63. Are you including results from DNA or RNA testing that were performed for clinical purposes using clinically validated diagnostic tests?

Transcription

1 63. Are you including results from DNA or RNA testing that were performed for clinical purposes using clinically validated diagnostic tests? Yes No Answer YES to this question if the testing is being done for the patient's clinical care but the results will be used in this research. Examples of DNA/ RNA testing done solely for clinical purposes: BRCA genes for Breast Cancer CFTR gene for Cystic Fibrosis Huntington Disease gene ApoE4 gene for Alzheimer s Topoisomerase I inhibitor for Irinotecan HFE gene for Hemochromatosis F8 gene for Hemophilia Fluorescent in situ hybridization (FISH) or cytogenetic testing for chromosomal abnormalities where clinically indicated CYP2C9 and VKORC1 for warfarin metabolism Enter NEXT QUESTION If Yes:64 If No:64 TEMPLATES If Yes: Protocol: 23. dna_rna_clinical_purposes_p.doc Genetic Testing for Clinical Purposes Consent: none If No: Protocol: none Consent: none 23. dna_rna_clinical_purposes_p.doc Genetic Testing for Clinical Purposes Use of Genetic Test Results Done for Clinical Diagnostic Purposes Describe the test results to be used in this study that are being done for clinical purposes such as: Performing clinically established genotype testing to determine response to drug/confirm a suspected diagnosis/detect whether a person carries a particular disease-associated allele, etc. 1

2 64. Are you doing sequence analysis or other testing of DNA/RNA as part of the research study? Yes No Answer this question YES if the study involves such things as: molecular profiling microarray testing HLA testing Performing clinically validated tests for research purposes (e.g.- subject would not have the test unless they enroll in the research) Examples of clinically validated tests: BRCA genes for Breast Cancer CFTR gene for Cystic Fibrosis Huntington Disease gene ApoE4 gene for Alzheimer s HFE gene for Hemochromatosis F8 gene for Hemophilia Fluorescent in situ hybridization (FISH) or cytogenetic testing for chromosomal abnormalities where clinically indicated Topoisomerase I inhibitor for Irinotecan CYP2C9 and VKORC1 for warfarin metabolism Answer this question NO if the study involves only such things as: pharamacokinetics pharmacodynamics immunohistochemical analysis such as antibody testing proteomics serum biomarkers such as C reactive protein (CRP) NEXT QUESTION If Yes:65 If No:74 TEMPLATES If Yes: Protocol: none Consent: none If No: Protocol: none Consent: none 2

3 NEXT QUESTION If Yes:66 If No:67 TEMPLATES If Yes: Protocol: none Consent: 17. HLA_testing_C.doc HLA Testing 23 risk_hla_germline_accidental_disclosure_c.doc If No: Protocol: none Consent: none Risk of Accidental Disclosure of HLA Results TEMPLATE SECTIONS 17. HLA_testing_C.doc HLA Testing HLA Testing A sample of your blood will be tested for HLA a form of genetic testing. HLA is a special protein commonly found in the body, especially in white blood cells. There are many different types of HLA. Because of this HLA testing is very good at figuring out things like if a person is a good match as an organ donor, how likely a person is to develop a disease or condition, or paternity testing (being able to figure out the biological parents of a person.) 23. risk_hla_germline_accidental_disclosure_c.doc Risk of Accidental Disclosure of HLA Results Risks of Genetic Information: If the full genetic research section is at the end of this consent form you may delete this section as it would be duplication. There is a small chance that your genetic information could be shared with others by mistake. In the unlikely event that your information was mistakenly shared and if it were linked to a medical condition, this could affect your ability to get or keep some kinds of insurance. If family members were to see the information it could also affect them. This could hurt family relationships. It is possible that you could be identified from the sample if someone has another sample from you. The two samples could be matched to then identify you from the sample given for this study. 3

4 66. Will HLA testing results be shared with subjects, their health care providers or be put in their medical records? Yes No NEXT QUESTION If Yes:67 If No:67 TEMPLATES If Yes: Protocol: 25. HLA_results_disclosed_P.doc Disclosing HLA Test Results Consent: 18. HLA_results_disclosed_C.doc HLA Test Results Disclosed If No: Protocol: none Consent: 19. HLA_results_not_disclosed_C.doc HLA Test Results Not Disclosed TEMPLATE SECTIONS 25. HLA_results_disclosed_P.doc Disclosing HLA Test Results Disclosing HLA Test Results 1. Explain why it is appropriate to provide participants with results. 2. Will the results be put into the subject s medical records? 3. What information will study participants receive? 4. At what point during the research will the results be disclosed? 5. Who will disclose the results to participants? 6. Will anyone other than the participant be informed of the results (e.g., health care provider)? 4

5 7. Will the test results affect the clinical care of the subject? 18. HLA_results_disclosed_C.doc HLA Test Results Disclosed HLA Test Results If you would like to know the results of your HLA testing, they will be shared with you by the researchers. In most cases it is not risky or harmful to know your HLA type. It is important that you know that sometimes the HLA result might affect your ability to get or keep certain kinds of insurance or it may affect your family relationships. This could make you feel anxious. Also, keep in mind that if you know your HLA type, you would be required, if asked, to share this information with your insurance company even if it is not in your medical record. You may wish to discuss the risks of knowing your HLA type with the researchers before you agree to this testing. 19. HLA_results_not_disclosed_C.doc HLA Test Results Not Disclosed HLA Test Results The results of the HLA testing will not be put in your medical records, and will not be shared with you, your health care provider or anyone else outside of the study team. 5

