Training for the Real World

Recent scientific breakthroughs promise significant payoffs for human health, with new discoveries opening the door to new pharmaceutical and therapeutic agents. But the potential health benefits of these discoveries are often threatened during clinical development by high risk of failure, high development costs, and a decline in the number of successful products reaching the marketplace. Since 1993, the U.S. Food and Drug Administration (FDA) estimates that yearly U.S. pharmaceutical R&D spending has more than doubled, while the number of new drug and biological submissions has decreased dramatically (see Figure 1). ¹

While a variety of factors can contribute to this decline, failure to reach the marketplace can in part be caused by not meeting stringent regulatory requirements, including good clinical practices (GCP) and the Code of Federal Regulations (CFR). Also adding to the failure rate are safety problems and effectiveness. Given these circumstances, the FDA estimates that a drug entering Phase I testing has only an 8 percent chance of reaching the marketplace.¹

Figure 1. Number of submissions of new molecular entities (NMEs) -drugs with a novel chemical structure-and biologics license application (BLA) submissions to FDA over a 10-year period. Similar trends have been observed at regulatory agencies worldwide.

Having well-trained study coordinators can be a key success factor for pharmaceutical and biotechnology companies facing these issues. As the individual responsible for day-to-day clinical trial activities, it is the study coordinator who can ensure standards are met and that any problems are spotted and taken care of immediately. Yet many of these professionals often go without the training needed to ensure the best results. This article discusses the importance of specialized training for study coordinators and identifies the curriculum that can offer value where theoretical training falls short.

The need for better training

Study coordinators come from a variety of medical backgrounds, from medical assistants to nurse practitioners. Although familiar with the standard tasks associated with the coordinator role, they may not be as well-versed on the particulars associated with clinical trials in specific therapeutic areas, including the gathering and reporting of quality data. Training can help, but it often falls short of meeting specific needs. Results of a survey sent in coordination with the Spanish Lung Cancer Group and published in March 2004 by BMC (BioMed Central) Medical Research Methodology found that less than half of the oncology study coordinator respondents had received specific training in oncology, clinical research, or GCP. Many of these same study coordinators were found to be involved in all aspects of clinical site coordination, as well as preparing IRB submissions, scheduling patient CT appointments, and assessing inclusion/exclusion criteria—tasks that require specialized training beyond what many have actually received.

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This lack of training can present a barrier to meeting regulated research expectations—the EU Directive, Health Insurance Portability and Accountability Act (HIPAA), and other regulatory and legal concerns. It increases the risk that standards may not be met because the study coordinator may not be aware of them. It also shifts the responsibility of preparing and managing study coordinators from the investigators to the individual study sponsor or monitor. This most often occurs during the course of clinical trials, which can interfere with a trial's process and timeline.

Where traditional training falls short

Usually academic in nature, traditional training courses teach the theoretical and historical aspects of clinical research and provide an abstract framework for conducting clinical trials. Other typical "how-to" programs focus on protocol-specific tasks such as how to administer informed consent. But this training does not successfully address issues that may be related to all the tasks associated with a study coordinator's role.

Between these two levels of education, there exists the practical stratum of knowledge that many study coordinators are lacking. Theoretical and tactical aspects should be bridged with the "how" and "why" of the study coordinator's role as it relates to a particular therapeutic area, product class, or country. This requires a curriculum that balances an explanation of the study coordinator's role, addresses specific aspects of job performance, and highlights the anticipated issues associated with a clinical trial.

For example, multiple breast cancer trials are performed throughout the United States, making competition for patient participation a major challenge. Study coordinators should learn when to anticipate slow recruitment rates and alert the organization conducting the trial, so that certain recruitment strategies can be changed if needed.

The need for this level of training grows with the complexity of clinical trials. Current clinical trials in oncology, for example, require the collection of multiple and often complex endpoints and sometimes use new, sophisticated technologies and tools for disease diagnosis and drug response measures. These factors have specific technical demands and need to be performed on a strict schedule as specified in each study's protocol. A well-developed knowledge base for study coordinators can ensure that these requirements are met sufficiently.

New training programs are emerging that offer a comprehensive approach to preparing study coordinators. They are designed to go beyond empirical training, providing a more complete set of tools for success. The following are specific topics to look for in a more complete study coordinator training program.

Figure 2. Study coordinators are responsible for communicating with many professionals during a trial.

Communicating effectively with all stakeholders. "Communicating in the Information Age," an April 2002 article in Applied Clinical Trials, identified that a project team performing poorly will often cite a breakdown of communication as the main cause of the problem.³ Study coordinators play a key role in preventing this problem. In addition to coordinating health care teams and caring for patients, study coordinators are responsible for communicating with trial personnel at varying levels of involvement, from sponsors to primary physicians (see Figure 2). Without adequate training, managing the shifting communication styles among these groups can be stressful. Training should arm study coordinators with adequate communication skills and the tools that allow them to disseminate information using the best methods, approaches, and technologies for each situation.

Understanding regulatory requirements and issues. Study coordinators need to understand the regulatory responsibilities of each organization involved in a clinical trial. Understanding these requirements and issues results in improved trial compliance. Look for a training course that identifies the regulatory responsibilities of site staff, ethics committees, and institutional review boards (IRBs), as well as the regulatory aspects of clinical trial documentation, legalities of informed consent, and resources in the event of a regulatory audit or citation. Ethics is also an important consideration. Training should help study coordinators consider three key ethical questions when recruiting for any clinical trial:

1) What are some of the things you need to think about to ensure the subjects are making a decision based on what they think is best for them?

2) How can you be sure that the subjects have truly given their consent or have truly volunteered?

3) What are the conflicts that could interfere with or influence an individual's willingness to volunteer or participate?

Understanding informed consent. Informed consent, which is a main element in protecting the rights and welfare of study subjects, is not simply a matter of having a subject sign a piece of paper. When creating informed consent, investigators are required to know and adhere to specific regulatory requirements related to a trial's therapeutic area. An informed consent form, for example, should be submitted for written approval by an IRB or international ethic committee (IEC) prior to the beginning of a trial and whenever important new information is added or changed.⁴ This responsibility, although typically that of an investigator, is often delegated to study coordinators who may not have previous knowledge or experience in the area. A consent form can fail its objective if a study coordinator does not understand the importance of word choice, regulatory requirements, or the overall trial objective.

Preparing for an audit. On average, the FDA conducts Bioresearch Monitoring (BIMO) Program audits on more than 700 clinical investigator sites, 250 IRBs, and 100 CROs each year.⁵ Several of these inspections have yielded evidence of problems. In 1993, for example, the FDA penalized a large California university IRB for infractions that included failure to report deaths.⁶ Understanding the importance of FDA audits and IRB practices, and using proper documentation, can help clinical trial investigators and sites avoid audits and subsequent penalties. Study coordinators often learn how to prepare for an audit and how to recognize what the auditor is looking for. But another, often-overlooked aspect is for study coordinators to know how to conduct themselves during an audit. This includes giving auditors access to every piece of information and ensuring complete transparency.

Contracting and budgeting appropriately. One of the major factors affecting a trial's timeline is the implementation of a contract with an investigator site. It often takes several months to receive approval by representatives for both the investigator and sponsor. Study coordinators can help improve the process by ensuring that it is reviewed and approved by the participating physicians or hospitals in a timely manner.

Developing a budget that accurately reflects the cost of performing a clinical trial is also a very complex process. Factors affecting the cost can include treatment regimen, therapeutic area, study phase, required clinical assessments, number of visits, and whether the investigator contracts independently or is affiliated with a teaching institution or hospital. These factors are continually changing, and so are the best practices used to deal with them. Study coordinator training courses should present solutions including creating a payment system, maintaining a tracking system to address budgetary issues, and offering skills in budget negotiation.

