Getting entrepreneurial

As drugs and their clinical trials become more specialized and patient populations more targeted, patient recruitment continues to evolve. We know that there is no easy answer for getting patients, but more and more, the right approach is about ingenuity and perseverance, not about a specific recruitment tactic.

What do you typically think of when you consider patient recruitment – advertising, Web outreach, direct mail? While each of these tactics may be effective for certain populations and indications, the path to success in patient recruitment is close collaboration and problem solving. Most sites know which tactics work best for their studies and for their patients – and this is where collaboration begins. It extends from there to the CRO, the sponsor and to all study partners. Once this collaboration and partnership is in place, a patient recruitment campaign can really take off, with creativity and ingenuity close behind. Recently, MMG helped a large pharmaceutical company enroll patients for a difficult population – children with schizophrenia – by focusing on strong site support and collaboration.

MMG, a pioneer in patient recruitment with 20 years in the business, illustrates the growing complexity of reaching the hard-to-reach.

The challenge

The study goal was to recruit 0.5 patients per site per month to meet an overall recruitment goal of 300 participants randomized in 2 years (July 2004 to July 2006). While 300 patients in 2 years may sound doable – even easy – there were several factors that made this goal highly challenging:

1. Tight regulatory environment – Participants in the study had to have a DSM IV diagnosis of schizophrenia and be 13 to 17 years old. The diagnosis also had to be confirmed by a child psychiatrist with the Schedule for Affective Disorders and Schizophrenia for School-Aged Children – Present and Lifetime Versions (K-SADS-PL).
2. Small patient population – Based on the diagnosis criteria in the protocol (placebo, no schizoaffective disorder allowed, placebo, hospitalization only for washout), 75 percent of prescreened patients did not qualify for the study.
3. Family involvement – Many children with schizophrenia have parents with schizophrenia, other mental health problems, and difficult family situations. This made it a challenge to get patients in for screening and follow-up appointments.
4. Site selection – Many of the sites in the study, particularly those outside the U.S., were inexperienced with patient recruitment for clinical trials. These same sites had greater difficulty getting parents to agree to a placebo-controlled trial.

The solution

When strategizing about how to overcome the challenges of this study, it was clear that centralized outreach efforts such as advertising and online promotion were not the best options. We had tried these methods on a previous study for the same indication without success and most sites agreed that these options would not work. Many of these families were in a state of crisis – either due to their child’s mental health issues or that of the parents. Parents were primarily interested in getting medical help for their children. Many consulted with doctors and advocacy groups, but few actually responded to ads by calling a phone number or screening via the website.

The sites needed close individual attention and support in reaching out to their current patients and potential referring colleagues. We also knew that every site would need to have a slightly different mix of materials to effectively recruit patients. Finally, even with robust support and customized recruitment kits, sites would require significant motivation, as reaching parents of children with schizophrenia would not only be difficult, but would require a lot of their time. We estimated that we would have to reach approximately 100 adolescents with schizophrenia to have 0.05 percent, or half a subject, randomize. This estimate turned out to be high.

Fostering collaboration

A project with this level of intricate site support requires that the CRO and sponsor be fully supportive of the patient recruitment firm’s work. Both the CRO and MMG had regular communication with all sites through calls and e-mails, and the sponsor’s medical director had routine visits with sites throughout the study.

We also implemented a monthly study coordinator (SC) conference call that was tied to an Application Note developed by MMG in association with a site that had success with a specific recruitment tactic. The Application Note set the focus for the conference call and the call was hosted by the SC responsible for the information. This not only helped to highlight the achievements of the hosting SC, but the information was readily accepted by the sites because it was coming from “one of their own”. Typical SC calls would have up to 20 people participating.

Customized site support

Embarking on a patient recruitment campaign often fills study coordinators with trepidation – how am I going to communicate with these patients? Will I meet my monthly goals? How do I reach people beyond the patients I see in the office? Where will I find the time to recruit patients and do screenings and administer the study?

