AwardeeInstitution/Contract#:JohnsHopkinsUniversity/ME-1303-6016

PrincipalInvestigator(Scharfstein,Daniel,Oscar)

1UpdatedJuly7,2015

PCORI INTERIM PROGRESS REPORT Use continuation pages as needed. Limit 20 pages, not including the Certification page.

Updated on Tuesday, July 7, 2015

Date:07/31/2015

TitleofProject:Sensitivity Analysis Tools for Clinical Trials with Missing Data

TypeofProgressReport: 6-month 12-month 18-month 24-month 30-monthOther(specifyintheboxbelow)

PeriodCoveredbythisReport:02/02/2015to07/31/2015

PrincipalInvestigator&InstitutionUpdatedContactInformation:

PIFirstName: Daniel

PILastName: Scharfstein

PIEmail: dscharf@jhu.edu

PIOfficePhone: 410-955-2420

AOFirstName: Marcy

AOLastName: DeSantis

AOEmail: mdesant9@jhu.edu

AOOfficePhone: 410-614-2635

InstitutionLegalName: JohnsHopkinsUniversity

Address(street,city,state,zipcode):

615NorthWolfeStreet

Baltimore,MD21205

Telephone: 410-955-3067

KeyPatientandOtherStakeholderPartnerContactInformation(uptothree):N/A

Name:

Telephone:

Email:

Name:

Telephone:

Email:

AwardeeInstitution/Contract#:JohnsHopkinsUniversity/ME-1303-6016

PrincipalInvestigator(Scharfstein,Daniel,Oscar)

2UpdatedJuly7,2015

Name:

Telephone:

Email:

AwardeeInstitution/Contract#:JohnsHopkinsUniversity/ME-1303-6016

PrincipalInvestigator(Scharfstein,Daniel,Oscar)

3UpdatedJuly7,2015

MILESTONES UPDATE ExpandonmilestonestatusintheAccomplishmentsandChallengessection.Addadditionalrowsifnecessary.

Recordeachmilestonelabel,name,description,andprojectedcompletiondate,asshowninAttachmentB(MilestoneSchedule)ofyourContract.AllmilestonesinAttachmentBshouldbelistedinColumnsA–D.ColumnE:Checkappropriateboxindicatingmilestonecompletionstatusduringreportingperiod.ColumnF:Selectactualdateofmilestonecompletion.ColumnG:Selectappropriatereasonfordelay/non-completionofprojectedmilestoneduringthespecifiedreportingperiod.Note:Retaininformationregardingmilestonecompletionfromallpreviouslysubmittedreports(e.g.,MilestoneUpdatessubmittedonthe18-monthreportshouldcontaininformationfromthe12-monthreport,andsoon).

ColumnA ColumnB ColumnC ColumnD ColumnE ColumnF ColumnGMilestoneLabel

(e.g.,B-1,etc.)

MilestoneName DescriptionProjectedCompletion

Date

Completed?(Yes/No)

DateCompleted

IfNotCompleted,ReasonforDelay

B-1 Website Expandregistrationonwebsitetoinclude

PCOresearchers

7/31/2014 Yes No 10/31/2014 Chooseanitem.

B-2 AdvisoryBoard ConveneMeeting 7/31/2014 Yes No 7/21/2014 Chooseanitem. C SubmitInterimProgress

ReportInterimProgress

Report7/31/2014 Yes No 7/31/2014 Chooseanitem.

D-1 Casestudies/trainingmaterials

CreatePCO-centeredcasestudyand

trainingmaterials

1/31/2015 Yes No 10/30/2015 Chooseanitem.

D-2 Shortcourses Facilitatetwoshortcourses

1/31/2015 Yes No 1/12/2015 Chooseanitem.

D-3 Adobeconnectsession Adobeconnectsessionwithusers

1/31/2015 Yes No 1/12/2015 Chooseanitem.

