Author: Mayra Cagganello

HSPP- Jan-Feb-Mar, 2019 – Newsletter

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Revised Common Rule (45 CFR 46)

The revised version of the regulation governing human subjects research (i.e. 45 CFR 46 also known as the Common Rule) became effective January 21, 2019.  Due to this revision, several IRB forms, templates, and policies have been modified.  Always refer to the HSPP web site to ensure you are using the most recent version of a form.

The following sections contain a summary of those changes.

    1. The Consent Form Template and Consent Checklist were revised to incorporate seven new elements of consent for federally funded/supported research. For those approved federally funded/supported research studies that are actively enrolling subjects, investigators should submit either at the time of continuation or through a request for modification a revised consent form with the new required elements.  Until such time as this review occurs studies are considered grandfathered under the current version of the Common Rule.  Subjects will not be required to be re-consented based solely on these changes.  For federally funded/supported studies that are closed to new enrollment the consent form will need to be revised only if there is another reason that triggers a change to the document.  For example if new risks are being disclosed, at the time the consent is revised to incorporate the new risk the consent would also have to be brought into compliance with the new requirements.    For previously approved non-federally funded/supported research, no changes are necessary; however, these new elements will be used as the guiding principle of consent elements moving forward.
    2. Waiver/Alteration of Consent:   If the research involves using identifiable private information or identifiable biospecimens, the investigator will need to explain in the waiver document why the research could not practicably be conducted without access to and use of the identifiable private information/biospecimens.If a waiver is necessary for federally funded/supported studies investigators must be sure to address the additional element describe above at the time the study is transitioned to the revised rule. Waiver of Documentation of Consent:  There is a new provision for allowing for waiver of documentation of consent.  Documentation of consent may also be waived if the subjects or legally authorized representatives are members of a distinct cultural group or community in which signing forms is not the norm, that the research presents no more than minimal risk of harm to subjects and provided there is an appropriate alternative mechanism for documenting that informed consent was obtained.
    3. Changes to Continuing Review Requirement: Unless otherwise required and justified by the IRB, continuing review will no longer be required for non-FDA regulated federally funded research that meets the criteria for expedited review. Investigators who have non-FDA regulated federally funded research that qualifies for expedited review will be asked to provide an expected completion date of the research, which will become the expiration date of IRB approval.  For previously approved research this may be provided as part of one last request for continuation (e.g. if IRIS has already generated a continuing review due task) or as part of a request for modification.  The PI will be required to submit a request for modification to extend this expected completion date if necessary.   The IRB may require justification for the expected completion date as it deems appropriate.              Note:   Continuing review is still a requirement for all FDA regulated research even if all subjects are in long-term follow-up or the research is in data analysis.

Any study that does not requires continuing review still need to submit a modification to the IRB prior to implementing changes to the conduct of that study except when the change is necessary to eliminate immediate hazards to subjects.  Modifications include, but are not limited to,  change in design, removal or change to survey tool, change in funding source, change to recruitment materials, adding or removing investigators, changing the title of the project, requesting additional subjects beyond the original approved number, changes to informed consent forms, or other correspondence with potential or current subjects.

4. Changes to the Initial Application Form in IRIS:   The IRB application form in IRIS was edited. The request for Exempt status categories and Expedited review categories were removed from the application and are now described in two separate word documents to be attached to the application form in IRIS. The following forms have been published in the IRB website and should be submitted when requesting a determination for exemption  or review under an of the expedited categories:

5.The following IRB forms have been updated and published in the IRB website:

Points to Remember When Relying on an External IRB

  • With the exception of reporting changes in study personnel,  once the determination is made to accept the external IRB as the IRB of Record, from that point forward the UConn Health investigator only deals with the IRB of Record for the review of continuations, modifications, unanticipated problems and non-compliance.
  •  The Principal Investigator is responsible for knowing and following the requirements of the reviewing IRB, inclusive of requirements for reporting subject complaints, non-compliance, unanticipated problems and outcomes of audits and inspections. The PI is responsible for ensure that the research team is also aware of and follows such.
  • Research for which IRB oversight has been deferred to an external IRB may still be subject to audit by the UConn Health Research Compliance Monitor.

Difference between Privacy and Confidentiality

Privacy applies to the individual and confidentiality applies to the data obtained from the  individual.

According to the IRB Guidebook, published by the Office for Human Research Protections (OHRP 1993): “Privacy can be defined in terms of having control over the extent, timing, and circumstances of sharing oneself (physically, behaviorally, or intellectually) with others. Confidentiality pertains to the treatment of information that an individual has disclosed in a relationship of trust and with the expectation that it will not be divulged to others, in ways that are inconsistent with the understanding of the original disclosure without permission.”

Therefore, the privacy of the subjects in a research study can be maintained by conducting the consent process, interviews, and procedures in a private room.  The confidentiality of the subjects’ data can be protected, for example, by storing the data on encrypted password protected computers.

Expanded Definition of “Clinical Trial” & ClinicalTrials.gov

 The Revised Common Rule expanded the definition of “clinical trial” with the intention of harmonizing with the National Institutes of Health’s definition. The expanded definition includes any “research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on biomedical or behavioral health-related outcomes.” Importantly, the revised definition includes studies that had not previously been considered clinical trials, like social and behavioral research.

What if my study meets the expanded definition of a clinical trial?

1) If your clinical trial is funded by a Federal department or agency, the Revised Common Rule requires that your consent form be posted on a public platform, like ClinicalTrials.gov, after the trial is closed to recruitment, and no later than 60 days after the last subject visit.

