The CenterWatch Monthly (September 2014) Data and tech-aided enrollment services a competitive advantage

1. October 2014 A CenterWatch Publication Volume 21, Issue 10
CROs driving changes in patient recruitment
Data- and tech-aided
enrollment services a
competitive advantage
By Karyn Korieth
PPD’s acquisition of Acurian last summer
signaled a significant change underway
in the patient recruitment landscape:
Major CROs now consider patient recruit-ment
services, once used primarily to rescue
under-enrolling studies, as a core activity in
study planning. Providing strategies for pa-tient
recruitment has become critical to stay-ing
competitive in the CRO marketplace.
The acquisition created a strategic advan-tage
for PPD, which is privately held, and al-lows
the company to more effectively compete
against other major CROs—including Quin-tiles,
Parexel and INC Research—that have
invested significant capabilities and resources
in recent years to build in-house patient re-cruitment
services or have partnered with
leading companies to enhance patient recruit-ment
offerings.
Average number of randomized patients per trial per site
All TAs, phase II and III clinical trials
“CROs are trying to make sure they best
meet their customers’ needs. PPD showed a lot
of vision and a lot of innovation by bringing
Acurian into the fold,” said Richard Malcolm,
Ph.D., executive vice president and general
manager for Acurian, a business unit of PPD.
“Other large CROs have recognized that (pa-tient
recruitment) is an important challenge
and are giving it more attention, but they have
chosen to do it in a different way.”
Large CROs have moved into the space
as the entire industry redefines patient re-cruitment
practice with new technologies.
Electronic medical records and other patient
Source: CenterWatch
data sources have allowed more effective and
cost-efficient targeting of patients. At the same
time, the internet and mobile devices have
opened more channels for raising awareness
about clinical trials and communicating with
patients. As a result, patient recruitment strat-egies
have become more strategic and compa-nies
use a mix of tactics—which include both
traditional and non-traditional strategies—
depending on what will be most effective for a
study in a specific patient population or thera-peutic
area.
“The landscape is becoming more and more
see Patient recruitment on page 9
Trials with in-home nurses poised to grow
© 2014 CenterWatch. Duplication or sharing of this publication is strictly prohibited.
see In-home trials on page 12
Higher expense, but may
improve recruitment and
retention for select trials
By Ronald Rosenberg
CenterWatch Staff Writer
The quest to both recruit and retain clini-cal
trial participants has spurred a vari-ety
of patient-centric initiatives—from
online patient communities to the use of
neighborhood pharmacies as trial sites.
But one idea not only has caught on, it has
spawned a successful niche industry: in-home
clinical trials.
Registered nurses conduct site visits in pa-tients’
homes. While in-home services have
been in existence for several decades, their
use had been limited primarily to patients ei-ther
too sick to travel or homebound. But that
is changing. Home healthcare visits now are
being used to “rescue” studies that are behind
on enrollment or unable to retain patients, by
making study participation more convenient
for patients who otherwise might not be able
to enroll.
Although little industry data exists on the
in-home clinical trials market, signs point to a
growing sector, as patient-centric approaches
expand to include those participants who
have work or family obligations or have dif-ficulty
getting to and from a site. For exam-ple,
some Alzheimer’s patients must rely on
family members to take them to site visits,
6.6
5.3
3.7
2003 2008 2013

2. see Patient recruitment on page 10
mainstream,” said Paul Evans, vice president
of feasibility and enrollment solutions at Par-exel,
which employs 50 staff members in its
patient recruitment function. “There was a
time when patient recruitment was a bolt up.
Now it is core to the activities that we carry
out. That is a major mind-set change.”
Meanwhile, standalone patient recruit-ment
companies are stepping up tactics and
developing innovative ways to reach potential
patients in order to compete in the changing
landscape. Many of these companies con-tinue
to hire new staff, expand operations
overseas and develop new technologies to im-prove
patient recruitment and retention.
“Our growth has come from innovation
and focus on new technologies—new ap-proaches
that further engage patients mak-ing
decisions,” said John Benbrook, CEO
of MMG, a global health communications
group that specializes in patient recruitment
and retention.
