• Give the subject information about the research
• Make sure the subject has time to consider all options
• Answer all of the subject's questions before the decision is made
• Make sure that all information is understood by the subject
• Obtain the subject's voluntary informed consent to participate
• Continue to inform the subject throughout the research study
• Continue to re-affirm subject consent to participate throughout the research study

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Consent Process Diagram

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Tools an investigator might use to assist the informed consent process

• Consent Form -- also called Informed Consent Form (ICF), Informed Consent Document (ICD) or Patient Consent Form (PCF)*
• Pamphlets or other reading materials*
• Internet information*
• Instruction sheets*
• Audio-visual presentations*
• Charts or diagrams*
• Discussions
• Consultation with others

• Provide a quiet, comfortable, and private setting for the informed consent process whenever possible.
• Explain the consent process to the subject.
• Make sure the subject has time to consider all options; allow subject to take the form home before signing (whenever possible).
• Consider the subject's reading abilities. Check to make sure WIRB has not disallowed subjects unable to read. If enrollment of limited or non-readers is allowed, involve an impartial witness in the informed consent process.
• Answer all questions.
• To the extent possible, make sure the subject understands enough information about the research study to give informed consent.
• To the extent possible, make sure the subject can consent free from coercion or other undue influence.
• Since the informed consent process continues throughout the subject's participation in the study, consent should be informally verified on a continuing basis.
• Significant new information must be given to the subject, and continuing consent documented in some way; for example, new risk information is often presented to the subject in an addendum to be signed by subjects who agree to continue to participate.

• Was the subject alert and, in your opinion, able to read and understand the language in the consent form?
• If the subject was unable to read the consent form, and limited or non-readers were allowed to participate, did you have an impartial witness present for the entire process? (An impartial witness is someone with adequate reading ability who is independent of the trial, who cannot be unfairly influenced by people involved in the trial, who attends the informed consent process if the subject or the subject's legally acceptable representative cannot read, who reads the informed consent form and any other written information supplied to the subject, and who is willing to attest to this by signing the consent form.)
• If the subject is not fluent in English, was an approved translation of the consent form provided in the primary language of the subject? Was there also a bilingual translator present to assist with the informed consent process? Note: a translator alone is not considered adequate.
• Was the subject under any pressure (for example, family pressure, lack of medical insurance) to participate in the research? Was this discussed?
• Did the subject take time to carefully read the consent form, or read it along with you?
• Were the risks as set forth in the consent form carefully explained to the subject?
• Are there any other risks or concerns not stated in the consent form and were these explained to the subject?
• Was the subject asked if he or she had any questions about the study?
  • Did the subject have any questions or concerns? If so, what questions or concerns did the subject ask about?
  • Were the subject's questions answered?
  • Was the subject satisfied with the answer(s) they were provided?
• Did the person conducting the consent discussion check for subject understanding by asking some basic questions about the research? Did the responses reflect adequate understanding?
• Did the subject express a clear decision to proceed with the study?
• Was the consent form signed by the person who conducted the informed consent discussion?
• Was the consent form signed by a witness (if required)?
• Was the consent form signed by the Principal Investigator (if required)?
• If a Legally Authorized Representative is allowed to sign for the subject, were additional concerns about the subject's understanding and assent considered and addressed?

• Assent is not required for subjects 6 years and younger
• Verbal assent is required for subjects ages 7 through 14 years using the assent section below and the information sheet for children.
• Verbal assent is required for subjects ages 15 through 17 years using the Assent section below and the information sheet for adolescents (the reference to “17 years old” is modified by the Board when the local age of majority is not 18).
• Adults, assent is required, when the adult is capable, using the assent section in the Consent form.

• The required elements (as defined by the regulations) must be appropriately included.
• The content of the consent form must be understandable to a non-scientist.
• No waiver of rights or other exculpatory wording may be present or appear to be present in the consent form.

• Submit a sponsor template consent form for review (for multicenter studies, the sponsor template has often already been submitted to WIRB and reviewed)
• Submit an investigator-written consent form for review
• Request WIRB write the consent form

• Consent forms should be written in simple, non-technical language for readers of a seventh-grade reading level who may not have taken science courses in school.
• Avoid statements that suggest any waiver of subject rights or release from liability of the investigator or sponsor.
• Avoid use of "I understand" or "you understand" language as this may imply a level of understanding that is not present, and may discourage questions, and write all of the consent form except the consent section in the second person ("you are asked to") rather than first person or third person.
• The consent section should be written in first person ("I consent to…").
• Avoid wording that is, or may seem to be, coercive or overly reassuring to a potential subject.
• Do not make claims of safety or efficacy for investigational articles or procedures.

