Denise Myshko

atient recruitment delays andlow-retention rates are key factorsin increasing development costs.To optimize both recruitmentand retention, there needs to be a

plan based on evidence, data, and a set of toolsthat will work.Recruiting patients is often a key pain

point for sponsors and contract research organ-izations, says Jonathan Sheldon, Ph.D., globalVP, Oracle Health Sciences. “Companies are looking to advanced tools

that make it easier to recruit patients for trials,such as incorporating patient data into a singleHealth Insurance Portability and Accountabil-ity Act (HIPAA) certified environment acces-sible to both life sciences and healthcare or-ganizations,” he says.The objective of using these approaches and

tools is to expedite recruitment of eligible pa-tients in clinical trials and to contain the drop-out rates through widening the reach and en-abling pre-selection, says Chitra Lele, Ph.D.,chief scientific officer, Sciformix.“The tools, including commercially avail-

able ones, help identify the right patient pooland target the right sites and patients, ulti-mately increasing the chances of a successfuland expedited trial,” she says. “The ultimategoal of all these approaches and tools is to op-timize the clinical development timelines andreduce the time to market.”The newest tools allow companies to reach

people where they are looking for information,says Ritesh Patel, global head of inVentiv Dig-

P

20 May 2014 � PharmaVOICE

progressive channels, immersive experience,and progressive techniques.“The traditional form of patient engage-

ment was to enroll a provider and the providerenrolls the patient and the patient has a rela-tionship with the provider,” Mr. Coman says.“Today, at the very beginning we are creatingtouch points to find patients in a branded ex-perience. Every one of those touch points hasto leverage core insights about why a patientmight want to enroll in the study. We have tocreate an experience that elicits a sense of pur-pose. We’re trying to create a 360-view of pa-tients as they have an interaction with aprovider, a website, and their family andfriends throughout the study.”Dr. Sheldon says the goal of such tools is to

help healthcare providers and research institu-tions to collaborate more efficiently withhealth sciences organizations, with the goal ofadvancing treatments and improving out-comes. “Specifically, they help to speed recruit-

ment timelines by collaborating more easilywith one or more healthcare institutions andimproving decision making by getting instan-taneous hypothesis testing results using highquality longitudinal clinical data during pro-tocol modeling/feasibility and validationprocesses,” he says.

Big Data Tools

Recent studies find that the use of big datato inform important decisions is now com-

ital + Innovation, the digital consultancy ofinVentiv, which works across different inVen-tiv companies. “Patients are not all looking on TV or a

newspaper, they are online, talking to eachother in forums,” he says. “There is a hugegrowth in patient communities such as Pa-tientsLikeMe, Inspire Health, and AllianceHealth. They have vast communities of pa-tients and caregivers who are active.”David Coman, senior VP, marketing, en-

gagement, and communications, Quintiles,says there also needs to be a transformation inthe way we think about patient recruitment.“It’s really about patient engagement,” he

says. “It’s not just about recruiting patientsand introducing them into studies. It’s abouthow to create an immersive experience for pa-tients that goes beyond just the tactical me-chanics of introducing a patient into a trial.This means we have to determine what is driv-ing patient behavior and develop the rightmix to engage patients.”Mr. Coman says this involves three things:

Data-DrivenRecruitmentPatient

New tools are being introduced to help pharmaceutical companies identify, screen, and retain patients in clinical trials.

E-PATIENTS ARE 60% MORE LIKELY

THAN THE GENERAL POPULATION

TO PARTICIPATE IN CLINICAL

RESEARCH.

