CONSENT FORM 12/19/08



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12/19/08 1001 University Place Evanston, Illinois 60201 www.northshore.org CONSENT FORM Phone (224) 364-7100 Fax (847) 570-8011 Intravesical Alkalized Lidocaine for the Treatment of Overactive Bladder (OAB), a Randomized, Prospective Double-blinded Controlled Trial Principal Investigator (name): Frank Tu, MD, MPH Principal Investigator telephone number: (847) 570-2520 Research Coordinator: Kristen Pozolo, BS (847) 570-1755 EXPLANATION OF STUDY: Nature and Purpose of Research Study: You are being asked whether you would be willing to volunteer to take part in this clinical research study because you have symptoms of an overactive bladder. This Consent Form gives information about the study that you will be able to discuss with your doctor. You are being given this information to help you decide if you would like to participate. If you have any questions, you can ask the study doctor and/or staff. The purpose of this study is to test whether a local anesthetic (Lidocaine) placed into the bladder is a rapid, sustained treatment for overactive bladder. The instillation of Lidocaine into the bladder will be compared with the instillation of a placebo (a nonactive substance). Although local anesthetics are used to treat many different pain disorders, they have not been approved for use inside the bladder by the FDA. Previous studies have found they may be a safe treatment for overactive bladder. You will undergo catheterization with instillation of fluid six times during a three week period. Because symptoms of overactive bladder often come and go, you will then be followed for improvement over a one year period afterwards. This study will include 100 subjects total. Of those subjects, 100 will be from NorthShore University HealthSystem. Explanation of Procedures: At an initial screening visit, you will be first asked to complete a basic medical history, focusing on your overactive bladder symptoms. You will have a small catheter placed into the bladder to test for infection or other causes of your symptoms. This screening study will determine if there are contraindications (such as untreated infection, unexplained blood in the urine, or pregnancy) for you to be in the study. Next, you will be asked to keep a diary of your normal EH06-092 Page 1/8 Amend. #6, Rev. dtd. 03/11/08 Consent Form is valid through 12/18/09

urinating patterns, which you will bring to the first treatment visit. The study doctors will perform standard tests of bladder function before the first treatment and also at three weeks after finishing the treatment (urodynamics). These tests include: - measuring if you retain any urine after emptying your bladder - measuring how much fluid your bladder can hold - measuring how fast you are able to empty your bladder - determining what volume of fluid makes you feel the need to void During the treatment part of the study, you will receive either instillation of local anesthetic or a saline solution (sterile salt water). The local anesthetic will have a buffered solution added to it to improve absorption into the bladder (sodium bicarbonate). These solutions will be placed into the bladder using a small bladder catheter. Which of the two solutions you receive will be determined at the first visit by random selection (like flipping a regular coin). Therefore, you will have a 50-50 chance of receiving the local anesthetic solution. This means that 50% of the total patients will not receive treatment but will instead be given the placebo agent consisting of the saline solution. Whether you are receiving Lidocaine or the saline solution, you will be catheterized a total of eight times. These treatments will be scheduled for twice a week for three weeks in the gynecology clinic. This is a double-blinded study, which means that neither you, your doctor or the research staff, will know the identity of the solution you are treated with until after the analysis of the data is completed. (In the event of an emergency, the blind can be broken.) After each week of treatment, you will fill out brief questionnaires at home monitoring any change in your symptoms. We will also ask you to inform us of any unusual side effects you experience from the medication. At three weeks, three months, six months, and one year after completing treatment, you will be asked to return to the clinic for follow-up visits. You will also be asked to fill out additional questionnaires related to your bladder health. Also, at three weeks post-treatment you will undergo the bladder tests (urodynamics) that were done at your first visit again. This will determine if treatment has improved the urine capacity of your bladder. At any time if you are not satisfied with being part of this trial, you may discontinue your participation and discuss further treatment. Alternative Therapy: You do not have to take part in this study for treatment of your bladder problems. Other treatments are: oral medications, or bladder instillation of local anesthetic or other medications. You may choose to have instillation of local anesthetic without participating in this study. You may also choose no further treatment. EH06-092 Page 2/8 Amend. #6, Rev. dtd. 03/11/08 Consent Form is valid through 12/18/09