2) If your clinical trial evaluates at least one drug, biological, or device product regulated by the FDA (See this decision checklist for more details), regardless of funder, you are required to register and post results on ClinicalTrials.gov.

3) If your clinical trial is NIH funded, in whole or in part, you are required to register the study and report results on ClinicalTrials.gov.

4) Regardless of funder, if you wish to comply with the ICMJE policy (followed by the BMJ, JAMA and many others journals) requiring registration as a condition of consideration for publication, you may voluntarily register your study with ClinicalTrials.gov.

For assistance with ClinicalTrials.gov, see our webpages and contact UConn Health’s ClinicalTrials.gov Administrator, Ellen Ciesielski (860-679-6004) in Research Integrity and Compliance Services.

HSPP- October-November-December, 2018

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Overview of Major Changes to the Common Rule (45 CFR 46)

The revised version of the regulation governing human subjects research (i.e. 45 CFR 46 also known as the Common Rule) became effective January 21, 2019. Accordingly, several IRB forms, documents templates, policies and the IRB applications in IRIS have been revised. It is the intention of the IRB that all federally funded/supported research will be brought into compliance with the revised regulation at the time of the continuing review that occurs on or after January 21, 2019.   Until such time as that review occurs those studies are considered grandfathered under the previous version of the regulation.  Investigators may request to transition to the revised regulation soon by submitting a request for modification.

 

The following sections contain a summary of the major changes.

The Consent Form Template and Consent Checklist have been revised to incorporate seven new elements of consent for federally funded/supported research. The new requirement regarding process and the new 7 elements of a consent are as follows

  • Consent must begin with a concise and focused presentation of the key information that is most likely to assist a prospective subject or LAR in understanding the reasons why one might or might not want to participate in the research. This part of the informed consent must be organized and presented in a way that facilitates comprehension
  • Informed consent as a whole presents information in sufficient detail relating to the research, and is to be organized and presented in a way that does not merely provide lists of isolated facts, but rather facilitates the prospective subject’s or LAR’s understanding of the reasons why one might or might not want to participate
  • One of the following statements if the research involves the collection of identifiable private information (IPI) or identifiable biospecimens (IB):
  • A statement that identifiers might be removed from the IPI or IB and that, after such removal, the information or biospecimens could be used for future research studies or distributed to another investigator for future research studies without additional informed consent from the subject or the LAR, if this might be a possibility;   OR
  • A statement that the subject’s information or biospecimens collected as part of the research, even if       identifiers are removed, will not be used or distributed for future research studies
  • If applicable, a statement that the subject’s biospecimens (even if identifiers are removed) may be used for commercial profit and whether the subject will or will not share in this commercial profit
  • If applicable, a statement regarding whether clinically relevant research results, including individual research results, will be disclosed to subjects, and if so, under what conditions
  • If applicable, for research involving biospecimens, whether the research will (if known) or might include whole genome sequencing (i.e. sequencing of a human germline or somatic specimen with the intent to generate the genome or exome sequence of that specimen).

For those approved federally funded/supported research studies that are actively enrolling subjects, investigators should submit either at the time of continuation or through a request for modification a revised consent form with the new required elements. Until such time as this review occurs studies are considered grandfathered under the current version of the Common Rule. Subjects will not be required to be re-consented based solely on these changes.

For federally funded/supported studies that are closed to new enrollment the consent form will need to be revised only if there is another reason that triggers a change to the document. For example if new risks are being disclosed, at the time the consent is revised to incorporate the new risk the consent would also have to be brought into compliance with the new requirements.

For previously approved non-federally funded/supported research, no changes are necessary; however, these new elements will be used as the guiding principle of consent elements moving forward.

To learn more about the new elements of consent please review IRB Policy 2011-008.0.pdf– Informed Consent – Forms

The revised regulation expands the definition of Legally Authorized Representative to now recognize that if State law is silent legally authorized representative means an individual recognized by institutional policy as acceptable for providing consent in the non-research context on behalf of the prospective subject to the subject’s participation in the procedure(s) involved in the research.

To learn more about the new changes to the consent process please review IRB Policy 2011-008.5.pdf – Informed Consent – Providing and Obtaining Informed Consent

 

Waiver/Alteration of Consent: When a waiver or alteration of consent is requested the following additional criterion must be met in order for the IRB to grant the waiver/alteration.

  • If the research involves using identifiable private information or identifiable biospecimens, the research could not practicably be carried out without using such information or biospecimens in an identifiable format.

If a waiver is still necessary (see below) for federally funded/supported studies investigators must be sure to address this additional element at the time the study is transitioned to the revised rule.

The revised regulation allows for certain activities regarding screening, recruiting or determining eligibility (e.g. telephone screening or chart reviews for the purpose of determining eligibility) to occur without a waiver/alteration if either of the following conditions are met:

  • The investigator will obtain information through oral or written communication with the prospective subject or legally authorized representative, or
  • The investigator will obtain identifiable private information or identifiable biospecimens by accessing records or stored identifiable biospecimens.

 

The above change has been already be implemented for non-federal studies, and as of January 21, 2019 will be implemented to federally funded studies. If a waiver had been previously approved but is no longer necessary, that document should not be included in the submission packet at the time the study is transitioned to the revised rule.

Note:   There has been no change to HIPAA and there must be adequate measures in place to protect the confidentiality of any information collected for the purpose of screening, recruiting or determining eligibility prior to informed consent.

