Chapter 5: THE INFORMED CONSENT

The Belmont Report provides Investigators with the basic ethical principles for conducting research with human subjects. The principle of “respect for persons” incorporates two ethical convictions. Individuals should be treated as autonomous agents; and persons with diminished autonomy are entitled to additional protection.

An autonomous individual is capable of establishing personal goals and completing actions toward the goals. Others may respect an individual’s autonomy by taking into consideration an individual’s opinions and choices while refraining from obstructing their actions unless the actions are harmful to self or others. In regards to research participation, respect for autonomy is addressed by giving an individual a choice to enter research voluntarily after being presented with adequate information. This is the premise of informed consent.

The ethical principle of “respect for persons” is met through voluntary, informed consent.

Informed consent is a person’s voluntary agreement, based upon adequate knowledge and understanding of relevant information, to participate in research or to undergo a diagnostic, therapeutic or experimental procedure. Informed consent is essential for studies involving humans. Participants need to understand why the research is being pursued, what procedures and time commitments are involved, and the potential risks and benefits. In addition, each participant must be given ample time to decide, there must be no degree of coercion, and the language must be clear enough for every level of understanding.

It is the responsibility of the Investigator to assure that consent is obtained by personnel knowledgeable about the study who are able to respond to questions by the study participant Investigators must obtain legally effective informed consent from each participant or from the participant’s legally authorized representative prior to his or her participation in the research, unless this requirement has been waived by the CPHS. The Investigator is also responsible for assuring that the consent document is signed and dated, at the time consent is given, by the participant or his or her legally authorized representative. Consent must be obtained before completion of any screening activities that are to be done solely for purposes of determining a prospective participant’s eligibility to be included in the research. Unless waived by the CPHS, participants must document their consent by signing a written consent document and will be given a copy of the signed consent.

For individuals who may have diminished autonomy either through age, maturity, or psychological state, investigators must assure that additional protections are in place (e.g., permission from legally authorized representative). The Federal regulations provide additional guidance on including participants with diminished autonomy (e.g., children, cognitively impaired).

Legally authorized representative - an individual or judicial or other body authorized under applicable law to consent on behalf of a prospective participant to his or her participation in the procedure(s) involved in the research.

An investigator must seek consent only under circumstances that provide the prospective participant, or his or her legally authorized representative, sufficient opportunity to consider whether to participate and to minimize the possibility of coercion or undue influence.

The informed consent process is necessary to ensure that subjects are fully informed about the research before deciding to volunteer as research subjects. The consent process is not a one time event, but an ongoing process throughout the subject’s participation in the research.

Informed consent does not mean obtaining signature on the consent document but a discussion process that is designed to provide the potential subject with adequate information to make an informed decision about participation in the research project.

While conducting the informed consent discussion, the person conducting the discussion should keep the following considerations in mind:

• The consent discussion should be conducted by the Principal Investigator, collaborator or a member of the study staff who is listed in the CPHS Application Form as the designated person for conducting the Informed Consent discussion.
  
  
• The consent discussion should take place in person. CPHS may approve of an alternate method of obtaining informed consent such as phone, fax, email or mail. But approval must be sought before using an alternate method.
  
  
• The consent should be obtained before performing any study procedures, including screening participants for study inclusion, unless waived by CPHS.
  
  
• Consent should be presented in a language that is understandable to the subject.
  
  
• Subjects should be approached in a conducive environment. CPHS may determine that it would not be appropriate to approach a subject immediately before a procedure or surgery, while in labor, while under sedation and any other situation where a subject might feel compromised.
  
  
• Subjects should be given adequate time to make decision about study participation prior to signing the informed consent document.
  
  
• The investigator should provide an adequate plan that minimizes the possibility of coercion or undue influence when consenting potential subjects.

Informed consent must be obtained from the research subject. However, when the subject population may not be able to give an effective consent, the investigator may seek CPHS approval for obtaining consent from the subject’s legally acceptable representative to provide consent on behalf of the subject.

CONSENT DOCUMENT

The CPHS must approve all consent documents, assent forms, and scripts. If these forms need to be changed for any reason, the changes must be approved by the CPHS prior to use of the revised consent document(s). Informed consent documents signed by participants must have the CPHS stamp that indicates the document was approved.

One common reason for delayed or pending protocols during the CPHS review process is an incomplete consent form, or a consent form written beyond the understanding of the participant population. For example, the CPHS will send back any informed consent form that uses scientific terminology or inadequate explanations for the research participants.