And the landscape will continue to evolve,
as patient recruitment remains one of the big-gest
challenges in clinical research. Accord-ing
to the Tufts Center for the Study of Drug
Development, 48% of sites either under-enroll
or fail to enroll subjects. A lack of study par-ticipants
delays new drugs from entering the
market and adds to overall drug development
costs. In addition, failing to enroll the re-quired
number of patients at sites can weaken
the statistical power and scientific validity of
a trial.
“No one in this industry can develop a
product without patients. Enrollment is the
longest and most costly stage of clinical de-velopment,
and most studies fail to meet their
recruitment targets,” said INC Research CEO
Jamie Macdonald. “It’s a frustration for CROs
and sponsors alike. There is a lot of work that
still needs to be done in order to best match
sponsor protocols, patients and, equally as
important, motivated investigators and mo-tivated
sites.
CROs driving change in practices
Major CROs have built in-house patient
recruitment services and strategic collabora-tions
with specialty patient recruitment firms
as they increasingly take over study conduct
and site management activities for sponsors.
Meeting patient recruitment milestones on
time and on budget has become a key mea-sure
of their success. Sponsors, which largely
rely on traditional media and physician refer-ral
practices to recruit patients, also are asking
their CRO partners to provide new opportu-nities
and innovative ways to find patients for
trials. As a result, major CROs have helped
drive change in patient recruitment practices.
“Pharma has always had some capability
in-house, but usually it’s been a small group
and probably not enough to be really effective
for them. As we have seen the move toward
more outsourcing and strategic partnerships,
more of the work has flowed to CROs, which
can take a broader view of how we go about
the job,” said Parexel’s Evans. “Pharma out-sourcers
are really looking to us for innova-tion
and better delivery. We have been able to
take a longer-term and, in some ways, more
innovative view of patient recruitment and are
able to bring fresh thinking to the problem.”
During the past three or four years, as the
idea of patient centricity has changed the way
the industry thinks about recruitment tactics
and advertising, leading CROs have been at
the forefront of developing new ways to con-nect
with patients, match them with research
opportunities and understand their perspec-tives
about clinical trial participation.
Quintiles, for example—which manages
relationships with more than three million
patients through its Digital Patient Unit—can
ask targeted groups of patients for feedback on
particular protocol requirements that might
be challenging for recruitment or mine its
data to inform study recruitment strategies
that take patient needs into consideration.
Other companies, including Parexel, use web
listening to understand what patients think
about their disease, treatment options and
trial opportunities.
“The most important way to attract pa-tients
into trials today is by understanding the
patient,” said Chris Frega, senior director and
head of global feasibility and patient recruit-ment
at Quintiles. “By understanding the pa-tient,
we can understand what messages will
resonate with them and whether it’s a study
that they are willing to participate in or not.
If we know where they are and how to reach
them, we can tailor our techniques to make
sure that we get those messages to them.”
CROs also use digital technologies to tar-get
patients and develop recruitment strate-gies.
Quintiles also has been a leader in using
electronic health records as part of its patient
recruitment strategies to determine whether
patient populations exist that can meet a pro-tocol’s
inclusion/exclusion criteria, what limi-tations
the protocol might place on the ability
to recruit patients and where potential study
October 2014 | The CenterWatch Monthly 9
IndustryNews
Patient recruitment
continued from page 1
Plan to actual enrollment performance
2012 screen to completion rates
Increase in planned total study
duration to reach target enrollment
Overall 56% 94%
Cardiovascular 59% 99%
CNS 61% 116%
Endocrine/Metabolic 41% 113%
Onoclogy 78% 71%
Respiratory 59% 95%
* Does not include screen failure rates
Source: Tufts CSDD, 2012 <csdd.tufts.edu>

3. IndustryNews
volunteers can be found. These technologies
can provide insight about patient conditions
and geographies, which gives companies the
ability to target patients with particular study
opportunities.
“You need to have a very strategic and con-trolled
process for targeting the particular
patients you are looking for. No longer are we
having to put out a wide message,” said John
Reites, senior director of health engagement
and communications at Quintiles. “It’s be-coming
much more strategic and much more
focused on the return-on-investment than
ever before.”
Sponsors historically have been reluctant to
spend money upfront on patient recruitment
services; CenterWatch analysis found only
6% to 7% of a typical study budget is allocated
for these services. Yet as use of metrics and
analytics increasingly lead to more predict-able
and cost-effective recruitment strategies
that can speed study enrollment and provide
a greater number of patients per site, sponsors
have become more willing to engage compa-nies
for patient recruitment services earlier in
the design or pre-study planning phase.