To learn more about the new changes to the waiver of consent please review IRB Policy 2011-008.2.pdf – Informed Consent – Waivers and Alterations

 

Waiver of Documentation of Consent: There is a new provision for allowing for waiver of documentation of consent. Documentation of consent may also be waived if the subjects or LAR are members of a distinct cultural group or community in which signing forms is not the norm, that the research presents no more than minimal risk of harm to subjects and provided there is an appropriate alternative mechanism for documenting that informed consent was obtained.

To learn more about the new changes to the waiver of documentation of consent please review IRB Policy 2011-008.2.pdf – Informed Consent – Waivers and Alterations

 

Changes to Continuing Review Requirement: Unless otherwise required and justified by the IRB, continuing review will no longer be required for non-FDA regulated federally funded research that meets the criteria for expedited review.

 

Investigators who have non-FDA regulated federally funded research that qualifies for expedited review will be asked to provide an expected completion date of the research, which will become the expiration date of IRB approval.   For previously approved research this may be provided as part of one last request for continuation (e.g. if IRIS has already generated a continuing review due task) or as part of a request for modification. The PI will be required to submit a request for modification to extend this expected completion date if necessary.   The IRB may require justification for the expected completion date as it deems appropriate.

Note:   Continuing review is still a requirement for all FDA regulated research even if all subjects are in long-term follow-up or the research is in data analysis. The IRB has already implemented this practice for expedited research that is not federally funded or subject to FDA oversight.

 

New Exempt Categories : There have been several revisions to the types of research that may be exempt and the exemptions may now apply to research that only incidentally includes prisoners as subjects (e.g. the research is aimed at involving a broader subject population and only incidentally includes a subject who became incarcerated after providing consent). These categories are applicable regardless of funding source. The new exemption categories are described in the form titled Request for Exemption

Any study previously granted an exemption remains grandfathered under that exemption.

Studies that had been approved through the expedited process that may qualify for exemption under the revised regulation will be transitioned to exempt status on a case-by-case basis as requests for continuation or modifications are received.

To learn more about the revised Exempt categories please review Policy # 2011-009.2.pdf – Institutional Review Board – Exemptions

 

Changes to the Initial Application Form in IRIS:   The IRB application form in IRIS has been edited. The request for Exempt status categories and Expedited review categories have been removed from the application and are now described in two separate word documents to be attached to the application form in IRIS. The following forms have been published in the IRB website:

  1. The following IRB forms have been updated and published in the IRB website:
  • Application Checklist for Expedited Review (to reference request for expedited review form)
  • Application Checklist for Exemption (to reference request for exemption form)
  • Consent Checklist Addendum to Transition to Revised Rule (lists only new elements of 45 CFR 46 to incorporate into prior version of ICF for studies approved prior to 1/21/2019)
  • Human Subject Determination Form (based on updated definitions and activities that are deemed not to be research)

 

RESEARCHMATCH NOW AVAILABLE IN SPANISH!

ResearchMatch (RM) is the national online recruitment tool that matches people interested in participating in studies with researchers throughout the U.S. There is no cost to UConn Health researchers to use ResearchMatch. Once you register as a researcher, you can review the population characteristics of the ResearchMatch registry, which includes over 135,000 people from every state in the country.

*NEW* ResearchMatch has just launched a Spanish version of the website inviting Spanish speakers to sign up in Spanish. Researchers from UConn Health are now able to connect with and recruit Spanish-speaking volunteers for their studies.

If you would like to use ResearchMatch, you will need IRB approval for this recruitment method, including approval of the contact message emailed to volunteers. ResearchMatch can be added to an already-approved study via a modification.

Interested in using ResearchMatch? Sign up now, attend an online training, or visit our webpage or contact Ellen Ciesielski for more information.

Already registered with ResearchMatch and want to recruit Spanish-speaking volunteers? Submit your ResearchMatch contact message and other materials translated into Spanish (consent form, questionnaires, etc.) for IRB approval and ensure you are prepared for inquiries from Spanish-speaking volunteers.

HSPP- July-August-September, 2018- Newsletter

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AAHRPP Site Visit 2018

 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.

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.  This is a two-step process.  Step 1, which has been completed, consisted of AAHRPP reviewing all 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.  While specific dates have not yet been determined, the next accreditation site visit will occur in the spring of 2019.

During the site visit, representatives from AAHRPP will conduct interviews and review studies records to ensure that policies and procedures have been implemented effectively.  AAHRPP representatives will interview the Institutional Official (Wesley Byerly), IRB members, HSPP staff, investigators and research study team members, and individuals that represent various research compliance functions, such as radiation safety, research pharmacy, scientific review, and conflicts of interest.  Individuals selected for such interviews will be asked questions about regulatory and ethical issues related to research with human participants and how they interact with the IRB. Investigators and research staff will also be asked about the conduct of their research studies.

In general, topics that may be included during an AAHRPP interview process include:

  1. Familiarity and compliance with HSPP/IRB polices and procedures
  2. Roles and responsibilities of investigators and research staff
  3. Obtaining and documenting informed consent
  4. Conflict of interest disclosures
  5. Minimizations of risks to research participants and protecting human subject’s rights and welfare
  6. Types of training individuals have received in human subject’s protections.

If you are selected for an interview, you will be notified a few weeks prior to the site visit.  An educational handout will be provided to help you to prepare.

In addition, you can request an educational session with the Educational Specialist to learn more about the site visit and possible interview questions.

