Approval Date: July 22, 2009 Approved Consent Version No.: #1 PI Name: Patti Gravitt IRB No.00000778

JOHNS HOPKINS BLOOMBERG SCHOOL OF PUBLIC HEALTH INFORMED CONSENT DOCUMENT

Study Title: The Natural History of HPV in Perimenopause Principal Investigator: Patti E. Gravitt, MS, PhD, Associate Professor of Epidemiology IRB No.: 778 PI Version Date:

Version 4; 6/30/09

What you should know about this study • • • •

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• •

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You have been asked to join a research study. This consent form explains the research study and your part in the study. Please read it carefully and take as much time as you need. You are a volunteer. You can choose not to take part and if you join, you may quit at any time. There will be no penalty if you decide to quit the study. Your decision to participate in this study or not will have no impact on your care at your doctor’s office or by your doctor. You will not be subjected to any experimental procedures or drugs as a result of participating in this study. No medical care, or test results will be provided to you as a study participant. Participating in the study is not a substitute for routine gynecologic care. Your gynecologist will be responsible for your cervical cancer screening. During the study, we will tell you if we learn any new information that might affect whether you wish to continue to be in the study. You can join this study if you are a woman and • you are 35 – 60 years old • you are not currently pregnant • you still have your uterus (have NOT had a hysterectomy) • you have no history of organ transplant • you have never been diagnosed with HIV If you are eligible and want to participate in this study, you must provide written consent before taking part in any study activities.

Page 1 of 9 Patti E. Gravitt, MS, PhD, Associate Professor of Epidemiology Version 4; 6/30/09

Approval Date: July 22, 2009 Approved Consent Version No.: #1 PI Name: Patti Gravitt IRB No.00000778

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If you want to enroll in the study but your doctor is ready to examine you before the consent process can be completed, we will ask you to sign a consent form for the collection of cervical specimens only. We will complete the consent process after your exam. If you change your mind, we will discard your specimens.

Purpose of research project We want to learn about human papillomavirus (HPV) infection in women as they age through menopause. HPV is a common virus that is picked up through sexual contact. Rarely, it can cause changes to a woman’s cervix (opening to the womb) that can lead to cancer. Little is known about the course of HPV infection in women over the age of 35. We want to study HPV infection in women who are age 35 to 60 to accomplish these specific aims: • • •

To study the course of HPV infection during the perimenopausal transition To see how often a new HPV infection is detected and how long the infection lasts in older women To identify factors associated with detection and clearance of HPV

To achieve our study goals, we plan to enroll a total of 1500 women. Why you are being asked to participate You may have been identified as a possible study participant through review of Johns Hopkins Women’s Health Clinic schedules. Clinic schedules list the names and dates of birth of patients with scheduled appointments. Because you are age 35 – 60, • •

you may have received an invitation in the mail to enroll in the study and a follow up call from a member of the study team You may have been approached in the clinic waiting area by a member of the study team.

Alternatively, you may have called us after seeing one of our brochures or posters or after talking to a friend or your gynecologist. Procedures If you agree to be in the study: Page 2 of 9 Patti E. Gravitt, MS, PhD, Associate Professor of Epidemiology Version 4; 6/30/09

Approval Date: July 22, 2009 Approved Consent Version No.: #1 PI Name: Patti Gravitt IRB No.00000778

a) You will be asked to come to your gynecology clinic or one of the Johns Hopkins Hospital General Clinical Research Centers (GCRC's), for a total of 5 study visits, including the enrollment visit. Study participation will occur over a two year time period with visits spaced approximately 6 months apart. Every effort will be made to coordinate with your schedule of routine care to minimize the number of extra visits necessary for study participation. b) At the time of enrollment, you will be given a schedule for your study visits. There will be a two month window within which to complete each visit. You will get a reminder postcard in the mail 1 month prior to the two month window. It will prompt you to call us to schedule your appointment. If you are due for an annual gynecologic exam, we will advise you to call your doctor’s office to schedule your appointment and notify us of the date and time of your appointment. The study nurse will meet you at the clinic for your appointment to ensure that study specimens and data are collected. These visits will be covered by your insurance because you are seeing your doctor for routine GYN care. When you come for study only visits the study nurse will schedule your appointment and neither you nor your insurance company will be charged. a) At each visit, three (3) cervical/vaginal specimens will be collected for study purposes only. These specimens will be collected during a speculum exam performed by your gynecologist, the study nurse, or one of the collaborating gynecologists practicing at your clinic location. This exam will be like the speculum exam you would have as a part of your annual exam and may be completed at the same time that you have your annual exam. You will be seen in a private exam room and given a gown and sheet for cover up. You will be asked to lie down on an exam table and place your feet in stirrups. A speculum of the smallest size possible will be placed in your vagina. The speculum allows the doctor or nurse to see your cervix (the opening to your womb). The doctor or nurse will first obtain a sample of your cervical fluids using a soft sponge that is about the size of your pinky fingernail. This sponge will be placed at the opening to the cervix and allowed to absorb cervical secretions for 30 seconds. Next, the doctor or nurse will touch a q-tip swab to the vaginal wall to collect vaginal discharge to determine the pH of the vagina. Your doctor will then proceed with your regular exam by taking a pap smear, if one is due, using a soft plastic “broom” and a brush. A pap smear is a test for cervical cancer that is part of your routine annual gynecologic exam. Page 3 of 9 Patti E. Gravitt, MS, PhD, Associate Professor of Epidemiology Version 4; 6/30/09

