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W finding the right population within the right time frame means doing your homework, looking at feasibility data, modeling time frames, metrics, and budget parameters.” Negative press is another uncontrollable factor that can slow patient enrollment, par ticularly if a drug is pulled from the market because of an adverse event and the clinical study is in the same therapeutic area. “Once enrollment or retention starts to lose ground, don’t sit around waiting for it to pick up on its own,” Ms. Moench advises. “Many people don’t realize there is a much higher cost to watchful waiting than planning effectively for a recruitment and retention program in the first place.” MediciGlobal has conducted financial modeling on the costs of waiting and deter mined that having a plan that can be quickly and easily deployed is more cost effective — even if the client never uses it — than trying to throw a plan together when it was needed yesterday and patients and time are lost. Another challenging situation occurs when patients have enrolled but fail to return for fol lowup visits because they either don’t under stood the instructions or don’t believe they need to come back. Whatever the reason, the time to respond and be proactive is immedi ately, Ms. Moench says. “Any red flag is just the tip of the iceberg, and a flexible plan with adequate contingen cies is absolutely critical to head off any prob lems before they get even bigger,” she says. According to Ms. Ice, lastminute fixes end up costing the sponsor company more money,
BY ROBIN ROBINSON
Katrina or 9/11, or even presidential elections; in fact, any occurrence that diverts patients’ focus away from their health. “While these events can’t be controlled, we need to have a plan in place to augment enroll ment if something does happen during a trial,” Ms. Ice says. She suggests adding backup study sites, lengthening the enrollment period, adding more aggressive media campaigns, or speaking at a national disease organization’s meeting to gain attention during these types of events. PLAN FOR ADVERSITY “For study success, we want to avoid having patient enrollment numbers dropping at all costs and to make sure this doesn’t happen, there needs to be a really good plan,” says Elizabeth Moench, president, CEO, and founder of MediciGlobal. “We need to look at the study through the patients’ eyes and understand where the stumbling blocks are likely to occur.” A solid analysis of the trial includes asking the study coordinators and members of the patient population involved for feedback on what they envision as potential areas for patient drop off. “It’s important to try to determine the point of clinicaltrial fatigue, or patients’ breaking point, by asking: `What would you do if you were asked to do this procedure, or that?”’ Ms. Moench says. “This may sound simple, but Without patients, and more importantly, without patients who stick with a program through the entire study, trial costs mount and study results are delayed. Overall, everyone — from the sponsor to the CRO to the enrolled patient — loses. This conundrum calls for solutions to strengthen the links in the patient recruit ment process: proactive planning, patient compliance programs, search engine optimiza tion, and protocol design, to name a few. Elements that can derail a clinical trial come in all shapes and sizes, so planning and risk management are the keys for keeping a clinical study on track. From the occurrence of a hurri cane to the availability of parking, every possi ble detail that might impact a trial must be scrutinized and a contingency plan needs to be at the ready. “When planning a clinical trial, it’s not a matter of if something will change, but a mat ter of when,” says John Benbrook, CEO of MMG. “Everything is an exercise in risk mit igation in order to navigate through the chal lenges of a trial.” And the challenges are many. From begin ning to end, the patientrecruitment process is fraught with obstacles that can throw even the bestplanned program off course. According to Tammy Ice, associate director of patient recruitment at INC Research, natu ral events or disasters consume the nation’s attention and at that point no one is interest ed in hearing about a clinical study. Ms. Ice has witnessed recruitment numbers dip during a national crisis such as Hurricane Strengthening the Clinical Recruitment Chain Step 7 A PROCESS The most crucial element in clinical trials — PATIENT RECRUITMENT — is also the weakest link in the chain of events leading to a study’s success. STEP 1 PV0308 LAYOUT 2/14/08 5:40 PM Page 22 difficult to break through the barrier and pen etrate the community to reach the population being sought. Partnering with trusted organizations within that community, such as a house of worship, community center, or other civic organizations can help overcome some of the barriers. “True community outreach programs can provide inroads into diverse patient popula tions,” Ms. Kottcamp says. “Many companies say they are doing community outreach, but if they are not partnering with the organizations that have the trust factor, their efforts are use less. It is about `feet on the