Your doctor can provide detailed information about your disease and the benefits of the options. You are free to discuss your disease and your prognosis with your doctor. POSSIBLE BENEFITS: This study will allow doctors to learn more about how this drug works in treating overactive bladder. Taking part in this study may or may not make your overactive bladder symptoms better. While doctors hope that this drug will be more useful in treating your disease than the usual treatment, there is no guarantee of this. If this is shown to be helpful, other patients with this disease may also benefit from treatment with this drug. There is the possibility that your condition may become worse while participating in this study. RISKS AND DISCOMFORTS: A. Catheterization: Urodynamics involves bladder catheterization (placing a sterile, narrow tube into your bladder to instill fluids or to remove fluids from the bladder). Instillation of the bladder medications (or placebo) will also require placement of this tube. Bladder infection is an uncommon risk from catheterization that can generally be treated with a few days of oral antibiotics. In addition, you may feel bladder or urethral discomfort, including urgency or frequency while the catheter is in place or while fluids are being instilled into your bladder. These sensations should not last more than a few hours. It is important to point out that half of the women who are in this study will undergo nine catheterizations without receiving any compounds with known medical properties (the placebo half will receive only sterile saline). B. Local anesthetic: The local anesthetic used in this study might have undesired effects. However, doctors do not know all the undesired effects that may happen. Undesired effects may be mild or very serious and can sometimes be life-threatening. Some undesired effects may go away soon after you stop taking the study drug. In some cases, the effects can be serious, long lasting or may never go away. The study doctor will watch you carefully for any undesired effects and will provide treatment for these effects. This may include stopping your participation in the study or giving you other medications. Although local anesthetic is poorly absorbed through the bladder, you may theoretically experience some systemic side effects. Side effects that have been reported by some patients using lidocaine for various medical reasons include confusion, dizziness, drowsiness, headache, constipation, nausea, vomiting, low blood pressure, urethral irritation, tingling sensations, or tremors. Rare, but EH06-092 Page 3/8 Amend. #6, Rev. dtd. 03/11/08 Consent Form is valid through 12/18/09

serious side effects include irregular heart rhythms, heart attack, methemoglobinemia (a serious condition where the blood is less able to carry oxygen to the tissues of the body), or seizures. Due to the investigational nature of this study, there may be other risks that are currently unknown. You should not become pregnant while on this study because local anesthetics could theoretically affect an unborn baby or a pregnant woman. You should also not be breastfeeding an infant/toddler, although the American Academy of Pediatrics does consider lidocaine to be compatible with breast-feeding. You should use effective birth control methods if you can become pregnant and you wish to participate in this study. If you become pregnant during this study, you should notify the study doctor for counseling and possibly to stop your participation in the study. Birth control may not prevent pregnancy; only total abstinence from sexual relations can guarantee prevention of pregnancy. If you suspect your birth control has failed, you should not rely on the result of one or several home pregnancy tests. Rather, you need to promptly contact your study doctor to arrange for more sensitive pregnancy tests. C. Non-treatment: Unfortunately, women receiving the placebo (nonactive substance) may potentially experience persistent or worsening overactive bladder symptoms. There is no evidence that a few months delay in treating symptoms predicts a worse outcome for women with this condition. Though the symptoms are not harmful, we cannot offer additional treatment for them while you are a subject. However, you can withdraw if you become too uncomfortable and receive additional treatment. EXPLANATION OF INVESTIGATOR'S AVAILABILITY TO ANSWER QUESTIONS: The study doctor will answer any questions you have based on current medical knowledge. Any new information or changes in the study that may affect your health or your willingness to continue in the study will be given to you as soon as they become available. CONFIDENTIALITY: If information from this study is published, presented at meetings or placed in a report, your name and other personal information will not be used. Every effort will be made to keep your personal medical information confidential. Your study related information may be examined by other researchers in this study, by the sponsoring organization (Berlex Foundation), by the NorthShore University HealthSystem Institutional Review Board, or by the Food and Drug Administration (FDA). EH06-092 Page 4/8 Amend. #6, Rev. dtd. 03/11/08 Consent Form is valid through 12/18/09

COMPENSATION DISCLAIMER: If you experience an injury/illness because of your participation in this research study, medical treatment for injuries or illness is available through NorthShore University HealthSystem. You and/or your health plan/insurance company will need to pay as no additional funds have been allocated to cover the costs for this treatment. Further information may be obtained from the Research Institute of NorthShore University HealthSystem. PAYMENT FOR PARTICIPATION: You will be paid $10 per visit for a total of $110 for 11 visits. ADDITIONAL COSTS: You should check with your insurance company to ensure that research related treatment is covered under your policy. There may be additional costs to you. EXPLANATION OF ABILITY TO WITHDRAW FROM STUDY: Your participation in this research study is voluntary. If you decide not to participate in this study, you can still receive medical care as usual. If you decide to participate now, you may leave the study at any time. No matter what decision you make, there will be no penalty to you and you will not lose any of your regular benefits. Your doctor may stop this study or your being a part of it without your consent. If this happens, it might be the result of a bad reaction you have to the therapy or new information that your physician learns about the safety or effectiveness of this treatment regimen. YOUR RIGHTS AS A RESEARCH SUBJECT: You may obtain additional information about your rights as a research subject from the Chairperson of the Institutional Review Board (IRB) or the IRB Coordinators, telephone - 224/364-7100. These are the individuals to whom you should report any problems or injuries that may be due to the research study. ******************************************************************************** EH06-092 Page 5/8 Amend. #6, Rev. dtd. 03/11/08 Consent Form is valid through 12/18/09

