F E AT U R E

Can web 2.0 reboot clinical trials?

Malorye Allison
Dozens of companies are trying to leverage social networking and other software tools to accelerate trials and reduce
their cost.

E nrolling patients in clinical trials is a peren-

© 2009 Nature America, Inc. All rights reserved.

nial challenge for sponsors. One-third of

trial sites fail to recruit a single patient and
fewer than 20% of clinical trials are completed
on time, with about half of the delays attrib-
uted to patient recruitment. Oncology trials in
particular are failing to meet enrollment goals
(Box 1).
Some see social networking tools on the web
as a remarkable opportunity to galvanize the
process of patient recruitment, perhaps even
a chance to completely reinvent the process of
clinical research itself. But new technology adop-
tion in clinical trials has traditionally been slow.
After years of complaints from investigators and
companies about how tedious and inefficient
paper-based trials are, still just half of all clini-
cal trials use electronic data capture, according

to Jim Rogers, CEO of Nextrials (San Ramon,
CA, USA), a software provider. “Electronic data
capture has a fair amount of traction.” But that
doesn’t mean other information technology
tools would by welcomed by the professionals
who plan and run trials.
For one thing, using social networking in this
way raises some worries, particularly around
privacy issues. “We are treading lightly in the
area of social media, because there are a lot of
concerns about disinformation on the web and
HIPAA,” says Gretchen Goller, patient recruit-
ment and compliance strategist at Sanofi-
Aventis (Paris). (HIPAA is the US Health
Insurance Portability and Accountability Act
that protects the privacy of individually identi-
fiable health information.)
That’s not stopping a pack of startups as well
as some established vendors with new tools from
trying to shake things up (Table 1). Within the
next year or two we’ll know whether this effort
will pay off.
Malorye Allison is a freelance writer based in
Acton, MA.
Companies are experimenting with social networking to speed clincal trials and even drug discovery.
Aiming for a revolution
Most pharma and biotech companies are not
focused on the Internet as the cure for their clin-
ical trial problems. Instead, they are concentrat-
ing on improving their relationships with the
doctors who work on the trials and the patients
their products are developed for. Sanofi-Aventis,
for example, tries to “make our [clinical trial]
sites see that we are in it for the long haul, and
that we are invested in these patients,” Goller
says. That means giving patients something
back, such as information about trial results.
Brian York, director of feasibility and patient
recruitment at Amgen (Thousand Oaks, CA,
USA), says his company is focusing on educa-
tion and training around patient screening tools
and consent forms.
But several new ventures are attempting to
build businesses by pushing the envelope when
istockphoto
it comes to clinical information. PatientsLikeMe
(Cambridge, MA, USA; http://www.patients
likeme.com/) has one of the most radical
approaches. In this online community, patients
share details of their health with other members
or, depending on their preferences, with anyone
on the Internet. Two of this site’s founders are
brothers—Ben and Jamie Heywood—who were
inspired to found the company by a third broth-
er’s battle with, and eventual death from, amyo-
trophic lateral sclerosis (ALS). PatientsLikeMe
has over a dozen communities around specific
diseases such as multiple sclerosis (MS), ALS,
AIDS and fibromyalgia. Their goal is to spawn
“a new system of medicine by patients for
patients”.
Besides a typical privacy policy, PatientsLikeMe
has an “openness philosophy” that distinguishes
it. “When you let crowds access the data does

nature biotechnology volume 27 number 10 october 2009 895

 feature

confidential, Novartis reportedly accelerated an

Box 1 Low-tech works too: boilerplate trial contracts MS trial by several months using the site2.
UCB has a different goal. The company wants
Oncology is both where many new therapies are being discovered and where the biggest
to learn more about the natural course of epi-
problems occur: only ~3% of patients participate in research. A recent analysis showed that
lepsy, which is one of its key indication areas.
more than one trial in five sponsored by the US National Cancer Institute failed to enroll a
“We are committed to learning as much as we
single patient. Only half the trials studied in that analysis recruited enough patients to do a
can about epilepsy,” says Jouko Isojarvi, senior
meaningful analysis3.
medical director, central nervous system, UCB.
These drastic circumstances prompted a lot of soul searching and produced some
“Although it is a challenge to approach this
surprisingly low-tech but potentially high-impact solutions to the problem. In the fall
kind of new information, we think that because
of 2008, the CEO Roundtable on Cancer released “common language” for clinical trial
this [site] is patient-to-patient they may be
contracts that could “reduce contract negotiation time from as many as 300 days to as
more open about the kind of information they
few as 30,” according James Doroshow, director, NCI Division of Cancer Treatment and
Diagnosis. The project brought collaborators and competitors from pharma, biotech and
share.” The company will develop surveys and
NCI together to figure out which sections of clinical trials contracts could be standardized.
other tools to glean information from the online
The group analyzed 80 clinical trial agreements and found that the final agreements community.
showed greater than 67% convergence on key sections. Delays due to contract negotiations
over the language in these documents can drastically slow down research and costs A new research model?
an estimated $1 million per day. The agreed-upon clauses are now available on the PatientsLikeMe and its collaborators, including
Roundtable’s Life Sciences Consortium website (http://ceo-lsc.org/). some patients, are also doing their own nontra-
© 2009 Nature America, Inc. All rights reserved.