street’ and getting out there and becoming ingrained in the com munity through a trusted partnership.” PICK THE RIGHT SITE AND SITE COORDINATORS Determining the right sites for a study has become easier through the recent emergence of datarich technology to help make selec tions. Five years ago, a sponsor might have used a broadbrush PR campaign to enroll patients. Now advanced healthcare data ana lytics can be a part of clinicaltrial recruitment strategies. “Sponsors used to say, `If we make people aware, they will come,’ but that wasn’t such an efficient strategy,” Mr. Benbrook says. “I am really excited about the new technologies and what they mean for the future. Historically, sponsors and CROs relied on selfreporting data and now there is a new cache of technology available by third parties to assess and confirm what a site’s actual access to patients will be.” Databases of deidentified electronic medi cal records provide increased transparency through aggregate verifiable data, which give sponsors a better sense of where physicians are and how many patients they have access to who may be eligible for the protocol. If possible, it would be helpful to deter mine what other types of studies are being done at the site, which can help with enroll ment, although sites are not always forthcom ing with what other studies are being con ducted there. Another tip is to assess the qual ity of the site staff and the turnover rate of the study coordinators, because they are the cru cial human touch with the patients. This is of particular importance for studies with visits scheduled over an extended period, as the coordinators are going to develop relationships with those patients, which enhances continu ity and completion performance. “Both recruitment and retention are key to effective fullpower accruals: having an estab lished study coordinator with a good attitude will have a significant impact,” says Rich Vachal, director of operations at XTrials Research Services. “The best bet is somebody who has been there for a while, who is com mitted to clinical research and not just doing the job as a temporary vocation.” To find the right study coordinators, Mr. Vachal suggests asking the right questions during the site qualification visit, for example, how they might go about encouraging patients who are possibly on the borderline of withdrawing from a trial; what their view of the process is; and what they believe is within their purview. A professional coordinator is crucial in keeping patients happy and fully engaged. “On average, the more enthusiastic the coordinator is, the higher patient retention is,” he says. “Clinical experience is certainly important, but the key difference is often a site coordinator who is fully engaged and focused and has command of the protocol and good relationships with trial management.” Relying on an experienced coordinator or investigator to help with decisions, such as local media buying, can be helpful and cost effective. “A study coordinator who has been in a location for a while and who has a history of clinical trials knows what types of local media are best, and a sponsor would be wise to con sult with him or her first before making a media buy,” Mr. Vachal says. As an example, he cites a recent experience he had with a sponsor who wanted to use a cer tain newspaper to promote a trial. According to Mr. Vachal, the clinicaltrial coordinator said, “I don’t recommend that. The sponsor is PATIENT recruitment I wish there was a magic bullet that would fix a clinical trial every time it falls behind schedule.Each specific challenge has to be evaluated and tackled head on. ANN KOTTCAMP ARGONAUTA COMMUNICATIONS STEP 2 particularly from unexpected expenses. This can be anything from rush charges at the printer to additional charges at the institu tional review board. Having to ask for more financing is an undesirable situation, and it puts everyone in panic mode. “Lagging enrollment creates a domino effect, costing the sponsor time and money,” she says. “Data entry is delayed, which impacts data management, so medical writing gets delayed, and so on down the line. These delays make a huge financial difference, even to big pharma companies.” To avoid costly situations, Ms. Ice suggests having a patient recruitment plan in writing that outlines the metrics to be used to signal when contingency strategies should be imple mented. “The biggest risk is waiting until the last minute to address and deal with enrollment issues,” Ms. Ice says. Misperceptions about the study process can also impede recruitment, especially in diverse or specialty patient populations. According to Ann Kottcamp, president of Argonauta Communications, there is a lot of mistrust in diverse populations and it is very 23 PharmaVOICE M a r c h 2008 JOHN BENBROOK MMG To mitigate the lack of physician support for clinical trials, pharma companies need to get behind a movement that raises awareness of the need for participants. PV0308 LAYOUT 2/14/08 5:41 PM Page 23 PATIENT recruitment better off using the morning daily that every one reads on the train on the way to work — it has a section for clinical trials.” Heeding the advice of the coordinator saved the sponsor time