David Selkirk has over 19 years of experience working for large and mid-size pharmaceutical companies and clinical research organizations. He will discuss the landscape of late phase clinical trials, including increasing regulations, the role of health technology assessments, and operational considerations. Key topics that will be covered include working with stakeholders, comparative effectiveness research, risk evaluation and mitigation strategies, patient reported outcomes, and contracting with vendors such as CROs. The future may see larger trials conducted with more independent oversight and accountability.
The late phase research environment has changed dramatically in recent years. Regulators in the US and abroad are demanding a more proactive approach to safety and risk management. In light of these changes, sponsors must begin working with their strategic research partners early in the investigative process to anticipate and plan for late phase studies.
Overview of the Patient-Centered Outcomes Research Institute (PCORI), how PCORI views Patient-Centered Outcomes Research and how this is related to PCORI’s major funding mechanisms.
The late phase research environment has changed dramatically in recent years. Regulators in the US and abroad are demanding a more proactive approach to safety and risk management. In light of these changes, sponsors must begin working with their strategic research partners early in the investigative process to anticipate and plan for late phase studies.
Overview of the Patient-Centered Outcomes Research Institute (PCORI), how PCORI views Patient-Centered Outcomes Research and how this is related to PCORI’s major funding mechanisms.
A guide to become clinical research associatepptxRidhimaPatel2
An integral part of modules in clinical research courses focus on the ethical standards that have to be implemented without compromising the quality of trial results.
Mechanisms for bringing together a broad range of stakeholders that share common interests in product
innovation to increase the number of impactful therapies for skin diseases such as alopecia areata.
Clinical research and its importance career in clinical researchRidhimaPatel2
This document is expressing the carrier opportunities in clinical research and how it important to learn clinical research for our society and the best institute providing absolute best training for the clinical research
Protocol Design & Development: What You Need to Know to Ensure a Successful S...Brook White, PMP
Solid protocol design is critical to clinical development. No matter how well executed a clinical study is, if the underlying design is flawed, it wasn’t worth doing. In this presentation, Dr. David Shoemaker, SVP R&D, and Dr. Karen Kesler, AVP Operations, will walk through the process of developing a protocol, explain the major considerations, and point out common mistakes and challenges.
What Happens After Your Device is Approved? Collecting Data in the Real WorldMedpace
In this workshop, Medpace will discuss key considerations for generating real-world evidence and how to apply critical insights in order to drive late-stage clinical research. To listen to this presentation, visit https://vimeo.com/168768256
A guide to become clinical research associatepptxRidhimaPatel2
An integral part of modules in clinical research courses focus on the ethical standards that have to be implemented without compromising the quality of trial results.
Mechanisms for bringing together a broad range of stakeholders that share common interests in product
innovation to increase the number of impactful therapies for skin diseases such as alopecia areata.
Clinical research and its importance career in clinical researchRidhimaPatel2
This document is expressing the carrier opportunities in clinical research and how it important to learn clinical research for our society and the best institute providing absolute best training for the clinical research
Protocol Design & Development: What You Need to Know to Ensure a Successful S...Brook White, PMP
Solid protocol design is critical to clinical development. No matter how well executed a clinical study is, if the underlying design is flawed, it wasn’t worth doing. In this presentation, Dr. David Shoemaker, SVP R&D, and Dr. Karen Kesler, AVP Operations, will walk through the process of developing a protocol, explain the major considerations, and point out common mistakes and challenges.
What Happens After Your Device is Approved? Collecting Data in the Real WorldMedpace
In this workshop, Medpace will discuss key considerations for generating real-world evidence and how to apply critical insights in order to drive late-stage clinical research. To listen to this presentation, visit https://vimeo.com/168768256
Making sense of large data sets has always been a daunting task, and every tool that makes the life of an analyst easier is worth exploring. There are 45,000 observational studies on the CT.gov database. This is how trial version of IBM Watson visualizes the data available. The dataset was minimally processed to reflect priority information requirements, in this case insight into the most commonly used study designs over time.