For M.D. Anderson Cancer Center and AstraZeneca’s “Project Zero Delay,” the two ditional research by collecting and analyzing
sponsors simply started doing many tasks in parallel that are typically done sequentially4. data on the site. For example, the group has
Some tasks usually performed after investigational new drug (IND) clearance by the FDA ~3,700 ALS patients, of which more than 400
were also done ahead of time instead. The result: a phase 1 clinical trial of a MEK inhibitor have taken lithium at some point. When pre-
was able to enroll its first patient two days after the FDA approved the IND. That same step liminary data came out in early 2008 suggest-
typically can take as long as three to six months. ing lithium might be a useful treatment for this
At the core of this new approach are “master agreements” and strategic alliances, which disease, PatientsLikeMe was able to immediately
AstraZeneca (London) has established with M.D. Anderson Hospital (Houston) and other start collecting data from members about the
medical sites, including Vanderbilt-Ingram Cancer Center (Nashville, TN, USA) and Baylor drug’s effects and graph it on the site. In a post
University (Houston). “Contracts and budgeting negotiations were slowing us down,” says on the site dated March 2008, Jamie Heywood
Steven Strand, AstraZeneca’s global director for external scientific affairs. “With these writes, “…we will run the first real-time, real-
agreements in place, it means we don’t have to renegotiate the terms for every new trial as world, open and nonblinded, patient-driven
we go along.” trial. We believe we will have the power, within
Strand says other companies are trying the same strategy and AstraZeneca has used it in months, to begin answering the question of how
the UK. “We’ve seen a 40% reduction in startup times with Manchester Cancer Research much lithium modifies the progression of ALS.”
Centre,” he says. This analysis will include data on more patients
These types of agreements are much easier for big companies to establish than for than any published study of the drug to date.
smaller ones. However, this could be the start of an evolution toward standard language and That paper hasn’t yet appeared, and Heywood
processes for these cumbersome administrative steps, for everyone. says they are still crunching the numbers.
PatientsLikeMe has recently partnered with
another innovative startup, personal genomics
that change the game? History says yes,” says disease progression similar to their own and company 23andMe (Mountain View, CA, USA;
Jamie Heywood, chairman of the company. participate in a community that discusses and http://www.23andme.com/) in a bold effort
Web 2.0 has already produced some surprises shares the latest breaking information on their to recruit 10,000 people with Parkinson’s for a
that are relevant for clinical trials. For one thing, condition and any new treatments that might study (Box 2, Fig. 3). 23andMe uses Illumina’s
although surveys indicate privacy is a hot but- improve care (Fig. 1). The ability to join a com- Human Hap 550+ BeadChips to read more
ton issue for healthy people1, that isn’t always munity, give each other support, share insights than 550,000 single nucleotide polymorphisms
the case for patients facing a life-threatening ill- about their disease and its treatment, see how (SNPs) across a customer’s genome. The com-
ness. On PatientsLikeMe, the data are all kept others with the same disease are doing, and learn pany then provides analysis regarding what is
anonymous and people are encouraged to use about clinical trials is enabled by the web plat- known about the association of those SNPs with
an alias, but they can add information that iden- form. In addition to several nonprofit groups, a person’s risk of certain diseases.
tifies them, like photos. PatientsLikeMe has partnerships with phar- As part of the collaboration, in July,
The site has more than 40,000 members, and maceutical companies Avanir Pharmaceutical PatientsLikeMe gave its Parkinson’s community
the company reports that about half of those (Aliso Viejo, CA, USA), Novartis (Basel) and tools already being used by its ALS community
have recently visited the site. Patients are not UCB (Brussels). to store their genotypes. “People were starting
required to input data to access the site, and its Novartis, Avanir and other groups have used to upload their genomes to the site,” Heywood
largest community is patients with MS, with the site to recruit individuals as subjects for stud- says. “We wanted to be able to do something
more than 13,000 members. ies. These partners can create pages on the site with that data.” That data are augmented with
The group is upfront that their business with links to online prescreeners that determine self-reported phenotypic data. Linda Avey,
model is selling aggregated anonymous data whether someone is likely to be eligible or not. cofounder of 23andMe, says the company will
to pharmaceutical, healthcare and other com- Although data on exactly how many patients look at how factors like ethnicity and environ-
panies. Members can find other patients with have been recruited through PatientsLikeMe are ment affect disease risk and treatments.

896 volume 27 number 10 october 2009 nature biotechnology

 feature

Table 1 Selected companies leveraging social media for clinical trial recruitment
Company Product Comments Milestones
23andMe Research Revolution: ten specific disease Launched in early July 2009, the site More than 350 patients have signed up for
groups/communities are “racing” to get encourages patients to “push research the ten specific Research Revolution commu-
1,000 patients signed up forward and see your DNA for $99.” nities; the largest community is migraines.
Diabetic Connect A social networking site with information This site is a platform that has been updated Approximately 50,000 registered users on
Urbana, IL therapy and online search for trials and replicated for the company’s new sleep Diabetic Connect. Recruited for several tri-
integrated into the site disorders site. Multiple new communities are als already. Currently doing one study that is
planned for obesity, senior health, arthritis, priced based on enrollment figures (that is,
back pain, general pain management. how many patients are enrolled and show up
for first appointment).
Emerging Med Website that allows patients to search for Patients create a profile that is matched Since December 2000, more than 115,000
Navigator cancer trials against eligibility requirements of more patients have used the site to find trials.
New York than 10,000 trials in the United States and
Canada. Dial-up “Clinical Trial Specialists”
provide additional advice and support.
Healogica Search algorithm and other tools to make it Includes an iPhone application and propri- 30,000 unique visitors since launch in
easier for patients to find clinical trials etary prescreening tool. Most sign-ups have Spring 2009. Over 1,000 patient sign-ups.
led to a connection to a trial or group of Over 20,000 structured trials in the database.
trials. Working on incorporating data from
international trials not in ClinicalTrials.gov
© 2009 Nature America, Inc. All rights reserved.

