CAFE Study IRB Protocol Submission 2002

8/13/2019 CAFE Study IRB Protocol Submission 2002

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\8~\...f{) .J-l )JJ- t/ Uruverslty ofMmnesota 1 s 91017q, 7~

i'J~ Request For The Approval For The Use Of Human Subject~ n Rese rh FED Healt~ an.dBiologi~al Sciences 0R IG,N F F? t;."tiIOnstztutlonal evzew oard ~ ecei~ Version /2001 0') IRe/lAC d ~ Uc cP

Project Title: Efficacy and Tolerability of Olanzapine, Quetiapine


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If Principal Investigator is faculty or staff, a Department bead signature is required.As Department Head, I acknowledge that this research is in keeping with the standards set by mydepartment and I assure that the Principal Investigator has met all departmental requirements forreview and a roval of this research.~. Charles Schulz, M.D. -11.19.01

d

Name of Departm~tHead, or D~ector of Research airvie~ I DateDateCo-Investigators responsibleor, or working on his projectshouldbe isted below.Include any ndividual who will have esponsibility or the consent rocess, irect datacollection from subjects,or follow-up. If thereare more han wo Co-Investigators, lease_attach ddit onalpagescontaining he following infonna~on.

Co-Investigator:Including middle initialand highesLeamed egreeS. Charles Schulz, M.D.

Telephone Number: 612.273.9820 Pager or Cell Phone: noneI Fax: ~-Department Name:

Mailing Address: Department of Psychiatry2 West Building/FUMC-Riverside2450 Riverside AvenueMinnea~olis, Minnesota [email protected] Address:

02-11-2002I Dateiginal Signature o Co-Investigator

Co-Investigators responsible for, or working on this project should be listed below.Include any individual who will have responsibility for the consent process, direct datacollection from subjects, or follow-up. If there are more than two Co-Investigators, pleaseattac~ additional paRescontai~Lng he following inf9rmation.John P. Vuchetich, M.D. Ph.d.o-Investigator:Including middle initialand highestearneddegree 612.273.9801 Pager or Cell Phone:elephone Number:---

I 612.273.7997Fax: University 0 Fairview 0 Other:epartment Name:Mailing Address: Department of Psychiatry2 West Building/FUMC-Riverside2450 Riverside AvenueMinneacolis. Minnesota 55454


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1. What is your research question? (Hypothesis).Pleasenote that thefollowing questions must be answered n lay languageor languageunderstood bya person unfamiliar with your area of research.Area-specific argon should beavoided or explicitly explained.Do not say "seeprotocol".

Schizophrenia affects approximately 1% of the population and accounts forapproximately 2.5% of the total health care expenditures in the UnitedStates. Schizophrenia is characterized by disorders in perception, content ofthought and thought processes (hallucinations, delusions), and extensivewithdrawal of individual's interest from other people and the outside world.People with schizophrenia are not able to distinguish between theirdelusions and realilty. They often have difficulty with cognition and memory.Onset typically occurs in the early to mid-20's for men and in the late-20's forwomen. The disease follows a chronic course with intermittent relapses,which are sometimes due to treatment interruption. It is estimated thatmedical treatment, social security payments, and lost wages due toschizophrenia amount to approximately $48 billion per year in the UnitedStates. Schizophrenia is one of the leading causes of hospitalization in theUnited States.Medical treatment of schizophrenia has been available since the early 1950'swith the discovery of the first antipsychotic drugs (neuroleptics). Thesedrugs represented a breakthrough in the treatment of schizophrenia,ameliorating the acute episodes and possibly preventing or decreasing therisk of occurrence of new episodes. However, these neuroleptics haveconsiderable limitations (e.g., marginal control of positive symptoms, noprevention or control of negative symptoms, no effect on cognitiveimpairment) and are associated with several debilitating side effects {e.g.,risk of extrapyramidal symptoms (EPS), elevation of serum prolactin,prolongation of QTc, and weight gain. More recently a class of medicationsknown as the atypical antpsychotics have been developed. Thesemedications have pharmacological properties such as 5HT2A/C and D2antagonism. To date, these medications appear to have a lower incidence ofserious side effects such as EPSand have been proven safe and efficaciousthrough clinical trials.It has been proposed that atypical antipsychotic medication should be used


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2. What research methods will you use? (How will you ask the question?)Attach a protocol if applicable.

What will the subjects be asked to do?.


