Nuts and BoltsNuts and Bolts

• Should/can you do a trial?Should/can you do a trial?

• ResourcesResources •• Contracts Contracts

• BudgetsBudgets •• Study team Study team

• SpaceSpace •• Recruitment Recruitment

• Start-upStart-up •• Forms Forms

• Adherence and follow-upAdherence and follow-up

• Money MattersMoney Matters •• Closeout Closeout

Should You Do a TrialShould You Do a Trial

• ExpensiveExpensive

• Difficult (recruitment, blinding, Difficult (recruitment, blinding, adherence, follow-up, regulatory adherence, follow-up, regulatory requirements, etc)requirements, etc)

• Long time to publish - no between Long time to publish - no between group comparisons until the endgroup comparisons until the end

• Often funded by pharma companiesOften funded by pharma companies

Should You Do a Trial, if...Should You Do a Trial, if...

• You are approached by a company…You are approached by a company…– is the question important?is the question important?– is the protocol goodis the protocol good–will you have access to data for publication?will you have access to data for publication?–can you do the trial within the budgetcan you do the trial within the budget

• You are asked to be project directorYou are asked to be project director–% salary support, effort, potential for pubs% salary support, effort, potential for pubs

• You apply to the NIH and get money!You apply to the NIH and get money!

Funding SourcesFunding Sources

• Small trialsSmall trials–NIH - R-03, R-21NIH - R-03, R-21–Specialty organizationsSpecialty organizations• AHA, ACS, ACOG, ADA, etcAHA, ACS, ACOG, ADA, etc• FoundationsFoundations

–Pharmaceutical, device companiesPharmaceutical, device companies

• Large trialsLarge trials–NIH - R-01, P-01, contractNIH - R-01, P-01, contract–DVA, AHCPR, CDC, DODDVA, AHCPR, CDC, DOD–Pharmaceutical, device companiesPharmaceutical, device companies

UCSF ResourcesUCSF Resources

• Senior colleagues in your dept/fieldSenior colleagues in your dept/field

• Experienced trialists and trial staffExperienced trialists and trial staff–Pub Med limited to Clinical TrialsPub Med limited to Clinical Trials–Search on UCSF and topicSearch on UCSF and topic

• UCSF CTSI BREADUCSF CTSI BREAD–designdesign–ethicsethics–statistical issuestatistical issue–database managementdatabase management

ContractsContracts

• Required if trial supported by industryRequired if trial supported by industry

• Must be approved by UCSF Clinical Must be approved by UCSF Clinical Contracts Unit & company’s legal divisionContracts Unit & company’s legal division– lots of puzzling legaleselots of puzzling legalese–you should understand and reviseyou should understand and revise–best to start with UCSF template, revise best to start with UCSF template, revise

and submit to companyand submit to company

• Between UCSF Regents and companyBetween UCSF Regents and company–signed by PIsigned by PI

Elements of a ContractElements of a Contract

• Scope of workScope of work

• Timetable for deliverablesTimetable for deliverables

• Budget and timing of paymentsBudget and timing of payments–get a bolus up frontget a bolus up front–don’t link payment to deliverables out of don’t link payment to deliverables out of

your controlyour control

• Ownership of data and publishing rightsOwnership of data and publishing rights

• Rules for breaking contractRules for breaking contract

• Confidentiality, indemnificationConfidentiality, indemnification

• Patents and inventionsPatents and inventions

BudgetsBudgets

• NIH-style (NIH, VA, AHCPR, CDC)NIH-style (NIH, VA, AHCPR, CDC)–prepared far in advanceprepared far in advance–governed by strict rulesgoverned by strict rules• funds restricted to categoriesfunds restricted to categories• permission for carry-over requiredpermission for carry-over required• certain expenses not allowedcertain expenses not allowed• subject to government auditsubject to government audit

• Pharmaceutical company budgetsPharmaceutical company budgets–prepared just before trial startsprepared just before trial starts–negotiablenegotiable– rules much more flexiblerules much more flexible

Money MattersMoney Matters

• Pre-award managerPre-award manager–help prepare budget and “face” pageshelp prepare budget and “face” pages–help with budget justificationhelp with budget justification–make sure you follow rules/timelinesmake sure you follow rules/timelines

• Post-award managerPost-award manager–pay salaries, buy equipment and suppliespay salaries, buy equipment and supplies–monthly report of expendituresmonthly report of expenditures–projections over life of trialprojections over life of trial

Who is the Study Team?Who is the Study Team?

• Principle investigatorPrinciple investigator

• Project director/clinic coordinatorProject director/clinic coordinator

• RecruiterRecruiter

• Data managerData manager

• Programmer/analystProgrammer/analyst

• StatisticianStatistician

• Quality control supervisorQuality control supervisor

• Administrative assistantAdministrative assistant

• Financial/personnel managerFinancial/personnel manager

How to Hire the Study TeamHow to Hire the Study Team

• Work with your department or Work with your department or unit personnel managerunit personnel manager–write a job descriptionwrite a job description–decide on job series, step, salarydecide on job series, step, salary–post the job at UCSF and advertisepost the job at UCSF and advertise– review resumesreview resumes– interviewinterview–selectselect

Where to Find the Study TeamWhere to Find the Study Team

• Other studiesOther studies

• UCSF employeesUCSF employees

• Recent graduates, studentsRecent graduates, students

• Friends and colleaguesFriends and colleagues

• Chronicle, webChronicle, web

Training the Study TeamTraining the Study Team

• Describe, emphasize and Describe, emphasize and demonstrate the importance of:demonstrate the importance of:–following the protocol/OMfollowing the protocol/OM–meeting recruitment goalsmeeting recruitment goals–complete adherence and follow-upcomplete adherence and follow-up–full outcome ascertainmentfull outcome ascertainment–maintaining participant safety and maintaining participant safety and

confidentialityconfidentiality–ethical conduct/GCPethical conduct/GCP–excruciating attention to detailexcruciating attention to detail

