Download five solutions for addressing antibiotic development

FIVE SOLUTIONS FOR
ADDRESSING ANTIBIOTIC
DEVELOPMENT CHALLENGES
Each year, 2 million people in the U.S. are infected with multidrug-resistant bacteria and at least 23,000
of those die as a direct result of these infections1. Similarly, in the European Union (EU), about 25,000
people die from these infections2 while the World Health Organization (WHO) has observed very
high rates of resistance in its regions3, signaling a worldwide threat to global health with devastating
implications. The crisis is only compounded by limited antibiotic development in recent years.
To address this situation, regulatory agencies are supportive of antibiotic development and various
legislative bodies are considering novel pathways. Many biopharmaceutical companies have stepped up
to develop novel antibiotics and address this urgent health crisis but often require outside assistance to
achieve development goals.
Contract research organizations (CROs) often serve as a partner to advance antibiotic development, but
when assessing potential collaborators, biopharmaceuticals should consider how their partners will
incorporate best practices and manage critical challenges in antibiotic studies:
1. IMPROVING SITE SELECTION AND ENGAGEMENT
Non-or low-performing sites draw on resources but deliver little trial input, affecting study timelines,
endangering data quality and undermining clinical return on investment (ROI).
Covance Solution:
A successful trial starts with selecting the right sites. Our Central Laboratory is the world leader in
clinical trial testing, giving us a unique perspective on site and investigator performance data. This
information feeds into our proprietary clinical knowledge base, Xcellerate® Forecasting & Site Selection.
Complementing our clinical intelligence, the LabCorp patient database can be used to identify the
highest-density regions for specific types of infections, such as Clostridium difficile (C-dif ), and match
them to nearby high-performing investigators with historic success in your trial type.
With custom recommendations for sites, investigators and geographic selections, you study will work
with investigators and sites that are more likely to meet your patient enrollment goals.
2. ACCELERATING PATIENT IDENTIFICATION
Antibiotic studies are particularly challenging for enrollment. Identifying patients prior to receipt of
alternative antibiotics is key, otherwise these patients are excluded, impacting your timeline.
1.
2.
http://www.cdc.gov/features/antibioticresistancethreats/
The bacterial challenge: time to react. European Centre for Disease Prevention and Control (ECDC)
and the European Medicines Agency (EMEA), 2009
3.
Antimicrobial Resistance Global Report of Surveillance. WHO, 2014
Covance Solution:
Based on our deep experience and understanding of patient flow, Covance’s proven Failure Mode Effects
Analysis (FMEA) process helps you manage the logistic complexities of hospital studies. We understand the
multifaceted patient identification and treatment needs in antibiotic trials requires a robust communication
pathway with each site’s infrastructure.
To better support enrollment, our clinical research associates (CRAs) review the patient identification options
with each site’s principal investigator (PI) and explore how these pathways can be optimized to support early
patient identification. Then, the clinical team pressure tests the infrastructure to determine who will identify,
randomize and dose patients from every point within the narrow enrollment windows.
Coupled with our site selection capabilities through Xcellerate, our recently completed antibiotic studies
experienced only 10% low/non-recruitment, as compared to the industry standard of 20-30%, further reducing
the time and cost for our clients and accelerating their development.
3. SUPPORTING YOUR DEVELOPMENT JOURNEY
The pathway to development approval can be slow and difficult in antibiotic studies. Meeting the primary FDA
and EMA requires patient compliance with the protocol, particularly with the primary assessment endpoints:
ETP (early time point), TOC (test of cure), and mortality visits, as per indication.
Covance Solution:
As your partner, we offer deep experience with harmonization of the primary analysis set per local regulations
and dual primary endpoints for multiple indications.
Patient identification has also become more critical due to intent-to-treat populations with acute bacterial skin
and skin structure infection (ABSSSI) or community-acquired bacterial pneumonia (CABP). We have
strategies in place to manage near-real-time evaluability review and patient compliance for primary/secondary
efficacy analyses.
We also work with sites to ensure they contact the patients at least a day prior to the scheduled ECA, TOC and
LFU visits (as required) to further aid in ensuring the patient’s return. There may be little incentive for a patient
to return for subsequent visits. Therefore, we place even greater emphasis on the need for site personnel to
encourage patients to return for the TOC and LFU visits, while proactively managing and following patient
compliance to ensure your study stays on track.
4. MAINTAINING INTEGRITY OF STUDY BLIND AND SUPPLY
ACCESS
Due to the intravenous route of most antibiotics, many studies face challenges with study blind integrity and
the need for on-site preparation, along with accessing supplies.
Covance Solution:
At Covance, we have proven site-blinding plans that critically evaluate the chain of custody at the site as well
as the staff involved with patient care and drug administration. We capitalize on interactive technology to help
support the maintenance of the study blind.
You can count on our experience in antibiotic studies to deliver robust process, procedures and teams
that maintain the blind integrity and manage your investigational product. Specific comparators introduce
additional challenges to consider such as drug levels and physical-chemical differences, but we know how to
successfully manage these issues. In fact, we have never had an antibiotic study miss evaluability
due to unblinding.
When you work with Covance, you also benefit from our sourcing relationships to manage vendors, procure
ancillary supplies and source comparators for appropriate country site distribution. We will handle the entire
process so you can focus on the resulting data.
5. ENDPOINT MANAGEMENT AND REACHING KEY EVALUABILITY
RATES
Microbiologic data drive multiple endpoints in your studies and help detect potential problems earlier. Near-real-time
evaluability assessments are critical in antibiotic studies to identify and proactively mitigate trends.
Covance Solution:
We provide sites with training to align with the exact protocol requirements and provide study tools that maximize
the site’s compliance with collection and processing of these samples. Early and ongoing analysis of microbiologic
rates ensures the goals of the protocol are being achieved while real-time monitoring of results allows for course
correction, higher quality and earlier trial completion.
At Covance, our physicians use a rigorous tool set and work closely with the operations team to ensure compliance
with critical visits and assessments that support evaluability.
Recently, this proven methodology has delivered evaluability rates that were 10% greater than the study target. In
addition, our evaluability has always been successful at meeting the primary endpoints in Covance antibiotic studies.
Covance offers expertise with nearly every antibiotic indication: ABSSSI, CABP, HABP, VABP, cIAI, cUTI, Bone and
Joint infection and bacteremia. Covering novel agents, novel mechanisms of delivery and new indications for existing
agents, you can leverage our medical and operational credibility to advance your antibiotic program.
This deep experience has translated into market success. Between 2010 and 2014, four antibiotics were granted
marketing authorization by the FDA. Covance ran the Phase II or III studies for three of those and managed the labs
for the fourth in the sponsor’s in-house study.
Drawing from our work with 159 infectious disease studies worldwide, involving more than 1,900 investigational
sites and managing more than 32,300 patients, we recognize that one size does not fit all. That’s why we offer flexible
processes and rapid scalability to adjust to shifting requirements at any stage in your development.
With Covance on your side, you can take advantage of our best practices for managing inherent challenges in
antibiotic studies. We have designed proactive approaches to successfully conduct a wide range of antibiotic studies
and can apply that knowledge to help advance your product and make a difference in global health.
Learn more about our drug development solutions at www.covance.com
Covance Inc., headquartered in Princeton, NJ, USA is the drug development business of Laboratory
Corporation of America Holdings (LabCorp). COVANCE is a registered trademark and the
marketing name for Covance Inc. and its subsidiaries around the world.
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