Bees -ers ML[CIURNREIRN PES

la UNIVERSITY OF PENNSYLVANIAIRESEARCH SUBJECT

INFORMED CONSENT FORM & HIPAAAUTHORIZATION FORM

Protocol Title: Investigational Link Between Uncharacterized

Environmental Exposure and Acquired BrainInjury

Principal Douglas Smith, MDInvestigator: 3 Floor Silverstein

3400 Spruce St.Philadelphia, PA 19104

Emergency Randel Swanson, DO, PhD

conict: |

cC Why am | being asked to volunteer?

You are being invited to participate in a research study because you haveexperienced an uncharacterized environmental exposure. This study will helpdetermine whether any symptoms you may have experienced are a result of thatexposure, along with monitoring how you proceed through prescribed therapiesand treatments. This study is sponsored by the United States Government. Yourparticipation is voluntary which means you can choose whether or not you wantto participate. If you choose not to participate, there will be no loss of benefits towhich you are otherwise entitled. Before you can make your decision, you willneed to know what the study is about, the possible risks and benefits of being inthis study, and what you will have to do in this study. The research team is goingto talk to you about the study, and they will give you this consent form to read.You may also decide to discuss it with your family, friends, or family doctor. Youmay find some of the medical language dificult to understand. Please ask theinvestigator and/or the research team about this form. Ifyou decide to participate,you will be asked to sign this form. Your doctor may be an investigator in thisresearch study. As an investigator, your doctor is interested both in your clinicalwelfare and in the conduct of this study. Before entering this study or at any timeduring the research, you may want to ask for a second opinion about your carefrom another doctor who is not an investigator in this study. You do not have to

participate in any research study offered by your doctor.

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« What is the purpose of this research study?

The University of Pennsylvania's Department of Neurosurgeryis interested inevaluating individuals who have experienced an uncharacterized environmental

exposure. By examining these individuals, will aim to:+ Determine the connection,if any, between the number of exposures

(along with descriptions of the exposure) and the symptoms thatindividuals reported.

«Follow how individuals are responding to prescribed therapies and

treatments.

« Compare the health of individuals to those of individuals with more well-

known medical conditions, such as traumatic brain injury.«Identify what pre-existing factors, if any, cause individuals to be affected

more negatively following uncharacterized exposure.«Recruit and enroll individuals who have not experienced an exposure to

act as the control group. The examinations performed on these individuals

oO will serve as a reference point when evaluating individuals who have

undergone exposure.

How long will | be in the study?This project will enroll approximately 35-50 subjects who experienced theunknown environmental exposure. Our department will review your history and

physical exam findings during your initial and follow-up visits, including responseto rehabilitation at the time you were diagnosed. As part of your of care, you will

have evaluations at baseline, 1 month, 3 months, 6 months, 12 months, and

annually after exposure for five years. Initial participation is required if you

consent, however, subsequent time points are voluntary based on your desire toparticipate. This includes specific collection of data at each time point. Forexample, if you feel comfortable participating in the blood draw portionofthestudy and not the imaging, it is up to your discretion.

co

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Additionally, this study will enroll 50-70 healthy control subjects (matched in age,c sex, race, and education) for reference during examination

What am | being asked to do?

You are being asked to take partin a study on individuals who have beenthrough an environmental exposure. When you come to Penn for your firstappointment, your doctor will review your medical history thoroughly, including:

« Demographics«History of Environmental Exposure and following symptoms+ Past Medical and Surgical History«Medication Review — your current medications at the time of your initial

doctor visit and newly prescribed medication for treating symptoms afterenvironmental exposure

«Findings of your past examinations (e.g.. physical examination, imaging,lab work, etc.) related to your environmental exposure

@ «Details of therapy prescribed for your environmental exposure«Follow-up reports from al of your prescribed therapy«Your work status andyour return to work plans.

Your doctor will ask you to provide a small blood sample at the time you arerecruited to the study and every time you come in for a follow-up appointment (1month, 3 months, 6 months, 12 months, and annually for § years after yourexposure). Your initial workup will also include a comprehensive set ofneuropsychological testing, aimed to evaluate your cognitive abilities.