AwardeeInstitution/Contract#:JohnsHopkinsUniversity/ME-1303-6016

PrincipalInvestigator(Scharfstein,Daniel,Oscar)

4UpdatedJuly7,2015

D-4 Manuscriptformonotonemissingdata

SubmitcasestudytoPCORfocusedjournal

1/31/2015 Yes No 10/30/2015 Chooseanitem.

E SubmitInterimProgressReport

InterimProgressReport

1/31/2015 Yes No 2/2/2015 Chooseanitem.

F AdvisoryBoard ConveneMeeting 7/31/2015 Yes No 11/31/2015 Chooseanitem. G SubmitInterimProgress

ReportInterimProgress

Report7/31/2015 Yes No 8/21/2015 Chooseanitem.

Clickheretoenteradate.

Yes No Clickheretoenteradate.

Chooseanitem.

Clickheretoenteradate.

Yes No Clickheretoenteradate.

Chooseanitem.

Clickheretoenteradate.

Yes No Clickheretoenteradate.

Chooseanitem.

Clickheretoenteradate.

Yes No Clickheretoenteradate.

Chooseanitem.

Clickheretoenteradate.

Yes No Clickheretoenteradate.

Chooseanitem.

Clickheretoenteradate.

Yes No Clickheretoenteradate.

Chooseanitem.

Clickheretoenteradate.

Yes No Clickheretoenteradate.

Chooseanitem.

Clickheretoenteradate.

Yes No Clickheretoenteradate.

Chooseanitem.

Clickheretoenteradate.

Yes No Clickheretoenteradate.

Chooseanitem.

Clickheretoenteradate.

Yes No Clickheretoenteradate.

Chooseanitem.

Clickheretoenteradate.

Yes No Clickheretoenteradate.

Chooseanitem.

PrincipalInvestigator(Scharfstein,Daniel,Oscar)

5

RECRUITMENT UPDATE

Projectsenrollingparticipantsinatrialmustcompletethissection.LeaveblankifnotapplicableRecordthetargetrecruitmentnumberforyourproject:_______________CompleteTable1toassistinrecruitmenttrackingoverthedurationoftheproject.Retaininformationregardingrecruitmentfromallpreviouslysubmittedreports.Addadditionalrowsasnecessary.ColumnA:recordthedateofeachinterimreport.ColumnB:recordthenumberofparticipantsscreenedforenrollmenttodate.ColumnC:recordthenumberofeligibleparticipantsofthosescreened.ColumnD:recordthetotalnumberofparticipantsenrolledinthestudytodate.ColumnE:recordthenumberofparticipantsprojectedtobeenrolledtodate.ColumnF:recordthetotalnumberofparticipantsretainedtodate.(Ifthenumberofparticipantsretainedislessthanthenumberenrolledinthestudy,pleaseexplainintheAccomplishmentsandChallengessection.)Table1Recruitment

ColumnA ColumnB ColumnC ColumnD ColumnE ColumnF

ReportDate

Screened

Participants

(N)

EligibleParticipants

ofthoseScreened(N)

Recruited

Participantsto

Date(N)

ParticipantsProjected

tobeRecruitedto

Date,PerProject

MilestoneSchedule

(N)

Retained

Participants

toDate(N)

Example6/15/2014

1000 800 650 750 650

PrincipalInvestigator(Scharfstein,Daniel,Oscar)

6

RECRUITMENT UPDATE (Continued)

CompleteTable2bylistingtheRacial/EthnicandGenderbreakdownoftheparticipantsenrolledinyourstudytodate.Ensuretotalsarecalculatedandappropriatelyrecorded.Ifyouhavenotcollectedthesedata,pleaseexplainwhy.

Table2Racial/EthnicandGenderEnrollmentTable*

Race Male(N) Female(N) Total(N)

AmericanIndian/AlaskaNative

Asian

Black/AfricanAmerican

Hawaiian/PacificIslander

White

Multi-race

Ethnicity Male(N) Female(N) Total(N)

Hispanic(Latino/Latina)

Non-Hispanic

*Ifmoredetailedinformationisavailableregardingracial/ethnicsubgroupsfortheparticipantsinyourstudy,pleaseprovidethatinformationinaseparatetable.

