following links were added to the IRB website under online resources for investigators:

• Regulatory Guidance for Academic Research of Drug and Devices 
• Is my Device Study Exempt from Investigational Device Exemption (IDE) Regulations?

 

 

Upcoming Changes in at the HSPP/IRB

 

Education & Development Specialist of HSPP:  As of 4/5/2024, Mayra Cagganello has transferred to a new position within UConn Health.  Mayra has worked for the HSPP for almost 13 years and her dedication and support to the HSPP and research community will be missed!

Investigators who need education, guidance on IRB submission and/or training with the IRIS submission system should contact the IRB at irb@uchc.edu

We wish Mayra the best in her new role!

 

 

 Bibliography

 2011-007.0.pdf – Definitions Applied to Policies

2011-021.0.pdf – Investigational Device Studies

Frequently Asked Questions about Medical Devices

OCTOBER, NOVEMBER, DECEMBER, 2023 – HSPP NEWSLETTER

 

The HIPAA Privacy Rule & Human Subjects Research – Overview

 

The HIPAA Privacy Rule (the “Privacy Rule”) may impose additional requirements to the federal human subjects protection regulations applied to all human subjects research.

 The purpose of this overview is to clarify concepts and apply them to commonly seen human subjects research activities/studies. Specifically, the sections below highlight some of the main provisions of the Privacy Rule as they relate to human subjects research.

A series of questions and answers explain the scope of the Privacy Rule, the difference between an Authorization, a Waiver of HIPAA Authorization and an Alteration of HIPAA Authorization.  In addition, several sections explain how to address the Privacy Rule in recruitment activities, and when using specimens for research studies.  Examples of research activities and the appropriate HIPAA forms are included in some of those sections.

 

Section A- Questions related to the Privacy Rule and Human Subjects Research

 

The Privacy Rule regulates the way certain organizations called covered entities under the Rule handle protected health information (PHI). Since UConn Health is a covered entity, investigators conducting research with UConn Health PHI need to address HIPAA.

 

Question: How do I know if I need to address the Privacy Rule in my research study?

Answer: The Privacy Rule affects research and researchers when either:

Research creates or generates PHI, or research requires access to and/or use of PHI.

If your study involves the use of PHI you must address the Privacy Rule within your application for approval. PHI means individually identifiable health information transmitted or maintained in any form (electronic means, on paper, or through oral communication) that relates to the past, present or future physical or mental health or condition of an individual. Health information is not considered PHI if it has been de-identified in accordance with the Privacy Rule (i.e., by expert analysis or by removing all identifiers specified in the Privacy Rule of the individual or of relatives, employers, or household members of the individual).

Examples of research studies for which the HIPAA regulations apply are:

• Studies using individually identifiable health information that is generated as part of a health care service.
• Studies gathering individually identifiable health information that is entered into a medical record.
• Studies gathering individually identifiable health information that is used to make treatment decisions.
• Retrospective or Prospective research studies involving the review of medical records.
• Research studies involving surveys, questionnaires or focus groups, which obtain PHI from patients receiving treatment.

 

 Question: When does the Privacy Rule not apply to research?

Answer: Research studies that do not use, disclose or create PHI are not subject to HIPAA regulations.

Examples of studies that are not subject to HIPAA:

• Studies that use tests that do not go into the medical record because they are part of a basic research study and the results will not be disclosed to the subject.
• Studies that review de-identified health information.
• Studies that obtain data from records open to the public.

• Interviews, focus groups, and surveys studies that collect information that is not considered health information (e.g., opinions, beliefs, wants/preferences, etc.)

 

 Question: What is the difference between HIPAA “Authorization” and Informed Consent?

Answer: An informed consent is the individual’s volunteer permission to participate in the research. The requirement to obtain the legally effective informed consent of individuals before involving them in research is one of the central protections provided for under the HHS regulations at 45 CFR part 46 ( AKA as the Common Rule).  The Common Rule’s focus is in protecting the safety of the individuals, their privacy, and confidentiality. To do so, the investigators need to include in the consent forms the applicable elements /information described in the Main Consent Form Checklist.doc .

The Privacy Rule, a different regulation, focuses on protecting the privacy and security of PHI. The Privacy Rule generally requires subjects to give written Authorization before a covered entity may use or disclose patients’ PHI for research. A signed HIPAA Authorization represents an individual’s agreement to the use and disclosure of the individual’s PHI for the specified research purpose.

An authorization must contain several required elements and statements, including but not limited to a description of the PHI to be used and disclosed, the person authorized to make the use or disclosure, the  researcher may make the disclosure, an expiration date, and, in some cases, the purpose for which the information may be used or disclosed.

 

Section B- Questions related to Waiver of HIPAA Authorization and Alteration of HIPAA Authorization

  

The IRB may approve a HIPAA authorization process which does not include, or which alters some or all of the elements of a valid written authorization, or waives the requirement for written HIPAA authorization if the IRB finds and documents that the use of the subjects’ PHI meets the criteria for a waiver.

In granting an alteration or waiver of HIPAA authorization, the IRB must determine that the alteration or waiver, in whole or in part satisfies each of the following criteria:

• The use or disclosure of PHI involves no more than minimal risk to the privacy of individuals, based on, at least, the presence of the following elements:
• an adequate plan to protect the identifiers from improper use and disclosure;
• an adequate plan to destroy the identifiers at the earliest opportunity consistent with the conduct of the research, unless there is a health or research justification for retaining the identifiers or such retention is otherwise required by law; and
• adequate written assurances that the PHI will not be reused or disclosed to any other person or entity, except as required by law, for authorized oversight of the research study, or for other research for which the use or disclosure of PHI would be permitted (i.e., under the HIPAA regulations).
• The research could not practicably be conducted without the waiver or alteration; and
• The research could not practicably be conducted without access to or use of the PHI.

 

  Question: What is the difference between a partial and complete Waiver of HIPAA Authorization?

 Answer: A waiver of HIPAA authorization is a determination that is made by the IRB.  An IRB can waive in full or in part the individual authorization required by the Privacy Rule to use and disclose PHI for research purposes.

Example of research study for which the IRB may grant a complete waiver of the Authorization:

• A research study limited to a retrospective review of medical records (HIPAA Waiver for the entire study).

Example of research study for which the IRB may grant a partial waiver of the Authorization:

• A research study collecting information during telephone screening (HIPAA Waiver for a portion of the study).

To request a waiver of HIPAA authorization the investigator must complete pages 1 and 2 of the HIPAA Request for Alteration or Waiver of Authorization.doc form and submit this document to the IRB for review and approval prior to using and/or disclosing PHI.

 

Question: Is it possible to get a HIPAA waiver to screen patient charts without having each patient first sign an Authorization form?

Answer: Yes. The Privacy Rule allows for certain activities regarding screening, recruiting or determining eligibility (e.g. chart reviews for determining eligibility) to occur without obtaining a HIPAA authorization.

The investigator must submit a HIPAA Request for Alteration or  Waiver of Authorization.doc . The waiver must be granted by the IRB before charts are screened.

 

Question: What is a HIPAA Alteration of the Required Elements and/or Statements?

Answer: A HIPAA Alteration of the Required Elements and/or Statements is a regulatory determination that is made by the IRB.  An IRB can approve to omit (waive), or change (alter) in part the individual authorization required by the Privacy Rule to use and disclose PHI for research purposes.

 

When investigators are planning to obtain an individual’s authorization to access their information, and they need to either remove (waive), or change (alter) some of the core elements or statements of an authorization, they must complete and submit Appendix A.  Appendix A is in the fourth page of the HIPAA Request for Alteration or Waiver of Authorization.doc form   The IRB must approve this request prior to the use and/or disclosure of PHI.

 

Example of an alteration of the authorization:

• An authorization that requires to remove (waive) the element that describes each purpose of the requested use or disclosure because providing the purpose of the study would affect the results of the study.

 

Examples of studies withholding information about the study purpose and/or reason for procedures, in order to prevent biasing the results:

• Subjects are asked to take a quiz for research but they are not told that the research question involves how background noise affects their ability to concentrate.
•  To further understanding of how representations of same sex couples depicted in commercials influence consumer behavior, subjects are exposed to advertisements featuring gay couples and straight couples while their heart rate, facial muscle movement, and sweat responses are recorded. Subjects are informed that their reactions to the commercials are being studied, but not that the researchers are examining if the sexual orientation of characters in commercials influences them.

 To request to alter the HIPAA authorization, the investigator needs to submit a HIPAA Request for Alteration or Waiver of Authorization.doc  and Appendix A.

 

 Example of research study that requires waiving documentation/signature of the authorization:

• Research on sensitive topics, such as domestic violence or illegal activities where the only link of a subject to the study is their signature on the authorization, and there is a risk of breach of confidentiality.

 To request a waiver of the participant’s signature on the HIPAA authorization, the investigator needs to submit a HIPAA Request for Alteration or Waiver of Authorization.doc  and Appendix A.

 

Section C- Questions Related to IRB Review and the Privacy Rule when Using Specimens for Research

 

Because the federal definition of human subjects research extends to people who are sources of biological specimens and identifiable private information, research with these materials often requires review and approval by the IRB. The level of IRB review  is based on the level of risk the study poses.

The risks of research with specimens potentially include one or both of the following:

• The risk of harm from procedures used to obtain specimens, and/or
• The risk associated with the loss of privacy and confidentiality due to personally identifiable information that may be associated with specimens.

Common questions involving research using human specimens are summarized below.

 

Question:  What type of IRB review is required for a research project using existing specimens? What HIPAA form do I need to submit?

  Answer: It depends on whether the existing specimens are identifiable. Existing specimens means the  specimens were collected for clinical purposes or for research studies other than the proposed research study.

If the existing specimens are not identifiable, and if the investigator will make no effort to re-identify the specimens, the specimens do not meet the definition of a human subject and IRB review would not be required.

On the other hand, if the specimens are identifiable, or efforts will be made to re-identify the samples, IRB review is required.

Research that only involves the use of existing identifiable specimens may qualify for exemption if one of the following is true:

• the specimens are publicly available
• Information is recorded in such a manner that the identity of the human subject cannot readily be ascertained directly or through identifiers linked to the subjects, the investigator does not contact the subjects, and the investigator will not re-identify subjects. In this case, the research may qualify for exempt status under Category 4.ii.

