Human Research Protection Program

When discussing informed consent, the first thing that generally comes to mind is the informed consent form. It is important to remember, however, that informed consent is a process, not simply a form. While the consent form is a key document obtained in the process of informed consent, it is only a physical reference and representation of the ongoing process as well as formal documentation.

The elements of informed consent are outlined in the consent form and include the following components:

1. Title of the study.

2. Names and affiliations of the primary investigator.

3. Study objectives.

4. Criteria by which subjects were chosen.

5. Study procedures.

6. Potential risk and discomforts to the subject.

7. Potential benefits to the subject, society and/or science.

8. Cost to the subject of participating in the study, and the compensation thereof.

9. Whether/how the subject's data will be used for future research.

10. Confidentiality of the subject's data.

11. Rights of the subject to participate or withdraw.

12. Investigator's and relevant insitutional review board's contact information.

1. An explanation of the use of incomplete disclosure.

2. A description of any experimental procedures that will be used.

3. A statement regarding any alternative procedures available to the subject.

4. The possibility of any unforeseeable risks.

5. The potential for compensation or treatment in case of injury.

6. The potential for termination without regard to consent.

7. Any additional costs to subjects.

8. The consequences of withdrawal from the research.

9. Whether the subjects will be provided with any significant new findings.

10. The number of subjects participating in the research.

11. The commercial use of biospecimens.

12. Whether clinically relevant research results will be provided to the subject.

13. Whether the research will or might include whole genome sequencing.

14. Whether the research is covered by a certificate of confidentiality

The consent document may not contain exculpatory language that waives or appears to waive subjects' rights.

To ensure informed consent, investigators must work to communicate clearly and effectively with their subjects, build trust and cooperation, openly and willingly explain their research, answer questions and be sensitive to the needs and concerns of their subjects.

When using an informed consent form, the investigator reviews each component of the form, encourages and answers any questions the subject has and allows ample time for the subject to deliberate on whether s/he would like to participate in the study. It is important that, when the investigator presents the information, the subjects' ability to comprehend is taken into account. In addition, the investigator must ensure that the subject knows his/her participation is completely voluntary and that they may withdraw from the research at any time.

For consent forms that are complicated and/or long — as are used with clinical/biomedical research — the form must begin with a concise and focused presentation of the key information that is most likely to assist a prospective subject in understanding the reasons why one might or might not want to participate in the research.

Note that the consent form is not a substitute for discussion; it is a summary of what was discussed. Once the subject agrees to participate and the investigator is confident the subject’s decision to participate is an informed one, the subject's signature on the form is obtained and the subject is provided with a copy of the consent document.

There are times when the use of an informed consent form would be impractical or detrimental to the study. In these cases, a waiver of documented informed consent may be requested of the Institutional Review Board. Such waivers may be granted under three conditions:

1. If the consent document would provide the only link to the subject and the principal risk of the research would be a breach of confidentiality.

2. If the risk to the subjects is minimal and consent would not be required outside the research context.

3. If the subjects are members of a distinct cultural group or community in which signing forms is not the norm.

In cases where a waiver of documented informed consent is granted, it is important for the investigator to understand that the waiver involves only the documentation of informed consent, not the process, and active consent must still be obtained.

Oftentimes, when documented informed consent is waived, the investigator will use an information sheet in its place. An information sheet follows the same format as the consent form and includes all the same elements. In lieu of the consent form, the investigator reviews and discusses the information sheet and obtains the subject's verbal consent.

In either case, the consent process is not over once consent has been obtained, but it continues throughout the subject's involvement in the research. Subjects should continually be encouraged to ask questions and request clarifications, and be reminded that they may withdraw from the research at any time. Maintaining consent is particularly important in cases where the subject's participation in the research is ongoing.

Note: The Institutional Review Board may approve an alteration of documented informed consent, as well, where one or more of the elements of informed consent are not included in the informed consent form.

In exceptional circumstances, the principal investigator may request a waiver or alteration of informed consent. The Institutional Review Board may waive the requirements of informed consent if all the following stipulations are met:

1. The research involves no more than minimal risk to the participants.

2. The waiver or alteration will not adversely affect the rights and welfare of the participants.

3. The research could not practicably be carried out without the waiver or alteration.

4. Whenever appropriate, the participants will be provided with additional pertinent information after participation.

5. 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.

Fully informed consent is not possible without all relevant information pertaining to the subjects' participation in research; therefore, the use of deception in human subjects research necessitates a waiver or alteration of informed consent.

 Children (defined in Massachusetts as persons under the age of 18, but vary state to state and country to country; the investigator must discuss the different state/national rules if they apply) are considered by the Federal Code of Regulations to be a "vulnerable population" due to their (assumed) inability to fully understand how to weigh the risks and potential benefits of research (or what they are), as well as their susceptibility to undue influence.