How to Make Postmarket Surveillance More Cost EffectiveApril Bright
When it comes to postmarket surveillance (PMS), it’s common for the costs to outweigh the value. But, by working with the right team, you’ll be able to execute a study that maximizes return on investment and minimizes the financial impact of conducting further observational research. Postmarket study challenges that must be addressed include enrollment delays, patient attrition, long-term follow-up, resourcing demands and global payor requirements. This session will provide a case study of one orthopaedic company’s seamless transition between postmarket approval and post-approval studies.
As UDI deadlines roll out, OEMs are left with many questions on implementation and compliance, including:
How does FDA recommend we direct mark screws and small implants?
How should we proceed as we await the guidance on the Convenience Kit exemption?
What are best practices for entering submissions to GUDID?
How is FDA enforcing UDI?
FDA officials will speak on UDI adoption and UDI data quality. Bring your questions. Ample time will be saved for Q&A.
All patients are different, and data collected during product development or Randomised Clinical Trials (RCT) does not always paint the full picture of everyday patients. RWE insights complement the manufacturing process and RCT findings, adding more value and providing real-world impact. While together data from the manufacturing process and RWD paint a fuller picture.
Due to the limitations of the study design, data from the manufacturing process and RCTs are inadequate for demonstrating an intervention’s long-term safety and effectiveness. Moreover, it is possible to compare multiple product or interventions in RWE.
Integrate RWE into clinical developmentIMSHealthRWES
With greater application of RWE throughout the pharmaceutical
lifecycle, learnings are emerging that offer guidance for
approaches to derive the maximum value. This article captures
the author’s experience at a leading international biotech, with
insights for smoothing RWE assimilation into clinical
development and realizing the benefits it brings.
Big data, RWE and AI in Clinical Trials made simpleHadas Jacoby
Technology is slowly but surely penetrating the healthcare industry in general and the clinical trials sector in particular. New and advanced solutions offer a variety of possibilities aimed to both improving existing processes and creating new and more efficient ones. And on top of all stands the desire to make clinical trials more patient centric.
In all of this, even though some of the technologies have yet to mature enough to meet the high quality standards necessary, it is important to know them and begin imagining the promise they hold for clinical trials.
The information in ISR’s Electronic Media Use in Academic Medical Center Patient Recruitment report sheds light on the benefits, challenges and strategies of electronic media use for clinical trial recruitment. We are currently in an era where Facebook, Twitter, and Google searches link all of us to a larger global community. Clinical sites are actively navigating how to apply these resources to connect with patients around the world. The report will help academic medical centers, site personnel and CRO/sponsors understand which channels and strategies will best help accomplish their recruitment goals, and which ones can be developed for increased success in this realm.
Patient Blood Management: Impact of Quality Data on Patient OutcomesViewics
Patient blood management (PBM) has been proven to improve patient outcomes and save hospitals millions of dollars. Ensuring the quality of your data is central to decision making and critical to having a strong PBM program.
Would you like to learn how your organization can improve patient outcomes by implementing a PBM program based on accurate data?
If so, view this presentation by blood management expert Lance Trewhella. Lance presents how to develop a successful, evidence-based, multidisciplinary PBM program aimed at optimizing the care of patients who might need transfusion.
You’ll learn:
• Current recommendations for blood transfusion utilization
• The impact of quality data on PBM programs
• Best data practices in PBM
The Role of Real-World Evidence in Supporting a Product's Value StoryCovance
Randomized clinical trials (RCTs) are the gold standard for gaining regulatory approval for marketing authorization for medical products. RCTs typically measure short-term efficacy and safety of a product compared to placebo in a fairly homogeneous population and under ideal, controlled conditions. In contrast, the real world consists of a heterogeneous population in which patient care is much less controlled and thus, more complex. Treatment decisions made in this setting are predicated on a wider array of co-morbid conditions, competing medications, physician preference and risk of adverse events than those observed in RCT populations. Evidence generated from real-world settings reflects this complexity, complementing evidence derived from rigorously controlled RCTs.