To address HIPAA submit a HIPAA Certification of De-Identification.doc

On the other hand, research involving previously collected specimens that have identifiers associated most likely qualifies for expedited review under category 5.  Use of specimen-associated identifiers must be restricted and privacy protection measures must be in place.

To address HIPAA submit HIPAA Request for Alteration or  Waiver of Authorization.doc

 

Question:  What type of IRB review is required for a research project using specimens that will be collected for research purposes by noninvasive means? What HIPAA form do I need to submit?

Answer: Research that involves the collection of specimens for research purposes by noninvasive means may qualify for Expedited review- under Category 3.

Examples of these noninvasive collections of specimens are:

1. Hair and nail clippings in a non-disfiguring manner
2. Deciduous teeth at time of exfoliation or if routine patient care indicates a need for extraction
3. Permanent teeth if routine patient care indicates a need for extraction
4. Excreta and external secretions (including sweat)
5. Un cannulated saliva collected either in an unstimulated fashion or stimulated by chewing gum base or wax or by applying a dilute citric solution to the tongue
6. Placenta removed at delivery
7. Amniotic fluid obtained at the time of rupture of the membrane prior to or during labor
8. Supra‑ and subgingival dental plaque and calculus, provided the collection procedure is not more invasive than routine prophylactic scaling of the teeth and the process is accomplished in accordance with accepted prophylactic techniques
9. Mucosal and skin cells collected by buccal scraping or swab, skin swab, or mouth washings
10. Sputum collected after saline mist nebulization.

 

You will need to submit a HIPAA Authorization to Use and Disclose PHI for Research Purposes.doc

Question:  What type of IRB review is required for a research project using specimens collected for research purposes by invasive means? What HIPAA form do I need to submit?

Research that involves the collection of specimens for research purposes by invasive means/using procedures that pose greater than minimal risk to participants must undergo full committee review by the IRB.

Examples of these invasive collections of specimens are:

• Collection of specimens through  a skin Biopsy
• Collection of specimen through a bronchoscopy, amniocentesis or colonoscopy.

 

You will need to submit a HIPAA Authorization to Use and Disclose PHI for Research Purposes.doc

Question: My research study involves collecting sputum and lung aspirates from clinical procedures involving chronic smokers that are otherwise going to be thrown away.  The specimens will be provided by the pathology department without identifiers. The pathologist will not be involved in the research.  Do I have to get IRB review?  If so, what HIPAA form do I need to submit?

 Answer: You do not need to submit an application for IRB review nor you need to submit a HIPAA form. Your research is considered secondary research that is not human subjects research because: (a) the specimens were originally collected for clinical care and not specifically for the purpose of the investigator’s current research, (b) the specimens do not come with individually identifiable information, and (c) there is no interaction or intervention done specifically for the research.

  

Section D- Questions related to the Privacy Rule & Recruitment Activities

 

The IRB may approve a research proposal in which an investigator will obtain information for the purpose of screening, recruitment or determining the eligibility of prospective subjects without the prospective subject’s HIPAA authorization, however the following conditions must be met:

• The investigator will obtain information related to screening, recruiting or determining eligibility through oral or written communication with the prospective subject.
• The investigator will obtain identifiable information or identifiable biospecimens for screening, recruiting or determining eligibility by accessing records or stored identifiable biospecimens.
• In order to access records or specimens for such purposes, there must be an established relationship between the investigator and the individuals whose records /specimens will be reviewed.  The investigator may delegate the review to designated UConn Health research staff.

 

Question: At what point in recruitment may we gather information about a potential participant (e.g., if a potential participant calls our office after seeing a flyer, may we screen that person/ ask them about their history, or do we need the person to complete a written HIPAA Authorization prior to screening)?

Answer: If the IRB has approved your recruitment plan, including a partial waiver of Authorization to permit you to collect PHI for screening without written Authorization, you may take the person’s contact and screening information.  Investigators must also submit to the IRB a phone script using the Sample Phone Script for Screening Prior to Consent.doc . The IRB must approve the script prior to collecting information from potential participants over the phone.

The potential participant should know that in order to evaluate whether he or she is a candidate for the research, the researcher will need to share the caller’s information, and the caller may need to share information, with a limited number of others who staff the study.  If the person is deemed qualified for the study, then he/she will be asked to come in to sign an informed consent and a HIPAA Authorization. To protect the privacy of the potential participant all the information they provide will be kept only if he/she qualifies to proceed and decides to participate in the study.

 

Section E- Questions Related to HIPAA Identifiers and Coded Data/Specimens

 

  Question: HIPAA specifies18 identifiers that must be removed to “de-identify” health information.  Is any one of these identifiers, all by itself, PHI?

 Answer: Not necessarily. PHI is information, including demographic information, which relates to (i) the individual’s past, present, or future physical or mental health or condition; (ii) the provision of health care to the individual; or (iii) the past, present, or future payment for the provision of health care to the individual, and that identifies the individual or for which there is a reasonable basis to believe can be used to identify the individual.  If the only identifier you have is a DOB and that DOB is not linked to any other health information and could not be sourced to a provider (e.g., UConn Health), the DOB alone would not be PHI.  However, if the DOB is coupled with other information, such as “a patient at UConn Health,” or “was one of 15 enrollees in a particular study,” this combination would be PHI.

 

 Question: What coded information or coded specimens means?

The Office of Human Research Protections (OHRP) has defined coded as:

•  identifying information (such as name or social security number) that would enable the investigator to readily ascertain the identity of the individual to whom the private information or specimens pertain has been replaced with a number, letter, symbol, or combination thereof (i.e., the code);

and

• a key to decipher the code exists, enabling linkage of the identifying information to the private information or specimens.

 

 OHRP considers the term investigator to include anyone involved in conducting the research. OHRP does not consider the act of solely providing coded private information or specimens (for example, by a tissue repository) to constitute involvement in the conduct of the research. Note that if the individuals who provide coded information or specimens collaborate on other activities related to the conduct of this research with the investigators who receive such information or specimens, then OHRP would consider such additional activities to constitute involvement in the conduct of the research.

Examples of such additional activities include, but are not limited to:

(1) The study, interpretation, or analysis of the data resulting from the coded information or specimens; and

(2) Authorship of presentations or manuscripts related to the research.

   

Question: Is coded information identifiable?

 Answer: The Privacy Rule considers coded information to be de-identified if the 18 specific identifiers of the individual or of relatives, employers, or household members of the individual, listed below are coded and the person cannot reasonably be identified.

However, that code needs to be assigned by someone other than the investigator.  The code cannot be derived from any identifiable piece of information or combination of pieces of identifiable information.  The key to the code cannot be accessible to the investigator or research personnel using the de-identified data.

• Names;
• Address (including street address, city, county, zip code). The initial three digits of a zip code may be used if, according to the current publicly available data from the Bureau of Census: 1) the area formed by combining all zip codes with the same three initial digits contains more than 20,000 people; and 2) the initial three digits of a zip code for a region containing 20,000 or fewer people is changed to 000;
• All elements of dates (except year) for dates directly related to an individual (birth
• date, admission date, discharge date, date of death), and all ages over 89 and all elements of dates (including year) indicative of such age, except that ages and  elements may be aggregated into a single category of age 90 or older;
• Telephone numbers;
• Fax numbers;
• Electronic mail addresses;
• Social Security numbers;
• Medical record numbers;
• Health plan beneficiary numbers;
• Account numbers (bank, retirement, credit card, etc.);
• Certificate/license numbers;
• Vehicle identifiers and serial numbers, including license plate numbers;
• Device identifiers and serial numbers;
• Web Universal Resource Locators (URLs);
• Internet Protocol (IP) address numbers;
• Biometric identifiers, including finger and voice prints;
• Full face photographic images and comparable images; and
• Any other unique identifying number, characteristic or code.

 

REFERENCES

 HIPAA Privacy Rule and Its Impacts on Research (nih.gov)

• Coded Private Information or Specimens Use in Research, Guidance (2008)

• 2011-014.0.pdf– Health Insurance Portability and Accountability Act (HIPAA) in Research 

• Use and Disclosure of Protected Health Information.pdf

 

 

 

The Association for Accreditation of Human Research Protection Programs
UConn Health Human Subjects Protection Programs Preparation for Reaccreditation

The Association for Accreditation of Human Research Protection Programs (AAHRPP) is an independent, non-profit accrediting body that works to protect the rights and welfare of research participants and promotes high-quality research through an accreditation process.

AAHRPP’s accreditation standards meet or exceed U.S. federal regulatory requirements and the International Committee on Harmonisation –Good Clinical Practice (E6) guideline for protection, and are reasonable, attainable, and representative of current best practices.

UConn Health’s Human Subjects Protection Program (HSPP) achieved AAHRPP accreditation in 2006. As an accredited organization, our HSPP must periodically apply for re-accreditation every five years. This is a two-step process.

Step 1, consists of a self-evaluation of our program, followed by an AAHRPP review of our policies and procedures to ensure they meet regulatory and accreditation standards.

Step 2 is an onsite visit by AAHRP representatives to ensure that our policies and procedures are followed. Once our HSPP is scheduled for the reaccreditation visit an announcement will be sent to the research community.

To complete the reaccreditation step 1, the HSPP has revised multiple IRB policies to reflect our current practices, add required information and standards for accreditation.

In the tables below is a list of the IRB polices and forms that have been revised along with a short summary of the revisions.

If you have questions regarding those changes please send an email to either irb@uchc.edu or contact the Education Specialist at cagganello@uchc.edu , 860-679-8802.

2009-001.0.pdf – Reporting Unanticipated Problems to the Institutional Review Board: Edited section under “Self-Reporting” to clarify that the Principal investigators are to report to the IRB any noncompliance with the protocol or directives of the IRB that was within the control of the research team within 5 business days of becoming aware of the event.

2009-003.0.pdf – Imposing and Lifting Suspensions of IRB Approval or Imposing Terminations of IRB approval: Updated to reflect current guidance on diversity, equity and inclusion (change he/she to they, his/her to their) and minor punctuation and grammar changes.

2009-005.0.pdf – Monitoring of IRB Approved Studies: Updated to reflect current guidance on diversity, equity and inclusion (change he/she to they, his/her to their) and minor punctuation and grammar changes.

