HUMAN GENETICS INITIATIVE

Clinical Protocol HUMAN GENETICS INITIATIVE Ancillary Study to A Comparison of Long-Acting Injectable Medications for Schizophrenia (ACLAIMS) National Institute of Mental Health Grant R01-MH081234 and RO1-MH081107-02 Version 1.0 February 16, 2010 Principal Investigators: Joseph McEvoy, MD Scott Stroup, MD, Matt Byerly, MD

TABLE OF CONTENTS 1 Specific Aims... 3 2 Subjects... 3 2.1 Persons eligible for this study include participants in the ACLAIMS study. Each site shall seek to enroll all current participants in the parent trial. Only participants, not participants relatives or other subjects, are to be enrolled in this study Inclusion/Exclusion Criteria... 3 3 Methods... 3 3.1 Blood Sample Collection... 3 3.2 Generation of Patient IDs... 3 3.3 Study Supplies... 4 3.4 Sample Shipping and Processing... 4 4 Human Subjects Issues... 4 4.1 Duration of study and subject s participation... 4 4.2 Full description of risks and measures to minimize risks... 4 4.3 Benefits to subjects and/or society... 5 4.4 Inducements for participation... 5 4.5 Costs to be borne by subjects... 5 4.6 Methods of Recruiting... 5 4.7 Informed Consent... 5 5 Procedures for Consent Form approval... 5 5.1 Consent discussion... 6 2

1 SPECIFIC AIMS The Human Genetics Initiative will result in the creation of cell lines of genetic material from the cohorts participating in the A Comparison of Long-Acting Injectable Medications for Schizophrenia (ACLAIMS) study that will be used in future studies to advance knowledge about schizophrenia.. The NIMH Center for Genetics Studies will create high quality lymphoblastoid cell lines to establish an infinitely renewable source of DNA for subsequent genetic analyses. The specific aims of the project are: a) To collect, prepare, and ship adequate blood samples from ACLAIMS participants with schizophrenia to the NIMH Center for Genetics Studies Cell Repository (Repository). b) To ensure that the confidentiality and rights of the participants are protected. 2 SUBJECTS 2.1 Persons eligible for this study include participants in the ACLAIMS study. Each site shall seek to enroll all current participants in the parent trial. Only participants, not participants relatives or other subjects, are to be enrolled in this study Inclusion/Exclusion Criteria Persons who have been randomized to study drug in the parent ACLAIMS trial are eligible to participate in this Human Genetics Initiative. 3 METHODS 3.1 Blood Sample Collection Blood samples will be collected by site personnel during the visit in which consent for the genetics initiative is obtained or the next convenient subject visit (see Methods of Recruiting in Section 5). Two yellow-top and one purple top tube sample tubes of blood will be collected. The tubes will be shipped to the Center for Genetics Studies following the procedures on the Flow Sheet for Blood Sample Procedures 3.2 Generation of Patient IDs A randomly assigned NIMH ID number and ACLAIMS subject ID will be used to track the vials. The NIMH number will be generated by the Collaborative Studies Coordinating Center according to the specifications of NIMH. The ACLAIMS subject ID is a numeric code. Sites will be provided with 4 ID labels with randomly assigned NIMH ID numbers 3 labels for the blood vials and 1 that goes on the NIMH Genetics Initiative: Clinical Trial Off NIHM collection form (NIHM Collection form). A copy of the NIHM collection form will be kept in the Clinical Binder. This will ensure that monitors can check to see if a blood sample was taken based on the label in the source document binder. Subject identities shall be protected because no direct personal identifiers will accompany the blood samples to the Repository. Detailed instructions for labeling, packaging and shipping blood sample tubes are specified in the Flow Sheet for Blood Sample Procedures 3