Approval Date: July 22, 2009 Approved Consent Version No.: #1 PI Name: Patti Gravitt IRB No.00000778

You have probably had a pap smear done many times in your life. After your pap is collected, a third study specimen will be obtained using another soft brush to test for HPV. The time that you are actually on the exam table will be less than 5 minutes. There will be no extra cost to you for any tests done for study purposes only. b) At each visit we will record your weight, height, waist circumference, and the date of the first day of your last menstrual period. We will ask your doctor to provide a brief summary of your gynecological exam on a check off form. c) At your first , third and fifth study visit the study nurse will collect 1 2 blood samples (2 – 4 tsps) We may use the blood for other HPV tests, blood cell count, and/or hormone tests. d) At each study visit you will be asked to complete an interviewer administered survey. For the enrollment, or first survey, we will ask questions about the medicine you take now or have taken in the past. We will ask you about your Pap smear and HPV testing history, your reproductive and sexual history, and your smoking and alcohol history. This survey will take about 45 minutes to complete. We will conduct the survey in a private place in clinic or you may schedule a telephone interview at a time that is convenient for you. The completed survey form will be identified by your study ID only – a number - not your name. At each follow up visit you will be asked to complete an interviewer administered survey asking you questions about what has changed since the previous visit. The follow up survey will take approximately 10 minutes to complete.

▼ Recruit

Cervical brush (HPV test) Cervical secretion (sponge test) Vaginal pH (q-tip swab to vaginal wall) Questionnaire ▼ ▼ ▼

Baseline ▲

6 months

12 months ▲

18 months

▼

24 months ▲

Annual gynecologic exam including pap smear Blood test Figure 1. Samples to be collected at each scheduled visit assuming enrollment occurs at an annual visit. Page 4 of 9 Patti E. Gravitt, MS, PhD, Associate Professor of Epidemiology Version 4; 6/30/09

Approval Date: July 22, 2009 Approved Consent Version No.: #1 PI Name: Patti Gravitt IRB No.00000778

e) We will ask you to tell us your address, phone numbers, e-mail address if you have one, as well as the same information for another person we can contact if we cannot reach you directly. Risks/discomforts You may feel uncomfortable with some of the survey questions. You should know that your name and contact information will not appear anywhere on the survey form. If you complete the survey in the doctor’s office we will conduct the interview in a private place. The pelvic examination may be a little uncomfortable and you may have some minimal spotting because of the brushes used to obtain specimens. Drawing your blood may cause some soreness and rarely a bruise may develop. Benefits There is no direct personal benefit to you from participating in this study. What we learn from the study may benefit other women as they age through menopause. Payment To thank you for being in our study, we will give you a small gift worth about $10.00 when you come for the first 4 visits and $50.00 when you complete the final study visit. Confidentiality All research projects carry some risk that information about you may become known to people outside the study. Johns Hopkins has rules to protect information about you. Federal and state laws also protect your privacy. This part of the consent form tells you what information about you may be collected in this study and who might see or use it. The people working on the study will collect information about you. This includes things learned from the procedures described in this consent form like the results of your pap test and your doctor’s summary of your speculum exam. We will collect, store and analyze the results from tests conducted in our research lab. We will collect and store your name, address, Page 5 of 9 Patti E. Gravitt, MS, PhD, Associate Professor of Epidemiology Version 4; 6/30/09

