Research is defined as "a systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge."

Activities which meet this definition constitute research, whether or not they are conducted or supported under a program which is considered research for other purposes. For example, some demonstration and service programs may include research activities.

What is the definition of a human subject?

Human subjects are defined as "living individual(s) about whom an investigator (whether professional or student) conducting research obtains (1) data through intervention or interaction with the individual, or (2) identifiable private information."

What is the role of an IRB?

Institutional Review Board (IRBs) are independent committees that protect the rights and welfare of human research subjects. An IRB shall review and have authority to approve, require modifications in (to secure approval), or disapprove all research activities.

May I use a central IRB for review of my research conducted at Maine Medical Center?

The Maine Medical Center IRB has jurisdiction over any human subject’s research activity (including data collection for research purposes) within Maine Medical Center or at any facilities owned by Maine Medical Center. The Maine Medical Center IRB will review the centralized review provided by the National Cancer Institute’s Central IRB (www.ncicirb.org), but will not review or accept the review of any other centralized IRB.

Do I have to use Maine Medical Center’s IRB if the work is going to be conducted in my private practice?

No, MMC does not have jurisdiction over research conducted outside of MMC. However, MMC IRB will review human subject research for private practice physicians who have staffing rights at MMC.

Is there a fee for the IRB service?

In keeping with current budget imperatives and the increased load of clinical research protocols, the MMC IRB charges a $2,000 fee for processing a research protocol through the IRB and $500 for reviewing a protocol via "Expedited Review". Extensive polling of other institutions within the SRA, AIAMC and AAMC show this practice to be customary and readily accepted by sponsors; this is in addition to the indirect charges applied to all research projects. Our experience with sponsors confirms this consensus position.

* The IRB Fee is charged by and administered by the Research Accounting Team, not the IRB itself. The fees collected do, however help to offset the costs of managing all protocols presented to the IRB and are credited to the MMCRI Department responsible for coordinating and managing the IRB.

* IRB Fees will apply to externally funded protocols reviewed by the IRB, but not to projects that lack external funding and not to projects presented with federal, state or local non�]commercial funding such as NIH or AHA grants. The fee applies to the protocol and is charged only once. Accordingly, there is no charge for amendments or annual reviews of existing protocols.

* The Research Accounting Team will access the IRB's computer database one week after the IRB meeting and determine which protocols are to be charged, gather billing information and bill the appropriate parties.

* Many sponsors will ask for a separate bill for the IRB charges and the Research Accounting Team will accommodate those requests. If special billing requests have not been made the IRB Fee will be recovered from the first $2,000 received from the sponsor. Indirect costs will not be applied to the IRB Fee.

* Waivers from the IRB Fee will be sparingly authorized by either the Director of Compliance or the IRB chairman.

Are there different levels of review?

There are 3 levels of review for human subject’s research. The level of review required will depend on the anticipated risk to the subject. Please see Research Categories for a complete explanation of the levels of review.

What do I need to submit to the IRB for approval?

For new projects that are not exempt from IRB regulation:

The following documents must be submitted. Please see the checklist at the beginning of the MMC IRB application for more details on how to complete the documents.

Pages 1-7 of the IRB application, submit page 7 with original signature(s)
Research Plan
Informed Consent Document (if applicable)
Peer Review with all original signatures
CV’s or resume(s) (if necessary)
Internal Services Checklist(s) (if necessary)
Study Classification & Website Information
HIPAA Privacy Form (if necessary)
Any other information you intend to give to a subject (e.g. advertising, questionnaires, letters, information sheets)
If you are requesting that your application be reviewed via an expedited procedure, please submit a cover letter, signed by the principal investigator, requesting expedited review

For New Human Subject Research Project which are Exempt from IRB regulation:

Request for Exemption from IRB Review Form, completed, with the original signature
Data collection sheet or tools

For All Amendments to Previously Approved Projects:

Amendment form, signed by the PI
Revised protocol (if necessary)
Revised informed consent document (if necessary)
Revised informed consent document with the changes highlighted (if necessary)
Summary of changes document from the sponsor (if applicable)
Copy(s) of any other additions/changes to the materials that are given to subjects, or used for advertising (if necessary)

How long does IRB review take?

The amount of time that IRB review requires depends of a number of things, including but not limited to, the completeness of the initial submission to the complexity of the issues involves. Generally, a protocol submitted for full board review will receive an administrative review within two days of the deadline. Completed IRB applications submitted by the deadline for full-board review are placed on that month’s agenda.