Given the level of experience the sites had with patient recruitment, site support was clearly essential. However, the CRO had also been given the task of supporting sites, so we partnered with them to:

• Communicate important information to the sites
• Gather metrics from sites
• Gain insights and perspective on how to tackle challenges throughout the study
• Provide a united front to the sites and sponsor and keep the lines of communication open.

In addition to the weekly teleconferences with all participating sites, MMG conducted individual site tactic teleconferences with the CRO, the PI, the SC and the site recruiter (if there was one) to brainstorm the best recruitment strategies for a given site. During these conversations MMG took into account site capabilities, PI and SC experience, the surrounding community and the clinic environment. The outcome of these calls was a list of agreed-upon strategies that the sites then put into action. These strategies were included in a letter that was sent via FedEx from the CRO to each participating site upon completion of the call. Almost immediately, MMG began to see an increase in screenings and randomizations. Many times, in anticipation of or closely following a conference call, site screening activity increased. In fact, randomizations increased by 15 percent after the first wave of site tactic calls began.

A broad selection of recruitment materials to choose from

This study included sites throughout the United States and around the world – more than 100 sites in 13 countries. Just as each site required varying levels of support, each site, particularly from country-to-country, required different materials. MMG created a variety of materials to meet sites’ varying needs:

Material	Use by sites
Posters	Internal reminder to site staff Within the site’s institution At community clinics In schools
Brochures/flyers	Site waiting rooms Health fairs Patient mailings Churches
Study reference card	Physician “Lunch and Learns” Grand rounds presentations Colleague mailings
PowerPoint presentation	MMG created a number of different presentations for the various audiences – physician colleagues, parents, school counselors – that addressed different aspects of the study “Lunch and learn” sessions Health fairs
“Dear Colleague” letter	Colleague mailings
“Dear Parent” letter	Patient mailings
Print advertisement	Health newsletters Community newspapers
Press release	Local interview opportunities for PIs
Advocacy group outreach materials	Articles placed in NMHA local chapter newsletters
Informed consent desktop presenter	Used in sites to assist families with the informed consent process
Placebo article on pediatric schizophrenia trials	Used with parents and caregivers as part of the informed consent process
Study Web site with screener	Used to share information about the study and to pre-screen potential participants

Motivation – a little competition never hurt anyone

Everyone knows that a competitive spirit can enliven any project. The sites for this study encountered challenges at every turn, and therefore had to keep motivation high to meet enrollment goals. MMG implemented a number of tactics to motivate sites and maintain that motivation throughout the program:

1. Study kick-off meeting – At the kick-off meeting, MMG gave the PIs and SCs an opportunity to provide input on the creative concepts for the study branding. This gave sites a sense of ownership and partnership in the recruitment program.
2. Monthly blast faxes – sent to actively recruiting sites to keep them aware of their recruitment numbers compared with the overall study recruitment.
3. Monthly newsletter – included protocol information and randomization by country, plus monthly projections for all sites. Typically, a site/SC was highlighted for a success story.
4. Enrollment challenge – An enrollment challenge was issued to sites monthly, offering a medically-relevant incentive item to sites for each randomized patient. A list of items was offered to SCs as a small token reward (less than $100) for their hard work on the study.
5. Booster meetings – These meetings were held for both PIs and SCs as a way to get the study top of mind. Interactive sessions focused around recruitment challenges and successes. The sponsor study staff, CRO project management and MMG staff also scheduled one-on-one sessions with PIs and/or SCs to discuss specific site issues.

For those sites that didn’t take part in the study challenges, some form of recognition was important to keep them going. Each active site received a small, branded appreciation item each month that came with a factoid about the scientific or clinical aspects of the study. The gifts served as a thank-you and the facts as a validation of the importance of sites’ efforts.

The results

MMG’s approach of collaboration, customized recruitment materials and site motivation strongly contributed to the success of this study, which screened 370 subjects and randomized 302 over a two-year period. A screen-fail rate of 18 percent indicates that only the most qualified patients were brought in for the study. Without the partnership between sites, the CRO, the sponsor and MMG, this level of success would not have been possible.