• Explain the purpose of the research study and the expected duration of subject participation, and include the approximate number of subjects involved in the study.
• Reassure readers that it is appropriate to ask questions, and that they may take the form home for consideration (if appropriate for the given research).
• State clearly that the study is research.
• State the status of the test article based on the country where the research is being conducted; for example, in the U.S., drugs are approved, vaccines are licensed, and devices are cleared or approved for marketing, otherwise they should be designated as "investigational."
• State the purpose(s) of the research; for example, drug protocols usually test for safety and may also test for tolerability and effectiveness.
• State why the person is being asked to participate in the study; for example, "You are being asked to participate in this study because you have been diagnosed with…"

• Describe the visits and procedures (to agree with the protocol), indicating which procedures are experimental.
• Briefly describe the study's design; for example, "This is a dose escalation study. As subjects participating in the study tolerate a specific dose level, the new subjects entering the study will be given a higher dose of the study drug."
• Explain the method used for determining if subjects will receive study drug or placebo, the method for assigning them to a group, and explain the chance of assignment to each group in the study.
• State the number of visits.
• Explain the length of study participation.
• Explain what happens at the visits. It is not necessary to list the procedures visit-by-visit, as detailed descriptions can result in an unnecessarily long consent form.
• Outline any additional participation requirements such as contraception requirements or prohibited activities.

• Describe any reasonably foreseeable risks and discomforts to the subject. Risks and discomforts must be stated in non-technical, lay person's language.
• Provide the risks related to all drugs required by the protocol, including rescue medications, over-the-counter analgesics, and approved control group drugs.
• Include the possibility of allergic reactions and that serious allergic reactions can be life-threatening.
• Describe the risks and discomforts of invasive or unusual procedures, including protocol-required biopsies.
• Describe the risks and discomforts of blood draws, if subjects will have blood drawn.
• Include a statement explaining that there may be risks of participation and side effects which are still unknown.
• Whether known or unknown, explain the risks to women who are pregnant or who become pregnant during the study.
• Include a statement that unknown risks and discomforts are possible; if appropriate, include unknown risks to an embryo or fetus if a subject (or a subject's partner) is or becomes pregnant.
• Where applicable, include the risk that the subject's condition may worsen while they are in the study (whether assigned to active drug or placebo).
• If the study drug will be taken home and there is no child-proof packaging or warning labeling, include a warning to keep it out of reach of children, or others who may not be able to read or understand the label.

• Describe any possible benefits to the subject or others; indicate that benefits are not guaranteed.
• If statements regarding direct benefits of participation are included, they should be qualified as "possible" or that they "may" occur.
• Receipt of procedures and study items may be listed as benefits to the subject, but not in conjunction with their being "free" or at reduced cost, as these statements imply a form of payment and thus should not be categorized as benefits. The FDA Information Sheet "Guidance for Institutional Review Boards and Clinical Investigators" (1998) states, "Payment to research subjects for participation in studies is not considered a benefit, it is a recruitment incentive." Forms of payment may be referenced elsewhere, but not listed as a benefit of participation.

• Describe appropriate alternative treatments or procedures, if available.
• List several alternatives to participation if they exist; alternatives may include alternative drugs or therapy, palliative care, hospice care, etc.
• The consent form may say, "your study doctor will discuss these with you."
• The section on alternatives should include a brief summary of the risks and benefits of the alternatives.

• Describe any known or anticipated costs to the subject.
• State who is responsible for the costs of the study-related items such as medications, procedures, device, visits, hospitalization and treatment for possible side effects.
• Indicate which procedures and items will be provided at no charge
• If insurance will be billed for anything, include information about possible costs to the subject or their insurance. If anything is being billed to insurance, discuss what happens if the insurance does not pay.

• Describe proposed payment for participation, if any, including proration.
• Any money or other incentive of monetary value should be listed in this section rather than the benefit section.
• If subjects are to be paid, state specifically for which visits subjects will receive payment and when such payment will be made; for example, "payment will be made at the end of each study visit," "payment will be made at the end of the last study visit" or "payment will be made within one month after the last study visit." Be as specific as possible to minimize confusion. Consider whether any aspects of the total amount or the proration plan may be coercive or unduly persuasive (WIRB does not routinely allow more than half the total payment to be assigned to the last visit). The Board may require revision of the payment or payment schedule.

• A meaningful description of the PHI, which can be edited for each study.
• A description of each purpose for the use and disclosure.
• Information about the subject's rights related to the authorization.
• Information about the expiration of the authorization. (California, Illinois, Indiana, Washington and Wisconsin state laws require an expiration date).
• Instructions on how to revoke the authorization.
• A statement about what may happen if the authorization is not signed.
• A warning that once information has been released, it may no longer be covered by the Privacy Rule and may be released again without further authorization.

