Centralized patient recruitment really works	May 2009

By Richard Malcolm, Ph.D., CEO, Acurian Inc.

Rick Malcolm, CEO of Acurian Inc., presents three case studies that illustrate the value of centralized patient recruitment

Despite the existence of patient recruitment companies for more than 20 years in the United States, there is a paucity of good data supporting this tactic. Pharmaceutical companies, however, continue to support both central and local recruitment efforts in an attempt to reduce delays or even speed up critical trials. As clinical study teams plan future trials, the availability of recruitment case studies would be of great value to assist the teams in evaluating their patient recruitment options.

Generally, case studies in local recruitment are not widely available. Further, few examples exist of the effects of central recruitment on measurable recruitment metrics. In many cases, due to tracking and other data collection limitations, case studies reflect a statement of the recruitment challenge, a summary of the tactics employed, and subjective comments such as, “The pharmaceutical sponsor was really happy and the study closed on time” as the only results. There are no specifics on how many patients from the recruitment campaign enrolled in the study, over what time frame, and what the influence was on study closing. There is even less information on the financial implications of spending money for patient recruitment. Are the costs offset by real savings in other study-related costs? Are costs justified in terms of time saved?

The following are three case studies that begin to fill that data vacuum about patient recruitment. Specifics include the size of the study, the number of patients sourced from a central campaign, the timing of the recruitment activity, and importantly, the effect of the patient recruitment on the time needed to complete enrollment. This information should enable clinical researchers to begin to better evaluate patient recruitment options.

A major pharmaceutical company needed to quickly enroll a large study of post-menopausal women who experienced hot flashes. From prior experience in this area, the sponsor knew it needed recruitment assistance to meet its aggressive enrollment target, especially due to stringent body mass index and hormone replacement exclusions in the protocol. This Phase III prospective study needed a total of 2,000 patients across 113 sites in the United States.
The sponsor approved a centralized patient recruitment campaign using direct-to-patient outreach, a study website, and a comprehensive enrollment tracking system.

Figure 1 shows the results. The central recruitment campaign supplemented the site recruitment, providing 1,003 randomized patients in less than seven months. The enrollment rate doubled from approximately 1.25 patients per site per month to 2.5 patients per site per month. Importantly, the sponsor avoided a seven-month delay that would have been unavoidable with solely site-based recruitment, and actually finished enrollment one month earlier than originally planned.

The sponsor of this Phase III study faced challenges enrolling patients despite the large number of people in the United States with elevated cholesterol. Requirements for LDL, HDL, and triglycerides within specific ranges greatly reduced the portion of the hypercholesterolemia population that would potentially qualify. The screen fail rate was approximately 80%; consequently, six months after the study started enrolling patients, it fell behind schedule. This large study required randomization of 1,800 patients across 186 sites in the United States.

The sponsor chose to supplement site-derived enrollment with a centralized recruitment campaign. This rescue project used both direct-to-patient outreach around the 186 sites and a comprehensive enrollment tracking system.

As shown in Figure 2, the centralized campaign increased the rate of enrollment, ultimately contributing over 400 randomized patients, nearly 25% of total enrollment. Projecting expected enrollment from the sites at a constant rate, one concludes that the centralized recruitment enabled enrollment to close six months earlier. Using this data from Figure 2, it appears that the sponsor would have saved an additional two months had it used centralized recruitment from the start of the study.

A major pharmaceutical company needed to accelerate enrollment for a group of four Phase III studies of a drug for overactive bladder. Two of the studies were under way, but not meeting the sponsor’s timelines for enrollment. The other two studies had yet to begin. This group of studies required 2,500 randomized patients across the four protocols.

To meet its enrollment timelines for these important studies, the sponsor supplemented site-derived enrollment with a centralized recruitment campaign that included direct-to-patient outreach and a sophisticated screening/tracking system that assigned potential patients to the appropriate protocol based on a pre-screening process. Figure 3 shows the results for one protocol.

The centralized recruitment campaign, employed from the start of this study, contributed approximately 400 of the 900 patients randomized into this study. Additionally, central recruitment nearly doubled the rate of enrollment and reduced the enrollment period by nearly four months.

Across the program of four studies, central recruitment generated more than 700 randomized patients, which was more than 25% of the total enrollment goal. Consequently, the sponsor closed enrollment on time for this group of studies and eight months early for one protocol.

Centralized patient recruitment in the United States has cost, which at times is significant – although relatively modest when compared to overall clinical-trial fees. In assessing whether this cost is justified, a sponsor should look at two areas: actual costs associated with conducting the study, and incremental revenue obtained through faster or earlier approval of the drug.

Clearly, closing enrollment a month earlier will result in a savings for direct costs such as CRO fees, central lab fees, EKG fees, etc. A 2007 study by Cutting Edge Information estimated that, on average, the operational costs of a Phase III study exceed $1 million per month. If this is accurate, for the case studies presented previously, the operational cost savings ranged from $6 million to $9 million. This alone is enough to more than offset the cost of the central recruitment campaigns employed, without ever considering the impact of an earlier approval.

Often, recruitment is employed for late stage, critical-path studies. It is reasonable to assume that the time savings in enrollment translates to a more rapid study completion, and this in turn will lead to an earlier new drug application submission, and ultimately, an earlier approval. For drugs in many therapeutic areas, an extra month of market exclusivity can generate a substantial amount of additional revenue. For example, the asthma market is estimated to be worth more than $15 billion annually in the United States. By garnering a 2% market share – a month in that market is worth approximately $25 million – many fold the expense of an effective centralized patient recruitment campaign. Together with the operational cost savings noted earlier, additional market opportunity provides strong justification for centralized patient recruitment.

Delays in meeting enrollment objectives for clinical trials are clearly a challenge that clinical teams will continue to face in the future. As teams wrestle with this issue, these case studies begin to demonstrate the value of centralized patient recruitment in the timely completion of clinical trials. These examples further show that the contribution of a centralized campaign is incremental to recruitment by sites from their own patient populations, databases, or other sources.

Increased experience in centralized recruitment, coupled with a greater body of case studies, allows for a more meaningful projection of the impact of a central campaign on enrollment timelines, further opening up this additional option for study completion. These few examples need to be supplemented by additional examples in other therapeutic areas. Additional data on recruitment will lead to better, experience-based decision making on using enrollment services as a standard part of clinical trial budgets.

Initial analysis strongly indicates that recruitment costs can be more than offset by savings in actual study costs and a more rapid time to market. Further, it appears in many cases that they produce a very high return on investment. Given both the increasing number of cases illustrating success and the strong financial justification with centralized patient recruitment, more attention needs to be given to this option when evaluating patient recruitment and enrollment challenges.

Richard "Rick" Malcolm brings over 22 years experience in healthcare management to his role as CEO of Acurian, a patient recruitment provider. Prior to joining Acurian, Dr. Malcolm was VP, business development, for Icon Clinical Research, a leading contract research organization. Dr. Malcolm started his career in healthcare at SmithKline Beecham Pharmaceuticals (now GlaxoSmithKline) where he had product marketing responsibility for several cardiovascular, gastrointestinal, depression, and anti-arthritic products. In addition to serving as the worldwide head for SBCL's Clinical Trials Center (now Quest's central laboratory), he has served in senior management and consulting roles at start-up pharmaceutical companies including The Medicines Company and Neutris Pharmaceuticals. Dr. Malcolm received his B.S. in Microbiology at the University of Michigan and his Ph.D. in Pharmacology at the University of Southern California.