Exculpatory Language - Informed consent documents may not contain any exculpatory language through which the participant is made to waive or appear to waive any of his or her legal rights, or release or appear to release the Investigator, the sponsor, the University, or its agents from liability for negligence. For example, “I waive any possibility of compensation for injuries that I may receive as a result of participation in this research,” is an unacceptable statement to include in a consent document.

Requirements for Informed Consent
The Federal regulations provides specific elements of consent that are required for obtaining legally effective informed consent (45 CFR §46.116). There are eight (8) required elements and six (6) additional elements that must be included when applicable. The additional elements should be evaluated for applicability to the study information and relevance to the decision by the participant to enroll. The iRIS system provides an informed consent form template to guide the PI in developing his/her own informed consent form, which should then be attached to the submission.

Eight Elements of Informed Consent

The eight (8) required elements are as follows:

1. 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;
   
   • This requirement encompasses most of the information to be communicated to the potential participant. It must be clear to the subject that this is research and he or she should know the purpose of the study, e.g., why are they being asked to participate.
   
   • This section should also include all of the procedures to be completed and the time commitment expected. For studies in which the commitment is lengthy and multiple procedures are part of a complex research design, it is helpful to include a table or chart clearly outlining the expectations. Describe the study activities in a clear sequence of events and indicate which activities are routine care versus those that are investigational in nature. Additionally, include a description of any screening activities that will be done solely to determine the participant’s eligibility for enrollment into the study. Questionnaires, assessment scales, surveys, interviews, or other study tools should be described, and sample questions provided if possible.
   
   • Audio or videotaping - If the study involves audio or videotaping, explain what will happen to the tapes after the study is completed or if a participant withdraws before completion.
   
   • If a student is conducting the research, this information should be included in the consent (e.g., thesis, dissertation).
   
   
2. A description of any reasonably foreseeable risks or discomforts to the subject;
   
   • The risks of procedures relating solely to research should be explained in the consent document, and especially for tests that carry significant risk of morbidity/mortality themselves. The explanation of risks should not minimize reported adverse events and should be based upon information presented in documents such as the protocol and/or investigator’s brochure, package labeling, and previous research study reports.
   • For studies involving minimal risk procedures or activities, potential risks may include the inconvenience for participation, psychological distress (even after participation), or physical discomfort, (e.g., frequent visits, time commitment, answering questionnaires, uncomfortable procedures). It is also applicable to discuss any risks due to a possible loss of confidentiality.
   
   
3. An adequate description of any benefits to the subject or others that may reasonably be expected from the research;
   • This description should include any potential for benefit to the subject and/or to society for generalizable knowledge.
   • Payments made to participants as compensation for their time may not be included as a benefit.
   
   
4. A disclosure of appropriate alternative procedures or courses of treatment, if any, that might otherwise be available to the subject;
   
   
5. A statement describing the extent, if any, to which confidentiality of records identifying the subject will be maintained;
   
   • An explanation should be given about who will have access to the data, where the data will be kept, for how long and whether the data, if retained, will be used for further research purposes and/or shared with other researchers for additional studies.
   
   • If the retained data are to be used for further research and/or data are to be shared with other researchers for additional or other research purposes, subjects should also be told whether identifiers will also be used or shared.
   
   • The consent form must describe the disposition of video and audiotapes taken of the subject. A statement should be included in the consent form as to whether the research data will become part of a permanent record for the subject (e.g., medical record) or held in the study record.
   
   • When applicable, explain any foreseeable circumstances under which the Investigator will be required to give information about the subject to third parties, (e.g. mandatory reporting of child abuse).
   
   • The iRIS system provides Investigators with template language for confidentiality.
   
   
6. For research involving more than minimal risk, an explanation as to whether any compensation and/or whether any medical treatments are available if injury occurs and, if so, what they consist of, or where further information may be obtained;
   
   • UTHealth investigators must use the following wording in all Informed Consent Forms:
   
   "If you suffer any injury as a result of taking part in this research study, please understand that nothing has been arranged to provide free treatment of the injury or any other type of payment. However, all needed facilities, emergency treatment and professional services will be available to you, just as they are to the community in general. You should report any such injury to (put the principal investigator's name and phone number here) and to the Committee for the Protection of Human Subjects at 713-500-3985. You will not give up any of your legal rights by signing this consent form."
   