Twenty (20) mL (about 17s tablespoons) of blood will be obtained during theinitial visit in blood collecting tubes exclusively for research purposes. Duringsubsequent visits, ten (15) mL (about 1 tablespoon) of blood wil be collected forresearch purposes. These samples will be collected by placing a needle in yourvein by a medical professional with appropriate training to draw, process and

co handle human blood products. Your blood will be stored indefinitely and used forfuture research. During the inital visit, 2 out of the tubes will be specificallyV: 03.22.2018 30f16

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drawn for DNA (one) and RNA (one). Subsequent blood draws will only occur for@ non-genetic testing purposes (two tubes per time point).

As a part of this study, you will also be asked to have an MRI scan of your brain.Your MRIs will be performed at the Hospital of University of Pennsylvania. Moreinformation on MRI scans and associated effects can be found in the next sectionof this document. Women of childbearing potential will have a serum or urinepregnancy test.Here is a table of time points:Table 1: Timing of Blood Collection and Neuroimaging

Cohort Tmonth| 3 months| 6 month | 12 month| Annuallyafter | after | after | after| xSys

Exposure| Exposure| Exposure|Exposure| afterexposure

Collection of X X X X Xclinical data asspecified above[wrx[x xX Tx7XTX|

@ Blood draw for XgeneticpurposesDNA/RNA

Blood draw for |X X x X X Xnon-geneticpurposes

(Serum/Plasma

Based on the timingof exposure and imaging review, it may not be necessary forYou to complete every time point visit Should this be the case, the investigatorwill decide which time points to collect

What are the possible risks or discomforts?

There will be minimal risk to you in this study, since there will not be anytreatment decisions made with the information collected. The greatest isk to youis the potential release of protected health information, but this risk is very smallThe University of Pennsylvania wil protect your records so that your name,

co phone number, and all other identifiable information will be kept private. Someadditional risks are involved when donating blood samples. The risks of bloodV: 03222018 40t16

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drawing include bruising, bleeding, infection, possible fainting, and rarely, nervec damage. Lastly, as described above, there is a very small risk of medical

complications from spending an extra 12 minutes on the MRI table each time youhave an MRI. Some of the MRI pulse sequences and equipment components arenot FDA-approved, but are considered to pose no more than minimal risk

Your blood could be used for genetic research. There are certain risksassociated with genetic analysis. These harms include stigmatization andinsurability. The results of the genetic testing performed by the tissue bank wilnot be recorded in your medical record.

There is a Federal law, called the Genetic Information Nondiscrimination Act(GINA), which generally makes it legal for health insurance companies, grouphealth plans, and most employers to discriminate against you based on yourgenetic information. This law may protect you in the following ways:

«Health insurance companies and group health plans may not request yourc genetic informationthatwe get from this research.

«Health insurance companies and group health plans may not use yourgenetic information when making decisions regarding your eligibility orpremiums.

«Employers with 15 or more employees may not use yourgeneticinformation that we get from this research when making a decision to hire,promote, or terminate you when setting the terms of your employment.

«All health insurance companies and group health plans have had to followthis law since May 21, 2010. All employers with 15 or more employeeshave had to follow this law since November 21, 2009.

Be aware that this new federal law does not protect you against geneticdiscrimination by companies that sell fe insurance, disabilty insurance, or long-term care insurance.

co ‘There may be other risks that are not known at this time. Tell the studyinvestigator or study staff right away if you have any problems.V: 03222018 50f16

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" What is an MRI?MRI (Magnetic Resonance Imaging)

A type of scan that uses radio waves to take detailed pictures. You will be askedto lie on an MRI table where the technologist will place a coil on the part of yourbody to be studied. You will be provided a blanket for comfort and earplugs sincethe MRI does make loud banging noises. You will still be able to hear someSound to ensure you can communicate with the technologist and can follow anydirection given throughout the MRI scan. The technologist will slowly slide youinto the MRI magnet where radio waves wil be transmitted into you. Your bodywill give off radio waves which will be picked up by the coils and made intodetailed pictures

