The Institutional Review Board will provide assistance with the IRB process for new and seasoned investigators.  If you have a question or need assistance with a research project, we are happy to help.  We are available for a phone call or an in-person meeting.  Please send an email to MMC_IRB@mainehealth.org to make your request. 

IRBNet

• Please see the IRB Main Page to Get Started.

• To get your questions answered, access the IRBNet Frequently Asked Questions (FAQs).

• If you are unable to locate the information that you need, please contact the IRB Office:  MMC_IRB@mainehealth.org.

IRB Office Hours

The Institutional Review Board will provide assistance with the IRB process for new and seasoned investigators. If you have a question or need assistance with a research project, we are happy to help.  We are available for a phone call or an in-person meeting.  Please send an email to MMC_IRB@mainehealth.org to make your request.

Approval Types

In an attempt to help you navigate through the regulatory process, the IRB Office has assembled this list of our “approval types” and their definitions.  If you have any questions about this list, or any suggestions for additions, please call our office (396-8240).

New Human Subject Research Proposals that may be Expedited:

The MMC IRB may review certain human subject’s research using an expedited review procedure, if it meets the requirements of the federal regulations.  This document is divided into the following sections:

Definition: An IRB may use the expedited review procedure to review some or all of the research appearing on the list (below) if it is found by the reviewer(s) to involve no more than minimal risk.

Please note:

1) The activities listed should not be deemed to be of minimal risk simply because they are included on this list. Inclusion on this list merely means that the activity is eligible for review through the expedited review procedure when the specific circumstances of the proposed research involve no more than minimal risk to human subjects.

2) The categories in this list apply regardless of the age of subjects, except as noted.

3) The expedited review procedure may not be used where identification of the subjects and/or their responses would reasonably place them at risk of criminal or civil liability or be damaging to the subjects financial standing, employability, insurability, reputation, or be stigmatizing, unless reasonable and appropriate protections will be implemented so that risks related to invasion of privacy and breach of confidentiality are no greater than minimal.

4) The expedited review procedure may not be used for classified research involving human subjects.

5) Investigators are reminded that the standard requirements for informed consent (or its waiver, alteration, or exception) apply regardless of the type of review–expedited or convened–utilized by the IRB.

Research Categories

(1) Clinical studies of drugs and medical devices only when condition (a) or (b) is met.

(a) Research on drugs for which an investigational new drug application (21 CFR Part 312) is not required. (Note: Research on marketed drugs that significantly increases the risks or decreases the acceptability of the risks associated with the use of the product is not eligible for expedited review.)

(b) Research on medical devices for which (i) an investigational device exemption application (21 CFR Part 812) is not required; or (ii) the medical device is cleared/approved for marketing and the medical device is being used in accordance with its cleared/approved labeling.

(2) Collection of blood samples by finger stick, heel stick, ear stick, or venipuncture as follows:

(a) from healthy, nonpregnant adults who weigh at least 110 pounds. For these subjects, the amounts drawn may not exceed 550 ml in an 8 week period and collection may not occur more frequently than 2 times per week; or

(b) from other adults and children2, considering the age, weight, and health of the subjects, the collection procedure, the amount of blood to be collected, and the frequency with which it will be collected. For these subjects, the amount drawn may not exceed the lesser of 50 ml or 3 ml per kg in an 8 week period and collection may not occur more frequently than 2 times per week.

(3) Prospective collection of biological specimens for research purposes by noninvasive means.

Examples: (a) hair and nail clippings in a nondisfiguring manner; (b) deciduous teeth at time of exfoliation or if routine patient care indicates a need for extraction; (c) permanent teeth if routine patient care indicates a need for extraction; (d) excreta and external secretions (including sweat); (e) uncannulated saliva collected either in an unstimulated fashion or stimulated by chewing gumbase or wax or by applying a dilute citric solution to the tongue; (f) placenta removed at delivery; (g) amniotic fluid obtained at the time of rupture of the membrane prior to or during labor; (h) supra- and subgingival dental plaque and calculus, provided the collection procedure is not more invasive than routine prophylactic scaling of the teeth and the process is accomplished in accordance with accepted prophylactic techniques; (i) mucosal and skin cells collected by buccal scraping or swab, skin swab, or mouth washings; (j) sputum collected after saline mist nebulization.

