MCGILL UNIVERSITY HEALTH CENTRE OFFICE OF RESEARCH ETHICS

- FREE AND INFORMED CONSENT –

Understanding the Informed Consent Process

Research involving human subjects at the McGill University Health Centre is conducted according to international ethical principles that require a prospective study subject to provide voluntary free and informed consent. The requirement is described in the Tri-Council Policy Statement Ethical Conduct for Research Involving Humans (Article 2.1 – 2.8). “A morally valid choice concerning the participation by a subject in research is a choice made: (1) by a competent person; (2) on the basis of adequate information concerning the nature and foreseeable consequences of the research, including all available options; and (3) without controlling influences or ulterior forms of constraint or coercion.” (adapted from the Nuremberg Code). Free and informed consent therefore refers to a person’s choice to become a subject of research and is brought about through dialogue between the research investigator or study representative and a prospective subject and/or the person’s authorized third party. Sufficient time must be allotted to communicate a thorough explanation of the study and of the responsibilities of both investigator and subject. The prospective subject must be given adequate time to consider the information before making the decision on participation to avoid coercion or undue influence. A morally valid choice also includes the concept of assent whenever the prospective subject is deemed not to be legally competent. The free and informed consent process is focused on exchanging questions to establish a dialogue about the research to the satisfaction of the prospective subject or the substitute decision-maker. The discussion is followed by the investigator’s determination that the person realizes what is required of a subject, and recognizes the related risks and potential benefits of participation. A prospective subject provides free and informed consent by agreeing to follow the research rules and procedures for the specified length of time and is asked to sign the Research Ethics Board (REB) approved consent document. The act of signing indicates that an educational process has taken place to the satisfaction of those involved. The signed consent document creates obligations under policy and law for the investigator and signals the subject’s agreement to accept the responsibilities of a study participant. The subject receives a copy of the signed document for future reference. To demonstrate respect for a person’s free and informed consent is viewed, therefore, as an ongoing exchange of information and not simply putting signatures on a piece of paper. The written consent acknowledges that the subject was given all relevant information, was afforded sufficient time to ask questions and consider the decision, and documents the subject’s choice. By “continuing to participate in the research”, a subject is in effect regularly reaffirming thoughtful consent for a voluntary act. If the original disclosure of information was incomplete or the investigator fails to share new information that could influence a subject’s willingness to continue in the study, then the integrity of the process underlying free and informed consent is compromised.

Version: 07/02

Seeking Free and Informed Consent

Procedures used to obtain informed consent should be designed to educate the target population in terms they can understand. In order for the research subject’s choice to be valid, it must be based upon all relevant information concerning the proposed research. Deciding what is “relevant” involves weighing available options. The investigator or the study representative initiates discussion to provide information concerning the purpose and nature of the study, the potential harms and possible benefits, the procedures involved with participation and, on balance, should not overwhelm the prospective subject with discussion of insignificant details or minutiae. To protect an individual from possible injury arising from cumulative medical acts such as extra blood drawing, exposure to radiation, drug interaction, or similar hazards, an investigator should determine if the prospective subject has recently, or is currently participating in other research. The investigator should directly inform the prospective subject concerning the level of privacy that will be maintained and that it is in the person’s best medical interest to inform the treating physician of participation in the research study. A disclosure of the requirements for documenting participation in the hospital file(s) should be communicated, and that inclusion of any research data in the medical record occurs only at the discretion of the REB. The investigator is obligated to disclose to the prospective subject the existence of any potential conflict of interest disclosed directly to the REB or to an institutional representative. The subject should also be informed concerning possible commercialization of the study findings or material. The investigator is ultimately accountable to ensure that the necessary study-specific information has been communicated effectively and that the written consent document contains all the required elements of free and informed consent.

Elements of Free and Informed Consent:

1. A statement that the study involves research; the reason for the subject’s selection; 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 all experimental procedures and approximate number of subjects to be involved in the study;

2. A description of reasonably foreseeable risks or discomforts to the subject and a statement that the treatment or procedure may involve currently unforeseeable risks to the subject or breast-feeding infant (or to the embryo or fetus if the subject is or may become pregnant);

3. A description of any benefits to the subject or others that may reasonably be expected from the research. If there is no benefit to participation for the individual subject, an honest declaration of that fact must be included;

4. A disclosure of appropriate alternative procedures or courses of treatment, if any might be advantageous to the subject. The subject must be informed should any standard treatment be withheld as a result of study participation;

