Centralized Patient Recruitment: Effectiveness and Cost Effectiveness

By Dr. Richard Malcolm

Despite the existence of patient recruitment companies for twenty years or more in the United States, there is a paucity of good data supporting this tactic. However, pharmaceutical companies 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.

“Clearly, closing enrollment a month earlier will result in a savings for direct costs such as CRO fees, central lab fees, EKG fees, etc. For the case studies presented previously, the operational cost savings ranged from $6-9 million. This alone is enough to more than offset the cost of the central recruitment campaigns employed”

Generally, case studies in local recruitment (providing patient recruitment funds directly to investigative sites) are not widely available. Further, few examples exist of the impact of central recruitment (funds provided to a company to run a centralized campaign) 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 like "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 impact was on study closing (perhaps because no one collected this data). 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?

Following are a few 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 impact 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.

Case Study 1: Women's Health
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 BMI 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 left 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.

Case Study 2: Hypercholesterolemia
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 left, 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.

Case Study 3: Overactive Bladder
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 underway, 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. Importantly, 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 over 700 randomized patients, over 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.

Cost Justification
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 three areas: actual costs associated with conducting the study, internal staff savings, and incremental revenue obtained through faster or earlier approval of the drug.

If you sit down and make a list, it may differ from study to study, from company to company, but you'll find that often there are a relatively large number of suppliers that are involved in the successful conduct of a study. It could include the central laboratory, the IVRS company and drug packaging supply company, an ECG company, a CRO, an imaging company, and so forth. If you note that each month that you need to continue the study, these people need to receive some sort of compensation for the continued time and effort they're putting in, you realize that there are significant out of pocket costs that are associated with delays or the conduct of the study.

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 recent study (Cutting Edge Information, 2007) 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 $6-9 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.

In addition to the budget neutral or the out of pocket aspect and the time savings, there's also a third element that needs to be considered here and that is internal staff savings; this is probably the most difficult to quantify, but it is real and it should be part of the equation. Essentially, when you're conducting a large phase 3 clinical trial, regardless of the vendors that you have selected to help you with the trial, a certain number of people within the pharmaceutical company are dedicated, either all or in part, to conducting the trial. If you're able to end enrollment, let's say four to six months sooner which is something that we've often seen, that means the trial itself should complete four to six months sooner and you have the opportunity to redeploy this internal staff to new projects sooner. Certainly, it isn't a cash savings but it is an opportunity to maximize the productivity of your staff.

So true ROI is a combination of all three of these elements - the reduction and out of pocket costs that you're paying to the vendors who conduct the trials, a savings associated with getting to the market sooner and having a longer period on the market where the drug is patent protected and finally, an ability to maximize the efficiency of your internal staff by reducing the amount of time they need to spend on a particular trial.

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 NDA submission, and ultimately, an earlier approval. Trying to quantify the impact of this earlier approval will depend on the therapeutic area of the drug, the market size, the expected share in the first year, the dollar revenue that that expected share is going to give you. And then it should also depend on what you expect in terms of revenue in the later stage as you move towards patent application. The reality is, if you accelerate approval, what you really do is pull a little bit of the revenue forward and get it more quickly than it would otherwise, but you also get a longer period of time, so you get more revenue at the end of the drug's life.

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 over $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.

Conclusion
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, PhD, Chief Executive Officer, Acurian
Rick brings over 22 years experience in healthcare management to his role as CEO. Prior to joining Acurian, Rick was Vice President, Business Development, for ICON Clinical Research, one of the world's largest Contract Research Organizations. 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. Rick received his BS in Microbiology at the University of Michigan and his PhD in Pharmacology at the University of Southern California.