• Outline the plans for compensation and/or medical treatment for research-related injury or illness, including who will be responsible for the costs.
• Explain what will happen if the subject gets injured. Explain how they will get treatment.
• Clearly state who will pay for treatment if the subject is harmed.
• Address what will happen if the subject's insurance is billed for the treatment, but refuses to pay.

• The research is minimal risk research for which compensation for injury language in the consent form is not necessary.
• There is no CTA for the research.
• The research is funded by a government agency (such as NIH) that does not offer compensation for injury.
• Upon receipt of WIRB approval documents, the investigator will check the CTA against the WIRB-approved consent form and resolve any conflicts via a request for a consent form modification to WIRB and/or a modified CTA before enrolling subjects. (The Principal Investigator’s signature is required for submitters who choose this option.)
• Upon receipt of WIRB approval documents, the investigator will check the CTA against the WIRB-approved consent form and resolve any conflicts via a request for a consent form modification to WIRB and/or a modified CTA before enrolling subjects. (The Principal Investigator’s signature is required for submitters who choose this option.)
• The PI’s hospital, university or medical center has a contract with WIRB for IRB services, and it has an established process for ensuring that the compensation for injury language in the CTA and in the consent form do not conflict.
• The PI’s hospital, university or medical center has an established process for ensuring that the compensation for injury language in the CTA and in the consent form do not conflict. (Submitters must provide a description of the process.)
• Sites may also submit plans that differ from any of the plans outlined above.

• Whom subject should contact with research-related questions.
• Whom to call if the subject has a research-related injury or illness (the Board prefers a physician be listed as the contact for injury or illness) or study problems.
• Whom to call if subjects have questions about their rights as research subjects (WIRB and, if desired, a local or institution IRB contact).

• State that the subject's participation is voluntary and that a subject may withdraw at any time for any reason.
• State that the subject's decision not to participate or to withdraw from the research early will involve no penalty or loss of benefits to which the subject is otherwise entitled.
• State that the subject's participation may be ended by the study doctor or sponsor at any time for any reason without the subject's consent. Include any specific reasons cited in the protocol. General reasons may also be included. Please note: the FDA may stop the research, but will not stop the participation of an individual subject.
• Include information on any risks involved with withdrawing early; for example, the need to taper the study drug, obtain follow-up, be placed on standard medication, etc.
• Indicate that subjects who withdraw after the start of the study may be asked to return for a final visit and final study procedures, and must return the study drug.

• Explain that significant new information that may be related to the subject's willingness to remain in the research will be provided to the subject.
• Identify the source of funding for the research.
• Disclose conflicts of interest (financial and otherwise).
• State that the subject will receive a copy of the signed and dated consent form.

• Include a statement of the subject's consent to participate, as well as an authorization to release medical (or research, as appropriate) records to the parties in the HIPAA authorization (or confidentiality) section, if applicable; and a statement that the subject is not giving up any legal rights by signing the consent form.
• Include a statement that the subject has read the information in the consent form or had it read to her/him (as appropriate); however, don't include statements which imply a level of comprehension, such as "I understand…"
• Include a statement that the subject's questions have been answered.

• Include appropriate signature and date lines for assent/consent as applicable
• If appropriate, include a signature block for an impartial witness (if the protocol does not exlude limited or non-readers from participation).
• Use the term "subject," rather than "patient" (except the term "participant" may be used in some behavioral research).
• Provide a space for the "Legally Authorized Representative" (LAR) to consent (if allowed by the protocol) and a place to indicate the LAR's relationship to the subject.
• Include a space for the person conducting the informed consent discussion to sign (required by ICH).
• Provide a line for the investigator to sign if desired by researcher or sponsor; however, this is not a WIRB requirement.
• Where applicable, provide a space to obtain the consent of a caregiver. Please note that the signature of the caregiver does not replace the signature of an LAR when required.

• Decrease sentence length.
• Limit each sentence to one thought or topic. Avoid run-on sentences.
• Use simpler words (select words with fewer syllables).
• Use common words. Remove technical jargon and medical terms.
• In discussing risks, use the symptoms the subject might experience rather than just the medical terms for the problem.
• Use short, simple paragraphs.
• Use correct basic grammar and form.

When evaluating a proposed word or phrase, consider whether a reader with no college education, no science background, and little or no exposure to the medical professions would easily understand it. Most words or concepts can be explained in simple language; however, the reader can be directed to ask the study doctor for an explanation of a complex item.

When drafting a consent form, frequently ask "Does the reader need this information in order to make an informed decision?" Avoid including excess technical information that would only confuse or intimidate a reader.
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v. Special Considerations for Subjects Who Do Not Speak English

All consent forms and other subject materials must be in a language easily understood by the subject, and all translations must be approved by WIRB. WIRB provides translations services for WIRB-approved sites only.