Version: 07/02

5. If a subject will receive compensation for expenses incurred by participation, or reimbursement for time and inconvenience, specific information concerning the terms of disbursement must be included. Any additional costs to the subject resulting from participation must be described;

6. For research involving more than minimal risk or including an invasive procedure, explanation must be included as to whether compensation and medical treatment would be available should injury occur, and if so, of what they consist and where further information may be obtained;

7. Anticipated circumstances under which the subject, investigator or sponsor may terminate participation without regard to the subject 's consent, i.e. when in the investigator's opinion, it would be harmful for the subject to continue;

8. A statement that any significant new finding to emerge during the course of the study that may affect the subject's willingness to continue participation will be disclosed to the subject;

9. An offer to answer questions and an explanation on whom to contact for answers to pertinent questions about the research, a research subjects' rights, and whom to contact in the event of a research-related problem. Telephone numbers for all these individuals should be included;

10. A statement that participation is voluntary, that the subject may refuse to participate, or discontinue participation at any time without penalty or loss of benefits to which the subject is otherwise entitled. Description of the consequences of a subject's decision to withdraw from the study, if any, and the procedures for an orderly termination of the subject’s participation;

11. A statement describing the extent to which confidentiality of records identifying the subject will be maintained. If study data or specimens will be banked, linked, shared, or otherwise made available to any person or organization other than the investigating team, sponsor and regulatory authorities, the purpose must be explained. If data will become part of the subject’s permanent medical record, the nature of the information and the purpose for the inclusion must be stated;

12. A statement of the offer to the subject to receive a copy of the signed consent document;

13. Space for names and dated signatures of the Subject and Person Conducting the Informed Consent Process to establish which member of the research team discussed the study with the subject. Where applicable, the authorization should include the signature of an authorized third party, including space to indicate relationship to the legally incompetent subject;

14. Space for name and dated signature of a Witness is required if the subject or authorized third party is unable to read. An impartial witness should be present during the entire informed consent discussion to attest that the information was accurately explained and consent freely given. The witness’ signature attests to the voluntary nature of the decision.

Version: 07/02

Assent for Research with Children

Assent in children is understood as a method of expression significant for recognizing autonomy It represents a child’s agreement to participate as a subject of research. The process provides the means for a child to communicate a negative preference on becoming a subject of research. “Respect for persons involves a recognition of the personal dignity and autonomy of individuals, and special protection of those persons with diminished autonomy.” (The Belmont Report) “A minor child, incapable of giving legally and ethically acceptable consent, may give assent.” (MRC Guidelines on Research Involving Human Subjects (1987)

The subject of participation of children in research is governed by Article 21 of the Quebec Civil Code (1994). It stipulates that, “A minor … may not be submitted [i.e., subjected] to an experiment if the experiment involves serious risk to health or, where he understands the nature and consequences of the experiment, if he objects” … “Moreover, a minor … may be submitted [subjected] to an experiment only if, where the person is the only subject of the experiment, it has the potential to produce benefit to the person’s health or only if, in the case of an experiment on a group, it has the potential to produce results capable of conferring benefit to other persons in the same age category or having the same disease or handicap. Such an experiment must be part of a research project approved and monitored by an ethics committee.”

MUHC Research with Children

Almost all pediatric research at the MUHC is conducted at the Montreal Children’s Hospital (MCH) site where the concept of assent from the child is central to decisions regarding study participation. If a parent “consents” to allow a child to participate and the child refuses “assent”, the child 's refusal should take precedence and the research may not be undertaken. Mere failure to object should not be construed as assent to participate. At the MCH a separate assent document, in addition to the written consent document is routinely required for studies for which minor children will be recruited. According to the age limits established by the study entry criteria, one assent document is required to be written in language understandable for children from 7 to 12 years of age, and a second assent form is required for children aged 13 to 18 years, with respect to cognitive norms and developmental maturity. Should recruitment of children younger than 7 years be required the informed consent process can include the child, but only the written consent of the parent or legal guardian is required.

An informed assent document for pediatric purposes must include the same elements of free and informed consent as required for written consent in an adult population.

Version: 07/02

The MCH REB is considered an authoritative resource concerning the ethical conduct of pediatric research at the MUHC. When a research study directed at an adult population also permits enrollment of minor children, the investigator is required to indicate child eligibility on the Application for Review. The Chair of the REB of Record at the adult site will consult with the MCH REB Chair concerning adequate evaluation prior to the study’s review. If adult research with potential for entry of a pediatric population is approved at an MUHC adult site, the MCH REB Chair must be consulted by the Chair of the REB of Record concerning appropriate monitoring for the approved study.