through partnerships in Europe and Asia.

iGuard Drug safety monitoring service that also Launched in October 2007, the site has Has 1.7 million members and adding
collects feedback from patients and shares quickly gained significant traction. ~30,000 per week. Doing approximately
that info three new research protocols per week.
Inspire Multiple communities around almost Partners with advocacy groups to create More than 120,000 registered members, who
200 support groups online communities. Members are notified have contributed more than 725,000 posts.
of trials. The company has four contracts in place, two
with a major pharma for trials in osteoporosis,
arthritis and lung cancer. For one of the can-
cer studies, Inspire already has a community
with ten times the number of members who
meet the initial inclusion criteria.
PatientsLikeMe Building 17 patient communities where Seeking to pioneer online research model. Approximately 40,000 members, across
people share experiences and post their 17 communities, about half of whom are
health data active at any point in time. Multiple sclerosis
community is largest at more than 13,000.
Private Access Privacy Layer, RecruitSource, TrialsFinder Advocacy groups and partners, such as As part of a pilot launched in May 2008,
Irvine, CA and Records agent: allow patients to share Pfizer, will collaborate with Private Access. 100 e-mails were sent to patients who are
private health data selectively with Groups can put a widget on their website registered at a Klinefelter Syndrome advocacy
researchers that lets patients join, set their privacy website. Forty-nine patients registered with
directives, and show their data to researchers the site within 2 weeks and all but one had
recruiting for trials. set up their privacy directives.
Sermo Sermo Panel Express Recently introduced, mainly used for protocol More than 110,000 physicians are members
design review. and have logged more than 40,000 discus-
sions and left more than 3 million comments.
Has deals with ten pharmas.
Susan Love’s Army of Website aimed at recruiting a million healthy Aims to “challenge the scientific community To date, the group has signed up more than
Women women of every age and ethnicity, including to expand its current focus to include breast 270,000 women and issued several “calls
Los Angeles, CA breast cancer survivors and women at high cancer prevention research conducted on to action.”
risk for the disease, to participate in research healthy women.”
TrialX Clinical trial search service that can access Emphasizes convenience for patients; for Gets upwards of 10,000 visitors per month.
PHR data. Available at the TrialX site or via example, drafts e-mails on behalf of More than 3,000 trial-matching searches
Twitter. patients for investigators. are done per month. A couple of hundred or
more messages exchanged between patients
and investigators per month. Some 50–100
people have used the Twitter application.
VisionTree/JDRF Clinical trial search service for people with Sponsored by well-established advocacy Over 5,000 patients preregistered and
diabetes Type 1 group that is itself sponsoring about 40 hundreds were added each day after launch.
clinical trials currently.

“Both groups think the current research para-
digm is not serving patients and is inefficient.
No one has figured out the right model yet,” says
Heywood. “With Parkinson’s we will come up
with a new system.” Patients will also have a say
in what research is done, and earlier and broader
access to results. Avey says, “Once you build a
community of patients, there is so much more
that you can do and that’s what the research
community hasn’t done. This is not about get-
ting a publication or a grant, it’s about how do
we make progress against these diseases.”
About the same time they inked this deal,
23andMe launched an entire new research
environment (23andWe), described as “a do-it-
yourself revolution in disease research.” Patients
can form their own 23andMe communities, and
23andMe scientists and collaborators will con-
duct research within any community that grows
big enough—reaching at least 1,000 patients.
Patients can participate in research by signing