   • HOWEVER, the costs for care of a research-related injury when a subject is enrolled in a study sponsored by a pharmaceutical company, MUST be covered by the company. The following is mandatory "in case of injury" language for pharmaceutical company sponsored protocols:
   
   "If you suffer any injury as a result of taking part in this research study, the sponsor of this study, (enter sponsor's name), will pay for reasonable and necessary medical expenses if the injury is a direct result of taking the study medicine or undergoing study procedures, and not due to the natural course of any underlying disease or treatment process. You should report any such injury to (put the principal investigator's name and phone number here) and to the Committee for the Protection of Human Subjects at 713-500-3985. You will not give up any of your legal rights by signing this consent form."
   
   
7. 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 24 hour contact number should be listed on the informed consent form for the investigator or key study personnel serving as the contact person, for questions regarding the research or injuries.
   
   
   • The CPHS office number and toll free number should be listed as who to contact for questions regarding subject’s rights. The informed consent document template includes standard language that will meet this requirement.
   
   
8. A statement that participation is voluntary, that refusal to participate at anytime will involve no penalty or loss of benefits to which the subject is otherwise entitled.
   
   • The informed consent document template contains language indicating the right to withdraw or refuse to participate without prejudicing subject’s health care.

Additional Elements of Informed Consent

Other pertinent study-related information that should be shared with the potential subject to aid in the decision to participate:

• A statement that a particular 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;

• When a study is greater than minimal risk and the effects of the procedure may be uncertain, a statement indicating that there may be risks to the subject which are unforeseen must be included.
  
• Template language is available within the informed consent document template on iRIS.

• Anticipated circumstances under which the subject's participation may be terminated by the Investigator without regard to the subject's consent;

• An investigator may need to withdraw a subject for not following the research procedures or if a subject’s safety is implicated.
  
• There may be other situations in which a subject would be withdrawn by the investigator. These situations should be described for the potential subject to assist in understanding all that will be expected in order to be a part of the study.
  
• Dissenting behaviors (e.g., refusing to cooperate, crying) should be listed for studies involving children. If there is active dissent, participation should not be considered.

• Any additional costs to the subject that may result from participation in the research;

• Should there be study related procedures that will be the financial responsibility of the subject (e.g., transportation, hotel), this information needs to be included.
  
• If there are procedures that will be billed to a subject’s health insurance and the subject is responsible for any co-pay, deductible or partial payment, this should also be included.

• Any consequences of a subject's decision to withdraw from the research and procedures for orderly termination of participation by the subject;

• Specific procedures that need to be followed in order for a subject to withdraw (e.g., contacting the PI or key study personnel) should be stated in the informed consent document.

• 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;

• As new information is gathered regarding the research, it is sometimes necessary to inform subjects of relevant findings that may impact their willingness to continue to participate . When this occurs, it may be necessary to consent the subjects again with the new information.

• The approximate number of subjects involved in the study.

• In evaluating the risks, a potential subject may make a different decision as to whether to enroll if they know that they are 1 of 10 participants versus being 1 of 10,000.
• When this is required, the CPHS typically asks that the subjects be informed as to how many will be enrolled at UTHealth and how many will be enrolled nationwide, if this is a multi-site study.

Format and Style of Informed Consent Documents

Standard Consent Document
• The CPHS encourages investigators to use the standard UTHealth consent form guidelines which are available in iRIS.

All information in such documents should be written in lay language, at a level understandable to the subjects in the study (6th to 8th grade reading level for adult subjects). There are resources available for checking the reading level of your document, such as http://www.literacytrust.org.uk/campaign/SMOG.html.

• The use of a 12-point font is recommended. A larger type size may be appropriate for some populations, such as children, the elderly, or the visually impaired.
  
  
• Documents must be typewritten.
  
  
• Documents should include headings for section of the informed consent.
  
  
• All consent forms must identify the subject population, for which the consent form is intended, (e.g., adults, parents-legal guardians, surrogates).
  
  
• The consent forms must be written in second person (e.g., you will be asked to. . .) which may help convey that there is a choice to be made by the subject.
  
  
• A place for the subject’s signature and date and time must appear on the consent document. A witness signature is not required.
  
  
• The consent document should include a statement telling the subject that he or she will receive a copy of the consent form.
  
  
• When applicable, the document should state that the research is being conducted to fulfill a requirement for a doctoral dissertation, master’s thesis or classroom assignment.
  
  
• The consent form should identify any external sponsor or funding agency.
  
