Investigator Handbook
Chapter 6: RESEARCH SUBJECTS

Guidelines to Recruitment of Research Subjects

Recruitment and selection of subjects must be equitable within the confines of the study.  The investigator may not arbitrarily exclude participants on the basis of gender, race, national origin, religion, creed, education, or socioeconomic status.

Inclusion of Women and Minorities in Clinical Research
Cultural diversity in subject selection is strongly encouraged. Clinical studies should be inclusionary, designed in such a way that the subject pool is representative in gender, race, ethnicity, and age of the local population affected by the condition being studied. Exclusion of particular subgroups may be justified in the following cases:

1. A specific scientific question is more appropriately addressed with a more targeted group,
   
2. Specific known risks of intervention (or other participation) warrant exclusion of specific groups,
   
3. Gender- or racial-neutrality has been previously demonstrated,
   
4. Redress of gaps in medical knowledge about specific groups,
   
5. Multicenter studies may achieve overall balance by choosing centers with complementary minority representation.

Subject enrollment need not be sufficient to provide high statistical power for calculating effects of gender and minority status on intervention effect in all cases. Investigators planning phase 3 clinical trials in which prior studies suggest a clinically “significant difference” in effect among subgroups or those in which differential effects are uncertain are encouraged to design the subject pool in sufficient numbers so as to provide a “valid analysis” in each subgroup.

Economically Disadvantaged Subjects
Investigators should consider added costs related to the research that might prevent participation by the economically disadvantaged. Justification for such cost must be fully explained in the IRB application.

Financial remuneration, reward, reimbursement for expenses, or other inducement for participation should not be so great as to be coercive to potential participants and should constitute reasonable compensation for the inconvenience of participating.

Subject Recruitment
Clinical studies should be advertised to and made accessible to an equitable group of individuals. In cases in which recruitment and/or retention of women or minority subjects may be difficult, a proactive program may be employed. Cultural sensitivity in approaching potential subjects is to be encouraged (e.g., respectful of language and custom). Barriers to participation in underrepresented groups should be anticipated and overcome prospectively (e.g., compensation for child care, lost wages or transportation; waiving of residency requirements; translation of advertising or educational literature and informed consent for non-English speakers). The extent of compensation will be reviewed critically by CPHS to ensure that it is appropriate to the context of the study and not potentially coercive to vulnerable subgroups. In order to ensure a diverse study population with sufficient statistical power to examine major gender and ethnic effects, large studies may consider the use of quota systems to manage enrollment.

To overcome lingering distrust of the medical and scientific establishment in minority populations, outreach programs may be used to inform local minority groups about the individual and collective benefits of participation in biomedical research. Follow-up in these groups with modest advertising of individual projects and discussion of results may be employed.

Recruitment Scripts
Prospective participants often have their first contact with a research coordinator or third party who follows a script to determine basic eligibility for the specific study. The IRB must review these procedures to assure that they adequately protect the rights and welfare of the prospective participants. The IRB must have assurance that any information collected about prospective participants will be appropriately handled. An investigator may contact potential subjects by telephone only if the investigator has ethically permissible access to the potential subject. If not, a recruitment letter stating that the investigator may call should be sent to the potential subjects. Repeated attempts to contact a research subject may be necessary and appropriate. However, once a subject is contacted, a single informed refusal to participate concludes the investigator's efforts. If an investigator plans to make repeated attempts to contact a subject, the subsequent methods should be described in the original protocol or in a request for change

Internet Recruitment
All advertisements and recruitment methods must be reviewed and approved by the IRB prior to implementation to assure that the information does not promise or imply a certainty of benefit beyond what is contained in the protocol and the informed consent document.

Students and UT Employees as Subjects
It is acceptable to enroll students in the UT Health Science Center at Houston, provided that:

• The students are not working in the same laboratory as the PI;
  
• The students do not report directly to the PI;
  
• The students are not in a class over which the PI has direct responsibility;
  
• Students, Staff, or Technicians enrolled in the study do not work in a laboratory that is in the sphere of influence of the PI;
  
• Recruitment does not involve coercion or undue influence.

Dear Patient Letters
The investigator may ask physician colleagues to send out general “Dear Patient” letters describing the study. The investigator may draft the letter with the treating physician’s signature, but may not have access to the patient names or the mailing addresses. If the investigator wants the letters to be individualized for the patients, the personalized information would have to be entered by the treating physician. Dear Patient letters should be submitted to CPHS for review and approval.

Dear Doctor Letters
The investigator may send a letter to colleagues (“Dear Doctor letter”) asking for referrals of potential or eligible subjects who are interested in the study. Communications directed to colleagues do not require IRB approval, but this method of recruitment should be stated in the protocol.

External Groups
If the investigator is planning to use a business, listserv, school, advocacy groups, etc. to recruit subjects, the IRB will need to see a letter from that organization giving the investigator permission to recruit.

Other methods may be acceptable. Please contact the IRB office (cphs@uth.tmc.edu) for assistance if a method is questionable or you are unsure if it will be appropriate.

Advertisements

Advertising and Recruitment Are Part of the Informed Consent Process!
Direct recruiting advertisements are viewed as part of the informed consent and subject selection process. When direct advertising is to be used, the IRB reviews the information contained in the advertisement and the mode of its communication to determine that the procedure for recruiting participants is not coercive and does not state or imply a certainty of favorable outcome or other benefits beyond what is outlined in the consent document and the protocol. This is especially critical when a study may involve participants who are likely to be vulnerable to undue influence.