3.3 Study Supplies Sites will be provided with kits that include the necessary materials to collect blood samples. Sites will be provided with materials when they have IRB approval. 3.4 Sample Shipping and Processing Each site will ship blood samples in to the NIMH Repository.The NIMH Center for Genetics Studies will create high quality lymphoblastoid cell lines to establish an infinitely renewable source of DNA for subsequent genetic analyses. After the cell lines have been established, clinical data, without patient identifiers, will be transferred to the NIMH Center for Genetics Studies by the Collaborative Studies Coordinating Center. The data will include clinical, diagnostic, laboratory, and therapeutic response data. The link between the genetic material and ACLAIMS data will be made using the coded ID numbers only. No personal identifiers will be attached to the genetic material. Sites will be required to make one sample shipment (with tubes filled with water) to the NIMH Center for Genetic Studies Cell Repository prior to shipping blood samples. This will establish the acceptability of the site s packing and documentation procedures. 4 HUMAN SUBJECTS ISSUES 4.1 Duration of study and subject s participation ACLAIMS participants will provide a blood sample for the Human Genetics Initiative on one occasion. Enrollment will continue for the duration of enrollment in the parent ACLAIMS study. Participants may be asked to submit a second sample if an adequate cell line is not established from the initial sample. (Cell line transformations are successful approximately 99% of the time at the Center for Genetics Studies. A small proportion of samples may be damaged in shipping.) 4.2 Full description of risks and measures to minimize risks There are no more than minimal medical or psychological risks associated with this research. Some people may experience discomfort, bruising, and/or other bleeding at the site where the needle is inserted. Sometimes people get dizzy or feel faint when their blood is drawn. Subjects will be offered comfort and support. An insurance company might consider participation in the study an indication of higher risk because it implies that there is a family history of a genetic condition. This might then hurt participants access to health or other insurance. If participants tell their doctor about participation in this study, this information may then become part of the medical record with this doctor. Insurance companies routinely have access to such records. We will not release information unless authorized by individual participants. Subject privacy will be ensured by generating unique patient IDs for this study as outlined in the Generation of Patient IDs section above. No data with direct patient identifiers will be sent to the Center for Genetics Studies or to other future researchers. The researchers have obtained a Certificate of Confidentiality from the Federal Government. 4

4.3 Benefits to subjects and/or society Subjects will not receive any direct benefit from this project. Individuals who might develop schizophrenia in the future, their family members, and future generations may benefit if genes that lead to such disorders, or genes that predict responses to different medications can be located. 4.4 Inducements for participation It is recommended that subjects be paid $20 for participating in the Human Genetics Initiative. Subjects will not receive any financial benefits from commercial products derived from the data. 4.5 Costs to be borne by subjects There are no costs to subjects for participating in the Human Genetics Initiative. 4.6 Methods of Recruiting The study clinician or study coordinator shall inform already randomized participants of the genetics study during the next scheduled visit after the site is cleared for implementation of the genetics study. Newly enrolling participants in the ACLAIMS trial shall be informed of the Human Genetics Initiative at the Screening Visit and shall be asked to enroll in at the first visit deemed appropriate by the site investigator. Only patients who have been randomized to study drug should participate in the Human Genetics Initiative. Site personnel will be encouraged to contact subjects who have dropped out or completed the study to request their participation in this genetics initiative. Subjects who have withdrawn consent will not be contacted. 4.7 Informed Consent The consent forms used are based on a template provided by the NIMH that are meant to conform to all applicable regulations (Appendix A). The consent form addresses the following: 1. Disclosure that biomaterials (DNA and cell lines) and clinical data (including diagnostic, laboratory, and therapeutic response and adverse event data) will be distributed as a national resource to researchers in the scientific community for genetic analyses; 2. Assurance that such data will be stored and maintained without personal identifiers; 3. Disclosure that analyses of these data will be conducted by other scientists not included on the current research team; 4. Disclosure that there is no plan to provide subjects with any financial benefits from commercial products derived from the data. 5. No plan to inform subjects of individual results. 5 PROCEDURES FOR CONSENT FORM APPROVAL Prior to initiation of data collection and prior to approval to the local IRBs, each Site shall electronically submit to Columbia University its consent form. Columbia University will submit these to NIMH. After approval by the NIMH, the consent form shall be submitted to the local IRBs for approval. The consent form must satisfactorily address items 1-5 above. A template of such a consent form will be provided to each site with highlighted language that should be standard among all sites and therefore should not be modified (Appendix A). 5

Within one week of approval by the Site s IRB, the approved consent form and letter of approval must be submitted to Columbia University, who will then submit to New York State Psychiatric Institute IRB and NIMH. Columbia University will notify participating sites when they can begin enrollment. 5.1 Consent discussion The consent discussion between the clinician/study coordinator and the participant shall emphasize: 1. That the decision to participate or not participate in the genetics study shall not affect participation in the parent study, the care received in the trial, or the care otherwise available. 2. That the data and the biomaterials shall be stored without direct patient identifiers so that participant anonymity will be preserved. 3. That the phenotypic data and biomaterials shall ultimately be shared with the scientific community for genetic analysis. 4. That there is no plan to provide subjects with any financial benefits from commercial products derived from the data. 5. That there is no plan to inform subjects of individual results. 6