 

Are you liable for ClinicalTrials.gov Civil Money Penalties?

 On September 18, 2018, the Food and Drug Administration (FDA) announced a draft guidance titled Civil Money Penalties relating to the Clinical Trials.gov Data Bank. The guidance addresses how the FDA Centers (Center for Drug Evaluation and Research, Center for Biologics Evaluation and Research, and Center for Devices and Radiological Health, for drug, biological, and device products, respectively) identify whether parties have failed to submit required clinical trial registrations, results, or certifications, or knowingly submitted false or misleading information.

The guidance explains that when a responsible party has potentially failed to comply with its disclosure obligations, the FDA will send a Preliminary Notice of Noncompliance Letter, and allow the responsible party 30 days to make corrections. If the FDA determines that the responsible party has still failed to comply, the FDA may issue a Notice of Noncompliance, assess civil monetary penalties, or seek an injunction and/or criminal prosecution. The statutory maximum for civil penalties is “not more than $10,000 for all violations adjudicated in a single proceeding,” plus “not more than $10,000 for each day that the violation continues” past the 30-day notification period.

The deadline to submit your comments on this draft, electronically or by paper, is November 20, 2018.

  • To check if your trial meets the criteria for ClinicalTrials.gov registration and results posting set forth by the FDA, see the checklist found here. Applicable clinical trials include those evaluating at least one drug, biological, or device product regulated by the FDA.

 

  • If your NIH-funded study involves human subjects, check here to see if it meets the NIH’s broad definition of a clinical trial and will require registration and results posting. NIH defines a clinical trial as a research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes.
  • For questions about ClinicalTrials.gov, please contact Research Compliance Monitor, Ellen Ciesielski at 860-679-6004

 

Does NIH require you to register your basic science research in ClinicalTrials.gov?

 NIH has released a Request for Information (RFI), Registration and Results Reporting Standards for Prospective Basic Science Studies Involving Human Participants. This RFI seeks input from the scientific research community and the general public regarding how best to implement the NIH Policy on the Dissemination of NIH-Funded Clinical Trial Information (NOT-OD-16-149) for prospective basic science studies involving human participants. NIH is specifically interested in learning more about studies that meet the NIH definition of a clinical trial (NOT-OD-15-015) but are not defined as applicable clinical trials (42 CFR Part 11), and also meet the definition of fundamental research. You can submit your comments here by November 12, 2018.

 

Access to Investigational Drugs through  Clinical Trials, the Expanded Access Program, or  the Right-to-Try Law

An investigational drug is one that has been tested in a laboratory and in animals and is being studied in human for efficacy and safety. Investigational drugs are not yet approved by the Food and Drug Administration (FDA) for use in the general population.

There are various mechanisms through which patients may obtain access to an investigational drug. These mechanisms include 1) clinical trials 2) the FDA’s expanded access program or 3) the recently passed Federal law known as the Right to Try Law. Each of these mechanisms will be discussed below and then compared in table format.

Clinical Trials: The standard mechanism for obtaining access to an investigational drug is through participation in a clinical research trial. A clinical research trial is conducted in accordance with a formal research protocol and its purpose is to evaluate the effectiveness and safety of an investigational drug. To participate in a clinical trial the patient must have the disease or disorder that is being studied and must also meet any specific inclusion or exclusion criteria defined in the research protocol. Patients can search for clinical trials that are being conducted at https://clinicaltrials.gov/.

Expanded Access Program: If participation in a clinical trial is not possible, access to an investigational drug may be sought through the FDA’s Expanded Access Program (EAP).

Access through the EAP may be appropriate when all of the following criteria are met:

  • The individual must have a serious/immediately life-threatening disease or terminal condition.
  • There must not be a comparable or satisfactory alternative therapy to diagnose, monitor, or treat the disease or condition.
  • The individual is unable to participate in a clinical trial.
  • Potential patient benefit justifies the potential risks of treatment.
  • Providing the drug to the patient will not interfere with the conduct of the clinical trial.

To apply for expanded access, the patient’s physician should first submit a request to the manufacturer of the investigational drug to obtain approval for the use of the product outside of the clinical trial setting. The manufacturer is under no obligation to approve such requests. If the manufacturer will provide the drug, the physician must then submit a request for approval to an Institutional Review Board (IRB) and to the FDA. An IRB is a committee that reviews the plan for the use of the drug to ensure that the rights and welfare of the recipient are protected. If FDA and IRB approval is provided, in the majority of cases the doctor must obtain informed consent from the individual who will receive the drug.  The individual’s consent is documented by signing an informed consent form that, among other things, describes the potential risks associated with the drug. More about the FDA’s Expanded Access Program is available at https://www.fda.gov/NewsEvents/PublicHealthFocus/ExpandedAccessCompassionateUse/default.htm

Right to Try Law: The Right-to-Try Law (RTT) was enacted on May 30, 2018. It is intended to provide terminally ill patients a more streamlined mechanism for access to investigational drugs. The Right to Try Law provides a right to request access to the drug. The manufacturer of the drug is under no obligation to grant such requests.

Like the EAP, the RTT law allows for the use of an investigational drug by a patient who has been diagnosed with a life-threatening disease or condition, who has exhausted approved treatment options, and who is unable to participate in a clinical trial involving the eligible investigational drug. An eligible investigational drug means a drug for which a Phase 1 clinical trial has been completed but the drug has still not been fully approved by the FDA. A Phase 1 clinical trial is done primarily to determine the dose of the drug that may be given safely to humans. Determining whether the drug is actually effective comes in later phases of the trial.

