Shift Health co-hosted a Product Development Boot Camp with the Global HIV Vaccine Enterprise. The Boot Camp afforded workshop participants an opportunity to discuss best practices, to learn from the experience of other experts and to create an enduring resource and toolkit that will serve the HIV vaccine field and beyond. Product development refers to the multifaceted, long-term, highly regulated process that brings promising new drugs, vaccines and medical devices to the populations who most need them. In fields such as HIV vaccine development, where the absence of commercial incentives can make it difficult for companies to lead this process on their own, inventors need to work in partnership with diverse stakeholders and funders to maximize the social and economic impact of their research. Anne Mullin, PhD, Engagement Leader, Director, Team Performance and Development at Shift Health, outlined the elements of planning for trial success: Build contingency plans around potential scenarios Define proactive and reactive responses in a prescriptive and unambiguous manner Ensure that contingency plans set the stage for future product access.

1. Shift Health is a healthcare strategy consultancy devoted exclusively to healthcare and life sciences. We work with government, academia,
industry, the not-for-profit sector and healthcare providers to amplify healthcare and research leadership, advance global health innovation and
achieve eminence in healthcare markets worldwide.
Product Development Boot Camp
6 November 2015
Planning for Trial Success
Dr. Anne Mullin
Engagement Leader
Director, Team Performance and Development

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Introduction

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Is your team prepared to react?
“[The company’s] stretch of bad, ugly,
not-good results just got longer. The
pharma giant, which recruited more
than 16,000 patients in a monumental
postapproval effort … says that study
failed…its primary endpoint … and
key secondary endpoints.”1
Addressing unexpected trial results in the absence of a comprehensive, consensus-
based plan can lead to a crisis situation and test the resolve of trial partners.
1 Modified from: http://www.fiercebiotech.com/story/ropes-glaxosmithkline-admits-another-phiii-debacle/2015-09-08
2 Modified from: http://www.nature.com/news/2009/090720/full/news.2009.707.html
“researchers halted a trial of the
vaccine … because it seemed to
increase the risk of HIV infection.
The failure of the trial … was a serious
setback for AIDS researchers, who
were at a loss to explain its
disappointing results.”2

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Planning Is Challenging Due To The Various Functions And Diverse
Stakeholders That May Be Involved
Contingency planning mitigates risks by anticipating the large array of issues
that drive trial complexity, duration and cost.
The complexity of late-stage trials makes contingency planning
critical—but also very challenging.
Addressing the complexities inherent to clinical trials makes
contingency planning critical—and also very challenging.
Regulatory
negotiation
Supply
chain
Manufacture
and scale-up
Technology
transfer
Vaccination of
placebo
Public
expectations
Media
exposure
Treatment
modalities
Geographic
scope
Trial
Size
Cross-sector
partners
Multiple company
functions
Drivers of
trial
complexity,
duration,
and cost

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Planning for trial success (and failure) should be proactive, systematic
and collaborative.
Efficacy
Safety
Operational
Clinical / Operational
Scientific
Manufacturing
Communication
Proactive
Reactive
Identify and Define
Scenarios
Outline and Categorize
Considerations
Develop and Prioritize
Action Plans
Regulatory
Commercial
These elements are often codified in a ‘Contingency Planning Roadmap’, which
arms decision-makers with a ‘playbook’ for managing risks.

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Elements of Planning for Trial Success

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Elements of planning for trial success:
1
2
3
Build contingency plans around potential scenarios
Define proactive and reactive responses in a
prescriptive and unambiguous manner
Ensure that contingency plans set the stage for future
product access

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Elements of planning for trial success:
1
2
3
Build contingency plans around potential scenarios
Define proactive and reactive responses in a
prescriptive and unambiguous manner
Ensure that contingency plans set the stage for future
product access

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A wide net must be cast to identify all potential trial outcomes—
those that are aspirational, realistic or unlikely.
Operational EfficacySafety
1
Suboptimal monitoring and
reporting of adverse events
Trial stops due to observed
serious adverse events
High frequency of adverse
events reported; trial
continues
Trial stops due to insufficient
enrollment, acquisition,
retention
Data collection issues at
certain sites impact overall
data quality
Supply chain disruptions
impact trial timelines
Trial stops due to efficacy
futility
Trial concludes within several
possible efficacy ranges
No correlate of protection
identified
The scenarios listed above are only examples of the dozens of safety,
operational and efficacy scenarios that could transpire.

