Presentation on theme: "Protocol Feasibility and Operationalization Framework"— Presentation transcript:
1Protocol Feasibility and Operationalization Framework Beth Harper, BS, MBAPresident, Clinical Performance Partners, Inc.
2Overview This will be a highly interactive session We will introduce you to new ways of thinking about the study feasibility / acceptance processPlease share and contribute (and keep an open mind!)Note: Our discussion will focus primarily on industry sponsored trials but many of the principles and concepts apply to any type of trial
3Predictable Enrollment Targets Realistic Enrollment Timelines DoableViableExecutableAchievableWhen we ponder whether a protocol is “feasible” what are we really trying to ascertain?What is the sponsor or CRO trying to ascertain?Are these in alignment?Predictable Enrollment TargetsRealistic Enrollment TimelinesSite SelectionSomething Else?
4The “Typical” ProcessWhat % of Time (or How Many Hours) Do You Spend on…Protocol SynopsisFinal Protocol, Budget, CTAAll Manuals, Job Aids, Etc.XX%Completing questionnaires / internal assessment process?XX% Study start up activities?XX% Creating Operational and Recruitment / Retention Plan?NoIRB and other committee approval?NoFeasibility QuestionnaireSelected as Site?YesSite Initiation visitFirst Patient InLast Patient InLast Patient OutYesBudget and Contract Approval~4-6 months~ 4-6 months~1 month~1-3 months3-6+ monthsPer Protocol
5DiscussionHow many of you have ever encountered an “unfeasible” protocol?What made it unfeasible?When did you determine that it was unfeasible?(note to Bonnie and Kate – at this stage we will use “sticky notes” to map the reasons to the typical timeline / process as depicted on next page – I would produce this page as a larger poster / flow diagram that we can have on the wall. We will also aim to estimate what % of the time we can determine a study is not feasible during the different stages)
6The “Typical” ProcessDepth, Detail and Quality of Information AvailableLoHiProtocol SynopsisFinal Protocol, Budget, CTAAll Manuals, Job Aids, Etc.NoIRB and other committee approval?NoFeasibility QuestionnaireSelected as Site?YesSite Initiation visitFirst Patient InLast Patient InLast Patient OutYesBudget and Contract Approval~4-6 months~ 4-6 months~1 month~1-3 months3-6+ monthsPer Protocol
7DiscussionHow many of you have ever experienced a “failed” or unsuccessful trial?What made it unsuccessful?When did you determine it was going to be, or was, unsuccessful?(Potential discussion points – lack of patients, lack of PI interest, safety issues, compliance issues, failure to secure budget, unanticipated amendments, etc.)
8Hindsight is 20/20Is there anything you could have found out earlier in the process that would have predicted failure?If so, what information would have helped and when would you like to have received it?Protocol SynopsisFinal Protocol, Budget, CTAAll Manuals, Job Aids, Etc.(note to Bonnie and Kate – at this stage we will again use sticky notes (different color) to add in different types of information and when we should get it in an ideal processNoIRB and other committee approval?NoFeasibility QuestionnaireSelected as Site?YesSite Initiation visitFirst Patient InLast Patient InLast Patient OutYesBudget and Contract Approval~4-6 months~ 4-6 months~1 month~1-3 months3-6+ monthsPer Protocol
9DiscussionEvery study is “feasible” given enough time, money and resourcesWhen studies fail it is primarily because of…The impact of a failed study is…Instead of asking the feasibility question, what if we started asking “is it worth the time, money, resources (and precious patients!) to take on this study”?How would this change your decision making process?What would it take to “fail fast” and quickly reject studies that will be unsuccessful?
10“Reverse Engineering” the Process Step 1Interest and enrollability assessmentStep 2Just Ask / Just TellStep 3Confirm Commitment and Recruitment Resource PlanStep 4Formalize operational and recruitment action plan
11Making Study Feasibility Assessments Work for Sponsors and Sites 10/9/2008Step 1AInvestigator InterestHiLowAvailability & Enrollability of Patient Population?Higher likelihood of success – pursue further information and maximize enrollment potentialMay be able to support with training, resources, recruitment assistance, etc. – pursue more information and validate realistic enrollment potentialLikely not worth investing more effort as it will be difficult to engage PI and sustain study enthusiasm even if a lot of potential patientsNot worth pursuing – quickly fail the study opportunity and provide rationale
12Step 1 A Decision MakingWhat else would influence the investigator’s interest?
14Enrollment Estimation High Level Funnel AnalysisPast Performance Evaluation
15Recruitment Funnel Calculator Note to Bonnie and Kate – I will aim to walk through all of these various tools and worksheets – we will do examples, critique the tools and processes….
