Adverse Events Update

Adverse events can be tricky to navigate! We have made additions to our Investigator Handbook that give more detail on adverse events to help. Please see the below information on adverse events that is included in the handbook you receive when you create your study in the Axiom Mentor System.

 

An Adverse Events is Any unforeseen occurrence with a research participant, including any abnormal sign, symptom, or raised level of risk, temporally associated with the participants’ involvement in the research, whether or not considered related to participation in the research.

 

A Serious Adverse Event is an adverse event where at least one of the following outcomes is a result of the research activities:

-Death

-Life threatening condition or event

-Inpatient hospitalization

-Persistent or significant disability, incapacity, or disruption of the subject’s ability to conduct normal life activities

-Condition that investigators deem to represent significant risk or hazard to the participant

 

Investigators are required to report any adverse event or serious adverse events that involves human subjects enrolled in the study that are determined to be unexpected and probably, possibly, or definitely related to the test article or research procedures. This should be reported to the IRB promptly, no more than 7 calendar days after the investigators learned of the event. The IRB will then make a determination as to the relation of the adverse event and any impact on human subjects, and if further action is required on the part of the investigator. Investigators are expected to take the findings from adverse events and make appropriate changes to the protocol to ensure safety of participants.

 

All greater than minimal risk studies will be required to maintain an ‘Adverse Event Table’ and submit it at each annual check-in. A table template will be provided at time of initial approval.

What is Human Subjects Research?

National and international ethics codes form a framework for the protection of rights and welfare of human participants in research. These codes have developed over time in response to research misconduct. Examples include horrific experiments conducted on prisoners by Nazi doctors during World War II and the withholding of proven treatment from poor Black men as part of a study of untreated syphilis in Alabama. The Belmont Report, the Nuremberg Code, and the Declaration of Helsinki led to the development of the human subjects in research codes we have today.

Two criteria must be met for a study to be considered human subjects research. First, the study must be considered research according to §46.102: “Research is a systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge.” Second, it must involve human subjects. According to §46.102, a human subject is “a living individual about whom an investigator (whether professional or student) conducting research:

  • Obtains information or biospecimens through intervention or interaction with the individual, and uses, studies, or analyzes the information or biospecimens; or
  • Obtains, uses, studies, analyzes, or generates identifiable private information or identifiable biospecimens.”

The following questions can help researchers determine whether their study fits the criteria of human subjects research:

 

Is the study considered research according to §46.102? If the answer is ‘No’, the study is not considered human subjects research. If the answer is ‘Yes’, the study is most likely human subjects research.

 

Will the study involve only secondary data or biospecimens collected for purposes other than this study, or belonging to deceased individuals?  If the answer is “yes,” the research may not be considered human subjects research, provided the data/biospecimens come from deceased individuals, the researchers do not have access to participant identifiers, and/or a broad consent or waiver of documentation of consent has been obtained (see §46.116 and §46.117).

 

Author: Mary Lannon, PhD

What is a Private IRB?

Private IRBs have no affiliation with specific clinical or academic institutions. They typically provide oversight into research studies that are not tied to an academic or clinical research facility, serve as a single reviewing body for studies operating across multiple sites, and/or review international studies. While there are many similarities between institutional IRBs and private IRBs, some differences exist.
All IRBs are subject to federal requirements for membership composition. Per §46.107 and §56.107, an IRB must have at least five members qualified through professional competence (experience and expertise). One advantage of a private IRB is the ability to incorporate members from diverse and expansive backgrounds. Many academic and clinical research IRBs are composed of members with experience related to their full-time role at the associated institution (school or medical facility). Private IRBs have the ability to utilize reviewers and consultants with expertise in specific subject areas or participant populations (e.g., prisoners, children, or pregnant women).
Another advantage of private IRBs is turnaround time. Institutional and clinical research IRBs typically meet monthly. A private IRB can process study applications on a timelier basis and convene a full board meeting as needed. The private IRB still adheres to the same federal guidelines as other IRBs, however their sole focus on research study reviews results in quicker turnaround times than what can be offered by institutional and clinical research IRBs where members have other duties to perform.
The composition of a private IRB allows for the review of any type of study; exempt, expedited, international and full board, regardless of whether the study is clinical, social,behavioral or educationsal in nature. Private IRBs provide options to researchers that have no affiliation with clinical or academic institutions to have studies reviewed and approved to satisfy funding requirements and/or lead to scholarly publishing of findings.