6 67. Are you specifically looking for differences in gene sequence, gene mutations or polymorphisms? Yes No If you answer YES to this question the protocol does not qualify for expedited review by the IRB. Make sure you answer NO to the question "Does this study meet Expedited approval criteria?" Answer this question YES if the study includes such things as: Using techniques such as single nucleotide polymorphism (SNP) to study allele differences, Gene sequencing analysis Polymorphisms. High throughput sequencing Genome-wide association study Using clinically validated tests for research purposes. Examples of clinically validated tests include: BRCA gene for Breast Cancer CFTR gene for Cystic Fibrosis Huntington Disease gene ApoE4 gene for Alzheimer s HFE gene for Hemochromatosis F8 gene for Hemophilia Fluorescent in situ hybridization (FISH) or cytogenetic testing for chromosomal abnormalities where clinically indicated Answer this question NO if the study includes ONLY such things as testing: DNA/RNA of a virus* antigens of a tumor* serum biomarkers [e.g. C Reactive Protein (CRP)] HLA Status Microarrays/ molecular profiling DNA fingerprinting to confirm results *Not the DNA/RNA/antigen of the individual 6

7 NEXT QUESTION If Yes:69 If No:68 TEMPLATES If Yes: Protocol: 26. genetic_testing_p.doc Genetic Testing Consent: none If No: Protocol: 24. nongermline_testing_p.doc Non-Germline Testing Consent: none SECTION TEMPLATES 24. nongermline_testing_p.doc Non-Germline Testing Genetic Research Describe the testing to be done such as: DNA/ RNA of a virus* Microbiome analysis (microbial sequences sampled from a human subject) Microarrays /Molecular Profiling Antigens of a tumor* Serum Biomarkers [e.g. C Reactive Protein (CRP)] DNA Fingerprinting to confirm results * Not the DNA/ RNA/antigen of the individual 26. genetic_testing_p.doc Genetic Testing See section at end of this document 7

8 68. Could the test results affect the subjects family relationships, health care or insurability in the foreseeable future? Yes No Enter POST DISPLAY TEXT Answer this question YES if you are doing something like DNA/RNA sequencing of the HIV virus or MRSA. Answer this question NO if you are doing something like DNA/RNA sequencing of a cold virus. NEXT QUESTION If Yes:74 If No:74 TEMPLATES If Yes: Protocol: none Consent: 23. risk_hla_germline_accidental_disclosure_c.doc Risk of Accidental Disclosure of HLA Results If No: Protocol: none Consent: none SECTIONTEMPLATES 23. risk_hla_germline_accidental_disclosure_c.doc Risk of Accidental Disclosure of HLA Results Risks of Genetic Information: If this section is repeated elsewhere in this consent or the full genetic research section is at the end of this consent form you may delete this section as it would be duplication. There is a small chance that your genetic information could be shared with others by mistake. In the unlikely event that your information was mistakenly shared, and if it were linked to a medical condition, this could affect your ability to get or keep some kinds of insurance. If family members were to see the information it could also affect them. This could hurt family relationships. 8

9 69. Does this study involve both specimen banking and specifically looking for differences in gene sequence, gene mutations or polymorphisms? Yes No Answer this question YES if you answered YES to both previous questions: Will any specimens be saved after this study is completed? Are you specifically looking for differences in gene sequence, gene mutations or polymorphisms? Enter NEXT QUESTION If Yes:70 If No:70 TEMPLATES If Yes: Protocol: none Consent: none If No: Protocol: none Consent: 20. genetic_testing_c.doc Genetic Testing only for consent See end of document for this section 9

10 70. Will the DNA/RNA or sequence analysis testing results be disclosed or will the subject have the option of receiving the results? Yes No Answer this question YES if: results will go in the subject s medical records results will be shared with the subject s health care provider if applicable: results will go to the child and or their parent/guardian Enter NEXT QUESTION If Yes:71 If No:71 TEMPLATES If Yes: Protocol: 28 gt_results_disclosed_p.doc Genetic Testing Results Disclosed to Subjects Consent: none If No: Protocol: 27. gt_results_not_disclosed_p.doc Genetic Testing Results Not Disclosed to Subjects Consent: none 10

