Better Budgeting for Patient Recruitment

As of 2000, there were approximately 7,500 clinical projects in the R&D pipeline worldwide, according to IMS Health. By 2003, analysts estimate the total number will grow to more than 10,000 clinical projects worldwide. CenterWatch reports that for each new drug application to FDA, pharma companies must conduct an average of 68 studies (Phases I-III) that need a total of 4,300 volunteers. With the expected increase in global R&D projects over the next year, the number of patients needed for enrollment is expected to grow by 15 percent annually.

In light of those challenges, patient recruitment programs are becoming increasingly important to pharmaceutical companies' success, and this article shows those responsible for recruitment how to better understand and manage the financial aspects of their task.

Budgeting Evolves

Until recently, patient recruitment was exclusively the physician investigator's role. Doctors drew patients largely from their own practices, and sponsors paid physicians for that access. A separate budget for centralized patient recruitment was rare.

As the number of clinical studies increased and competition among companies testing similar compounds grew, it became necessary to find new methods for attracting participants. Individual study sites began spending money on promotional campaigns. For every success, there were several failures, and the duplication of effort among sites was inefficient and wasteful.

Then sponsors began to analyze the return on investment for patient recruitment initiatives, challenging all those involved in clinical studies to evaluate decentralized versus centralized campaigns and budgets. Clinical research organizations (CROs) were the first to attempt centralized programs. But, lacking expertise in direct-to-consumer promotions, they found it necessary to hire others to develop recruitment communications. Many of the first centralized recruitment budgets were inflated, even exorbitant. More recently, the pooling of patient recruitment expertise from throughout the clinical study community-sponsors, sites, CROs, site management organizations, and communications agencies-has led to a more strategic approach to budgeting.

Accelerating and improving patient recruitment for clinical studies remains critical. According to CenterWatch, every day that a clinical study is delayed costs an estimated $37,000 in out-of-pocket expenses, and further, results in lost revenue from the potential product. Developing and managing a budget is essential to protect future profits. There is no substitute for being first to market with a new or improved product, and that potential must be factored into the budgeting process.

Develop a Profile

Before creating a budget, it is important to develop a protocol recruitment profile by answering several key questions. Project leaders should keep that profile as a reference throughout the recruitment planning, budgeting, and contracting process.

• How many randomized participants does the study need?

• How many patients must be screened to enroll the target number?

• How many sites are planned?

• Where will they be located?

• How much of the recruitment effort-if any-can the sites handle?

• Is the study pivotal for an FDA submission or is it an early phase?

• How important is the product to the company's business strategy?

• Does the sponsor have recruitment experience in the therapeutic category?

• What is the time frame for beginning and completing the study?

• How onerous are the inclusion/exclusion criteria?

• What is the incidence of the disease/ condition?

• Are competitive treatments already available?

• Are all sites under a central or local Institutional Review Board (IRB)?

Recruitment Funnel

To attain the target number of patients, recruiters' promotional efforts must reach a great number of potential participants. Recruiters then winnow down the large pool of candidates by scrutinizing individual eligibility and appropriateness for the study-creating a "funnel" effect. That method starts with the desired outcome and works "backward" to determine the promotional reach.

The first step is to determine how many individuals an investigator will need to medically examine in order to randomize one patient into the study. Next, research planners will need to determine how many people must pass a preliminary screening of key demographic requirements and basic medical history to be considered appropriate for an in-person medical evaluation. The last step is to determine how many people must call the study site in response to the promotion to generate the target number of individuals who will pass the preliminary screening. (See "The Funnel,")

The Funnel

The pre-established protocol profile helps project leaders determine the number of individuals they need to reach, which has a significant effect on the budget. For example, in a diabetic neuropathy study, ten patients might need to be screened to enroll one. But the promotional campaign may need to reach 1,000 people to generate the ten qualified callers who will result in one enrolled patient. In that scenario, the ratio of callers to enrollees is so great that the investigative site may not be able to handle the volume of inquiries. Thus, the budget would need to be expanded to allow for additional personnel or for the use of a centralized response center to field patient inquiries.

Budget Factors

No matter how large or small the study, certain factors don't change. A set level of funding for strategy, research, and development is required. Other factors are variable and depend on the number and location of markets and the number of sites and patients. Evaluating all the factors helps determine the budget's size and scope.