Author: Mary Lannon, PhD

Waiver of Documentation of Consent

It may be surprising, but not all research requires subjects to sign a consent form. Many types of research can be reasonably conducted without written consent documentation. Depending on the level of risk, and if the consent form would be the only link between the participants and the research, then a waiver of documentation of consent could be granted by the IRB.

When a waiver of documentation of consent would be appropriate for the research:

  • Anonymous online survey with a ‘click to continue’ function
  • Verbal phone interviews
  • No greater than minimal risk study
  • The research could not be conducted without it
  • The signature on the consent form linking the subject to the research actually poses a risk

In the Solutions IRB digital application there is an area to choose “Requesting a Waiver of Documentation of Consent”. This will signify that you are applying for the waiver and will prompt you to answer follow up questions regarding the waiver.

 

Written by: McKenzie Long

Alteration of Consent

An alteration of consent is when the [IRB [. . . approves] a consent procedure that omits some or alters some or all of the elements of informed consent]. The IRB may grant alterations to your informed consent form if specific criteria are met. In this article we will discuss these specific criteria, along with examples of when an alteration of consent may be granted.

 

For a waiver of informed consent to be granted the following criteria must be met;

  • The research involves no more than minimal risk.
  • The research could not be carried out practicably without the waiver. (*Please note this cannot simply be because it is more convenient for the researcher to not obtain consent.)
  • The waiver will not adversely affect the rights and welfare of the subjects.
  • When appropriate, the subjects will be provided with additional information about their participation.

 

Below are examples of when an alteration of consent may be granted, pending the above is met;

  • In research that involves deception or in cases where subject knowledge of the purpose of research may alter their responses. You may need to omit some information from participants in order to answer your research question. E.g. they are told they are completing a survey on overall happiness but in reality you are looking to see if the room temperature has an effect on a person’s mood
  • Where medical records or biospecimens are being reviewed and identifiers will not be kept with the data.
  • When obtaining consent from a large number of individuals in a retrospective chart review is not practical
  • In research examining public benefit or service programs not regulated by the FDA that looks at or evaluates procedures for obtaining benefits or services, changes or alternatives to these programs, or changes in methods or levels of payment for these programs.

 

To read more about alteration and waiver of consent and when they apply, please refer to CFR at § 46.116.f(2). If you would like to talk through waiver of consent and your study, please feel free to reach out to the Solutions IRB administrative team, at reviews@solutionsirb.com or 1-855-226-4472.

 

Author: Cora Crawford

Who are Prisoners in Research?

Prisoners are classified as a vulnerable population per CFR 46 Subpart C. A question an IRB sometimes faces is exactly who are prisoners? While the answer seems clear, some grey areas do exist with this vulnerable population.

The prisoner definition per §46.303 states, “…any individual involuntarily confined or detained in a penal institution.” Based upon this definition an individual being held in a prison or jail is a prisoner. However, what about individuals on a work release program or staying in a halfway house as part of their reintegration back into society; should we consider those individuals ‘prisoners’ when they are the study population?

Individuals on a work release status that requires them to return to the facility at night are prisoners since they are still considered detained. Individuals residing in a halfway house require a more in-depth understanding of the release conditions to the halfway house to determine a ‘prisoner’ status.

The full definition per §46.303 specifies that individuals being detained in other facilities that, “…provide alternatives to criminal prosecution or incarceration in a penal institution…” meet the criterion of being prisoners. Therefore, if failure to return to the halfway house at night or leaving without permission would result in the individual being returned to an incarceration facility, the answer is yes, they are prisoners. However, if the individual can leave the halfway house without penalty, technically they should not be considered a prisoner for research purposes.