Engage and Retain Patients in Long-term Observational StudiesJohn Reites
Traditionally, real-world and late phase studies require sites to enroll, engage and retain patients and collect and record patient reported outcomes (PRO), which can be burdensome to both sites and patients. Overtime, sites and patients may lose motivation to participate, contributing to high patient dropout rates, increased study costs and site dissatisfaction. This session will focus on innovative approaches for effectively engaging and retaining patients in long-term studies, such as: identifying design and operational considerations with conducting long-term observational research, understanding site and patient retention challenges, and examining engagement strategies and opportunities for improving retention and compliance.
Integrated Health Information to Examine, Empower and EngageH-Connect Compusoft
Electronic Ecosystem to build a universal Electronic Health Record and Health information exchange.
Deliver care through information technology,
Enhance health research, analysis & compliance
Improve efficiency, quality and reduce cost of healthcare. Online health records and Clinical Decision Support System (CDSS) at http://www.hconnect.co.in/
Combining Patient Records, Genomic Data and Environmental Data to Enable Tran...Perficient, Inc.
The average academic research organization (ARO) and hospital has many systems that house patient-related information, such as patient records and genomic data. Combining data from a variety of sources in an ongoing manner can enable complex and meaningful querying, reporting and analysis for the purposes of improving patient safety and care, boosting operational efficiency, and supporting personalized medicine initiatives.
In this webinar, Perficient’s Mike Grossman, a director of clinical data warehousing and analytics, and Martin Sizemore, a healthcare strategist, discussed:
-How AROs and hospitals can benefit from a systematic approach to combining data from diverse systems and utilizing a suite of data extraction, reporting, and analytical tools, in order to support a wide variety of needs and requests
-Examples of proposed solutions to real-life challenges AROs and hospitals often encounter
Solving the operational challenges of oncology clinical trialsRoberto Lara
This executive briefing explores new strategies for solving your oncology clinical operations challenges. It also features valuable insights into how you can enrich your site selection, speed up your start-up times and maximize patient recruitment opportunities here in North America.
A Leading Patient Experience Survey Platform by MedStatix - White Labeled for...MedStatix, LLC
Improving Patient Experience. Improving Practice Performance.
MedStatix, LLC, offers a WHITE LABELED, cloud-based specialty-specific patient experience survey platform that is bundled and/or resold by leading EMR/EHRs and other integrated healthcare service providers as a value-add to their products.
The patient experience platform uses data science and predictive analytics learned from data hosted on the platform to enable healthcare providers to improve quality of care, patient retention rates and risk profiles of physician practices.
The patient experience platform pinpoints specific, actionable problems where practices can improve their service through its easy-to-implement, yet sophisticated technology solution for monitoring and measuring patient experience by each provider across an organization.
With over a decade delivering over one million patient surveys for over 25 pharmaceutical brands, as well as customer feedback platforms and analytics for Fortune-class brands, MedStatix enables their resellers to provide their customers with exceptional practice improvement opportunities.
Rising Importance of Health Economics & Outcomes ResearchCitiusTech
Health Economics & Outcomes Research (HE&OR) guides stakeholders to make informed decisions regarding patient access to drugs and services. This document highlights specific use cases for healthcare information technology that add value to HE&OR.
Chapter 4 Knowledge Discovery, Data Mining, and Practice-Based Evi.docxchristinemaritza
Chapter 4 Knowledge Discovery, Data Mining, and Practice-Based Evidence
Mollie R. Cummins
Ginette A. Pepper
Susan D. Horn
The next step to comparative effectiveness research is to conduct more prospective large-scale observational cohort studies with the rigor described here for knowledge discovery and data mining (KDDM) and practice-based evidence (PBE) studies.