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4. Subject Populationa)


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Location of Subjects During Research Data Collection~ (Check all that apply)D Elementary/Secondarychools- Specify:ommunityClinic

I Prisons/Halfway houses

Fairview Southdale HopitalFairview Ridges Hospital- Specify:ther FairviewFacilities

Specifyther HospitalsUniversity Campus (nonclinical)-

Specifyther Special Institutionsd)

e)

t


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justification for unevengenderenrollment.-List criteria for inclusion and exclusion of subjects in this studyInclusionCriteria: 1. Meets DSM IV criteria for schizophrenia disorder,schizophrenia, or schizophrenia disorder.2. Has no previous history of significant pharmacologicaltreatment with an antipsychoticmedication (greaterthan a total of 16 weeks of treatment).3. Between 16 and 40 years of age.4. Psychotic symptoms must have persisted at least onemonth and not more than five years (60 months).5. Able to fully participate in the informed consentprocess, or have a legal guardian able to participate inthe informed consent process.6. Female patients of childbearing potential must beusing a medically accepted means of contraception.7. Score on at least one PANSSpsychosis items (Pi, P2,P3, PS, or P6) greater than and/or equal to and CGISeverity score greater than and/or equal to 4(moderate) at point of maximum severity of illness todate.ExclusionCriteria: 1. Past history of any DSM-IV psychotic disorder withrecovery. Recovery is defined as a period of at leastthree months with no active positive symptoms.2. Patients with heavy co-morbid substance use, wherethe presenting psychotic symptoms are judged by thestudy physician as likely to be substance induced.

3. Female patients who are either pregnant or nursing.4. Known history of mental retardation.5. Non-English speaking ( mastery of English insufficientto participate in study evaluation procedures).6. Serious, unstable medical illness.7. Known allergy to any study medication.8. At serious suicidal risk.9. Participation in clinical trial of an investigational drugwithin 30 days of visit one.4.1)


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Specify:inority Group(s) and Non-English Speakers~ Pregnant Women AppendixC must be attached- Fetus/Fetal Tissue-r== Elderly Subjects (65 and over)Provide rationale for using special populations--These groups are considered "vulnerable" or require special consideration by thefederal regulatory agencies and by the IRB. Suggestion: Researchers should notselect subjects on the basis of discriminatory criteria. Selection criteria that excludeone sex or racial group require a clear scientific rationale for the exclusion (SeeA endix C .Rationale: The goal of this study is to compare the effectiveness of,quetiapine, olanzapine, and resperidone for the treatment ofI~ individuals suffering from a first episode of psychosis. This

study will collect valuable information for physicians andpatients to use while planning treatment.

) 5. Recruitment5. a) Describe bow subjectswill be dentified and recruited.Attach a copy of any and all recruitment materials to be usede.g.advertisements,bulletin board notices,e-mails, etters, or phone scripts.

5. b) Initial ContactDescribewho will make initial contact, and how it will be made. f subjectsare chosen rom records, ndicate who gave approval for use of the records.If records are "private" medical or student records, provide the protocol,consent orms, letters, etc. for securing consentof the subjectsof the records.Written documentation or the cooperation/permission rom the holder orcustodian of the records should be attached. (Initial contact of subjectsidentified through records search must be made by the official holder of therecord, i.e. primary physician, therapist, public schoolofficial.)


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5. c) Is the study sponsoroffering any ncentive connectedwith subjectenrollment or completion of the study (i.e. finders fee, recruitment bonus,etc.) that will be paid directly to the researchstaff~ No 0 Yes. f yesdescribe.

5. d) Will subjects receive nducementsbefore or rewards after the study?0 No ~ Yes. f yes, leaseescribe.Pleasenote that this information must he ncluded n the consentorm, under heheading "Compensation, and not in tIle "Benefits" section.Also, paymentsormultiple visitsshould beproratetL

5. e) Will the subjects be charged for research elated procedures? f yes, explaincharges, ncluding estimatedamounts. This information must be specified nthe consentdocument.

~ No DYes. Iryes,please escribe.