2011-006.1.pdf – Additional Protections – Pregnant Women, Fetuses or Neonates: Minor grammar changes.

2011-006.4.pdf – Additional Protections – Other Vulnerable Groups: Updated to reflect current guidance on diversity, equity and inclusion (change he/she to they, his/her to their) and minor punctuation and grammar changes.

2011-006.5.pdf – Additional Protections – Fetal Tissue Transplants: Updated to reflect current guidance on diversity, equity and inclusion (change he/she to they, his/her to their) and minor punctuation and grammar changes.

2011-007.0.pdf – Definitions Applied to Policies: Added definition of benign behavioral intervention. Edits to reflect current guidance on diversity, equity and inclusion (change he/she to they, his/her to their).  Included revised common rule.

2011-008.1.pdf – Informed Consent – Process The general section was revised to request information about the informed consent methods and documentation and to alert the investigator that prospective IRB approval is required for any subsequent modifications made to the methods of obtaining consent or documentation of informed consent whether they are done by hard copy or electronically.

• Changes to the process of obtaining consent by Phone / Fax to include that the individual obtaining consent must be approved by the IRB to consent and that such individual should have sufficient knowledge of the study to conduct the conversation and to answer any questions,; and the consent conversation should include an in-depth review of the consent document allowing sufficient time for questions to be asked and answered.
• The process for obtaining consent via videoconference (e.g., WebEx, Zoom) was added with an explanation of how this process must be conducted.
• A section about obtaining electronic documentation of consent was added with details of compliance expectations and acceptable methods and processes to obtain electronic signatures.
• A section about electronic informed consent process when consent is not witnessed by study personnel was added to alert researchers that the investigator planning to use this method should discuss this plan with the IRB prior to submitting this method for approval to ensure this method is appropriate for the research (e.g., in compliance with applicable regulations).
• Edits to reflect current guidance on diversity, equity and inclusion (change he/she to they, his/her to their).

2011-008.5.pdf – Informed Consent – Providing and Obtaining Informed Consent: Updated to reflect current guidance on diversity, equity and inclusion (change he/she to they, his/her to their) and minor punctuation and grammar changes.

2011-009.0.pdf– Institutional Review Board – Membership: Updated to reflect current guidance on diversity, equity and inclusion (change he/she to they, his/her to their) and minor punctuation and grammar changes.

2011-009.11.pdf – Institutional Review Board – Studies Conducted in Foreign Locations: Updated to reflect current guidance on diversity, equity and inclusion (change he/she to they, his/her to their) and minor punctuation and grammar changes.

2011-009.14.pdf – Institutional Review Board – Human Subject Research Determinations: Updated to reflect current guidance on diversity, equity and inclusion (change he/she to they, his/her to their) and minor punctuation and grammar changes.

2011-009.2.pdf – Institutional Review Board – Exemptions: Policy was edited to remove language related to pending adoption of the revised common rule and revisions to applicability of exemption 4(iii) at UConn Health.

2011-009.3.pdf – Institutional Review Board – Expedited Reviews : Policy was revised to include a complete list of the criteria for approval when conducting initial or continuing review for expedited submissions. In addition, when submissions are returned to the investigators with a status of “Approved Contingent,” the IRB reviewer can now add a deadline for the investigator to respond to the contingencies sent in a Response form.

2011-009.4.pdf – Institutional Review Board – Convened Meeting Operations: Policy was revised to add that when virtual IRB meetings are conducted the agenda item (inclusive of supporting documents) are shared on the screen in the videoconference.

2011-009.7.pdf – Institutional Review Board – Assignment of Status Codes: Policy was revised to clarify the IRB will assign the study status code “Closed by PI” to a study under oversight of an external IRB when the external IRB grants the request.  Under the status code title: “Inactive-Administratively Closed” the following was added: the IRB Administrator will assign this status code to exempt research after the anticipated completion date has passed.

2011-009.8.pdf – Institutional Review Board – Appeals Process: Policy was revised to indicate that when a principal investigator (PI) submits an initial appeal letter, it can be completed through a written correspondence (i.e., not limited to IRIS response).  Also, the letter sent by the IRB in response to the appeal made by the PI will contain a wet-ink or electronic signature of the IRB Chair.  In addition some edits were made to reflect current guidance on diversity, equity and inclusion (change he/she to they, his/her to their).

2011-009.10.pdf – Institutional Review Board – More Frequent Review: Policy Appendix -A was revised to remove Panel 3 and CICATS.

2011-009.12.pdf – Institutional Review Board – Criteria for Approval: Policy was revised to clarify that students can be considered subjects who are likely to be vulnerable to coercion or undue influence.  In addition, policy revised to remove language indicating ‘if’ the revised common rule is implemented (see section describing limited IRB review).

2011-009.13.pdf – Institutional Review Board – Lapse in IRB Approval: Policy was revised to describe that investigator are notified either by email or iRIS correspondence about the need to submit a request for extension of the anticipated completion date or close the study.

2011-009.15.a.pdf – Institutional Review Board – Reliance on UConn Health as IRB of Record: Policy was revised to indicate SMART IRB template may be used to execute reliance agreements. The Office of Human Research Protection reliance agreement template was removed as it not preferred since it does not meet AAHRPP standards.

2011-009.15.b.pdf – Institutional Review Board – Reliance on External IRB: Trinity Health was added as an institution with which UCONN Health has an established collaborative agreement for minimal risk studies conducted by a student, fellow or resident. Also, policy now contains that when requesting reliance on an external IRB for a student/resident/fellow project, UCONN Health IRB may request the original approval letter to ensure the research is minimal risk.

2011-011.0.pdf – Research Personnel: Policy revised to include principal investigator (PI) responsibility to ensure the confidentiality and security of research records and data as described to the IRB in the submission materials, and to cooperate with all aspects of internal or external audits and inspections.

2011-012.0.pdf – Conflict of Interest – Research Personnel: Updated to reflect current guidance on diversity, equity and inclusion (change he/she to they, his/her to their) and minor punctuation and grammar changes.

2011-012.1.pdf – Conflict of Interest – IRB Members: Updated to reflect current guidance on diversity, equity and inclusion (change he/she to they, his/her to their) and minor punctuation and grammar changes.

2011-015.0.pdf – Recruitment and Payment:  Policy was revised to indicate that external researchers looking to advertise recruitment in UConn Health broadcast (e.g., Lifeline) messages do not need HSPP/IRB permission. Also revised to include procedure to use UConn Health as a recruitment site when UConn Health is not engaged.   Added edits to reflect current guidance on diversity, equity and inclusion (change he/she to they, his/her to their).

2011-016.0.pdf – Scientific Review: Policy was revised to include the Clinical Research Center and funding foundation as acceptable entities who may have conducted the scientific review of studies submitted for full board review.

2011-020.0.pdf – Humanitarian Use Device: Updated to reflect current guidance on diversity, equity and inclusion (change he/she to they, his/her to their) and minor punctuation and grammar changes.

2011-022.0.pdf – Study Drug – General: Updated to reflect current guidance on diversity, equity and inclusion (change he/she to they, his/her to their) and minor punctuation and grammar changes.

2011-022.2.pdf – Investigational Drug/Biologic – Expanded Access for Treatment Use, Including Single Emergency Use: Updated to reflect current guidance on diversity, equity and inclusion (change he/she to they, his/her to their) and minor punctuation and grammar changes.

2011-023.0.pdf – Educational Requirements: Updated to reflect current guidance on diversity, equity and inclusion (change he/she to they, his/her to their) and minor punctuation and grammar changes.

2011-025.0.pdf – HSPP Evaluation / Institutional Support: Policy was revised to include minor updates to title of HSPP manager, and removing executive committee.

2014-034.0.pdf – Additional Requirements – Department of Education (Federal): Policy was revised to include that an email confirming with all of the information included in the FERPA verification form may be acceptable, provided the email is from the person at the school with the authority to grant the permission and sent from that individual’s institutional email address.  Added edits to reflect current guidance on diversity, equity and inclusion (change he/she to they, his/her to their).

Application Checklist for Initial Exempt Application  .doc: Exempt submission checklist Added the following requirements:  When submitting for Exempt determination under Exempt category 4.iii a confirmation that the data will remain protected under HIPAA for 4.iii is required.   If the protocol involves sharing data with indirect identifiers such as sharing a Limited Data Set with an external investigator the UConn Health investigators should provide confirmation they have in place a Data Use Agreement.    If the protocol involves sharing coded data the UConn Health investigators should provide confirmation they have a Don’t Ask /Don’t Tell agreement in place.

Application Checklist for Initial and Continuing Review Expedited .doc : Expedited submission checklist Added the following requirement:
When using electronic informed consent (eIC) (confirmation of part 11 compliance, hard copies of materials, access to eIC platform)
Application Checklist for Initial and Continuing Review Full Board.docx

Application Checklist for Initial and Continuing Review Full Board.docx : Added the following requirement : When using electronic informed consent (eIC) (confirmation of part 11 compliance, hard copies of materials, access to eIC platform).

Request for Exemption Form .doc: Request for Exemption Category 4.iii. was revised to be less restrictive but still ensure HIPAA protection for review as required under the exemption.

 

Guidance on Closure of Human Subject Research Studies

 

A research study should be closed by the Principal Investigator (PI) once all human research activities are completed regardless of whether a study is subject to the continuing review requirement. To do so, a closure form should be submitted to the IRB through the iRIS submission system for each non-exempt human research study (e.g., studies approved under Expedited review or Full Board review). The closure form should be submitted before the expiration of IRB approval, however, the PI can also submit a closure form after they have received a notice of lapse of approval.

If the study is an exempt study, the PI may allow the IRB approval to expire. When approval of an exempt study expires, the IRB will administratively close the study, but this does not invalidate the exemption. The research, as proposed to the IRB, may continue; it is not necessary to keep the exemption actively registered with the IRB.

A closure form allows the IRB to have a summary of the following information:
• the findings of the study
• the final enrollment data
• whether the study met the recruitment goals, and
• whether any of the following events occurred since the last approval (initial or continuing review):
o subject complaints
o unanticipated problems involving risk to subjects or others,
o unexpected profile of adverse events in terms of frequency and/or severity,
o non-compliance with or deviation from the approved protocol or procedures,
o audits, inspections or monitoring visits by internal or external personnel.
o any publications, presentations, trademarks, patents, etc. related to the study.

