Notes

Outline

IRB 101 Old Issues & New Regs Jacqueline S. Marinac, Pharm.D.

Question 1: The initials IRB stand for? A.  Institutional Review Board B. Investigational Review Board C. Irrational Review Board D. Irate Radical Board

Question 1: The initials IRB stand for? A.  Institutional Review Board B. Investigational Review Board C. Irrational Review Board D. Irate Radical Board

TYPES of IRBs at UMKC for Human Research Adult IRB Pediatric IRB Social Sciences IRB Questionnaires Surveys

Make-up of IRB > 5 members with varying backgrounds Diverse with racial and cultural sensitivities Men and Women one nonscientific fields 1 member not affiliated with hospital No member may participate in approval of project with conflict of interest. May invite expert reviewers, nonvoting

Authority of IRB Approve, review, require modifications of research Require documented informed consent, waive consent Require IND, or IDE (INVESTIGATIONAL devise exception) Notify investigators in writing of decision Opportunity to respond in person or in writing Conduct continual review of research/year Authority to terminate or suspend research

Question 2: All are under the authority of the IRB  review EXCEPT: A. Risk reasonable to anticipated benefits B. Selection of subjects is equitable C. Informed consent will be documented D. Adequate provision to protect privacy and maintain confidentiality

Question 2: All are under the authority of the IRB  review EXCEPT: A. Risk reasonable to anticipated benefits B. Selection of subjects is equitable C. Informed consent will be documented D. Adequate provision to protect privacy and maintain confidentiality E. All are correct!!!

Criteria for IRB Approval Risk to subject are minimized Risk reasonable to anticipated benefits Selection of subjects is equitable Informed consent will be sought Informed consent will be documented Adequate monitoring for safety Adequate provision to protect privacy and maintain confidentiality

INFORMED  CONSENT

Informed Consent Nuremberg code (1949) Helsinki Doctrine of the World Medical Association (1964) United States regarding Institutional Review Boards     (Jan 27, 1981) Informed consent  (May 30, 1980)

Nuremberg Code 1949 Alternative means condition no other way to obtain this info except human experimentation Value Condition researchers have anticipated benefit Investigation of risk benefit Informant consent Fairness constitute selection of subjects is fair

Question 3 When a subject signs informed consent he/she waives right to future legal action? A. True B. False C. I don’t know

Informed Consent Legally effective informed consent or legally authorized representative Subject has sufficient opportunity to consider whether or not to participate and minimize the possibility of coercion or undue influence Documentation of Informed Consent: Written informed consent, signed by the individual with a copy to the subjects Information must be in a language understandable, 5th-6th grade education for TMC patients best NO waiving of legal rights or releases the sponsor from liability for negligence

Is getting subject to sign a consent document all that is required for informed consent? Verbal approval does not satisfy for informed consent Subjects signature provides documentation of agreement to participate--only 1 part of process Giving subject adequate information Opportunity to consider all options or alternatives Opportunity to ask questions Assuring comprehension of materials  Voluntary agreement to participate Continue to provide information as needed.

CAPACITY TO CONSENT Does the subject/patient have the ability to: Understand medical problem proposed treatment alternatives to proposed treatment Appreciate any reasonable foreseeable consequences of proposed treatment any reasonable consequences refusal treatment Make decision not based upon delusions depression or coercion Etchells et al . Can Med Assoc J 1996;155:657.

Question 4: All of the following are required elements of informed consent EXCEPT? A.  Alternatives to being in the study B. What part of study is “experimental” C. Voluntary participation D. Study budget

Question 4: All of the following are required elements of informed consent EXCEPT? A.  Alternatives to being in the study B. What part of study is “experimental” C. Voluntary participation D. Study budget

Basic Elements of Informed Consent State that the study involves research Purpose Duration of research Description of the procedures Which procedures are experimental Foreseeable risks or discomforts

Basic Elements of Informed Consent Any benefits--often overstated Appropriate alternatives Extent of confidentiality Whether compensation or medical treatment is available if injury occurs Who to contact for answers to questions Participation is voluntary & No penalty refusal to participate or withdraw

Other Elements In Informed Consent Risk to fetus Circumstances for termination by investigator without subject consent Additional costs to subject Consequences of subject’s decision to withdraw Significant new findings which may influence further subject participation Number of subjects Receiving active or placebo medicine