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1
Case Study: Five potential scenarios were developed to prepare the
HVTN 505 study team for an upcoming DSMB review meeting.
DSMB
Review
Trial terminates due to safety
concern
Trial continues according to
established plan
Trial terminates due to
operational futility
Trial demonstrates positive
vaccine efficacy
Trial terminates due to
efficacy and activity futility
The contingency plan provided the trial team with a clear plan of action to
respond to the DSMB recommendation and communicate effectively with the
media and participants.
The contingency plan
established specific response
plans for various outcomes.
The sudden termination of the
trial triggered implementation of
a multi-pronged communication
strategy, including dissemination
of tailored materials to trial
volunteers and the media.

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Elements of planning for trial success:
1
2
3
Build contingency plans around potential scenarios
Define proactive and reactive responses in a
prescriptive and unambiguous manner
Ensure that contingency plans set the stage for future
product access

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Effective response plans are the product of a disciplined reflection on
priorities and constraints.
2
Responses should be proactive and reactive—proactive to avert and minimize
risks; reactive to respond to and manage risks.
When to Act?
What to Focus On?
What is Needed?
Defining specific triggers and thresholds for
action/escalation provides clarity on timing.
Reflecting on likelihood and impact focuses attention on
high-risk events and responses.
Outlining detailed responses provides an understanding of
resource requirements and gaps.
Effective response plans are informed by a disciplined reflection on
priorities and constraints.

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A single scenario can be associated with multiple proactive and
reaction actions.
2
Poor
Retention
Proactive Reactive
Employ surveillance tools to
remind volunteers
Assess retention rate and
loss to follow up relative to
forecasted model
Focus on enrolling subjects
that can complete study
Assess study completion
rates periodically
Strengthen physician-
volunteer relationship
Study
Delays
Operational
Futility
Request to increase
enrollment from FDA
Follow “Crisis” SOPs
Stop enrollment and
vaccinations
Unblind volunteers
Finalize datasets and
conduct analyses

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Case study: Contingency planning to prepare for outcomes, risks and
scenarios of a Phase 3, multinational vaccine clinical trial.
The contingency plan has guided a number of proactive manoeuvers and will
continue to direct activities during the course of the trial.
Safety
2013 2014 2015 2016 2017 2018 2019
Operational Futility
Efficacy Futility
Vaccine Efficacy < 70%
More attention required Less attention required
Study Duration
5-year Phase 3 study
involving 250 clinical
centres
Detailed response
plans, with proactive
and reactive
components
Preparation based on
likelihood of occurrence
and potential impact
2

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Elements of planning for trial success:
1
2
3
Build contingency plans around potential scenarios
Define proactive and reactive responses in a
prescriptive and unambiguous manner
Ensure that contingency plans set the stage for future
product access

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Contingency planning has broader access implications when
predetermined efficacy levels are demonstrated.
3
Contingency planning will inform parallel access planning efforts and ensure that
partners are prepared to provide access to a successful product in a timely manner.
Licensure
application
Manufacturing
scale-up
Deployment
strategy
Vaccine access planning
Operational
Vaccine Efficacy:
30-50%
50-70%
70%+
Safety
Contingency
Planning Scenarios
Example
Access Plan
Considerations

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Case Study: RV144 set a precedent for the importance of multi-
faceted and timely planning in a complex HIV vaccine trial.
Contingency planning is a critical mechanism for compelling partners and stakeholders
to have discussions around key issues that will have implications for overall planning
efforts and eventual vaccine access.
3
Framework of efficacy triggers
Manufacturing and scale-up
considerations
Identified scenarios and
oriented partners around a
collective response to trial
outcomes
Contingency Planning
Worked with regulators to
build competencies for
vaccine licensure
Regulatory Capacity-
Building
Defined access timelines
and commitments under
different efficacy scenarios
Access Strategy

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Success Factors and Impact

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Key success factors
Contingency planning must be:
Comprehensive in assessing all potential events and outcomes—
whether positive or negative—regardless of initial perceived likeliness
Consensus-driven to align expectations and secure commitments
across diverse partners and stakeholders
Coordinated through a central point of contact and/or project manager
to ensure timely communication and harmonization of activities across
partners and stakeholders
Flexible to enable adjustments in response to new information and/or
evolving partner commitments

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Impact
Ensures that all stakeholders are prepared to respond and act in a
unified and decisive manner
Streamlines implementation of the appropriate scientific, clinical and
operational responses
Manages public expectations by guiding communication of trial
events with volunteers, the public, and medical community
Ultimately, effective contingency planning will result in cost-effective
trial management, comprehensive risk mitigation and efficient
coordination of partners, participants and the public.

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