Enrollment: Situation Difficult But Manageable

Life Science Leader

life scienceBy Michael Rosenberg, M.D., MPH

September 2009 - A recent article in The New York Timesdescribed how a variety of enrollment issues are hindering progress in oncology research. If anything, the article understates the challenges of enrollment. The focus on oncology excluded discussion of widespread enrollment problems in other therapeutic areas. Centerwatch indicates that only 10% of U.S. studies enroll on time, and only 15% of studies in all geographical areas. Slow enrollment has profound consequences for timelines and costs, ultimately harming sponsors, healthcare providers, and patients.

While there are no easy solutions to the complex challenges of enrollment, it is clear that improving enrollment performance requires a strategy with two elements:

  • We must cast a wide net and, in many cases, this means recruiting outside the United States.
  • We must wring every possible efficiency out of the enrollment process.

Casting a wide net is essential for a variety of reasons. In the United States, there are often multiple studies competing for patients in the same therapeutic area, and the standard treatment is likely to seem the better choice for more potential study participants. In some other countries, patients are more likely to consider the standard treatment inadequate. The patient is making the same calculation about the best personal course, but different inputs result in different decisions in different regions.

Efficiency Increases Are Key

Conducting studies offshore is not a magic solution to enrollment challenges. Regardless of where studies take place, it is essential to increase the efficiency of enrollment processes. This requires more proactive management and more timely and detailed metrics of enrollment performance, including continuous assessment of enrollment strategies, messaging and media, referral sources, reasons for screen failures, and the effects of different inclusion/exclusion criteria. Such metrics inform management decisions that optimize enrollment based on realities in the field. The specific issues that hinder enrollment vary with each study and, for each study, by investigational site. Only detailed tracking can enable effective management and identification of best practices in each case.

Closely tracking and proactively managing enrollment at sites in distant areas is even more challenging than in the United States. Differences in time zone, culture, and language can hide performance problems until they have become severe and costly. Nevertheless, the combination of closer tracking and tighter management with distant geographies is the best solution to current enrollment challenges.

The pervasiveness of the Internet makes this combination possible in many parts of the world, but far from automatic. The ability to manage via the Internet varies greatly among systems. Some current Web EDC (electronic data capture) software, for example, largely ignores the need for close tracking of operations such as enrollment. Other advanced EDC systems do systematically and continuously track key measures affecting enrollment. These systems have produced excellent results in the field. The most effective systems collect data for performance metrics as patient visits are occurring in the field and put the information on a sponsor’s desktop before the patient leaves the site.

A study of metastatic breast cancer provides an example of effective tracking across geographic areas. This study was initiated in the United States, but with backup plans for quick expansion elsewhere. When enrollment proved disappointing from the outset, we knew why enrollment was slow. Too few patients were being evaluated for inclusion (as opposed to too many screen failing or other reasons). We quickly initiated backup sites in Russia, the United Kingdom, and two other countries. With continued close tracking, this strategy enrolled an average of slightly over 31 patients per month, the fastest-enrolling study of its type in the published literature. This helped get the product to market a year ahead of schedule.

Enrollment will remain a challenge into the foreseeable future. However, the combination of timely metrics and proactive management has already shown the ability to improve enrollment performance despite the many challenges.