Unlike the EAP, the RTT law eliminates the need for approval from the FDA and Institutional Review Board and it provides the sponsor and physician protection from liability associated with harm caused by use of the investigational drug. While the RTT law does specify that the treating physician must obtain the informed consent of the patient, unlike the EAP, the RTT law does not specify the required elements of that informed consent.

Because the RTT law is fairly new, it is not yet clear whether this mechanism will be accepted by manufacturers of investigational drugs.

The following table describes the major similarities and differences of the three current processes by which seriously ill patients may obtain access to investigational drugs.

 

Clinical Trials Expanded Access Program Right –to Try-Law
Who can participate? Patients with a condition for which a drug is being developed who meet the inclusion criteria for the trial.

 

 Patients with a serious/immediately life-threatening disease or terminal condition, unable to participate in a clinical trial. Patients with a serious/immediately life-threatening disease or terminal condition, unable to participate in a clinical trial.

 
Investigational Drug Not FDA Approved Not FDA Approved Not FDA Approved, Phase 1 trial completed

 
FDA Approval Required Required Not Required
IRB Approval Required Required Not Required
Informed Consent Required and must include specific elements required by regulation

 

 Required and must include specific elements required by regulation

 

 Required, but no specific elements are identified

 

 
Manufacturer Obligated to Provide the Investigational Drug Yes, to those individuals  who provide informed consent to participate in the trial No No
Liability waived for any risk associated with Drug No No Yes

 

How can I learn about research studies that are looking for volunteers?

To find ongoing studies that are currently recruiting participants at UConn, you can explore the following online listings:

To search for trials recruiting nationally, please check out the websites below:

 

HSPP- April- May-June, 2018 – Newsletter

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Clinical Trials – What you need to Know

Did you know the public clinical trials registry, ClinicalTrials.gov, was created in February 2000 in support of a 1997 federal law requiring public registration of clinical trials? It was designed as a web-based catalog of clinical trials to serve as a resource for the patient and research community alike. The law has since expanded to require more types of clinical trials research to be registered, and for some trials, results are also required to be posted.

Did you know there are at least 4 organizations that may require you to register your study on ClinicalTrials.gov? The FDA, National Institutes of Health (NIH), International Committee of Medical Journal Editors (ICMJE) and World Health Organization (WHO) each have rules about registering. For more details on each, please click here.

Did you know the NIH and ICMJE have expanded their definitions of a clinical trial to include behavioral trials? Click here for NIH’s definition. Click here for the ICMJE definition.

Did you know that for studies that require results to be posted per the federal law with completion dates after 1/18/17, a final version of the IRB-approved protocol document and statistical analysis plan must be uploaded to the ClinicalTrials.gov record? Limited information may be redacted. For details, click here.

Should your study be registered with ClinicalTrials.gov?

For more information, see our webpages or contact Ellen Ciesielski (eciesielski@uchc.edu, 860-679-6004) in Research Compliance Services.

 

Inclusion of Children in Research

When a Principal Investigator (PI) proposes a research project that will involve an intervention or interaction with children, the PI must demonstrate to the IRB that the additional protections afforded to children by regulations have been addressed. The Department of Health and Human Services (DHHS) and the Food and Drug Administration (FDA) have each established regulations governing the inclusion of children in research and the UConn Health IRB has incorporated these regulations into policy.  When proposing a research study that will include children as subjects investigators should review the following material:

  • IRB Policy 2011-006.0, Additional Protections for Certain Populations – General Policy,
  • IRB Policy 2011-006.3, Additional Protections for Certain Populations – Children,
  • Form D, Additional Protections for Children Involved as Subjects in Research

In order for the IRB to approve a research protocol that will enroll children, the IRB must assess the information provided by the PI and be able to determine that the research falls within one or more of the following permissible categories and that the plans for obtaining the assent of the child and permission of the parents are appropriate. The examples provided within each category were taken from the Collaborative Institutional Training Initiative (CITI) Program.

Category 1: Research not involving greater than minimal risk.

Minimal risk means that the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests.

To be approvable under this category, the IRB must find that the research presents no greater than “minimal risk” to children, and that adequate provisions are made for soliciting the assent of the children and the permission of their parents or guardians. The IRB may determine that permission from one parent is sufficient.

Examples of Research Projects That May Fall Within Category 1

  • A study to determine the relationship between maternal age and head circumference at birth. Measurement of head circumference is part of the normal newborn examination, and is therefore minimal risk.
  • A study to determine the incidence of asymptomatic proteinuria in school age children. The research involves the analysis of a voided urine collection, which is minimal risk.

Category 2: Research involving greater than minimal risk but presenting the prospect of direct benefit to the individual subjects.

This category is inclusive of research in which more than minimal risk to children is presented by an intervention or procedure that holds out the prospect of direct benefit for the individual subject, or by a monitoring procedure that is likely to contribute to the subject’s well-being. The IRB may approve research under this category only if the IRB finds and documents that:

(a) The risk is justified by the anticipated benefit to the subjects;

(b) The relation of the anticipated benefit to the risk is at least as favorable to the subjects as that presented by available alternative approaches; and

(c) Adequate provisions are made for soliciting the assent of the children and permission of their parents or guardians.   The IRB may determine that permission from one parent is sufficient.

Examples of Research Projects That May Fall Within Category 2:

A pilot study of a shorter duration of antibiotic treatment for uncomplicated otitis media. The potential benefit associated with the shorter duration of treatment is increased compliance, and a reduced rate of antibiotic-related diarrhea. The risk associated with the shorter duration of therapy is a higher likelihood of treatment failure.