Source: Blue Chip Patient Recruitment

FAST FACT

Published in May 2014

Copyright 2014 by PharmaLinx LLC

21PharmaVOICE � May 2014

Patient Recruitment

Another company using big data tools isShire Pharmaceuticals. “We started to mine electronic health

records (EHR) — we have access to 25 milliondeidentified health records — and we use thatdata to ask questions related to the patient co-hort we are looking for so we don’t end uplooking for patients that don’t exist,” saysJoseph Kim, clinical operations director atShire. “For example, if we considered doing astudy on pediatric asthma and we wanted tolook at the subpopulation of those who havehigh blood pressure or who are taking drug Aand not drug B, we could access those data tomake sure those patients exist. Without ana-lyzing a robust EHR dataset, we’re left to piecetogether a picture of how prevalent this popu-lation is through key opinion leaders and theliterature alone.”Another company, inVentiv Health, also is

working with electronic medical records forpatient recruitment. The company is workingwith a network of EHR providers to send clin-ical trial invitations to patients at the point ofcare in the doctors’ offices. “There are ways that we could set up with

the EHR companies a method or an indicatorthat would trigger a message that would popup during patient visits with their doctors,”says Jim Carroll, VP, product management, atInVentiv Clinical Trial Recruitment Solutions.“If, for example, a patient is being treated fordiabetes and is not controlled with existingtreatments, that patient could be offered anopportunity to participate in a clinical trial forpatients who are not well controlled using cur-

monplace in business but rarely used in clini-cal trial planning. Big data allow the industry to look at clin-

ical trials in a very different way, says LizMoench, president and founder ofMediciGlobal.“For example, you could overlay prescrib-

ing data with e-patient search activity to iden-tify the hottest markets that could have beenmissed when recruiting for a trial,” she says.“We have to go where the patients are insteadof going to the same wells, which are runningdry, and trying to push patients to studies.”She says electronic medical records systems

that can be plugged into recruitment and IVRSdata will lead to integrated functionalities.“Data integration is where the focus will

be in the next year to two years,” Ms. Moenchsays. “The issue is how rapidly can they be de-ployed with minimal amount of hands-on im-plementation. Then those systems have to in-tegrate with other screening and recruitmentsystems so that you have a complete pictureend to end.”A data-driven approach to patient recruit-

ment is increasingly being followed, based ondata from electronic health records, patientdatabases containing anonymized health data,demographic and epidemiological data, his-torical clinical trial data and secondary data,Dr. Lele says. “This includes data-driven approaches to

protocol feasibility, statistical projections ofdisease prevalence, and predictive analytics forsite selection,” she says.Dr. Lele says while there is a gap in struc-

ture and content between data documentedduring patient care and data required for pa-tient eligibility assessment, EHR data on a

patient’s age, gender, disease state, and otherparameters can be used for an effective screen-ing process with an intelligent selection of pa-tients and patient data. “The growth of electronic health data is

paving the way for a more efficient, scalablemethod to recruit patients for clinical trials,”she says. “Electronic health records form thebasis of initial pre-selection of patients. TheEHR data can be queried for eligibility crite-ria using screening algorithms, to expeditethe screening process and get to the eligiblepatients faster.”Janssen is one pharmaceutical company

using direct-to-patient techniques in clinicalresearch studies. Quintiles worked withJanssen to enroll patients for a study thataimed to determine which patients respond toa TNF inhibitor for rheumatoid arthritis. Toenroll patients in an outcomes-based, PhaseIV study, Quintiles collected and analyzedmedical records direct from patients to com-pare patient reported outcomes relative withphysician-reported data. Then an invitationand a sample collection kit were sent to pa-tients for biomarker testing. “Instead of patients going to a lab or a doc-

tor’s office, we sent the information to pa-tients,” Mr. Coman says. “In the traditionalmodel, the patient burden was to go to thedoctor’s office, sign paperwork, enter a bunchof data, go to a lab, and there may be multi-ple visits. Now this is done in the home. Thetraditional model of having physician investi-gators who recruit patients took six months toget the first patient enrolled. Using this newmodel, the first patient enrolled took six min-utes. We were able to find 1,000 patients in18 weeks.”