nature biotechnology volume 27 number 10 october 2009 897

 feature
© 2009 Nature America, Inc. All rights reserved.
Figure 1 PatientsLikeMe offers people a chance to network with others, learn about their illness and
find out about clinical trials.
up for a community and buying either the $99
“Research Edition” of the company’s genotyp-
ing service, or the whole package at the regular
$399 price. Patients can also become “research
captains” by helping the company recruit more
community members. Top recruiters will get the
chance to speak to the research team about what
research is done and how.
Ten disease areas have been started, including
migraines, severe food allergies, celiac disease
and testicular cancer. The project was launched
in early July and as Nature Biotechnology went
to press, migraines seemed to be leading the
race with just over 140 patients signed up.
Interestingly, 23andMe is going after some of the
same communities as PatientsLikeMe, including
MS and ALS. “Obviously, they are trying to grow
their online communities,” Heywood says.
Although it’s an intriguing model, some ques-
tion how easy it will be to verify the data. People
may be mistaken, misinformed or even pur-
posefully submitting someone else’s data for one
reason or another. There are also questions as to
self-reporting bias—the tendency of people not
to report their symptoms objectively, particu-
larly if they are influenced by other patients. But
perhaps 23andMe’s greatest challenge is to show
that genotyping research is relevant to clinical
practice. “We have the best model to show the
value of SNPs,” says Avey.
Another leading community site is
DiabetesConnect, which was created by Alliance
Health (Salt Lake City, UT, USA), a healthcare
898 volume 27 number 10 october 2009 nature biotechnology
PatientsLikeMe
marketing firm. Here patients can share infor-
mation and get what is now called “information
therapy”—articles, videos and podcasts about
wellness and various conditions and how to
manage them. They can also find out about
clinical trials.
The director of client services, Joe
D’Alessandro, says that the core of Alliance
Health’s business is generating leads for medi-
cal products companies. The company recently
branched out into clinical trial recruitment
and is “meeting customer’s goals,” he says, after
netting more than 50,000 registered members.
“About 20% of the members are responsible for
80% of the activity on the site,” he says. That
ratio is likely to be a crucial one. If patients are
only visiting a site briefly, and then never return-
ing, it will be hard to keep a flow of trial recruits
coming.
Happy with the site’s progress, the company
has launched a similar sleep disorders site and
plans to launch several more.
Docs too
Patients are not the only group served by social
networking sites. Sites like ozmosis (http://www.
ozmosis.com/) and Sermo (Cambridge,  MA;
http://www.sermo.com/) have communities
exclusively for physicians, who join the site to
trade insights, ask questions and set up net-
working groups. Sermo has ~110,000 physi-
cians signed up. So far they’ve logged more than
40,000 discussions and left more than 3 million
comments. The company makes money by sell-
ing information gleaned from the community
and selling access to its doctors to government,
academic, finance and healthcare organiza-
tions.
Sermo also supports clinical trials in several
ways. Using its “Panels Express” service, 10 to 20
physicians with specific areas of expertise can be
recruited within as little as a day. Sermo reports
that all the physicians in its database have been
credentialed and authenticated, and that they
span 68 specialties and all 50 states. Physicians
can be recruited to participate in protocol
design review, or discussions about ethics, bio-
statistics and adaptive trials. The company can
also do surveys for site selection and feasibility
studies.
Sermo has 50 clients and deals with “ten of
the top twelve pharmaceutical companies,”
according to Pam Randhawa, vice president of
strategic development at Sermo. “We have also
done work with the FDA [US Food and Drug
Administration] and with the CDC [US Centers
for Disease Control (Atlanta, GA, USA)] on
influenza.” Those deals cover a range of activi-
ties. The company has done at least two proto-
col design reviews so far. Because it’s all online,
customizable and the physicians are active in the
community, “we can help companies get feed-
back upfront,” Randhawa says. “In some cases,
you could save as much as six months by using
our service,” she claims.
Taking a lesson from Detroit
iGuard (Princeton, NJ, USA) takes a novel
approach. Before founding the company,
CEO Hugo Stephenson spent several years
running phase 3b and phase 4 studies for the
giant contract research organization Quintiles
Transnational (Research Triangle Park, NC,
USA). As drug safety concerns became more
pronounced, he realized that the current adverse
event monitoring systems were inadequate. “To
do safety studies, you have to recruit doctors
who have patients,” he says. “I’d be lucky to get 3
out of 100 doctors that I asked, and 50% of those
recruited drop out within a year.” Stephenson
wrote a white paper outlining a more efficient
system. He says Quintiles management read the
paper and said, “Let’s do it.”
Stephenson’s approach is modeled after what
US carmakers do. “You can drive a car around
a test track 10,000 times, but until you are driv-
ing it in the snow, up a steep road, with four
kids in the back and a trunk full of luggage, you
don’t know how it will operate in those con-
ditions,” he says. Drugmakers have the same
problem because their products are tested in
homogenous populations then released into the
real world where they are used under a much
broader range of conditions.