The risk associated with this research (e.g. treatment failure) appears to be greater than minimal but can be justified by the anticipated benefit (reduce rate of antibiotic diarrhea); and there is the prospect of direct benefit to the child (increased compliance, shorter exposure time, and a reduced rate of antibiotic-related diarrhea). If the risk-benefit relationship is as favorable as the one seen with standard care (e.g. use of the antibiotic for standard time frame), this research would be approvable under this category.

Use of a placebo, or routine monitoring for safety, is not considered to provide direct benefit to subjects.

Category 3: Research involving greater than minimal risk and no prospect of direct benefit to individual subjects, but likely to yield generalizable knowledge about the subjects’ disorder or condition.

 

This category is inclusive of research in which more than minimal risk to children is presented by an intervention or procedure that does not hold out the prospect of direct benefit for the individual subject, or by a monitoring procedure which is not likely to contribute to the well-being of the subject. To be approvable under this category, the children to be enrolled must have the disorder or condition under study (i.e. a healthy control group would not be allowable) and the IRB must find and document that:

(a) The risk represents a minor increase over minimal risk;

(b) The intervention or procedure presents experiences to subjects that are reasonably commensurate with those inherent in their actual or expected medical, dental, psychological, social, or educational situations;

(c) The intervention or procedure is likely to yield generalizable knowledge about the subjects’ disorder or condition which is of vital importance for the understanding or amelioration of the subjects’ disorder or condition; and

(d) Adequate provisions are made for soliciting assent of the children and permission of their parents or guardians. In most cases permission from both parents is required.

Examples of Procedures That May Involve Minor Increase Over Minimal Risk:

  • Catheterized urine collection
  • Skin biopsy or bone marrow biopsy
  • MRI scan with sedation

Example of Research That May Fall Within Category 3:

A study to determine the clinical relevance of a new technique to quantitate minimal residual disease (MRD) during therapy for acute lymphoblastic leukemia in children. The study requires one additional bone marrow aspirate be performed during the course of treatment. Therapy for the subject will not be altered based on the results of the assay. However, if it can be shown that the presence of MRD predicts poor outcome, in the future, patients with MRD can receive more intensive treatment and increase their chance of cure.

It can be argued that the risk of a bone marrow aspirate in a child is only a minor increase over minimal risk. Further, the risk appears commensurate with risks inherent in the subject’s actual medical situation, and the research may yield knowledge of vital importance about the child’s disease (leukemia).

Category 4: Research not otherwise approvable which presents an opportunity to understand, prevent, or alleviate a serious problem affecting the health or welfare of children

 

For research not otherwise approvable that presents an opportunity to understand, prevent, or alleviate a serious problem affecting the health or welfare of children the IRB must find and document:

  1. That the research presents a reasonable opportunity to further the understanding, prevention, or alleviation of a serious problem affecting the health or welfare of children; and
  1. b)   For studies funded or supported by DHHS, the Secretary, or for studies subject to FDA oversight the Commissioner, after consultation with a panel of experts in pertinent   disciplines (for example: science, medicine, education, ethics, law) and following opportunity for public review and comment, has determined either:

(1)       that the research in fact satisfies the conditions of one of the aforementioned categories, as applicable, or

(2)       (i) the research presents a reasonable opportunity to further the understanding, prevention, or alleviation of a serious problem affecting the health or welfare of children; (ii) the research will be conducted in accordance with sound ethical principles; (iii) adequate provisions are made for soliciting the assent of children and the permission of their parents or guardians.

General Requirements for Assent and Permission:  

 Assent means an affirmative agreement to participate in research used with those who are not competent or not of legal age to provide informed consent. Failure to object may not be construed as assent.

 For children to participate in research, the IRB must determine that adequate provisions are made for soliciting the assent of the children when in the judgment of the IRB the children are capable of providing assent. The IRB will take into account the ages, maturity, and psychological state of the children involved. The judgment may be made for all children to be involved in research under a particular protocol, or for each child. When the IRB determines that assent is required, it shall also determine whether and how assent must be documented.

The IRB may determine that assent is not a necessary condition for proceeding with the research if the capability of some or all of the children is so limited that they cannot reasonably be consulted or that the intervention or procedure involved in the research holds out a prospect of direct benefit that is important to the health or well-being of the children and is available only in the context of the research.

Permission is the agreement of parent(s) or guardian to the participation of their child in research. Permission is generally documented by have the parent(s)/guardian sign an informed consent document.

For research studies not involving greater than minimal risk (Category 1 ) and research involving greater than minimal risk but presenting the prospect of direct benefit to the individual subjects (Category 2) the IRB may find that the permission of one parent or guardian is sufficient. For research studies involving greater than minimal risk and no prospect of direct benefit to individual subjects, but likely to yield generalizable knowledge about the subjects’ disorder or condition (Category 3), and for research studies not otherwise approvable which presents an opportunity to understand, prevent, or alleviate a serious problem affecting the health or welfare of children (Category 4), both parents/guardians must give their permission unless one is deceased, unknown, incompetent or not reasonably available, or unless only one parent has legal responsibility for the care and custody of the child.

If the IRB determines that a research protocol is designed for conditions or for a subject population for which parental or guardian permission is not a reasonable requirement to protect the subject (e.g., neglected or abused children) it may waive the consent requirements provided an appropriate mechanism for protecting the children who will participate as subjects in the research is substituted, and provided further that the waiver is not inconsistent with Federal, state or local law.