It is important to note that individuals serving sentences under some form of community corrections (probation/parole) are not considered prisoners under the CFR definitions, however similar special considerations such as the risk of coercion need to be considered. These will be discussed in future articles.

Author: Ron Wallace, PhD

Waiver of Consent

The IRB may grant a waiver of informed consent in certain instances. (Not to be confused with a waiver of consent documentation, where consent other than written consent is obtained, please see our article Waiver of Documentation of Consent if you would like more information). A full waiver of consent completely waives the requirement to obtain informed consent. However, in order for a full waiver of informed consent to be granted there are certain criteria that must be met. In this article we will discuss the specific criteria, along with examples of when a waiver of informed consent may be granted.

 

For a waiver of informed consent to be granted the following criteria must be met;

  • The research involves no more than minimal risk.
  • The research could not be carried out practicably without the waiver.
  • The waiver will not adversely affect the rights and welfare of the subjects.
  • When appropriate, the subjects will be provided with additional information about their participation.

 

Below are examples of when a waiver of consent may be granted, pending the above is met;

  • Retrospective chart reviews
  • Studies of existing pathology specimens
  • Public observation studies

 

If you have questions regarding your study and if a waiver of consent may apply, you can refer to the CFRs at § 46.116.f. If you would like to talk through things please feel free to reach out to the Solutions IRB administrative team, at reviews@solutionsirb.com or 1-855-226-4472.

By: Cora Crawford

General Elements of Consent

Welcome to the start of our Informed consent article series! Solutions IRB is excited to bring you weekly articles covering the different types of consent, informed consent, waiver of consent documentation, waiver or consent, alteration of consent and broad consent. For this initial article we are going to go over the basic elements of informed consent described in the CFRs as well as elements that Solutions IRB look for.

CFR Informed Consent Elements

  1. A statement that the study involves research, an explanation of the purposes of the research and the expected duration of the subject’s participation, a description of the procedures to be followed, and identification of any procedures that are experimental;
  2. A description of any reasonably foreseeable risks or discomforts to the subject;
  3. A description of any benefits to the subject or to others that may reasonably be expected from the research;
  4. A disclosure of appropriate alternative procedures or courses of treatment, if any, that might be advantageous to the subject;
  5. A statement describing the extent, if any, to which confidentiality of records identifying the subject will be maintained;
  6. For research involving more than minimal risk, an explanation as to whether any compensation and an explanation as to whether any medical treatments are available if injury occurs and, if so, what they consist of, or where further information may be obtained;
  7. An explanation of whom to contact for answers to pertinent questions about the research and research subjects’ rights, and whom to contact in the event of a research-related injury to the subject;
  8. A statement that participation is voluntary, refusal to participate will involve no penalty or loss of benefits to which the subject is otherwise entitled, and the subject may discontinue participation at any time without penalty or loss of benefits to which the subject is otherwise entitled; and
  9. One of the following statements about any research that involves the collection of identifiable private information or identifiable biospecimens:
    1. A statement that identifiers might be removed from the identifiable private information or identifiable biospecimens 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 legally authorized representative, if this might be a possibility; or
    2. 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.

Things Solutions IRB requires/looks for.

  1. Two forms of contact for the PI/research team
  2. A statement similar to the following. “If you have questions about your rights as a research subject, you may contact Solutions IRB at (855) 226-4472 or participants@solutionsirb.com.”
  3. Solutions IRB’s contact information listed after the PI’s
  4. A consenting statement at the end of the consent form, such as “by clicking continue you give your consent to participate” or “By signing you consent to participate”
  5. If audio recorded during the interview, and a statement that they can or cannot participate if they do not agree to be audio recorded.
  6. If a study will have audio or video recordings, a check box to agree to be audio recorded during the interview, and a statement that they can or cannot participate if they do not agree to be audio recorded.
  7. Clear withdrawal instructions, e.g, how, who to contact, what happens to their data if they withdraw.
  8. If applicable, how will participants receive payment, e.g. electronic email, or by mail?
  9. If applicable, in what form will compensation be received, e.g. cash, or by gift card?
  10. If applicable, When will potential participants receive compensation?
  11. If applicable disclosure of any conflicts of interest
  12. Consent forms must be paginated
  13. Must be at an appropriate reading level for the population, general population is an 8th grade reading level.