Question 5: In order to conduct research on older children,  which is NOT true? A. UMKC Pediatric IRB approval needed B.  Assent of child may be required C.  Consent of 1 or 2 parent(s) or adult guardian required D.  Studies cannot be done on persons < 18 years age

Question 5: In order to conduct research on older children,  which is NOT true? A. UMKC Pediatric IRB approval needed B.  Assent of child may be required C.  Consent of 1 or 2 parent(s) or adult guardian required D.  Studies cannot be done on persons < 18 years age

Special Populations Children Pregnant females Fetus Prisoners Mentally disabled Emergency patients

Exemptions from Informed Consent: Emergency Use of a Test Article Informed consent cannot be obtained because of inability to communicate Time is not sufficient to obtain consent No available alternative that provides equal or greater likelihood of saving subjects life Independent review 5 working days by          other physician Documentation IRB within 5 working days

Waive Informed Consent Consent is the only record linking subject with research participation Research presents no more than minimal risk of harm and involves no procedures for which written consent is normally required.

Question 6: A resident wants to conduct a patient chart-review for his required research project.  What is the next step? A.  No IRB approval since chart review only B. IRB approval and maybe exempt or expedited review C. Call your IRB office to find-out

IRB REVIEW PROCESSES EXEMPT Expedited Review Full Review

EXEMPT FROM IRB REVIEW Survey or Interview Sensitive aspects not EXEMPT e.g., sexual behavior, illegal behavior, ETOH use, etc Contents could jeopardize liability or standing of interviewee Observation of Public Behavior Teaching Practices if within normal educational setting

EXEMPT REVIEW (CONT.) Educational tests Cognitive, Diagnostic, Aptitude, Achievement No identifiable links to subject Existing Data, documents, records or path specimens No identifiable links to subject on data collection sheets

Question 8: You want to do your resident project on stored samples from previous studies in the Gold 5 lab.  What is required? A. No IRB approval since samples are already collected B. IRB approval and maybe exempt or expedited review C. Cannot be done without permission of persons who gave samples D. Call your IRB office to ask

EXPEDITED REVIEW Appropriate for studies which involve Minimal Risk Reviewed by Chair of IRB and/or other experienced IRB members Submit in writing to IRB recommendations All IRB authority exists EXCEPT: Cannot disapprove of the research--only done in conjunction with full review process “kick” review to full committee review

Expedited Review Collection of hair, nails deciduous teeth and permanent teeth if medical extraction indicated, excreta including sweat, saliva (uncannulated), placenta after delivery, amniotic fluid at time of labor. Recording of data in persons > 18 years using noninvasive procedures (e.g.: weighing, testing sensory acuity, ECG, EEG, temp, echo.)  Does NOT include x-rays, microwave. Collection of blood by venipuncture < 450 mL per 8 week period and no more than twice weekly in over 18 nonpregnant healthy subjects.

Expedited Review Voice recordings Moderate exercise in healthy volunteers Study of existing data, records, specimens. Research of perception, cognition without manipulation of subject’s behavior. Research on drugs or devices for which an IND exception or IDE is not required.

FULL REVIEW ALL OTHER RESEARCH Necessary Information in Packet to IRB 4 Copies Protocol Informed Consent Budget Synopsis--max 5 pages Drug Brochure and Letter of Indemnification if applicable

FULL IRB REVIEW IRB required to meet min. quarterly Human Adult IRB at UMKC Joe Solomone, Chair Sheila Anderman-- Research Coordinator TMC Adult IRB meets bimonthly 2nd and last Tuesday of the month All advertising approved by IRB Investigator must attend IRB meeting to address questions

NEW REGULATIONS

New Regs Financial interest of investigators FDA requires sponsor drug/device disclose interests of investigators Compensation to investigator proprietary interest--eg: patent Equity interest in sponsor Payment in form of grant, equipment, retainers for consultation or honoraria FDA Print Media 301-827-6242

Research Misconduct Claiming the ideas or words of another to be one's own. Including false statements or data in research proposals, progress reports, publications, or related documents. Manipulating research procedures or data so as to bias results. Failure to give appropriate recognition to people who have made significant contributions to the research. Misuse of confidential material such as manuscripts and grant proposals received in the peer review process and proprietary information or materials.

