Manual for Conducting Human Subject Research

Informed Consent Requirements (Updated 02/06/2008)

7.1 The Process of Informed Consent and its Exceptions.

Informed consent is an ongoing process during which information is presented to an individual to enable them to voluntarily decide whether or not to participate in or continue participation in a research study. Informed consent for research involves presenting the research information (the categories of which are required by the federal regulations) orally obtaining written consent on an HRRC approved consent form prior to entering a subject into a study and documenting the consent process in the subjects’ medical record or research file.

The HRRCs may waive the requirement for both obtaining informed consent (Sections 7.5.4 and 7.5.5) and for documenting consent (Section 7.5.3) under certain circumstances. However, unless an investigator has obtained approval for other than the standard, written informed consent from the HRRC, the investigator may not alter the method by obtaining consent in any other way, including over the telephone. FDA does not recognize "telephone consent," with a consent form signed after entry of the subject, as legally sufficient informed consent. (FDA does permit emergency treatment without informed consent, Section 9.2, but the patient may not be included in any report of prospectively conceived research activity.)

Investigators should keep in mind that informed consent is an ongoing process. Thus, where an investigator obtains new information that may impact the subject’s continued willingness to participate in the research (e.g., new information about the drug, adverse events, and alternative new treatments), this information should be provided to the subjects, after review and approval by the HRRC. Investigator should also refer to the “HSC Clinical Research Working Guidelines on Obtaining and Documenting Consent” located on the HRRC web site.

7.2 Presentation

In presenting research information and obtaining informed consent, investigators should consider:

  1. The consent form document does not replace the verbal presentation provided where the participant has the opportunity to ask questions
  2. The potential subject’s physical and mental state when choosing an appropriate time to present the research information.
  3. The consenting process should occur over a period of time (which may include days or weeks) to allow time for the individual to consider whether to participate and to discuss the research with his/her family.
  4. It is best to present the research information separately from standard clinical or hospital information, and emphasize the difference between the conduct of the research and regular patient care. A copy of the consent form should be provided to the participant to take home.
  5. The Principal Investigator and a member of the study team are to be available to answer any questions or concerns the participant may have during the decision process.
  6. If a treatment study, a family member or person involved in the care of the participant should be encouraged to participate in the consenting process.
  7. Where particularly complex issues are discussed, an investigator might consider testing the subjects understanding of the information by asking questions about the presentation.
  8. The Investigator and/or research staff conducting the consent process should ask the subject if they have been given adequate time to make a decision and if the consent is written in a language they can understand.
  9. The investigator and/or research staff must minimize the possibility of coercion or undue influence, while providing information about the research and during the consenting process.

    Once the participant has agreed to participate, the subject reads the consent form (or it is read to him or her) then signs and dates it. The research member involved in the consent process and present at time of signature must also sign and date the consent form.

    Any new information that may impact the subject’s continued willingness to participate in the research will require the information be presented to the participant and often requires the participant to sign a revised consent form. This can only occur after HRRC approval of new information.

  10. The HRRC may choose to have representatives observe the informed consent process in response to concerns about study risks, the conduct of the study, about alleged non-compliance or as part of the Clinical Research Quality Improvement Monitoring Program.

7.3 Content Requirements for Consent Forms

Consent forms must be understandable by potential subjects. Understanding is facilitated by translating technical language into lay language at about a fifth grade level. There are programs available that will assist in translating technical consent form information into lay language. In addition, glossaries are available from a number of web sites and publications. Please contact the HRRC Support Office for more information.

The regulatory requirements are discussed below, but are set forth in a simple to follow and Sample Consent Form . Following this sample will ensure that all consent forms (including those generated by sponsors) address the required elements for informed consent.