and money and expe dited enrollment. SEARCH ENGINE OPTIMIZATIONTO REACH PATIENT POPULATIONS Search engine optimization is another tool that can help strengthen the recruitment pro cess by sending the right message to the right patient, according to Wendy White, president and founder of Siren Interactive. Search engines are the No. 1 source for Internet users seeking health information; 80% of American Internet users, or some 113 million adults, have searched for information on at least one of 17 health topics. Most Internet users start at a general search engine when researching health and medical advice online, reports Pew Internet & American Life Project. Another Pew survey found that half (51%) of those living with a disability or chronic dis ease go online, compared with 74% of those who report no chronic condi tions. Fully 86% of Internet users living with a disability or a chronic illness have looked online for informa tion about at least one of 17 health topics, compared with 79% of Internet users with no chronic conditions. Epatients with chronic con ditions are more likely than other epatients to report that their online searches affected treatment decisions, their interactions with their doctors, their ability to cope with their condition, and their dieting and fitness reg imen. “Newly diagnosed patients represent just 5% of overall health information seekers, and make up 40% of online health information seekers,” Ms. White says. “Likewise, chroni cally ill patients make up 35% of health infor mation seekers but represent 50% of Web traffic for health information. This makes search engine strategy a good fit for reaching niche and chronically ill patients. We are noticing a trend toward more niche markets with the advent of more personalized medicine. Online channels provide more opportunities to reach niche markets and for those markets to reach out to the brands.” Understanding the behaviors of health information seekers makes it easier to know how to attract them by using either paid or organic searches, as well as how to retain them as active members to the site by creating a hub or community for them to opt in to. “In niche markets it’s about creating a space where patients can talk among them selves, about what they want to talk about, and where they can contact the manufactur ers,” Ms. White says. For example, a pharmaceutical brand mar keter discovered that a certain patient popula tion was referring to itself by the subdisease category name, which differed from what the pharmaceutical brand communications had been calling patients in marketing pieces. Subsequently, Web pages were specially devel oped using the same language that the patient population was using, including the name they called themselves, and according to mar keters, the brand began to realize better trial enrollment results. “Fewer patients viewed those pages but they were exactly the right people who need 24 M a r c h 200 8 PharmaVOICE WHO’S ONTHIRD? CCORDING TO ELIZABETH MOENCH, PRESIDENT, CEO, AND FOUNDER OF MEDICIGLOBAL, IN RECRUITMENT,THE RULE OF THIRD DEFINITELY APPLIES. Whether it is the percentage of the sites that will perform well, the percentage of patients who are at risk of discontinuing,or the percentage of patients whowill require more information about the clinical trial, the rule of thirds always applies. “On average, and across all therapeutic areas, 30% of sites won’t perform, 30% will have slow patient enrollment,and 30% will do well,” Ms.Moench says.“The same scenario applies to patient retention.” She says the third principle also works for how patients react to trial information:a third want to know as much as possible,a third want some information,and a third just want to knowwhat they need to do to par ticipate in the trial and follow the doctor’s recommendations. Ms.Moench says patients respond similarly to DTC marketing efforts as well. “A third will ask some questions,a third will not,and another third will come in fully informed and ask for a specific prescription,”she says. Ms.Moench recommends that keeping this rule in mind when planning a clinical trial will help to design a program with enough flexibility to appeal to and address all of the thirds. Source:MediciGlobal,King of Prussia, Pa. For more information, visit mediciglobal.com. STEP 3 A ELIZABETH MOENCH MEDICIGLOBAL One of the most critical words in the recruitment and retention market is flexibility. If there isn’t flexibility to allow for change or adaptation, the recruitment or retention program for the clinical trial is in trouble. PV0308 LAYOUT 2/14/08 5:41 PM Page 24 PATIENT recruitment 25 PharmaVOICE M a r c h 2008 ed to receive that information; so instead of a big blast that was sent out to everyone, a more targeted approach with the right information was the better option,” Ms. White says. “Posi tioning trial recruitment this way can produce a fabulous ROI.” Sound Bites from the Field PHARMAVOICE ASKED EXPERTS INTHE FIELDTO IDENTIFYWHATTHEY BELIEVE ARETHEMOSTCOMMONMISTAKESBEINGMADE IN THE INDUSTRY INTERMS OF STRATEGIC PLANNING FOR PATIENT RECRUITMENT. DIANAL.ANDERSON, PH.D., is President,CEO,and Founder of D.Anderson & Company,Dallas,a global patient recruitment and