“ Because the Web is such a

tractable medium and because

clinical trials are so metrics

driven, it’s the perfect arena in

which to gamify the

recruitment and retention

process. ”BRYAN FARROW / TrialNetworks

“ The growth of electronic

health data is paving the way

for a more efficient, scalable

method to recruit patients for

clinical trials. ”DR. CHITRA LELE / Sciformix

22 May 2014 � PharmaVOICE

Patient Recruitment

rently available treatment options. That is an-other very targeted way we can get a commu-nication to the audience that is going to bemuch more likely to participate based on theirunderlying condition.”The company also is with working Adheris

Health (also an inVentiv company) to deliverclinical trial invitations to patients on behalf ofpharmacies. As a result, the company has ac-cess to prescription data across 175 millionAmericans, Mr. Carroll says.“We could build a cohort of patients within

the prescription databases to understand howmany patients are, in fact, available for out-reach with a very targeted communication foran invitation to participate in a trial,” he says.“We’re able to do this in a very unique fashionto patients who meet the clinical trial criteriato see if there is interest. We are able to do thatthrough partnerships with pharmacy chains.”Dr. Sheldon says clinical trial alerts (CTAs)

can be generated by EHRs and allow patientsto be quickly notified when a trial becomesavailable that could benefit them. “This takes the work of selecting partici-

pants off of the physician conducting the trial,and further enables patients to select trials thatwould work for their benefit,” he says. “OnceEHRs are widely adopted, health data will bemuch more available to physicians and clinicaltrial sponsors, making it much easier for themto identify what patients fit the criteria fortheir trials.”Mr. Patel says countries outside the United

States are moving forward with efforts to cre-ate a national system of health records thatcould be used for clinical research.In the United Kingdom, for example, the

National Health Service plans to go paperless

by 2018. This will require digital records to becompatible. Interim deadlines include onlineaccess to individual records by March 2015and for all digital information to be fully avail-able across the NHS and social care services byApril 2018. This effort could result in £1.7billion a year being able to be reinvested backinto the UK healthcare system, according to astudy by PwC.Mr. Patel says this will likely be more com-

plicated in the United States. “We have 300 or so different kinds of

EMRs providers,” he says. “It is very frag-mented. Getting consolidated data will be dif-ficult.” In 2013, the National Ambulatory Medical

Care Survey (NAMCS) EHR Survey showedthat about 78% of office-based physicians usedany EHR system. Hospital adoption of EHRsystems has more than tripled since 2009, ac-cording to a 2013 study by The Office of theNational Coordinator for Health InformationTechnology, part of the U.S. Department ofHealth and Human Services.Scott Connor, VP of marketing at Acurian,

part of PPD, points out that EHRs still have along runway before they take off as a truly ef-fective method for patient recruitment. “These repositories have inherent issues

around consistency of the data, privacy con-cerns, adoption rates and others that are al-ready widely acknowledged,” he says. “But themajor issue for me is that unless the EHRopens an explicit, direct-to-patient channel tocommunicate a therapeutically and geograph-ically appropriate trial, it is simply another po-tential tool to use a proxy for identifying pa-tient populations. EHR/EMR existencedoesn’t mean that you can contact these indi-

viduals directly. Until then, EHRs and EMRswill rely on intermediaries, for example, treat-ing physician who is probably not the PI, tocommunicate a trial, which effectively re-moves the power from the patient.” Mr. Connor says the use of electronic data is

most valuable for protocol feasibility to the ex-tent that there is the representative data toquery with statistical significance.Dr. Lele says one challenge is that, in most

regions, it’s difficult to find an EHR systemthat can be meaningfully used for patient re-cruitment. “When EHRs are available, they may not

contain all the data required to determine pro-tocol eligibility and the available data may notbe complete,” she says. “It may also be difficultto write code to effectively query the data if theeligibility criteria are complex. EHR data haveto be used in an ethical and responsible man-ner in clinical research. Ensuring this will re-quire close collaboration between variousstakeholders — government, industry, hospi-tals, patient groups, and technology vendors— and evolution of global standards for shar-ing health data.”

