Subject recruitment is a process by which populations of patients (volunteers)

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1 Peer Reviewed Recruitment always takes longer than initially anticipated, unless you have planned well. Mark Metzner, BA Charles H. Pierce, MD, CPI Subject Recruitment Are You Prepared to Succeed? Subject recruitment is a process by which populations of patients (volunteers) with prescribed characteristics (as defined in the study protocol) are sought and enrolled into a clinical trial. Recruitment always takes longer than initially anticipated, unless you have planned well. Recruiting volunteers involves much more than simply placing ads for, or answering phone calls from, potential study participants; it means identifying obstacles before and during enrollment and using ever-growing aggregate experience to predict performance. These obstacles may include finding effective recruiting personnel, facing competition for volunteers from other sites/offices, perfecting and following a complex protocol or study design, managing the duration of a long-term study, negotiating the location/availability of potential participants, and identifying innovative, positive ways to engage them with studies. In the following sections, we will discuss these matters in turn. Recruitment Professionals Finding the right staff to handle subject recruitment can be challenging, especially when the position is often treated as entry-level or held by someone as a secondary responsibility. However, not everyone can perform the job; it requires tenacity, rapport-building skills, enthusiasm, and, critically, delivery of the research site s message in a manner that encourages confidence with the potential volunteer. The best recruiters are bulldogs who keep after what can be a very repetitive set of tasks by always making that next call and maximizing their days in a very self-directed way. They do not require prompting, prodding, or prizes to be productive consistently in the face of either a large amount of work or possible tedium. The best recruiters are naturally empathic, and use their empathy to help build rapport with volunteers. People, for the most part, seek someone they feel they can trust when calling a medical facility; thus, recruiters who have genuine empathy screen more and schedule more people. Furthermore, the best recruiters realize enthusiasm is contagious. If they are excited about the study, the subject will be, too. Enthusiasm validates empathy and cements rapport. Lastly, the best recruiters are salespeople. They know that the message has to be delivered in accordance with the tenets of good clinical practice (GCP). They are professionals who use institutional review board (IRB)-approved documents and realize that they have to seek to build understanding with Issues in Clinical Research x 39

2 the volunteer. If they do not have the training or confidence to address subject concerns about clinical research or the study in a polished way, they will lose rapport (and the site will lose opportunity). The Competition The next obstacle, competition, is a double-edged sword. Many prescribe to the theory that any advertising for any clinical trial is good for everyone in the industry. However, unless a site is an exceptionally well-developed brand, the reality is that any competition demands its attention. Finding the right staff to handle subject recruitment can be challenging, especially when the position is often treated as entry-level or held by someone as a secondary responsibility. When recruitment efforts follow GCP and volunteers are appropriately identified and informed, competition always has an effect on the overall available subject pool. Sites have to be sure they are getting both good placement and appropriate separation from their competitors. For a site, being aware of competitors advertising and making adjustments to one s own messages based upon the competing messages and media choices are necessary parts of the recruiting process. Trends in Protocols By far, changes mandated by regulatory authorities in study design and basic inclusion/exclusion requirements have had the most dramatic impact on recruiting efforts in the past years (see Figure 1). Protocols in all phases of clinical research have Figure 1 Protocol Complexity and Administration Burden (All Therapeutic Applications, All Phases) Unique procedures per protocol (median) Total procedures per protocol (median) Total investigative site work burden (median units) Total eligibility criteria n/a Median number of CRF pages per protocol n/a Source: Tufts Center for the Study of Drug Development become more and more restrictive; what used to be two or three studies are streamlined into a single protocol; and the Food and Drug administration (FDA) has taken a more direct, active role in specifying what procedures and volunteer populations are most appropriate for studies targeting different conditions. AN OPINION ABOUT MARKETING... Evaluating a protocol for recruiting purposes, therefore, now involves much more than simply plugging the inclusion/exclusion information into the database. Recruiters have to look at the concomitant medications, the schedule of procedures, and the potential visit schedule for volunteers; all will, in some way, affect enrollment. It is critical to understand that marketing does not have the ability to place people into studies. Marketing rings the phone. That s it. Regardless of the metrics others may have presented to you, there is NO direct, mathematical correlation between media spending and randomized patients. The proof is in a simple scientific concept: reproducible results. If provided the same study seeking the same population with the same media budget with the same media choices 0 times, it would be happenstance if the key metrics were the same twice out of the 0 attempts. Efforts to quantify marketing into a performance metric have been assumed accurate without being held to any principles or standards. The panacea of data seems more alluring than the basis of creating it. Marketing creates opportunity at variable levels influenced by innumerable factors. The metrics associated with the effort begin and end at response rates and return on investment for those responses. Beyond the initial response (and/or the appropriate motivation to respond), marketing is an inappropriate data point. Did marketing explain how the study worked? Did marketing skillfully guide an interested subject through the telephone screen; through the informed consent form; through the screening visit? In all cases, no. People did that not marketing. A site s systems, procedures, and practices make enrollment happen. The warmth of a well-trained human voice, the care of medical professionals, and the experience of study clinicians enable it. Marketing does not. Marketing is nonrepeatable and cannot exist in an appropriate vacuum to be used as anything other than a tool. Advertising is fundamentally persuasion and persuasion happens to be not a science, but an art. William Bernbach, one of the three founders in 1949 of the international advertising agency Doyle Dane Bernbach (DDB) 40 x Monitor JUNE ACRP