Training Meeting and ManualTraining Meeting and Manual

• Purpose and design of the trialPurpose and design of the trial

• Each measurements and visit procedureEach measurements and visit procedure–methodsmethods– qualified personnelqualified personnel– calibration and testing calibration and testing

• Completing and altering study formsCompleting and altering study forms

• Data entry or submissionData entry or submission

• Safety and ethical issuesSafety and ethical issues

• Certification and training of new staffCertification and training of new staff

Team LeadershipTeam Leadership

• Management training usefulManagement training useful

• You are responsible and the bossYou are responsible and the boss

• Keep your staff happyKeep your staff happy– involvement in the trialinvolvement in the trial–salary, working conditionssalary, working conditions– level of responsibilitylevel of responsibility

• Set an exampleSet an example

• Promote good staff interactionsPromote good staff interactions

• Some staff should be firedSome staff should be fired

SpaceSpace

• ConsiderationsConsiderations– accessibility, parkingaccessibility, parking– design and décordesign and décor– privacyprivacy– clinical needs, special testsclinical needs, special tests– safety measuressafety measures– COSTCOST

• CRCs (separate application)CRCs (separate application)

• Medical spaceMedical space

• Off campus rentalOff campus rental

RecruitmentRecruitment

• Hire an experienced Hire an experienced recruiterrecruiter

• Provide adequate Provide adequate time and moneytime and money

• Monitor resultsMonitor results

• Make changesMake changes– different approachesdifferent approaches–more centersmore centers– longer recruitmentlonger recruitment– change eligibilitychange eligibility

0

20

40

60

80

100

120

140

160

1 2 3 4 5 6

Month

Goal

Actual

RecruitmentRecruitment

• Databases Databases – Kaiser, DMV, HCFA, registriesKaiser, DMV, HCFA, registries

• Referral from providersReferral from providers– hospitalhospital - special sites- special sites– clinicclinic - PPOs- PPOs

• AdvertiseAdvertise– hospital, clinics, special sites, churcheshospital, clinics, special sites, churches– radio, newspaper, TV, internetradio, newspaper, TV, internet– celebrities, leaderscelebrities, leaders

MailingMailing

• TargetedTargeted– administrative, hospital, clinic, pharmacy, administrative, hospital, clinic, pharmacy,

transplant, etctransplant, etc– identify likely eligiblesidentify likely eligibles– use relationship with the list sourceuse relationship with the list source– follow HIPPA and confidentiality rulesfollow HIPPA and confidentiality rules

• MassMass– DMV, Voter Registration, HCFA, private DMV, Voter Registration, HCFA, private

companiescompanies– categorize by age, gender, categorize by age, gender, ++ethnicityethnicity

• EmailEmail

Start-upStart-up

01020

30405060

708090

Effort Time

Start-up

Trial

• ProtocolProtocol

• Operations ManualOperations Manual

• FormsForms

• CHR approvalCHR approval

• HiringHiring

• TrainingTraining

• Database designDatabase design

• ValidationValidation

Forms - A Very Big DealForms - A Very Big Deal

• Define variablesDefine variables

• Determine method of data entryDetermine method of data entry– Data entry by humans - more flexible, more Data entry by humans - more flexible, more

effort for data entry, more prone to erroreffort for data entry, more prone to error– Machine readable forms - form design less Machine readable forms - form design less

flexible, less effort for data entry, fewer flexible, less effort for data entry, fewer errors in data entryerrors in data entry

• Use prior forms - forms librariesUse prior forms - forms libraries

• Pretest, validatePretest, validate

Adherence and Follow-upAdherence and Follow-up

• Monitor ratesMonitor rates

• Obtain contact dataObtain contact data

• Pleasant, professional staffPleasant, professional staff

• Develop personal relationshipsDevelop personal relationships

• Encourage resumption of meds and Encourage resumption of meds and return to follow-upreturn to follow-up

• Cards, small gifts, meetings, partiesCards, small gifts, meetings, parties

Quality ControlQuality Control

• Documented SOPsDocumented SOPs– protocolprotocol– operations manualoperations manual– statistical analysis planstatistical analysis plan

• Training and certification of staffTraining and certification of staff– ethical conduct of researchethical conduct of research– measurementsmeasurements– data entrydata entry

• Performance reviewPerformance review

Quality ControlQuality Control

• Special procedures for quality controlSpecial procedures for quality control– study drugstudy drug– laboratory procedureslaboratory procedures– DSMB reports and other statistical analysesDSMB reports and other statistical analyses– data qualitydata quality• missing, out of range, illogicalmissing, out of range, illogical• variation by site, investigator, staff membervariation by site, investigator, staff member

• Periodic checks of source dataPeriodic checks of source data

• Periodic reports (missing forms/data, Periodic reports (missing forms/data, queries, differences, drift)queries, differences, drift)

CloseoutCloseout

• Final visit and post-trial plansFinal visit and post-trial plans–make final measurementsmake final measurements–say goodbye and thank yousay goodbye and thank you–inform of test resultsinform of test results–?inform of treatment status?inform of treatment status–?inform of trial results?inform of trial results–?make clinical recommendation?make clinical recommendation

SummarySummary

• Trails are costly and complicatedTrails are costly and complicated–get advice from experienced colleaguesget advice from experienced colleagues–use UCSF servicesuse UCSF services• financial, legal, CHRfinancial, legal, CHR• CRCsCRCs• design, ethics, statistical consultationdesign, ethics, statistical consultation• database design and managementdatabase design and management