  
• Informed consent forms for pharmaceutical sponsored protocols that are supplied by the pharmaceutical company should not be submitted to the CPHS unless they are revised using the CPHS format and language as detailed above.
  

Letter Format

A Letter of Information may be more appropriate depending on the nature of the study. The exact title of the research study should appear at the top of the form, followed by the HSC#. The CPHS recommends that the letter model the template consent form to assure that all required elements are addressed. It is suggested that separate paragraphs with headers be created to address the required elements.

Consider the age of the participant and cognitive abilities
The assent form should take into consideration the age, maturity and psychological state of the child. The CPHS recommends that the forms be grouped as follows:

• Assent form for children 7 – 12; and
• Assent form for children 13 – 17.

ASSENT - Agreement by an individual not competent to give legally valid informed consent (e.g., a child or cognitively impaired person) to participate in research.

Children ages 13 – 17 may sign a form with language similar to that presented to the parents or legal guardians. However, it is preferable for the child’s form to be simplified in age appropriate language. Often times the parental permission form will need additional information that may not be pertinent to the child regarding the decision to participate. For more information on consent and assent for participants under the age of 18, see Chapter 5.

Translating Consent Documents

For non-English speaking participants, a translated copy of the consent form must be added; verbal translations are not acceptable. The CPHS office does not provide translation services for informed consents. However, Spanish consent forms will be reviewed and approved for content. If you need translation assistance, please contact an outside company. Listed below are a few local translation companies.

Transperfect Translations (713) 650-0440

International Language Assoc. (713) 206-0910

ALS Translation & Interpreting (713) 227-3500

In addition, the Patient Relations Department at Memorial Hermann Hospital offers translation services. They can be contacted at 713-704-2020.

Subjects who do not read – When enrolling subjects who are illiterate, the consent document should be fully discussed with the subject and the subject should be given an opportunity to ask questions or for clarification. The person authorized to obtain consent may either:

• make a note that the subject cannot read but that the consent document was fully explained, the subject had adequate time to ask questions, and that he/she acknowledged that they understood what was explained and agreed to participate,
  
  OR
  
  
• if there is someone of legal age accompanying the subject, then that person may sign the consent document indicating that the consent document was fully explained, the subject was provided ample opportunity to ask questions, and that the subject understands what has been explained and has agreed to participate. The person signing the consent document should also include a note describing what their relationship is to the subject.

Waivers or Changes to the Informed Consent

As with any change to your protocol, if the Informed Consent Form is changed, it must be submitted in iRIS with the changes highlighted. A revised protocol must also be submitted, if applicable, with changes highlighted there also. All changes must be approved by CPHS before implementing.

If revisions to the informed consent form are approved, then all old copies of the Informed Consent Form must be destroyed. Only informed consent documents with a CPHS statement, approval, and current date may be used when obtaining consent.

Guidelines for Enrolling Emergency Department Patients in Research Studies

The following procedure pertains when studies plan to enroll patients/subjects while in the Emergency Department (ED) of either Memorial Hermann Hospital or LBJ General Hospital.

• Before submission of your protocol for review and approval by the CPHS, you must contact the Research Director of the Division of Emergency Medicine (ED) or the Department Chair, to discuss the logistics of your study; e.g. how the investigators are to be contacted by ED personnel, how patients are to be recruited and enrolled, how informed consent will be obtained, etc.
  
  
• You must submit a letter of support from the ED for your study which will indicate to CPHS that such appropriate arrangements have been made with the Division of Emergency Medicine
  
  
• A copy of your protocol, CPHS forms, CPHS approval letter, and data collection forms must be submitted to the Director to be included in the Emergency Department's Research Protocol Book. This protocol book allows all investigators, attendings, residents, and staff rotating through the ED to be informed as to which patients are eligible to be enrolled in certain studies and the procedures to follow.
  
  
• When your study is ready to be implemented you will be responsible for providing an in-service to all relevant personnel in the ED.

Protocols Using Deception in Research

CPHS recognizes that some research may, by necessity, involve deception. Therefore, the following have been constructed as guidelines for investigators whose research may fall into these areas:

• The research must be well designed.
  
• The investigator must give a rational explanation and appropriate justification for the use of deception.
  
• All protocols involving deception must be thoroughly reviewed by CPHS weighing those elements against the risk/benefit balance for the subject.