Recruiting Through Social Media

Social media is gaining ground as an im-portant tool to improve the clinical researchprocess through more effective engagement ofpatient communities, but drug sponsors areproceeding cautiously, according to an analysisrecently completed by the Tufts Center for theStudy of Drug Development.Nearly all drug sponsors have developed

corporate policies to steer employee use of so-cial media, but the lack of comprehensive, co-ordinated processes across most organizations

“ Centralized monitoring

of data from EDC and IVR

becomes important for

retaining patients in trials. ”ERIC SILBERSTEIN / TrialNetworks

“ Recruitment involves an

immersive experience for patients

that goes beyond just the tactical

mechanics of introducing a patient

into a trial. ”DAVID COMAN / Quintiles

“ Placing clinical trial ads

on social media sites is not

engaging in social media.

That is advertising. ”JOSEPH KIM / Shire

24 May 2014 � PharmaVOICE

Patient Recruitment

has meant that the companies that are usingsocial media in drug development are doing soin a siloed and experimental fashion, TuftsCSDD found.Key concerns voiced by drug sponsors

about using social media in clinical trials focuson violating patient privacy and confidential-ity, jeopardizing research integrity, and influ-encing study volunteer receptivity to partici-pating in clinical trials. The use of social media for patient recruit-

ment is fairly limited; in fact, on average com-panies were using social media in about 11%of their trials, says Mary Lamberti, Ph.D., sen-ior project manager at Tufts CSDD.“Companies are using Facebook, YouTube,

patient communities as well as advocacygroups to spread awareness about clinical tri-als,” she says. “That is more for informationalpurposes. Companies that are using socialmedia are using it more as a one-way push, andthere is not a lot of two-way interactive en-gagement.”In fact, only one in five companies that use

social media directly interacts with patients,according to the Tufts CSDD survey; mostcontract out engagement to a third-party oruse more passive approaches, including plac-ing banner ads on social media sites.Dr. Lamberti says this is because of unclear

FDA guidelines on the use of social media. “The FDA put out guidance just this year,

but that was focused mostly on postmarketingtrials,” she says. “In terms of using socialmedia for recruitment and retention, there isnothing specific and companies are concernedabout usage.”In January 2014, the FDA issued a draft

guidance for using interactive media — blogs,social networking sites, online communities,and live podcasts — for approved products.Under this guidance, a company would haveto submit materials for FDA review any com-munication on sites that are owned and con-trolled or operated on behalf of the company.The agency will take into consideration howmuch influence the company exerts on thecontent. If a company collaborates on or haseditorial, preview, or review privilege over thecontent, then it is responsible for the content.The issue of control also extends to its em-ployees when they are acting on behalf of thecompany, such as a company-directed tweetfrom an employee’s private account.“In the future, I think there will be more

usage of social media, but there are still somechallenges,” Dr. Lamberti says. “This includesovercoming internal challenges, gaining regu-latory approval, concerns about adverse eventreporting, and concerns about country specificregulations.”Dr. Lamberti says some companies are be-

ginning to establish governance committees toaddress some of these challenges and to createa central system to manage and track socialmedia projects. Mr. Kim says social media can be used ef-

fectively but has to be approached differently.“Placing ads on social media sites is not en-

gaging in social media; that is advertising,” hesays. “Engaging in social media is about lis-tening and engaging with the audience in anauthentic way, in near real time.” Mr. Kim says it’s important for pharmaceu-

tical companies to understand how patientsuse social media.“There is a good deal of evidence that pa-

tients are connecting to each other while theyare in research studies,” he says. “While pa-tients perceive a benefit to this, they are alsounknowingly engaging in some risky behav-iors, sharing insights on ways to inappropri-