What are some of the main areas of concern to IRBs when reviewing protocols?

Are the risks to the research subjects minimized?
Does the study promise an acceptable risk/benefit ratio?
Is the selection of subjects equitable? Are there appropriate justifications for the inclusion/exclusion criteria?
How and from where will the subjects be recruited?
Does the consent form contain the required elements?
Are there adequate provisions to protect the subjects confidentiality?
Does the research plan provide adequate provisions for monitoring date to ensure patient safety?

What are the required elements for an informed consent document?

In seeking informed consent, the following information shall be provided to each subject:

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 which are experimental;
a description of any reasonably foreseeable risks or discomforts to the subject;
a description of any benefits to the subject or to others which may reasonably be expected from the research;
a disclosure of appropriate alternative procedures or courses of treatment, if any, that might be advantageous to the subject;
a statement describing the extent, if any, to which confidentiality of records identifying the subject will be maintained;
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;
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; and
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.

When appropriate, one or more of the following elements of information shall also be provided to each subject:

a statement that the particular treatment or procedure may involve risks to the subject (or to the embryo or fetus, if the subject is or may become pregnant) which are currently unforeseeable;
anticipated circumstances under which the subject's participation may be terminated by the investigator without regard to the subject's consent;
any additional costs to the subject that may result from participation in the research;
the consequences of a subject's decision to withdraw from the research and procedures for orderly termination of participation by the subject;
A statement that significant new findings developed during the course of the research which may relate to the subject's willingness to continue participation will be provided to the subject; and
the approximate number of subjects involved in the study.

Please see the MMC IRB Informed Consent Template for suggested language.

What needs to be included in my research plan?

For review, the MMC IRB requests three copies each of any commercial sponsor’s protocol and investigator’s brochure, OR three copies of the grant for projects receiving non-commercial funding. Since these are usually too voluminous to be copied to all the individual IRB members, the investigator must provide a concise summary of the Research Plan. This should be written in language that can be understood by people without medical training, yet should provide enough detail to allow evaluation of its scientific merit, of potential risks to human subjects and of significance of the knowledge to be gained as a result of this study. It must be written in the following format:

Introduction

State the problem and hypothesis

Background

Previous work that has been done by others or yourself

Specific Aims and Significance

List of the purposes of the study

Materials and Methods

Identify all risks/benefits to human subjects

Identify what is research and what is standard care

Described patient population

Describe how subjects will be identified, including who will obtain informed consent, if applicable

Describe the follow-up, if applicable

Analytical Methods

Describe how the data will be analyzed

What are the rules regarding IRB review of Off Label Uses?

When the intent is the "practice of medicine" and a marketed product is used in a manner that is not approved in the labeling, the FDA does not require the submission of an Investigational New Drug Application, Investigational Device Exemption, or review by an Institutional Review Board. It is the physician’s responsibility to base off label use on firm scientific rationale and on sound medical evidence and to document the product’s use and effects.

However, if the physician uses or plans to use data collected from off label use of an approved drug or device to prove or disprove an hypothesis, he or she must then follow the regulations and guidelines as put forth in the Code of Federal Regulations including obtaining FDA approval, and IRB approval.

What is "Emergency Use"?

Emergency Use is defined as the use of an investigational product in a human subject with a life-threatening condition in which no standard acceptable treatment is available and in which there is insufficient time to obtain IRB approval for an investigational study.

The following conditions must be met to justify emergency use:

there is a high likelihood of death or serious outcomes unless the course of the disease is interrupted; (AND)
no alternative method or recognized therapy is available that provides an equal or greater likelihood of saving the subject’s life; (AND)
the subject is in a life-threatening situation requiring intervention before review at a convened meeting.

The Procedures for Emergency Test Product Use:

The emergency use of an unapproved investigational drug requires an IND or IDE. Contact the manufacturer and determine if the drug or device can be made available for emergency use under the company’s IND/IDE.

The sponsor may request acknowledgment that the IRB is aware and recognizes such emergency use. If required this acknowledgment can be obtained in an expedited mechanism through contact with the Office of Regulatory Affairs.

