There is no doubt that
clinical research is critical to the advancement of medicine and public health.
But conducting such research is a complex, resource-intensive endeavor that
relies on a multitude of stakeholders, workflows, processes, and information systems.
Clinical trials play an essential role in the drug development process by effectively
demonstrating the efficacy and safety of a pharmaceutical compound – but they
are not for the faint of heart, conducting even one is a monumental task with complex
processes and issues that can surface and derail a study’s timeline. As a result,
delays in regulatory filing, market entry, and ultimately, the delivery of new
therapies to patients are all too common.
With a large number of
drugs coming off patent, known as the patent cliff, there is intense pressure
to speed clinical trials and restrain costs, but inefficiencies tied to
complicated protocols, globalization, and paper-based methods have stalled these
also need an efficient process for eliminating unsuccessful trials earlier or
intervening before a “rescue” is required, which enables resources to be
deployed more effectively. Because clinical trials are a major overhead,
improved cost control and effective management of resources are key corporate objectives.1
According to the Clinical Trials Transformation Initiative (CTTI), most of the
costs incurred in clinical trials are associated with human time and effort, so
unnecessary complexity can be both burdensome and expensive.2
notwithstanding, the sheer number of potential therapies that are coming into
the clinic is exasperating patient enrollment challenges. Unfortunately, such
enrollment barriers mean treatment options often don't make it to patients in a
timely matter, if at all. According to a report from a major National Cancer
Institute (NCI) and the American Society of Clinical Oncology (ASCO) sponsored
conference, “Poor enrollment onto trials threatens to slow progress in cancer
care at a time when advances in science are enabling new opportunities for
prevention and treatment.”3
TECHNOLOGY BRINGS OPPORTUNITIES & CHALLENGES
Growth in regulatory
complexity and global outsourcing has created unique challenges and a multitude
of technological solutions aimed at automating clinical operations. Technology solutions
in the eClinical stack, such as clinical trial management system (CTMS),
electronic data capture (EDC), electronic trial master file (eTMF), and study startup
(SSU), represent quantum leaps forward for the industry, but also have their
share of challenges. The reality is that often these systems are not
integrated, resulting in an array of technologies that offer invaluable, yet
different, views of the clinical research environment. Frequently, lack of or poor
integration between such critical systems
leads to manual reconciliation of data that is
linked but resides in two or more different
systems, representing a time sink for study
teams that not only reduces their productivity
but can lead to delayed or poor
decision-making. It also does little to promote
collaboration; disparate systems inevitably
lead to a proliferation of Excel spreadsheets
across the organization used by individuals to
track key data for which there is no single
source of the truth. The problem goes far
beyond a technology integration challenge. At
its core, clinical research paradigms are
shifting, driven by new technologies that move
the focus from back-office data capture and aggregation tools that are loosely integrated to cloud-based apps and modern application development architectures that enable teams to collaborate in real-time.
It’s long overdue. Cloud-based
technology has been transforming many sectors of the economy and now it is finally
poised to address clinical trials - one of the most manual, error prone,
complex, bureaucratic, and, above all else, expensive bottlenecks in the
pursuit of new disease treatments.
According to research by leading analyst
firms IDC and Forrester, the cloud has become a core element of an enterprise’s
technology strategy.4 Over the past few years, the conversation
around cloud adoption has moved from “if” to “when” and “how.” The cloud
remains one of the most disruptive changes in computing in years with a
compelling value proposition that continues to propel adoption. It now drives transformative
innovation, enabling organizations to compete more effectively by instantiating
processes that deliver reduced cycle times and increased productivity. The
emergence of a global computing cloud heralds the arrival of entirely new
classes of innovation across applications and markets, including healthcare.
Technology adoption is most obvious at
the front end of healthcare, where health payment solutions, data analytics tools,
telehealth, wearable devices, and other products and services are addressing the
needs of both businesses and consumers. But just as important is what’s happening
behind the scenes, in the healthcare system’s back-end infrastructure.5
While many individual aspects of the clinical
trial process could be enhanced, Janet Woodcock, MD, Director, Center for Drug
Evaluation and Research (CDER) at the Food and Drug Administration (FDA), calls
for a focus on “transformational change in the way clinical research is conducted.”6
She describes a vision of clinical research in the United States akin to the national
highway system or the national energy grid – in other words, infrastructure, which
could link research and community practice, and facilitate universal participation
in the generation of new clinical evidence and its subsequent adoption by
But what exactly does clinical trial infrastructure
mean? In 2010, the National Academy of Sciences took a look at the key elements
a clinical trial infrastructure.7 They published the results of a
workshop conducted by the Institute of Medicine (IOM) on transforming clinical
research in the United States. A number of workshop participants lamented that
most clinical trials are conducted in a “one-off” manner. The term “one-off” alludes
to the current situation in which the necessary components of a trial (usually
a single coordinating center and multiple research sites) are brought together
for a discrete period of time and disbanded once the trial is completed.
Significant time, energy, and money are spent on bringing the disparate resources
for each trial together. Some workshop attendees suggested that efficiencies could
be gained by streamlining the clinical trials infrastructure so that those investigating
new research questions could quickly draw on resources already in place instead
of reinventing the wheel for each trial. Sadly, the clinical trial
infrastructure is much the same today as it was in 2010, but growing
discontent, dismal performance metrics, financial pressures, and new technologies
are finally moving the needle. And while automation has been strongly focused
on study conduct, stakeholders are becoming increasingly aware that better
study startup (SSU) processes are linked to shorter clinical timelines renewing
an emphasis on better infrastructure, resulting in
better study quality, faster start-up times, and
fewer costly one-offs.
