D. Review ProcessesIn all facets of review, the IRB members are instructed to trust that the information submitted is truthful, accurate and complete. Members are asked to notify the Chair or the staff person or to raise an objection at the meeting if they have reason to believe that this is not the case. Members are encouraged to request further information on any relevant topic.
Guidelines provided within this document for approval and consent are generally accepted standards that may be amended and refined based on IRB precedent.1.Investigator & Site Reviews
Each application will be made in the name of a principal investigator for each study.
The research sponsor may allow more than one principal investigator "pending approval" unless the investigators are vying for the same subject pool.
Each application will designate the facilities to be involved. Sites may be added at any time during the time a protocol is active.
a. Investigator Qualifications
- A member in good standing of the Medical Staff, Hospital Staff or the community at large.
- A member of the Medical Staff should be Board certified or be eligible in the specialty area, or be licensed in the appropriate area, and have training necessary for conduct of the procedures in the study.
- A willingness to abide by the requirements of informed consent, and to assure that all investigators using the protocol are instructed in the principles of informed consent.
- A willingness to subject participants to the rigors of a scientific protocol and to protect them from it if that should be required and to require an equal level of introspection from all investigators enrolling patients on the protocol.
- An assertion that they have not been disqualified or had an unexplained deficiency investigation letter from the FDA.
- An understanding of the requirements of research.
- Have safety features appropriate to study needs.
- Have a place where private conversation can be held.
- Provide for sensitive management of subject care with minimum subject inconvenience for research purposes.
- Have appropriate chart handling procedures sufficient to protect the confidentiality of the subjects.
- Have appropriate drug handling procedures to provide safety and accountability.
- Be capable of providing medical translation services in languages appropriate to the subjects using the facility.
2. Protocol Review
In order to approve a study, the IRB must find that all of the following requirements are satisfied:
a. Risks to subjects are minimized by
- Using procedures consistent with sound research design and which do not unnecessarily expose subjects to risk, and
- Whenever appropriate, by using procedures already being performed on the person for diagnostic or therapeutic reasons.
b. Risks to subjects are reasonable in relation to anticipated benefits, if any, to subjects, and the importance of the knowledge that may be expected to result.
In evaluating risks and benefits, the IRB should consider only those risks and benefits that may result from the research (as distinguished from risks and benefits of therapies that subjects would receive even if not participating in the research).
The IRB should not consider possible long range effects of applying knowledge gained in the research (for example, the possible effects of the research on public policy) as among those research risks that fall within the purview of its responsibility.
c. Selection of subjects is equitable. In making this assessment, the IRB should take into account the purposes of the research and the setting in which the research will be conducted.
The NGHS IRB requires justification for exclusion of some categories of subjects such as the elderly or very young or women of childbearing potential. Equitable selection requires consideration of the fairness of inclusion criteria and of exclusion criteria.
The NGHS IRB requires researchers to obtain a pregnancy test on potential participants, who could possibly be pregnant, PRIOR to enrolling them in any protocol/study that precludes pregnant women.
d. Where appropriate, the research plan makes adequate provisions for monitoring the data collected to ensure the safety of subjects.
e. Where appropriate, there are adequate provisions to protect the privacy of subjects and to maintain the confidentiality of files.
f. Appropriate additional safeguards have been included in the study to protect the rights and welfare of subjects when some or all of the subjects are likely to be vulnerable to coercion or undue influence such as:
- Persons with acute or severe physical or mental illness, or
- Persons who are economically or educationally disadvantaged.
45 CFR 46.111
3. Informed Consent Review
Informed consent consists of both a verbal process and a document covering the main points of information necessary for consent. The IRB will look for evidence that both the process and the documentation of the process have been considered. Questions of literacy and language generally will be considered as well as privacy and timing.
Informed consent will be sought from each prospective participant or the participant’s legally authorized representative as described within this document. Likewise, waiver from the obligation to gain consent may be approved also as described herein.
a. Translation - Oral
NGHS approved translators are available through organizational services. Approved translators are required for review of the informed consent document with the potential participant. Family members may be present.
Languages spoken by 5% or more of the local population, for which a translated document might be necessary, include:
Vietnamese (optional, depending on population studied)
b. Assessing Comprehension
Though it is difficult for an IRB to assess assurances of comprehension, the researcher should provide for some means of assessing comprehension.
c. Recruitment and Advertisements
Recruitment activities are considered to be part of the process leading to consent. The information obtained during this time is information that will be used by a subject when agreeing to participate.
All efforts to advertise a trial must have prior IRB approval. Advertisements are defined as recruitment activities designed to alert potential subjects about the existence of a study. The IRB will review those advertisements that are locally generated as well as national advertising by the research sponsor.
Advertisements might include:
- Display or classified print advertising
- Videotaped "infomercials"
Recruitment materials for which IRB approval is not required include:
- Listings in databases (i.e. PDQ, CenterWatch, etc) that include only objective descriptions
- Interviews on broad medical topics (investigators should make every effort to label investigational activities as investigational.)
The requirements for all advertising are that it be fair, unbiased and not misleading. It should never stress any inducements. While it is not a 'mini-consent" it should be a very brief introduction. No claims can be made about safety or effectiveness. A positive outcome should not be presumed.
Explanation: The "Therapeutic Misperception" is an incorrect perception that what is being offered is therapy rather than an opportunity to assist learning if the therapy is useful. Advertisements should not say, for instance, "A new way to treat...".
At a minimum an advertisement should include:
- A brief summary of the eligibility criteria,
- A brief statement of the objective and the major procedures and, if lengthy, the time involvement, and
- A method for contacting the sites.
