HISTORY OF INFORMED CONSENTHISTORY OF INFORMED CONSENT

– Human subjects research has a checkered past

–Nazi experiments 1935-1945– “Extensive, willfully harmful experimentation”–Nuremberg war trials for participants–USA government testing in World War II to

develop vaccines, malaria drugs, long acting penicillin on non-consenting orphaned children, retarded and mentally ill persons, prisoners and conscientious objectors

EXPOSE IN NEW ENGLAND JOURNAL OF MEDICINE, 1966

EXPOSE IN NEW ENGLAND JOURNAL OF MEDICINE, 1966

– Jewish Home for the Aged residents injected with live cancer cells–Willowbrook children’s home residents

given hepatitis virus– Tuskagee syphilis study 1972; African

American men with untreated syphilis– Tea room trade 1967: Observation of sexual

activity

CODES IN RESPONSE TO ETHICAL VIOLATIONSCODES IN RESPONSE TO ETHICAL VIOLATIONS

–Nuremberg code 1949–Geneva convention –Belmont report 1979–NIH Title 45 1981-1991– International ethical guidelines from the

Council for International Organizations of Medical Sciences in Collaboration with the World Health Organization 1993–Helsinki code 1964, 1997, 2001

INFORMED CONSENTINFORMED CONSENT

Ranges from nod of headSpoken to written From general to specific To ultra specificTreatment treated more lightly than

research, but equally important

REQUIREMENTSREQUIREMENTS

Patient must receive explanation of risks, consequences, benefits, and alternatives

Must be written and spoken in a language that the patient understands

Patient must give consent without coercion or persuasion

Be competent / have legal right to competence Should not have received narcotics x amount time prior Advance directive or will may not be witnessed by

anyone having financial interests Witnesses need to be 18 years of age For treatment issues, it is also appropriate to discuss

when the decision will be revisited

BASIC ELEMENTS OF RESEARCH CONSENTBASIC ELEMENTS OF RESEARCH CONSENT

– Study involves research purpose– Procedure risks and benefits to subject and others– Appropriate alternatives– Confidentiality of records, discs, tapes, papers– Compensation and medical treatment– Whom to contact– Voluntary– Refusal = no loss of benefits– Expected duration; Withdraw at any time– IRB approval and approval of agency– Consents may need to be anonymous or verbal, “By

participating in this, I grant consent..”

ADDITIONAL ISSUESADDITIONAL ISSUESCosts to subjectApproximate number of subjectsGovernment or program approvalConsequences of withdrawalFuture risks, to person, pregnancy,

fetus, embryoWhen can the researcher terminateHow new findings may affect study

WHAT IS AN IRB?WHAT IS AN IRB? Helsinki declaration of 41st world medical

assembly Committee membership must include

scientists, non scientists, institutional, and non institutional members

Must be at least five members, must be of ethnic diversity to reflect surrounding community, all five may not be of same gender or profession

The IRB must keep written records and respond to submitted proposals in writing

INSTITUTIONAL REVIEW BOARD SPECIFIC FUNCTIONS:INSTITUTIONAL REVIEW BOARD SPECIFIC FUNCTIONS:

Approve , disapprove, or modify research proposals

Conduct continuing review of research involving human subjects

Observe adequacy of the consent process Suspend or terminate approval of

research which violates ethical principles or that is associated with any potential or unexpected serious harm to participants

WAIVERS TO THE FULL IRBStudies of Minimal RiskWAIVERS TO THE FULL IRBStudies of Minimal Risk Hair, nails, plaque, excreta, secretions 18 or older, non pregnant, good health Not more than 450 ml of blood in 8 weeks Recorded speech Exercise by healthy individual Records, charts, specimens Studies of perceptions Non stressful

STUDIES ON PREGNANT WOMENSTUDIES ON PREGNANT WOMEN Must be preceded by animal studiesPreceded by studies on non-

pregnant personsMust meet the health needs of fetus

or motherMust not be related to termination of

pregnancyCannot be given money to terminate

FETAL STUDIESFETAL STUDIES Must be of minimal risk Fetus must need health care Mother and father must be fully competent

and fully informed Other regulations for fetal tissue, placenta

material Often dependent on political process, i.e.,

Bush and Reagan versus Clinton

OTHER SPECIAL RESEARCH POPULATIONSOTHER SPECIAL RESEARCH POPULATIONS Prisoners (non coercion) Non competent persons (permission of

guardian) Animals (special regulations regarding

pain and sacrificing) Children have special regulations, but

rather than forbid research with children as was done after Nuremberg trials, now this is being encourages to test appropriate drug dosages, etc.