PrincipalInvestigator(Scharfstein,Daniel,Oscar)

7

ENGAGEMENT REPORT (Annual report only)

Descriptiveinformationonengagementofpatientsand/orotherstakeholdersshouldbereportedineachannualreport(i.e.,atyear1,year2,etc.butnotat6monthsor18months).Thisreportisintendedtocapturetheperspectiveoftheresearcher(s)onyourteam.Youwillbegiventheopportunitytonominatepatientand/orstakeholderpartnerstoprovideadditionalengagementinformationtoPCORI.Usethelinkbelowtocompletethisreport.YourUsernameisyourPCORIcontractnumber(noletters,dashes,orspaces).Provideyourengagementreporthere: https://live.datstathost.com/PCORI-Collector/Survey.ashx?Name=Engagement_Report_Login Whenyouhavecompletedthequestions,recordyourconfirmationcode:__________

AwardeeInstitution/Contract#:JohnsHopkinsUniversity/ME-1303-6016

PrincipalInvestigator(Scharfstein,Daniel,Oscar)

8UpdatedJuly7,2015

ACCOMPLISHMENTS AND CHALLENGES Use continuation pages as needed. Limit three pages.

Discussanddocumentstudyprogressandallsignificantevents.Inparticular,pleasediscuss:

• Anysignificantchangefromthefundedproposal,includingchangesinthestudyprotocol,engagementplan,endpoints,samplesize,etc.Includereasonsforthesechanges.PleasenotethatyoushoulddiscusschangeswithPCORIprogramstaffpriortoimplementation.Nosignificantchange.

• Progressandaccomplishmentsachievedduringthereportingperiod,withreferencetoplanned

projectactivities,milestones,andplanningfordissemination.

Solvedmethodologicalissuesregardingconfidenceintervalconstructionandintermittent

missingdata.PresentedposterattheFDAORSISymposiumandgaveshortcourseatthe

SocietyofClinicalTrialsAnnualMeetinginArlington,VA.PostedanewRversionofSAMON.

CompletedmanuscriptaboutthemethodologyunderlyingSAMON,whichwillbesubmittedto

theJournaloftheAmericanStatisticalAssociationby8/31/2015.RecordedlectureforPCORIonmethodsforanalyzingstudieswithmissingdata.

• Progressonyourengagementplanduringthereportingperiod,relativetotheactivitiesoutlinedinyourapplication.

Weinteractedinformallywithsomemembersofouradvisoryboardregardingtechnical

issues.

• Challengeswithprojectprogress(e.g.,delaysinIRBapproval,delaysinrecruitmentofsites,participantretentionissues).Haveyouovercomethesechallenges?Ifyes,pleasedescribe.Ifnot,whatresourcesorguidancedoyouneed?

Thegreatestchallengewassolvingmethodologicalissuesregardingconfidenceinterval

constructionandintermittentmissingdata.Sofar,thesesolutionsappearadequate.

o Describeanybarriersthatyouareexpectingtooccurinyourprojectinthenextsix

monthsandwaysyouplantoovercomethem.AccesstoPCO-orienteddatasets.Identificationofvenuesforshortcourses.

Disseminationofmethodsandsoftware.Weplantoworkwithouradvisoryboardto

addresstheseissues.

• SummarizeanysignificantactionstakenbytheIRB,DSMBorotherregulatoryoversightbody

duringthereportingperiod.

Notapplicable.

AwardeeInstitution/Contract#:JohnsHopkinsUniversity/ME-1303-6016

PrincipalInvestigator(Scharfstein,Daniel,Oscar)

9UpdatedJuly7,2015

• Challengeswithpatientandstakeholderengagement.Haveyouovercomethesechallenges?Ifyes,pleasedescribe.Ifnot,whatresourcesorguidancedoyouneed?

WecouldusetheassistanceofPCORItohelpdisseminateourmethodsandsoftware,for

example,throughthePCORIlistserv,socialmedia,newsfeeds,andmethods

meetings/seminars.