(4) Collection of data through noninvasive procedures (not involving general anesthesia or sedation) routinely employed in clinical practice, excluding procedures involving x-rays or microwaves. Where medical devices are employed, they must be cleared/approved for marketing. (Studies intended to evaluate the safety and effectiveness of the medical device are not generally eligible for expedited review, including studies of cleared medical devices for new indications.)

Examples: (a) physical sensors that are applied either to the surface of the body or at a distance and do not involve input of significant amounts of energy into the subject or an invasion of the subjects privacy; (b) weighing or testing sensory acuity; (c) magnetic resonance imaging; (d) electrocardiography, electroencephalography, thermography, detection of naturally occurring radioactivity, electroretinography, ultrasound, diagnostic infrared imaging, doppler blood flow, and echocardiography; (e) moderate exercise, muscular strength testing, body composition assessment, and flexibility testing where appropriate given the age, weight, and health of the individual.

(5) Research involving materials (data, documents, records, or specimens) that have been collected, or will be collected solely for nonresearch purposes (such as medical treatment or diagnosis). (NOTE: Some research in this category may be exempt from the HHS regulations for the protection of human subjects. 45 CFR 46.101(b)(4). This listing refers only to research that is not exempt.)

(6) Collection of data from voice, video, digital, or image recordings made for research purposes.

(7) Research on individual or group characteristics or behavior (including, but not limited to, research on perception, cognition, motivation, identity, language, communication, cultural beliefs or practices, and social behavior) or research employing survey, interview, oral history, focus group, program evaluation, human factors evaluation, or quality assurance methodologies. (NOTE: Some research in this category may be exempt from the HHS regulations for the protection of human subjects. 45 CFR 46.101(b)(2) and (b)(3). This listing refers only to research that is not exempt.)

New Human Subjects Proposals that may be Exempt from IRB Review:

All human subject research is subject to federal regulations, with a few exceptions.  These exceptions may be granted an “exemption” from IRB review.  The following is a list of the most common categories of research that are considered exempt.  Please keep in mind that only the IRB may grant an exemption, the investigator must go to the IRB to receive an exemption.

1) Research conducted in established or commonly accepted educational settings, involving normal education practices.  This category may include children

2) Research involving the use of educational tests (cognitive, diagnostic, aptitude, achievement) for which subjects cannot be identified, or release of the information would not be harmful to the subject.  This category may include children

3) Research involving the use of survey procedures or interview procedures or observation of public behavior for which subjects cannot be identified, OR release of the information would not be harmful to the subject.  This category may not include children.  If subjects are 18 years of age or younger parental consent is required.  Research may be reviewed by expedited procedures – do not use this form.

4) Research involving the collection or study of existing data, documents, records, pathological specimens, or diagnostic specimens, if these sources are publicly available OR if the information is recorded by the Investigator in such a manner that subjects cannot be identified, directly or through identifiers linked to the subjects

5) Unidentifiable human body parts, sections or samples obtained from a morgue

New Human Subject Research Proposals that may not be reviewed via an expedited procedure, and are not exempt:

If your new, human research proposal does not fit the definition of what may be reviewed via an expedited procedure, and it is not exempt from IRB regulations, it must be reviewed by the fully convened committee (i.e. at an IRB meeting).  Typically these protocols involve novel medications or devices, which are under the Food and Drug Administration’s (FDA’s) jurisdiction (i.e. are under IND or IDE, or are not approved for marketing).  Some other protocols, in which the risk is perceived to be “more than minimal” will also be reviewed by the fully convened committee.  The fully convened committee must also review humanitarian Use Devices (HUD or HDE’s).