MRI RisksFlying Objects: The known risks associated with this study are minimalImplanted medical devices and metallic foreign fragments inside your body may

eo pose a risk if you were to enter the MRI magnet room. Therefore, questions.regarding medical and work history will be asked prior to your exam. Thegreatest risk is a magnetic object flying through the air toward the magnet andhitting you. To reduce this isk, we require that all people involved with the studyremove all magnetic metal from their clothing and all magnetic metal objects fromtheir pockets. No magnetic metal objects are allowed to be brought into themagnet room at any time except by approved personnel. In addition, once youare in the magnet, the door to the room will be closed 5 that no oneinadvertently walks into the room.

Magnetic Fields Health Risks Statement: There is no known health riskassociated with exposure to magnetic fields during an MRI. There are minimalrisks from the loud noise associated with the MRIscanner and from thediscomfort of lying on a hard surface. We shall provide you with protectiveearplugs as necessary and make every attempt to ensure your comfort with

. blankets, etc. during your ime in the scanner.

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Pregnancy: Although there are no known risks related to MRI on pregnantCc womenora fetus, there is a possibility of yet undiscovered pregnancy related

disks,Incidental Findings Clause: This MRI is not a clinical scan. It is possible that

during the course of the research study, the research staff may notice an

unexpected finding(s). Should this occur, the finding(s) will be considered by the

appropriate personnel and the PI will inform you if necessary. These possible

finding(s) may or may not be significant and may lead to anxiety about yourcondition and to further work-up by your physician.

What if new information becomes available about the study?During the course of this study, we may find more information that could be

important to you. This includes information that, once learned, might cause youto change your mind about being in the study. We will notify you as soon aspossible if such information becomes available.

« What are the possible benefits of the study?During the course of this study, we may find more information that is beneficial toyou. We also may be able to use information gained from the study to createtargeted therapies and treatments for you and others who have been exposed.

‘You may not get any benefit from being in this research study.

What other choices do | haveif | do not participate?

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The choice to let us collect and store your blood and other medical informationc for research purposes is up to you. No matter what you decide to do, it will not

affect your care. Your blood and other de-identified medical information will be:used only for research and will not be sold. If you decide now that your blood andother medical information can be collected for research, you can change yourmind at any time. Just contact us and let us know in writing that you do not wantus to use your blood samples, or other information for research. Then the bloodwill be destroyed, and no longer used for research.

Will | be paid for being in this study?

‘There will be no monetary compensation for participation in this study.

Will | have to pay for anything?

There are no costs to you for participating in this study. You are stil responsiblefor any deductibles or applicable co-pays for routine office visits, scans and bloodwork thatwould occur even if you were notin the study.

What happens if | am injured from being in the study?

We will offer you the care needed to treat injuries directly resulting from taking part inthis research. We may bil your insurance company or other third partes, f appropriate,forthe costsof the care yougetfor the injury, but you may also be responsible for some.of them.

There are no plans for the UniversityofPennsylvania to pay you or give you othercompensation forthe injury. You do not give up your legal rights by signing this form.

youthinkyou have been injured as a resultof taking part n tis research study, tel theperson in chargeof the research study as soon as possible. The researcher's name andphone number are listed in the consent form.

When is the Study over? Can | leave the Study before it ends?

This study is expected to end after all participants have completed all visits, andc all information has been collected. This study may also be stopped at any time

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by your physician, the Department of State, or the Food and Drug Administration« (FDA) without your consent because:

«The Primary Investigator feels itis necessary for your health orsafety. Such an action would not require your consent, but youwill be informedif such a decision is made and the reason forthis decision.

«You have not followed study instructions.

«The Sponsor, the study Principal Investigator, or the Food andDrug Administration (FDA) has decided to stop the study.

If you decide to participate, you are free to leave the study at anytime.Withdrawal will not interfere with your future care.

What information about me may be collected, used or sharedwith others?