This guidance explains the circumstances in which a non-exempt human research study may be closed from IRB oversight, as well as ongoing researcher responsibilities that apply to closed studies.

Things to Consider before Closing Research Studies

• Investigators should honor wishes of the sponsor or funding source to keep the study open or to close the study. Some funding entities require IRB approval for the duration of the funding, even if human research activities are complete, or they may not allow the study to close without the sponsor’s permission. It is the PI’s responsibility to be aware of, and comply with, those requirements.

• Sponsors, contract research organizations (CROs), or coordinating center personnel may need to verify or monitor individually identifiable study data at a specific site where human subjects activities have been completed. The study team should verify whether these organizations require the studies to be open when conducting their monitoring visits. IRB approval must be maintained while these activities are occurring.

• Whenever possible, prior to closing a study, data should be permanently de-identified.

When to Close a Study

• For studies requiring continuing review (e.g., some Expedited studies and all full board studies ) a requests for closure should be submitted at the time the next continuation application is due or within 30 days after the completion of all study activity involving the use of private identifiable information or biospecimens, whichever comes first.

• Moreover, a closure form should be submitted to the IRB if the if the research study was not conducted or was canceled, or if each of the following conditions exist:
o The research is permanently closed to the enrollment of subjects
o The subjects have completed all research-related interventions
o The research is no longer active for long-term follow up of subjects
o Data has been de-identified.

• When a Principal Investigator terminates employment with UConn Health, the PI may submit a closure form to the IRB. Alternatively, the PI may submit a modification form requesting transfer of the study to another eligible Principal Investigator.
Retired investigators with Emeritus status at UConn Health may be permitted to keep the study open and continue as the PI with approval from the HSPP Director.

• When a student-led project is completed, the study should be closed with the IRB. This should occur prior to the student’s departure / graduation.

IRB Process of Expired studies, Lapsed Studies and Closure Forms

• Expired studies: If approval for continuation of non-exempt research is not sought, or a request to extend the expected completion date has not been received within a reasonable time frame (e.g., 30 days), IRB staff will administratively close the study and send a written notification to the Principal Investigator of the administrative closure. The research activity may not continue and a new application may be required to resume research activity.

• Lapsed studies: If approval of the study has lapsed due to lack of a response to contingencies or a request for continuing approval or to extend the completion date has not been received the study may administratively be closed. The IRB will send a written notification to the PI. Prior to closure the IRB will issue a final request for response by email to the PI and study contacts and the PI will be given a reasonable period within which to respond (e.g. one or two weeks).

• Closure forms: When a closure form is submitted, the IRB will review any new information provided in the closure form and determine whether any additional action is required on the part of the IRB or the investigator. Upon review of the closure form, the status of the study is changed in the iRIS system (e.g., “Closed by PI”) and an outcome letter is issued confirming the closure.

Principal Investigator Responsibilities with Closed Studies

The principal investigator (PI) continues to have responsibilities for a study even when IRB oversight of a study is no longer required. These responsibilities include:

• Verifying all research activities have been completed. The PI should ensure that all research-related activities, interventions or interactions with human subjects or individually identifiable data have been completed at the site(s) approved under the Principal Investigator’s IRB application at the time a closure form is submitted to the IRB or at the time of approval expiration, whichever occurs first.

If after a study is closed, the PI wishes to engage in an activity such that the criteria for closure listed above would no longer be met, the Principal Investigator must submit a new application for IRB review and approval for the use of the previously collected data.

• Record Retention Research data from the completed study should be stored and protected in the manner approved by the IRB and consented to by the research participant so as to maintain the privacy and confidentiality of the participants.

Per HSPP Policy 2011-024.0.pdf – File Requirements & Record Retention Requirements , investigators must maintain research records for three years beyond the completion/termination of the study. Investigators should be aware that other laws and requirements (e.g., funding agency) may require a longer record retention period. Per the HIPAA regulation, investigators are to retain documents relating to uses and disclosures, authorization forms for 6 years from the date of creation or the date when it last was in effect, whichever is later.

Investigator should be familiar with the record retention format described in the UConn Health HSPP Policy 2015-024.1.pdf – Record Retention Format .

Investigators should ensure that any specific regulatory and/or sponsor requirements are met for record retention or submission of reports.

• Confidentiality and Data Security. If the PI is maintaining identifiable private data or specimens, the protections described in the IRB application and to subjects must be maintained for the time frame described. The PI must continue to honor any commitments made to participants as part of the approved research (e.g., providing information about study results; payment for research participation).

• HIPAA authorization. The PI may have obtained HIPAA authorization from subjects to access their medical records, with an expiration date that is far in the future. If the PI still has permission to access medical records at the time they want to close the study that permission expires upon study closure.

 

 

U.S. Department of Health and Human Services Food and Drug Administration
Common Inspection findings from 2017-2022

 

The Food and Drug Administration (FDA) has released their Bioresearch Monitoring (BIMO) Fiscal Year 2022 Metrics. Below is a partial description of the common inspection findings from 2017-2022. The full report can be found here: https://www.fda.gov/media/165853/download

Common Sponsor-Investigator Inspectional Observations:
• Failure to maintain and/or retain adequate records in accordance with 21 CFR 312.57; accountability for the investigational product; Investigator Statement (FDA 1572); Financial disclosures.
• Failure to select qualified investigators and/or monitors, ensure proper monitoring of the study and ensure the study is conducted in accordance with the protocol and/or investigational plan.
• Failure to submit an Investigational New Drug (IND) application.
• Inadequate subject protection; informed consent issues.
• Failure to notify FDA of termination of investigator.

Common Sponsor/CRO Inspectional Observations:
• Failure to ensure proper monitoring of the study and ensure the study is conducted in accordance with the protocol and/or investigational plan.
• Failure to meet the abbreviated requirements for investigational device exemptions (IDEs).
• Failure to maintain and/or retain adequate records in accordance with 21 CFR 312.57; accountability for the investigational product; Investigator Statement (Form FDA 1572); Financial disclosures.
• Failure to submit an Investigational New Drug (IND) application; IND safety report.
• Failure to submit current list of all participating investigators to FDA at six-month interval after FDA approval of the study.

Common Clinical Investigator Inspectional Observations:
• Failure to comply with Form FDA 1572 requirements, protocol compliance
• Failure to follow the investigational plan; protocol deviations
• Inadequate and/or inaccurate case history records; inadequate study records
• Inadequate accountability and/or control of the investigational product
• Safety reporting; failure to report and/or record adverse events
• Inadequate subject protection; informed consent issues

 

Difference Between De-Identified Data Sets and Limited Data Sets
&
Limited Data Sets and Data Use Agreements

 

Under the Health Insurance Portability and Accountability Act (HIPAA) de-identified data is data from which all 18 HIPAA identifiers that could be used to identify an individual or the individual’s relatives, employers, or household members have been removed.

Unlike a de-identified data set, a limited data set is still considered Protected Health Information (PHI). As defined by HIPAA, limited data sets (LDS) are data sets stripped of certain direct identifiers that are specified in the Privacy Rule. They are not de-identified information under the Privacy Rule.

A limited data set is protected health information that excludes the following direct identifiers of the individual or of relatives, employers, or household members of the individual: (1) names; (2) postal address information, other than town or city, State, and zip code; (3) telephone numbers; (4) fax numbers; (5) e-mail addresses; (6) social security numbers; (7) medical record numbers; (8) health plan beneficiary numbers; (9) account numbers; (10) certificate/license plate numbers; (11) vehicle identifiers and serial numbers; (12) device identifiers and serial numbers; (13) web URLs; (14) Internet Protocol (IP) address numbers; (15) biometric identifiers, including fingerprints and voiceprints; and (16) full-face photographic images and any comparable images.

Distinct from de-identified data, a limited data set contains protected health information that is associated with indirect identifiers as defined in the HIPAA privacy rule. Protected health information in limited data sets may include the following indirect identifiers: town, city, state and zip code, and dates directly related to an individual, including birth date, admission date, discharge date and date of death.

The table below describe in detail the HIPAA identifiers that must not be present in a de-identified data set or in a limited data set.

 

 

DATA ELEMENT	DE-IDENTIFIED DATA SET	LIMITED DATA SET
Names.	Remove	Remove
Postal address information.	Remove	Remove
Town, city, state and zip code.	Remove	Can retain city, town, state or full zip code.
All elements of dates that are directly related to an individual, including birth date, admission date, discharge date, death date, and all ages over 89 and all elements of dates (including year) indicative of such age, except that such ages and elements may be aggregated into a single category of age 90 or older.	Remove	Remain
Telephone numbers, fax numbers; e-mail addresses, web URL addresses, IP addresses.	Remove	Remove
Social security number, medical record number, health plan beneficiary number, any account number, certificate or license number.	Remove	Remove
Vehicle identifiers and serial numbers, including license plate numbers, Device identifiers and serial numbers.	Remove	Remove
Full-face photographic images and any comparable images, Biometric identifiers, including fingerprints and voiceprints.	Remove	Remove
Any other unique identifying number, characteristic or code.	Remove	Remove

 

Limited Data Sets and Data Use Agreements

If indirect identifiers must be kept within a limited data set (LDS) in order to perform a research study and the information is to be disclosed outside of UConn Health, the principal investigator must enter into a Data Use Agreement (DUA) with the data recipient. A DUA may also be utilized when UConn Health is the  recipient of a LDS. Only after the agreement has been executed can the limited data set be used/disclosed.

This DUA is required under the HIPAA Privacy Rule. This agreement establishes the ways in which the information in the limited data set may be used, the purpose for which it was disclosed, and identifies who is permitted to use or receive the information.

Moreover, the DUA stipulates that the recipient will use appropriate safeguards to maintain the confidentiality and protect the data from further disclosures.

Since the data use agreements establish institutional obligations and bind the institution to the terms of the agreement, investigators are not authorized to execute research DUAs. UConn Health DUAs for research related activities are processed through the Office of Sponsored Programs Sponsored Program Services (SPS) or the Office of Clinical and Translational Research (OCTR). The specific contacts in these offices are listed below:

• If the DUA is related to a Clinical Trial contact: Donald Deyo, Contract Specialist (deyo@uchc.edu), or the OCTR main inbox (octrclinicaltrial@uchc.edu).