The IRB must approve the final copy of all advertisements to include flyers that will be posted on bulletin boards or used as handouts, and broadcast on radio, television or through other venues (e.g., mass email).

Advertisements to recruit subjects should be limited to the information the prospective subjects need to determine their eligibility and interest. The following information should be included:

• That volunteers are being recruited for research,
  
• The name and address of the institution conducting the research,
  
• The purpose of the research,
  
• In summary form, the criteria that will be used to determine eligibility for the study,
  
• A brief list of participation benefits, if any (e.g. a no cost health examination),
  
• The time or other commitment required of the subjects,
  
• The location of the research and the person or office to contact for further information

The advertisement should not, either explicitly or implicitly:

• State or imply a certainty of favorable outcome or other benefits beyond what is outlined in the consent document and protocol,
  
• Make claims that the drug, device or biologic is safe or effective for the purposes under investigation,
  
• Make claims that the test article is known to be equivalent or superior to any other drug, biologic or device,
  
• Use terms such as “new treatment," "new medication" or "new drug" without explaining that the test article is investigational,
  
• Promise "free medical treatment," when the intent is only to say subjects will not be charged for taking part in the investigation. Advertisements may state that subjects will be paid, but should not emphasize the payment by such means as larger or bold type. Advertisements should not state the amount that will paid, or
  
• Include compensation for participation in the form of a coupon good for a discount on the purchase price of the product once the product is approved for marketing.
  
• Include any exculpatory language.
  

Advertisements to be Taped for Broadcast
When advertisements are to be taped for broadcast, the IRB must review the final audio/video tape. The IRB must review and approve the wording of the advertisement prior to taping to preclude re-taping because of inappropriate content. The review of a taped message prepared from IRB approved text may be accomplished through expedited review procedures.

New Advertisements Introduced After IRB Approval
If an investigator decides to begin advertising for participants after the study has received IRB approval, the advertising will be considered as an amendment to the ongoing study. When such advertisements easily reflect the consent form, the Committee Chairperson can choose to review and approve the advertisement using expedited procedures. When the comparison is not obvious or other complicating issues are involved, the advertisement may necessitate full Committee review.

Finders Fees

Accepting or paying a "finder's fee" for the referral of patients or subjects into a research study is NOT allowed under Texas law and as such may not be a practice of any UTH employee. Under § 102.001 of the Texas Occupations Code, a state employee is guilty of a third degree felony offense if they pay or accept ANY remuneration for soliciting a patient. Anyone else who violates this section of the Texas Occupations Code may face a civil penalty of up to $10,000 per violation.

This does not mean that patients cannot be referred into an appropriate study. However, you may not offer to pay or agree to accept any payment for such referrals. This includes overt and covert payment as well as payment in kind such as bartered goods or services.

If you are approached with such payments or if there is a question as to whether something constitutes an incentive or bonus payment, please contact the CPHS office at 713-500-3985.

Payments to Subjects

Payments to research subjects for participation in studies is not considered a benefit, nor should it appear to induce a subject to enroll. The amount and schedule of all payments should be described in the IRB application at the time of initial review, including a summary of both the amount of payment and the proposed method and timing of disbursement to assure that neither are coercive or present undue influence. Procedures for prorating payment should the subject withdraw should also be considered when submitting the IRB application and informed consent documents.

Timing of Payments
Credit for payment should accrue as the study progresses and not be contingent upon the participant completing the entire study. Unless it creates undue inconvenience or a coercive practice, payments to subjects who withdraw from the study may be paid at the time the study would have been completed had they not withdrawn. For example, in a study lasting only a few days, it may be permissible to allow a single payment date at the end of the study, even to subjects who withdraw before completion.

Completion Bonus
While the entire payment should not be contingent upon completion of the entire study, payment of a small proportion as an incentive for completion is acceptable, providing that such incentive is not coercive.

Disclosure of Payments
All information concerning payments, including the amount and schedule of payment(s), should be set forth in the informed consent document.

Advertisement of Payments
Advertisements may state that subjects will be paid, but should not emphasize the payment or the amount to be paid, by such means as larger or bold type.

Alterations in Payments
Any alterations in subject payments or liberalization of the payment schedule must be reported to the IRB prior to implementation as an amendment.

Reporting of Payments
The Internal Revenue Service (the IRS) requires that UT Health Science Center at Houston (or whomever is paying the subjects for their participation) report payments in excess of $600 per calendar year on Form 1099-Misc. The filing of these forms necessitate that the name and social security number of the subject be collected on a Form W-9 and released to the Office of Accounting to process the Form 1099-Misc. The collection and release of this information must be addressed thoroughly in the informed consent document so that it is clear to the participant that his or her identity will be released for the purpose of payment and reporting.

Vulnerable Populations

As addressed in the Belmont Report, human subjects must be accorded respect as autonomous beings. However, it also states that there are several categories of persons that have diminished autonomy and must be treated with a more elevated level of protection and a more widely defined relationship between risk and benefit. If a human subject has diminished capacity for understanding a consent or if they are in a disadvantaged situation and are therefore, easily manipulated, then the protection from risks is a greater priority. Each case must be treated differently according to its disadvantage. Some special categories of vulnerable populations include children, pregnant women, neonates, fetuses, and prisoners. These are not the only vulnerable populations. Others include cognitively impaired individuals, the elderly, students, employees; any population possibly vulnerable to coercion or undue influence.

Children

There are four classifications of research involving children based on the degree of risk and the benefit to individual participants. For any protocols involving children, PIs should submit the Pediatric Risk Assessment Form in iRIS to indicate the level of risk in their studies. These categories are briefly described below.

Minimal Risk: 

• This protocol does not involve risk (physical or emotional) greater than that ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests. 
• Only one parent need give consent.

Greater than minimal risk and direct benefit: 

• This protocol does involve greater than minimal risk but also presents the prospect of direct benefit to the individual subject.
• Only one parent need give consent.

Greater than minimal risk and no reasonable prospect of direct benefit: 

• This protocol does involve greater than minimal risk and no reasonable prospect of direct benefit to the individual subject but is likely to yield generalizable knowledge about the subject’s disorder or condition.
• Both parents or legally appointed guardians must give consent unless one parent or guardian is deceased, unknown, incompetent, not reasonably available, or does not have legal responsibility for the custody of the minor.

Research not otherwise approvable: 

• This research is not otherwise approvable but presents an opportunity to understand, prevent, or alleviate serious problems affecting the health or welfare of children. 
• Requires approval by the Secretary of Health and Human Services
• Requires consent of both parents or guardians.

Parental Permission

The investigator will always be required to obtain parental permission documents and may not approach the child for assent until written permission has been given. Permission of one parent is sufficient if the research involves minimal risk; permission of both parents is necessary if the research involves more than minimal risk. However, if one parent is deceased, unknown, incompetent or reasonably unavailable, or if one parent has legal responsibility or custody of the child, one parent permission is acceptable.

1. The CPHS must determine for each protocol whether the permission of both parents is necessary, and the conditions under which one parent may be considered “not reasonably available”.
2. Parental permission may sometimes be insufficient to protect the child’s interests particularly when the interests of one child conflict with those of a sibling or other relation. In such cases, CPHS may seek legal guidance to clarify authority.

Children Who are Wards of the State
Children who are wards of the state, an agency, institution, or entity can be included in approved research only if it is either related to their status as wards or the research is conducted in schools, camps, hospitals, institutions, or similar settings in which the majority of children involved as participants are not wards. In this way, if the research is not related to the experience and environment of a ward, their status is made equal with the other non-ward participants.

However, if the research is approved under 45 CFR §46.409(a) the CPHS must require appointment of an advocate for each child who is a ward.
The advocate will serve in addition to any other individual acting on behalf of the child as guardian or in the place of a parent.

• One individual may serve as advocate for more than one child.
  
• The advocate must be an individual who has the background and experience to act in, and agrees to act in, the best interest of the child during the child’s participation in the research.
  
• Aside from their duties as an advocate or member of the CPHS, the advocate must not be associated in any way with the research, the investigator, or the guardian organization.
  

Obtaining Assent from a Child

The difference between assent and consent is a child assents without the complete understanding of the purposes of the research and consent happens when there is a complete understanding of risks, benefits, purposes of the research, and their rights as human research subjects.

The investigator must make their best effort to ask the child for permission in order to determine if he/she assents. In determining this, the investigator takes into account the child’s age, maturity, and psychological state. This judgment may be made for all children involved in research under a particular research protocol, or for each child. The child should be given an explanation of the research procedures in a language that is appropriate to the child’s age, experience, maturity, and condition. This includes a discussion of any discomforts or inconveniences, or if the child will be required to spend time in an unfamiliar place.

For some research activities, the CPHS may require that either a CPHS member, research intermediary or an advocate for the child be present during the assent and permission procedures to verify the child’s understanding and to support the child’s preference. The CPHS may also require that the parents or a close family member be present during the research, especially if a young child will be exposed to significant discomfort or inconvenience, or if the child will be required to spend time in an unfamiliar place.

Waiver of Assent
Generally, the child’s veto of participation is sufficient to make the child ineligible for inclusion in the study. However, the parent or guardian, with CPHS and physician approval, may override the veto if the intervention will benefit the child. The CPHS may determine that the assent of the child is not necessary:

• When the research offers the child the possibility of a direct benefit that is important to the health or well-being of the child and is available only in the context of the research; or
  
• When research involves the provision of experimental therapies for life-threatening diseases such as cancer.

CPHS should be sensitive to the fact that parents may wish to try anything, even when the likelihood of success is marginal and the probability of extreme discomfort is high. Should the child not wish to undertake such experimental therapy, difficult decisions may have to be made. In general, if the child is a mature adolescent and death is imminent, the child’s wishes should be respected.

Compensation
The presence of parents or guardians as authorities over children complicates considerations of reimbursement and compensation. Should children be compensated for time commitment when they would not be compensated for their time in daily life? Can compensation to parents for time commitment cloud their judgment in giving permission to participate? (See Reimbursement and Compensation)

Some investigators wish for compensation to be useful to the children who participate. Gift certificates or small tokens of appreciation may be offered to children at the close of the study, while reimbursement to the parent who must provide transportation, meals, lost time from work etc, also may be so given. These reimbursements may be mentioned during the consent process with the parents.

Points to consider:

• Efforts to make up for the discomforts of children participating in research by the offer of a reward may be coercive. Such efforts may pose an opportunity to reconsider the risks and benefits of the study as well as to consider whether the decision to participate is clouded by the prospect of a reward.
  
• Above all, there should be a balance in the favor of the subject as to benefit or compensation. The child should receive a “thank you gift” while the parent should, if possible, be reimbursed for travel and parking expenses as well as for time off from work.
  
• See Reimbursement and Compensation for guidelines.

School-Based Research
Research conducted with school students holds special concerns as it relates to coordination with school districts and schools as well as obtaining informed permission from parents. Early in the planning for the research project, investigators must establish contact and potential collaboration within the school district from which potential subjects will be drawn. Procedural requirements vary between school districts as to parental permission and children's assent.

In general, obtaining active informed permission of parents will be expected of investigators. However, certain circumstances may lead a school district to prefer alternative means of permission and assent (for example, the provision of a document containing a description that the child will participate in the study unless the parent expresses a choice for the child not to participate is preferred by some districts). It follows that such a procedure can only be possible for certain kinds of research such as surveys, research in which no identifiers are recorded; and research that does not involve questions of sensitive nature.

Prospectively obtained informed parental permission and assent are required for research involving:
Interventions with children;
Review of academic, behavioral or school-clinic medical records;
Surveys with questions of a sensitive nature (i.e. sexual behavior, illicit substance use, criminal behavior or family relationships).

Points to consider:
Assent in a school setting should be done in a way so that children not willing to participate in a study will not be identified or embarrassed by their decision. Research personnel, not the schoolteacher, should explain the study and invite study participation.

Other Suggestions for Researchers:
Present the families with a list of questions that should have been covered during the consent/assent process. The family should read over the list before they sign onto the study to make sure that they understand the study and what is being asked of them (include outline of standard care versus experimental care). The principal investigator may petition the CPHS if some aspect as outlined above cannot be met.

Texas Law on Consent to Treatment of Children
A child may consent to medical, dental, psychological, and surgical treatment for the child by a licensed physician or dentist under certain limited conditions that include if the child:

• Is on active duty with the armed services of the United States of America;
  
• Is legally married;
  
• Is 16 years of age or older and resides separate and apart from the child’s parents, managing conservator, or guardian and manages his/her own financial affairs regardless of the source of funds;
  
• Consents to diagnosis/treatment of infectious, contagious, or communicable disease that is required by law or a rule to be reported by the licensed physician or dentist to a local health officer or Texas Department of Health;
  
• Is unmarried and pregnant and consents to hospital, medical, or surgical treatment, other than abortion, related to the pregnancy;
  
• Consents to examination and treatment for drug or chemical use; or
  
• Is unmarried, is the parent of a child, and has actual custody of his or her child and consents to medical, dental, psychological, or surgical treatment for the child.

Informed Consent by Persons Under the Age of 18

The concept of independent informed consent can only be applied in situations for which the law recognizes the decision-making rights attributed in adulthood. Emancipation into adulthood before age 18 is only afforded by a court of law and occurs when the adolescent is a resident of Texas and the following are in place:

• Age of 17, and fully self-supporting financially; OR
  
• Age of 16, living away from parent’s home and fully self-supporting financially
  Independent informed consent by persons under age 18 for purposes of healthcare is recognized by state law for teenagers who are:
• pregnant where consent to treatment is related to the pregnancy but not abortion,
  
• parents consenting to treatment for their child but not for themselves, or
• seeking healthcare for sexually transmitted disease, mental health or substance abuse.

Because children could avoid or delay healthcare for these conditions if parental permission was required, the state has offered means for obtaining care in the face of individual and community health risk. In the absence of specific law relating to health care research, the CPHS recognizes decision-making authority for research in these conditions and follows the state's health care criteria in its guidelines for research:

Pregnancy and Teen Parents
Texas state law recognizes the independent decision-making authority for informed consent by children who are pregnant or who are parents themselves. In these cases, an adolescent may make decisions about her own prenatal healthcare and the care of her child. Because the law is silent on independent informed consent to research, the CPHS limits the approach of those under the age of 18 for inclusion into research to:

• Pregnant adolescents making decisions about research within the context of their own prenatal care; or
  
• Adolescent parents making decisions about research participation for their child(ren);
  AND
  
• the clinical trial is considered a part of community standard for prenatal care. (AIDS or cancer trials, for example, which may include experimental medication as part of the plan of care); or
  
• the research aims to answer psychosocial questions related to adolescent prenatal health; or
  
• are decisions by an adolescent as the parent giving permission for a child to participate in any research for which the child is qualified.

Sexually-Transmitted Disease
Texas state law recognizes the independent decision-making authority for informed consent by children who seek routine examinations for sexual health and/or treatment for a sexually transmitted disease.

Again, because the law is silent on independent informed consent to research, the CPHS limits the approach of adolescents to participate in research to:

• Adolescents seeking examination and/or treatment for sexually transmitted disease; and
  
• Psychosocial research, which is related to sexual health; or
  
• The clinical trial is considered a part of community standard of care.

Mental Health and Substance Abuse
Mental health and substance abuse services may also be sought independently by adolescents. The law is silent on whether adolescents may give informed consent to research similar to informed consent for treatment.

The CPHS thus limits independent informed consent to:

• adolescents seeking examination and/or treatment related to mental health or substance abuse; and
  
• psychosocial research which is directly related to mental health or substance abuse; OR if
  
• the clinical trial is considered a part of community standard of care.

Points to consider:

• Be certain to forewarn parents that research findings concerning their teenage adolescents will be shared with them only with permission from the adolescent in question.
  
• Is there sufficient privacy provided for discussion between the researchers and adolescents?

Pregnant Women, Neonates or Human Fetuses

Research involving women who are or who may become pregnant should receive special attention from investigators because of a woman’s additional health concerns during pregnancy and because of the need to avoid unnecessary risk to the fetus. Further, in the case of a pregnant woman, the investigator must consider when the informed consent of the father is required. Procedural protections beyond the basic requirements for protecting human research subjects are prescribed in the Federal regulations for research involving pregnant women.

Pregnant women or fetuses may be involved in research if all of the following conditions are met:

1. Where scientifically appropriate, preclinical studies, including studies on pregnant animals, and clinical studies, including studies on non-pregnant women, have been conducted and provide data for assessing potential risk to pregnant women and fetuses; and
   
2. The risk to the fetus is caused solely by interventions or procedures that hold out the prospect of direct benefit for the woman or the fetus; or if there is no such prospect of benefit, the risk to the fetus is not greater than minimal and the purpose of the research is the development of important biomedical knowledge which cannot be obtained by any other means; and
   
3. Any risk is the least possible for achieving the objectives of the research; and
   
4. If the research holds out the prospect of direct benefit to the pregnant woman, the prospect of a direct benefit both to the pregnant woman and the fetus, or no prospect of benefit for the woman nor the fetus when risk to the fetus is not greater than minimal and the purpose of the research is the development of important biomedical knowledge that cannot be obtained by any other means, her consent is obtained in accord with the informed consent provisions according to regulations; and
   
5. If the research holds out the prospect of direct benefit solely to the fetus then the consent of the pregnant woman and the father is obtained in accord with regulations, except that the father’s consent need not be obtained if he is unable to consent because of the unavailability, incompetence, or temporary incapacity or the pregnancy resulted from rape or incest; and
   
6. Each individual providing consent under paragraph (D) or (E) of this section is fully informed regarding the reasonably foreseeable impact of the research on the fetus or neonate; and
   
7. For children who are pregnant, assent and permission are obtained according to regulations found in the section above; and
   
8. No inducements, monetary or otherwise, will be offered to terminate a pregnancy; and
   
9. Individuals engaged in the research will have no part in any decisions as to the timing, method, or procedures used to terminate a pregnancy; and
   
10. Individuals engaged in the research will have no part in determining the viability of the neonate.
    

Research Involving Neonates

Research involving neonates is allowable if all of the following conditions are met:

1. Where scientifically appropriate, preclinical and clinical studies have been conducted and provide data for assessing potential risks to neonates; and
   
2. Each individual providing consent is fully informed regarding the reasonably foreseeable impact of the research on the neonate; and
   
3. Individuals engaged in the research will have no part in determining the viability of a neonate; and
   
4. The following requirements of the paragraphs below have been met as applicable:

Neonates of uncertain viability
Until it has been ascertained whether or not a neonate is viable, a neonate may not be involved in research covered by this section unless the following additional conditions have been met and the CPHS determines that:

1. The research holds out the prospect of enhancing the probability of survival of the neonate to the point of viability, and any risk is the least possible for achieving that objective, or
   
2. The purpose of the research is the development of important biomedical knowledge which cannot be obtained by other means and there will be no added risk to the neonate resulting from the research.

The legally effective informed consent of either parent of the neonate or, if neither parent is able to consent because of unavailability, incompetence, or temporary incapacity, the legally effective informed consent of either parent’s legally authorized representative is obtained in accord with subpart A of 45 CFR §46, except that the consent of the father or his legally authorized representative need not be obtained if the pregnancy resulted from rape or incest.

Nonviable neonates
After delivery nonviable neonates may not be involved in research unless all of the following additional conditions are met:

1. Vital functions of the neonate will not be artificially maintained; and
   
2. The research will not terminate the heartbeat or respiration of the neonate; and
   
3. There will be no added risk to the neonate resulting from the research; and
   
4. The purpose of the research is the development of important biomedical knowledge that cannot be obtained by other means; and
   • the legally effective informed consent of both parents of the neonate is obtained in accord with subpart A of 45 CFR §46, except that the waiver and alteration provisions of 46.116(c) and (d) do not apply.
   • However, if either parent is unable to consent because of unavailability, incompetence, or temporary incapacity, the informed consent of one parent of a nonviable neonate will suffice to meet the requirements of this paragraph 45 CFR §46.205(c)(5) except that the consent of the father need not be obtained if the pregnancy resulted from rape or incest.
   • The consent of a legally authorized representative of either or both of the parents of a nonviable neonate will not suffice to meet the requirements of this paragraph 45 CFR §46.205(c)(5).

Viable neonates
A neonate after delivery, that has been determined to be viable may be included in research only to the extent permitted by and in accord with the requirements of subparts A and D of 45 CFR §46. [45 CFR §46.205(d)]

After the Delivery: Using Placenta or Deceased Fetus

Research involving, after delivery, the placenta; the dead fetus; macerated fetal material; or cells, tissue, or organs excised from a dead fetus, shall be conducted only in accord with any applicable Federal, State, or local laws and regulations regarding such activities.

If information associated with material described above is recorded for research purposes in a manner that living individuals can be identified, directly or through identifiers linked to those individuals, those individuals are research subjects and all pertinent parts are applicable.

When your Research Does Not meet the Above Noted CPHS Requirements

If the CPHS does not believe the research protocol meets the requirements detailed in 45 CFR §46.204 or 45 CFR §46.205, the Secretary of the DHHS will conduct or fund the research only if:

A. The CPHS finds that the research presents a reasonable opportunity to further the understanding, prevention, or alleviation of a serious problem affecting the health or welfare of pregnant women, fetuses or neonates.

B. The Secretary of DHHS, after consultation with a panel of experts in pertinent disciplines (for example: science, medicine, ethics, law) and following opportunity for public review and comment, including a public meeting announced in the Federal Register, has determined either:

1. That the research in fact satisfies the conditions of 45 CFR §46.204 as applicable; OR
   
2. The following:
   a. The research presents a reasonable opportunity to further the understanding, prevention, or alleviation of a serious problem affecting the health or welfare of pregnant women, fetuses or neonates.
   b. The research will be conducted in accord with sound ethical principles.
   c. Informed consent will be obtained in accord with the informed consent provisions of subpart A and other applicable subparts of this section.

Definitions
Dead fetus - A fetus that exhibits neither heartbeat, spontaneous respiratory activity, spontaneous movement of voluntary muscles, nor pulsation of the umbilical cord.
Delivery - Complete separation of the fetus from the woman by expulsion or extraction or any other means.
Fetus - Product of conception from implantation until delivery
Neonate - A newborn
Nonviable neonate - Neonate after delivery that, although living, is not viable
Pregnancy - Encompasses the period of time from implantation until delivery. A woman shall be assumed to be pregnant if of reproductive potential and exhibiting any signs of pregnancy, such as missed menses, until the results of a pregnancy test are negative or until delivery
Viable - As it pertains to the neonate, means being able, after delivery, to survive (given the benefit of available medical therapy) to the point of independently maintaining heartbeat and respiration. The Secretary of Health and Human services, may from time to time, taking into account medical advances, publish in the Federal Register guidelines to assist in determining whether a neonate is viable for purposes of this subpart. If a neonate is viable, then it may be included in research only to the extent permitted and in accordance with the requirements of subparts A and D of this part.

Research Involving Prisoners

The special vulnerability of prisoners makes consideration of involving them as research subjects particularly important. Prisoners may be under constraints which because of their incarceration could affect their ability to make a truly voluntary and not coerced decision whether to participate in research. To safeguard their interests and to protect them from harm, special ethical and regulatory considerations apply for reviewing research involving prisoners. For this reason, any research that includes prisoners cannot be exempt from review by the CPHS.

The definition of “minimal risk” was used in the Informed Consent chapter of this Handbook, however, this definition has another version when applied to prisoners only. 

Criteria when Enrolling Prisoners in Research

Research involving prisoners will be approved only if the following conditions are met:

1. If the research represents
   
   • A study of the possible causes, effects, and processes of incarceration, and of criminal behavior, provided that the study presents no more than minimal risk and no more than inconvenience to the subjects; or
   • A study of prisons as institutional structures or of prisoners as incarcerated persons, provided that the study presents no more than minimal risk and no more than inconvenience to the subjects; or
   • Research on conditions particularly affecting prisoners as a class (for example, vaccine trials and other research on hepatitis which is much more prevalent in prisons than elsewhere; and research on social and psychological problems such as alcoholism, drug addiction, and sexual assaults); or
   • Research on practices, both innovative and accepted, which have the intent and reasonable probability or improving the health or well-being of the subject.
   
   
2. Any possible advantages accruing to the prisoner through his or her participation in the research, when compared to the general living conditions, medical care, quality of food, amenities and opportunity for earnings in the prison, are not of such a magnitude that his or her ability to weigh the risks of the research against the value of such advantages in the limited choice environment of the prison is impaired.
   
   
3. The risks involved in the research are commensurate with risks that would be accepted by non-prisoner volunteers.
   
   
4. Procedures for the selection of subjects within the prison are fair to all prisoners and immune from arbitrary intervention by prison authorities or prisoners. * Unless the principal investigator provides to the CPHS justification in writing for following some other procedures, control subjects must be selected randomly from the group of available prisoners who meet the characteristics needed for that particular research project.
   
   
5. The information is presented in language which is understandable to the subject population.
   
   
6. Adequate assurance exists that parole boards will not take into account a prisoner’s participation in the research in making decisions regarding parole, and each prisoner is clearly informed in advance that participation in the research will have no effect on his or her parole.
   
   
7. Where the CPHS finds there may be a need for follow-up examination or care of participants after the end of their participation, adequate provision has been made for such examination or care, taking into account the varying lengths of individual prisoners’ sentences, and for informing participants of this fact.
   
   
8. The PI must provide documentation of approval from the detention or correctional facility involved to the CPHS prior to approval.

When a Subject Becomes a Prisoner during the Research
Should a research subject become incarcerated, and the protocol was not originally reviewed and approved for prisoners:

• The PI must promptly notify the CPHS of the event.
  