Approval Date: July 22, 2009 Approved Consent Version No.: #1 PI Name: Patti Gravitt IRB No.00000778

date of birth, and telephone number. You will be asked to respond to surveys and answer questions about private details of your personal life. Be assured that the information we collect from you throughout your involvement in the study will be kept strictly confidential. Your survey responses and lab test results will be identified only by your unique study ID. Your name will not appear anywhere on the survey responses, lab results, or any specimens. Study data will be stored in secure, password protected databases at the Johns Hopkins Bloomberg School of Public Health. Your identifying information – name, address, and telephone number - will be stored in a separate location, under double lock and key and in a stand-alone password protected database. Generally, only people on the research team will know that you are in the research study and will see your information. The research team will see your information as we collect, store and analyze it to achieve our study goals. Sometimes other people at Johns Hopkins may see some of the information we have collected about you. This is generally limited to people from the Office of Research Subjects at the Johns Hopkins Bloomberg School of Public Health who review research studies to ensure the safety of research participants. Sometimes people outside of Johns Hopkins may need to see the information we will collect about you for this study. Examples include government groups and safety monitors. This is generally limited to people from our sponsoring institution, The National Cancer Institute, who may audit us under the provisions of our research grant. We will use and allow access to your information only as described in this form. We try to make sure that everyone who needs to see your information keeps it confidential – but we cannot guarantee this. Two years after the last subject has enrolled, the patient identifiers (names) will be removed from the database. The de-identified information will be stored indefinitely. If you withdraw from the study, we will stop collecting and storing new information about you, but we will continue to use, store, and allow access to the information collected prior to withdrawing from the study as described above.

Page 6 of 9 Patti E. Gravitt, MS, PhD, Associate Professor of Epidemiology Version 4; 6/30/09

Approval Date: July 22, 2009 Approved Consent Version No.: #1 PI Name: Patti Gravitt IRB No.00000778

We cannot do this study without your permission to use and allow access to your information as described above. You do not have to give us this permission. If you do not, then you may not join this study. Biological specimens The cervical and blood specimens collected from you during this study are important to science. You will not own the biological specimens after you give them to the study. You will not receive any financial benefit from any product or idea created by the investigators using the data or materials collected from you. Cost of participation in the study There will be no charge to you or your health insurance provider for any extra, or study only visits. Biological specimens are processed at the Johns Hopkins Bloomberg School of Public Health and collaborating research laboratories. There will be no charge to you for lab tests conducted for research purposes. What happens if you leave the study early? Your participation in this study is strictly voluntary. You may stop participating in the study at any time. Participating or not participating in the study will have no impact on your care at this office or by your doctor. There is no penalty or adverse consequence to you as a result of leaving the study early. What if you are enrolling in the study but your gynecologist is not a Hopkins affiliated provider? You can complete your enrollment and follow-up visits at the General Clinical Research Centers at Johns Hopkins Hospital or Bayview Medical Center or at any of the participating clinics sites depending on the availability of space and research staff. These visits will be for study purposes only and will not be a substitute for routine gynecologic care. The study visits will be in addition to your routine GYN visits. The research nurse will perform the speculum exam and collect the study specimens. When you consent to participate in the study we will ask you for permission to contact your GYN provider for the results of your paps obtained during the 2 year study period as well as any follow up if you have an abnormal pap. Page 7 of 9 Patti E. Gravitt, MS, PhD, Associate Professor of Epidemiology Version 4; 6/30/09

Approval Date: July 22, 2009 Approved Consent Version No.: #1 PI Name: Patti Gravitt IRB No.00000778

What if you don’t have health insurance or lose your health insurance during the study period? If you don’t have or lose your health insurance during the 2 year study period, you may continue to see us for study only visits. The study nurse will perform the speculum exam and collect study specimens as described in this consent form. We are not funded to provide for your routine cervical cancer screening in the event that you are or become un-insured at any time during the 2 years that you are a study participant. However, we will encourage you to contact your local health department for information on obtaining affordable cervical cancer screening. We will not be able to collect study specimens when you are seen at a health department clinic. We will have to schedule a separate exam at one of our sites for a study visit. If you have insurance at the time of study enrollment but become uninsured before completing the study, you may choose not to continue in the study, however, losing your insurance will not make you ineligible to continue to participate in the study. You should ask the principal investigators listed below any questions that you may have about this research study. You may contact the investigators at any time during the study or in the future if you have questions about the study. Who do I call if I have questions or problems? •

If you have any questions or concerns about your participation in this study, please call Dr. Patti Gravitt, the principal investigator of the study at 443-287-6179 or Dr. Anne Burke, co-investigator of the study at 410-550-3060.

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Call or contact the Johns Hopkins Bloomberg School of Public Health IRB Office if you have questions about your rights as a study participant. Contact the IRB if you feel you have not been treated fairly or if you have other concerns. The IRB contact information is:

Address:

Johns Hopkins Bloomberg School of Public Health 615 N. Wolfe Street, Suite E1100 Baltimore, MD 21205 Telephone: 410-955-3193

Page 8 of 9 Patti E. Gravitt, MS, PhD, Associate Professor of Epidemiology Version 4; 6/30/09

Approval Date: July 22, 2009 Approved Consent Version No.: #1 PI Name: Patti Gravitt IRB No.00000778

Toll Free: Fax: E-mail:

1-888-262-3242 410-502-0584 [email protected]

What does your signature on this consent form mean? Your signature on this form means: • • •

You have been informed about this study’s purpose, procedures, possible benefits and risks. You have been given the chance to ask questions before you sign. You have voluntarily agreed to be in this study.