3 How Long is Too Long? The next obstacle in recruiting is the duration of the study. This is especially true in early-phase research, where extended in-patient stays or repeated procedural stays can adversely affect the available pool of participants. Latephase studies often suffer the same fate from their additional months or years of mandated follow-up visits. In the early-phase example, even with a vast pool of available participants, the visit schedule can make it virtually impossible to find people who can make all of the study visits. For late-phase work, volunteers, ever savvier than they are given credit for, may decline to be enrolled in a long-term study if several short-term ones are available. Finders, Keepers The last two obstacles are intertwined. Locating and engaging potential study volunteers is a challenge for sites that do not have helpful resources present from past studies, database recruitment efforts, or the private practices of the principal investigator or subinvestigators for a particular study. Even if the indicators show a site has a worthwhile database for judging study feasibility, actually enrolling the study in full is not a guaranteed matter. As an example, one stumbling block may be that maintaining the intentions of the protocol normally requires one or more amendments, which routinely feature adjustments to inclusion/ exclusion criteria. Unless a site is an exceptionally welldeveloped brand, the reality is that any competition demands its attention. For site purposes, knowing the people in the database allows for not only finding them when a study begins, but for addressing issues surrounding the volunteer experience. Managing how people interact with the site and its various personnel is essential, as very few people have personal experience to draw from when considering clinical research (see Figure 2). One of the most prevalent issues is study participants knowledge (or lack of knowledge) about what research really is and their role in the process. Even though most Americans have never had direct experience with research, a combined 74% cite they are very or somewhat to participate (see Figure 3). Understanding a volunteer s motivation within a site s database is the key to proper planning. Understanding a volunteer s motivation within a site s database is the key to proper planning. Why are they using the site? What has the site done to make itself attractive to them? What factors most affect the site s ability to generate attention to, and fulfill enrollment of, its studies? Which performance metrics actually make a difference at the site? In a MedWatch survey from 02, 941 respondents provided feedback on the factors that reduced their willingness to participate in clinical trials: 63% - Risk of side effects 62% - Inconvenient location of the clinical pharmacology unit 46% - Possibility of receiving a placebo 29% - Requirement of confinement 21% - Inadequate compensation The value of the site database is significant. Knowing why people participate at a particular site out of all the possible sites in a region allows that site s managers to tailor the recruit- Figure 2 Few Americans Have Participated in Clinical Research Have you or anyone in you family ever participated in clinical research? No 85% Yes 15% Source: Your Congress-Your Health Survey, June 09 Charlton Research Company for Research!America. ment efforts for its studies appropriately, and makes recruiting management easier. National-level information (see Figures 4 and 5) from the Center for Information and Study on Clinical Research Participation (CISCRP) may be useful to Figure 3 Many Americans Likely to Volunteer for Clinical Research Please consider your own possible participation as a volunteer in clinical research. How would you be to participate in a clinical research study? Not % Would not participate 6% Somewhat 44% Very 30% Source: Your Congress-Your Health Survey, June 09 Charlton Research Company for Research!America. x 41

4 help frame recruitment planning or philosophies at a site, but will not exactly reflect any particular site s marketplace or database. Keep in mind that each cache of volunteers is unique. Once site recruiters understand their database, they can get to know their participants. This is where the value proposition behind participation starts for the subject. Recruiters who cannot build and maintain rapport will have same-study and repeat-study subject retention issues. Establishing trust is a team effort in which every person who contacts a subject is part of the process. Overwhelmingly, it is the relationships subjects have with the staff they encounter that foster a healthy atmosphere for recruiting at a site. This phenomenon is highlighted in information from CISCRP about focus groups with study volunteers: Focus group participants unanimously agree that their personal relationships with study staff influence their decision to volunteer and their willingness to complete participation. The overwhelming majority of focus group participants praised the support system of study staff including physicians, nurses, and trial coordinators as highly skilled, personable, and accessible. Volunteer-study staff relationships form and solidify at several critical junctures. With the right messages and modes of communication, research sites can reach out to potential volunteers at decisive moments and invite them to begin conversations that could grow into lasting commitments to the center and its staff. To be effective, the education provided before and after trials must reflect what volunteers expect, need, and want to know about clinical research. (excerpted from Factors That Most Inform and Educate Clinical Research Participants, 09, Figure 4 Which One of the Following Do You Think is the Most Common Reason for Participating in Clinical Trials Percent A site s staff must be ambassadors of the site and respect the volunteers as its most valuable asset and resource. Volunteers are the keystone in the research process, without which the integrity of clinical trials cannot be supported. Conclusion It can be argued that successful recruiting including community outreach is the single most important factor in the vitality of any site, therefore the Figure 5 In General, How Safe Do You Think Clinical Research is for People Who Participate Percent make money help others Being sick and seeing no other options Source: CISCRP/ODC Survey, February by CISCRP. 19 Having no insurance and needing medical care receive higher quality medical care and more attention Not sure/ don t know 08 (N=1,000) 06 (N=900) 05 (N=1,000) 04 (N=1,000) Very Somewhat Not very Not at all Not sure/ don t know Source: CISCRP/ODC Survey, December 04, October 05, April 06, and February by CISCRP x Monitor JUNE ACRP