Timing. When a budget is developed affects the decision about which elements to include and which to eliminate because the timelines for their implementation fall outside the recruitment window. The earliest moment to consider the budget is during the development of the study protocol. Decisions about patient definition and selection, duration of study, location of research sites, and other factors affect recruitment efforts. Planning the budget at this point provides the most control over options and choices.

Study launch is a second common point at which recruitment budgets are developed. When patient recruitment isn't identified as a problem until this stage, it may be too late for some options. But there is still an opportunity for project leaders to bring a proposal to management and perhaps prevent some of the lost time and revenue that occurs when studies go into rescue mode. Rescue mode-when patient recruitment isn't recognized as a problem until after the study has started-is the most costly form of recruitment. Once options are limited, costs are at a premium.

Difficulty of protocol. Once the study protocol is written, it can be used to estimate the recruitment cost per patient ratio. Protocol factors that often increase recruitment difficulty-and therefore expense-include a placebo study arm, satisfactory existing treatments in the therapeutic category being studied, and the need for invasive patient procedures. Factors that might make recruitment easier include the likelihood of medical insurance coverage, wide demographic population being studied, and the use of a central IRB.

Number of patients/sites. Both of these factors increase costs incrementally. More patients mean higher promotional costs. Likewise, the more sites in the study, the more money companies must spend to cover additional media markets and the costs of creating and producing materials.

Location of sites. Locating multiple sites in one media market is a cost-saving strategy. Placing them in densely populated areas also serves to increase the number of potential participants without spending more for outreach.

Management priorities. How important is the product being studied to the sponsor's overall business strategy? If it already has a revenue stream and the study will help to extend or expand its profits, management will probably be more willing to spend money on recruitment to shorten the study's duration. Project leaders should not assume that, because patient recruitment was not budgeted as a separate effort in the past, management will not support a sizeable recruitment budget today.

Choosing a Model

One of the first considerations in setting a patient recruitment budget is to determine whether to use a decentralized or centralized budget, or a combination of both. Under a decentralized model, study sites manage the entire process of patient interaction. In a centralized model, the sponsor originates strategy and media materials, then communicates the message and disseminates the materials to investigators and sites.

Once the rule, decentralized budgets may soon become the exception. Still, there are some instances that make decentralization the optimum choice. When the number of trial participants is small, for instance, distributing recruitment funds to individual sites may be more efficient than managing the process from a central office.

Centralizing the budget is usually the most effective recruitment model. For large trials and those in Phase IIb or later, centralization offers economies of scale and prevents duplication. Centralization also results in more effective tracking. When sponsors use call centers as a central source of collecting information, they don't have to depend on numerous sites to submit recruitment promotion data reports. Project managers can determine early whether enough resources are being used to generate the targeted number of participants.

Sometimes a combination of centralized and decentralized budgeting works well. For example, sponsors might launch a recruitment promotion through a centralized TV or radio campaign, then allow individual sites to run print ads as needed to complete enrollment.

Competitive Edge

The method of motivating site personnel to recruit patients is also a budget consideration. There are two basic models: competitive and performance-based.

Competitive. In this structure, sponsors financially reward individual sites according to the number of patients they enroll, and multiple sites compete to recruit the most patients. Sponsors challenge clinics to recruit a minimum number of patients at a certain fee per patient evaluated and allow them to increase earnings by recruiting more than the quota. Thus, those that are good at recruiting generate more revenue for their research effort. Less effective sites receive less funding or are dropped from the study. Media support must be provided equally across markets to create a level playing field.

Performance-based. An alternative approach is to budget fixed amounts unevenly among the sites based on past performance. In this model, higher performers receive higher budgets, ensuring higher recruitment rates. Sites may be divided into several tiers. At the lowest tier are those that are unlikely to reach their quota and receive only a set amount of promotional support. For middle-tier sites, some extra funds can help them reach beyond their recruitment quota, and top performers receive the greatest budget support.

Knowledge of site recruitment performance is key to deciding between a competitive or alternative model. For sites lacking a history of performance, a competitive model may be a good choice. It can help establish a performance level, and it gets patients enrolled quickly, because sponsors reward the first sites to enroll the most patients. On the other hand, if some sites are proven high performers, allocating them the greatest portion of the recruitment funds makes more sense. In that case, it is less important to enroll patients quickly than to enroll them at a consistently high rate.