The following personal health information will be collected, used for research,Cc and may be disclosed during your involvement with this research study:

«Name, address, telephone number, medical record number and date ofbirth

«Personal and family medical history«Information from a physical examination that generally also includes blood

pressure reading, heart rate, breathing rate and temperature:«Current and past medications or therapies«Results and reports from any imaging studies performed (eg. MRI, etc.)

Why is my information being used?

Your information is being used by the research team to contact you during thestudy. Your information and resus of tests and procedures are used to:

+ Dothe research+ Oversee the research

co «See ifthe research was done right

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Who can see or use my information? How will my personalc information be protected?

The following individuals may use or disclose your personal health information for

this research study:

«The Principal Investigator and the Investigator's study team«Authorized members of the workforce of the University of Pennsylvania

Health System (UPHS) and the School of Medicine, and University ofPennsylvania support offices, who may need to access your information in

the performance of their duties (for example: for research oversight andmonitoring, to provide treatment, to manage accounting or billing matters,etc).

As part ofthe study, the Principal Investigator, the study team and others listed

above, may disclose some of your personal health information, including the

results of the research study tests and procedures. This information may bedisclosed to The Office of Human Research Protections, a regulatory and safety

oversight organization.

c We will do our best to make sure that the personal information obtained during

the course of this research study will be kept private. However, we cannot

guarantee total privacy. Your personal information may be given out if required

by law.If information from this study is published or presented at scientific

meetings, your name and other personal information will not be used.

Once your sample or other medical information is collected, it will not be labeled

with your personal information. Each person in the study gets assigneda studynumber, and only this number gets attached to the blood samples. Only yourdoctor and the research team will know which samples are yours at the research

center. Testing of your blood will be conducted at laboratories within the

University of Pennsylvania Health System (UPHS). Inorderto keep accurate

accounts of identifying information, visits, and research data an electronic.medical record will be used as described below. If results of the research done

using your blood or medical information are presented or published, your name

C and identifiable information will not be used.

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c All documents regarding your participation in the study will be strictly confidentialand keptin a secure location in the University of Pennsylvania'sNeurosurgery Clinical Research Division. Only personnel authorized by theprincipal investigator will have direct access to the blood samples. Your personalidentifying information will only be released with your express written permissionor by IRB approval. Samples and all records associated with samples will belabeled only with a numeric code. Sample labels will contain no donor personalidentifiers.

The Principal Investigator or study staff will inform youifthere are any additionsto the list above during your active participation in the trial. Any additions will besubject to University of Pennsylvania procedures developed to protect yourprivacy.

Electronic Medical Records and Research Results

c What is an Electronic Medical Record and/ora Clinical Trial ManagementSystem?

An Electronic Medical Record (EMR) is an electronic version of the recordofyourcare within a health system. An EMR is simply a computerized version ofa papermedical record,

Adinical trial management system (CTMS) is used toregister your informationas a participant in a study and to allow for your research data to beenteredistored for the purposes of data analysis and any other required activityfor the purpose of the conduct of the research.

Ifyou are receiving care or have received care within the University ofPennsylvania Health System (UPHS) (outpatient or inpatient) and areparticipating in a University of Pennsylvania research study, information relatedto your participation in the research (i. laboratory tests, imaging studies and

co clinical procedures) may be placed in your existing EMR maintained by UPHS,

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Information related to your participation in clinical research will also be containedc in the CTMS.

If you have never received care within UPHS and are participating in a Universityof Pennsylvania research study that uses UPHS services, an EMR will becreated for you for the purpose of maintaining any information produced fromyour participation in this research study. The creationofthis EMR is required forYour participation in this study. In order to create your EMR, the study team willneed to obtain basic information about you that would be similar to theinformation you would provide the first time you visit a hospital or medical facilty(i.e. your name, the name of your primary doctor, the type of insurance youhave). Information related to your participation in the study (i. laboratory tests,imaging studies and clinical procedures) may be placed in this EMR.‘Once placed in your EMR or in the CTMS, your information may be accessible toappropriate UPHS workforce members that are not part of the research team.Information within your EMR may also be shared with others who are determined

o by UPHS to be appropriate to have access to your EMR (e.g. health insurancecompany, disability provider, etc.).