“ Unless the EHR opens an

explicit, direct-to-patient channel

to communicate an appropriate

trial, it is simply another

potential tool for identifying

patient populations. ”SCOTT CONNOR / Acurian

“ The clinical data from EMR

systems have to be de-identified

based on HIPAA requirements

and managed securely. ”DR. JONATHAN SHELDON

Oracle Health Sciences

ately get into research and sharing theirprogress with each other. Though they are onlytrying to help each other, this behavior cancause them to harm themselves and the re-search. For example, they are sharing what theplacebo tablets might look or taste like or howto go to a local lab to get blood drawn to see ifthey are taking active medication. They end upunblinding themselves, which can hurt the sci-ence. This will be a runaway train if left un-managed.”Mr. Kim says ideally it’s important to set

up some type of controlled environment wherepatients can connect with each other in a safeway.“Patients want to connect,” he says. “If we

don’t give people a safe place to connect, theywill do it anywhere. Someone has to create aplatform so that patients can connect througha social media channel safely. I’m not talkingabout setting up a Facebook page. I thinkthere needs to be a place that is purposely builtfor research participants to connect, wherethere are safeguards built in. Patients also needto be educated about the game of research. I’mlooking for partners to help build this for theindustry.”Mr. Connor says the best use of social media

continues to be IRB- and ethics committee-approved advertising that is placed within so-cial media channels. “What we have found over the past five

years is that social media channels are becom-ing increasingly nuanced and are capturingmore geographically targeted information,which is important to increasing the cost-ef-fectiveness of patient recruitment,” he says.“Remember, clinical trial advertising is onlycost-effective if you can narrow your reach tospecific boundaries around the sites conduct-ing the trial. The other important social mediafactor is that it has opened the aperture to sup-porting sites on a more global basis. Theworldwide acceptance of online is muchgreater than traditional marketing methods,both by regulatory agencies and potential sub-jects. Social media is just one part of thatglobal online equation. It is by no means apanacea, but it does work with the right ap-proach and management.

Borrowing from the Game World

Another new technology for recruitmentuses techniques from engagement strategy torecognize and reward people for recruitingmilestones.Because the Web is such a customizable

medium and because clinical trials are so met-rics-driven, it’s the perfect arena for motiving,through quantitative feedback and friendlycompetition the actions sponsors want to en-courage, actions such as enrollment and reten-

26 May 2014 � PharmaVOICE

Patient Recruitment

SOUND BITES FROM THE FIELD

AARON FLEISHMAN leads thesocial innovation and advocacyoutreach teams at BBK Worldwide.

Today’s best practices for patientrecruitment and retention are defined by di-versifying your strategy, integrating into pa-tients’ daily lives, and building a communityof partnerships.

We are finding customized mobile appli-cations to be a successful recruitment and re-tention tool, but traditional tactics, such as tel-evision, radio, and Internet continue to proveeffective. Simply put, patients’ preferencesvary. When you focus on the patient and de-velop diverse strategies that speak to themdirectly, meeting them where they are, yourchance of success will rise dramatically.

It is important to remember that it is notalways tools, but people that create the foun-dation for positive patient recruitment andretention. Involving advocacy groups notonly early on, but throughout the lifecycle ofa study, actively demonstrates a commitmentto providing patients and their caregiverswith accessible information from a trustedvoice. By making an investment in advocacyoutreach, your recruitment and retention willfoster awareness and education about clini-cal research, resonating with patients andempowering them to make better-informeddecisions about study participation.

LANCE NICKENS is president ofThe Patient Recruiting Agency.

Best practices would be: under-stand your protocol and the de-

mographic profile of the patient you need;understand the implications of the locationof your site(s); understand how to effectivelybudget for recruitment; invest time to select adedicated, experienced patient recruiting

and retention company early; understand po-tential recruiting and retention challenges andcreate a plan in advance to increase ROI and re-duce the risk of needing a rescue mission; createan effective outreach program supported withthe right type of services and tracking/reportingtechnologies; plan for call handling from patientpopulation for immediate pre-screening; and beforward thinking regarding the right kind of ma-terials needed for the patient demographic.

NEIL WEISMAN is executive VP andgeneral manager at Blue Chip PatientRecruitment.

If you want to meet your clinical trialrecruitment and retention goals, there are twoessential factors to ensure your campaign is ef-fective and cost-efficient: know your patientsand ready your sites.