Carmakers solved their problem by having
customers register their vehicles and then col-
lecting data during regular maintenance visits.
This way, the carmaker is the first to know if a
particular model has a defect. To mimic that
system, Stephenson developed iGuard—a med-
ication monitoring service for patients.
The company advertises its free service
through a variety of “channel partners,” such
as credit rating sites and pharmacies. “We don’t
focus just on health sites,” Stephenson says. “We
go wherever there are lots of people.” In the
course of their regular business activities, these
partners ask their customers if they would like
to enroll in a medication monitoring service.
To join, patients fill out a simple form listing
the medications they take, their age, sex, race,
the medical problems they have, and an e-mail
address.
© 2009 Nature America, Inc. All rights reserved.
From that point on, the system becomes high
tech. At the site, patients can add information
to their online profile, share feedback about
their own response to medications and request
that their doctors be copied on certain types of
alerts. iGuard not only notifies members about
safety alerts concerning their medications, it also
screens for drug-drug and drug-disease interac-
tions. Patients learn what certain medications
are being used for, what common side effects
are, how effective the drug seems to be and what
people “wish they were told” before starting a
medication.
Patients like the service. During a recent recall
of digoxin pills that contained twice the required
dose, one iGuard patient commented that when
she went to return her medication, she found
that her pharmacist didn’t even know her pills
had been recalled. If iGuard hadn’t alerted her,
she might have continued taking the too strong
dose, Stephenson says.
Launched in October of 2007, iGuard
already has 1.7 million members and is add-
ing about 30,000 patients per week. The
company’s primary message is “Are you tak-
ing a chronic medication and if so are you
interested in getting safety and recall infor-
mation?” Stephenson admits that since 200
million patients are using prescription drugs
in the United States, recruiting more patients
will be a priority for a while. Even so, iGuard
has enough patients to get busy on the profit-
making side of its business model. “Our busi-
ness is identifying patients for clinical research
projects,” he says.
The company reports that as of the end of
August, iGuard had recruited more than 2,500
patients for more than 60 cross-sectional and
prospective trials. iGuard is working on three
new research protocols a week, and these cover
a range of study types, including safety, drug
response and observational studies (e.g., deter-
nature biotechnology volume 27 number 10 october 2009 899
feature
Box 2 Google cofounder wades into Parkinson’s research
A glimpse of his genome turned Google cofounder Sergey
Brin (Fig. 3) from entrepreneur into research supporter. Brin’s
mother suffers from Parkinson’s disease. In March 2009, after
learning he is also at risk for the disease, the billionaire, whose
wife, Anne Wojcicki, cofounded 23andMe, announced he would
help to fund a Parkinson’s research project on the site.
23andMe aims to recruit 10,000 individuals for the study,
and will build an online community. In addition, the Parkinson’s
Institute and Clinical Center (Sunnyvale, CA) and The
Michael J. Fox Foundation (New York) have agreed to promote
the project to their members. Social networking pioneer
PatientsLikeMe is also letting Parkinson’s sufferers know about
the study.
Patients who enroll will enjoy a steep discount, paying just Figure 3 Google founder
$25 compared with the typical $399 fee for the complete Sergey Brin has become part
23andMe service fee. Brin will foot the rest of their bill. of the clinical trial revolution
on the web.
Patients who sign up will get the entire spectrum of data
provided by 23andMe, including their results for mutations
in the LRRK2 gene—considered the strongest genetic association with inherited Parkinson’s
disease, based on studies to date5.
23andMe aims to create a new research process for unraveling the roots of complex
diseases. “By using the Internet to query and interact with the research cohort, this platform
significantly increases the efficiency and reduces the cost of recruiting participants and
conducting research,” a company press release says.
If it comes true, it would have profound implications for genomic studies. Genome-
wide association studies have lost much of their luster because so few have yielded robust
associations. A growing number of researchers believe that many more clinically valid links will
only be found once researchers are truly looking across the entire genome to find rare variants.
mining the natural history of certain types of forms are trying to make that process quicker,
conditions). easier and more efficient, so patients don’t have
The company claims iGuard can accelerate to read through the descriptions of hundreds of
study timelines by 4–6 months. Stephenson trials they aren’t eligible for. Recruiters search
describes one sponsor whose drug was only through patients who have elected to share their
working in a subset of patients. “[Instead of] diagnosis, and perhaps more information, either
spending $10 to $15 million on a trial, they anonymously or directly.
used iGuard to reach out to 400 patients who The matchmaker model failed the first
had responded to the drug and 400 who had time around, when pioneer Veritas Medicine
failed.” Those patients underwent genetic test- (Cambridge, MA, USA), which launched in
ing as part of the study, which they volunteered 1999, folded last year. Veritas began with online
for, “and the company got the data it needed,” recruitment using the matchmaker model, but
Stephenson says. this didn’t go as well as planned; the company
“iGuard has a robust community and people changed its strategy, but was ultimately unable
are trusting it with a lot of intimate and pri- to keep investors interested.
vate information,” says Mark Uehling, founder The new generation of online recruitment
and editor of clinical trials news site ClinPage startups says things are different now. “Veritas
(Lincoln, MA, USA). “That’s a true community was too early to the market,” says Jean-Luc
and one that demonstrates public interest in Neptune, CEO of Healogica (New York; http://
research.” www.healogica.com/), one of the companies
reinventing this approach. “The Internet has
Matchmakers evolved significantly since the late 1990s and
Many of the new sites are primarily match- early 2000.” Neptune should know. Veritas
makers that connect patients and researchers cofounder Josh Schultz sits on Healogica’s
recruiting for clinical trials. Patients can already board. Sharib Khan, CEO of TrialX (New York;
search ClinicalTrials.gov (http://www.clinical- http://www.trialx.com/), one of Healogica’s
trials.gov/), the site where the US government competitors, agrees with Neptune. “Eighty
directs drug companies and other organizations percent of people in America who are online
to post their ongoing trials (Box 3). New plat- are now searching for health information,” he