• If the DUA is unrelated to a Clinical Trial contact: Jennifer Pomales pomales@uchc.edu

The table below describes whether IRB review approval is required for a de-identified data set or for a limited data set, and when a Data Use Agreement is required.

 

	DE-IDENTIFIED DATA SET	LIMITED DATA SET
IRB Review/Approval	IRB and Investigator can determine the project /research is Not Human Subject research. May be used in any manner, not regulated under HIPAA.	If the data is not readily identifiable, IRB can determine Not Human Subject Research. IRB does not require HIPAA Authorization or Waiver.
Data Use Agreement	Not required.	Required. UConn Health DUAs for research related activities are processed through the Office of Sponsored Programs Sponsored Program Services (SPS) or the Office of Clinical and Translational Research (OCTR).

 

OHRP’s Common Rule Webinar

Join the introduction-level, webinar titled “Unlocking the Mysteries of the §46.111 Criteria for IRB Approval of Research.”

This presentation will explain the criteria for IRB approval of research and include case studies and interactive quizzes to demonstrate the way the criteria can be applied.
Date: Tuesday, July 11, 2023, 12:00 PM EDT
Spots are limited. Registration is required to attend and receive a certificate of attendance.

Register for this webinar at: https://www.zoomgov.com/webinar/register/WN_9RbRyAwjQY2N_kRxFPbT-w

FDA Warning Letter Regarding the Failure to Submit INDs for the Conduct of Clinical Investigations 

with an Investigational Product that met the Definition of a Combined Product.

 

Inspections of clinical trials are conducted as a part of the U.S. Food and Drug Administration (FDA)’s Bioresearch Monitoring Program.  These inspections are designed to evaluate the conduct of research and to help ensure that the rights,   safety, and welfare of human subjects have been protected.  Below you will find a short summary of a warning letter issued because of the failure to submit an investigational new drug application.

 

Warning Letter to Dr. David M. Lubeck/Arbor Centers for EyeCare

 On November 18, 2022, the FDA issued a warning letter to Dr. David M. Lubeck/Arbor Centers for EyeCare.  The FDA officials inspected Dr. Lubeck study and concluded that the investigator did not adhere to the FDA regulations governing the conduct of clinical investigations and the protection of human subjects. Specifically, the investigator failed to submit an Investigational New Drug application (IND) for the conduct of a clinical investigation with investigational new drugs that is subject to 21 CFR 312.2(a) [21 CFR 312.20(a), 312.20(b), and 312.40(a)].

The FDA argued that the investigational product used in combination with another drug comprised  both a drug and a device components and was therefore a combination product within the meaning of section 503(g) of the FD&C Act (21 U.S.C. 353(g)).

Furthermore, the FDA underlined that because the primary mode of action of the investigational combination product was attributable to the product and because the product met the definition of a drug under section 201(g) of the FD&C Act, an IND was required for any clinical investigation of the investigational combination product used in such Protocol.

Among other important issues noted in this investigation was that the investigator did not wait the 30 days to enroll subjects in the study.  An IND does not go into effect upon FDA’s receipt of the IND submission. Rather an IND generally goes into effect 30 days after FDA receives the application, or on earlier notification by FDA that the clinical investigation in the IND may begin (21 CFR 312.40(b)). The FDA emphasized that FDA regulations require a sponsor to submit, and to have in effect, an IND before initiating a clinical investigation that must be conducted under an IND in accordance with 21 CFR 312.40.

For more details about the inspection of this study and the findings of the FDA please review the Warning Letter to Dr. Davd M. Lubeck.

Developing a Mobile Health App?

Updated FTC-HHS online tool helps developers understand which federal laws apply

 

 

The Federal Trade Commission (FTC) in conjunction with the Department of Health & Human Services (HHS) Office for Civil Rights (OCR), the HHS Office of the National Coordinator for Health Information Technology (ONC), and the Food and Drug Administration (FDA) have updated the Mobile Health App Interactive Tool. This tool is designed to help developers of health-related mobile apps understand what federal laws and regulations might apply to them.   The guidance tool asks developers a series of high-level questions about the nature of their app, including about its function, the data it collects, and the services it provides to users. Based on the developer’s answers to those questions, the guidance tool will point the app developer toward detailed information about certain federal laws that might apply to the app. These include the FTC Act, the FTC’s Health Breach Notification Rule, the Children’s Online Privacy Protection Act (COPPA), the Health Insurance Portability and Accountability Act (HIPAA), the Federal Food, Drug and Cosmetics Act (FD&C Act), and the 21st Century Cures Act and ONC Information Blocking Regulations.

 

Developers and others seeking more information about how the HIPAA Rules might apply to their health apps should visit OCR’s HIPAA and Health Apps page, which contains information on how HIPAA applies to a range of example health app scenarios and offers key questions to consider in determining when HIPAA’s regulations cover a particular health app.

 

IRB Forms – Update

The following forms were updated in the IRB website:

1. Sample Cover Letter for a Survey Study.docx (09/02/2022)
2. Application Checklist for Initial and Continuing Review Full Board.docx (09/02/2022 – New Contact Information for Institutional Biosafety Committee )
3. Application Checklist – Single Patient Expanded Access .docx(9/22/2022)
4. Request for Exemption Form .doc(09/30/2022)
5. Guidance for Completing Continuation Form.docx (10/12/2022)
6. Guidance for Preparing a Chart Review Study .docx(10/12/2022)
7. HIPAA Authorization to Use and Disclose – Spanish.doc (11/7/2022)

 

The following forms were added to the IRB website:

 

• Instructions for Facilitated Review for Collaborative Research with Neighboring Facility .docx(10/12/2022)

• Request for UConn Health as a Recruitment Site -Without Engagement(12/14/2022)

 

The following educational resources were added to the IRB website:

• NIH Policy for Data Management and Sharing (effective 1/25/2023)
• NIH Guide for Writing a Data Management & Sharing Plan
• Data Storage Finder (tool from Cornell University)

 

National Institute of Health (NIH) Policy for Data Management and Sharing

Investigators Resources

 

 

The National Institute of Health (NIH) has posted a one-page handout “The Who, What, Where and When of the NIH Data Management and Sharing (DMS) Policy” summarizing the most important information for investigators regarding the NIH Policy for Data Management and Sharing.  Click on the image to go to their website and explore the info/links in the handout.

 

The University of Pennsylvania has shared the following resources on its website to aid investigators to comply with the National Institute of Health (NIH) Policy for Data Management and Sharing

 

• DMS Plan Format Page

NIH’s checklist that walks researchers through the elements of a DMSP

• NIH FAQs on the DMSP

NIH is constantly updating its FAQ page on the DMSP. Check back for your questions.

• NIH Webinars

Includes NIH webinar recordings and registration information for upcoming presentations.

• NIH Guidance for Informed Consent

Provides points to consider and sample language for informed consent documents of research studies which plan to store and share data and/ or biospecimens for future use.

• DMPTool Guide

Penn Libraries uses DMPTool to assist with writing data management plans. DMPTool is a resource researchers can use to draft data management plans. The new NIH DMSP template is available in the tool. We can provide comments on your DMSP if you need assistance. See our contact information on this page.

• NIMH Sample DMSPs

The National Institute of Mental Health (NIMH) has developed four example DMSPs that are consistent with NIMH and NIH requirements.

• NIH Institute and Center Data Sharing Policies

NIH institutes and centers may have other data sharing requirements in addition to the NIH DMS Policy. Make sure to read your applicable policy carefully.

• NIH DMS Policy: Applicable Activity Code

A comprehensive listing of all NIH activity codes that generally require applicants to submit a Data Management & Sharing Plan

• ICPSR’s Guide to Sharing NIH Data

Provides an overview of ICPSR’s NIH funded archives and recommendations for designating ICPSR for your data to meet the requirements of the NIH DMSP.

• Working Group on NIH DMSP Guidance

Created by librarians and other research support professionals, this working group has created a variety of resources that researchers can use to prepare for the NIH DMS Policy implementation. Resources include glossaries, a DMSP checklist for researchers, and an example DMSP for the 2023 expectations.

• Ten simple rules for maximizing the recommendations of the NIH data management and sharing plan

Recent article on the NIH DMSP policy that covers 10 key recommendations for creating a DMSP that is both maximally compliant and effective.

• Data Management Resources

Research Data & Digital Scholarship Data Sharing Services

NIH Repositories

 

Cornell University has excellent resources and tools on its website to aid investigators to comply with the National Institute of Health (NIH) Policy for Data Management and Sharing.

 

In addition, the NIH National Library of Medicine has posted the following resources:

 

• NIH CDE Repository
• NIH Data Sharing Repositories
• NIH Data Sharing Policies

 

 

Office of Human Research Protection (OHRP) Luminaries Lectures Series

Educational Resources for Investigators

 

The Office of Human Research Protection  Luminaries Lectures Series features videos by esteemed individuals with thought-provoking insights on diverse aspects of human research protections.

Some of the recently added videos are listed below.  These videos are covering the challenges of research during public health emergencies and research studying usual care practices, as well as thoughts from representatives in the research community on how to promote diversity and engagement in research participation:

• “The Covid Drug Wars” – What We Learned from the Front Lines
• “Unusual Practices Masquerading as Usual Care”
• “Vulnerability, Justice, Equity, and Engagement: A Conversation About Public Health and Human Subjects Research”

Click here and start watching!

 

Changes in the HSPP/IRB

  

Administrative Manager and Deputy Director of HSPP: Julia Blair has been named Administrative Manager of the HSPP, after filling the role on an interim basis since June following Deb Gibb’s retirement.  She can be reached at jblair@uchc.edu and (860) 679-7555.

 

HSPP- July, August, September, 2022 – Newsletter

Revision to Exemption Category 4 (iii)

To ensure the protection of identifiable private information (IPI) at UConn Health in compliance with The Privacy Rule, the HSPP will limit use of the exemption 45 CFR 46.104(d)(4)(iii):
Secondary research uses of identifiable private information, [when] the research involves only information collection and analysis involving the investigator’s use of identifiable health information (not biospecimens) when that use is regulated under [HIPAA].
Exemption 4(iii) applies to secondary research ‘use’ of the IPI which is protected under HIPAA, however the release, transfer or provision of access to a non-covered entity / third party would constitute a ‘disclosure’ where the IPI is no longer protected and the exemption would not apply.
Effective October 1, 2022, to ensure compliance with HIPAA and the Common Rule (45 CFR 46), the UConn Health HSPP will restrict the use of exempt category 4(iii) to studies where the Principal Investigator is UConn Health faculty (whose home/primary institution is UConn Health) and the data is not shared outside UConn Health or with non-UConn Health personnel.
New applications to the IRB seeking approval for secondary research use of identifiable private information which do not qualify for exemption under category 4 should request expedited review by the IRB. More information on exempt and expedited submissions can be found on the HSPP website or by contacting the HSPP Education Specialist, Mayra Cagganello at x8802 or cagganello@uchc.edu.