• CPHS will remind the investigator that all research interactions and interventions with, and obtaining identifiable private information about, the now-incarcerated prisoner-subject must cease until all of the requirement of Subpart C have been satisfied with respect to the relevant protocol.

RESEARCH INVOLVING COGNITIVELY IMPAIRED PERSONS

As a general principle, incapable persons should not be involved in research that can be conducted with capable subjects. Inclusion of cognitively impaired persons may be permitted by CPHS if such research provides societal benefit, particularly one that is not otherwise available outside of the research setting.

Cognitively Impaired – Having either a psychiatric disorder (e.g. psychosis, neurosis, personality or behavior disorders) an organic impairment (e.g. dementia) or a development disorder (e.g. mental retardation) that affects cognitive or emotional functions to the extent that capacity for judgment and reasoning is significantly diminished. Others, including persons under the influence of or dependant on drugs or alcohol, those suffering from degenerative diseases affecting the brain, terminally ill patients, and persons with severely disabling physical handicaps, may also be compromised in their ability to make decisions in their best interests.

Competence – The capacity to act on one’s own behalf; the ability to understand information presented, to appreciate the consequences of acting (or not acting) on that information, and to make a choice. Competence may fluctuate as a function of the natural course of a mental illness, response to training, effects of medication, general physical health, and other factors. Therefore, mental status should be re-evaluated periodically.

Incapacity – The inability to understand information presented, to appreciate the consequences of acting (or not acting) on that information, and to make a choice. Often used as a synonym for incompetence.

Incompetence – The inability to manage one’s own affairs. Often used as a synonym for incapacity.

Institution – A residential facility that provides food, shelter, and professional services (including treatment, skilled nursing, intermediate or long term care, and custodial or residential care).

UTHSC-H shall follow the Texas Health & Safety Code - Chapter 313. Consent To Medical Treatment Act for research consent matters unless clearly inapplicable because there is no applicable Texas law specific to research consent. If an adult patient of a home and community support services agency or in a hospital or nursing home is comatose, incapacitated, or otherwise mentally or physically incapable of communication, an adult surrogate from the following list, in order of priority, who has decision-making capacity, is available after a reasonably diligent inquiry, and is willing to consent to medical treatment on behalf of the patient may consent to medical treatment on behalf of the patient:

1. the patient's spouse;
   
2. an adult child of the patient who has the waiver and consent of all other qualified adult children of the patient to act as the sole decision-maker;
   
3. a majority of the patient's reasonably available adult children;
   
4. the patient's parents; or
   
5. the individual clearly identified to act for the patient by the patient before the patient became incapacitated, the patient's nearest living relative, or a member of the clergy.
   
6. Any dispute as to the right of a party to act as a surrogate decision-maker may be resolved only by a court of record having jurisdiction under Chapter V, Texas Probate Code.
   
7. Any medical treatment consented to under this section must be based on knowledge of what the patient would desire, if known.
   
8. Notwithstanding any other provision of this chapter, a surrogate decision-maker may not consent to:
   i. voluntary inpatient mental health services;
   ii. electro-convulsive treatment; or
   iii. the appointment of another surrogate decision-maker.
   

Review Process – CPHS will review the proposed research and ensure that the conditions set forth in this policy and procedures are met. The research proposal may be reviewed by exempt, expedited or Full Board Review process according to UTHSC-H policies and procedures. CPHS shall consider the appropriateness of enrolling cognitively impaired persons in research. Besides the usual criteria for review of research outlined in policy and procedure on Initial Review, CPHS shall also consider the following:

Degree of Risk – Research that presents more than minimal risk should involve cognitively impaired persons only when the research holds prospects of direct benefit to these individuals. A minor increase over minimal risk may be permitted in research involving institutionalized individuals only where research is designed to evaluate an intervention of foreseeable benefit to their care. If a research study poses more than minimal risk and no prospect of direct benefit to the individuals, CPHS should obtain advice from experts regarding the appropriateness of the research study.

Selection of Subjects – Research involving persons whose autonomy is compromised by disability or restraints on their personal freedom should bear some direct relationship to their condition or circumstances. The researchers should not choose persons who are institutionalized as a convenient sample for studies that bear no relation to their situation.

Limiting Risks – CPHS should ensure the protocol includes a description of appropriate psychological or medical screening criteria to prevent or reduce adverse reactions to the therapeutic and research procedures. When appropriate CPHS might require other health care providers involved in the care of these patients to be consulted to ensure that the research will not be detrimental to ongoing therapeutic regimens.

Assessing Competence - As a general rule, all adults, regardless of their diagnosis or condition, should be presumed to be competent to consent unless there is evidence of a serious mental disability that would impair reasoning or judgment. Even those who do have a diagnosed mental disorder may be perfectly able to understand the concept of being a research volunteer, and capable of consenting to or refusing participation. Mental disability alone should not disqualify a person from consenting to participate in research; rather, there should be specific evidence of individuals’ incapacity to understand and to make a choice before they are deemed unable to consent.

Documenting Capacity – For all research, regardless of study population, the person who obtains the subjects consent must determine that the person has sufficient capacity to give consent. This is documented by the signature in the consent form of the person obtaining consent. In research that involves cognitively impaired persons, CPHS shall consider the need for independent assessment of capacity. CPHS may set qualifications for the person making assessment such as requiring a psychiatrist or geriatrician to make this assessment. The independent assessment should be documented by a formal note that is dated and signed.