Drafting the Informed Consent or Assent Document

The consent document presents a written explanation of the research to summarize the discussion including explanation of the study objectives and procedures, related risks and potential benefits, and the rights and responsibilities of the study subject, investigator and sponsor. Written consent documents the dialogue that led the subject to decide voluntarily whether or not to participate.

Rules and regulations governing informed consent are subject to change and revision.

Standards for drafting the written consent to document the process may change over time. The consent document should be revised when deficiencies are noted, or when additional information will improve the ongoing consent process. The investigator should be prepared to update a consent document at the REB’s request. The consent document must provide supplementary information concerning a specific feature of the research study (e.g., genetic testing, tissue banking). Once approved, a consent document remains valid until a request to modify a study treatment, condition or procedure, is approved by the REB. The modification is approved by the REB as a study amendment resulting in a revised consent document, and that becomes the only valid version. Significant new information revealed during the course of the research that could affect the risk assessment or subject’s willingness to continue in the study must be communicated to the REB prior to informing a subject. Use of an addendum to the valid approved consent document may be acceptable to the REB under certain conditions, and requires REB approval prior to disclosure to the subject. Asking a subject already enrolled in the study to sign a revised consent document generally should be avoided, except as specifically required by the REB.

Simple explanation of terms enhances communication and promotes informed decision.

Ø The consent document must be identified by date located in the document “footer” on every page. The “footer” date must be revised each time a revision is proposed to an REB- approved consent document.

Ø The REB-approved version of the consent document presented to a prospective subject will be in either English or French, as preferred by the potential subject or authorized third party.

Version: 07/02

Ø Use of any acronyms in the study title (e.g. SMART, CURE or HEALTH) should be avoided on the consent document as such use could potentially be misleading or coercive.

Ø The consent document should be written in everyday language. “Legalese”, scientific jargon, or technical terms should be avoided. Think of the document primarily as a teaching tool not as a legal instrument. Specialized terms should be defined in parenthesis to improve comprehension.

Ø The typeface should be a comfortable, readable size, avoiding fine print. Formatting such as boldface, underline or UPPERCASE should be restricted to emphasize critical information.

Ø It is recommended that the text be written using simple declarative sentences, at an appropriate level for the target population (e.g., child or adult).

Ø Ideally, the document for use in a competent adult population should be coherent to a person with an eighth grade reading level. The final draft of the written consent could be reviewed by a person unfamiliar with the research to test for comprehension.

Ø The use of section headings to separate the content of the document is helpful and makes the written consent easier to read. The consent document usually does not fit onto one page and additional pages are used as long as they convey essential information.

Ø Use of the form “You understand” is not helpful and therefore discouraged. The phrase is suggestive of, rather than indicative of understanding, or may be relied upon as a substitute for sufficient factual information. Avoid phrasing such as “You will”, “You must”, “You have been told”, or “If you refuse”, as such statements are considered overly prescriptive or coercive.

Ø Research terms like “anonymized”, “double-blind”, “will be followed” or “randomization” should be defined or explained as the prospective subject may not understand the usage.

Ø When expressing quantities of blood to be drawn for testing please use easily understood equivalents such as teaspoons, not milliliters.

Ø Whenever possible use simple graphics, flow diagrams, tables, and itemized or bulleted lists in place of lengthy narrative.

Ø The consent document cannot include any statement through which the subject is made to waive or appear to waive any legal rights, or releases or appears to release the investigator, sponsor, institution, or their representatives from liability for negligence.

Study Consent Document Translation

Initial translation of the study consent document may be submitted for REB review with the original language version, or when submitting the “revised” original language version.

Version: 07/02

According to REB recommendations, the investigator incorporates all revisions into both language versions, revises the date only in the original language version, and submits both language versions to the REB. The translated version bears the word draft in place of the date in the document “footer”. Following the validation process, the Translator replaces the word draft with the date of the REB-approved version in the document “footer”. Both language versions are valid and identified as the REB-approved consent document according to the corresponding “footer” dates. Validation of translated consent documents is mandatory at the MUHC to certify that all necessary revisions are made to ensure that both the French and English versions reflect the content of the REB-approved consent document, according to the “Procedure to Standardize Translation of Consent Documents for Human Subjects’ Research at the McGill University Health Centre”. The costs involved with the initial translation and all translated amended consent documents are considered a study-related expense. Cost recovery can be deferred to the study sponsor, or absorbed by the investigator. The costs involved with the translation validation are considered an institutional expense and cost recovery will be invoiced by the Office of Clinical Contracts for payment by the RI- MUHC.

Version: 07/02