5 Figure 6 Steps in the Recruitment Process 1 Develop a Plan Move from feasibility discussions to active planning quickly. Assemble your team(s). Communicate items important to the protocol, regulatory issues, and GCP to the appropriate members of each team. Develop a plan to recruit, screen, enroll, retain, and complete evaluable subjects. Review your available pool of subjects from your database and set expectations. Understand how success is to be measured. 2 Choose a Strategy The primary source of participants for your study should come from your database. However, if you have a local media budget, you should plan to use it. Know your media choices and and Internet options, and make media choices early. Know what has worked before with this indication/population/study design. Make sure you use static resources like your website to recruit. Recognize any special attention your target subject population requires and customize your plan for it. Review business and trade relationships that might provide you access to subjects. Coordinate enrollment timing with sponsor/irb approval and/or site initiation visit and start on time. 3 Foresee Barriers Understand that the recruiting process is designed to dismiss those who do not qualify and may, in its course, uncover other obstacles causing retention issues. Additional demands on the patient (i.e., participation takes more time than expected) Protocol complexity that is confusing to volunteers and/or staff Side effects of the drugs Fear of the experiment Poor understanding of procedures Distrust of medicine/hospitals/doctors in general Lack of genuine understanding during the informed consent process 4 Prepare for Special Populations You cannot be too prepared if you have a unique population, especially in terms of IRBrelated issues. Start early and look for challenges and cultural differences Identify and remove barriers Understand any gender, language, religious, or trust issues Provide additional training 5 Actively Recruit Recruiting is a full-time job. Make the time for your recruiter(s) to recruit. Use database metrics daily Add new ideas and strategies when required Enable recruiting staff Meet enrollment deadlines Track your results 6 Monitor and Adjust Your plan will need active management. Essential in the process is a robust tracking system with subject accrual reports communicated widely to the study team. Dismiss unwanted, noncompliant, or otherwise unevaluable subjects Allow your message to work before altering its content or media choice Update screening materials with unique circumstances regarding clinical screening Know who is prequalifying and who is not prequalifying, and why Catalog successes and disappointments staff assigned to this function must be dedicated, organized, and well trained (see Figure 6 for a review of the steps to take in recruiting). Failure to plan for recruiting that will lead to full enrollment on an on-time basis is to result in disappointment. The effects of recruitment shortfalls are economic ripples that pulse through an entire site; staffing is not maximized, space is unused, study milestones are not met, and sponsors are less to offer future projects. To avoid these issues, sites should concentrate on accepting only those studies for which patients can be recruited efficiently from the site s own database. Furthermore, recruiters must know the characteristics and motivations of the people who participate in the site s studies, use marketing appropriately as a tool, and make the experience as educational and rewarding as possible for volunteers, in order to encourage repeat engagement in studies. Above all, recruiters must plan to succeed; manage the plan through the enrollment window; and remember to celebrate when the goals are reached. Mark Metzner, BA, is associate director for recruiting and community affairs with Medpace Clinical Pharmacology in Cincinnati, Ohio. After a career of more than years in radio broadcasting and consultive marketing sales, he has spent the past eight years managing a call center environment, creating and placing marketing, and supporting enrollment for clinical research in Phases I IV. He has also been a presenter at recruiting-related industry conferences over the past few years, including presentations with his coauthor for this article. He may be reached at m.metzner@medpace.com. Charles H. Pierce, MD, CPI, is medical director of the Metabolic and Atherosclerotic Research Center, a unit of Medpace, Inc., and immediate past chair of the Board of Trustees of the Academy of Clinical Research Professionals, ACRP s affiliate overseeing certification program functions. He also gives webinars about risk management through knowledge of GCP regulations and investigator responsibility, so that members of the investigative team understand the regulations and the ethics of clinical research. He has been active in clinical research for more than years, including developing Phase I and IIa trial units and performing medical monitoring in both drug and device studies, and has delivered webinar presentations on the subject of this article. He may be reached at charles@pierce1.net. x 43