If you want to reach patients, whether it’sthrough ads, posters, online search, etc., youneed to first understand them. What motivatesthem? What are their aspirations and fears? Howdoes their disease affect their life? What chal-lenges does the protocol pose? Listening to pa-tients, through market research, one on one in-terviews or social listening tools, are great waysto gather this information. With these insights,you will be able to craft communications that ef-fectively reach and motivate them to respond.

Generating patient inquiries is only the firstpart of the process. No matter how successfulyour outreach campaign, sites must be ready tofollow up on inquiries in a timely manner. Theyneed to pre-qualify, schedule, screen, randomize,and retain subjects throughout the trial. Spon-sors should identify resources for sites to best fa-cilitate recruitment and retention efforts, includ-ing easy-to-use systems to track in-practice andoutreach referrals, coordinator training, and sub-ject/coordinator tools and motivational pro-grams.

PharmaVOICE asked industry experts about best practices for recruiting and retaining patients in clinical trials.

tion of qualified subjects, protocol adherence,and data entry, says Bryan Farrow, director ofcommunity engagement at TrialNetworks.“Because there are a lot of discrete measur-

able entities in a trial, every time a patient isscreened or randomized, that gives us a way torecognize the people at the site level for mile-stone achievements,” he says. “In this way, weare able to recognize individuals for their ef-forts, which inspires them and their peers toaccomplish even more.”Infinity Pharmaceuticals used this strategy

for a Phase II oncology study. Working with

TrialNetworks, Infinity initiated a 30-day en-rollment challenge across all sites in the pro-gram. A daily leaderboard recognized sites andawarded virtual “badges” for certain mile-stones, such as enrolling the first patient. Theresult was a significant increase in site engage-ment and ultimately patient enrollment.“The badge by itself is not what motivates

people,” says Eric Silberstein, co-founder andCEO of TrialNetworks. “What motivates peo-ple is recognition in front of their peers for per-forming well. This type of program also cre-ates real follow through on the goals.”

Technology for Retention

Mr. Patel says inVentiv is starting to usemobile apps and text messaging for retention. “We are now exploring how burgeoning

wearable technology can be used,” he says.“We are also looking at whether we can deploylive video chat for some studies.”Mr. Carroll points out that regardless of

technology, retaining patients in clinical trialsrequires an understanding of behavior.“We are using behavioral science to under-

stand patients who have a condition, their mo-tivations and potential barriers, their habits,and how they currently consume content,” hesays. “That is a research exercise that we un-dertake very early on in the strategy develop-ment process because that helps us to under-stand the patient and the care team. It is reallyimportant in this world of patient centricitythat we really understand the full context ofthe patient and can use that understanding tocommunicate with patients. Depending onwhat we find in that research process, that ul-timately determines the methods for us to con-nect with patients based on an understandingof where they are and then also what to usewith them to make sure they are staying en-gaged throughout the trial.”Dr. Lele says there is an enhanced focus on

patient retention since the per-protocol sub-group of patients is critical; for example, cen-tral statistical surveillance and other risk-basedmonitoring strategies are used to flag retentionissues and customize retention strategies, in-cluding use of social media.Mr. Kim says while there are bright and

shiny tools for retaining patients — such astext message reminders and appointment calls— the key is finding out what patients expectand need.“We really need to understand what retains

the patient,” he says. “There is data out thereon retention, but no one has done a deep diveinto why a patient will continue. Naturally, wecan assume that some things can turn off pa-tients, such as rude staff, an unclean site, in-convenient hours, and a burdensome protocol.But I believe the real opportunity is engagingpatients in the bigger story of clinical re-search.”Retention, especially in a large trial, is a

constant battle, Mr. Silberstein says.“The approach we take is to get feeds of

data from EDC and IVR and look for concern-ing situations such as a late or missed patientvisit or somebody who has temporarily ceaseddrug,” he says. “We have an automated systemto assign action items to monitors and sites tomake sure that appropriate follow up occurs toprevent issues from escalating. It’s a form ofcentralized monitoring around this very im-portant challenge.” PV