  1. Purpose of Study - 45 C.F.R. 46.116(a)(1); 21 C.F.R. 50.25(a)(1) - This section requires a clear and accurate statement that the study is research, and an explanation regarding the purposes of the research. To allow subjects to make an informed decision whether to participate, this section should clearly explain if a study is a pilot study or a phase I drug study, informing the subject that he or she will be the first to participate in the treatment, intervention, or process. This section also explains the approximate number of subjects for drug and device studies. This section also identifies any drugs/devices/or procedures that are experimental. If the research involves a drug or device being studied under an IND or IDE, the consent document should identify the item as being investigational.
  2. Procedures - 45 C.F.R. 46.116(a)(1); 21 C.F.R. 50.25(a)(1) - This section fully describes procedures that will be used, preferably in order of their occurrence, identifying all experimental procedures, and the approximate duration for each procedure or activity. For instance, a survey study may explain that the subject will be asked to answer x number of questions about topic, which should take about x minutes to complete. Each type of study’s procedures are described, e.g., a genetic testing study would describe whether samples will be linked, who will have access to information and codes, whether samples may be used for a secondary research use and/or commercial development, and if so, whether subjects will be re-contacted, among other things. This section also addresses the expected duration of the subject’s participation.
  3. Potential Risks or Discomforts Potential Risks or Discomforts - 45 C.F.R. 46.116(a)(2); 21 C.F.R. 50.25(a)(2) - In this section, the investigator must clearly explain any risks or discomforts which are reasonably foreseeable. The investigator should explain, in lay language, the statistical probability of risk occurrence, risk prevention measures, reversibility, and treatment, as known. In behavioral research, investigators should consider such risks as stress, embarrassment, breach of confidentiality, etc. Thus, a study that may elicit sensitive information, or information that may stigmatize a subject or a group, could present significant risks. In fact, genetic research, particularly where disease information that may be elicited is not already known, would generally not be considered to be minimal risk, even if the only physical procedure involved was a blood draw. If the research involves investigational drugs or devices, or if the research involves procedures where the risk profile is not well known, then the consent document should disclose that the particular treatment or procedure may involve risks to the subject that are currently unforeseeable. If the research involves procedures where the effects on the embryo or fetus are not well known and the research includes women of child bearing potential, then the consent document should disclose that if the subject became pregnant, that the particular treatment or procedure may involve risks to the embryo or fetus that are currently unforeseeable, and any required pregnancy prevention measures should be discussed.  There may also be known risks to a fetus or embryo should pregnancy occur; if this is the case, state the potential risks.  (The consent document should also disclose any unknown or possible risk if a male study participant were to impregnate a female partner, and any required pregnancy prevention measures.  For details on contacting a partner who becomes pregnant by a research subject to follow the outcome of the pregnancy and delivery of the infant, see section 11.5 Research Involving Partners or Family Members of Study Participants.
  4. Anticipated Benefits Anticipated Benefits - 45 C.F.R. 46.116(a)(3); 21 C.F.R. 50.25(a)(3) - A subject or society, or both, may benefit from research. If there are any direct benefits to the subject reasonably expected from the research, the consent form must state them. Direct benefit may be possible treatment of an illness or knowledge of value to the subjects (e.g., the results of a physical examination, an educational test, etc.). The potential benefits should not be overstated or guaranteed.
    For example:
    "Based on the experience with this drug in [patients with a similar disorder, animals, etc.] Researchers believe the drug may be of benefit to subjects with your condition [or as good as current standard therapy with less side effects]. But, people respond differently to therapy, so no one can know in advance whether this will be helpful to you in your case"
    If there are no benefits to the participant that are expected, this section must state so.
    This section should also explain the potential benefits to society, for example, the advancement of knowledge, improved safety, or the potential health benefits to others. All research should have some potential benefit for society; if it is not intended to provide any useful information, it should not be conducted. An example of a statement regarding expected benefits where no benefit to the subject is expected is as follows:
    "You should not expect to benefit directly from this research. However, your participation in this research may lead to information that could help individuals who are suffering from x disease if it identifies a new and better way to treat such people."
    Note: Payment for participation is not a benefit of the research and must not be listed as a benefit.
  5. Alternatives to Participation Alternatives to Participation - 45 C.F.R. 46.116(a)(4); 21 C.F.R. 50.25(a)(4) - In this section, the investigator must state any available alternative procedures or course of treatment that might be advantageous to the subject. Alternatives might be no treatment at all, or watchful waiting. When appropriate, the relative risks and benefits of the therapeutic intervention compared to the research should be stated. Where a medical protocol is not therapeutic, the form should explain that because the research is not therapeutic, the only alternative is not to participate in the research.
  6. Confidentiality of Records - 45 C.F.R. 46.116(a)(5); 21 C.F.R. 50.25(a)(5) - This section must explain the extent to which information obtained in connection with the research and that could identify the subject will remain confidential and will not be disclosed without the subject’s permission. Consent forms should generally refrain from broadly stating that records will be kept confidential, because a number of agencies or people may have access to the records. For example, the sponsor will have access to the information. In the case of FDA regulated research (research that involves any food, including dietary supplements, that bear a nutrient content claim or a health claim, infant formulas, food and color additive, drug for human use, medical device for human use, biological product for human use, or electronic products, or research whose data may be submitted to the FDA or held for inspection by the FDA), the consent document should disclose specifically that the FDA might inspect the records. In addition, the HRRCs, OHRP, or even other physicians and nurses, where emergency care must be given to a subject, may have access to the information. Also, the investigator or others may use the records to publish articles. While the subject will not be identified, the information in the records will be used, so the information is not kept strictly confidential. Further, research records may be subpoenaed in a court of law (where a research study involves sensitive topics, researchers should consider applying for a Certificate of Confidentiality (Section 6.1.3)). Thus, these and other limits on confidentiality, including the State of New Mexico requirement for reporting of suspected child abuse or neglect (Section 32A-4-3 NMSA 1978), adult abuse or neglect (Section 27-7-1 et seq. NMSA 1978), resident abuse and neglect (Section 30-27-1 et seq. NMSA 1978), reportable communicable and infectious diseases including HIV/AIDS, sexually transmitted diseases and tuberculosis and nontuberculous mycobacterial infections must be clearly explained in the consent form, as applicable. Likewise, the consent form must include (when applicable) such reportable events as certain wounds, health conditions related to environmental exposures and certain occupational injuries, adverse vaccine reactions, cancer, and birth defects. For example:
    "Participation in research will involve a loss of privacy, but information about you will be handled as confidentially as possible. Representatives of ABC Company [funding agency], the University of New Mexico Health Sciences Human Research Review Committee that oversees human research and the Food and Drug Administration [where applicable] will be permitted access to your records. Further, because this study involves questions regarding child abuse, you should be aware that New Mexico law requires anyone learning of suspected abuse or neglect to report it to authorities. Also, your participation in the study and information in your study records may be disclosed to your doctors and nurses, and may be disclosed as otherwise provided by law. Your name will not be used in any published reports about this study."
    Note: Where a research study involves sensitive topics, researchers should consider applying for a Certificate of Confidentiality (Section 6.1.3). (These certificates should not be used to attempt to avoid reporting of suspected abuse or neglect, however.)
  7. Payment for Participation - This section should describe (how much and when) any payments to be made to subjects. It is appropriate for reimbursement to cover the costs of parking fees, travel, lost time from work, child care, etc. However, the nature, amount and method of payment or other compensation must not constitute undue inducement to subjects participating in the research. For this reason, payments should not be unnecessarily large and should be prorated, in accordance with FDA guidelines, so as not to coerce a subject into completing a study from which he or she wishes to withdraw.
  8. Financial Obligation Financial Obligation - This section should state all financial obligations the subject may incur as a result of participation in the research study, including any hospital charges, laboratory or pharmacy fees, etc. It should indicate whether the study drug or device is being provided free of charge. Subjects should be told whether they and/or their insurance company will be billed for any of their treatment. They should also be told that most health plans, insurance companies, and HMOs do not do not cover experimental treatments, and whether they will be responsible for those costs. For VAMC research, disclose that a veteran-participant will not be required to pay for care, except for applicable copayments for medical care and services not rendered as part of the VA-approved study.
  9. Emergency Care and Compensation for Injury - 45 C.F.R. 46.116(a)(6); 21 C.F.R. 50.25(a)(6) - For studies that are greater than minimal risk, subjects must be told whether any compensation and/or medical treatment is available if injury should occur as a result of the research; the extent and nature of the compensation should be explained. Please do not include this if your research is only minimal risk (e.g. non-sensitive survey research).
    The following language is required for studies conducted at the UNMHSC:
    "If you are injured as a result of this study, the University of New Mexico Health Sciences Center will provide you with emergency treatment at usual charge. No commitment is made by the UNMHSC to provide free medical care or money for injuries to participants in this study. [Use with drug/device sponsor: The Sponsor of the study may cover the costs of required medical care due to use of the study drug in some cases.] If you have any questions about these issues, or believe that you have been treated carelessly in the study, please contact the Human Research Review Committee at the University of New Mexico Health Sciences Center, Albuquerque, New Mexico 87131, (505) 272-1129 for more information."
    Sponsors will frequently agree to pay for injuries or adverse events arising out of research studies. Investigators should be familiar with the terms of the agreement so that they can discuss this with the prospective subject, and include the proper information in the consent form as appropriate.  For VA research, disclosure that in the event of research-related injury the VA has to provide necessary medical treatment to a participant injury by participation and that all regulations pertaining to the participation of veterans as participants, including requirements for indemnification in case of research-related injury, apply to non-veteran participants enrolled in VA-approved research.
  10. Contact Information - 45 C.F.R. 46.116(a)(7); 21 C.F.R. 50.25(a)(7) - Investigators are required to provide names and numbers of persons to contact if the subject has questions regarding the research during working hours, and the name of the principal investigator and number to call for after hours emergencies or research-related injuries.
    In addition, questions regarding a subject’s legal rights, and research related injuries, should be directed to UNMHSC Human Research Review Committee at (505) 272-1129.
  11. Participation and Withdrawal - 45 C.F.R. 46.116(a)(8); 21 C.F.R. 50.25(a)(7) - This section must indicate that participation is voluntary, refusal to participate will involve no penalty or loss of benefits to which the subject is otherwise entitled, and that the subject may discontinue participation at any time without penalty or loss of benefits to which the subject is otherwise entitled. Whenever there are potential medical or health consequences of a subject’s decision to withdraw this should be disclosed in the consent document (Example: If a subject chose to stop taking an experimental antihypertensive drug, he/she might be at an increased risk for a “cardiovascular event” if another medication isn’t taken in it’s place). In addition, where applicable, the consent form should also state any anticipated circumstances under which the subject’s participation may be terminated without regard to the subject’s wishes, for example, for adverse reactions, if the investigator feels that it is in the best interest of the subject, if the sponsor decides to stop the study, or for the subject’s non-adherence to protocol instructions. Further, if a subject will need to continue in some form of treatment due to entry into the study that should be explained to the subject as well. Lastly, this section should describe the procedures for subjects’ orderly termination if they decide to withdraw or are withdrawn by the sponsor/investigator.
    An example of a statement follows:
    "Your participation in this research is strictly voluntary. You have the right to choose not to participate or to withdraw your participation at any point in this study without prejudice to your future health care or other services to which you are otherwise entitled. [where appropriate: "Although you are free to decide to stop participating in the research at any time, because you are entering into a study of x, you will need follow-up treatment consisting of x.] [where appropriate: "The investigator may decide to withdraw you from this research activity without your consent if he feels that your continued participation places you at too much risk (describe)."]  "The sponsor may also withdraw your participation or stop the study at anytime."
  12. New Findings - 45 C.F.R. 46.116(b)(5); 21 C.F.R. 50.25(b)(4) - Federal regulations require that if new information--such as a change in the risk/benefit ratio, new alternatives to participating to the research, or new and significant adverse events--develops during the course of the study, the subject will be informed so that he or she may consider whether to continue to participate in the study. In this section, the investigator should inform the subject of this.
    "You will be informed of any significant new findings that become available during the course of the study, such as changes in the risks or benefits resulting from participation in the research or new alternatives to participation that might change your mind about participating."
    Should new information develop, the investigator should bring it, and the revised consent form, to the HRRC for review and approval.
  13. Disclosure of Possible Benefits to Investigator- Any possible financial benefits that might accrue to the investigator should be disclosed in the consent form. For instance, the California Supreme Court held that where an investigator was involved in commercialization activities regarding a subject’s tissue, it was a breach of fiduciary duty and lack of informed consent to fail to inform the subject of this prior to entering him into the research. See Moore v. Regents of University of California, 271 Cal. Rptr. 146 (Cal. 1990).
  14. Closing Paragraph -
    SIGNATURE OF RESEARCH SUBJECT OR LEGAL REPRESENTATIVE
    Required Statement:

    "You will be given a copy of this consent form to keep. By signing this consent form, you are not waiving any of your legal rights, claims, or remedies. If you have questions about your legal rights as a research subject, you may call the UNMHSC Human Research Review Committee at 272-1129.”

    “You have read (or someone has read to you) the information in this consent form. You have had an opportunity to ask questions and all questions have been answered to your satisfaction. By signing this consent form, you willingly agree to participate in this study.”

    1. Name of Subject
    2. Name of Legal Representative (this line should be omitted unless the IRB has approved the inclusion of adults unable to consent as subjects)
    3. Name of Parent or Guardian (this line should be omitted unless the IRB has approved the inclusion of children as subjects)
    4. Signature and date of Subject (or Legal Representative *The Legal Representative should be omitted unless the IRB has approved the inclusion of adults unable to consent as subjects)
    5. Signature and date of Parent or Guardian Date (same as subject’s assent)
    6. Signature and date of Investigator or Team Member
    7. For VA research, name, signature and date of witness whose role is to witness the subject's (or legal representative's) signature.

    Note: If the HRRC or sponsor requires a witness to the consenting process in addition to the witness to the participants signature, a note to that effect must be placed under the witness's signature line.

    "I have explained the research to the subject or his/her legal representative [and to his or her parent or guardian, where applicable], and answered all of his/her questions. I believe that he/she understands the information described in this document and freely consents to participate."
    Name of Investigator [or member of team]
    Signature of Investigator and Date (same as subject’s)

    A copy of the signed and dated consent document should be given to the person signing the consent document.

7.4 Who May Provide Informed Consent?

7.4.1 Adults and Emancipated Minors

In New Mexico, adults and emancipated minors are considered legally competent to make healthcare decisions, including to provide informed consent for participation in human research.

  1. In New Mexico, an “emancipated minor” means a person under the age of 18
    1. who is or ever has been married even if the marriage was annulled;
    2. is currently on active duty in military service of the United States of America; or
    3. is age 16 or 17 and has been emancipated by Court Order and the Order does not exclude the emancipated minor’s authority to make health care decisions for himself or herself.
  2. A minor emancipated pursuant to New Mexico law does not meet the definition of “Children” as defined in federal regulations governing human research at 45 C.F.R. 46.402(a), unless a court-ordered emancipation prohibits the emancipated minor from making health care decisions for himself or herself. In every case, once an emancipated minor attains the age of 18, the individual is an adult.
  3. An emancipated minor is authorized to consent to his or her own medical treatment, and by parallel application, to research.
  4. A minor is not emancipated by pregnancy, living apart from their parent or legal guardian even if living with another adult or living with another person in a marriage-like relationship. Thus, such a minor cannot consent to health care treatment or associated research unless the treatment falls within one of the limited exceptions under New Mexico law.

7.4.2 Assessing a Subject’s Capacity to Consent and use of a Legally Authorized Representative (LAR)

The OHRP Guidebook provides guidance on the issue of consent for cognitively impaired individuals or people with psychiatric disorders. Such individuals may or may not be able to provide legal informed consent. "The general rule is that all adults, regardless of diagnosis, should be presumed competent to consent unless there is evidence of serious mental disability that would impair reasoning or judgment.... There should be specific evidence of an individual’s incapacity to understand and to make a choice before they are deemed unable to consent."