If a non-English speaking subject may receive benefit from study participation, and that benefit is not available outside of the study, under very restricted circumstances WIRB may allow an ad hoc translation of the consent form if time or financial restraints affect the subject’s safety. Please request WIRB review of these situations.

• WIRB-Arranged Translations:

Translations requested on WIRB’s Initial Review Submission Form are sent to a qualified translator after the English materials are finalized and mailed to the site. This timeline ensures the materials sent for translation are the final version.

If a research study is approved without a translated consent form and a non-English speaking subject later qualifies for enrollment, the site can obtain a translated version of the consent form for use in consenting the subject by submitting a request to the WIRB Translations Department. The request should identify the Sponsor, Sponsor Protocol Number, Investigator and the language requested. The subject cannot be enrolled until they have received the WIRB-approved translated consent. If WIRB is asked to provide a price quote for the translation, the translation process will not begin until WIRB receives authorization to proceed.

WIRB bills an administrative fee for translation services in addition to the translator’s fee. The bill is sent to the party requesting the translation or their designee (WIRB requires written confirmation that the designee will accept the invoice). Sites who subsequently request the translation are billed only the administrative fee, unless their consent form includes site-specific changes that require additional translation.

WIRB suggests that before sites request a translation, they check with their sponsor to determine if the sponsor already has made a translation or arrangements for translation, and if not, if the sponsor is willing to pay for a WIRB translation.

• Sponsor/CRO/Site Translations:

The WIRB-approved version of the consent form or other materials may be translated and submitted to the Board along with a Certification statement signed by the translator that identifies the specific translated documents and attests to the translator’s fluency and the accuracy of the translation from English to the target language (see sample format below). The Board requests that all translations be performed by a certified translator. The translation must correspond to the WIRB approved version of the material; therefore, a translation of the sponsor template consent form or materials is not acceptable.

If the translation is acceptable, the approval date will be affixed by WIRB staff and an approved copy sent to the site.

Other documents (e.g., subject diaries, subject instructions) need to be legible (faxed copies often are not legible) and accompanied by a translator certification statement.

Sample Certification Statement:

CERTIFICATION

I hereby certify that I am fluent in English and (name of language) and that I have, to the best of my knowledge and belief, made a true and complete translation from English to [name of language] of the WIRB® approved [name of document; e.g., Research Subject Information and Consent Form, Advertisement] for [sponsor / protocol number], [WIRB® protocol number] this ___________ day of ___________, [month, / year].

 

________________________________________
(Signature of Translator)

Name of Certification (ATA, DSHS, other)____________
Certificate No.______________________________

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vi. Special considerations for gene transfer (gene therapy) consent forms

Because the area of gene transfer (experiments involving the deliberate transfer of recombinant DNA, or DNA or RNA derived from recombinant DNA, into human research participants) is relatively new, special efforts must be made to avoid perpetuating a "therapeutic misconception" about gene transfer research. The following is based on Appendix M (NIH Guidelines for Research Involving Recombinant DNA Molecules, April 2002).

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Word Choice in Gene Transfer Consent Forms:

Use the term gene transfer instead of gene therapy. Replacing the term "therapy" with "transfer" helps diminish any implication of effectiveness.

Use agent instead of drug or medicine to refer to the investigational gene transfer product.

Try to avoid the use of the terms "treatment," "therapy" or "therapeutic" (because these words may imply effectiveness). The following are some suggested techniques for avoiding extensive use of the term "treatment":

• Substitute the word "dosing" or "group" for "treatment"
• Substitute the name of the agent for the word "treatment"

Address the increased possibility of loss of confidentiality because of media and public focus on the research.

Example: Research studies involving gene transfer have received a great deal of attention from the media. Although every effort will be made to protect your identity and that of your family, this attention may result in a greater risk than usual that information concerning your study participation will appear publicly without your consent.

• Inform subjects that an autopsy will be requested if the subject dies.
  
  Example: In the event of your death, an autopsy will be requested. This would be done to provide additional information about the research. Your family, and your "legally authorized representatives" have the right to refuse the autopsy even if you sign this consent form.

Consider the special characteristics of the gene and vector involved and discuss common and/or unknown risks:

• Where will the agent end up in the body?
• How long will the agent be in the body?
• Can it be transmitted to others (horizontal transmission to those in contact with the subject, or vertical transmission, to offspring via egg or sperm)?
• Is there a risk of leukemia (with retroviral type gene transfer vectors) or other types of cancers or conditions (for example with angiogenesis-type agents)?
• Are there special precautions which must be taken because of these risks?