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					Pilot Studies Nuts and Bolts
Deborah Grady, MD, MPH Professor of Medicine Associate Dean for Clinical and Translational Research UCSF

Pilot Studies
• Small studies aimed at helping you:
– plan the best study possible – determine that the study can be done – get funding for your study

• Distinguish from pretesting of questionnaires or measurements • Phase I and phase II trials
– phase I - determine toxicity – phase II - determine best dose

Why Do a Pilot Study?
• Feasibility
–determine if you can do it

• Logistics
–determine the fastest, easiest, most costeffective way to do it

• Sample size
–estimate rate in placebo group, effect size, variance

• To convince funders you can do it

Feasibility
• Feasibility of recruitment
– obtain data or survey centers, participants – conduct a „pilot trial‟ (with or without control) and measure time, expense of recruitment

• Feasibility of interventions, measures
– can overweight/obese persons perform the 8 yoga postures and practice at home? – will there be side effects? – can participants do 2-h GTT and other tests?

• Feasibility of follow-up, adherence

Logistics and Cost
• What staff are needed?

• How long do visits take?
• Where will ppts park? • Can ppts answer questionnaires while completing GGT? • How much will the trial cost?

Sample Size Estimates
• To determine sample size for full-scale trial
–Rates of outcome in typical participants –Estimate of effect size –Variability of the main outcome

How Big Should Pilots Be?
• “It depends”
• Sample size estimates rarely useful • Traditions and guesses
–NCI phase I trials start with 3 –Pilots for feasibility often 5-20 –Pilots to estimate effect size can be large

• Often depends on resources and time

Do Pilots Need Control Groups?
• “It depends”
• Phase I trials (maximum tolerable dose)
– generally uncontrolled

• Phase II trials (minimum effective dose)
– generally controlled

• Feasibility and logistics
– controls generally not needed

• Effect size/sample size estimates
– controls helpful

Funding for Pilots
• Local institution
– Academic Senate – Research Allocation Program (RAP)

• NIH R03, R21, U34, K awards
• Other
– disease foundations – pharmaceutical companies – mentors

• Can sometimes be done without funding

IRB Approval for Pilots
• Like any study, pilots involving people (or medical records) need IRB approval

• Testing questionnaires, developing yoga postures, etc. that are devised and pretested with advisors and staff generally do not need IRB approval

Nuts and Bolts
• • • • • • Resources • Contracts Budgets • Study team Space • Recruitment Start-up • Forms Adherence and follow-up Money Matters • Closeout

Funding Sources
• Small trials
–NIH - R-03, R-21, R-01 –Specialty organizations/foundations • AHA, ACS, ACOG, ADA, etc • Foundations –Pharmaceutical, device companies

• Large trials
–NIH - R-01, P-01, U-01 –VA, AHRQ, CDC, DOD –Pharmaceutical, device companies

UCSF Resources
• Senior colleagues in your discipline

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

• UCSF CTSI BREAD
–design –ethics –statistical issues –database development and management

Contracts
• Required if trial supported by industry • Must be approved by UCSF Industry Contracts Unit & company‟s legal division –lots of puzzling legalese –you should understand and revise, esp. scope of work –best to start with UCSF template, revise and submit to company • Between UCSF Regents and company –signed by PI

Elements of a Contract
• Scope of work • Timetable for deliverables • Budget and timing of payments
–get a bolus up front –don‟t link payment to deliverables out of your control

• • • •

Ownership of data and publishing rights Rules for breaking contract Confidentiality, indemnification Patents and inventions

Budgets
• NIH-style (NIH, VA, AHRQ, CDC)
–prepared far in advance –governed by strict rules • funds restricted to categories • permission for carry-over required • certain expenses not allowed • subject to government audit

• Pharmaceutical company budgets
–prepared just before trial starts –negotiable –much more flexible

Money Matters
• Pre-award manager
–help prepare budget and “face” pages –help with budget justification –make sure you follow rules/timelines

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

Who is the Study Team?
• • • • • • • • • Principle investigator Project director/clinic coordinator Recruiter Data manager Programmer/analyst Statistician Quality control supervisor Administrative assistant Financial/personnel manager

How to Hire the Study Team
• Work with your department or unit personnel (HR) manager
–write a job description –decide on job series, step, salary –post the job at UCSF and advertise –review resumes –interview –select

Where to Find the Study Team
• Other studies

• UCSF employees
• Recent graduates, students

• Friends and colleagues
• Chronicle, web

Training the Study Team
• Describe, emphasize and demonstrate the importance of:
–following the protocol/operations manual –meeting recruitment goals –complete adherence and follow-up –full outcome ascertainment –maintaining participant safety and confidentiality –ethical conduct of research –excruciating attention to detail

• Formal training and certification of staff

Operations Manual and Training Meeting
• Purpose and design of the trial • Each measurement and visit procedure
– methods – qualified personnel – calibration and testing

• Completing and altering study forms • Data entry or submission

• Safety and ethical issues
• Certification and training of new staff

Team Leadership
• Management training useful • You are responsible and the boss • Keep your staff happy
–involvement in the science –salary, working conditions –level of responsibility

• Set an example • Promote good staff interactions • Some staff should be fired

Space
• Considerations
– accessibility, parking – design and décor – privacy – clinical needs, special tests – safety measures – cost

• CRCs (separate application)

• Medical space
• Off campus rental

Recruitment
• Hire an experienced recruiter
• Provide adequate time and money • Monitor results • Make changes
– different approaches – more centers – longer recruitment – change eligibility

Recruitment
• Databases
– Kaiser, DMV, HCFA, registries

• Referral from providers
– hospital – clinic - special sites - PPOs

• Advertise
– hospital, clinics, special sites, churches – radio, newspaper, TV, internet – celebrities, leaders

Mailing
• Targeted
– administrative, hospital, clinic, pharmacy, transplant, etc – identify likely eligible persons – use relationship with the list source – follow HIPPA and confidentiality rules

• Mass
– DMV, Voter Registration, HCFA, private companies – categorize by age, gender, +ethnicity

• Email

Start-up
• Protocol
• Operations Manual • Forms

• IRB approval
• Hiring • Training

• Database design
• Database validation

Forms - A Very Big Deal
• Define variables
• Determine method of data entry
– Data entry by humans - more flexible, more effort for data entry, more prone to error – Machine readable forms - form design less flexible, less effort for data entry, fewer errors in data entry

• Use prior forms - forms libraries
• Pretest, validate

Adherence and Follow-up
• Monitor rates • Obtain contact data • Pleasant, professional staff • Develop personal relationships

• Encourage resumption of intervention and return to follow-up
• Cards, small gifts, meetings, parties

Quality Control
• Standard Operating Procedures
– protocol – operations manual – statistical analysis plan – data and safety monitoring plan

• Training and certification of staff
– ethical conduct of research – Measurements and other visit procedures – data entry

• Performance review

Quality Control
• Special procedures for quality control
– – – – study drug laboratory procedures DSMB reports and other statistical analyses data quality • missing, out of range, illogical • variation by site, investigator, staff member

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

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

Summary
• Trails are costly and complicated
–get advice from experienced colleagues –get materials used in prior trials –use UCSF services • financial, legal, IRB • CRCs • design, ethics, statistical consultation • database design and management


				
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