Objectives
At the completion of this chapter the reader will be prepared to:
1.Define the goals and processes employed in knowledge discovery and data mining (KDDM) and practice-based evidence (PBE) designs
2.Analyze the strengths and weaknesses of observational designs in general and of KDDM and PBE specifically
3.Identify the roles and activities of the informatics specialist in KDDM and PBE in healthcare environments
Key Terms
Comparative effectiveness research, 69
Confusion matrix, 62
Data mining, 61
Knowledge discovery and data mining (KDDM), 56
Machine learning, 56
Natural language processing (NLP), 58
Practice-based evidence (PBE), 56
Preprocessing, 56
Abstract
The advent of the electronic health record (EHR) and other large electronic datasets has revolutionized efficient access to comprehensive data across large numbers of patients and the concomitant capacity to detect subtle patterns in these data even with missing or less than optimal data quality. This chapter introduces two approaches to knowledge building from clinical data: (1) knowledge discovery and data mining (KDDM) and (2) practice-based evidence (PBE). The use of machine learning methods in retrospective analysis of routinely collected clinical data characterizes KDDM. KDDM enables us to efficiently and effectively analyze large amounts of data and develop clinical knowledge models for decision support. PBE integrates health information technology (health IT) products with cohort identification, prospective data collection, and extensive front-line clinician and patient input for comparative effectiveness research. PBE can uncover best practices and combinations of treatments for specific types of patients while achieving many of the presumed advantages of randomized controlled trials (RCTs).
Introduction
Leaders need to foster a shared learning culture for improving healthcare. This extends beyond the local department or institution to a value for creating generalizable knowledge to improve care worldwide. Sound, rigorous methods are needed by researchers and health professionals to create this knowledge and address practical questions about risks, benefits, and costs of interventions as they occur in actual clinical practice. Typical questions are as follows:
•Are treatments used in daily practice associated with intended outcomes?
•Can we predict adverse events in time to prevent or ameliorate them?
•What treatments work best for which patients?
•With limited financial resources, what are the best interventions to use for specific types of patients?
•What types of indi ...
2. David Selkirk
9 yrs working for large pharma
10 yrs working for mid-size CRO
Core skills
• executive leadership
• operational excellence - late phase focus
• business development
• international perspective
ABOUT THE PRESENTER
5. PATENTS
Huge number of
blockbusters
coming off
patent
Lower cost
generic
alternatives will
flood the market
Pressure to
demonstrate
Small Molecules Biologics
Source: IMS Sales Data as well as Jeffries & Company estimates
6. REAL WORLD
“The conditions under which products are
examined for regulatory approval, are generally not
the conditions under which they are actually
used...” (ISPOR 2010)
Evaluate how the real world impacts the safety and
efficacy of a therapy
Value of the therapy in terms of economics and
outcomes that matter to patients
7. STAKEHOLDERS
Sponsor Groups
• Health economics &
outcomes research (HEOR)
• Epidemiology
• Medical Affairs
• Safety /
Pharmacovigilance
• Clinical Operations
• Marketing / Product
Management
Physicians
Patients
Payers
8. COMPARATIVE EFFECTIVENESS
RESEARCH (CER)
No standard definition, but general consensus
Comparison of one treatment to one or more other
treatment
Comparison of treatments is not limited to
medications, i.e. outcomes, healthcare utilization,
QoL, etc.
Inclusive of both risks & benefits
10. INTERNATIONAL
REQUIREMENTS
FDA Amendment Act (FDAAA) enacted in
2007, giving significant new powers to the
FDA for inspection & follow-up
Volume 9A of The Rules Governing
Medicincal Products in the European
Union - Guidelines on Pharmacovigilance
for Medical Products for Human use
MIHARI Project in Japan is collected post-
marketing surveillance data from multiple
sources, eg. claims databases, clinical trials,
ADRs, etc.