The choice of an appropriate mechanism would depend upon the nature and purpose of the activities described in the protocol, the risk and anticipated benefit to the research subjects, and their age, maturity status and condition.

 

Inclusion or Wards in Research

 Children who are wards of the state or any other agency, institution, or entity can be included in research involving greater than minimal risk and no prospect of direct benefit to the individual subjects, but likely to yield generalizable knowledge about the subject’s disorder or condition (Category 3) or research that is not approvable under a defined regulatory category but that presents an opportunity to understand, prevent, or alleviate a serious problem affecting the health or welfare of children (Category 4) only if the research is related to their status as wards, or is conducted in schools, camps, hospitals, organizations, or similar settings in which the majority of children involved as subjects are not wards.

Each child must have an advocate appointed who has the background and experience to act in, and agrees to act in, the best interests of the child, and who is not associated in any way with the research, researchers, or guardian organization.

 

Human Subjects Protection Program – January-February- March , 2018 -Newsletter

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Delay of Revised Common Rule and Revised UConn Health IRB Policies  

Implementation of the revised version of the Federal regulation governing federally funded/supported research (i.e. 45 CFR 46, also known as the Common Rule) has been delayed until July 19, 2018. In spite of this delay, the UConn Health IRB has moved forward with implementing several changes that aim to reduce regulatory burden on investigators while still offering protection to research participants, complying with current regulatory requirements and being prepared to comply with the revised requirements.

Several IRB forms, templates and policies have been revised. Understanding the reasons for these changes, what has been changed and to what type of research these changes apply may aid investigators in complying with IRB polices as well as with federal regulations.

The following table lists the UConn Health IRB polices that have been changed, a description of the change and the IRB forms that have been modified due to the policy revisions.

 
Name of the Revised Policy Description of the Policy Change IRB Forms changed due to this Policy Revision
2011-008.0 -Informed Consent – Forms This policy has been revised to include the additional elements of consent put forth in the revised version of 45 CFR 46.

 

These elements, while currently optional, will become required for Federal Funded /Supported (FFS) research only if the proposed revised regulation is implemented. If implemented these elements will be required for FFS research initially approved after the effective date of the regulation or for FFS research approved prior to the effective date of the revised rule that is still enrolling subjects and that is being transitioned to review under the revised rule.

 

While the applicable regulatory criteria for consent will be used as the general premise for all consent forms, when the research is not federally funded or supported, nor subject to FDA oversight, the IRB may exercise judgement when determining if the elements of consent have been appropriately addressed.

 

New elements of consent:

 

*  The prospective subject or the LAR will be provided with the information that a reasonable person would want to have in order to make an informed decision about whether to participate, and will be given an opportunity to discuss that information.

*  The ICF must begin with a concise and focused presentation of the key information that is most likely to assist a prospective subject or LAR in understanding the reasons why one might or might not want to participate in the research. This part of the informed consent must be organized and presented in a way that facilitates comprehension.

 

*  Informed consent as a whole presents information in sufficient detail relating to the research, and is be organized and presented in a way that does not merely provide lists of isolated facts, but rather facilitates the prospective subject’s or LAR’s understanding of the reasons why one might or might not want to participate.

 

*One of the following statements if the research involves the collection of identifiable private information (IPI) or identifiable biospecimens (IB)

(i) A statement that identifiers might be removed from the IPI or IB and that, after such removal, the information or biospecimens could be used for future research studies or distributed to another investigator for future research studies without additional informed consent from the subject or the LAR, if this might be a possibility;   OR

(ii) A statement that the subject’s information or biospecimens collected as part of the research, even if identifiers are removed, will not be used or distributed for future research studies.

 

*  A statement that the subject’s biospecimens (even if identifiers are removed) may be used for commercial profit and whether the subject will or will not share in this commercial profit.

 

*  A statement regarding whether clinically relevant research results, including individual research results, will be disclosed to subjects, and if so, under what conditions.

 

*  For research involving biospecimens, whether the research will (if known) or might include whole genome sequencing (i.e. sequencing of a human germline or somatic specimen with the intent to generate the genome or exome sequence of that specimen).

  

Consent Form Checklist 

 

Consent Form Template

Policy 2011-008.1 – Informed Consent – Process This policy has been changed so that the IRB may approve a non-federally funded or supported research proposal in which an investigator will obtain information or biospecimens for the purpose of screening, recruitment or determining the eligibility of prospective subjects without the informed consent of the prospective subject (and without the need for waivers or alterations), if either of the following conditions is 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 private information or identifiable biospecimens for the purpose of 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.

*  Appropriate measures must be in place to protect the confidentiality of the data being utilized.

 

If the revised regulation is implemented in July this provision will be extended to federally funded/supported research.

 

Electronic Informed Consent (eIC) Process

The investigator should give to the IRB access to the e-consent platform to review the usability of the eIC materials to ensure that they are easy to navigate and that the user may navigate forward or backward within the system, or stop and complete the process at a later time. The investigator must also ensure there is a mechanism in place whereby subjects may ask and obtain answers to questions.

 

When eIC is proposes subjects must still be provided the option of the consent process occurring in person using a paper based consent form.

 

 

 Text in the IRB application in the section regarding confidentiality has been revised to make it clear that the provisions for protecting the confidentiality of the data as described in the IRB application extend data collected during screening.