Legally, children are not able to provide informed consent on their own behalf; therefore, obtaining informed consent for the involvement of children as research subjects is a two-step process: the investigator must obtain informed consent from the child's parent(s), guardian(s) or legally authorized representative as well as assent from the child, assuming s/he is capable.

Obtaining informed consent from a child’s legally authorized representative involves the same process as does obtaining informed consent from an adult on their own behalf. The pertinent information regarding the research is reviewed with the representative, and the representative is encouraged to ask questions to ensure an informed decision is made. When appropriate, the legally authorized representative should discuss the research with the child.

After documented informed consent has been obtained from the legally authorized representative, the investigator must, assuming the child is capable, also obtain informed assent (the active affirmation of a desire to participate in the research) from the child. In determining whether a child is capable of assenting, the investigator should take into account the age, maturity and psychological state of child. This judgment may be made for all children to be involved in research under a particular protocol, or for each child. When a child is capable of providing assent, s/he should be given an explanation of the proposed research procedures in language that is appropriate to the child's age, experience, maturity and condition.

Informed assent may be written or it may be verbal, depending on the age of the child and the appropriateness of requiring the child to give written assent. Either way, informed assent, as with informed consent, is an ongoing process.

Note that children who turn 18 during the course of the research must be re-consented, or give informed consent as an adult, and be given the opportunity to withdraw their participation in the research.

Waiver of Assent

An institutional review board may waive the requirements for obtaining subject assent in circumstances in which the subject population does not have the capacity to comprehend the research or associated procedures. This judgment may be made for all subjects involved in the research or for each child individually. If the IRB determines either of the following to be true, then the assent of the child is not a necessary condition for proceeding with the research:

• The capability of some or all of the subjects is so limited that they cannot reasonably be consulted.

• When the research offers the subject the possibility of a direct benefit that is important to the health or well being of the subject and is available only in the context of the research.

The IRB will take into account the age, maturity and psychological state of the subjects involved in determining whether a waiver of assent is appropriate.

Waiver of Consent

An instiutional review board may, for the protection of the subjects, waive the requirements for obtaining parental or legally authorized representative consent if the IRB determines that a research protocol is designed for conditions or for a subject population for which parental or authorized representative permission is not a reasonable requirement (for example, neglected or abused children). In such cases, there must be another mechanism in place for the protection of the subjects.

 When an investigator conducting research obtains identifiable private information about a living individual, that individual becomes a research subject, regardless of whether that person is the individual with whom the investigator is having an interaction. For example, if the research involves asking the primary subject to provide identifiable private information about a third party, that third party then becomes a subject in the research. As such, all of the regulatory requirements for protecting that individual obtain.

The Institutional Review Board can determine whether informed consent needs to be sought from third party subjects, or whether it can be waived. In making this determination, the IRB relies on both the requirements for a waiver (noted earlier in this section) and the importance of the information to the research.

Investigators whose research may involve so-called "secondary subjects" are encouraged to contact the IRB staff to discuss how to best protect the rights and welfare of these subjects in a given project.

Much social research being done today involves subjects whose primary language is not that of the investigator and special precautions must be taken in these cases. (For simplicity purposes, we will assume the investigator's primary language is English.) However, informed consent must always be obtained in a language in which the subject is comfortably fluent. In those instances where the subjects do not speak English, the informed consent form should be translated into the primary language spoken and understood by the subjects, and an interpreter hired to translate throughout the informed consent process.

It is important that you not rely on family members or friends of the subjects. Instead, you should hire a professional with whom you can discuss the study in detail. It is important that the interpreter fully understands your research or s/he may not communicate the information accurately. In addition, it is important that the subjects feel comfortable answering and/or asking questions freely.

In those instances where a subject has some competency in English, the investigator may be tempted to forgo the use of an interpreter. The investigator must be careful, however, to be sure the subject is truly proficient in English. There are often times when a subject believes s/he is proficient "enough" and so does not inform the investigator — or even realize — that both s/he and the researcher would be better served by the use of an interpreter.

Even when language is not an issue in the informed consent process, cultural barriers may still exist in both local and international research. When dealing with subjects whose culture, for example, reveres education, the subjects' inclination may be to agree to participate in the research simply out of respect for the investigator. The investigator should be aware, therefore, of the potential for cultural differences between his/her subjects and him/herself.

When conducting research internationally, the Brandeis Institutional Review Board may require the investigator to obtain approval from the local equivalent of the IRB where the research is to take place. In cases where there is no local equivalent, investigators may be required to obtain approval from local experts or community leaders in lieu of a local IRB.

In such cases, the investigator should be cognizant of local culture, mores and attitudes that may affect subjects' informed consent. For example, the local IRB equivalent may be a council of elders whose own approval of the research may imply to the subjects a requirement to participate in the research.

• Belmont Report

• Centers for Disease Control and Prevention: U.S. Public Health Service Syphilis Study at Tuskegee

• Code of Federal Regulations 45 CFR part 46