11 SECTION TEMPLATES 28. gt_results_disclosed_p.doc Genetic Testing Results Disclosed to Subjects Disclosure of Genetic Research Results to Subjects Some genetic research is directly related to a patient s medical care (e.g. HLA testing in bone marrow transplant or immune therapy). For many studies, however, it is unrelated to their current care. It would be unethical to provide results to subjects before clinical significance is definitively established. On the other hand, if there is a good chance that the research will yield results that could affect the subjects medical care, it may be appropriate to tell subjects that they may choose to receive results. In those situations, care should be taken to implement security procedures that will provide assurance that the genetic information will remain strictly confidential. In many cases, however, it may be more appropriate to refer subjects to genetic testing laboratories that are better equipped to deal with both testing and counseling. If providing subjects with results, care must be taken in how that information is conveyed and, if necessary, counseling should be offered. 1. Explain why it is appropriate to provide subjects with results. 2. What information will study subjects receive? 3. At what point during the research will the results be disclosed? 4. Who will disclose the results to subjects? 5. Will anyone other than the subject be informed of the results (e.g. health care provider)? 6. Will genetic counseling be provided? 7. If yes, will genetic counseling also be provided before testing? 8. If future research yields results that are clinically meaningful or significant, would those results be disclosed to the subject? Why or why not? 9. Even if results may not be clinically valid, (recognized by FDA or generally recognized by practitioners in the field as established) might they affect a subjects clinical care? Third Party Concerns 1. Will family members be directly involved in the research? 2. If yes, how and by whom (e.g., an investigator, a subject, a support group) will those family members be recruited? 3. Are any vulnerable subjects or populations involved in the research? 11

12 27. gt_results_not_disclosed_p.doc Genetic Testing Results Not Disclosed to Subjects Genetic Research Results Not Disclosed to Subjects 1. Why will you not disclose genetic research results to subjects? 2. If future research yields results that are clinically meaningful or significant, would those results be disclosed to the participant? Why or why not? 3. Even if results may not be clinically valid (recognized by FDA or generally recognized by practitioners in the field as established), might they affect a subject s clinical care? 12

13 71. Will this testing be done in children under the age of 18? Yes No NEXT QUESTION If Yes:72 If No:73 TEMPLATES If Yes: Protocol: none Consent: none If No: Protocol: none Consent: none Enter 13

14 72. Will results from a child be disclosed to the child, their parent/guardian or their health care provider? Yes No Enter NEXT QUESTION If Yes:73 If No:73 TEMPLATES If Yes: Protocol: 29. gt_results_children_disclosed_p.doc Genetic Testing (Minors) Consent: none If No: Protocol: none Consent: none 14

15 SECTION TEMPLATES 29. gt_results_children_disclosed_p.doc Genetic Testing (Minors) Disclosing Test Results From a Child While parents/guardians may legally consent to such genetic research, in most cases children should not be included in such research if results will be provided and it is unrelated to their current medical care. This sets up a situation where children or their parents/guardians are provided with information that the child, had he or she been an adult, would have elected not to know and/or that the child might not want to know when he or she reaches adulthood. The potential harm to the emotional health and well-being of the child, and the parents interactions with that child if identified to have the disease later in life, could be significant. 1. Does the study involve research where predictive genetic information may be obtained about children that is unrelated to their current medical care? (Note- any disclosure of results to participants must be approved by the IRB-HSR.) 2. Is there an intervention to treat, cure, or prevent the disease or condition? 3. Will the intervention be more effective if begun before age 18? 4. Will a parent/guardian give consent and, if able, will the child give assent to the disclosure? If the answer to any of the above is NO, results relating to minor participants should not be disclosed. Parents should be reminded that the research is not a substitute for clinical care, including genetic counseling and testing. 15

16 73. Is there any possibility that data from this study may someday be used for a Genome-Wide Association Study (GWAS)? Yes No A GWAS study is any study of genetic variation across the entire human genome that is designed to identify genetic associations with observable traits (such as blood pressure or weight), or the presence or absence of a disease or condition. Whole genome information, when combined with clinical and other phenotype data, offers the potential for: increased understanding of basic biological processes affecting human health, improvement in the prediction of disease and patient care, and ultimately the realization of the promise of personalized medicine. The NIH Policy for Genome Wide Association Studies (GWAS) applies to protocols for which the NIH will cover the cost of the GWAS analysis via a grant or contract that was submitted for NIH funding after January 25, Competing GWAS applications to NIH must include a GWAS data sharing plan as part of the research plan or outline why such data sharing is not appropriate. The institution must provide a certification including IRB verification of key points in order for the phenotype/ genotype data to be submitted to the NIH GWAS databank. For additional information see the IRB-HSR Website on GWAS at NIH GWAS website at You should answer YES if the study will be funded by the NIH and includes analysis of the entire genome. Enter NEXT QUESTION If Yes:74 If No:74 16

17 TEMPLATES If Yes: Protocol: none Consent: 21 gwas_c.doc GWAS Submission If No: Protocol: none Consent: none SECTION TEMPLATES 21. gwas_c.doc GWAS Submission Genome Wide Association Studies If GWAS (genome-wide association studies) may be performed, include the following language. It may be revised to reflect whether the GWAS data will be restricted to the disease under study and related research, or can be used for unrelated research. We will also perform a whole genome analysis on your DNA sample. Usually researchers study just a few areas of your genetic code that are linked to a disease or condition. In whole genome studies, all or most of your genes are analyzed and used by researchers to study links to (signify here whether the GWAS data will be limited to the disease under study and related disorders or "many diseases or conditions"). If the data will be sent to NIH or other data repositories, include the information below: In order to allow researchers to share test results, the National Institutes of Health (NIH) and other central repositories have developed special data (information) banks that collect the results of whole genome studies. The NIH or other data banks will store your genetic information and may share it with other researchers to do more studies. We do not think that there will be further risks to your privacy and confidentiality by sharing your whole genome analysis with these databanks; however, we cannot predict how genetic information will be used in the future. The information will be sent with only a code number attached. Your name or personal information will never be given to them. There are many safeguards in place to protect your information while it is stored in repositories and used for research. There is a small chance that your genetic information could be shared with others by mistake. In the unlikely event that your information was mistakenly shared, and if it were linked to a medical condition, this could affect your ability to get or keep some kinds of insurance. If family members were to see the information it could also affect them. This could hurt family relationships. It is possible that you could be identified from the sample if someone has another sample from you. The two samples could be matched to then identify you from the sample given for this study. 17