We are excited to bring this series to you! If you have any questions please reach out to us at reviews@solutionsirb.com or 855-226-4472.

Author: Cora Crawford

Minimizing Risk

It is the responsibility of IRB members to thoroughly review a research plan and decide whether to approve a protocol. When reviewing research Solutions IRB’s guidelines address three ethical principles that are fundamental to human subject protection, these being: respect for persons (respect for the right of self-government), beneficence (do no harm, maximize benefits, and minimize harms), justice (equal distribution of research burdens and benefits).

An IRB assures that adequate safeguards are incorporated into research design such as: frequent monitoring, the presence of trained personnel who can respond to emergencies, or coding of data to protect confidentiality are examples. For a study to be deemed minimal risk, the probability and magnitude of harm or discomfort in that study must be no greater than those ordinarily encountered in daily life.

Any study may contain diverse types of risk, such as: physical risks, psychological risks, social/economic risks, loss of confidentiality, and legal risks. Researchers are expected to take steps to minimize any potential risks. These include:

  • Using procedures that are consistent with sound research design
  • Not exposing subjects to unnecessary risk
  • Using procedures already being performed on the subjects for diagnostic or treatment purposes.
  • Prescreening to identify and eliminate high-risk participants,
  • Providing participants with as much information as possible during informed consent and debriefing.

Researchers must be sure that any risks involved in the research are reasonable in relation to the protocols anticipated benefits.

Authors: Ayn O’Reilly and Bridgette Moralez

Protocol Deviations

While protocol deviations are not defined by the Code of Federal Regulations (45CFR46 or 21CFR50), for Solutions IRB, a protocol deviation occurs when the activities occurring within a study stray from the Institutional Review Board-approved protocol. Deviations may be minor or major. They may be known to the PI prior to their occurrence or after they occur. Some deviations can be prevented through good protocol and consent form writing. If a deviation should happen in your study, there are specific steps that you should follow to report it quickly to the IRB.

Some deviations are minor, such as a subject signing the consent form wrong, or a survey being administered differently than was originally described. Generally, deviations like these can be quickly dealt with. Major deviations may require revisions to the study protocol, or other study documents, some may even raise the overall level of risk in the study, or rise to the level of an adverse events or noncompliance.

Some protocol deviations are known to the researcher before they occur (for example, providing life-saving treatment to a subject who becomes seriously ill while participating in study activities); others are only discovered after the fact (a signature was left off of a consent form). Whether the deviation is known prior to its occurring or after does not necessarily impact how serious that deviation is.

Not all potential protocol deviations can be anticipated ahead of time, some can be addressed through good protocol writing that anticipates where problems might occur. For example, if multiple office visits are required in the protocol, the researcher will want to make sure that the timing of such visits is reasonable. Potential deviations can also be avoided by creating a clear and comprehensive consent document. When a researcher wants subjects to complete multiple surveys, that needs to be explained in detail. Finally, many deviations can be avoided through adequate training of the research team. Make sure all of your people understand what is expected of them and what the details for the study are.

When a protocol deviation happens, it is very important to report the deviation to the IRB. This should be done as soon as it is identified, or within 5 business days of knowledge of the event. Please follow these steps:

  1. Log into your profile and access your protocol ID.
  2. Scroll to the bottom of the page and you should see a “protocol deviation” tab.
  3. Select the tab, then select “new protocol”
  4. Fill out the necessary information.
  5. Once this is all completed, Solutions IRB will review the submission
  6. Solutions IRB will walk you through any remaining processes.
  7. In some instances, you may be instructed to make certain changes—for example to your consent form, or more education for your staff may be required.
  8. Finally, the Chair will send a notification that the Protocol Deviation has been acknowledged.

Authors: Ayn O’Reilly & Josephine Rudy