 

National Institute of Health (NIH) Policy for Data Management and Sharing

The National Institute of Health (NIH) Data Management and Sharing policy was published on October 29, 2020, and will go into effect on January 25, 2023. The two year delay in implementation was planned to give time to institutions to learn and prepare for enactment of the policy.

This policy applies to all research funded (in whole, or in part) or conducted by NIH that results in generation of scientific data. The goal of this NIH Data Management and Sharing policy is to benefit everyone, namely investigators, funding agencies, the scientific community, and, most importantly, the public. Data sharing provides more effective use of NIH resources by avoiding unnecessary duplication of data collection. It also conserves research funds to support more investigators. As stated in this policy “data sharing enables researchers to rigorously test the validity of research findings, strengthen analyses through combined datasets, re-use hard-to-generate data, and explore new frontiers of discovery.”

The NIH DMS Policy requires researchers to submit a plan to preserve, to share the data and to show compliance with said plan.

The NIH has made available multiple educational materials to inform and educate researchers about this policy at sharing.nih.gov. Below please find the links to the webinars

Webinar I: Understanding the New NIH Data Management and Sharing Policy –
o Resource Slide Deck
o Webinar Recording

Webinar II: Diving Deeper into the New NIH Data Management and Sharing Policy
o Resource Slide Deck

To access the frequently asked questions regarding this policy please click on 2023 Data Management & Sharing Policy

Uconn Health – Research Participant Feedback Form
Now available in Redcap

The Human Subjects Protection Program (HSPP) is responsible for ensuring that studies are conducted in compliance with internal policies, federal regulations and ethical standards. When research participants complete and submit a Research Participant Feedback Form, the HSPP is able to learn about the study volunteer experiences.

Participants can access the Research Participant Feedback form in two ways:
1) Download the form from the IRB website at http://research.uchc.edu/rcs/hspp/volunteers/. Forms must be completed and emailed or faxed following the instructions on the form.
2) *NEW* Research participants may submit this form electronically by accessing the REDCap form at https://redcap.link/UConnHealth-Feedback-Research from a computer or mobile device.

The IRB and HSPP encourage the research community to help research volunteers to complete this form.

IRB Forms – Update

The following updates have been made to IRB forms:

Added new contact information to the following forms:
• Application Checklist for Initial and Continuing Review Full Board.docx (09/02/2022 – New Contact Information for Institutional Biosafety Committee)
• IRB Website : Related Departments and Committees-
Institutional Biosafety Committee (IBC): Investigators must obtain approval from the IBC prior to seeking local IRB approval for research studies that deal with recombinant DNA. Investigators may contact Vijayasmitha Rayadurg in the Office of Research Safety for additional information.

Added new template language to the following form:
• Sample Cover Letter for a Survey Study.docx (09/02/2022)

Changes to the Requests for Exemption form to limit Exempt Category 4 (iii) to researchers and activities internal to UConn Health.

• Request for Exemption Form .doc (09/30/2022)

 

Continuing Review Guidance

Considerations for When the IRB Evaluates the Progress of a Research Study

According to Robert J. Amdur & Elizabeth A. Bankert. IRB Management and Function. 2nd Edition., Jones & Bartlett, 2006, “Continuing review is a monitoring mechanism that assures that continuing safeguards are in place to protect the rights and welfares of research participants.”

When a Protocol/study is submitted for renewal or continuing review the investigator is to report the study progress and findings. When conducting the continuing review, OHRP recommends that IRBs evaluate the following issues to determine whether the study’s approval should be renewed:

Consistent with the IRB-approved Protocol
The IRB should confirm that the information provided by the investigator at the time of continuing review is consistent with the research protocol previously approved by the IRB.

Total Subject Enrollment
Evaluating information about the number of subjects enrolled in the research at the time of continuing review may allow the IRB to ascertain whether enrollment is consistent with the planned number of subjects described in the IRB-approved protocol. Has accrual progressed as planned? If not, will this affect the ability of the researchers to complete the study?

A marked difference between the actual and expected rates of enrollment may indicate a problem with the research project that requires further evaluation, including whether the research project is likely to provide sufficient data to answer the scientific question(s) being posed.

Subject Withdrawals
Subjects may discontinue their participation in research at any point for various reasons (e.g., serious adverse events, conflicts with the investigators, transportation problems, etc.).
The IRB’s continuing review procedures in general should provide for review of:
• The number of subjects who discontinued their participation; and
• A summary of the reasons for the withdrawals, if known.
IRB review of this information may shed light on problems related to the conduct of the research.

To provide an accurate account of the enrollment data, UCONN Health IRB recommends that prior to completing a Continuation form in the iRIS submission system, the Principal Investigator should have the enrollment information for the study available. If this is not the first request for continuation (e.g. study has been open form more than one year), the enrollment data should build off of the previously submitted request for continuation. Investigators should use the enrollment data in the previously approved continuation form as a starting point. The Enrollment Guidance.docx should be reviewed to provide an accurate account of enrollment numbers, screen failures or withdrawals.

Office of Human Research Protection (OHRP) – Resources
Luminaries Lecture Series

OHRP continues to add new videos to help the research community learn about multiple topics.
Click here to view the latest videos of distinguished speakers from OHRP’s Research Community Forum co-sponsored with Northwell Health this past May.
New additions include:
• The COVID Drug Wars That Pitted Doctor vs. Doctor
• Improving Health Equity in Clinical Research
• Vulnerability, Justice, Equity, and Engagement, A Conversation Public Health and Human Subjects Research
• Unusual Practices Masquerading as Usual Care

HSPP Newsletter – April, May, June, 2022

 

FDA Warning Letter Regarding the Failure to Ensure IRB Continuing Review and Approval of Protocol

Inspections of clinical trials are conducted as a part of the U.S. Food and Drug Administration (FDA)’s Bioresearch Monitoring Program.  These inspections are designed to evaluate the conduct of research and to help ensure that the rights, safety, and welfare of human subjects have been protected.  Below you will find a short summary of a warning letter issued because of the failure to obtain continuing review of a study and failure to perform study procedures as required by the protocol.

 

Warning letter to Sabine S. Hazan, M.D.

On February 28, 2022, the FDA issued a warning letter to Dr. Hazan.  The FDA officials who inspected the study concluded that the investigator did not adhere to the FDA regulations governing the conduct of clinical investigations and the protection of human subjects.  Dr. Hazan failed to obtain continuing review and approval for her study.  Specifically, her study IRB approval lapsed. During the course of this lapsed period, she enrolled and randomized subjects into the protocol, and administered investigational drugs to subjects. In addition, she was unable to provide a corrective action plan to prevent the recurrence of this type of violation in the future.

The FDA emphasized that the failure to ensure continuing IRB review and approval, impeded the IRB’s ability to determine the adequacy of the application to conduct the protocol.  This raised significant concerns about the extent to which subjects’ rights and welfare were protected at that site during the lapse in approval.

For more details about the inspection of this study and the findings of the FDA please review the Warning Letter – Sabine S. Hazan, M.D. February 28, 2022

 

 Warning letter to Smitha C. Reddy, M.D. / ACRC Studies, LLC

On May 27, 2022, the FDA issued a warning letter to Dr. Reddy.  The FDA officials who inspected the study concluded that the study as it was implemented raised significant concerns about the safety of subjects enrolled and the reliability of data at that site.

Dr. Reddy failed to ensure that the investigation was conducted according to the investigational plan. Specifically, the investigator did not ensure subjects randomized to an assigned treatment arm received the correct drug for that group, and there was a failure to adhere to procedures for the blinding of staff.

The FDA emphasized that the principal investigator is ultimately responsible to ensure that the study is conducted properly and in compliance with FDA regulations, both to protect the rights, safety, and welfare of study subjects and to ensure the integrity of study data.  Additionally, the FDA required corrective actions to include retraining of the investigator on study drug administration, not just study staff.

For more details about the inspection of this study and the findings of the FDA please review the FDA Warning letter to Smitha C. Reddy, M.D./ACRC Studies, LLC

Office of Human Research Protection (OHRP) – Resources

 

The Office of Human Research Protection (OHRP) has launched two interactive programs to help explain the expectations for investigators in applying the Common Rule review criteria of equitable selection of subjects in research and minimizing research risks for participants. These resources are valuable for investigators to understand and fulfill these specific requirements for protecting human participants in research.

To access these interactive programs click on links below.

Equitable Selection of Subjects : This is a 30-minute scenario which examines how investigators could apply the concept of equitable selection of subjects in research

Minimizing Risks in Research : This is a 30-minutes scenario which examines the concept of research risks and how these risks to participants could be identified and minimized.

 

Human Subjects Training – Frequently Asked Questions

 

 I am a new resident/student at UCONN Health and I completed CITI Training under my affiliation with a former institution.  Is that CITI Certificate valid at UConn Health?

If an individual is to be included in an IRB application and that person has recently become affiliated to UConn Health (e.g. a new student), that person should attach the CITI Training certificate completed under his/her former affiliation.  If the courses previously completed are comparable to the ones required by UCONN Health IRB that individual will not need to complete additional training.  If not, he/she must complete training under his/her affiliation to UConn Health.  The CITI Program will give credit for any modules he/she have completed under other institution’s affiliation and will require completion of modules that are specific to UConn Health.

To affiliate an account in the CITI Program with UConn Health, individuals should log into the CITI program, and click on “Add Affiliation” listed under the “Courses” Menu.  To

find UConn Health in the drop down box, the following words “University of Connecticut“ must be typed.  Then, select “University of Connecticut Heath Center”.  To complete the process, check the box next to the statement: “I AGREE to the Terms of Service for accessing CITI Program materials”   and check the box with the statement: “I affirm that I am an affiliate of University of Connecticut Heath Center.” Last, click on “Continue.”