________________________

Print name of Adult Participant

________________________ Print name of Person Obtaining Consent

_____________________________

Signature of Adult Participant

Date

_____________________________ Signature of Person Obtaining Consent

Date

Give one copy to the participant and keep one copy in study records

Page 9 of 9 Patti E. Gravitt, MS, PhD, Associate Professor of Epidemiology Version 4; 6/30/09

Principal Investigator: Patti E. Gravitt, PhD Title of Research Project: The Natural History of HPV in Peri-menopause CHR #: 778

Consent for Storage of Biological Specimens Cervical cell and blood samples will be collected during your participation in this study as part of the research aims. We will store the samples until the end of the study (10 years from now) and use them to meet our research objectives as described in this consent form. We would also like to store any part of the specimen that is left over to use for other research during the study period and in the future. After the end of the study, with your consent, the samples may be stored indefinitely in a biospecimens repository to be made available for future research that is performed after our study has ended. Possible uses include other studies related to cervical cancer as well as studies not related to cervical cancer but that might contribute to the body of knowledge about the health of women in this age group. The Principal Investigator will decide whether or not your specimens are appropriate for use in other research projects. We may share your biological specimens with other researchers. Before your biological specimens are put to any other use not related to this research project, the proposed new use will be reviewed and approved by an Institutional Review Board (IRB). The IRB is a group of doctors, scientists, and community members. It reviews research and protects the rights and welfare of research subjects. You will not be contacted prior to future use of your biological specimens unless you request it. We will keep your specimens for the 10 year study period and indefinitely with your consent. If we complete our research and no longer need to keep your specimens, we will destroy them. We will also destroy the specimens if we lose our funding for storage. You may participate in the study but decline storage of your biological samples for uses other than those specified in the HIP Study consent. In this case, your samples will be tagged and discarded after the primary HIP study test result has been obtained. If you agree to storage of your biological material for other research you may withdraw your consent at any time. If you want to withdraw your samples from storage, contact Dr. Patti Gravitt at 443-287-6179. You may also call the Office for Research Subjects at 1-888262-3242 or FAX (410) 502-0584. You can also write a letter to: OFFICE FOR RESEARCH SUBJECTS Room E1100, JHSPH 615 N. Wolfe Street, Baltimore, MD 21205

HIP Study: CHR 778, Dr. Patti Gravitt Consent Form V3 post review 11 6 08

Your specimens will be labeled with a special code. Your name will not appear on the biospecimen label. Shared specimens will not be accompanied by any information that would identify you as their source. Neither you nor your doctor will receive research information or test results from the research. Research information and test results will not be placed in your medical record or used in your care. Choices for Future Research Use Please read each statement below and think about your response carefully. Check either “yes” or “no” for each statement. Do you agree to (circler ‘YES’ or ‘NO’ for each): YES

NO

Storage of your samples to use for future research on cervical cancer?

YES

NO

Without further contact? If no, with contact to ask permission to use the sample for a specific study? YES NO

YES

NO

Storage of your samples for future studies related to any health related issue (for example, menopause, hormones, heart disease, diabetes,).

YES

NO

Without further contact? If no, with contact to ask permission to use the sample for a specific study? YES NO

YES

NO

Share your samples with other investigators outside of Johns Hopkins?

YES

NO

Without further contact? If no, with contact to ask permission to use the sample for a specific study? YES NO

After completion of specimen storage consent form, obtain signatures separately for this consent on the following page.

HIP Study: CHR 778, Dr. Patti Gravitt Consent Form V3 post review 11 6 08

If you have read this document and you have been given the chance to ask any questions about storing your specimens now or at a later time, please sign your name below. PRINT NAME OF SUBJECT: __________________________________________

Signature of Subject or Legally Authorized Representative

DATE

Signature of Person Obtaining Consent

DATE

(This section should be completed when the subject is unable to read or write.) If this consent has been read and explained to you and you have been given the chance to ask any questions about storing your specimens now or at a later time, please sign or make your mark below. PRINT NAME OF SUBJECT:__________________________________________________

Subject’s Mark or Signature

DATE

Signature of Person Obtaining Consent

DATE

Signature of Witness (Must be different than the person obtaining consent.)

DATE

HIP Study: CHR 778, Dr. Patti Gravitt Consent Form V3 post review 11 6 08