18 If the data will be used for unrelated studies, include the following: Research using your whole genome information is important for the study of virtually all diseases and conditions. Therefore, the databank will provide study data for researchers working on any disease, which could include conditions such as HIV/AIDS, cancer, mental illness, and others. 18

19 74. Does this study meet Expedited approval criteria? Yes No NO CHANGES TO TEMPLATES OR DISPLAY TEXT 19

20 81 Will this study be monitored by a Data and Safety Monitoring Board? Yes No NEXT QUESTION If Yes:82 If No:82 NO CHANGES TO TEMPLATES OR DISPLAY TEXT 20

21 82. Does this protocol ONLY involve the prospective collection of additional specimens for specimen banking and or genetic research? Yes No Genetic Research includes any type of analysis described in the previous questions that is being done as part of the protocol and NOT as part of the clinical care of the patient outside of this protocol. If you answer this question YES it means that there is no additional study intervention/study procedures other than collecting the specimen (e.g. administration of drug/ use of a device/xrays etc). Answer this question YES if you are doing such things as: Collecting an extra ml of blood or spinal fluid to be used for research Taking an extra biopsy or extra tissue for research purposes Answer this question NO if you are doing such things as: Using tissue taken for clinical purposes and pathology has completed their tests and then provided you with a sample of the tissue Using tissue that is leftover and would normally have been discarded. NEXT QUESTION If Yes:114 END If No:83 TEMPLATES If Yes: Protocol: Enter 52. hipaa_criteria_for_studies_with_consent_p.doc HIPAA Criteria (with consent) This section is not different than used before not copied here. Consent: NONE NOTE- they do receive the Stand alone GT/TB consent template 1. tissue_genetic_consent_only_template.doc Tissue Genetic Consent Only Template See Stand alone consent at end of this document. If No: Protocol: none Consent: 21

22 53. tissue_banking_genetic_testing_c.doc Tissue Banking and or Genetic Testing SECTION TEMPLATES 53. tissue_banking_genetic_testing_c.doc Tissue Banking and or Genetic Testing See section at end of this document 22

23 REMAINING LARGE SECTION TEMPLATES 26. genetic_testing_p.doc Genetic Testing- PROTOCOL GENETIC RESEARCH Background 1. Briefly describe the nature and purpose of the genetic research (what will be tested and how): 2. Could any genetic findings affect current treatment or therapy? Risks of Genetic Research Some things to keep in mind as completing this section: Most genetic risk is probably future risk. It may be difficult now to anticipate confidentiality risks that participants may face one, five or ten years from now by being in this study at this time because the technology is not yet developed. In the future, it is possible that genetic testing results will be used more broadly by employers or insurers or considered by them. Since it is difficult to assess that risk now, participants should be provided with information that informs them of that uncertainty and the possibility that risk not present now may exist in the future. Sometimes the actual study will be important in determining the future uses of such testing; in that case, provisions should be made to inform participants of any risks that become more apparent as the study progresses. 1. Risks of Accidental Disclosure/Loss of Confidentiality Many risks associated with genetic research are related to breaches in confidentiality. You should consider the mechanisms through which breaches might occur and the consequences of those breaches. Risk is related to the amount of data stored about a subject, the security of the data storage, the more likely linkages, and the seriousness of any condition related to the data. Where the genetic study is linked to an already diagnosed disease, the risk to the subject may be minimal, but there may still be some significant risk to the family. 1.a. If there were an accidental disclosure of this research data, could it affect either the subject or the subject s family member(s)? Please explain how. 1.b. What data will you be keeping about a subject? 23

24 Examples: genetic results, clinical data related to the results, etc. 1.c. Where are you keeping this data and/or specimens? Examples: central registry, central repository, data on excel spreadsheet maintained by study team 1.d. Are there any documented correlations or associations that might be outside the study? Example, a study focusing on correlations between APOE-4 and brain trauma may reveal information about a participant s risk for early-onset Alzheimer's Disease even though that information is not part of the actual study. 2. Social risks Misconceptions are often an important source of potential discrimination. Recent studies have shown that employers often fail to distinguish between having a genetic mutation and the possibility of becoming symptomatic with a disease. Examples of types of social risks: health insurance, life insurance, disability insurance, employment, stigmatization, stress upon family relationships, change in reproduction plans, immigration status, forensic implications, and mistaken paternity. While we have federal and state legislation that protects some of this information, it does not cover many types of insurance, and data show that even with it, some discrimination still occurs. Keep in mind that these risks may vary; a condition that implicates disability insurance may have a minimal impact on life insurance. 2.a. If there were a deliberate or accidental disclosure of the results or associated data from this research, could an insurer or employer think that it would affect the insurability or employability of the subject? (Do not consider any legal restrictions on use of the information). Example, if a long-term care insurer has received information about a subject s APOE4 status, the status would affect the subject s insurability. 2.b. If there were a deliberate or an accidental disclosure of the results or associated data from this research, could it affect reproductive plans of the subject or the subject s family member(s)? If so, how? 24