INDIVIDUAL PROVIDING EXPLANATION: The procedures and/or investigations described in the above paragraphs have been explained to you by (print): Name of Person Explaining Study Signature of Person Explaining Study Date Signed (PRINT) (Sign) (Date) If you have additional questions at any time during the study, you may contact the Project Director, Dr. Tu, at telephone (847) 570-3879. CONSENT TO PARTICIPATE: I understand that the activities will be supervised by Dr. Tu and whomever he may designate as his assistants. I have read this explanation of activities to be followed or have had it read to me. With this knowledge of the nature and purposes of the activities, treatment, the possible attendant risks and discomforts, the possible benefits and the possible alternative methods of treatment, I hereby authorize the performance of the activities described in this consent form. I have read and discussed the explanation of this study with the study director and/or staff. I have had enough time with the study director and/or staff to discuss all of my questions and concerns. I willingly consent to be a part of this study. I will receive a signed and dated copy of this Consent Form. Subject s Name (Please PRINT) Subject's Signature Date Signed EH06-092 Page 6/8 Amend. #6, Rev. dtd. 03/11/08 Consent Form is valid through 12/18/09

Authorization for the Release of Protected Health Information The Federal government created a rule called the Health Insurance Portability and Accountability Act of 1996 (HIPAA). This rule is designed to protect the confidentiality of your protected (private) health information (PHI). Your protected health information is information about you that could be used to find out who you are. For this research study, this includes information in your existing medical records needed for this study and new information created or collected during the study. This Data Privacy Statement explains how your PHI will be used and who it will be given to ("disclosed") for this research study. It also describes your privacy rights, including your right to see your protected health information. By signing the authorization document for this study, you will give permission ("authorization") for the uses and disclosures of your PHI that are described in this document. If you do not want to allow these uses, you should not participate in this study. Note, you will not be allowed to participate if you do not sign this form. If you agree to participate in the research study, your private health information will be used and disclosed in the following ways: The study Investigator and staff will use your medical records and information created or collected during the study to conduct the study. The Investigator will use the study data for research purposes to support the scientific objectives described in the consent form. Your study data may be shared with regulatory authorities in the United States and other countries, and the Institutional Review Board overseeing this study. Study data that does not directly identify you may be published in medical journals or shared with others as part of scientific discussions. Your original medical records, which may contain information that directly identifies you, may be reviewed by the Institutional Review Board overseeing this study, and regulatory authorities in the United States and other countries. The purpose of these reviews is to assure the quality of the study conduct and the study data, or for other uses authorized by law. The Investigator will not disclose PHI to insurance companies unless required to do so by law, or unless you provide separate written authorization to do so. Your medical records and study data may be held and processed on computers. Your personal health information may no longer be protected under the HIPAA privacy rule once it is disclosed by your study Investigator to these other parties. EH06-092 Page 7/8 Amend. #6, Rev. dtd. 03/11/08 Consent Form is valid through 12/18/09

You have the right to see and copy your personal health information related to the research study for as long as this information is held by the study Investigator or research institution. You may cancel your authorization at any time by providing written notice to the study Investigator. If you cancel your authorization, the study Investigator and staff will no longer use or disclose your personal health information in connection with this study, unless the study Investigator or staff needs to use or disclose some of your personal health information to preserve the scientific integrity of the study. The study Investigator will still use study data that was collected before you canceled your authorization. If you cancel your authorization, you will no longer be able to participate in the study. However, if you decide to cancel your authorization and withdraw from the study, you will not be penalized or lose any benefits to which you are otherwise entitled. Your authorization for the uses and disclosures described in this authorization does not have an expiration date. Subject s Name (Please PRINT) Subject's Signature Date Signed EH06-092 Page 8/8 Amend. #6, Rev. dtd. 03/11/08 Consent Form is valid through 12/18/09