ANIMAL REGULATIONSANIMAL REGULATIONS

Extremely strict Enormous amount of work done to secure

rights of animals Extremely well treated, well cared for in

laboratories May not be allowed to suffer from pain Must die with dignity

1993 NIH REGULATIONS1993 NIH REGULATIONS Stress inclusion of women and minorities in

research Include peer panel review, I.e., breast cancer

survivors involved in project selection Human genome project began and has full

ethical component Financial conflicts of interest now revealed International research has new inclusion of

autonomy which has been difficult to obtain in societies who do not value this concept

International AIDS studies have been a source of conflict; now new regulations

PATIENT SELF DETERMINATION ACT, 1990

PATIENT SELF DETERMINATION ACT, 1990

Patient may delineate wishes now for the futurePatient has the right to make choicesPatient has the right to refuse treatmentPatient has the right to execute an advance directivePatient has the right to select a surrogate decision maker

RESEARCH ON NEWBORNSRESEARCH ON NEWBORNS Right to freedom from pain, loud noises,

and visual intrusions Right to be comforted by parents Much discussion about how to obtain

informed consent for researched treatment during birth emergencies

Many have critiqued that elements of NICU care are not research based

CONSENT FOR CHILDREN RESEARCH/TREATMENTCONSENT FOR CHILDREN RESEARCH/TREATMENT Parent or guardian consent Both parents Risk justified by benefit Generalizable knowledge Serious health problem for children Sound ethical thinking behind any study

necessitating children as subjects Panel of experts Assent and permission Parent present during the procedure

CONCRETE OPERATIONALISMCONCRETE OPERATIONALISM

Thought to need to be at least 12 to show moral development and operationalize

Most countries state 16 years of ageRecently important in trial and

incarceration issues

YOUNG CHILDRENYOUNG CHILDREN Must have information explained at a

developmentally appropriate level about why they are a candidate for study or treatment

Must be told what is the nature of the treatment/experiment and how will it feel in terms familiar to them

Should feel free of coercion by parents or health care professionals

Should be willing to do it When too young to legally give research or

treatment consent, have most recently been asked to give assent

ASSENTASSENT CHILD ASSENT: “I understand that I do not

have to be part of this research even if my parents give permission for me to do it. I also know that I can stop being part of this research even if my parents want me to stay in it.”

PARENTS: “I understand that assent of my child will be solicited. I understand that my child is free to refuse to participate in this research and to withdraw from this research even if I have given permission or wish him/her to continue.”

VULNERABLE CHILDRENVULNERABLE CHILDREN One or no parents Parents mentally retarded or disturbed Foster care or institutional placement Children with AIDS or dying children Cognitive disorders or attention deficit Physical or sensory impairment Genetic disorders Ethnicity differing from the researcher

(although now push to include multiple cultures in a study)

NEW PEDIATRIC PROBLEMNEW PEDIATRIC PROBLEM Research and treatment has traditionally been

done for the good of the minor patient Parents may consent to such research or

treatment New phenomena of transplants from minors to

sibling Consent for the good of “other” -- Is this ethical?

Legal? Are “designer babies” ethical?