“As we get better, the role will get bigger
and bigger and we will see patient recruit-ment
continuing to occupy an important spot
in the conduct of clinical trials and, probably,
a larger spot in the pre-study planning rather
than the mid-study rescue,” said Malcolm,
adding today as much as two-thirds of Acu-rian’s
work is commissioned by sponsors
prior to the start of studies, a change from
eight years ago when the company often was
an agent of last resort.
As CROs move to the front line in manag-ing
site relationships for sponsors, they have
the ability to improve patient recruitment
practice by supporting sites and helping im-prove
their productivity.
INC Research has structured its patient
recruitment strategy around having a solid
relationship with its sites, which ultimately
are responsible for recruiting patients, and
supporting site efforts to deliver patients for
a trial. The CRO first identifies the most ap-propriate
investigators and sites for specific
trials and then helps site staff understand
what motivates patients to participate in tri-als,
how to engage patient groups and what
factors either aid or hinder retention. As part
of its program, INC built teams of specialists
with a blend of marketing and clinical back-grounds
to support standardized outreach,
education and recruitment of patients; these
specialists are integral in supporting the site
staff assigned to handle screening and enroll-ment
activities.
“We continue to look for ways to deepen
our understanding of patient populations
and what motivates them, so that we can find
them and place them with the right study,”
said Macdonald. “Our knowledge comes
from a deep understanding of historical data
and patient demographics. This information
allows us to provide sites with patient-centric
data sets and develop a wide range of tools
and materials that can support staff and trial
participants.”
Recruitment firms step up tactics
Questions have been raised about how
standalone patient recruitment firms can
compete against large, global CROs in the
changing marketplace, particularly as trials
become more global and complex. Health-care
Communications Group (HCG), which
specialized in rescuing trials in trouble, for
example, exited the industry two years ago.
Some wonder if CROs ultimately will push
other patient recruitment companies out of
business in the near future.
Yet senior executives—from both major
CROs and patient recruitment companies—
see a continued role for specialized patient
recruitment service companies. Some CROs
partner with these companies rather than
build in-house capabilities and want to col-laborate
with providers that have specific
knowledge of a market, disease or geographic
area to recruit patients for a particular study.
Importantly, both CROs and patient recruit-ment
firms believe the smaller companies can
continue to thrive by innovating and improv-ing
patient recruitment practices.
“We certainly can’t hope to have all of the
expertise we need in-house, and we certainly
can’t expect that all of the innovation will
come from us,” said Parexel’s Evans. “We
enjoy working with small, innovative com-panies
and tapping into what they have that
is exciting and vibrant. It’s a market of ideas
out there.”
Bonnie A. Brescia, co-founder of BBK
Worldwide, which was instrumental in defin-ing
the patient recruitment landscape when
the company was founded in 1983, said the
patient recruitment market always has looked
to expert, functionally specific companies for
new ideas.
“We got started because we were pushing
the envelope and applying new areas of exper-tise
and skill set,” said Brescia.
Niche companies, which may offer only a
Patient recruitment
continued from page 9
Why do physicians refer few patients?
Lack of information about the study 58%
Lack of time to evaluate the study 30%
Unsure where to refer patient 28%
Lack of time to discuss options with patient 9%
Fear of liability 5%
Fear of losing patient to PI 3%
Note: Multiple responses offered Source: CenterWatch survey of 244 physicians, 2012
10 The CenterWatch Monthly | October 2014

4. single patient recruitment product, also have
emerged. TrialReach, which makes patient-friendly
clinical trial content available across
a large number of web sites, and Trialbee, a
European clinical trial matching company,
are two examples of specialty companies that
have launched during the past five years.
At the same time, CenterWatch’s experi-ence
with its more traditional trial listings
demonstrates growing patient interest in on-line
access to clinical trial information. Its
Clinical Trial Listing Service has seen grow-ing
usage from sponsors, CROs and niche
provider companies in response to rapid
growth in patient traffic to its site—from
84,000 unique visitors per month in 2010 to
more than 200,000 unique patient visitors per
month this year.