 feature
© 2009 Nature America, Inc. All rights reserved.
Figure 2 TrialX iPhone app lets patients and
doctors search for clinical trials by location,
indication or treatment, share it with friends
or family, and call a clinical trial investigator.
(Source: TrialX)
says. “Clinical trial information is one of the top
searches.”
Good prescreening tools for patient selec-
tion are key. Of the patients who seek out trials,
many are not qualified for the ones they apply
to. That wastes time and can be demoralizing.
Trials have also gotten increasingly complex; the
more sophisticated screening tools use branch-
ing where the next question depends on the
patient’s previous answer. It also helps to be able
to divert patients quickly away from trials they
aren’t eligible for, to those they are.
One problem with aggregating clinical trials
is that trial descriptions are written by different
people who don’t always use the same terminol-
ogy. Healogica has artificial intelligence software
that standardizes those listings, using natural
language processing. That means patients don’t
have to understand things like specific ranking
scales, they just describe their status in their pro-
file. The platform includes proprietary search
software that lets them identify the narrowest
set of questions you can ask someone to deter-
mine if they are eligible for a trial, according to
Neptune. “By answering about ten questions in
less than a minute, we can reduce the number
of trials a patient retrieves from several thou-
sand to a handful,” he says. Tapping into the cell
phone software boom, Healogica now has an
application that lets patients use the company’s
tools from their iPhone.
Like Healogica, TrialX is trying to make it
easier for patients and researchers to find each
900 volume 27 number 10 october 2009 nature biotechnology
other. Visitors can search the site’s database
and, if they want, ask for follow-up e-mail
updates as new trials are added that fit their
search criteria. TrialX is also one of the first
companies that connects to a patient’s per-
sonal health record (PHR)—online records
that patients set up themselves—to help them
match up with trials. The company has arrange-
ments with the two other pioneers in this field,
Microsoft (HealthVault; Box 4) and Google
(GoogleHealth). Patients can connect their PHR
to the TrialX software, which will pull relevant
information for a clinical trial search.
Another entry into TrialX is Twitter, the social
networking site that allows people to broadcast
messages of 140 words or less. Patients send a
“tweet” to @trialX, preceeded by “CT” describ-
ing the type of clinical trials they are seeking.
“If you say, ‘I am 35 years old, have multiple
sclerosis, and live in New York,’ we can tweet
you back a tiny link that brings you to a list of
trials,” says cofounder Sharib Khan. TrialX has
also automated many steps for patients: a single
click generates a message telling an investigator
the patient is interested in the trial.
TrialX just made an agreement with
CenterWatch (http://www.centerwatch.com/),
one of the world’s largest online databases of
active clinical trials. The deal gives TrialX access
to more clinical trials data while CenterWatch
gets plugged into social media, and investiga-
tors who use its service have a new source of
patients. Khan says his company also has plans
for an upcoming iPhone application (Fig. 2).
Advocacy groups’ advantage
Although some people seem to tolerate, if not
enjoy, posting data about their health online,
many are squeamish about sharing any per-
sonal information on the web. These patients are
unlikely to be tweeting about the kind of trials
they are looking for or chatting in online forums
about their disease.
Private Access (Irvine, CA, USA) CEO Robert
Shelton knows about this first hand, as he is also
the chairman of the advocacy group Knowledge,
Support & Action. The group serves individuals
who have one or more additional X or Y chro-
mosomes, such as Shelton’s son, who was prena-
tally diagnosed with Klinefelter Syndrome. The
group uses that name because members did not
want to receive mail stamped with the phrase
“Klinefelter Syndrome Association.”
Some patients with Klinefelter Syndrome
don’t even tell family members or their primary
care physician about their condition, Shelton
says, “and everyone has certain information they
want to keep private.” This concern has also led
to a proliferation of forms and legislation aimed
at guarding privacy. Different states, hospitals
and providers may have different requirements
around preserving privacy. In President Barack
Obama’s health information technology stimu-
lus package, “there are more than 50 pages about
privacy,” Shelton says.
The cornerstone of Private Access’s business
is Privacy Layer, a program that secures data
but allows the owner of that data to make them
accessible to specific individuals on a case-by-
case basis. This subtle but important twist of
the social networking model makes certain that
patients have control of their data and can learn
as much as they want about someone before
they bare it to an individual, let alone to a large
group.
Researchers provide information about who
they are, where they are based and the type of
trial they are doing. Once they are authenticated
and approved to use the system, they can browse
among the registered patients, some of whom
will remain anonymous and others who will
have chosen to be identified. A researcher can
send an introductory e-mail to patients who
appear to be eligible for their trial. Even as they
reveal more and more data to confirm that they
are indeed eligible, patients can choose to stay
anonymous or to share their identity. Besides
this layered system for connecting researchers
and patients, the software comes with multiple
layers of security and an audit log that tracks
activity.
An intriguing aspect to the service is how it
relies on “trusted intermediaries” and leverages
Private Access’s partnership with the Genetic
Alliance (Washington, DC), a non-profit health
advocacy group that represents over 1,000 dis-
ease advocacy groups and more than 150 million
people. Shelton believes that patients are more
likely to use the service if it is recommended
by people they know and trust. Each advocacy
group will have a chance to review and test the
service. If they like it, they can promote it to their
members.
When members set about enrolling, they’ll be
able to choose one of several “intermediaries,”
or guides, to step them through a detailed ques-
tionnaire that gathers the data needed to help
them find trials. A photo of each intermediary
guide appears on the screen. If the patient has
registered with Private Access as a member of
an advocacy group, a leader of that group may
become their guide.
Genetic Alliance’s president and CEO Sharon
Terry guides pseudoxanthoma elasticum (PXE)
patients. Terry also chairs PXE International, an
advocacy group for those with this rare genetic
disease that affects elastic tissue. She and her
husband Patrick founded that group in 1995,
after discovering that both her children suffer
from PXE.
“Having someone you trust in front of you
is part of the equation,” says Shelton. “The