25 2.c. If there were a deliberate or an accidental disclosure of the results or associated data from this research, could it stigmatize the subject? If so, how? Examples: alcoholism, drug abuse, gender identity issues, dementia, etc. 3. Psychological risks Examples of types of psychological risks: impact of results, impact of disease knowledge without treatment, disclosure of vague or uncertain results, stress related to other family members 3.a. If there were a deliberate or an accidental disclosure of the results or associated data from this research, could this cause psychological stress to the subject or a family member (include rational and irrational reactions)? Example, if a child is diagnosed with a genetic condition, might a parent feel responsibility or guilt? 4. Harm to the community 4.a. If your study involves an ethnic or cultural group, will the results affect that community? YES NO If Yes, explain the risks: For example, could the genetic information be used to cause a group or community of people to be vulnerable to discrimination based on actual or perceived associations, e.g. Ashkenazy Jews and the BRCA genes, or alcoholism or other addictions within ethnic or cultural groups? Where a study may raise community risk, it may be a good idea to conduct focus group discussions with community representatives before the protocol is finalized. 4.b. How will the risks listed above be minimized? 4.c. How will these risks be communicated to participants? Example: subjects will be notified of the risks during the consenting process Information Accompanying Specimens or Data to be Used for Genetic Research 25

26 1. What information will be on the label of the specimen to be used for genetic research? The IRB advises that you do not include HIPAA identifiers such as name, medical record number, subject initials on the label. 2. What information will be "linked to" or will accompany the specimen to be used for genetic research? (e.g. type of clinical information, type of demographic data, HIPAA identifiers such as name, Medical Record Number) 3. If identifiers will be linked to specimens/ data, when will the identifiers be destroyed? NA After specimen is linked to clinical data but before genetic analysis is completed. After specimen is linked to clinical data and immediately after the genetic analysis for the individual participant is completed. After specimen is linked to clinical data and immediately after the genetic analysis for all participants is completed Link to identifiers will not be destroyed Other describe: 26

27 Confidentiality and Collection/Storage of Specimens to be Used for Genetic Research 1. Will any information/ the consent form/ results regarding genetic research be placed in the participant s medical record? 2. How much material (e.g. blood, tissue) will be collected for genetic research and how will it be collected? 3. Who will be responsible for storing the specimens for genetic research? (e.g. sponsor, UVa PI, tissue bank/procurement facility, tissue bank outside of UVa)? 4. If stored at UVa-where will the specimens to be used for genetic research be stored? (e.g. a refrigerator/freezer in a lab, a room-provide room number, or specific location). Note: To protect confidentiality, whenever possible, you should consider using a central facility/repository such as the UVa Biorepository and Tissue Research Facility. 5. Will another research institution or entity outside of UVa ever have control over the specimens? Yes No, If yes, 6. List the name of outside institution/entity. 7. List the information that will be on the specimen label when the specimen is sent outside of UVa. 8. Will any additional information be sent with the sample? Yes No (e.g clinical information, HIPAA identifiers located on a separate piece of paper/ computer file) 9. If yes, list what will be sent: Note to Study Team: If you plan to ship specimens outside of UVa, personnel performing this function must have taken the appropriate training from the Department of Transportation. Contact SOM CTO for training information. Note to IRB Staff: If the information sent outside of UVa with the specimen meets the criteria of Identifiable and the study does not have a consent form- the disclosure would require Tracking under HIPAA regulations. If it meets the criteria of a Limited Data Set, a Data Use Agreement will be required. 10. Can participants withdraw their specimens or request that they be destroyed?

28 Note: the answer to this question must be yes unless the specimens are stripped of all HIPAA identifiers. Third Party Concerns 1. Will family members be directly involved in the research? If yes, how and by whom (e.g., an investigator, the participant, a support group) will those family members be recruited? If no, does this study have any implications for the participant s family members? If yes, will that information be shared with relevant family members?