retention firm offering subject recruitment programs.For more information,visit dandersoncompany.com. “ Anumberof variables contribute to the success of a clinical trial.Among these are the establishment of rapport,trust,and mutual commitment to study goals among research sites,the CRO,and the sponsor.From these relationships arise enthusiasm among sites to embrace andexecute recruitment strategies proposed by the CRO,sponsor,and outside agencies.Leveraging investigator and site loyalty is a missed opportunity.Fostering relationships andbuilding trust require time andeffort and cannot be fully accomplished at the initial investigator meeting.The lines of communication must remain open to ensure recruitment strategies are understood and therefore fully executed. In doing so,sites will bebetter equipped to manage challenges as they arise, andemploymethods to avert needless study delays.Taking the time to invest in relationships maybe the best recruitment strategy of all. ” DONNABEASLEY is a Founding Partner andVPof Operations at Praxis Communications Inc., Brentwood,Tenn.,a clinical services provider specializing in patient recruitment.For more information, visit gopraxis.com. “ The most commonmistake in terms of strategic planning for recruitment is the lack thereof.Many companies don’t think about recruitment until it’s a problem and then it becomes a rescue situation.While sponsors recognize that enrollment remains the top factor for study delays,they often rely on sites “ The most commonoversight in recruitment is failing to build flexibility into the trial system. While a strategic plan focuses the organization onmarketing tactics and study execution, it is just as important to build in elasticity to properly manage recruitment andmeet client expecta tions.Specifically,every study should have a Plan B. It’s important to anticipate the worst case scenario,whether it bedifficult primary feasibility, miscalculating timing,underestimating incen tives,or unanticipated competition from other studies.First and foremost,however,get Plan A right. It’s important to identify trigger points early in the recruitment plan.Once established, monitoring the metrics throughout the study to recognize the triggers can help activate Plan B as early as possible.Assessing study flow can reduce these issues,particularly for companies with multiple sites. Identifying and correcting any trial at the critical points of preparation can smooth study conduct. ” KATHLEENB.DRENNAN is Managing Director of Iris Global Clinical Trial Solutions,Chicago,which provides clinicaltrial solutions that integrate patient recruitment,retention,and investigator site support.For more information,visit iristrials.com. “ To few pharma companies are integrating strategic planning in the clinicaltrial process. The traditional process is still entrenched in many companies,and they are slow to change.Usually,clinical teams build the clinicaltrial protocol first; recruit as many investigator sites as possible,many times without knowing how to best identify the optimum strategy to locate the right patients; and then launch the patient recruitment campaign to drive qualified patients to the site. This approach leads to unsuccessful outcomes, such as inefficiencies and costly delays in clinicaltrial completion. ” andCROs,rather than consider a proactive alternative to managepatient enrollment.Sites aren’t experts in recruitment.Companies need to focus onexpediting the recruitment process through up front feasibility analysis of the protocols, followed bydevelopment and implementation of strategically planned recruitment programs.Up front budgeting andplanning will save millions in lost revenue and reduce direct costs. ” JAIMECOHEN is a Research, Planning and Analysis Leader at BBKWorldwide,Newton,Mass.,a patient recruitment firm that provides clinicaltrial sponsors with global study enrollment technologies,products,and services.For more information,visit bbkworldwide.com. “ There seems to be a lack of clear articulation and careful consideration of the impact of a company’s business objectives on the patientrecruitment timeline.Although all parties would agree that reducing the enrollment period is a high priority, depending on the vantage point,there maybe other priorities.This type of strategic oversight often occurs during the country selection process for a particular protocol or suite of protocols.For example,Country Amaynothave ideal characteristics for patient recruitment as compared with Country B,which mayneed to be included because it is a large postapproval market for the drug.To maximize enrollment potential,while also adhering to business priorities,there should be a weighting and ranking of business and recruitment objectives — leaving the teams with enough information to proactively develop strategic plans to balance any recruitment deficits. ” RUSSELLM.DIXON,M.D., is the Medical Director for Early Clinical Development at Covance Inc., Princeton,N.J.,a drug development services company. For more information, visit covance.com. PV0308 LAYOUT 2/14/08 5:41 PM Page 25 PATIENT recruitment Pharma companies attempting to recruit patients are taking a big risk by not investing in search engine