ADOLESCENTSADOLESCENTS

Adolescents are a distinct group with emerging cognitive abilities

Although NIH requires racial, ethnic, and gender inclusion, age has not been addressed

Yet research in this age group is very important, as health indicators for adolescents are declining

ADOLESCENTSADOLESCENTS National movement to understand adolescents better Specifically how puberty affects drug distribution and

metabolism More about Human Papilloma Virus and cervical cancer Social deficits and pregnancy; Social deficits and HIV Resiliency- How to increase this trait

ADOLESCENTSADOLESCENTS

Have the right to consent to care without parental involvement regarding

Reproductive issues; contraception, abortion Drug and alcohol treatment

ADOLESCENTSADOLESCENTS

May be considered an emancipated minor: By marriage Judicial decree Consent of parent Failure of parents to meet responsibilities Self supporting and living separately Differs from state to state Refers to medical treatment but not other

rights, i.e., voting, alcohol, cigarettes

NEW ADOLESCENT ISSUESNEW ADOLESCENT ISSUES Most adolescent research takes place in schools U.S. Department of Education requires parental consent for

unemancipated minors However, minors are not necessarily children under the law Areas adolescents are considered mature minors:

contraceptive services pregnancy sexually transmitted infections substance abuse mental health services

RISK TO ADOLESCENT RISK TO ADOLESCENT

If low risk, may be able to simply notify parents that study is taking place and assume passive parental consent unless they send a written objection

If high risk, parents should give actual consent This is a debated issue in the laws about abortion with strong feelings on all sides

STUDIES OF CONSENTSTUDIES OF CONSENT

Usually 93-100% passively agree to study and did mean it

Usually only 30-60% will send active consent due to being busy

There is a bias in which parents do send back notes to home which is a threat to the validity of the study

COST FOR ACTIVE PARENTAL CONSENTCOST FOR ACTIVE PARENTAL CONSENT

Extensive follow up is expensive Additional calls, letters, prizes, contests,

incentives for child, parents, and school staff can cost up to $25 per student

If school is involved, may be lower cost

LEGAL STANDARDS OF COMPETENCYLEGAL STANDARDS OF COMPETENCY

Evidence of choice Reasonable outcomes Rational reasons Understanding

If problems with adolescent consent, related to emotional factors such as anxiety, not chronilogical age or cognitive development

PASSIVE CONSENTPASSIVE CONSENT

If school agrees, passive consent is most likely acceptable if the “probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those encountered in daily life or during the performance of routine physical or psychological examinations or tests.”

CONFIDENTIALITYCONFIDENTIALITY Adolescent gives informed consent Investigator protects privacy Certificate of confidentiality may need to be

obtained Storage assures confidentiality Investigator encourages teen to discuss

research with parent or adult Protocol must be established if study identifies

that teen needs assistance

CERTIFICATES OF CONFIDENTIALITYCERTIFICATES OF CONFIDENTIALITY

Issued by the National Institutes of Health (NIH) Protect investigators and institutions from being compelled to

release information that could be used to identify research study participants

Allow the investigator and others who have access to research records to refuse to disclose identifying information in any

– civil– criminal– administrative– legislative, or other proceeding, whether at the federal, state, or local level

Statutory Authority Statutory Authority

Section 301(d) of the Public Health Service Act (42 U.S.C. 241(d))

Secretary DHHS may authorize persons engaged in:– biomedical– behavioral– clinical– other research – to protect the privacy of individuals who are the subjects of that research.

Authority has been delegated to the NIH.

Identifying InformationIdentifying Information

Broadly defined

Not just name, address, social security number, etc.

Includes any item or combination of items that could lead directly or indirectly to the identification of a research participant.

Eligibility Eligibility

For IRB-approved research collecting identifying information

If disclosure could have adverse consequences for subjects or damage:

– financial standing – employability – insurability, or reputation

NIH or PHS funding not required

Examples of research with potential adverse consequences for subjects

Examples of research with potential adverse consequences for subjects Collecting genetic information Collecting information on psychological well-being of

subjects Collecting information on sexual attitudes, preferences

or practices Collecting data on substance abuse or other illegal risk

behaviors Studies where participants may be involved in litigation

related to exposures under study (e.g., breast implants, environmental or occupational exposures)