29 53. tissue_banking_genetic_testing_c.doc Tissue Banking and or Genetic Testing Insert title as applicable: Specimen Banking/Genetic Research Introduction You are also being asked to provide samples of your describe what is being taken e.g. tissue/blood/saliva to be used for research. Your sample(s) might help doctors learn more about diseases or treatments that might help other people in the future. What Sort of Research Will Be Done On Your Sample(s)? If you are doing genetic research or if you anticipate, anytime in the future, using the banked specimen for genetic research you should insert the following sentence: Your sample(s) may be used for genetic research (to learn about diseases that are passed along in families). Describe what information is being sought through this testing here. Participants should be informed of what information may reasonably be expected to result from the use of their sample, including whether the research results will be related to the clinical care of the participants. Your sample(s) may be used by various researchers here at the University of Virginia or elsewhere. Your sample(s) will become the property of (insert name of institution or sponsor). The research may lead to the development of a commercial product or may involve yet undiscovered technologies. There are no plans to pay you if this occurs. Insert one of the following sentences as applicable: You may not be in this study if you do not agree to donate your sample(s). OR This part of the study is optional. You do not have to agree to donate your sample(s) in order to be in the first part of this study. How Will Your Sample(s) Be Labeled? Your sample(s) will not be labeled with your name or other information that would identify you directly. Insert as applicable Instead, it will have a unique code that allows for it to be linked to some of your health information that will be kept (insert where file kept, e.g., on a computer with limited access in the Principal Investigators office, or in the Sponsor s offices at Pittsburg, PA ). This link means that your specimen can be identified but only indirectly. We can find out if we need to know which sample is yours. OR It also will not be coded in any way that we could ever figure out the sample(s) came from you. What Are the Benefits To Donating Your Sample(s) For This Study? If there is no benefit, insert the following: The research that is done with your sample is not meant to help you. But, doctors hope that in the future it will help people who have other diseases or conditions.

30 If there is benefit insert the following The research that is done with your sample may benefit you in the following way: State them. (e.g. documented pharmacokinetics related to genetic results) What Are The Risks of Donating Your Sample(s) For This Study? Risks to Privacy: Insert name of responsible party will be responsible for storing your sample and for protecting your privacy. One of the risks to you is the release of information from your health records. The University of Virginia will do its best to protect your records so that facts about you and your health will be kept private. The chance that information identifying you will be given to someone else is very small. However, we cannot guarantee it will be safe. If you are doing only Specimen Banking insert: (Do not use this if there is any possibility that the sample(s) might be used for genetic research in the future.) There are certain risks of having some types of health information given to other people by mistake. In the unlikely event that this happens, it could cause discrimination or mental harm to you or your family members if others were to see this information. The results could be that you may not be able to get or keep some kinds of insurance. Or it could hurt family relationships. If you are doing only Genetic Research insert: Because everyone has unique DNA, it is possible, although very unlikely, that someone could identify you through your DNA if they have another sample of your DNA. If there are any specific risks related to the type of genetic research that you are doing- list those here. Consider social, psychological, and community risk. For additional information to make these determinations see Things for the researcher to consider regarding risk of genetic research at the end of this document. The additional information should be deleted after you have written this section of the consent. Information about your genetic make-up could mean that you and your family members could face problems that could lead to getting or keeping some kinds of insurance. If doing both Genetic Research and Specimen Banking insert: Because everyone has unique DNA, it is possible, although very unlikely, that someone could identify you through your DNA if they have another sample of your DNA. If there are any specific risks related to the type of genetic research that you are doing- list those here. Consider social, psychological, and community risk. For additional information to make these determinations see Things for the researcher to consider regarding risk of genetic research at the end of this document. The additional information should be deleted after you have written this section of the consent. Information about your genetic make-up could mean that you and your family members could face problems that could lead to getting or keeping some kinds of insurance. There is no way to predict all the possible risks of this research. Risks of having your blood drawn: (only insert this section if not listed elsewhere in the consent form) Having blood drawn may cause: pain (common), a bruise (sometimes), fainting or passing out (not very often), and infection (rare).

31 If the people doing the study are exposed to your blood or body fluids in a way that could give them a disease, your blood may be tested. The tests might check for: hepatitis, HIV (Human Immunodeficiency Virus), or other infections. You and the person exposed would be told the test results. However, your name would be kept private. If your test is positive for hepatitis or HIV, we will tell you how to find counseling. You may want help in understanding what the results mean for you. Will You Find Out the Results of the Research on Your Sample(s)? If results will not be disclosed insert: Neither you, your health care provider, nor anyone in your family, will receive the results of any research done on your sample(s). The results will not be put in your health records. Therefore, results from any research done on your sample(s) will not affect your medical care. This helps protect you and other members of your family from harm that might be caused by this information. If subject has the option of getting results insert: You will have the option to receive or not receive your results. Please check one of the options below: I do want to receive my genetic test results. I do NOT want to receive my genetic test results If you do decide to receive your results the following information is important for you to know: You will get describe what information participants will receive You will only get information that might be useful to you and your doctor. These results will be placed in your medical records. Both your doctor and your insurance provider will have access to the results. You will be told the results after the study is complete. If the results show that a certain treatment might help you, Choose appropriate text: you will be referred/ that treatment will be provided to you by insert name. / Your health insurance should cover / you would be expected to pay for/ the University of Virginia will pay for/ any necessary treatment. You will meet with a genetic counselor before/ both before and after the testing is done. The genetic counselor will explain the possible risks and the results of the name of test. The results of this study may reveal something about the health of some of your family members. Explain what information that would be. You may be encouraged to share this information with your family. Sometimes, a test result may show that one or both of a child s parents is not the real birth parent. If this happens, we will not share this information with anyone, including you. We would only disclose this information if the law said we had to. If results will be disclosed insert: You will get describe what information participants will receive You will only get information that might be useful to you and your doctor. These results will be placed in your medical records. Both your doctor and your insurance provider will have access to the results. You will be told the results after the study is complete.