16Historical Performance Report Card Example On Average we get our 1st patient in within 24 daysAndOn Average we achieve 76% of our enrollment targetsDiscussion:What metrics do you capture?Are they value-added to your decision making? The sponsors?Challenges /opportunities with collecting this information (e.g., Research Resonance Network)
17Estimated Enrollment Contribution XX from outside sourcesXX from our own databaseXX from referralsTotal Enrollment Contribution = XX within XX Month(Estimate will be validated upon site selection decision and availability of detailed protocol
18Step 2: “Just Ask / Just Tell” Typical process “pain points”:Not enough information / evidenceNot enough timeRestricted questionnaire formatsPerceived “non value added” informationNot enough CONVERSATIONS!Potential solutions:Provide EVIDENCE“Reverse feasibility” questionnaires and site profilesDetermine must haves for site selectionDiscuss and negotiate timelines, expectations, interest and information needs
19Critique of “Reverse Feasibility” Questionnaires Discussion:Has anyone used something similar? What was the outcome?What would you change?How might the process work?
21Enrollment Validation – An Ideal Process High Level Funnel AnalysisDatabase EstimateSample Chart ReviewEstimate the Remaining Funnel Loss RatiosIdentify GapsNow that you have a more detailed protocol
22Step 1 Set up the “leaky pipe” calculations to estimate loss ratios Use benchmark data or past historical performance dataStep 1“guesstimate the #: and confirm with the database queryUse benchmark loss ratios or update with historical data if available
23Step 2a Database Estimate 100 subjects in 1 year I/E CriteriaCan be determined at Pre-ScreeningEMR -queriable criteriaDefine query parameters (e.g., ICD-9 Codes)Run Query with primary diagnostic code onlyRun query with remaining codes / characteristics to determine % loss due to e-Pre-screening criteriaChart review criteriaCan only be determined at Screening**After obtaining informed consent100 subjects in 1 yeare.g., 35% e-Pre-screening Loss
24Adjust for e-Prescreening loss ratio Step 2bUpdate CalculatorConfirm the starting # based on your database query of the # of patients with diagnosisAdjust for e-Prescreening loss ratio
25Step 3a Sample Chart Review Further segment and prioritize the remaining pre-screen criteriaOut of the above group pull random charts to review against all protocol criteria and document what percent of those patients meet the pre-screen criteriaIf no patients quality out of the 20, pull an additional chartsUse this to determine the remaining pre-screening loss ratioCombine with the e-pre-screening ratio to determine the full pre-prescreening loss ratio20 charts3 / 20 patients meet pre-screening criteria85% loss at chart review pre-screeningE-Pre-Screening Loss 35%2 (average)60% Total Pre-Screening Loss Ratio
26Adjust for Total Pre-Screening Loss Ratio Step 3bUpdate CalculatorConfirm the starting # based on your database query of the # of patients with diagnosisAdjust for Total Pre-Screening Loss Ratio
27Estimate Remaining Loss Ratios Step 4Estimate Remaining Loss RatiosEstimate the loss ratios across the full recruitment funnel.For consent declines, consider distance, age range (work hours/school hours), and other study burdens to estimated the consent refusal ratioEstimate screen:fail and post randomization losses based on prior site / sponsor experienceRemaining loss ratios estimated based on evaluation of study burdens, remaining eligibility criteria restrictions and prior sponsor or site experience
28And the overall conversion ratio The Enrollment Validation ResultsThese fields are auto calculated showing the realistic # of patients you can enroll, randomize and complete in 1 year from within your own internal pool of patientsAnd the overall conversion ratio
29Recruitment Resource Plan Provides justification for budget and demonstrates clear proactive thinking about recruitment tactics, resources and materials!
33Study Implementation Plans Note: We probably won’t have time to go into great detail but we could at least discuss and share ideas of what makes a good “implementation” or operational plan – for sites and for patients to ensure compliance and efficiencyBecome friends with your CTMS / Excel / Visio!
34Pulling it All Together If we follow this “optimized” process…How many of the typical study failures and pain points could we eliminate?]Could our resources be better utilized?Could we make quicker “reject” decisions?Could we improve our likelihood of success?Why or why not?Note to Bonnie / Kate: here we go back to the “typical” process and earlier discussion / stickies and see how many can be removed and what is still left and we discuss how these could be overcome)
35Reflection Please answer the following… The one or two things I really like about this approach is (are)…The key concerns I have about the proposed process and/or tools are…One or two things I would recommend to change or adapt the process for our site would be…Remaining thoughts, questions, comments?
36Beth D. Harper, BS, MBA President, CPP, Inc Beth D. Harper, BS, MBA President, CPP, Inc