Meanwhile, standalone patient recruit-ment
firms are stepping up tactics to compete
in this new environment. Some are building
partnerships to access sophisticated metrics
and analytics, which have become critical
to targeting patient recruitment campaigns.
Others are developing new ways to use tech-nology,
such as mobile apps or interactive
videos, to recruit patients more effectively.
Specialty communications groups also have
created cutting-edge advertising campaigns
more likely to attract the attention of potential
trial participants and their families.
“For BBK specifically, the competitive land-scape
hasn’t changed much because we are
constantly innovating and developing new
products that allow us to stay ahead of the
curve,” said Aaron Fleishman, head of social
strategy at BBK Worldwide.
MMG, through an exclusive partnership
with a healthcare technology called MedRe-spond,
has introduced a new video-based
education program in many recruitment
campaigns that allows patients to ask ques-tions
about a trial opportunity in their own
words through a study web site or mobile app.
The system then selects a pre-recorded vid-eo,
which already has been approved by the
study’s IRB or ethics committee, to answer the
questions. The platform also gives sponsors
Percentage of sites randomizing one or more patients per trial
89% 92% 91% 87%
All regions Europe Asia Pacic North America Latin America
first-hand, de-identified information about is-sues
and concerns about the study raised by
patients and their caregivers; MMG’s special-ists
can use the information to refine recruit-ment
and retention strategies and messaging.
“If you think about how people are digest-ing
their information today, video is where it
is,” said MMG’s Benbrook, who said pilot pro-grams
have shown an “exponential boost” in
enrollment rates compared to trials for which
patients receive only traditional study educa-tion
materials. “If you think about a study web
site, no matter how good that content is, you
hope that the patient is going to engage. If they
have a question, how do they get their ques-tion
answered? On one particular study, indi-viduals
were logging in three different times,
on average, and spending an hour on the web
site. They were able to ask questions anytime
and get those questions answered.”
MMG also has established a key partner-ship
with a company called DarkMatter,
which has an analytic tool that can access
more than 500 billion U.S. healthcare claims
and physician data records, which strengthens
MMG’s ability to target its outreach depend-ing
on the indication, study requirements and
patient populations.
Earlier this year, BBK Worldwide intro-duced
the use of streaming radio, where users
listen to custom radio stations streamed via
the internet, as a tactic that could be used for
global patient recruitment. BBK found more
than 45% of the population listens to global
streaming radio and a majority keep their in-ternet
browser open while streaming, which
80%
Source: Tufts CSDD, 2012 csdd.tufts.edu
allows companies to engage that audience
with banners or videos that could drive po-tential
patients directly to an online screener.
BBK also has been heavily involved in de-veloping
mobile applications that can support
patient recruitment and retention while also
allowing sponsors and sites to monitor patient
data in real time and change tactics as needed
based on that information. In addition, the
company uses social media to build relation-ships
with advocacy groups. The efforts are
part of BBK’s wider approach of using ana-lytics
and technology to understand which
patients to target for a particular study, what
needs to be communicated and the most ef-fective
and efficient communication channels,
which might include traditional media, online
advertising, advocacy groups or mobile apps.
“How people receive messages is a dynamic
field and it is never going to stop changing,”
said Brescia. “The media that reaches target
audiences has and always will continue to
evolve. One of our philosophies and business
strategies is we have a team of people who are
paying attention to what are these new ways of
distributing messages.”
A few healthcare communications compa-nies
that specialize in patient recruitment also
have developed more creative media advertis-ing
campaigns to attract greater attention to
trial opportunities. U.K.-based Langland has
been on the forefront of developing edgy, cre-ative
patient recruitment campaigns, includ-ing
a notable TV commercial for U.K.-based
Synexus Clinical Research, which sought
see Patient recruitment on page 12
October 2014 | The CenterWatch Monthly 11

5. IndustryNews
to build a database of potential study par-ticipants
with asthma. The campaign used
live-action film and stop-motion footage to
tell the story of a “little lost breath.” Another
campaign, which targeted students for a vac-cine
study, used humor in its slogan: “We’re
Looking for Ways to Spread the Love, Not
the Meningitis.”
“Being different, you can generate more
noise and increase the value of what you are
doing,” said Kate Spencer, managing part-ner
of Langland. “Quite often we are pulled
in as a rescue when an ad has been running
for months and months and months and pa-tients
just have not responded. We have been
able to demonstrate that with something that
does stand out a bit more and does make an
emotional connection with our audiences.