Adults and emancipated minors who lack competence or decisional capacity:

  1. Adults or emancipated minors, who are determined by a court to lack competence, or by two health care providers to lack decisional capacity for health care decisions, are entitled to have health care decisions made for them by a legally authorized representative (“LAR”). However, research involving persons who lack competence or decisional capacity should be limited to research involving minimal risk or the research-associated treatment should be expected to provide some benefit to the impaired person.
  2. In New Mexico, a LAR is a person’s agent for health care decisions appointed when they were competent or had decisional capacity in a document such as a durable power of attorney or orally stated to the person’s health care provider who makes notation of such a direction in the person’s records, by a court-ordered guardian with powers to make health care decisions, or by a health care decision- maker, referred to as a “surrogate” in the law, according to the priority classes in descending order of priority as set forth in the New Mexico Uniform Healthcare Decisions Act, Section 24-7A-5, NMSA 1978 (2000). The agent, guardian or surrogate decision-maker as defined in the Uniform Healthcare Decisions Act meets federal regulations for legally authorized representative.  Researchers are encouraged to contact legal counsel for guidance on other state's laws regarding the "legally authorized representatives." The statutory classes for surrogate decision-makers, in descending order of priority, are :
    1. the spouse, unless legally separated or unless there is a pending petition for annulment, divorce, dissolution of marriage or legal separation;
    2. an individual in a long-term relationship of indefinite duration with the patient in which the individual has demonstrated an actual commitment to the subject similar to the commitment of a spouse and in which the individual and the subject consider themselves to be responsible for each other’s well-being;
    3. an adult child;
    4. a parent;
    5. an adult brother or sister; or
    6. a grandparent; or if none of the above are available, then
    7. an adult who has exhibited special care and concern for the patient, who is familiar with the patient’s personal values and who is reasonably available so long as this person is not an owner, operator or employee of a health-care institution at which the subject is receiving medical care unless the subject is related to this adult by blood, marriage or adoption.
  3. When treatment with psychotropic medications is required for an adult or emancipated minor who lacks decisional capacity or competence, informed consent must be obtained from the individual’s court-appointed mental health treatment guardian, Mental Health Code, NMSA 1978 Sections 43-1-1, et seq. (1977, as amended through 1999), or the court-appointed a legal guardian authorized with such powers.
  4. An adult’s lack of “competence” is almost always a permanent, progressive condition. On the other hand, lack of decisional capacity is often a temporary condition due to reversible medical conditions. However, if it appears that a person’s lack of decisional capacity is permanent and or progressive, it is advisable for a plenary guardian to be appointed under the New Mexico’s Uniform Probate Code, NMSA 1978 § 45-5-301 through 45-5-315 (as amended through 2003), in order to make decisions on behalf of the person in all areas of life or as may be limited by the court-issued letters of guardianship. If the person’s family lacks resources to file a petition for guardianship or the provider believes there is no family member available or appropriate to serve as a guardian for the person, then the Adult Protective Services Division of the Children, Youth & Families Department should be contacted.
  5. When human research is conducted at a VAMC facility, a patient who lacks decisional capacity or competence may be enrolled as a subject in research when informed consent is provided by the subjects legally authorized representative. “Legally authorized representative” means an individual or body authorized under applicable law to provide permission on behalf of a prospective subject to the subject’s participation in the procedure(s) involved in the research. For the purposes of this Handbook, a legally authorized representative includes not only a person appointed as a health care agent under a Durable Power of Attorney for Health Care (DPAHC), a court appointed guardian of the person, but also a next-of-kin in the following order of priority unless otherwise specified by applicable state law: spouse, adult child (18 years of age or older), parent, adult sibling (18 years of age or older), grandparent, or adult grandchild (18 years of age or older.)

7.4.3 Differences and similarities between the LAR as defined by VA human research subject regulations and New Mexico law.

  1. An LAR as defined under the VHA Handbook 12000.5, HA Handbook 12000.5, Requirements for the Protection of Human Subjects in Research, and an LAR pursuant to the New Mexico Uniform Healthcare Decisions Act are consistent with each other, with one significant and several insignificant differences. The most significant differences between the New Mexico law and the regulations governing research at a VA facility is that the VA regulations do not include “an individual in a long-term relationship” with the subject among the priority classes and that there is not a provision for an emancipated minor to be treated as an adult for health care decisions. Thus, the VA requirements do not allow decisions to be made on behalf of a vulnerable adult by another co-habiting adult who is not legally married to the patient. (Individuals who are married at common law according to the laws of a particular state in which they resided at the time they declared themselves married are considered legally married in New Mexico.) With regard to an “emancipated minor,” however, the VA regulations would recognize a spouse of any age to make decisions for a patient lacking decisional capacity or competence. Also, although the VA regulations include an adult grandchild among the priority classes and New Mexico law does not, this difference is insignificant in effect. An adult grandchild would be included as a LAR if no other member of a higher priority class is reasonably available, an adult grandchild would have priority over a non-related member of class (g).
  2. The New Mexico Uniform Healthcare Decisions Act also provides that health care decisions may be made by an agent appointed by the adult or emancipated minor when the patient had capacity or competence or by a court-appointed guardian whose powers include health care decision-making. The document is ordinarily referred to as a durable power of attorney. Agency through a durable power of attorney for health care decisions is also recognized by the VA regulations.
  3. In all cases except where the individual has a court-appointed guardian with health care decision-making powers, the individual must have been determined to lack decisional capacity. Under New Mexico law, the subject may object to the determination that he or she lacks decisional capacity and to the proposed surrogate decision-maker. If the subject objects, the law provides that the district court has jurisdiction to make health care decisions or to appoint a health care decision-maker over the objections of the individual.