Drafting a Budget

Although most companies crave a budget standard, there is no industry-wide accepted practice for patient recruitment budgeting. Wide variations in allocations exist, but budgeting is most often approached from one or two perspectives. In the first, planners build the budget from the ground up depending on the assessment of the protocol and its recruitment challenges. In the other approach, a fixed budget is allocated to the initiatives that provide the greatest return on investment-measured by the number of patients enrolled.

From the ground up. In this scenario, project leaders evaluate each protocol to determine its relative difficulty of enrollment. When a direct-to-consumer promotional campaign is required to meet enrollment goals, some planners use an average of $1,500 per enrolled (randomized) patient as a baseline for budgeting. For example, if 750 individuals must be recruited for an influenza study that has been assessed as having an average difficulty, $1,125,000 would be budgeted. For a study that requires patients to undergo multiple endoscopies and has extensive exclusion criteria, planners might project that the protocol has twice the recruitment difficulty than the influenza study. In that case, the budget would be based on an assumption of $3,000 per randomly enrolled patient. (For a complete list of budget components, see "The Expense List.")

The Expense List

Fixed. Often project managers have a fixed amount of money to invest in patient recruitment, regardless of evidence that suggests a bigger budget may be necessary to complete the task. In that situation, it is important to evaluate all of the potential program elements on an ROI basis. It may be more prudent to allocate all of a $250,000 budget to a single promotion if that activity has the potential to generate 50 percent of the patients required.

After Budgeting

It's important to create a contingency budget to accommodate changes and unexpected circumstances. And many studies require ongoing recruitment efforts, which may need additional funding. Also, once budgets are complete, it is essential to gain the confidence and approval of management to go forward.

No matter how thorough the initial planning, inevitably there will be changes during the recruitment period that no one has anticipated. Contingency budgets give project managers the resources to respond to factors such as miscalculations, failure to receive approval from all IRBs, addition or withdrawal of sites, and changes in protocol. Generally, a contingency budget should be planned below the line of the main budget.

If a study runs 26 weeks or longer, it is worth budgeting funds to retain patients in the study. For multi-year studies, a retention budget, separate from patient recruitment and contingency plans, is mandatory. As with patient recruitment estimates, there are no accepted industry standards for patient retention budgeting. Experienced planners estimate costs at an average of $100 per patient per retention year as a starting point. If the study is complicated and requires more frequent interaction with patients, it may require a higher budget.

Even the most carefully thought out budget does not guarantee management support for new approaches to recruitment. It is necessary to understand the politics and dynamics of the sponsor company's management style. Knowledge of its previous experience, confidence level, and commitment to a product or study are important in planning the strategy for achieving budget approval. For example, some sponsors are more comfortable with the idea of outsourcing patient recruitment, while others are less familiar with the process.

Outsourcing supervisors. There is a growing trend in the pharma industry to identify internal individuals and departments to serve as resources and sometimes gatekeepers in the budgeting process. Based in the company's clinical, financial, or communications areas, they provide links to outsourcing, evaluation of suppliers, guidance through the competitive bidding process, negotiation procedures, and more. Teaming with those experts and gaining their endorsement can greatly assist in selling the budget to management.

One-shot vs. phased approvals. Depending on the company's past experience, there are different strategies for seeking approval. If project leaders' confidence in a budget is high, and the management has had positive experiences in budgeting patient recruitment, then one-shot, or comprehensive, budget approval may be possible. If confidence is low, and the company has had little or unsatisfactory experience with centralized patient recruitment, it might be best to seek budget approval in several stages.

Performance projections. It is an easy and worthwhile exercise to anticipate management challenges to a patient recruitment budget. For each element in a recruitment campaign, it is critical to project the performance of that effort, calculate related costs, and prepare performance metrics, including the number of inquiries, referral ratios, and enrollees that could result from each element. Such numbers can estimate the success of the recruitment effort, support a proposed budget, and convince management of the value of various media efforts.

Recruitment Success

In 2000, an estimated 86 percent of all clinical studies failed to enroll the required number of patients on time. And on average, US clinical studies are delayed by 366 days. With the daily out-of-pocket cost for a clinical study at roughly $37,000, those delays are significant. Combine those expenses with the cost of losing out on daily product sales averaging $1.3 million-up to $11 million for blockbuster drugs-and timely recruitment becomes a huge consideration.

With so much at stake, developing a thoughtful, strategically sound budget plan up front can shorten the recruitment phase and reduce delays. Ensuring that patient recruitment budgeting is an integral part of the process will contribute to the drive toward successful drug development and marketing.