If you have any questions about the type of review your new, human subject research project may need, please contact our office

All “Key Personnel” should be named on any new IRB proposal submitted for review. We recommend, however, that a study protocol/plan not include individual names, but rather explain a person’s role on the project (e.g. Principal Investigator, Research Coordinator, Sub-Investigator).

When adding new Key members to your study team, please submit an amendment in IRBNet. Completion of training as well as completion of a Financial Interest Disclosure will be required of all key personnel.

Key Personnel are defined as follows:

  • Principal Investigator (who is ultimately responsible for the management and oversight of all research study staff)
  • Research Personnel directly involved with study participants or their personally identifiable information
  • Faculty mentors/advisors who provide direct oversight of study procedures

Examples of Non-Key Personnel include, but are not limited to:

  • Technicians or staff performing their normal duties (Phlebotomists, Medical Assistants, Imaging Techs)

Please note: Non-key research personnel, summer student interns and short-term assistants may perform data transcription, but may NOT carry out duties such as obtaining informed consent.

Any adverse event associated with the use of the drug/device or research intervention which results in any of the following outcomes:

–       Death

–       A life-threatening adverse event

–       Inpatient hospitalization or prolongation of existing hospitalization

–       A persistent or significant disability/incapacity

–       Congenital anomaly/birth defect

Important medical events that may not result in death, be life-threatening or require hospitalization may be considered a serious adverse event when, based upon appropriate medical judgment, they may jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the outcomes listed above.

Unexpected Adverse Event

An adverse event is considered “unexpected” if it is not listed in the investigator brochure, protocol or informed consent, if an investigator brochure is not required or available and if the severity or sensitivity is not consistent with the risk described in the general investigational plan or informed consent document.

Note: the natural progression of a subject’s underlying disease, disorder or condition is “expected.”

An expected adverse event described in the investigator brochure or informed consent document may be considered unexpected if the severity or the specifics of the event is significant.  For example:  hepatic necrosis would be unexpected (by virtue of greater severity) if the investigator brochure referred only to elevated hepatic enzymes or hepatitis.  Diarrhea is an expected event of the drug therapy however a patient becomes severely dehydrated and hospitalized (the hospitalization is considered a SAE that has not been defined in the existing study documents).

A  Serious Adverse Event is considered related if there is a reasonable possibility, in the opinion of the Principal Investigator or the sponsor that the serious adverse event was likely to be caused by the study subject’s participation in the research procedures.

Local is defined as enrolled by a MMC/MMP/MaineHealth/PenBay/Maine General investigator or enrolled in a study coordinated/Sponsored by an MMC PI.

The process of de-identification, by which identifiers are removed from the health information, mitigates privacy risks to individuals and thereby supports the secondary use of data for comparative effectiveness studies, policy assessment, life sciences research, and other endeavors.

“Safe Harbor” Method: Identifiers That Must Be Removed to Make Health Information “De-Identified”

(i) The following identifiers of the individual or of relatives, employers or household members of the individual must be removed:

(A) Names;

(B) All geographic subdivisions smaller than a State, including street address, city, county, precinct, zip code, and their equivalent geocodes, except for the initial three digits of a zip code if, according to the current publicly available data from the Bureau of the Census:

(1) The geographic unit formed by combining all zip codes with the same three initial digits contains more than 20,000 people; and

(2) The initial three digits of a zip code for all such geographic units containing 20,000 or fewer people is changed to 000.

(C) All elements of dates (except year) for dates directly related to an individual, including birth date, admission date, discharge date, date of death; and all ages over 89 and all elements of dates (including year) indicative of such age, except that such ages and elements may be aggregated into a single category of age 90 or older;

(D) Telephone numbers;

(E) Fax numbers;

(F) Electronic mail addresses;

(G) Social security numbers;

(H) Medical record numbers;

(I) Health plan beneficiary numbers;

(J) Account numbers;

(K) Certificate/license numbers;

(L) Vehicle identifiers and serial numbers, including license plate numbers;

(M) Device identifiers and serial numbers;

(N) Web Universal Resource Locators (URLs);

(O) Internet Protocol (IP) address numbers;

(P) Biometric identifiers, including finger and voice prints;

(Q) Full face photographic images and any comparable images; and

(R) Any other unique identifying number, characteristic, or code; and

(ii) The covered entity does not have actual knowledge that the information could be used alone or in combination with other information to identify an individual who is a subject of the information.