7.4.4 Children

"Children" are defined as "persons who have not attained the legal age for consent to treatments or procedures involved in the research, under the applicable law of the jurisdiction in which the research will be conducted." 45 C.F.R. 46.202(a). See section 6.2.1 regarding circumstances when a “minor” is not considered a “child” for research purposes.

Children may not be enrolled in research without the "permission" (agreement under standard consent provisions, Section 7.3) of a parent or guardian (and of both parents for research of greater than minimal risk, with no prospect of direct benefit to individual subjects, see Section 6.2.1). The HRRCs are often asked who qualifies to provide consent for a child. As noted, the federal regulations require that the person be either the parent or the guardian. A "guardian" is a person "who is authorized under applicable State or local law to consent on behalf of a child to general medical care." 45 C.F.R. 46. 402(e). Under New Mexico law, a person appointed through the court system as a child’s legal guardian may consent to inclusion of the child in research. To enroll the child, guardianship papers should be presented. There may be other legal mechanisms of granting permission to a person other than the parent to consent to health care that may suffice as well (such as a health care power of attorney). Where there is any question whether a particular person is permitted under the law to consent to the inclusion of the child, the investigator should contact the Office of the University Counsel for the HSC.

In addition to parental/guardian permission, investigators are required to obtain the "assent" of the child. Assent is "a child’s affirmative agreement to participate in research. Mere failure to object should not, absent affirmative agreement, be construed as assent." 45 C.F.R. Section 46.402(b). The HRRCs generally require assent to be obtained from all children age 7 and older, unless the nature of the research dictates otherwise (for example, research on brain injured children). The investigator should use a separate simple assent form (in language appropriate for a child).

7.5 Modification (including Waivers) of Informed Consent

7.5.1 No Deviation from Written Informed Consent in Research without HRRC Approval

The general rule is that to involve a subject in research, the investigator must obtain documentation of informed consent, as provided in Section 7.3. In some cases, however, the HRRC's are permitted to waive the requirement that a consent form be signed. In those instances, the consent is obtained orally. In other situations, the HRRCs may waive particular elements of informed consent or waive the requirement for informed consent entirely. Unless these modifications are approved by the HRRC in writing, they may not be used.

7.5.2 Short Form Informed Consent

Federal regulations recognize a "short form" of the documentation of informed consent. 45 C.F.R. 46.117(b)(2); 21 C.F.R. 50.27(b)(2). The short form process does not alter any of the elements of informed consent required to be given to a subject. Rather, it merely allows the elements to be provided to the subject orally, along with a written summary. The "consent form" states only that consent information has been provided (rather than detailing in writing all of the information). Specifically, the short form process consists of 1) a written summary of what will be presented to the subject; 2) a written "short form" which states that the elements of Section 7.3 have been presented; and 3) an oral explanation of the summary information in front of a witness, who must be conversant in both English and the language of the subject. Both the summary and the short form must be approved by the HRRC and signed by the witness. The person obtaining consent (i.e. the investigator) must sign and date the summary only. The subject (or legally authorized representative) signs and dates only the short form consent. Copies of the written summary of the information, and of the short form documenting the consent are given to the subject or the subject's legally authorized representative. Note that the Albuquerque VA Medical Center does not allow use of the short form consent.  If non-English speakers are being enrolled in VA research, informed consent documents must be translated into the language of the participant and be approved by the HRRC prior to use.

7.5.3 Waiver of Documentation of Informed Consent:

There are two (2) situations either of which may lead the HRRCs to agree that a consent form need not be signed, although informed consent must still be obtained orally: 1) where the only record linking the subject and the research would be the consent form and the principal risk of harm from the research is a potential breach of confidentiality (such as with sensitive survey or interview research). In this case, the subject is asked whether he/she wants the documentation linking the subject with the research and his/her wishes govern; or 2) where the research presents no more than minimal risk* and involves no procedures for which written consent is normally required outside of the research context. 45 C.F.R. 46.117(c); 21 C.F.R. 56.109(c).

*Minimal risk means that the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examination or tests. Investigators should be aware that genetic research would not generally be considered to be "minimal risk" research in that social, psychological, and economic risks are also considered.

Under this consent modification, even though a consent form isn’t signed and retained, informed consent still must be obtained orally (all the elements of Section 7.3). The HRRC may also require that the investigator provide a written explanation of the study (which the HRRC approves) to the subject.