A circumstance may arise in which an existing IND/IDE does not exist or the manufacturer is unwilling to sponsor the physician under an existing IND/IDE. In such situations, the FDA may issue an IND/IDE directly to the physician. Requests for such authorization can be made by telephone:

The Drug Information Branch (301) 827-4573

Division of Emergency and Epidemiological Operations (202) 857-8400 (off hours)

Notify the Investigational Drug Service that an emergency investigational drug has been ordered (215) 349-8817 or the off-hours pager (215) 960-9565. Provide your name, the patient’s name, the name of the agent to be used, the IND number and an office or pager number where you may be reached

A consent form must be typewritten and signed by the patient or by the patient’s legally authorized representative before the agent is administered.

Exception: subjects who are in need of emergency medical intervention but cannot give informed consent because of their life-threatening medical condition and who do not have a legally authorized person to represent them. In such circumstances, the investigator and a second physician who is not otherwise participating in the investigation or care of the patient must document:

the criteria that the patient met for emergency use of investigative article
AND the lack of alternatives
AND the inability to obtain consent from the subject
AND the methods used to reach a legal representative and/or relatives
AND the lack sufficient time to obtain the aforementioned consent

The physician must submit a report to the IRB within 5 working days after the use of the test product. The report should include details of the emergency situation that warranted use of the test article, the protocol that was followed, a copy of the signed consent form, and any adverse events.

FDA regulations require that any subsequent use of the investigational product have prospective IRB approval. Data from emergency use situations may not be utilized for investigational purposes.

I made a change in my project, do I need to get approval from the MMC IRB before I initiate the change? or

The sponsor sent me changes to my protocol, do I need MMC IRB approval?

The MMC IRB must approve ALL changes to your approved project, including very minor changes, unless they are made to remove immediate hazard to a subject. For example, if you change your inclusion/exclusion criteria slightly, that needs to be approved by the MMC IRB prior to you initiating the change. Other examples of amendments include (but are not limited to): changes to your questionnaires or survey instruments; addition of advertisements or subject information material, scientific changes to the protocol, formatting or wording changes in your informed consent document, formatting or wording changes in your protocol or research plan, addition or deletion of investigators. Please use our Amendment Request Form to report ALL changes to your approved protocol.

One of the subjects has been hurt while participating in my study, do I need to report that to the IRB?

YES! ALL serious and unexpected adverse events must be reported PROMPTLY to the MMC IRB, even if they are not related to the protocol.

What is the definition of a serious and unexpected adverse event (SAE)?

Serious: Death, a life threatening adverse drug or device experience, hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity, or a congenital anomaly/birth defect.

Unexpected: Any adverse drug/device experience, the specificity or severity of which is not consistent with the current investigator brochure or consent form.

How do I report a serious and unexpected adverse event?

We have a form! Please submit all of your serious and unexpected adverse events on a “Serious Adverse Event Report Form” either the single or multiple report format. Reports of serious and unexpected adverse events that you receive from other participating sites/investigators (for multi-center studies) must be reported on a “Serious Adverse Event Report Form” also.

My sponsor sent MedWatch forms (OR sent SAEs that occurred at another site), what do I do with these?

Please refer to “How do I report a serious and unexpected adverse event?” Also note, the MMC IRB reviews reports of only serious and unexpected adverse events as determined by you, unless your sponsor requests that the IRB review all adverse events.

My study approval has an expiration date, how do I renew my study if the work is not complete?

Our office will send you a Progress Report approximately 8 weeks prior to the expiration date of your study. This report must be completed and returned if you wish to continue work on the project after the expiration date. Under the federal regulations, the IRB must conduct continuing reviews no less than once per year, with no exceptions (please see 45 CFR 46.109(e) or 21 CFR 56.109(f)). The MMC IRB cannot grant extensions of the approved time without a completed progress report.

I have completed the work on my project, do I still need to complete the Progress Report prior to the expiration date?

YES! If you do not submit a completed progress report to close your study the MMC IRB will be forced to terminate your study (per 45 CFR 46.109(e) or 21 CFR 56.109(f)). When the IRB terminates a study because of lack of continuing review, that termination must be reported to the institutional official, the funding agency, and the FDA (if appropriate).

A new person is working on this project, is there any required training for this person?

Any person, including Co/Sub-investigators, office nurses, research coordinators, etc. in contact with subjects for research purposes and/or human research subject data will need to complete the CITI training through the University of Miami. Please contact the IRB office or check the MMC Intranet site for the latest copy of the directions. Also, please note, if you are adding an investigator or changing investigators, you need to submit an amendment form.