11. RISK EVALUATION &
MITIGATION STRATEGIES (REMS)
Medication guides are almost always in place
Communication plans are required in roughly ⅓ of cases
ETASU are unlikely, as are distribution system
restrictions
Source: Tabulation made from the FDA website of approved REMS
12. NEED FOR POST-MARKETING
SURVEILLANCE
# of patients described in a
NDA (eg. 2,000) can increase
1000-fold after introduction
to the market (eg. 2,000,000)
This ‘tip of the iceberg’ is
not representative of the
broad demographics across
the population
Demonstrative of need for
post-marketing surveillance,
eg. Vioxx, Avandia
14. VALUE FOR COST
Treatment
A or B?
Treatment A Cost
Treatment B Cost Outcome B
Outcome A
∆Cost ∆Outcome
Does the benefit (outcome differential) justify the cost?
15. PATIENT REPORTED
OUTCOMES
A measurement based on a report
that comes directly from the
patient (i.e. study subject) about
the status of a patient’s health
condition without amendment or
interpretation of the patient’s
response by a clinician or anyone
else. A PRO can be measured by
self-report or by interview
provided that the interviewer
records only the patient’s
response.
Source: Guidance for Industry Patient Outcome Measures: Use in Medical Product Development to Support Labeling Claims. US FDA December 2009
16. OUTCOMES
Life expectancy / survival
Relief of symptoms
Improved patient functionality (eg. independence,
ability to work, social activity, exercise, cognition,
etc.)
Better side-effect profile
Convenience / mode of delivery
Health-related quality of life
17. HTA GLOBAL FOOTPRINT
Source: http://www.inahta.org/Members/ (International Network of Agencies for Health Technology Assessment)
18. NICE
National Institute for Clinical Excellence (UK)
Produces guidance on public health, health
technologies (i.e. pharmaceuticals, interventional
procedures, devices & diagnostics) and clinical practice
Makes recommendations based on clinical efficacy
relative to the cost involved
All activities underpinned by the need for transparency,
collaboration & involvement of stakeholders
http://www.nice.org.uk/
20. OVERVIEW
Post & peri-approval studies can be very large with
100s - 1,000s of sites often recruiting 1,000s - 10,000s
of patients
Often involve multiple international countries and
have a duration of several years
Ratio of ‘prescribers’ to ‘researchers’ is weighted
toward the former
• may not have study coordinators
• may not have GCP training
• office logistics focused on patients, not documentation
21. DESIGN: WHAT DO YOU WANT
TO DO WITH THE DATA?
Epidemiology
• burden of disease
• health care system
• incidence rates, survival, etc.
Retrospective data
abstraction
• review of claims database,
national registries such as those
from Nordic countries, or into
patient medical charts
• ensure no clinical interpretation
needed by abstractors
Observational study
Expanded access
program
REMS
Disease/product/
pregnancy registry
Comparative
effectiveness vs. efficacy
Safety surveillance and/
or risk management
22. CLINICAL TRIAL PROCESS
tegic"goals"
udy?
"how"the"
ould"be"
al"Studies:"
perational!Plan!from!the!Bottom!Up
REPORTS
PATIENT ENROLLMENT,
OUTCOMES TRACKING,
DATA COLLECTION
SITE
SUPPORT
ANALYSES
PUBLICATIONS ABSTRACTS, PRESENTATIONS
MEETINGS
n"budget"and"ROI
arch"goals?
w"if"you’ve"
?