7.5.4 Waiver or Alteration of Elements of Informed Consent for Minimal Risk Studies

The HRRCs may waive the requirement for informed consent entirely (writing and oral presentation), or waive some of the required elements of informed consent (Section 7.3), if it finds the following criteria are met:

  1. The research involves no more than minimal risk to subjects; the waiver will not adversely affect the rights or welfare of the subjects; the research could not practicably be carried out without the waiver or alteration; and whenever appropriate, subjects will be provided with additional pertinent information after participation (45 C.F.R. 46.116(d)); or
  2. The research or demonstration project is conducted by or subject to the approval of state or local government officials and is designed to study, evaluate, or otherwise examine a) programs under the Social Security Act, or other public benefit or service programs; b) procedures for obtaining benefits or services under those programs; c) possible changes in or alternative to those programs or procedures; or d) possible changes in methods or levels of payment for benefits or services under those programs; and e) the research could not practicably be carried out without the waiver or alteration (45 C.F.R. 46.116(c)).

NOTE: Investigators occasionally suggest that research on biological samples, or using medical record information, automatically qualifies for a waiver of informed consent, citing the lack of physically risky procedures. However, such research does not qualify for an automatic waiver for a number of reasons. First, where any samples or data to be used will be collected prospectively (i.e., after the proposal to the HRRC, even if it will be collected for non-research reasons), it is not likely that the third requirement of paragraph 1, above--which requires that the research not be able to be practicably carried out without the waiver--will be met. The principle of respect for persons requires consent to be obtained where at all feasible. Second, even in retrospective research (where the samples/data already exist), the research may not be "minimal risk" for social, psychological, or other reasons. Risks related to disclosure of information (such as from genetic research) must be considered. Some such research may have significant effects on the subject’s psychological well-being, insurability, etc. In addition, even in retrospective research, the waiver may not be necessary to permit the research to be practicably carried out. That it may be inconvenient for investigators to obtain consent, alone, does not meet this requirement.

NOTE: Studies involving FDA regulated products are not eligible for waiver of informed consent under these provisions. Thus, the use of biological samples for research involving in vitro diagnostic products, for example, are not eligible for consideration of a waiver of informed consent.

7.5.5 FDA/OHRP Waiver of Informed Consent for Research on Emergency Therapies

Both FDA and OHRP permit the HRRCs to approve a research project designed to test new emergency therapies which--due to the critical condition of the patient and the need to administer the therapies within a short amount of time--may necessitate enrolling the subject in the research before a legally authorized representative is available to provide informed consent. 21 C.F.R. 50.24 (FDA); 61 Fed. Reg. 51531 (Oct. 2, 1996) (HHS). These federal waivers, however, require that this type of research be conducted in accordance with state law, as well as meet strict requirements. New Mexico law does not specifically address the propriety of enrolling subjects into research studies without informed consent. Typically, treating patients without obtaining consent may result in a claim of battery or lack of informed consent. However, because there is no New Mexico law that prohibits the conduct of this research, and the research is only permitted where there is no acceptable alternative treatment and the research holds out the prospect of direct benefit to the subject, we believe that these studies may be conducted at the UNMHSC, provided that all of the protections of the federal regulations are strictly followed. An HRRC approval of a project under this waiver will permit investigators to enroll subjects who are unable to provide consent into their studies. Among other protections, this regulation/waiver uses a "community consultation" process to obtain the views of the community from which the likely subjects will be drawn, as well as the community in which the research will be conducted, prior to the initiation of research (discussed below). There are strict criteria that must be met for the HRRCs to approve such projects. These criteria are summarized below. If an investigator is interested in pursuing this type of research project, it is recommended that he or she contact the HRRC Support Office for more information before submitting an application.

To approve an acute care informed consent waiver project, an HRRC must find and document (specifically noting the concurrence of a physician unrelated to the study) the following:

  1. The administration involves a life-threatening situation; the available treatment is unproven or unsatisfactory; and collecting of valid scientific evidence (which may include randomized placebo-controlled investigations) is necessary to determine safety and effectiveness;
  2. Obtaining consent from the subject or his or her legally authorized representative is not feasible because:
    • Subject’s medical condition is such that he or she cannot consent;
    • Intervention must be administered before it is feasible to obtain consent from the legally authorized representative; and
    • There is no reasonable way to identify prospectively subjects likely to become eligible for participation in the research;
  3. Participation in the research holds out prospect of direct benefit to subject:
    • Life threatening situation necessitates the intervention;
    • Animal and preclinical studies support the potential direct benefit of intervention for individuals;
    • Risks of the investigation are reasonable in relationship to:
      • What is known about the medical condition;
      • Risks and benefits of standard therapy; and
      • Risks and benefits of proposed intervention
  4. The investigation could not practicably be carried out without the waiver (research would be "practicable" without the waiver of recruitment if consenting subjects only would not bias the science and the research would not be unduly delayed by restricting it to consenting subjects);
  5. The investigator:
    • Has defined the length of the therapeutic window based on scientific evidence;
    • Is committed to attempting to contact and obtain consent from the legally authorized representative within the window rather than proceeding without consent;
    • Will summarize efforts to contact the authorized representative at the time of continuing review;
    • Is committed to contacting within the window the subject’s family member and asking if he or she objects (if obtaining consent from the subject or legally authorized representative is not possible); and
    • Will summarize efforts to contact the family member at the time of IRB continuing review;
  6. The HRRC has:
    • Approved the informed consent procedures and documents to be used with the subject or the legally authorized representative; and
    • Approved procedures and information to be used when providing family members the opportunity to object;
  7. There has been acceptable community consultation. Community consultation (including consultation by the HRRC, as appropriate) must occur with the communities from which the subjects will be drawn and in which the research will be conducted before HRRC approval. The purpose of this consultation is to give these communities the opportunity to understand the proposed clinical investigation and its risks and benefits, and to discuss and raise objections to the investigation. The HRRCs must consider this community discussion when reviewing the investigation, and may decide, among other things, that it is appropriate to exclude certain groups from participation, or that wider community consultation is necessary. The HRRCs may consider:
    • Having public meetings in the community to discuss the protocol (some institutions have used church meetings, club meetings, and special meetings, among other things);
    • Establishing a separate panel of members of the community from which the subjects will be drawn;
    • Including consultants to the HRRC from the community from which the subjects will be drawn (this alone would not be sufficient however); and
    • Developing other mechanisms to ensure community involvement and input in the HRRC’s decision making process (such as using the media, professional surveyors, etc.).

    The HRRCs are responsible for listening to and considering the community’s support, concerns, etc., and then ultimately deciding whether the investigation should be modified, approved, or disapproved. Thus, the community consultation will take place before the HRRC can approve the project. While a sponsor may provide the HRRCs information on community consultation, the HRRCs bear the responsibility for ensuring the adequacy of the community consultation requirements. In addition, the HRRCs have the responsibility for deciding what information should be disclosed to the community (information on risks/benefits, relevant information from the investigational brochure, information on informed consent and on the protocol);

  8. There has been public disclosure to the communities prior to initiation of the study including plans for the study, and risks and benefits (may be a multimedia approach, e.g., advertisements, news programs, etc., as well as meetings). FDA states that the type of disclosure will depend upon the size and diversity of the community, and the cohesiveness of those in the community from which the study subjects are likely to be drawn. However, simply placing an advertisement in the paper is not sufficient. Public disclosure need not take place before the HRRC approves the project but must take place before the study begins;
  9. There are adequate plans for public disclosure to the community (as well as other researchers) at the completion of the study, including demographics of the study and results of the study;
  10. An independent data monitoring committee has been established (generally by the sponsor, comprised of individuals not otherwise connected with the study);
  11. Procedures are in place to inform at the earliest opportunity each subject (if competent), legally authorized representative, and/or family member of:
    • The subject’s inclusion in the study;
    • Details of the study and other information in the informed consent document;
    • The opportunity to discontinue subject’s participation;
  12. That FDA (for drugs and devices, including marketed products) has reviewed and approved the proposed waiver project under a separate IND or IDE; and
  13. If the research is not subject to FDA regulation, that the HRRC has documented this and notified OHRP that it has approved a waiver of informed consent.

If the HRRC approves a requested waiver, it must provide the sponsor with a copy of the information that has been publicly disclosed prior to initiation and at completion of the study. Sponsors must provide this information to FDA.

The IRB, investigator, and the sponsor must retain records for three (3) years after the clinical investigation is completed and make the records accessible to FDA.

If the HRRC does not approve a requested waiver, it must document its findings, including its reasons for disapproval and provide this promptly to the clinical investigator and the sponsor. Sponsors are required to report a disapproval to FDA and to other clinical investigators involved in and IRBs reviewing a substantially equivalent (or the same) investigation.

NOTE: The waiver is not applicable for VA research and research involving prisoners, fetuses, pregnant women, and human in vitro fertilization, pursuant to HHS requirements.

7.5.6 Waiver of Parental Permission Requirement for Studies Involving Children

In addition to the general provisions permitting waiver in Section 7.5.4, investigators may apply for (and the HRRCs may grant) a waiver of the requirement for parental permission if the research protocol is designed for conditions or for a subject population for which parental or guardian permission is not a reasonable requirement to protect the subjects (for example, neglected or abused children), provided that an appropriate mechanism for protecting the children who will participate as subjects is substituted, and that the waiver is not otherwise inconsistent with federal or state law. 45 C.F.R. 46.408(c). The choice of an appropriate mechanism would depend upon the nature and purpose of the activities described in the protocol, the risk and anticipated benefit to the research subjects, and their age, maturity, status, and condition. In its recommendations that resulted in the regulations, the National Commission for the Protection of Human Subjects Biomedical and Behavioral Research provided two examples of what it thought would be appropriate mechanisms, noting in some instances the consent of a mature minor should be sufficient and in others court approval may be necessary.

NOTE: This waiver does not apply to FDA regulated research.