advocacy group leaders can tell their members,
‘I think this is something you should look at.’”
Leaders of these groups, such as Shelton himself,
often know a great deal about these diseases. “If
you look on ClinicalTrials.gov you’ll find three
trials for the condition my son has,” Shelton says,
“But I’ll know about ten to fifteen such trials.”
Private Access is still evolving its business
model. The company recently signed a non-
exclusive collaboration with Pfizer (New York)
and is in discussions with leading trial recruit-
ment firms and contract research organizations.
Shelton claims that his company will drop the
cost of recruitment “by an order of magnitude
and drastically cut the time it takes.” In July 2009,
the company rolled out the first pilot service to
the Knowledge, Support & Action community.
By the end of August, 45 out of 100 invited mem-
bers of the community had enrolled. Once the
© 2009 Nature America, Inc. All rights reserved.
pilot is completed and Private Access expands
into other disease groups, Shelton predicts the
company will rapidly expand. “We will have
thousands of users in a few months, hundreds
of thousands in a year, and million in a couple
of years,” he says.
Having a connection to the advocacy commu-
nity could be a big advantage. “If someone comes
out with an interesting drug, you don’t hear it
in a tweet, you hear it from an advocacy group,”
says Nextrials’ Rogers. “Powerful resources are
being put into these advocacy sites.”
The Juvenile Diabetes Research Foundation
(JDRF) recently launched Clinical Trials
Connection website (https://trials.jdrf.org/
patient/) for type 1 diabetics. Built by VisionTree
(San Diego), the site helps patients sort through
clinical trials based on location and the types of
patients being sought. Members can save ‘favor-
ite’ trials, compare those and receive updates
about new trials they may be eligible for.
JDRF already has a vital social networking
site for type 1 diabetics (http://www.Juvenation.
org/), which has ~6,000 members. The organi-
zation also promoted the new clinical trials site
aggressively by running a special “What does
hope look like?” campaign on cable TV and
elsewhere.
Over 5,000 patients preregistered for Clinical
Trials Connection, and since its launch in July,
an average of 500 people have been signing
up each day, according to VisionTree. “On the
first day we went live, I already got two e-mails
from industry partners saying they had received
inquiries they would not have gotten otherwise,”
says Paul Strumph, chief medical officer & vice
president, medical affairs at JDRF.
Inspire (McLean, VA) (http://www.inspire.
com/) is a site that is already recruiting
patients for a range of trials, thanks to multiple
communities. The site launched in 2005 and
uniquely builds communities in partnership
nature biotechnology volume 27 number 10 october 2009 901
feature
Box 3 The access dilemma
“Clinical trials” is among the most searched for term on the Internet and yet thousands of
trials are delayed or abandoned because they can’t get enough patients. One problem is that
doctors don’t have the time to learn about all the trials their patients might be eligible for.
ClinicalTrials.gov is meant to help with that. After AIDS activists won the right to online
clinical trial information in 1989, other disease groups lobbied for the same thing. In 1997
a new law mandated that companies post all of their trials online, and ClinicalTrials.gov was
launched in February 2000 to facilitate that. This proved an instant “culture change,” says
Terry Toigo, director of the Office Of Special Health Issues. Suddenly, information that had
been closely guarded had to be posted on the Internet.
Since then even more changes have taken place, largely thanks to the FDA’s Office of
Special Health Issues and the advocacy group Abigail Alliance, which aims to give patients
easier access to experimental drugs. “People had started complaining to Congress about the
site,” says Toigo. “We did the best we could to improve it.”
The range of trials listed has expanded to include trials for all diseases—not just those
that are serious and life threatening—and medical devices; companies are also required to
post trial results and provide links to related FDA approval notices and National Institutes of
Health documents. Adverse events reporting is now also required. Consumers should be able
to access a range of information about a drug that has been tested in clinical trials. There
is also now a $10,000 fine for companies that fail to post, or those that post inaccurate
information. To date, “no enforcement actions have been taken,” says Toigo.
But more important, is it helping with recruitment? As of April 2009, more than 75,000
trials had been listed on the site, but no study has been done to see if more patients are
getting into trials. “You can go to companies and get anecdotal evidence,” says Toigo, “but
I’m not sure the government could [study this issue] because it would mean capturing
personal information, which is illegal.”
Despite all the improvements, ClinicalTrials.gov still does not list all ongoing trials, and
companies such as Healogica exploit that by promising users they will see more trials
through the company’s products. They also say they can help patients narrow the number of
leads they must follow.
with advocacy groups. Its biggest memberships ogy could be pivotal. “I think the most prom-
are around weight loss, support for premature ising tool is mining electronic health records,”
infants and lung cancer. Confidentiality agree- says Rogers. “That way you could look for the
ments don’t allow the site to divulge num- sites that have enough patients that you want
bers, but a spokesperson says that in terms of to include.” Having successful sites—doctor’s
recruitment for clinical trials, “we have been offices or clinics that enroll lots of patients—is
pleased so far, and in one example we reached the traditional magic ingredient for a success-
a sponsor’s goals eight months [sooner] than ful trial.
the time allotted.” Patients, too, they say, like Rogers says he’s only aware of two compa-
the system. nies that can do that now: Greenway Medical
Partnerships with advocacy groups thus Technology (Carrollton, GA, USA) and Cerner
seem quite promising, but success for websites Corporation (Kansas City, MO, USA). Greenway
devoted to patient recruitment is likely to rest on spans mostly smaller community clinics, whereas
the same things all sites live and die by—traffic Cerner has more hospital settings. This is a good
and stickiness. Companies need enough of the start, but Rogers thinks the next big step will be
right kind of patients coming to their site, and for a company like his to be able to look across
coming back again and again. their much bigger networks of sites. The soft-
ware for that doesn’t exist yet, but when it does,
Critical junctures he says it will be “evolutionary.” One complica-
Despite all the activity in this sector, few people tion is privacy, which is “always huge,” Rogers
outside of social media are pointing to it as the says. Most hospitals can mine electronic health
promised land, yet. There is a broadly accepted records (EHRs) without breaking the law as long
view that someday technology will deliver a huge as they avoid using data that could identify the
payoff: the ability to integrate and analyze data patient. Different institutions, however, have dif-
across the entire healthcare continuum, from ferent regulations about that.
basic research through clinical trials and patient For EHR mining to become really big, many
care. In the short term, however, experts see a more hospitals and doctors’ offices need to go
couple of key spots where smart use of technol- to electronic record keeping. So far, adoption
 feature