rics"(impacted"
)
LEGAL, REGULATORY, IRB REVIEW
MATERIALS PRODUCTION AND DISTRIBUTION SITE RECRUITMENT AND TRAINING
NEWSLETTERS
STRATEGY
ANALYSIS PLAN COMMUNICATIONS PLAN
DATA COLLECTION FORMS,
PROCESSES, AND LOGISTICS
SCIENTIFIC ADVISORY PANEL
SITE IDENTIFICATION (FIELD
INVOLVEMENT)
Source: Jeff Trotter’s Presentation on Observational Research at the 2010 ISPOR Annual Meeting
23. THE CONTINUUM
Randomized Controlled Trials
Efficacy Data
randomized
protocol driven
high internal validity
extensive inclusion/exclusion
criteria
high cost
Observational Studies
Effectiveness data
non-interventional
adapted to usual care
higher generalizability
few exclusions (allows comorbidities)
lower cost
Experiment Real World
24. STREAMLINED DATA
COLLECTION & CLEANING
Tight focus on collecting only the endpoints specified in the
protocol
• avoid the ‘nice to know’ trap
High utilization of drop-down menus and check boxes, with
little to no free text
Pre-programmed disease and concomitant medication
choices
Data management plan specifying authority to make simple
revisions to data
• edit checks must be simple and few in number
• must be able to deal with missing or incongruous data that is commonplace with PRO
25. RISK-BASED SDV
Not necessary to verify 100% of all source data
• Select the data points most important for the study’s conclusions
to be drawn - fit for purpose
• Review the areas where inconsistencies most commonly occur,
i.e. concomitant medications & adverse events
Ensure patient safety is monitored carefully
regardless of efficacy measurements
Include ‘remote’ management through call
centers and an EDC system
Important to establish lines of communication
and escalation of issues with site staff upon site
initiation
• what issues can be addressed via e-mail, phone, in-person
Establish a plan of how to scale up SDV if
there are data integrity concerns
26. MOTIVATION
Consider motivation for both the Investigator and for the
patients to become involved
• there may be no medical benefit for patients to participate, so focus on removing the
barriers to enrollment, i.e. reimburse mileage & parking, hotels for out-of-town
patients, etc.
• collect names of relatives who consent to be contacted if patient is unresponsive
• compensation offered to PIs is generally low so the data collection process must be in
alignment with their clinical practice
Publication can be an attractive possibility for some site staff
Sponsorship of industry symposia and/or memberships
Retention is important in multiple year trials
• vouchers have been used for on-line redemption of various products
27. CONSENT
Depending on the applicable regulations, the
need for patient consent can be waived if
certain criteria are met; some of which are:
• patient is deceased
• no way to reach patient due to long duration between data
collection and current study
• data collection in generalities instead of specifics, eg. age
range rather than specific birth date
• typical example is a retrospective chart review
Always need an ethics committee’s approval
to waive the need for patient consent
If consent is required, always train site staff
on how to administer it, and how to
document it
29. CONTRACT RESEARCH
ORGANIZATIONS
Very large multinational clinical trial operation
corporations that are growing with preferred
provider relationships in place with large
multinational sponsor organizations
Mid-sized CROs are specializing in niche markets,
i.e. late phase, device, early phase, etc.
Others include central labs, electronic database
providers, call centers, IVRS, packaging/labelling/
distribution,
30. ELECTRONIC DATA CAPTURE
Validated, 21CFR11-compliant system
Rapid & cost-effective set-up
Library of forms available to minimize
design time & cost
Multi-language capabilities - Asian
characters
eLearning capabilities built-in and
available on demand
Allow for mid-study changes in CRF
for protocol amendments
Real-time report generation, ideally
allowing customized data searches
Connection with EHR (electronic
health records)
32. ACCOUNTABILITY
Data collection, analysis, interpretation and
publication to be done independently of the sponsor
• Clinical trial management
• Statistical analysis
• DSMB
• Clinical study report
Who takes responsibility; NIH, regulator, HTAs,
AHRQ, IQWiG, others?
Make data available for academia/regulators to
perform meta-analysis
33. EVOLUTION
Much larger trials incorporating a much broader base of patients,
necessary for market approval?
Sponsors will still fund the research but decision-making to be done
independently?
Full transparency of all exchanges with the sponsor?
Media scrutiny and perhaps sensationalization of results?
34. PUBLICATION
Is it feasible to publish all clinical trial results funded
by commercial sponsors?
• Not all results are scientifically interesting
• Not all submissions are accepted for publication
• Submissions are expensive and consume sponsor staff time
Establish a standard that commercial sponsors submit
clinical trial results at least xx times?
Post protocols & study data on medical journal
websites