• PCORIisinterestedinmonitoringprojectadherencetoPCORI’sMethodologyStandards.YourProgramOfficerwillreviewcompliancewithMethodologyStandardsandworkwithyoutodevelopaplanforfollow-uponallimportantmethodologicalissues.Aspartofthisreport,youmayprovidedocumentationofadherencetoStandardsthatapplytoyourongoingresearch.Youmayincludeadditionaldocumentswiththisreport,forexample,afinalstudyprotocol.

NotApplicable

AwardeeInstitution/Contract#:JohnsHopkinsUniversity/ME-1303-6016

PrincipalInvestigator(Scharfstein,Daniel,Oscar)

10UpdatedJuly7,2015

PROGRESS STATEMENT FOR PUBLIC USE Limit 250 words.

Describenotableprogresstodate,preliminaryresults,orengagement/stakeholderexperiencesusingnontechnicallanguagethatisreadyforpublicuse.(Note:ThisinformationmaybepubliclydisseminatedbyPCORI.)WepostedanewversionoftheRsoftwarepackageSAMONonthewww.missingdatamatters.org

website.

AwardeeInstitution/Contract#:JohnsHopkinsUniversity/ME-1303-6016

PrincipalInvestigator(Scharfstein,Daniel,Oscar)

11UpdatedJuly7,2015

FINANCIAL STATUS UPDATE Limit two pages.

Describeanysignificantdeviationsincostsandbudget,howthosedeviationsaffectedthestudyprogress(e.g.,staffingandcostestimates),andanyanticipatedneedforbudgetmodifications.Significantdeviationsareconsideredanyadjustmentthatexceeds25%ofabudgetcategory.Therehavenotbeenanysignificantdeviationsincostsandbudget.

AwardeeInstitution/Contract#:JohnsHopkinsUniversity/ME-1303-6016

PrincipalInvestigator(Scharfstein,Daniel,Oscar)

12UpdatedJuly7,2015

KEY PERSONNEL EFFORT UPDATE Use continuation pages as needed. Limit one page.

KeyPersonnelchangesinexcessof25%ofcontractedlevelofeffort,mustbereportedannually.

Reporttheindividual’srole,changeinpercentageeffort,andanexplanationforchanges.Ifyouhavemorethanfivechangestoreport,pleaseincludeadditionalinformationunder“ExplanationofChanges.”SendPCORIabiosketchforallnewkeypersonnelworkingontheproject.

XNochangesinkeypersonnel

Name(First,Last) TitleContractedPercentage

EffortActualPercentageEffort

% % % % % % % % % %

ExplanationofChanges: Noteanyproposedchangestokeypersonnelinthenext6months,ifapplicable,andprovideanexplanationforchanges,below.Addrowsasnecessary.Ifyouhavemorethanfiveproposedchangestoreport,pleaseincludeadditionalinformationunder“ExplanationofChanges.”SendPCORIabiosketchforallnewkeypersonnelworkingontheproject.

XNotApplicable

Name(First,Last) TitleContractedPercentage

Effort

ActualPercentage

Effort

% % % % % % % % % %

Explanationofchanges:

AwardeeInstitution/Contract#:JohnsHopkinsUniversity/ME-1303-6016

PrincipalInvestigator(Scharfstein,Daniel,Oscar)

13UpdatedJuly7,2015

PUBLICATIONS UPDATE

REMINDER:Pleasemakesurethatallpublications/communication/mediapiecescontainthefollowingacknowledgementofPCORIfunding:“Researchreportedinthis[work,publication,article,report,presentation,etc.]was[partially]fundedthroughaPatient-CenteredOutcomesResearchInstitute(PCORI)Award(##-###-####).”

Pleasemakesureyourpublicationsthatpresentresearchfindings,conclusionsorothereditorialcontentalsoincludethisdisclaimer:“The[views,statements,opinions]inthis[work,publication,article,report]aresolelytheresponsibilityoftheauthorsanddonotnecessarilyrepresenttheviewsofthePatient-CenteredOutcomesResearchInstitute(PCORI),itsBoardofGovernorsorMethodologyCommittee.”