Box 4 Microsoft consolidates health offering

IT giant Microsoft is a standout not just because of its size, but
because it also has one of the first PHR platforms—HealthVault—
and because of an intriguing life sciences acquisition it
recently made. PHRs are online records that patients create for
themselves, filling them with data from their medical record,
from doctor’s visits or that they collect themselves, like glucose
levels. PHRs usually have less detail and are less reliable than the
official electronic medical record at the doctor’s office or hospital.
Nonetheless, companies like TrialX and Microsoft think PHRs can
play a pivotal role in recruitment.
In putting together an integrated system, Microsoft started by
developing its Amalga software for hospital information systems.
The platform, called a “unified intelligence system,” allows a
hospital to aggregate all the data it needs to run its various parts,
including human resources, accounting, laboratories, pharmacies
and clinics. Amalga helps address the problem of integrating
disparate health information because it can pull from a variety
© 2009 Nature America, Inc. All rights reserved.
The company is extending Amalga into research first via
HealthVault. “You can imagine an application for HealthVault, through
which the consumer opts into clinical trials,” says Karkanias. If the
investigator needed to see the patient’s recent glucose measurements
before accepting him or her into a trial, the patient could retrieve that
data from his or her PHR. Microsoft’s biggest competitor in the PHR
arena now is Google, with its GoogleHealth product.
Thanks to Microsoft’s recent acquisition of Rosetta Biosoftware
(Seattle) from Merck, Amalga also now has a life sciences research
product that handles genomic, proteomic and metabonomic data.
Karkanias says that software can translate across the several well-
known industry standards for representing genetic information.
“When it came to a buy it or build it decision, and Rosetta was
available, that was an easy decision to make,” he says.
One hundred hospitals are reportedly using Almalga’s healthcare
product already. As the number of HealthVault and Amalga
Life Sciences users expand, Microsoft has a bold vision of data

of programs and then present all the data about a patient in
one single, customizable view. The software also makes more
types of analysis possible. “A typical electronic medical record
is focused on that specific task,” says Jim Karkanias, director
of applied research and technology at Microsoft. Through
Microsoft’s partners, hospitals can buy Amalga-friendly programs
for physician order entry, storing and retrieval of images, and a
variety of other tasks.
Electronic data capture programs for clinical trials can also
be plugged in, says Karkanias. “In an EDC environment from a
company like Phase Forward or MediData, you have features like
edit check and data validation,” Karkanias explains. “Amalga can
read those data and integrate it with data from other programs.”
storage that is well-guarded but, with proper authorization, moves
seamlessly from one environment to the next, reaching from the
consumer, across the clinic, into clinical trials, out to the research
environment, and back. Patients would be able to populate their
PHR from an EHR at the hospital or doctor’s office. Clinical trial
recruiters could scan the PHRs of patients who have given their
permission, cherry-picking the right kinds of patients for their
trials. Every part of the process would be online and automated.
As mobile health expands, cell phones will play an increasing
role in research as well. “You could imagine an allergy study going
on where the patient’s phone is reporting on their location and
some kind of service is automatically recording the pollen counts
at those sites,” Karkanias says.

in the United States is poor, with only about
28% of providers adopting the electronic
form, but there is hope that the government’s
$20 billion health information technology
stimulus package, and the various incentives
and penalties it calls for, will help EHRs spread.
In countries like The Netherlands and New
Zealand, meanwhile, almost all the providers
are already wired.
ClinPage’s Uehling also sees hope around
the integration of electronic medical records
and the electronic data capture (EDC) soft-
ware used to collect data during trials. “That is
potentially revolutionary, and it is much farther
along than most people know,” he says. “The
larger EDC companies aren’t there yet, but the
smaller ones are.”
When EDC and EHR systems can speak to
each other, doctors and their staff don’t have
to learn new systems to participate in a trial.
“That really speeds up their work and elimi-
nates some of the regulatory burden,” Uehling
says. Investigator attrition is, after all, at the heart
of the problem. “If some of these sites that are
enrolling one patient could start enrolling six,
that’s huge,” he says.
Currently, there are subsets of EDC and EHR
programs that can connect. “What we need is
complete interoperability between the two types
of systems,” Uehling says.
Meanwhile, if more members of the public
set up PHRs, that could also mean more busi-
ness for companies that connect to PHRs. The
barrier here seems to be twofold: it can be costly
and difficult to actually get your data into a
PHR, and the public is still largely mistrustful.
Surveys show that the majority of Americans
think PHRs are a good idea, yet don’t trust them
to be secure. “Consumer demand for PHRs and
online health services will take off when con-
sumers trust that personal information will
be protected,” Markle Foundation (New York)
president Zoë Baird is quoted as saying in a
recent press release.
Plenty of room for progress clearly exists.
In the meantime, the flurry of social network-
ing sites for patients will likely keep expand-
ing. “It’s the hot thing and nobody wants to
be left behind,” says Jodi Andrews of ProTrials
(Mountain View, CA, USA). Hopefully, the ride
won’t be too bumpy and some of these new
products will help advance research and acceler-
ate the development of improved treatments.
1. Westing, A.F. How the Public Views Privacy and Health
Research (National Academy of Sciences, Washington,
DC, 2007).
2. Arnst, C. Health 2.0, Patients as Partners, Business
Week, December 4, 2008 <http://www.businessweek.
com/magazine/content/08_50/b4112058194219.
htm>
3. Ramsey, S. & Scoogins, J. Practicing on the tip of an ice-
berg? Evidence of underpublication of registered clinical
trials in oncology. Oncologist 13, 925–929 (2008).
4. Kurzrock, R. et al. Project zero delay: a process for accel-
erating the activation of cancer clinical trials. J. Clin.
Oncol. 27, 4433–4440 (2009).
5. Greggio, E. & Cookson, M.R. Leucine-rich repeat kinase 2
mutations and Parkinson’s disease: three questions. ASN
Neuro. published online, doi: 10.1042/AN20090007
(14 April 2009).

902 volume 27 number 10 october 2009 nature biotechnology