Source: HHS.gov, Guidance Regarding Methods for De-identification of PHI in Accordance with the HIPAA Privacy Rule, 11/26/12

https://www.hhs.gov/sites/default/files/ocr/privacy/hipaa/understanding/coveredentities/De-identification/hhs_deid_guidance.pdf

“Coded”:

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

Comparison to the HIPAA Privacy Rule

The Privacy Rule is a Federal regulation under HIPAA, 1996. The Privacy Rule permits covered entities under the Rule to determine that health information is de-identified even if the health information has been assigned, and retains, a code or other means of record identification, provided that:

  1. the code is not derived from or related to the information about the individual;
  2. the code could not be translated to identify the individual; and
  3. the covered entity under the Privacy Rule does not use or disclose the code for other purposes or disclose the mechanism for re-identification (see HHS guidance entitled, Institutional Review Boards and the HIPAA Privacy Rule, page 6, Q and A #3, at http://privacyruleandresearch.nih.gov/pdf/IRB_Factsheet.pdf – PDF).

Regarding condition (1) above, in contrast to the Privacy Rule, information that is linked with a code derived from identifying information or related to information about the individual is not considered to be individually identifiable under the HHS regulations for the protection of human subjects at 45 CFR 46, if the investigators cannot readily ascertain the identity of the individual(s) to whom the coded private information or specimen pertains. Therefore, some coded information, in which the code has been derived from identifying information linked to or related to the individual, would be individually identifiable under the Privacy Rule, but might not be individually identifiable under 45 CFR 46 (the Code of Federal Regulations for Protection of Human Subjects).

Source: HHS.gov,  Coded Private Information or Specimens Use in Research, Guidance (2008)

https://www.hhs.gov/ohrp/regulations-and-policy/guidance/research-involving-coded-private-information/index.html

The NIH Definition of a “Clinical Trial”:   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.

Source: NIH.gov, https://grants.nih.gov/grants/guide/notice-files/NOT-OD-15-015.html

ClinicalTrial.gov definition of “Clinical Trial”:   A clinical study in which participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. The assignments are determined by the study protocol. Participants may receive diagnostic, therapeutic, or other types of interventions.

Source: Clinicaltrials.gov, https://clinicaltrials.gov/ct2/about-studies/glossary#C

ClinicalTrial.gov definition of “Clinical Study”:  A research study using human subjects to evaluate biomedical or health-related outcomes. Two types of clinical studies are Interventional studies (or clinical trials) and Observational studies.

A departure from or failure to follow the research protocol/plan, without prior approval of the IRB, which compromises the safety or increases/decreases the risk benefit determination of a future or current participant. Examples: Violation of inclusion or exclusion criteria, errors with the administration/application of an investigational product, medication errors, failure to obtain ICF, missing ICF without source documentation.

Enrolled participants: individuals who are eligible for participation (i.e., meet the inclusion criteria for the study), have given informed consent and participated in some or all of the study procedures (excluding screening procedures where applicable).

Screened participants: individuals who have given informed consent and participated in screening procedures to determine eligibility. Note that informed consent is required before any data can be collected for screening purposes. A screening process where persons are simply informed of inclusion/exclusion criteria and allowed to self-identify as eligible for enrollment does not require informed consent because no data about the individuals are collected.

Screen failures: individuals who have given informed consent and participated only in screening procedures to determine eligibility, but who were determined to be ineligible to take part in the study. Screen failures are not considered to have enrolled in a study.