32 If the results show that a certain treatment might help you, Choose appropriate text: you will be referred/ that treatment will be provided to you by insert name. / Your health insurance should cover / you would be expected to pay for/ the University of Virginia will pay for/ any necessary treatment. You will meet with a genetic counselor before/ both before and after the testing is done. The genetic counselor will explain the possible risks and the results of the name of test. The results of this study may reveal something about the health of some of your family members. Explain what information that would be. You may be encouraged to share this information with your family. Sometimes, a test result may show that one or both of a child s parents is not the real birth parent. If this happens, we will not share this information with anyone, including you. We would only disclose this information if the law said we had to. What If You Change Your Mind About Donating Your Sample(s)? If you decide now that your sample(s) can be kept for research, and later change your mind, you can simply withdraw the sample(s) at that time. To withdraw you will need to write to the Principal Investigator listed on the first page of this form. We will then destroy any of your sample that has not already been used. However, if your sample has been used in research, the information that we have learned will remain in the study, even if you withdraw. Unless you withdraw from the study, permission for researchers to use your sample and to use and share your private health information for this study will never end. What Are Your Other Choices if You Do Not Want To Donate Your Sample(s)? The only choice is not to be in this study/this part of the study. OR You do not have to be in this study/this part of the study. You can get the usual care even if you choose not to be in this study/this part of the study. The usual care would include state appropriate alternative procedures or courses of treatment if any that might be advantageous to the participant. Will You Be Paid For Donating Your Sample(s)? You will not/will be paid to donate your sample(s). If subjects will be paid with money insert the following section. You will be paid $ for donating your sample(s) by indicate the type of compensation-check, gift certificate etc. You should get your payment about insert time frame after donating your sample(s). The income may be reported to the IRS as income. If you owe money to any Virginia state agency, the state can use the money you earn in this study to pay those debts. These state agencies include the UVa Medical Center, VCU Medical Center or a college or university. The money may be withheld to pay back debt for such things as unpaid medical bills, taxes, fines, child support. Even if this happens, the money you earn may be reported to the IRS as taxable income. Will Donating Your Sample(s) Cost You Any Money? No

33 Things for the researcher to consider regarding risk of genetic research Where the genetic study is linked to an already diagnosed disease, the risk to the subject may be minimal, but there may still be some significant risk to the subject s family members. Many risks associated with genetic research are related to breaches in confidentiality. You should consider the mechanisms through which breaches might occur and the consequences of those breaches. Risk is related to the amount of data stored about a subject, the security of the data storage, the more likely linkages, and the seriousness of any condition related to the data. Consider documented correlations or associations that might be outside the study (e.g. APOE-4 and earlyonset Alzheimer s Disease) Keep in mind generally-held public misconceptions as well as scientific realities. Misconceptions are often an important source of potential discrimination. Social risks If the genetic information on this subject were inadvertently disclosed or made public would he/she or a family member potentially be exposed to: a. loss of or increased premiums for health insurance b. loss of or increased premiums for disability insurance c. loss of or increased premiums for life insurance d. loss of employment or promotion w/in employment (Keep in mind that some employers may discriminate on the basis of potential future absenteeism and reduced productivity costs. Even minor conditions may be the basis of employment discrimination) e. social stigmatization f. changes in reproduction plans g. problems with immigration status If there are social risks, state them as specifically as possible. The most common social risk involves insurance risk; therefore consider using the following language with changes as appropriate: Risks to Your Insurance or Family Planning, Once you have been told a test result, you may have to reveal the result when you apply for health, life, disability, or other insurance. This is true whether or not the result is entered into your medical record. Some insurance companies may consider genetic results in making insurance decisions. They may decide not to offer coverage, to limit coverage, or to charge a higher premium for coverage. You may want to review and make any changes in your insurance coverage before testing. However you should know that the Genetic Information Discrimination Act of 2008, along with other Federal Laws, generally prohibits health insurers or health plan administrators from requesting or requiring genetic information of an individual or the individual s family members, or using it for decisions regarding coverage, rates, or preexisting conditions. The law also prohibits most employers from using genetic information for hiring, firing, or promotion decisions, and for any decisions regarding terms of employment. However, this law does not protect your ability to get or keep other kinds of insurance such as life insurance or long term care insurance. If the patient is encouraged to share information with family members, add this paragraph if appropriate: You may be encouraged to share information with other family members. But some family members may not welcome the information. And you may find out some things you didn t want to know as well. For example,