You actually can turn that around fairly
quickly and have a much more effective re-sponse,”
she said.
Many companies have been reluctant to
use more innovative patient recruitment
techniques or cutting-edge campaigns out
of fear they might somehow violate regula-tions.
Yet Mitchell Parrish, J.D., a regulatory
attorney who provides legal counsel to IRBs
and their clients, said there isn’t any prob-lem
with creative tactics from a regulatory
perspective, as long as they comply with the
FDA’s current guidelines about recruiting
study subjects.
“IRBs need to be open to all forms of ad-vertising.
The IRB industry is not here to
stymie development or take away creativity
in effectively advertising for clinical trials.
What the IRBs are here to do is protect the
rights, safety and welfare of participants and
to ensure research complies with applicable
regulations,” he said. “If an advertisement is
compliant, is not detrimental to participants
and is accurate, then researchers should re-main
free to spend their money how they
wish and invest in whatever advertising is
necessary to help meet target enrollment.”
Looking ahead
The landscape will continue to grow and
evolve since the problem of recruiting pa-tients
into clinical trials cannot be solved
easily. CROs are expected to continue build-ing
in-house capabilities and partnerships
that strengthen their patient recruitment of-ferings.
Standalone and specialty companies
will continue to thrive as long as they create
new ideas that can bring patients into clinical
trials. Yet no one can predict what new tac-tics
might emerge to improve patient recruit-ment
strategies moving forward.
“People always talk about patient recruit-ment
like somewhere out there is a silver
bullet, a solution that is going to absolutely
open up this problem for us and solve it. I re-ally
don’t think that is what we are looking
at,” said Parexel’s Evans. “Overall, it’s about
raising awareness with patients, support-ing
the sites to deliver and having a broad
range of tools available so that you can target
the right protocol to patients. There is never
going to be a silver-bullet solution to patient
recruitment.”
Karyn Korieth has been covering the clinical
trials industry for CenterWatch since 2003.
Her 30-year journalism career includes work
in local news, the healthcare industry and
national magazines. Karyn holds a Master’s
of Science degree from the Columbia Univer-sity
Graduate School of Journalism. Email
Karyn.korieth@centerwatch.com.
Patient recruitment
continued from page 11
leading to scheduling difficulties and stress,
which in-home trial visits could eliminate.
“In-home clinical care patients are a sliver
of the overall number of clinical trials, as
90% or more of trials have no at-home visits,”
said Rick Heth, executive vice president of
PCM Trials, a six-year-old, at-home clinical
trials company that is part of PCM, a long-time
provider of home-care services. “Mobile
nursing visits are all about making life easier
for subjects.”
Proponents of home visits point to faster
enrollment, higher retention rates and in-creased
compliance among trial partici-pants—
the dropout rate is a mere 3%—as
12 The CenterWatch Monthly | October 2014
major reasons that despite the additional cost
of home visits, total trial costs are similar
to those using traditional site visits. Patient
dropout rates in traditional trials can range
from 15% to 30%, with sponsors spending ex-tra
to over-enroll patients to meet required
enrollment targets. And compliance and re-tention
can be difficult for patients who live a
distance from sites and are not always able to
make scheduled site visits.
While acknowledging the cost differen-tial—
some in the industry estimate the aver-age
home visit can cost up to 50% more than
the average site visit—proponents maintain
that cost is offset by the fact that the spon-sor’s
overall development timelines can be
reduced by months, or even years, over con-ventional
studies. They also cite the ability to
enroll fewer, more productive, sites.
“We are starting to see more companies,
like Genentech, creating outsourcing special-ist
positions to oversee home healthcare ser-vices,
or companies adding home healthcare
services to their outsourcing specialist’s re-sponsibilities,”
said Gail Adinamis, founder
and CEO of GlobalCare Clinical Trials, one
of the largest at-home service companies. In
1992, she created the business model for cen-trally
managed in-home and alternate site
services for clinical trials. She launched and
headed three subsidiaries for national home
healthcare companies (Caremark, Coram
and OptionCare) before launching the first
independent ambulant care company fo-cused
specifically on clinical trials, Clinical
Resource Network (now Symphony Clinical
In-home trials
continued from page 1