Inthetablesbelow,recordinformationregardingpublicationsandpresentations(scientificandnon-scientific)relatedtoyourPCORI-fundedresearchthatoccurredasofthereportingdate.Retaininformationsubmittedinpreviousreports.Publicationsand/orpresentationsbyanymemberoftheresearchteam,includingpatientandstakeholderpartners,shouldincludethose:

• Inpreparationtobesubmitted.• Thathavebeensubmittedtoapublication.• Thathavebeenacceptedtoapublication.• Thatarein-press.• Thathavebeenpublished.

a) PeerandNonPeer-ReviewedPublications(e.g.,scientificpublicationsandnon-scientificpublicationssuchas,organizationaljournals,

magazines,newsletters,newspapers,blogs,otherlaypress)

AwardeeInstitution/Contract#:JohnsHopkinsUniversity/ME-1303-6016

PrincipalInvestigator(Scharfstein,Daniel,Oscar)

14UpdatedJuly7,2015

Author(s) Date Title

Type(e.g.,manuscript,abstract,poster,

newspaperormagazine

article,blog,other)

Nameofpublication

URL,ifapplicable

Status(e.g.,inpreparation,submitted,accepted,in

press,published)

PEERREVIEWED

Scharfstein,Rotnitzky,Abraham,McDermott,Chaisson,Geiter

7/26/2015

OntheAnalysisofTuberculosisStudieswithIntermittentMissingData

Manuscript

AnnalsofAppliedStatistics

www.missingdatamatters.org

InPress

Wang,Scharfstein,Colantuoni,Girard,Yan

6/25/2015

InferenceinRandomizedTrialswithDeathandMissingness

Manuscript

Biometrics www.missingdatamatters.org

UnderRevision

Scharfstein,McDermott,Diaz,Carone,Lunardon,Turkoz

8/31/2015

GlobalSensitivityAnalysisofRepeatedMeasuresStudieswithInformativeDrop-out:ASemi-

Manuscript

JournaloftheAmericanStatisticalAssociation

Submitted

AwardeeInstitution/Contract#:JohnsHopkinsUniversity/ME-1303-6016

PrincipalInvestigator(Scharfstein,Daniel,Oscar)

15UpdatedJuly7,2015

ParametricApproach

Colantuoni,Scharfstein,Wang,Needham,Girard

8/21/2015

AccountingforMortalityandMissingDatawhenComparingOutcomesAcrossTreatmentGroupsinRandomizedTrials

Manuscript

AnnalsofInternalMedicine

InPreparation

Scharfstein,McDermott

8/21/2015

GlobalSensitivityAnalysisofClinicalTrialswithMissingPatientReportedOutcomes

Manuscript

ClinicalTrials InPreparation

NON-PEERREVIEWED

Kharazzi,Wang,Scharfstein

4/18/2014

ProspectiveHER-BasedClinicalTrials:TheChallengeofMissingData

Editorial JournalofGeneralInternalMedicine

www.missingdatamatters.org

Published

AwardeeInstitution/Contract#:JohnsHopkinsUniversity/ME-1303-6016

PrincipalInvestigator(Scharfstein,Daniel,Oscar)

16UpdatedJuly7,2015

b) Presentations(e.g.,invitedtalk,localprovidermeeting,webinar,YouTubevideo)

Presenter(s) Date TitleType(e.g.,oral,poster,

YouTubevideo,webinar,other)

NameandLocation(e.g.,conference/meetingnameandlocation,

recordedwebinarwithURL,localmeetingname

andlocation)

Audience,ifknown(e.g.,researchers,patients,clinicians,policymakers,

students,communityorganizations)

Status(e.g.,inpreparation,submitted,accepted,completed)

PEERREVIEWED

NON-PEERREVIEWED

McDermott 8/3/2014 GlobalSensitivityAnalysisofRepeatedMeasuresStudieswithInformativeDropout:ASemi-ParametricApproach