Study start-up, a perpetual
bottleneck in clinical trials, includes activities, such as country selection,
pre-study visits, site selection and initiation, regulatory document
submission, contract and budget execution, and enrolling the first patient.
Jeff Kasher, President of
Patients Can’t Wait, and formerly VP Clinical Innovation and Implementation at
Eli Lilly and Company, comments “With globalization expanding its footprint,
improved study start-up is essential for building speed into the clinical development
process. Conducting clinical trials in places with unfamiliar regulatory pathways
and limited infrastructure is highlighting the value of study start-up
technology that allows for better SOP and regulatory compliance.”
HOW THE CLOUD IS TRANSFORMING STUDY START-UP: THE “CONNECTED EXPERIENCE”
Agile companies are
seizing opportunities around the cloud to drive innovation by creating
operational efficiencies and engaging study teams in new ways. Whether an
enterprise wants to consume or offer cloud services - they can leverage the
cloud to achieve new levels of the “Connected Experience” across the clinical
research value chain, from the study team to investigators and contract
research organizations (CROs).
So what does the
“Connected Experience” look like in the context of study start-up? Timeline
reductions are achieved using: alerts (which are automatically triggered as the
clinical trial unfolds), document collection, and version control and status
reporting, which reduce the number of hand-offs, errors, and downtime events
that can occur during the start-up phase of clinical trials. The use of a
purpose-built study start-up tool allows for the seamless sharing and
visibility of documents and associated information in real-time (globally)
facilitating hand-offs. Delays due to documents sitting in siloed email boxes
are eliminated as role management ensures continuity in the absence of a team
member and real-time reporting negates the need for status meetings, where dated,
manually prepared reports are reviewed for budget and timeline compliance.
The SSU infrastructure
allows milestones to be tracked, improves communications among partners, acts
as a central repository for study documents, and integrates the flow of information
from various data sources in a compliant manner.
With the advent of
intelligent document routing technology, stakeholders have the ability to
support country-specific document regulatory workflows. This functionality
automates compliance with SOPs, which, in conjunction with regulatory
guidelines, help improve the operational efficiency of clinical trials.
Historically, regulations have not provided specific guidance on the format or
content of SOPs, allowing companies to design SOPs that best conform to their
unique practices.8 But the long history of their being confusing,
overly complex, or existing in paper format has led to their less than consistent
use, even avoidance.
changes represent a transformational change envisioned by Woodcock, combing
data integration with innovative cloud-based solutions and advanced APIs for
seamless integration. Using this approach, bottlenecks that typically occur throughout
the start-up phase of clinical trials are reduced, bringing greater efficiency
to the critical path and tighter adherence to timeline and budget. With these and
other innovations dependent on integrated data, the unsexy plumbing at the backend
of the healthcare system has never been more important and represents a plethora
of opportunities to reduce costs, streamline processes, and shape the future of
an industry that services all.
THE CLOUD IS THE KEY TO CONNECTING THE CLINICAL RESEARCH VALUE CHAIN
As clinical trials
continue to evolve, drug companies will no longer be able to rely on existing,
tried-and-tested manual methods or point solutions for success. Technology
integration in the eClinical stack, though a necessary component of the
solution, is not sufficient to bring about the step change in productivity that
has to happen. Why? Collaboration and the “Connected Experience” means more
than just being able to access the same data. It requires the translation of
that data into targeted information based on user roles. It also requires the
ability to distribute work throughout the team, with appropriate approvals and
audit trails along the way, through configurable workflows. It’s a new paradigm
driven by service-oriented, cloud-based solutions that leave the unsexy plumbing
of traditional clinical trial systems behind. The result? An end-to-end clinical
trials infrastructure utilizing “best-of-breed” technologies to meet the formidable
challenges that lie ahead.
1. Pharmaceutical Clinical
Development: Electronic Data Capture (EDC) as a means for e-clinical trial
2. Transforming Clinical
Research in the United States: Challenges and Opportunities: Workshop Summary. http://www.ncbi.nlm.nih.gov/books/NBK50882/.
3. The National Cancer
Institute–American Society of Clinical Oncology Cancer Trial Accrual Symposium:
Summary and Recommendations. October 15, 2013, doi: 10.1200/JOP.2013.001119. http://jop.ascopubs.org/content/9/6/267.long.
4. 5 IT industry
predictions for 2016 from Forrester and IDC. Available at:
5. Techcrunch “Unsexy
Plumbing,” Integrated Data and The Future of the Healthcare System. http://techcrunch.com/2015/12/06/unsexy-plumbing-integrated-dataand-the-future-of-the-healthcare-system/.
6. Transforming Clinical
Research in the United States: Challenges and Opportunities: Workshop Summary. http://www.ncbi.nlm.nih.gov/books/NBK50882/.
7. Institute of Medicine
(US) Forum on Drug Discovery, Development, and Translation. Transforming
Clinical Research in the United States: Challenges and Opportunities: Workshop Summary.
Washington (DC): National Academies Press (US); 2010. 1, Introduction.
Available from: http://www.ncbi.nlm.nih.gov/books/NBK50879/.
8. Kumar M. SOPs: Least
understood, most important tool to ensure regulatory compliance. Regulatory
Focus. October 2011. Available at: https://www.amarexcro.com/articles/docs/RAPS_Focus_SOPs_Oct2011.pdf.
Accessed February 15, 2016.
this issue and all back issues online, please visit www.drug-dev.com.
Morgan is a technology and life sciences management professional with
more than 15 years of experience in the application of informatics and
bioinformatics to drug discovery. He currently heads up the Marketing and Brand
Development functions at goBalto, working with sponsors, CROs, and sites to
reduce cycle times and improve collaboration and oversight in clinical trials.