Pre-Screen failures: individuals who were evaluated for study eligibility based upon available information (medical records, conversation, etc.) and determined to be ineligible prior to obtaining consent.

If you are unsure whether your study meets the clinicaltrials.gov definitions as an applicable project and requires posting on clinicaltrials.gov, or have any other questions, please contact the MMC IRB office, 661-4474 or mmc_irb@mainehealth.org, for guidance.

Recruiting Study Subjects

FDA requires that an Institutional Review Board (IRB) review and have authority to approve, require modifications in, or disapprove all research activities covered by the IRB regulations [21 CFR 56.109(a)]. An IRB is required to ensure that appropriate safeguards exist to protect the rights and welfare of research subjects [21 CFR 56.107(a) and 56.111]. In fulfilling these responsibilities, an IRB is expected to review all the research documents and activities that bear directly on the rights and welfare of the subjects of proposed research. The protocol, the consent document and, for studies conducted under the Investigational New Drug (IND) regulations, the investigator’s brochure are examples of documents that the IRB should review. The IRB should also review the methods and material that investigators propose to use to recruit subjects.

A. Media Advertising:

Direct advertising for research subjects, i.e., advertising that is intended to be seen or heard by prospective subjects to solicit their participation in a study, is not in and of itself, an objectionable practice. Direct advertising includes, but is not necessarily limited to: newspaper, radio, TV, bulletin boards, posters, and flyers that are intended for prospective subjects. Not included are: (1) communications intended to be seen or heard by health professionals, such as “dear doctor” letters and doctor-to-doctor letters (even when soliciting for study subjects), (2) news stories and (3) publicity intended for other audiences, such as financial page advertisements directed toward prospective investors.

IRB review and approval of listings of clinical trials on the internet would provide no additional safeguard and is not required when the system format limits the information provided to basic trial information, such as: the title; purpose of the study; protocol summary; basic eligibility criteria; study site location(s); and how to contact the site for further information. Examples of clinical trial listing services that do not require prospective IRB approval include the National Cancer Institute’s cancer clinical trial listing (PDQ) and the government-sponsored AIDS Clinical Trials Information Service (ACTIS). However, when the opportunity to add additional descriptive information is not precluded by the data base system, IRB review and approval may assure that the additional information does not promise or imply a certainty of cure or other benefit beyond what is contained in the protocol and the informed consent document.

FDA considers direct advertising for study subjects to be the start of the informed consent and subject selection process. Advertisements should be reviewed and approved by the IRB as part of the package for initial review. However, when the clinical investigator decides at a later date to advertise for subjects, the advertising may be considered an amendment to the ongoing study. When such advertisements are easily compared to the approved consent document, the IRB chair, or other designated IRB member, may review and approve by expedited means, as provided by 21 CFR 56.110(b)(2). When the IRB reviewer has doubts or other complicating issues are involved, the advertising should be reviewed at a convened meeting of the IRB.

FDA expects IRBs to review the advertising to assure that it is not unduly coercive and does not promise a certainty of cure beyond what is outlined in the consent and the protocol. This is especially critical when a study may involve subjects who are likely to be vulnerable to undue influence. [21 CFR 50.20, 50.25, 56.111(a)(3), 56.111(b) and 812.20(b)(11).]

When direct advertising is to be used, the IRB should review the information contained in the advertisement and the mode of its communication, to determine that the procedure for recruiting subjects is not coercive and does not state or imply a certainty of favorable outcome or other benefits beyond what is outlined in the consent document and the protocol. The IRB should review the final copy of printed advertisements to evaluate the relative size of type used and other visual effects. When advertisements are to be taped for broadcast, the IRB should review the final audio/video tape. The IRB may review and approve the wording of the advertisement prior to taping to preclude re-taping because of inappropriate wording. The review of the final taped message prepared from IRB-approved text may be accomplished through expedited procedures. The IRB may wish to caution the clinical investigators to obtain IRB approval of message text prior to taping, in order to avoid re-taping because of inappropriate wording.