Oral JointStatisticalMeetings,Boston,MA

Researchers Completed

Scharfstein 9/18/2014 GlobalSensitivityAnalysisofRepeatedMeasuresStudieswithInformativeDropout:ASemi-ParametricApproach

Oral AndreiYakovlevColloquium,UniversityofRochester,Rochester,NY

Researchers Completed

Wang 9/24/2014 InferenceinRandomizedTrialswithDeathandMissingness

Oral ASABiopharmaceuticalSectionFDA-IndustryWorkshop,Rockville,MD

Researchers,Practitioners

Completed

AwardeeInstitution/Contract#:JohnsHopkinsUniversity/ME-1303-6016

PrincipalInvestigator(Scharfstein,Daniel,Oscar)

17UpdatedJuly7,2015

Scharfstein 12/8/2014 GlobalSensitivityAnalysisofRandomizedTrialswithMissingData:RecentAdvances

Oral ShortcourseatDemingConference,AtlanticCity,NJ

Researchers,Practitioners

Completed

Scharfstein,Wang,McDermott

1/12/2015 AnalysisofRandomizedTrialswithMissingData

Oral,AdobeConnect ShortcourseatJohnsHopkinsUniversity,Baltimore,MD

Researchers,Practitioners

Completed

Scharfstein 4/27/2015 GlobalSensitivityAnalysisofRandomizedTrialswithMissingData

Poster FDAORSISymposium Researchers,Practitioners,PolicyMakers

Completed

Scharfstein 5/17/2015 GlobalSensitivityAnalysisofRandomizedTrialswithMissingData

Oral ShortcourseatSocietyforClinicalTrials,Arlington,VA

Researchers,Practitioners

Completed

Scharfstein 7/31/15 AnalysisofProspectiveStudieswithMissingData

OnlineLecture JohnsHopkinsUniversity,Baltimore,MD

Researchers,Practitioners,PolicyMakers

UnderEditorialReview

AwardeeInstitution/Contract#:JohnsHopkinsUniversity/ME-1303-6016

PrincipalInvestigator(Scharfstein,Daniel,Oscar)

18UpdatedJuly7,2015

PUBLICATIONS UPDATE (Continued)

c)PeerReviewRejectionNotificationsIfapplicable,provideinformationregardingscientificarticle(s)submittedforpublicationandrejected,duringthereportingperiod.

Author(s) DateRejected TitleType(e.g.,

manuscript,abstract,poster,other)

Nameofpublication URL,ifapplicable

PrincipalInvestigator(Scharfstein,Daniel,Oscar)

19

ADDITIONAL DOCUMENTS All attachments should be combined with this document and submitted to PCORI as one PDF.

Additionally, please complete the “Other Publications” section below, if necessary.

Anydocumentsthatyoufeelarerelevantandnoteworthycanbeshared,suchas:• Copiesofdraftsofinstruments,datadictionaries,educationalmaterials,manuals,orother

projectdeliverables,ifnotalreadydelivered• Abstractsfrompresentationsmadetoprofessionalgroupsorassociations• Summariesofpreliminarydata• Bibliographies• SummariesfromDSMBmeetings• Finalstudyprotocol• Othercommunicationsefforts• Copiesofreportsfromanyconsultantsoradvisors,whereapplicable• Otherdocumentsormaterials,asappropriate

PrincipalInvestigator(Scharfstein,Daniel,Oscar)

20

CERTIFICATION

This document must be certified by the Principal Investigator and the designated Administrative Official (AO).

PrincipalInvestigator:

IcertifythatI,asthePrincipalInvestigator,havereviewedandapprovedthisdocument(andanyassociatedattachments,ifapplicable).PIFirstName:DanielPILastName:ScharfsteinDate:8/21/2015AdministrativeOfficial:

IcertifythatI,asthedesignatedAdministrativeOfficial,havereviewedandapprovedthisdocument(andanyassociatedattachments,ifapplicable).AOFirstName: AOLastName: Date: