Hands-On Therapeutic Training

The ideal scenario to deliver global clinical trials is to use project teams that already have conducted one or more studies in the same therapeutic indication. This experience provides the teams a "leg up" on preparing the protocol, identifying and selecting sites worldwide, and managing the conduct of the study to produce a quality and on-schedule outcome.

The reality, however, is that many companies today cannot afford to have indication-specific project teams hanging around waiting for the next trial. As a result, there is increased emphasis on the ability to provide high-quality, relevant training—usually on short notice—to newly formed project teams as they begin to execute a study.

With the right approach, an indication-specific training module can be created to provide the project team detailed exposure to the difficult issues they will face. The ideal training outcome is to have the project team feel as if they have already conducted a similar study. This is done by developing a stimulating and interactive training agenda¹ that uses real-life case studies and provides attendees a chance for "hands-on" experience² with information from recent studies.

Who needs training?

Some training programs focus on specific aspects of a study, such as monitoring or site start-up. However, this approach may not provide sufficient depth of experience for the team to be able to "hit the ground running," nor does it incorporate therapeutic-specific topics or team building to ensure the best possible team collaboration for the customer. The best training successes occur when all team members are included—from the project manager to the medical writer and everyone in between. When the entire team trains together, each team member learns more about his or her colleagues' roles and how they can more effectively interface to produce a quality product for the customer.

Typical prospectus

Therapeutic-specific team training should provide a complete experience, covering topics of broad interest and relevance to the project team. We now have experience preparing 12 therapeutic training modules, covering various indications in oncology, neurology, and psychiatry. The format described below has proven to be to be very effective for training both local and international project teams, and refinements have been made as we gain experience with this approach. A breast cancer training module is used as an example, but this format has worked equally well for other therapeutic areas. Table 1 shows the topics covered in a typical therapeutic-specific training module.

Table 1. Prospectus for a therapeutic-specific project team training module

Disease background

For the section on disease background, the training team is generally able to engage an internal medical officer or staff physician. If the necessary expertise is not available internally, it is also possible to draw on established relationships within the medical community. The disease background presentation on breast cancer was an interactive lecture format providing detailed information on the topics shown in Table 2. The presentation made liberal use of graphics and encouraged discussion from all participants.

Table 2. Breast cancer topics used in a therapeutic-specific training module

Protocol designs and clinical endpoints

To provide the audience real-world experience with the breadth of protocol designs used in breast cancer studies, this component of training provided an overview of four different protocols: two Phase I studies, one Phase II study, and one Phase III study. The regimens being tested included chemotherapeutic agents and a vaccine. Wherever possible, we used protocols for which the corresponding case report forms (CRFs) were also available so they could be used in the monitoring practical. Protocol designs can also be taken from the scientific literature (using PubMed searching

³

) and from the Web site of the U.S. FDA,

⁴

which is a particularly rich source for protocol designs and accompanying study metrics. Each protocol discussion included the topics shown in Table 3. Key clinical measures used in breast cancer trials were an important focus and included discussion of the most common clinical endpoints, such as Response Evaluation Criteria in Solid Tumors (RECIST) for measuring target and nontarget lesions,

⁵

the Eastern Cooperative Oncology Group (ECOG) performance scale,

⁶

"time to event" definitions, and survival curves.

Site selection is key

Site selection is a critical element of study start-up, as the entire study may suffer if sites are chosen poorly. Accordingly, our therapeutic training places strong emphasis on the site selection process, beginning with a discussion of the desired qualifications for a breast cancer study site. A regulatory specialist discusses approval issues specific to breast cancer trials, so the project team knows what to expect from institutional review boards and ethics committees. Audience participation is encouraged in this discussion; we have found that audience members often have valuable insights that benefit the team.

Table 3. Protocol topics discussed in a therapeutic-specific training module

We draw from experience to share examples of site start-up from previous breast cancer studies and encourage the use of historical performance metrics to choose the best sites. A metric that we find particularly useful is the Site Performance Ratio, which is simply the number of patients recruited by a site divided by the average recruitment for the study. Ratios above one signify above-average enrollment, whereas ratios below one are below-average performers (see Table 4). Our experience has shown that when it comes to recruiting patients, past performance is a strong predictor of future performance.

Table 4. Breast cancer site performance metrics

Examples of recruitment curves from previous breast cancer studies also are shared and discussed with the project team (Figure 1). This background helps the team make reasonable predictions for the new trial regarding enrollment. Understanding the enrollment drivers also helps the project team strategize for enrolling the new trial. This part of the training module includes a presentation by a patient recruitment specialist, who provides sample enrollment strategies and sample recruitment toolkits that the team can use with the new trial. Recruitment toolkits typically include a waiting room brochure, a small poster for the exam room wall, a camera-ready newspaper advertisement, a sample physician-to-physician referral letter, and instructions for creating postings on Web sites.

Figure 1. Example of recruitment curves from previous breast cancer studies.

Safety

Because the nature and frequency of adverse events differs widely according to indication, a Safety Specialist or Medical Officer presents on the expected adverse events (AEs) and serious adverse events (SAEs) likely to be encountered in a breast cancer trial. This information can be found in the package insert for similar chemotherapeutic agents. For oncology studies, the safety presentation includes a discussion of the Common Toxicity Criteria used to grade AEs and SAEs in chemotherapy trials. The safety discussion also provides a forum to learn about the types of concomitant medications these patients are likely to be taking. Each relevant medication is covered in detail in terms of its indications, dose levels, and possible adverse events.

Monitoring

The monitoring practical is the most difficult part of the training module to organize, but seems to be the part attendees enjoy most. This segment begins with a 30-minute lecture on the challenges of monitoring a breast cancer study and the differences in working with breast cancer sites as opposed to sites for other indications. A "hands-on" practical follows the lecture and includes a series of mock patient charts, which are used as source documents. Generation of the mock charts can be somewhat difficult due to current concerns for patient confidentiality, but since there is no need for any patient identifiers to be included, they can be assembled with some perseverance. If too many hurdles are encountered, it is also possible to work with patient vignettes that include much of the same information but are easier to assemble.

Project teams are presented with a set of completed case report forms (CRFs) for each mock chart or vignette and are invited to monitor the CRFs, looking for errors. One or two errors are "planted" per CRF page and the audience enjoys finding the errors and discussing the corrections. Prizes can be offered for finding the errors, thus encouraging audience participation. Frequently, the audience finds errors that we were not aware of!

Global considerations

Since many project teams are global, subject matter experts representing each of the countries in which the study will be conducted are involved in the training. This improves the sense of identity and belonging of individual team members and enhances collaboration globally.

⁷

A key challenge is to find time slots that allow collaborative training across multiple time zones. For project teams in North America and Europe, training can be scheduled during the mornings in North America so that the European members can avoid evening hours. An eight-hour training module would typically be scheduled in two half-days. An advantage of this approach is that employees can continue their ongoing obligations without disrupting work flow.

Conducting training across multiple geographies also is a challenge and requires the presence of facilitators at each location. We engage a Web-based electronic classroom through which dozens of locations can be connected simultaneously for training. Although the resulting geographic diversity of the training makes it more engaging for the project teams, room scheduling and arranging for facilitators in multiple locations can become a major undertaking.

When the Pacific Rim is included in the global team, it may be necessary to conduct the training more than once, or for some geographies to attend training at odd hours. For team members who are not able to attend a live training event, the sessions are available through archived Webcast recordings available anytime, anywhere—truly meeting the need for quality training at a moment's notice.

Earning CEU credits

Many CRO and biopharmaceutical company employees are members of trade organizations requiring ongoing education and appreciate being able to earn continuing education unit (CEU) credits for training experiences. Accordingly, it is useful to align the training with an organization such as the International Association for Continuing Education and Training (IACET) so as to be able to offer CEU credits to project teams participating in training. The offering of CEU credits requires that each lecture within a module has well-defined goals and learning objectives. These must be written in advance of the training and reviewed for educational integrity and clarity. In most scenarios, CEU credits are awarded in one-hour increments, so each lecture should be a minimum of one hour. This sometimes necessitates the pooling of related topics and use of multiple speakers within a lecture.

Trainee feedback and lessons learned

In the interest of continuous improvement, we have solicited feedback from trainees on this approach to therapeutic-specific project team training. The feedback has been positive, with most trainees reporting that the training was valuable and that they felt better-prepared for their new assignment, and more effective at it. They appreciate an interactive approach. Some of the strongest feedback was that presentation of routine concepts, such as how to conduct a monitoring visit, be avoided. Thus, we have learned to emphasize audience participation in the training and to counsel the presenters to avoid routine topics. Ongoing focus groups and feedback continue to help us strengthen these training modules.

Conclusions

In an environment where companies cannot afford to have therapeutic-specific project teams waiting for the next study, "just-in-time," hands-on, therapeutic-specific training can allow rapid deployment of a well-trained project team. With more studies being conducted worldwide,

⁸

it becomes important to provide this training globally, and in a format that maintains the interest of the project team while delivering the skills they need. Project teams prefer this training approach over traditional training and feel it improves their effectiveness in running a new study.

References

1. K. Kruse and J. Keil,

Technology-Based Training: The Art and Science of Design, Development, and Delivery

(Jossey-Bass/Pfeiffer, San Francisco, 2000).

2. J.M. Taekman, G. Hobbs, L. Barber, B.G. Phillips-Bute, M.C. Wright, M.F. Newman, M. Stafford-Smith, "Preliminary Report on the Use of High-Fidelity Simulation in the Training of Study Coordinators Conducting a Clinical Research Protocol," Anesth Analg, 99 (2) 521-527 (2004).

3. http://www.ncbi.nlm.nih.gov/PubMed.

4. http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm.

5. P. Therasse, S.G. Arbuck, E.A. Eisenhauer, J. Wanders, R.S. Kaplan, L. Rubinstein, J. Verweij, M. van Glabbeke, A.T. van Oosterom, M.C. Christian, S.G. Gwynther, "New Guidelines to Evaluate the Response to Treatment in Solid Tumors," Journal of the National Cancer Institute, 92 (3) 205-216 (2000).

6. F. Roila, M. Lupattelli, M. Sassi, C. Basurto, S. Bracarda, M. Picciafuoco, E. Boschetti, G. Milella, E. Ballatori, M. Tonato et al., "Intra and Interobserver Variability in Cancer Patients' Performance Status Assessed According to Karnofsky and ECOG Scales," Annals of Oncology, 2 (6) 437-439 (1991).

7. L.C. McDermott, N. Brawley, W.W. Waite, N. Brawley, World Class Teams: Working Across Borders (John Wiley & Sons, Inc., New York, 1998).

8. M.J. Lamberti, S. Space, S. Gambrill, "Going Global," Applied Clinical Trials, 13 (6) 84-92 (2004).

William K. Sietsema, PhD, is vice president of clinical regulatory strategic planning with Kendle, 441 Vine St., Suite 1200, Cincinnati, OH 45202, (513) 763-1315, fax (513) 381-5870, email: sietsema.william@kendle.com. He is also adjunct professor of pharmaceutical sciences with the University of Cincinnati.