Who, outside of the School of Medicine, might receive myinformation?

As part of the study, the Principal Investigator, the study team and others listedabove, may disclose your personal health information, including the ress of the

research study tests and procedures. This information may be disclosed to thoselisted below:Oversight organizations:«The Food and Drug Administration«The Office of Human Research Protections«The United States Department of State:

Once your personal health information is disclosed to others outside of UPHS orc the School of Medicine, it may no longer be covered by federal privacy protection

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regulations. The Principal Investigator or study staff will inform you if there areoc any additions to the lst above during your active participation in the trial. Any

additions will be subject to University of Pennsylvania procedures developed toprotect your privacy.

How long may the School of Medicine use or disclose mypersonal health information?

Your authorization for use of your personal health information for this specificstudy does not expire.

Your information may be held in a research database. However, the School ofMedicine may not re-use or re-disclose information collected in this study for apurpose other than this study unless:«You have given written authorization«The University of Pennsylvania's Institutional Review Board grants

permissionC «As permitted by law

Taking Back Your Permission to Use or Disclose Your Personal HealthInformation:

To take back your permission to use odisclose your personal health informationyou must write to your study investigator at the address listed on Page 1 of thisconsent form. If you do this, you will no longer be allowed to be in this study. Anyinformation that has already been collectedatthe time you take back yourpermission will be kept and, where the law allows, your personal healthinformation, will continue to be used by Douglas H. Smith, MD or other partiesinvolved with the study. No new data wil be collected about you after youwithdraw from the study.

Rights to Your Data:You may have the right to access, correct and make a copy of your medicaland/or clinical study records as allowed by applicable privacy laws. You may ask

oc to see your records by requesting such records from Douglas H. Sith, MD or

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the facility where the study is being conducted. However, to ensure the valid© results of the study, you agree that you may not be able to review or make a

copy of some of your records related to the study until after the study has beencompleted.

When you, or your legal representative, sign this document, you agree to theaccess, collection, processing and transfer of your personal health information asdescribed in this informed consent document. If you do not sign this form, youcannot be in the study.

Can| change my mind about giving permission for use of my information?

Yes. You may withdrawortake away your permission to use and disclose yourhealth information at any time. You do this by sending written notice to theinvestigator for the study. If you withdraw your permission, you will not be able tostay in ths study.

oO What if | decide not to give permission to use and give out myhealth information?

‘Then you will not be able to be in this research study.

You will be given a copy of this Research Subject HIPAA Authorizationdescribing your confidentiality and privacy rights for this study.

By signing this document, you are permitting the School of Medicine to use anddisclose personal health information collected about you for research purposes.as described above.

Who can | call with questions, complaints or if I'm concernedabout my rights as a research subject?

If you have questions, concerns or complaints regarding your participation inthis research study or if you have any questions about your rights as a researchsubject, you should speak with the Principal Investigator listed on page one of

& this form. If a member of the research team cannot be reached or you want to

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talk to someone other than those working on the study, you may contact theco Office of Regulatory Affairs with any question, concems or complaints at the

University of Pennsylvania by caling (215) 898-2614.

When you sign this form, you are agreeing to take part in the following portionsof the research study that you designate below. . This means that you haveread the consent form, your questions have been answered, and you havedecided to volunteer. Your signature also means that you are permitting theUniversity of Pennsylvania to use your personal health information collectedabout you for research purposes within our institution. You are also allowing theUniversity of Pennsylvania to disclose that personal health information tooutside organizations or people involved with the operations of this study.

1 agree to the collectionof data from my medical record for research purposes.

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1 agree to my imaging data to be used for research.

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1 agree to the collection of blood samples that will be processed for genetictesting purposes.

Hyves Ono

1 agree to the collection of blood samples that will be processed to plasma andserum for non-genetic testing purposes.

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Acopyofthis consent form will be given to you

Mac Lents Jub bzo|zoe>« Name of Subject (Please Print) Signature of te

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puss Swann Jiilllbe, Gfz0/20@Name of Parson Obtaining Signature Die

ConsentT Print)

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