New Regulations Fines for research misconduct Civil penalties --HHS pursue FDA levy Violations of informed consent and other up $ 250,000 per investigator or up to $ 1 million/institution. HHS Fact Sheet 2000.06.06

Mandatory Education By October 1, 2000 anyone submitting NIH grants or proposals for contracts must: Complete approved education program Site on internet http://ohsr.od.nih.gov

Subject Recruitment IRB must review methods to           recruit subjects Advertisements--seen as part of informed consent process and subject selection Particularly important for vulnerable populations Audiotapes, flyers, newsprint ads IRB may approve of wording

FDA --Guidelines Advertising Name and address or researcher/facility Condition or purpose for study Eligibility criteria Brief list of benefits if any Time or other commitment required Location of contact person

Advertising Study No claims that drug, biologic or device Safe Effective for purpose being tested Equivalent or superior to other drugs, biologics or devices Cannot promise “free medical treatment” when intent means no charge for study May state subjects paid, but not emphasize how much or the payment May be coercive to some

GENETIC STUDIES

GENETIC STUDIES: CONSENT Conveying generic information guidelines for disclosure information what does info mean what information receive Counseling Available What qualified person deliver the info Counseling with consent process and results Social and Psychological risks outlined consent How will findings of nonpaternity, or other incidentals be handled?

GENETIC STUDY RECRUITMENT Subject recruitment Family members involved How will recruitment be conducted? Proband Support Groups Personal physician Investigator ? Risk of coercion or undue influence Source of research data Consent of family needed?

Individual Confidentiality Protected against disclosure of personal info to other family members How individual privacy assured for pedigree studies Option NOT to receive information Has consent to disclose to family physician been obtained? “Research results will NOT be told to you or your physician except for a few reasons. These are situations in which a life-threatening medical problem is found for which medical treatment may prevent or cure long-term medical problems.  If such a situation would occur, do you want us to first  contact you, then if you choose, your doctor?”

CONFIDENTIALITY SAMPLES/DATA How data protected from third parties--employers, insurance, etc. How/where data be stored and will be coded “Your tissue and data will be given a code number.  The list that links your code number to your name will be kept separate from the research data.  The list will be kept in a locked file and only the head study doctor and only members of the research team will ever see the list.  Every effort will be made to protect your research data. There is however, always a chance it may be come known.” Certificate of Confidentiality needed?

SAMPLE DISPOSITION Can tissue/samples stored used for new studies? Future contact of subjects for additional consent “Can a member of the research staff contact you to ask you to do future research studies other than this one?” “Can we give your tissue or results (with code numbers only) to persons doing research in similar fields? They will NOT receive your name or any other identifiable material.” Assurance of sample destruction

FUTURE USE SAMPLES Assurance subjects can withdraw data or samples in future “It is your choice to be in the study.  You may choose not to be in the study or stop at any time. If you choose to be in the study that uses code numbers and later change your mind, to stop being in the study call….Any research results already found cannot be destroyed or taken out.”

GENETIC PUBLICATION Publication plans threaten privacy or confidentiality of subjects Consent needed for publication of identifiable material

GENETIC CONSENT FORM “Some genetic research may find that you are a “carrier” of a genetic problem or disease.  This could mean that you or members of your extended family may have an increased risk of getting the disease.  The person who is the “carrier” does not have the disease but my pass the disease to their unborn children.” “An insurance company might think your being in genetic research puts you at higher risk and may refuse to insure you.”

GENETIC CONSENT FORM “If your being in a genetic study becomes known outside the research, (for example, if your being in the study were put in your medical record) you and family member s my be unable to get health, life or disability insurance.” “You might have trouble getting a job or be fired from your current job. This could happen if you choose to talk about your being in the study with your doctor, but don’t ask that the information be kept out of your medical record. “ “If genetic or any other information is in your medical record, insurance companies may be able to see it.”

IRB APPROVAL Notified in writing of the decision Opportunity to appeal the decision Study Number--on all documents Following Approval Annual review by IRB re: progress Must notify IRB for the following: Change in protocol Increase in subjects by > 10% Change in inclusion/exclusion criteria Side effects and outcome of events Termination of study