optimization, because mar keting efforts could inadvertently boost results of other trials. The risk is that trial managers could be feeding their competition if that brand is search optimized and their brand is not, Ms. White says. She cites the following example: a small niche brand in a very broad therapeutic area had been “totally optimized for search” when a much larger brand in the same therapeutic area aired a major TV push encouraging view ers to go to the brand’s Website. But the larg er brand was not optimized for search engines, so when viewers forgot the brand name but remembered the therapeutic category and used search engines for their research, they ended up on the niche brand’s site. “This small brand got a surge of hits off the bigger brand’s dollar,” Ms. White says. “Brands of all sizes need to be prepared for online optimization.” INCREASE AWARENESS OF CLINICAL RESEARCH Physicians who are unaware of clinicaltrial options can throw a monkey wrench in the recruitment process. Low physician participa tion is a considerable challenge for the indus try, according to Mr. Benbrook of MMG. “The greatest single influencer for patients to join a clinical trial is the advice of their physicians,” he says. “A strong endorsement from physicians has the biggest impact on patients joining a trial. The biggest challenge — and this number is staggering — is that only 5% of physicians in the United States are participating in research. There is a huge gap in the number of physicians who are support ing clinical trials and the number of physi cians and patients needed to meet enrollment goals.” Mr. Benbrook cites a couple of reasons why physicians are hesitant to join the ranks of investigators: the lack of focus and training on research in medical school, coupled with the labor intensity of the trials, make it a hard sell to timestarved physicians. There is a very large percentage of physi cians who conduct one clinical trial and do not ever conduct a second one, Mr. Benbrook says. Sponsors can mitigate the lack of physician support by getting behind a movement to raise general awareness around the need for clinicaltrial participants and physicians. “Educating research and nonresearch physicians about study opportunities and the need for volunteers can go a long way in changing the public perception about clinical trials,” Mr. Benbrook says. For example, in response to a crucial need for Alzheimer’s research participants, MMG was asked to support an Alzheimer’s Associa tion clinicaltrial initiative program to raise awareness of research opportunities to patients, their caregivers, and physicians. MMG created a taskforce of physicians and researchers in each of the five pilot cities — Indianapolis, Tulsa, Okla., San Francisco, Providence, R.I., and Atlanta — to raise research awareness for professionals dealing with Alzheimer’s patients. To reach further 26 M a r c h 200 8 PharmaVOICE A CLINICAL STUDY FOCUSING ON PATIENT COMPLIANCE HARMACENTRA IS CURRENTLY CONDUCTING A STUDY ON PATIENT COMPLIANCE WITHIN A GLAUCOMA CLINICAL TRIAL WITH THE ROLLINS SCHOOL OF PUBLIC HEALTH AND THE SCHOOL OF MEDICINE AT EMORY UNIVERSITY. Fundedby a grant from the National Eye Institute at the National Institutes of Health,the study is focus ing on how a technology option can increase patient adherence to prescribed treatment regimens.The technology, developed by PharmaCentra, is called the WellTouch system, which provides glaucoma patients with tailored and interactive telephone messages to increase treatment compliance.Customized printed materials are also being sent to the 250 participating patients. According to Dan Berman, chairman and CEO of PharmaCentra, the study aims to identify the causes of patient noncompliance with glaucoma treatments and then provide an individually tailored, lowcost, and effective intervention to improve compliance. According to PharmaCentra,almost 30% of all patients stop taking prescribed medications within the first few months of treatment. Patients in the program receive information that is specifically relevant to their glaucoma status,along with tips and strategies that will aid in treatment compliance. In turn, study investigators will be able to track patient progress and monitor their level of compliance.Study participants will be interviewed every six months over an 18month time period to gather data that will help determine treatment compliance related to prescription refills, appointment keeping,and medication taking.Additionally,a cost analysis of the study will be conducted. “The results will give insight into patient recruitment,outcomes,and messaging behaviors,particular ly with asymptomatic chronic illnesses such as diabetes, hypertension, and high cholesterol,” Mr. Berman told PharmaVOICE.“What we learn from the study will help in designing better content and partnerships that will drive better patient outcomes.” Source:PharmaCentra,Atlanta.For more information, visit pharmacentra.com. WENDYWHITE SIREN INTERACTIVE Using search engine optimization is really more of a pull technique than a push tactic, and it involves providing the right answers to the questions patients are asking. STEP 4 P PV0308 LAYOUT 2/14/08 5:41 PM Page 26