Achieving the best study design. Study coordinators should be familiar with various study designs, the advantages and disadvantages of each design, the process of randomization, and the reason for inclusion/exclusion criteria. For instance, a study designed for a hypertension trial will not be successful for an oncology trial. Likewise, an oncology trial that is testing a biological compound may not have the same primary endpoint in its trial design as one testing a cytotoxic agent. Understanding the differences helps in prioritizing issues during the day-to-day implementation of research protocols. Mastering the overall study design and randomization schema can also substantially improve study compliance, resulting in the reduction of inadvertent protocol deviations and decrease in the subject attrition rate in clinical studies.

Continuous training

The incorporation of continued training is an important element that many popular programs neglect to focus on. Leaders in training now recommend that topics ranging in subject level from beginning to intermediate—including those stated previously—be covered over the first several years of a study coordinator's career. Training may begin with a "basics" course with background sessions in ethics, contracts and approvals, and informed consent. It should then move into intermediate training to provide practical, more therapeutic-specific, mid-level training. Look for a program that provides additional value, such as those that offer accreditation credits for SoCRA or other professional certifications. Other offerings to look for are "handbook" courses addressing such details as required approvals, and even email networks and other tools to provide study coordinators with access to peers.

This mid-level approach is increasingly being used in various regions and has been a part of the Canadian clinical research industry for several years. The Northern Alberta Clinical Trials and Research Centre (set up as a joint venture of the University of Alberta and Edmonton's Capital Health Authority) provides orientation, education, and networking to more than 200 study coordinators in Northern Alberta. Its program represents a progression of training during the first two years of a study coordinator's career. This format offers two distinct benefits. It allows for repeated exposure of important topics for better comprehension and retainment, and presents key information at the most pertinent time during a study coordinator's professional development.

Although the value of study coordinator training in clinical research is generally well accepted, a quantitative framework to assess the outcomes has not been formally established to date. More qualitative benefits can be observed that help make the connection between effectively training study coordinators and achieving clinical research success. These include improved site relationships, higher quality of work done at sites, and better facilitation of dialogue among all study participants.

By better preparing study coordinators for their responsibilities, the quality of work and compliance with expectations and regulations can increase. The benefit of this applied knowledge is the ability to put best practices into place to substantially improve compliance. Training is the key to ensure that study coordinators are prepared not only theoretically but practically as well, being able to effectively adapt to different situations and different requirements. New trends in training are exceeding traditional limitations to provide this level of knowledge. Organizations taking advantage of these trends are helping to shape the increasing expectations of today's clinical trials.

References

1. U.S. Department of Health and Human Services,

Innovative or Stagnation: Challenges and Opportunity on the Critical Path to New Medical Products,

www.fda.gov/oc/initiatives/criticalpath/whitepaper.html

. March 2004.

2. F. Rico-Villademoros, T. Hernando, J.-L. Sanz, A. López-Alonso, O. Salamanca, C. Camps, R. Rosell, "The Role of the Clinical Research Coordinator-Data Manager-in Oncology Clinical Trials," BMC Medical Research Methodology, 4 (6) 1471-2288 (25 March 2004) http://www.biomedcentral.com.

3. R.J. Anderson, "Communicating in the Information Age: It's Still All About Human Behavior," Applied Clinical Trials, 1 (April 2002).

4. U.S. Department of Health and Human Services, Guidance for Industry—E6 Good Clinical Practice: Consolidated Guidance, http://www.fda.gov/cber/guidelines.htm. posted April 1996.

5. C. Hommel, "FDA's Oversight of Clinical Trials Overview of GCP Bioresearch Monitoring Program," PowerPoint presentation, http://www1.va.gov/resdev/fr/ao_compliance_training/FDAs_Oversight_of_Clinical_Trials.ppt. 25 February 2004.

6. R.C. Thompson, "Protecting 'Human Guinea Pigs,'" FDA Consumer Special Report on New Drug Development in the United States, January 1995.

Barry Strack is training director with Endpoint Research and New Directions: Study Coordinator Training Program, 2595 Skymark Ave., Suite 210, Mississauga, Ontario L4W 4L5, (416) 282-8885, fax (416) 626-2063, email: info@endpointresearch.com.