To select the correct learning group and courses, follow the “Course Enrollment Questions” posted at  https://ovpr.uchc.edu/services/rics/hspp/citi-instructions/

 

Recent Articles Published by a Central IRB

 

ADVARRA IRB:  

 What do I do about Incidental Findings in Research? If you are conducting research that has a potential to uncover an incidental finding, it is best to plan ahead for how you’ll treat the result and if you plan to return that result to a participant. This article describes the plans and consideration to communicate incidental findings to research participants.

eClinical Regulatory Trends Impacting Clinical Research   For the past two years, the clinical research industry has seen an acceleration in staff shifting to a remote, work from home model. While this was initially in an effort to keep everyone safer from the COVID-19 pandemic, many organizations are permanently moving toward a remote or hybrid work model for their staff.  This article discusses how has this shaped current regulatory trends, the benefits of eClinical suite, and the consideration when adopting an eClinical suite.

 

IRB Forms – Update

Added new contact information to the following forms:

• Human Subject Research Determination Form.doc
• dbGaP Access Request Form for IRB Certification.docx
• Participant Feedback Form.doc
• Participant Feedback Form in Spanish.docx
• HIPPA Assurance of Preparatory to Research or Decedent Research .doc
• Instructions for Students Residents or Fellows Doing Research_at_Hartford HealthCare_or_CT Children’s Medical Center.docx

Added Federal required Overview section to:

• Sample Consent for Registry (05/10/2022).doc

 

Upcoming changes in at the HSPP/IRB and the OVPR

 

• Vice President for Research: Dr. Pamir Alpay has been appointed Interim Vice President for Research, Innovation & Entrepreneurship while Dr. Radenka Maric is serving as Interim President of the University of Connecticut.
• Associate VPR and Institution Official: Dr. Victor Hesselbrock has been named Interim Associate Vice President for Research Integrity and Regulatory Affairs and Institution Official following Dr. Byerly’s departure.
• Manager and Deputy Director of HSPP: Deb Gibb retired June 1, after 19 years with the HSPP.  Julia Blair will serve as interim manager of the HSPP.

 

HSPP – January, February, March, 2022- Newsletter

 

How to Write a Low Literacy Informed Consent Form

Obtaining informed consent in non-exempt research is a process required by federal regulations –the U.S Department of Health and Human Services ( HHS) at 45 CFR 46 and the U.S. Food and Drug Administration (FDA) at 21 CFR 50.   The consent process typically includes providing a written consent document containing the required information along with an oral presentation of that information to prospective participants. However, for a consent process to empower individuals to voluntarily participate in a study or not, the information in the consent document must be presented in a language they can understand.   The readability of a consent form is essential to enable potential participants to have sufficient comprehension of the elements that facilitate a decision. The language used in consent forms should not be complex.   An 8^th grade reading level is the suggested benchmark to use as the readability index.

Investigators conducting clinical trials should consider literacy of potential participants when preparing consent documents.

John Hopkins Office of Human Subjects Research  and Elizabeth Winslow offers the following guidance for preparing consent forms:

 

• Recommendations to lower the reading level of consent forms:

 Words

• Use words familiar to the non-medical reader.
• If possible, keep words to 2- 3 syllables or fewer.
• Use common, familiar words

Sentences/Paragraphs/Print Size & Type:

• Write short, simple, and direct sentences.
• Keep paragraphs short and limited to one idea.
• Use active verbs.
• Use the second person (you) not third person (the participant) to increase personal identification.
• Avoid contractions.
• Use page numbers
• Use at least 12-point font and consider a larger font based on your audience.
• Check the text to see if each idea is clear and logically sequential.
• Avoid large blocks of printed text.

 Avoid Complex Medical Terminology

• Avoid medical Terminology. If a medical term must be used, define /explain it
• Be consistent with use of all terminology, such as drug names and abbreviations.
• Use the appropriate abbreviation the first time a drug name is used in the consent.

 Abbreviations:

• Spell out abbreviated terms the first time you use them
• Abbreviation terms such as DNA, HIV and AIDS that have come to be accepted as standard by your proposed study population need not be spelled out.
• Do not use e.g. or etc., use instead, “for example,” “so forth.”
• Spell out acronyms when first used.

 Pictures

• Use photos, graphics, tables, illustrations or diagrams if they will help clarify procedures.

Numbers

• Use numerals rather than words for numbers, e.g., “10” instead of “ten,” “1 out of 4” instead of “one out of four.”

 

Tips to Describe Study Procedures

• Consent forms for projects that involve collection of blood or other fluids should include the amount(s) to be taken.  Do not use ml. or cc. as a volume measure; give a volume equivalent in teaspoons or tablespoons. Rather than abbreviating such words as teaspoon and tablespoon, please spell them out.
• Do not use symbols such as “>”; use “greater than.”
• Describe study design procedures such as “double blind,” “randomized,” and “placebo/controlled” when the concept(s) is/are first introduced. Example: “A placebo is an inactive substance that looks like the study drug, but contains no medication.”
• Do not use the words “treatment” or “therapy” to describe an investigational drug, device or procedure. Use the term “study drug” not “study medication” when the drug is investigational.  The word “medication” or “medicine” should only be used if the drug is commercially available for that particular condition.
• Do not use the term “treatment” or “therapy”” if one of the study arms will be a placebo. Instead, use words like: “study product”, “study drug or placebo”,  “study regimen” or “study procedure
• Do not describe investigational drugs, devices or procedures as “new.”For investigational drugs or devices, state they are investigational or “experimental” and describe that term (e.g., the word “investigational” means the study drug is not approved by the U. S. Food and Drug Administration (FDA) and is still being tested in research studies.) Be consistent in using “investigational” throughout the consent form.
• Use “research study,” instead of “trial.”
• Use the word “participant” in the consent form instead of “patient” since this is research.  However, you may use “patient” when referring to the person prior to his/her entering the study.
• When describing randomization for 2 groups use, “like the flip of a coin,” for more than 2 groups, use “like drawing numbers from a hat.”

To check the grade level of a consent document, the investigator can implement the following steps. 

For Microsoft Word:

1. on the “File” tab, click the “Options” button;
2. on the “Proofing” tab, under “When correcting spelling and grammar in Word”, make sure “Check grammar with spelling” is selected;
3. under “When correcting spelling and grammar in Word”, select the “Show readability statistics” check box.  Click on OK
4. Click on the “Review Tab”
5. Click on “Spelling & Grammar”

After the grammar check is complete, Word displays a message box showing you the readability grade-level.

 

D- The following websites and word substitution file are helpful for drafting consent forms:

1. a)  Glossary of medical words: (http://kidshealth.org/kid/word/)
   b)  Clinical Research Glossary: (http://www.firstclinical.com/icfglossary/)
   c)  Glossary of lay terms: (http://humansubjects.stanford.edu/general/glossary.html)

 

• The following Checklist for Low Literacy Informed Consent Forms .pdf has been posted in the UCONN Health IRB website

 

 

Checklist How to write a Low Literacy Informed Consent Form
Recommendations to lower the reading level of consent forms	Check
Words
Use words familiar to the non-medical reader
If possible, keep words to 2- 3 syllables or fewer
Use common, familiar words
Sentences/Paragraphs/Print Size & Type
Write short, simple, and direct sentences
Keep paragraphs short and limited to one idea
Use active verbs
Use the second person (you) not third person (the participant) to increase personal identification
Avoid contractions
Use page numbers
Use at least 12-point font and consider a larger font based on your audience
Check the text to see if each idea is clear and logically sequential
Avoid large blocks of printed text
Avoid Complex Medical Terminology
Avoid medical terminology. If a medical term must be used, define/explain it
Be consistent with use of all terminology, such as drug names and abbreviations
Use the appropriate abbreviation the first time a drug name is used in the consent
Abbreviations
Spell out abbreviated terms the first time you use them
Abbreviated terms such as DNA, HIV and AIDS that have come to be accepted as standard by your proposed study population need not be spelled out
Do not use e.g. or etc., use instead, “for example,” “so forth.”
Spell out acronyms when first used
Pictures
Use photos, graphics, tables, illustrations or diagrams if they will help clarify procedures
Numbers
Use numerals rather than words for numbers, e.g., “10” instead of “ten,”  “1 out of 4” instead of “one out of four.”
Tips to Describe Study Procedures
Consent forms for projects that involve collection of blood or other fluids should include the amount(s) to be taken.  Do not use ml. or cc. as a volume measure; give a volume equivalent in teaspoons or tablespoons. Rather than abbreviating such words as teaspoon and tablespoon, please spell them out.

 

Checklist How to write a Low Literacy Informed Consent Form
Tips to Describe Study Procedures	Check
Do not use symbols such as “>”; use “greater than.”
Describe study design procedures such as “double blind,” “randomized,” and “placebo/controlled” when the concept(s) is/are first introduced. Example: “A placebo is an inactive substance that looks like the study drug, but contains no medication.”
Do not use the words “treatment” or “therapy” to describe an investigational drug, device or procedure. Use the term “study drug” not “study medication” when the drug is investigational.  The word “medication” or “medicine” should only be used if the drug is commercially available for that particular condition
Do not use the term “treatment” or “therapy”” if one of the study arms will be a placebo. Instead, use words like: “study product”, “study drug or placebo”
Do not describe investigational drugs, devices or procedures as “new.” For investigational drugs or devices, state they are investigational or “experimental” and describe that term (e.g., the word “investigational” means the study drug is not approved by the U. S. Food and Drug Administration (FDA) and is still being tested in research studies.) Be consistent in using “investigational” throughout the consent form.
Use “research study,” instead of “trial.”
Use the word “participant” in the consent form instead of “patient” since this is research.  However, you may use “patient” when referring to the person prior to his/her entering the study.
When describing randomization for 2 groups use, “like the flip of a coin,” for more than 2 groups, use “like drawing numbers from a hat.”
To check the grade level of a consent document, the investigator can implement the following steps
For Microsoft Word: 1.    on the “File” tab, click the “Options” button; 2.    on the “Proofing” tab, under “When correcting spelling and grammar in Word”, make sure “Check grammar with spelling” is selected; 3.    under “When correcting spelling and grammar in Word”, select the “Show readability statistics” check box.  Click on OK 4.    Click on the “Review Tab” 5.    Click on “Spelling & Grammar” After the grammar check is complete, Word displays a message box showing you the readability grade-level.