Consent in Research Involving Cognitively Impaired Persons – In general, informed consent is required or waived according to the policy and procedure on Informed Consent. Consent may be sought from legally authorized representative with prior CPHS approval. CPHS shall consider whether investigators must solicit prospective subjects’ assent (i.e., the willing and, to the extent possible, knowledgeable participation of those unable to give legally valid consent) in addition to the permission by the legally authorized representative.

Persons who are Institutionalized – When the research poses more than minimal risk and has no prospect of direct benefit to the individuals -

• Court appointed guardian may consent on behalf of the persons formally adjudged incompetent.
  
• Officials of the institution in which incompetent patients reside (even if they are the patient’s legal guardian) are not generally considered appropriate, since their supervisory duties may give rise to conflicting interests and loyalties.
  
• Investigators must assess if conflicting interests exist for the legally authorized representative due to financial pressures, emotional distancing, or other ambivalent feelings common in such circumstances.

Confidential Follow-up Forms

Confidential follow-up forms, or any other linkage between subject codes and identifiers, can be submitted to sponsors only upon assurance from the sponsor that such forms will be submitted to them in sealed envelopes with the notation that they may not be opened without specific permission from this Committee (CPHS).

These sealed envelopes, in addition to the aforementioned information, MUST have the university's name, the PI's name, the protocol number and title, and MUST be marked CONFIDENTIAL.

Should the need arise to notify research subjects of additional information that has come to light about the study drug or device, the CPHS must approve the mechanism for such notification and specifically require that it be channeled through the original PI or the patient's attending physician.

This procedure has been used successfully in the past and preserves the confidentiality of the subject/patient as well as the relationship between the physician/investigator and the subject/patient.

Genetic Research

The greatest risks to subjects participating in genetic research is the inappropriate release of personal and private information. Therefore, how investigators maintain confidentiality of data and specimens collected during the study is a primary concern to the CPHS. The protocol and informed consent form should address the following points:

• That all study information is coded and personal identifiers maintained securely;
  
• That the consent form includes information about who will receive information derived (e.g. the patient, family members, non-participating family members, family physician, other physicians, other investigators);
  
• To add information as to whether clinically relevant information may be uncovered during the course of the study and give the subjects the opportunity to decline receiving this information;
  
• If children are to be research subjects, how will consent be obtained; how will data be handled;
  
• Add the fact that participants may derive no benefit from participation;
  • Study data should not be recorded in the patient's medical record; separate research records with controlled access are preferred;
  
• Will a family pedigree be published or presented? Will there be a possibility of individually identifying subjects?
  
• Inform subjects of any special risks associated with their participation (e.g. changes in family relationships, risks to privacy, confidentiality, insurability, employability, immigration status, paternity suits);
  
• Indicate if general study results will be made available to subjects;
  
• Will genetic counseling be made available? Who will pay for this counseling?
  
• Indicate if the specimens will be maintained for a limited time or indefinitely, or will be discarded;
  
• If clinically relevant information is developed over time ask if the patients wish to be re-contacted;
  
• If you intend to share specimens acquired during the research with other investigators, this information must be included in the consent form and subjects given the choice whether they are willing to permit this or not;
  
• Should there be a potential commercial value derived from the research, the subject must be informed as to whether they will be asked to waive any rights or control over the tissue so used.
  • Subjects must be advised as to which of the items listed above may be declined without impacting participation.

Additional Consent Language for Genome Wide Association Studies

Purpose: The purpose of Genome Wide Association Studies (GWAS) is to compare your genetic information (information passed down to you from your parents that determines all of your traits such as your eye color and body size) with genetic information from other individuals to look for similarities and differences that may help doctors find new or better treatments for many diseases (such as asthma, cancer, diabetes, heart disease, mental illnesses, etc).

If you agree to take part in this study your DNA (genetic information) will undergo genome-wide analysis (all of the instructions that make up your body) and your genotypic (the genetic code) and phenotypic (the expression of the genetic code) data will be shared for research purposes through the NIH GWAS data repository.

Risks of GWAS – The greatest risk of sharing your genetic information is the possible loss of your privacy. Although no identifiable information (name, address, etc.) will be given to the National Institutes of Health (NIH) (the federal government agency that will store your genetic information), the possibility exists that your genetic information may be taken, used for reasons outside of this project and linked back to you. If your genetic information is linked back to you in the future, it may be used by employers and insurance agencies to discriminate you, or by law enforcement to link you (or your family member) to a crime.

If you are part of a small community or a special group of people, your genetic information may be used to draw conclusions about your community or group. Your information may also be used to increase the information available about genetic differences between groups or communities. Genetic differences that cause health problems can lead people to have negative ideas about certain groups or communities.

You should also be aware that the NIH GWAS database is the property of the U.S. government and that these records are subject to the Federal Freedom of Information Act. If people request information under this act, NIH may be required to release records, including your genetic data, but will not release identifying information about you.

Study Withdrawal – You can withdraw your consent to take part in this GWAS study at anytime. If you withdraw your consent, the study doctor will request that your information be removed from the governmental data bank for future sharing. However, if your genetic information has already been given to other researchers, it can not be taken back.

Return of GWAS Results - there is no plan to return to you or your doctor the results from this GWAS study.