No claims should be made, either explicitly or implicitly, that the drug, biologic or device is safe or effective for the purposes under investigation, or that the test article is known to be equivalent or superior to any other drug, biologic or device. Such representation would not only be misleading to subjects but would also be a violation of the Agency’s regulations concerning the promotion of investigational drugs [21 CFR 312.7(a)] and of investigational devices [21 CFR 812.7(d)].

Advertising for recruitment into investigational drug, biologic or device studies should not use terms such as “new treatment,” “new medication” or “new drug” without explaining that the test article is investigational. A phrase such as “receive new treatments” leads study subjects to believe they will be receiving newly improved products of proven worth.

Advertisements should not promise “free medical treatment,” when the intent is only to say subjects will not be charged for taking part in the investigation. Advertisements may state that subjects will be paid, but should not emphasize the payment or the amount to be paid, by such means as larger or bold type.

Generally, FDA believes that any advertisement to recruit subjects should be limited to the information the prospective subjects need to determine their eligibility and interest. When appropriately worded, the following items may be included in advertisements. It should be noted, however, that FDA does not require inclusion of all of the listed items.

1. the name and address of the clinical investigator and/or research facility;
2. the condition under study and/or the purpose of the research;
3. in summary form, the criteria that will be used to determine eligibility for the study;
4. a brief list of participation benefits, if any (e.g., a no-cost health examination);
5. the time or other commitment required of the subjects; and
6. the location of the research and the person or office to contact for further information.

Clinical Trials Registration

A clinical trial is “any research project that prospectively assigns human subjects to intervention and concurrent comparison/control groups to study the cause-and-effect relationship between a medical intervention and a health outcome. Medical interventions include any intervention used to modify a health outcome.” This definition excludes many phase I studies (where the primary goal is to assess major unknown toxicity or to determine pharmacokinetics), but includes the majority of phase III studies (where the primary goal is to affect clinical practice). The ICMJE website recommends that if the trial falls into a “gray zone” between these two extremes, that investigators should “err on the side of registration.”

The principal investigator is ultimately responsible for making sure registration requirements are met.

  • For NIH-sponsored trials, the principal investigator will register the trial in conjunction with the institute providing funding
  • For Industry-sponsored trials (industry-written protocol), the sponsor of the protocol should register the trial
  • For investigator-initiated trials (including those that industry supplied drug, device or grant funds), the principal investigator should register the trial
  • For trials that the principal investigator has an IND or IDE, the principal investigator should register the trial
  • For multi-site trials (specifically non-industry written protocols), registration should be coordinated by the “lead site” or “coordinating center” to prevent duplicate registration

Please note, even if the local principal investigator is not responsible for registering the trial, he/she is responsible for verifying registration occurred (please ask your sponsor, and then verify that it happened).

According to the ICMJE website, acceptable registries must:

  • Accessible to the public at no charge
  • Open to all prospective registrants (investigators are able to register without restriction by geographic location, academic affiliation, patient demographics, or clinical condition)
  • Managed by a not-for-profit organization
  • Have a mechanism to ensure the validity of the registration data
  • Electronically searchable
  • Include the required data elements

To register your clinical trial with clinicaltrials.gov, please go to their protocol registration system at prsinfo.clinicaltrials.gov . Maine Medical Center does not have an organizational account, so please follow the directions to establish an individual account.

While the clinical trial will need MMC IRB approval prior to registration, the information in the posting does not need to be approved prior to submission for posting.

While the clinical trial will need MMC IRB approval prior to registration, the information in the posting does not need to be approved prior to submission for posting.

In order to submit the results of a clinical trial for publication to a journal that subscribes to the International Committee of Medical Journal Editors (ICMJE) requirements for publication, the clinical trial must be registered with a public registry prior to subject enrollment.

Institutional Review Board

1 Riverfront Plaza
Westbrook, Maine 04092
207.661.4474
mmc_irb@mainehealth.org

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