 

 

ResearchMatch, an Online Recruitment Tool

 

ResearchMatch.org is a national online recruitment tool for health research, funded by the National Institutes of Health and maintained at Vanderbilt University. ResearchMatch connects health researchers with individuals interested in volunteering through its secure online matching tool, available in English and Spanish. UConn Health is part of the ResearchMatch Network and there is no cost to UConn Health researchers to use ResearchMatch. There are currently over 160,000 (and counting!) registered volunteers across the country.

 

To see if ResearchMatch might be useful to you, register now to conduct a feasibility analysis:

Register here: https://www.researchmatch.org/researchers/. (You do not need to be a Principal Investigator to register.) The registration process takes less than 10 minutes. Registration grants you “feasibility access” to search the current ResearchMatch volunteer population for demographic and health information of volunteers within a designated geographic area.

 Then, if you decide to use ResearchMatch to conduct participant recruitment, you will need IRB approval. Once approved, you may request “recruitment access” in ResearchMatch and upload your IRB approval letter and your IRB-approved contact message. Recruitment access will give you the ability to send your contact message to volunteers that you select. If a volunteer agrees, you will be given access to his/her contact information in order to contact about possible study participation.

 The next ResearchMatch Training is April 14, 2022 at 3:00 pm.

For questions about how to use ResearchMatch for your health research, please contact ResearchMatch Liaison, Ellen Ciesielski eciesielski@uchc.edu or visit https://ovpr.uchc.edu/services/rics/hspp/resources/researchmatch/.

 

 

Office of Human Research Protection (OHRP) – Resources

  

• OHRP New Informational Resource Flyer with its Very Own QR Code!

OHRP’s new Informational Resource Flyer includes a QR code allowing anyone with a smart phone access to a free online library of trusted resources about research and research participation. Print, display, and distribute this flyer at your centers for the benefit of prospective research participants!

Find the flyer here together with other informational materials (in English and Spanish) that you may wish to print and provide for potential research participants! These resources are free and you do not need permission to distribute them.

 

• New Interactive Training Programs on IRB Reviews!

OHRP launched two interactive training programs on considerations for reviewing and designing research involving human participants.

OHRP created these programs to enable investigators and IRB reviewers to be cognizant of the importance of diversity, inclusion, and risk minimization in research participation.

Click here to access our other scenarios!

 

• Recordings of OHRP Presentations on Human Subjects Research and Investigator Responsibilities for Protecting Participants in Research!

 

What is Human Subjects Research? A Review of the Common Rule and its Application provides helpful explanation on the complex concept of human subjects research and how to address related considerations in the NIH grant application process.

 What Investigators Need to Know About IRB Review helps investigators understand the thoughts and considerations needed for writing a successful plan to protect human research participants that would pass the muster of reviewers.

These videos will help investigators with the NIH grant application and IRB review process.

 

 

HSPP- October-November-December, 2021- Newsletter

 

FDA Warning Letter Regarding the Failure to Submit INDs for the Conduct of Clinical Investigations with an Investigational New Drug

 

Inspections of clinical trials are conducted as a part of the U.S. Food and Drug Administration (FDA)’s Bioresearch Monitoring Program.  These inspections are designed to evaluate the conduct of research and to help ensure that the rights, safety, and welfare of human subjects have been protected.  Below you will find a short summary of warning letters issued because of the failure to submit investigational new drug applications.

 

Warning letter to Kaleido Biosciences, Inc

On September 7, 2021, the FDA issued a warning letter to Kaleido Biosciences, Inc.   The FDA officials inspected two of Kaleido’s studies and concluded that investigators did not adhere to the FDA regulations governing the conduct of clinical investigations and the protection of human subjects.

Kaleido investigators thought that the product used in their investigations was subject to regulations as medical food but not subject to regulations as a drug.  However, the FDA inspectors concluded that the product was intended for use as a drug, and not as a food.

The argument established by the FDA to support their conclusion is based in the definition of food vs a drug in the use of a clinical investigation.  The FDA argued that the purposes of this clinical investigation was to evaluate the efficacy of a food product as treatment of a disease and, consequently, the food in this trial was seen as a drug.   Therefore, use of the food product in the clinical trial is not exempt from the investigation new drug requirements.

For more details about the inspection of these studies and the findings of the FDA please review the warning letter to Kaleido Biosciences, Inc.

 

Warning letters  to Jon B. Cole, MD, and Lauren R. Klein, MD., MS.

The FDA regulations require a sponsor to submit, and to have in effect, an investigational new drug application (IND) before initiating a clinical investigation of a drug in human subjects, unless the clinical investigation qualifies for an exemption (see 21 CFR 312.20 and 312.40(a)).

The FDA determined that Dr. Cole  and Dr. Klein failed to comply with these requirements while using marketed drugs in two studies.

The investigators thought that an IND was not needed, and argued that the medications administered to subjects were not part of a research intervention but were provided only for clinical purposes.   In addition, the investigators stated that if their clinical investigations were subject to FDA jurisdiction, they met the criteria for exemption from the investigational new drug requirements.

Contrary to the investigators, the FDA auditors concluded that the studies were designed to study the safety and efficacy of those marketed drugs products. In addition, the FDA determined the drugs were not delivered in the course of medical practice, but for research purposes. “The FDA underlined that whenever an investigator limits his choices, his patients’ choices, and the choices of the people working for them in the treatment of patients, then he/she is conducting a clinical investigation. This is different from the practice of medicine, where the primary intent is to treat the individual patient.”

Moreover, the FDA inspectors determined these clinical investigations did not meet the criteria for exempt since these investigations increased the risks or decreased the acceptability of the risks associated with the use of the drug products.

For more details about the studies mentioned above, the FDA’s thinking regarding IND requirements for market drugs and FDA views of clinical use vs. clinical investigation, please click on the links to the warning letters seen below:

• Warning letter to Jon B. Cole, MD
• Warning letter to Lauren R. Klein, MD., MS

  

Medical Devices

 Medical device products are regulated by the FDA’s Center for Medical Devices and Radiological Health (CDRH).  Depending on the device classification and other factors, the Code of Federal Regulations, Title 21, defines the requirements to approve or clear devices sold in the United States.

Investigators planning to conduct research with medical devices should learn the FDA status of a device.  The investigator should determine whether the device has been approved, cleared for marketing, or whether it is an investigational device. When used in research it is important that the informed consent form accurately identify the type of device being used as approved, cleared, or investigational (see FDA guidance).

Reviewing the following information will allow investigators to understand the process by which the FDA classifies devices, clears devices, and approves devices. The sections below includes excerpts from the document titled Is it really FDA approved? and the FDA webpage on the Premarket Notification 510(k) clearance process.

 

Overview of Device Regulation

FDA classifies devices, or more accurately device types, in order to identify the degree of regulations for that product area.  Classification is based on two factors:  the device description/its physical characteristics, and the intended use.

FDA classifies devices into Class I, II, or III.  The class of the device generally increases with its degree of risk. Regulatory control increases from Class I to Class III. The device classification regulation defines the regulatory requirements for a general device type. Most Class I devices are exempt from Premarket Notification 510(k); most Class II devices require Premarket Notification 510(k); and most Class III devices require Premarket Approval.

A description of device classification and a link to the Product Classification Database is available at “Classification of Medical Devices.”  To learn more about how medical devices are classified, please watch the FDA educational video titled: How is my Medical Device Classified?

Note – A registration number with the FDA only means the FDA is aware of the manufacturer and device, and does not mean the device is ‘FDA cleared’ or ‘approved.’ (see more info here)

 

Cleared Devices

The FDA may clear a device for marketing through the 510(k) process, when the manufacturer demonstrates the device is substantially equivalent to a predicate device. A claim of substantial equivalence does not mean the device(s) must be identical. Substantial equivalence is established with respect to intended use, design, energy used or delivered, materials, performance, safety, effectiveness, labeling, biocompatibility, standards, and other applicable characteristics.  The 510K clearance process does not require submission of clinical data to support the claim.

A device which is “cleared” to market should not be deemed the same as a device that has been “approved” by the FDA through a Premarket Approval (PMA) application.

 

Approved Devices 

To receive FDA approval to market  devices, manufacturers must demonstrate with sufficient, valid scientific evidence (i.e., submitting clinical data to support a claim) that there is a reasonable assurance that the devices are safe and effective for their intended use.

 

Investigational Devices

An investigational medical device is one that is the subject of a clinical study designed to evaluate the effectiveness and/or safety of the device.  An application for an Investigational Device Exemption (IDE) is to be submitted by the Sponsor or investigator to use the investigational device/unapproved device in a clinical study.

Data collected during these clinical studies is to be included in a future marketing application. The IDE application enables manufacturers to ship a device from one state to another when conducting a clinical study on the device without being subject to most other provisions of the Federal Food, Drug, and Cosmetic Act.

An IDE application may also be required for a legally marketed device that has been modified and/or intended for a new use.

Clinical studies with investigational devices of significant risk must be approved by FDA and by an Institutional Review Board (IRB) before the study can begin. Studies with devices of no significant risk must be approved by the IRB only before the study can begin.

Investigators conducting research with medical devices are to include in their initial application and informed consent forms whether their devices are approved devices, cleared devices or investigational devices.

 

Inclusion of Certificate of Confidentiality Language in Consent Forms for NIH funded Studies

 

In October 2017, NIH updated its Policy for issuing Certificates of Confidentiality (Certificates or CoCs) for NIH-funded and conducted research. These Certificates protect the privacy of participants by limiting the disclosure of identifiable, sensitive information.

Informed consent forms of NIH funded studies must include the required language regarding the Certificate of Confidentiality (CoC) and the protections it offers. This requirement is already listed in the Main Consent Form Template .doc (page 8) and the Main Consent Form Checklist.doc  (Page 4)

More information about Certificates of Confidentiality is available at https://grants.nih.gov/policy/humansubjects/coc.htm

 

IRB Forms – Update

 

The submission checklists for IRB applications have been updated.

The updates include:

• Changing the point of contact for I.T. security
• Clarifying details regarding the need for letters of permission to conduct research
• Clarifying details regarding the FERPA verification form
• Clarifying details regarding the use of recruitment tag lines for on-line postings