Other issuesOther issues

Issued for single, well-defined research projects Certificates granted to Institutions based on PI’s

application Sometimes issued for cooperative multi-site

projects– Must have a coordinating center or “lead” institution – Lead institution can apply on behalf of all institutions

associated with the multi-site project. – Lead institution must ensure that all participating

institutions conform to the application assurances

PROJECTS NOT ELIGIBLE FOR A CERTIFICATE PROJECTS NOT ELIGIBLE FOR A CERTIFICATE

Not research Not collecting personally identifiable information Not reviewed and approved by the IRB as

required by these guidelines Collecting information, that if disclosed, would

not significantly harm or damage the subject

REQUIREMENTSREQUIREMENTS

Must tell subjects that Certificate is in effect in Informed Consent form

Must provide fair and clear explanation of Certificate’s protection, including

– limitations and exceptions Must document IRB approval and IRB qualifications Must provide a copy of the informed consent forms

approved by the IRB PI and Institutional Official must sign application

ASSURANCES ASSURANCES Agree to protect against compelled disclosure

and to support and defend the authority of the Certificate against legal challenges

Agree to comply with Federal regulations that protect human subjects

Agree to not represent Certificate as endorsement of project by DHHS or NIH or use to coerce participation

Agree to inform subjects about Certificate, its protections and limitations

BOUNDARIES OF PROTECTION BOUNDARIES OF PROTECTION

Protects data collected between date of issuance and date of expiration

Protects those data in perpetuity Does not protect against voluntary disclosure:

– child abuse– threat of harm to self or others– reportable communicable diseases– subject’s own disclosure

Must disclose information about subjects for DHHS audit or program evaluation or if required by the Federal Food, Drug, and Cosmetic Act

AN IMPORTANT CAVEATAN IMPORTANT CAVEAT Certificates of Confidentiality do not obviate the

need for data security Data security is essential to the protection of

research participants’ privacy Researchers should safeguard research data

and findings. Unauthorized individuals must not access the

research data or learn the identity of research participants

FOR ADDITIONAL INFORMATION

FOR ADDITIONAL INFORMATION Go to the Certificates of Confidentiality Kiosk at http://grants1.nih.gov/grants/policy/coc/index.htm Kiosk includes:

– background information and Instructions– application information for extramural investigators– application information of intramural investigators– FAQs– contact list– reportable communicable diseases policy

PARENTAL AUTHORITY PARENTAL AUTHORITY

Family privacy safeguards parental autonomy in child raising, while at the same time attempting to safeguard each child’s entitlement to parents who care and feel responsible and who are held accountable for meeting child’s needs

PARENTAL AUTHORITYPARENTAL AUTHORITY

In the United States, parents are granted wide discretion but generally have not been granted the right to disadvantage a child’s health and safety

DECISION MAKING FOR CHILDRENDECISION MAKING FOR CHILDREN Generally allows parents to make decisions Best interest of child are examined Family context also taken into account In rare occasions, family and care providers at

odds on treatment decisions May be parents insisting on futile care May be providers insisting on unproven

treatment

SURROGATE DECISION MAKINGSURROGATE DECISION MAKING

Generally assumed that parent has best interest of child at heart

Health care providers may disagree Often stated “Parent too stressed to make

logical decision”

THREE CONDITIONS MAY OVERRIDE PARENTAL AUTONOMY IN THE USATHREE CONDITIONS MAY OVERRIDE PARENTAL AUTONOMY IN THE USA

1. The medical profession is in agreement about the treatment

2. The expected outcome of the treatment is what society agrees to be right for any child (a chance for a normal life or a life worth living)

3. The expected outcome of denial of treatment would mean death for the child

OVERRIDING PARENTAL CONSENTOVERRIDING PARENTAL CONSENT

In emergency medicine, care has been provided if parent not available

In emergency or non emergent medicine, if parents are available but disagree, court order must be obtained

Guardian ad litem may be appointed Both sides have the right to be heard Patient has the right to transfer care In historical instances, families have had no

opportunity for due process, whereas health facility has been heard. Consent has been granted to physicians by court on behalf of child’s best interests

Many cases of court order have occurred in people of color or new immigrants

AMERICAN ACADEMY OF PEDIATRICSAMERICAN ACADEMY OF PEDIATRICS

Informed Consent, Parental Permission, and Assent in Pediatric Practice (RE9510)

Religious Objections to Medical care (RE9707)

SONOMA STATE UNIVERSITY INTERESTSSONOMA STATE UNIVERSITY INTERESTS

Class projects do not have to go through IRB However, if the intent is to publish, must go

through IRB Need to give them time to respond and ask

questions Form available on line