34 you may learn that a family member is adopted. This may sometimes cause relationships in families to change. Other members of your family may also learn things about your health or risk of genetic disease. Psychological risks Could the genetic information involved in this study cause psychological distress due to: a. new knowledge of a disease or predisposition to a disease--especially where there is no treatment b. disclosure of vague or uncertain results c. incidental information (e.g. disease markers, paternity) d. guilt (it is fairly common for parents to feel guilty about passing on defective genes to their children; also subjects who test negative for a condition may feel guilty in relation to afflicted family members) e. family stress; different family members wishing different amounts of information or participation If there are psychological risks, consider using the following language with changes as appropriate: Learning Facts that are Frightening, Hurtful, Stressful to Family Relations, or Other Information that Makes Someone Feel Guilty Some people may be upset knowing that they have a gene that increases the risk for developing insert description. They may feel angry or shocked or deny they have it. They may worry about their health and family. They may feel differently about themselves. They may worry about passing the gene to their children. They may worry about medical costs or insurance. Finding out that one does not carry the gene can be upsetting, too. The person may feel guilt as well as joy. Anyone with these concerns will be referred to a genetic counselor. Community harm Could the genetic information be used to cause a group or community of people to be vulnerable to discrimination based on actual or perceived associations, e.g. Ashkenazi Jews and the BRCA genes, or alcoholism or other addictions within ethnic or cultural groups. If there are community risks, consider using the following language with changes as appropriate: Risks to People Belonging to Certain Ethnic or Cultural Groups Discrimination may occur when people believe that a certain ethnic or cultural group has an increased genetic risk of a disease, disability, or addiction. Someone belonging to that group may become a social outcast. They may even suffer insurance or employment discrimination. There is no way to predict all the possible risks of this research. Genetic research is always changing. We may learn of other physical, social, or psychological risks in the future.

35 1. tissue_genetic_consent_only_template.doc Tissue Genetic Consent Only Template Consent to be in a Research Study for Insert as applicable Specimen Banking/Genetic Research 1. Participant s Name 2. Medical Record # Principal Investigator: insert name, address and phone # Sponsor: What is the Purpose of this Form? This form will help you decide if you want to be in the research study. You need to be informed about the study before you can decide if you want to be in it. You should have all your questions answered before you give your permission, or consent, to be in the study. This is called an informed consent form because it informs you before you sign to give your consent. We encourage you to discuss this with your family and friends. If you do want to be in the study, you will need to sign this form to give your consent. You will get your own copy of this signed form for your records. Introduction You are being asked to provide samples of your describe what is being taken e.g. tissue/blood/saliva to be used for research. Your sample might help doctors learn more about diseases or treatments that might help other people in the future. How Many People Will Take Part in This Study? Up to X people will be in this study at UVA. What Sort of Research Will Be Done On Your Sample(s)? If you are doing genetic research or if you anticipate, anytime in the future, using the banked specimen for genetic you should insert the following: Your sample may be used for genetic research (to learn about diseases that are passed along in families). Describe what information is being sought through this testing here. Participants should be informed of what information may reasonably be expected to result from the use of their sample, including whether the research results will be related to the clinical care of the participants. Your sample(s) may be used by various researchers here at the University of Virginia or elsewhere. Your sample(s) will become the property of (insert name of institution or sponsor). The research may lead to the development of a commercial product or may involve yet undiscovered technologies. There are no plans to pay you if this occurs. If HLA testing will be done on specimen insert the following section.

36 HLA Testing A sample of your blood will be tested for HLA, a form of genetic testing. HLA is a special protein commonly found in the body, especially in white blood cells. There are many different types of HLA. Because of this HLA testing is very good at figuring out things like if a person is a good match as an organ donor, how likely a person is to develop a disease or condition, or paternity testing (being able to figure out the biological parents of a person.) If HLA test results will not be disclosed insert the following section. HLA Test Results The results of the HLA testing will not be put in your medical records, and will not be shared with you, your health care provider or anyone else outside of the study team. If HLA test results will be disclosed insert the following section. HLA Test Results If you would like to know the results of your HLA testing, they will be shared with you by the researchers. In most cases it is not risky or harmful to know your HLA type. It is important that you know that sometimes the HLA result might affect your ability to get or keep some kinds of insurance or it may affect your family relationships. This could make you feel anxious. Also, keep in mind that if you know your HLA type, you would be required, if asked, to share this information with your insurance company even if it is not in your medical record. You may wish to discuss the risks of knowing your HLA type with the researchers before you agree to this testing. If GWAS (genome-wide association studies) may be performed, include the following language. It may be revised to reflect whether the GWAS data will be restricted to the disease under study and related research, or can be used for unrelated research. Genome Wide Association Studies We will also perform a whole genome analysis on your DNA sample. Usually researchers study just a few areas of your genetic code that are linked to a disease or condition. In whole genome studies, all or most of your genes are analyzed and used by researchers to study links to (signify here whether the GWAS data will be limited to the disease under study and related disorders or "many diseases or conditions"). If the data will be sent to NIH or other data repositories, include the information below: In order to allow researchers to share test results, the National Institutes of Health (NIH) and other central repositories have developed special data (information) banks that collect the results of whole genome studies. The NIH or other data banks will store your genetic information and give it to other researchers to do more studies. We do not think that there will be further risks to your privacy and confidentiality by sharing your whole genome analysis with these databanks; however, we cannot predict how genetic information will be used in the future. The information will be sent with only a code number attached. Your name or other identifiable information will never be given to them. There are many safeguards in place to protect your information while it is stored in repositories and used for research. There is a small chance that your genetic information could be shared with others by mistake. In the unlikely event that your information was mistakenly shared, and if it were linked to a medical condition, this could affect your ability to get or keep some kinds of insurance. If family members were to see the information it could also affect them. This could hurt family relationships. It is possible that you could be identified from the sample if someone has another sample from you. The two samples could be matched to then identify you from the sample given for this study.