 
Policy 2011-008.2 – Informed Consent – Waivers and Alterations This policy has been changed to incorporate the new requirement for a waiver or alteration of consent. Per the new requirement, if the research involves using identifiable private information (IPI) or identifiable biospecimens (IB), the investigator must explain why the research could not practicably be carried out without using such IPI or IB.   This element is now applicable to all research requesting a waiver or alteration.

 

This policy also now includes new option to grant a waiver of documentation of consent for non-federally funded or supported research. This new option may apply when the subjects are members of a distinct cultural group or community in which signing forms is not the norm, the research presents no more than minimal risk of harm to subjects and there is an appropriate alternative mechanism for documenting that informed consent was obtained. The IRB will evaluate alternative mechanisms on a case-by-case basis based on information put forth by the PI.  If the revised regulation is implemented in July this provision will extend to federally funded / supported non-exempt.

 

 

 Request for Full or Partial Waiver Informed Consent

 

Request to Waive Documentation of Consent

Policy 2011-008.5 – Informed Consent – Providing and Obtaining Informed Consent

 

 This policy has been modified to allow obtaining consent from a “next of kin” for adults who are not mentally retarded.

 

If the potential participant does not have an appointed legally authorized representative (e.g., individuals designated as having power of attorney for health care, individuals designated as health care representatives) next-of-kin for adults who are not mentally retarded can consent on behalf of a prospective subject as defined in institutional policy 2012-05 titled Legal Representative for Health Care Decisions.

 

 None
Policy 2011-023.0 – Educational Requirements. This policy has been changed so that human subjects protection training for all research (exempt, expedited, full board or facilitated review), will be verified for all study personnel at the time of initial approval and on an individual basis at the time a request for modification is received to add a person to the study. In order for training to be considered current it must have been completed within the past three years.

 

 

 none
Policy 2011-009.3 –Institutional Review Board – Expedited Reviews This policy has been changed so that continuing review may not be required for non-federally funded/supported, non-FDA regulated research.

When continuing review is not required, the approval period for an expedited study will be from the date of approval through the expected completion date of the project.   If necessary the PI may submit an expedited request for modification to continue the study beyond that date.

 none

 

Frequently Asked Questions Related to CITI Training, IRIS System and Facilitated Review

 

I completed my CITI human subject’s protection training recently.  Should I submit my CITI Training Certificate to the IRB?

If an external investigator completed CITI training through another institution, s/he must submit proof of having completed human subject’s protection training to the IRB because the IRB does not get automatically notified of such completions.

If the investigator is affiliated with UConn Health, he/she does not need to submit a certificate of completion. The IRB staff receives the CITI Training certificates one day after individuals have completed the training. Designated IRB staff enter the course completion information into a master training list (Excel) posted in the IRB website and into IRIS. This master training list (Excel) is updated every two weeks. Therefore, investigator should check this list often. In order for the IRB to update the training records in the IRIS system investigators affiliated with UConn Health must have logged into IRIS at least once. Therefore, investigator who have never before log into IRIS should do so right after they have completed the CITI Training. To log into IRIS investigator should click on the following link: https://imedris.uchc.edu , enter their UConn Health network credentials in the ID and PW boxes found in the IRIS logging page, and click on Log in.

 

I am going to submit an application to UConn Health IRB for review and approval.

Do I need to request an account in IRIS?

Every individual who is affiliated with UConn Health can use the UConn Health ID and password to log into IRIS. Therefore, individuals affiliated with UConn Health (faculty, staff, students, residents, and fellows) do not need to request an account in IRIS.

 

On the other hand, individuals external to the UConn Health will need to request an account in IRIS. To do so the external investigator must complete the online request form accessible from the IRIS home page. Investigators must complete all the required fields on the form indicating why the account is necessary and with whom at UConn Health he/she will be working. The IRB designated staff may contact the person in UConn Health to confirm that the creation of this account is necessary. Accounts will be created within 1-2 business days.

 

I have completed an application for IRB review in IRIS. I do not see the sections that allow me to attach documents for review? What should I do?

Unfortunately, the IRIS system currently has a glitch that does not transition the application form to the submission package where you can attach documents.  Follow the steps listed below when you get to the last section of the application for initial review and you see a sign stating: “Study Application Completion. You have completed the Study Application process. Click here to go to the …”

  • click on the “Back Button” ( located in the upper right hand corner)
  • Click on “Study Assistant” menu
  • click on “My Studies” sub-menu,
  • Open the study, and there you will find Section 1- Submission Packet to the Review Board.
  • Click on “Save and Continue to the Next Section” to build the following sections of the forms that will allow you to attach documents.

 

I am affiliated with UCONN Health (e.g. faculty member, student, employee, or resident, fellow) and I will be part of a study conducted at another institution. That institution has reviewed and approved the study. Do I need approval from the UConn Health IRB?

Yes, if you are affiliated with UConn Health and you are acting in that capacity, your involvement in a research study engages UConn Health in the research and therefore the UConn Health IRB must be involved.   However, as opposed to conducting a formal review the UConn Health IRB may elect to rely on the IRB of the other institution. To determine if the UConn Health IRB will do this you, you must submit an application for facilitated review to the UConn Health IRB. By submitting this application you will obtain an official determination from the UConn Health IRB as to whether oversight for the study will be deferred to the external IRB. In order for the UConn Health IRB to defer oversight a written agreement must exist between to the two institutions.  This agreement is referred to as an IRB Reliance Agreement.  Investigators may contact the IRB to determine if such an agreement is in place or needs to be established.