When deception is part of the research design, the deception must be absolutely necessary to the research and subjects must be thoroughly debriefed after their participation is complete. For such protocols we suggest the following language be added to the consent form:

"We are going to tell you the overall intent of the research in which you are being asked to be a subject but not all of the details because this might influence the way in which you participate. Once your participation is complete, you have every right to know all of the details and the research physician or staff will inform you of those details."

and/or

"The research may contain elements of deception, but the CPHS reviews all research protocols to ensure that you are informed of any part of the research that might cause you harm. Once your participation is complete, the researcher will inform you of the details."

Consent for use of Fetal Tissue in Research

Any investigator proposing to use fetal tissue must complete an application form for CPHS review and approval. The application must include a copy of the consent form used to obtain consent for donating the tissue. CPHS must be assured that the woman donating tissue has been given an opportunity to understand the procedures, any possible risks to her privacy or well-being, and to assure that she has an opportunity to give free and informed consent to the donation. Tissue may only be obtained from women over the age of 18.

The timing of the already agreed-upon surgical procedure must not be changed for research purposes; postponement is not permitted.

Regardless of the circumstances of donation, whether by spontaneous miscarriage and subsequent retrieval of any remaining tissue or by elective abortion, the tissue may only be obtained from a dead fetus.

A two-step consent process is necessary. The woman should sign the appropriate surgical consent form for the underlying surgical procedure. Only after giving consent to the surgery, may the woman be approached for the research donation of fetal tissue. This should occur prior to the administration of any sedative, with adequate time to consider the request and ask any questions to ensure that an informed decision is made.

A consent form for the research donation should include the following information:

• a statement that the fetal tissue will be used in research and a short description of the reasons for the research
  
• a statement that the decision to donate or not, will not affect the planned surgical procedure; that there will be no modification in the procedure; no additional risks or discomforts associated with the donation
  
• a statement that the tissue will not be identified and that the woman will not be identifiable
  
• a statement as to whether any special tests of the woman or fetus will be performed (blood tests for infection, HIV, etc.). If so, whether the information will be available to the woman donating the tissue
  
• a statement that there will be no additional costs to the woman as a result of the decision to donate
  
• a statement that there is no benefit to the woman for the donation
• a statement that if the woman chooses to withdraw consent for the research donation, she may do so
  
• a statement giving the name and telephone number of the investigator indicating a willingness to answer questions

Consent for Stored Specimens

In the event that the PI is going to maintain and use residual specimens from a research subject, care must be taken when establishing the tissue bank or repository. Guidances by the Department of Health and Human Services can be found at the following two websites:

http://www.hhs.gov/ohrp/humansubjects/guidance/reposit.htm
http://www.hhs.gov/ohrp/humansubjects/guidance/cdebiol.htm

In addition, the protocol and informed consent form should address the following points:

• that all study information is coded and personal identifiers will be maintained securely;
  
• that the consent form includes information about who will receive information derived (e.g. the patient, family members, physicians, other investigators);
  
• that information as to whether clinically relevant information may be uncovered during the course of the study and give the participants the opportunity to decline receiving this information;
  
• if children are to be research participants, clarify how consent will be obtained and data will be handled;
  
• that participants may derive no benefit from participation;
  
• that study data should not be recorded in the patient’s medical record – separate research records with controlled access are preferred;
  
• whether a family pedigree will be published and if there is a possibility of individually identifying subjects;
  
• whether there are special risks associated with participation, such as changes in family relationships, risks to privacy, confidentiality, insurability, employment, immigration status, paternity, etc.;
  
• whether general study results will be made available to subjects;
  
• whether genetic counseling will be made available and at whose cost;
  
• that the specimens will be maintained for a limited time or indefinitely, or if they will be discarded;
  
• whether participants will be contacted in the future if clinically relevant information is discovered;
  
• whether specimens will be shared with other investigators and, if so, how the participants can decline this part of the protocol;
  
• whether there is potential commercial value to be derived from the research and whether participants will be asked to waive any rights or control over the tissue so used;
  
• that neither the PI nor the participant has any ownership or proprietary interest in the specimens; and,
  
• that the right of the participant to withdraw from the study does not necessarily mean the participant has the right to have any samples destroyed, stored indefinitely, or request that they be anonymized.

Telephone Consent

Telephone consent for enrollment in a clinical trial is not allowed by the CPHS. If the consent document can be faxed to the legally authorized representative, and an opportunity is provided to ask and answer questions with that person, then a faxed, signed consent document can be used to enter the subject into the research study.

UTHealth’s Compliance Hotline (1-888-472-9868)
For other questions, please call us at 713-500-7943.