6. Risks and Benefits


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6. a)Does the Research Involve:_;;k~ck all that applv)

Any surgical processIgj Administration of drugs, chemical, or biological agents,or devices.AttachAppendix E

Major changes in diet or exerciseUse of private records (medical or educational records)- Possible invasion of privacy of subject or familyDenrivation of Dhvsiolo ical reQuirements such as nutrition or sleepManipulation of psychological or social variables such as sensory deprivation,social isolation, psychological stresses

~ Any probing or personalor sensitivenformation n surveysor interviews~ Use of a deceptive echnique,e.g.,placebo,-louble-blind, etc. (suggestion: fdeception s part of the experimental design, he protocol must nclude adebriefing procedure, which will be followed upon completion of the study orupon withdrawal of a subject. Attach a description of the debriefing protocol

and any related materials.)Presentationof materials which subjects might consideroffensive, hreatening,~ "~~g ::a~in~ Specify:ther risks

6. b) Describe he precautions that will be taken to minimize the risk to thesubjects.

Administration of physical stimuli (beyond what is described on the SocialandBehavioral ~~~es form)


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6. c) Why are the risks and inconveniencesmentioned above reasonable?What is the expectedscientific yield from the project? Please ustify the risksin relation to the anticipated benefits o the subjects, and in relation to theimportance of the knowledge hat may reasonablybe expected o result fromthe research.

Benefits of ParticipationList any anticipated direct benefits o participation in this researchproject.If none, state that fact here and in the consent orm. The benefit of receivingtreatment is not necessarilya benefit o participation in the researchproject.That distinction is central to the informed consentprocess.

7. Biological SamplesBlood drawing, marrow biopsy sampling, biopsy of other tissues, etc.If samplesof body fluids or tissuesare taken as part of this researchproject,state how much and how often the samplesare taken. The consent ormmust nclude lay term equivalents or the amounts, e.g. easpoons tc. Pleasedistinguish procedures hat are diagnostic from procedures hat areperformed solely or research.


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Patients will have their blood drawn at screening, month 3, month 6, andthe final visit. Approximately two tablespoons of blood will be drawn.I Hair samples (small amounts) will be collected for Radioimmunoassay forthe detection of substances of abuse. These samples will be collected at.visits screen, 6 month, and end of study.

7. b) Will DNA be collected?~ No 0 Yes. f yes,attachAppendix .

7. c) Will tissue/bloodsamplesbe stored with identifiers?~ No DYes. If yes,attachAppendixD.

8. Care of subjects in case of an accidentSelect rom one of the following compensation ptions isted below. This language must beincluded in the consent orm. If a specialcontract to pay for research elated injuries exists,attach documentation or IRB record.)D Non-sponsor-fundedompensation

In the event hat his research ctivity results n an injury, treatmentwill be available, ncludingfirst aid, emergencyreatment nd ollow-up careasneeded.Care or such njuries will be billedin the ordinary manner, o you or your nsurance ompany. If you think that you havesufferedaresearchelated njury let the studyphysicians now right away.

~ Sponsorundedcompensation:In the event hat his research ctivity results n an injury, treatmentwill be available, ncludingfIrst aid, emergencyreatment nd ollow-up careasneeded. Care or such njuries will be billedin the ordinarymanner, o you or your nsurance ompany. The sponsor f the studyhassomefunds available o pay for care or injuries resulting directly from being in this study. If you hinkthat you havesuffereda researchelated njury and that you maybe eligible for reimbursementfsomemedicalcare costs, et he studyphysiciansknow right away.

D If the preferred injury compensation anguage s unacceptable o the studysponsor, he following alternative languagemay be used:Undersomecircumstanceshe sponsor f the study will pay for care or injuries esultingdirectlyfrom being in the study. If you want nformationabout hosecircumstances r if you hink youhavesuffereda researchelated njury let the studyphysiciansknow right away.


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9. Confidentiality of DataDescribe provisions made o maintain confidentiality of the data.

Where will the data be kept and for how long will it be kept?

The data will be retained for a minimum of fifteen ears.

What security provisions will be used?Who will have accesso the collecteddata?The study documentswill be kept secure. The investigator and study staff will haveaccess o the data. Accesswill be provided for the sponsor's monitoring visits. Uponre uest, he Universi of Minnesota IRB and FDA will be allowed access.

9. d) Will data identifiying the subjectsbe made available to anyone other thanthe Principal Investigator, e.g.,FDA, study sponsor?0 No ~ Yes. Please xplainbelowand n the consentorm.

Will the data be part of the medical chart or other permanent record?~ No 0 Yes. Please xplainbelowand in the consentorm.

I IExpedited Review0.


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After careful consideration of risks and review of the expedited review categories ithas been determined that this research fits the precise requirements ofcategory # -of the "Expedited Review" provision of 45 CFR 46, (see page vii.).The research could be considered of "minimal risk" to participants based on thosei guidelines. (Note: Most research will not fit the categories for expedited review.)The decision to route the study via expedited review process will be determinedupon review of the completed application by the IRB.

11. Informed Consent Process11. a) Prepare and attach a consent orm for IRB review.Pleasesee he sample consent orm and follow it carefully. Do not submitsponsor prepared forms without editing the form to include IRB standardlanguage.See he IRB Web site for the informed consent utorial:www.research.umn.edu/subiects.htm.

11. b) Describe what will be said to the subjects to introduce the research.Do not say "see consent orm". Write the explanation in lay language.Hyouare using telephonesurveys, elephones cripts are required.

11. c) What questions will be asked to assess he Subjects' understanding?Pleaseanswer how you will assess ubjects' understanding of the consentprocess.Questions requiring "yes/no" answersdo not do that very well.Pleaseask subjects o explain the purpose of the study to you along with therisks and the henefits o themselves s participants. Their answers o thesequestionsshould allow you to determine if they understand he study andtheir part in it. If they do not understand, nformed consenthas not beenachieved even f the subjectssigned he consentdocument.

The informed consent process for this study will include a formal procedllre


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11. d) In relation to the actual data gathering, when will consentbe discussed nddocumentationobtained?(e.g., pre-operatively, or severaldays before?)Be specific.Written consent will be obtained prior to all study procedures.

1~" Will the investigator(s)be securing all of the informed consent?~ Yes D No. If no, please name the specific ndividuals who will obtain informedconsentand include their job title and a brief description of your plans to train theseindividuals to obtain consentand answersubjects' questions.)I IYou have reached the end of this form. Please make sure that you have responded to every question on thisapplication (even if your response is "not applicable"). Submit 12 copies plus the original for Full Review, and 3copies plus the original if you are requesting Expedited Review. Please send the application to:Research Subjects' Protection ProgramsIRBD528 Mayo Memorial BuildingMMC 820420 Delaware Street S.E.Minneapolis, MN 55455See the meeting "Meeting Dates and Deadlines" page on the Research Subjects' Protection Programs' Webpage: httR://www.research.umn.edu/subiects/index.html to find out the date of the meeting at which yourapplication will be reviewed. If you have any questions, please call us at 612-626-5654.


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Research Staff are any personnel ou wish o be ncluded n correspondenceelated othis studye.g. studycoordinators.Name: Ruth M.ThomsonDepartment Name: University U Fairview Other:Address:

)Ambulatory Research CenterDepartment of Psychiatry606 24th Avenue SouthSuite 602/Fairview Professional BuildingMinneapolis, Minnesota 55454

I TeleDhone Number: I 612.627.4823E-mail: I [email protected]

0 Check here if this is Fairview SystemResearch not Universityfaculty staff s u den ).


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Peer Review -Is this research subject to review by another Committee?(If so complete the requested information)IIt is the responsibility of the PI to secure the appropriate approval from theseCommittees and document that approval to _the RB.

Committee Date ofSubmission---Institutional Animal Care and Use Committee (IACUC) Not Applicable

Cancer Protocol Review Committee (CPRC) Not ApplicableAll University Radiation Protection Committee Not Applicable

Not Applicableonflict ManagementCommittee-Nursing ResearchCommittee Not ApplicableNot Applicableeneral Clinical ResearchCenterNot Applicablether IRB (name)(i.e., if you areparticipating in amulticenter trialwhich requires theapproval of otherIRB's)Pendingther (specify) Dean's Review/Conflict ofInterest Review/DepartmentalReview


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~-..Jo./erability of Olanzapine, Quetiapine and Risperidone in the Treatment of First i

DesignOverview

is a randomized, double-blind, flexible dose, multicenter study of up to 400 patients24 centers meeting DSM IV criteria for a first episode of a non-affective

psychotic disorder (schizophrenia, schizo affective disorder, schizophreniform disorder).Ranqomization will be equally distributed to one of three groups':'olanzapine (2.5-20mg/day) , quetiapine (100-800 mg/day), and risperidone (0.5-4 mg/day).3.2. Rationale for Study Design, Doses and Control GroupsThe study includes two principal phases, and a third optional continuation phase. Phase 1is a screening phase, where patient eligibility is determined. Phase 2 is a 52-week doubleblind treatment phase. Drug will be initiated at the lowest possible dose in the dose range,and will be titrated according to a protocol, based on clinical response. During phase 2,study visits will occur at weekly intervals during the first 6 weeks of treatment, every twoweeks from week 6 to week 12, and then monthly.All patients will receive a standardized 5 session psychosocial intervention that will provideeducation about psychotic disorders and the treatment of psychotic disorders, and addresstreatment adherence.

3.2.1. Phase 1During phase 1 study subjects will participate in initial study evaluations to determine:

and to collect baseline clinical information. Study1 of 3 weeks. To determine eligibility2 the study physician must. review t results of all screening evaluations.

criteri III be discontinued at VO, and VO--

phase 1

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3.2.3. .Visit IntervalsBelow are the allowed and recommended visit intervals:

Phase 1: Screening 1-21 days 2 days" Phase 2: VO-V5 5-9 days 7 days

"-,II ~IIII ~ , -

3.2.2. Phase 2 .Phase 2 is a 52-week double blind, randomized, treatment phase of the study. Subjects willhave weekly visits from visit 1-6, biweekly visits for visits 6-12, and then monthly visitsthereafter.


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Storage and Inventory ManagementAll product Will be monitored in a secure, limited access area at controlled roomtemperature.

and notifying theat the site falls

site up to its

Quintiles will be responsible for'monitoringstudy drug inventory atdistribution centerbelow its re-order point,respective target level).The Quintiles interactivestudy drug rep.lacement re-orderingThe Quintiles IVR system willexpired 60 days prior to theexpiratfon at the sites andprevent a subject

drug asdrug

date to

Specific procedures for usingManual to be distributed at site

~) 3.4.1.3.The investigator, his/her designee or a hospital pharmacjst must maintain an adequaterecord of the receipt and distribution of all trial supplies using the Drug Accountability Form.These forms must be available for inspection at any time. Trial drug prescription, dispensingand compliance will be captured on the case report forms and will be source validated byQuintiles monitors.

3.4.2. Doses and Treatment Regimens3.4.2.1. Dosing

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--ml~~ t~"l~~retion of the clinician with a minimal period between dose increases of 48 hours.Dose increases should be made based on cli~ical response and tolerability, and it isrecommended that the length of the dosing intervals be increased if the subject experiencesmedication side effects. The recommended initial target dose is 2 study pills BID (e.g;BID of olanzapine, 200 BID quetiapine, or 1 mg BID of risperidone). The maximum dose is-8 capsules a day administered in a BID schedule. BID dosing must be maintained, and it isrecommended (but not required) that the larger dose be given in the evening when the splitdoses are not equal. Dose decreases may be at any time and at any dosing increment atthe discretion of the study clinician.


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',,",,:;, -~,\.

Efficacy and Tolerability of Olanzapine, Quetiapine and Risperidone in the Treatment of.fir~tEpisodePsychosis: A Randomized Doui)le Blind 52 Week Comparison -', "".-,In many cases the subject will enter the study on antipsychotic treatment. Here, the clinicianmay chose to simultaneously decrease the prior antipsychotic and increase the studyantipsychotic (e.g. cross-titrate the medications). Less frequently, the clinician may chose toabruptly stop the prior antipsychotic and initiate the study antipsychotic. The studyphysician should use his or her best clinical judgment when making decisions abouttransition from prior antipsychotic to the study antipsychotic.The following initial dosing schedule is recommended,but th~ clinician should individualizetreatment in each ~ubiect based on toler~bilitv and clinic~1 response:

3'.4.2.2. Discussion of Dosing DesignThe dosing range was chosen to allow clinicians maximal flexibility in dosing eachantipsychotic medication in first episode patients. ~h~posing:trange1t.akes4trit'Q\thejfa'cco4Pf

usually respondq~'c ~~~O:"{ &$;,::,~-Q,-,Gj;;"'.ed1~o~andwill be more likely to develop adverseeffects if the highest dose range of the antipsychotic medication is used. 1::/J,e~taai:b;g:~a5"S~

the..riskof ~acut~ ~dverse~ffects, and to max}mi.~~ init.i,al;t,oJ"~,(~bijitY,9f,e;ach",~eq).g,~ti9,n.i ore rapid

-.,c..,~". ...;titr~~~on ra.te,couldinfl~te discontinuation rates due to acute adverse effects, and thus

Documents

CAFE Study IRB Protocol Submission 2002