4. Consent Documentation Review
Per FDA’s Information Sheet Guidances: Guidance for Institutional Review Boards, Clinical Investigators and Sponsors, "Frequently Asked Questions’ (1998) and ‘Guide to Informed Consent’ (1998):
"…the IRB has the responsibility and authority to determine the adequacy and appropriateness of all the wording in the consent…
21 CFR 56.109 (a), 111(a)(4) and 111(a)(5)
"An IRB may require inclusion of any additional information which it considers important to a subject’s decision to participate in a research study…
21 CFR 56.109 (b)
"…the IRB of Record is the final authority on the content of the consent documents that is presented to the prospective study subjects."
The IRB recognizes the dilemma faced when attempting to transmit complex and technical protocols to lay subjects. The Board will seek to approve the shortest consent form possible consistent with the needs of the study. Attachments such as a schema, calendars, or illustrations are encouraged.
It is recommended that the Informed Consent Document (ICD) be provided at the 5th – 7th grade reading level in at least a 12-point font size. Suggestions are available as to techniques that may be used to achieve and test the reading level.
Additionally, technical and scientific terms should be adequately explained using common or lay terminology. Provisions must be made for subjects who have difficulty reading due to visual or educational impairments.
NGHS Guidelines for Patient Education Materials
The language of the consent document should be in the second person style (i.e. "you"), which may help convey that there is a choice to be made by the participant.
The document should make it clear that a copy of the consent, signed by the subject and investigator or the investigator's designee, must be provided to the subject.
Informed consent will be appropriately documented, in accordance with the following options:
Option One: Written Consent Form Signed By Subject Or Legally authorized Representative. The DHHS and the FDA regulate the documentation of informed consent by specifying the elements and by requiring, in most circumstances, that a consent document be used.
45 CFR 46.116 & 21 CFR 50
The basic elements to be included in every informed consent document are:
- A statement that the study involves "research".
- An explanation of the purpose of the research.
- The expected duration of the subject's participation.
- A description of the procedures to be followed, and identification of any procedures that are experimental.
A description of any reasonably foreseeable risks or discomforts to the subject.
This section will include information on physical risks and may include information on legal, financial, social risks and risks to loss of privacy/confidentiality. Each sub-section will be identified.
A description of any benefits to the subject or to others that may reasonably be expected from the research.
This section will include information on personal physical benefits and may include information on social legal, financial or social benefit.
- Descriptions of appropriate alternative procedures or courses of treatment, if any that might be advantageous to the subjects.
- Any costs to the patient or third party payers that may result from participation in the study.
A statement describing the extent, if any, to which confidentiality of records identifying the subject will be maintained.
Access by the IRB, the funding agency and any sponsor must be mentioned. Harm from a breach of privacy is occasionally the only risk and, as such, this information is often found in the risk section.
- 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.
"Minimal risk means the risks of harm anticipated in the proposed research are not greater, considering probability and magnitude, than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests."
45 CFR 46.102(i)
An explanation of who to contact for answers to pertinent questions about the research and research subjects' rights, and who to contact in the event of a research related injury to the subject.
This person will be involved with the IRB rather than with any of the research bases. The consent form will not name a specific person but will give a title and phone number.
- A statement that participation is voluntary, that refusal to participate will involve no penalty or loss of benefits to which the subject is otherwise entitled, and that the subjects may discontinue participation at any time without penalty or loss of benefits to which the subject is otherwise entitled.
Additional Consent Elements
- While the practice appears to be to include all optional elements in every consent form, NGHS is also concerned about forms that are too long and involved to be understood. Therefore, these elements are to be included only if they are pertinent to the circumstances of the protocol.
- 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.
Such circumstances can include emergence of adverse events, failure to gain FDA clearance, or failure to adhere to protocol.
- 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 subjects willingness to continue participation will be provided to the subject.
New findings are not likely to emerge during a 2-hour interview or a venipuncture; they are likely to emerge during a multi-year treatment.
The approximate number of subjects involved in the study.
45 CFR 46.116(b)
Informed consent information should be presented ‘in language understandable to the subject’. Should a non-English speaking subject be eligible for a study in which there is no translated consent form, the IRB should be informed by the next Board meeting. If time allows, the document should be translated. The investigator should present plans to support continued consent in the primary language.
Option Two: Oral Presentation Using Short Form. As an alternative to standard written informed consent documents, an oral presentation of informed consent information may be used for non-English speaking participant provided:
- The witness/translator is fluent in both English and the language of the participant.
- A written summary of what is presented orally (i.e. the IRB approved English language informed consent document) is prepared. At the time of consent, the person obtaining the consent and the witness/translator signs the summary.
- A short form written consent document, stating that the elements of consent have been presented orally, is in a language understandable to the participant. At the time of consent, the participant and the witness/translator should sign the short form.
The IRB must receive all foreign language versions of the short form document as a condition of approval. Expedited review of these versions is acceptable if the protocol, the full English language informed consent document, and the English version of the short form document have already been approved by the convened IRB.
45 CFR §46.116 & §46.117
OPRR Memo: Nov. 9, 1995
Option Three: Waiver Of Documentation. The IRB may waive the requirement to obtain a signed consent form for some or all subjects if the IRB finds either:
That the only record linking the participant and the research would be the ICD and the principal risk would be potential harm resulting from a breach of confidentiality; or
45 CFR 46.117 (c)(1)
That the research presents no more than minimal risk of harm to subjects and involves no procedures for which written consent is normally required outside of the research context.
45 CFR 46.117 (c)(2)
In cases in which the documentation requirement is waived, the IRB may require the PI to provide participants with a written statement regarding the research.
- That the only record linking the participant and the research would be the ICD and the principal risk would be potential harm resulting from a breach of confidentiality; or