How important is it to employ the services of a contract research organization (CRO)? Ask yourself these questions. Do you or members of your staff…

• Know what knowledge and experience it takes to manage a research study? Do you have the expertise and experience to manage the study?
• Know how much time it takes to manage the study? Do you have the time to devote to manage the study properly?
• Know what it costs to employ the services of a competent CRO? Do you have adequate budget allocated?

Real World Example
Like many managers, I [Greg Stephens] learned the value of a CRO the hard way. After retiring from Abbott Nutrition I joined a start-up nutraceutical ingredient company as chief operating officer. Being a dietitian and having management experience in research and development (R&D) at Abbott, I took responsibility for the company’s clinical research program, as well as regulatory affairs, and sales and marketing, all with a staff of two (including me).

The flagship product, a highly concentrated oat beta-glucan, qualified for the FDA-approved heart health claim (21 CFR 101.81). Still, we needed to demonstrate to customers that our product actually delivered results. Because of my R&D experience, I decided to forgo the expense of employing a CRO. I took responsibility for managing the study. After all, it was merely a simple, straightforward, 12-week feeding study with clear endpoints.

After interviewing respected researchers at several universities, I selected a well-known professor who had strong experience in grain science. We agreed on project terms including protocol, publishing rights, timing, fees, etc. The university assigned primary oversight to a bright PhD student and we were quickly underway.

We agreed on a weekly summary report and conference call to discuss progress and any issues. Enrollment began. The first red flag appeared when I heard that enrollment was progressing less than projected on the study time. I was advised not to worry.

Due to my COO responsibilities, I didn’t have time to conduct frequent on-site reviews. As weeks went on, enrollment lagged. The investigator and I agreed on some tactics to get back on track.

Then I learned that the study coordinator was on maternity leave. Study responsibilities were assigned to another student. A visit to the principle investigator seemed to renew enthusiasm with the professor assuring me she would become more involved. Study participant enrollment appeared to improve. Soon, however, due to subject dropouts and other problems my confidence waned. In reality, enrollments soon came to a near standstill.

I began to understand why the clinical research associates I’d worked with previously spent so much time communicating with and visiting clinical research sites.

Thinking financial pressure may help get us moving, I ceased payments to the university. This had no effect at all, other than phone messages to respond to from accounts receivable. Our Board was getting impatient, to say the least. They in turn applied more pressure (on me) to see results. Soon I was devoting a significant amount of my time driving the project. Finally, many, many months late, the results were in.

Even at that point it was not smooth sailing. Our contract with the principle researcher included the caveat that they were not to publish findings until our company had the opportunity to review the results. However, without our review, the principle investigator submitted an abstract for presentation at a major professional meeting and subsequent publication.

What I thought would take little of my time actually was beyond time consuming, as well as stressful and distracting from my other responsibilities. Bottom line: I wish I had more closely evaluated the role and benefits of a competent CRO. Here’s your opportunity to better understand what and how a CRO may benefit you.

What’s A CRO & What Do They Do?
Initially, contract research organizations (CROs) supported medical device companies with only product testing and validation. Today, CROs offer a variety of services, so you’ll want to evaluate your research needs carefully, prior to starting your search for the optimal CRO.

The International Conference on Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) defines a contract research organization as:
“A person or an organization (commercial, academic, or other) contracted by the sponsor to perform one or more of a sponsor’s trial-related duties and functions:

• A sponsor may transfer any or all of the sponsor’s trial-related duties and functions to a CRO, but the ultimate responsibility for the quality and integrity of the trial data always resides with the sponsor. The CRO should implement quality assurance and quality control.
• Any trial-related duty and function that is transferred to and assumed by a CRO should be specified in writing.
• Any trial-related duties and functions not specifically transferred to and assumed by a CRO are retained by the sponsor.
• All references to a sponsor in this guideline also apply to a CRO to the extent that a CRO has assumed the trial-related duties and functions of a sponsor.”

Whether you use a CRO or not, you as the sponsor, are ultimately responsible for ethical study design, adherence to regulatory and legal obligations, and validity and reliability of the data and its interpretation.

Strategic Planning & Execution
CROs can provide you with the expertise and labor to conduct research but you first need to know what you need and want from one. Here is the 10,000-foot view of the steps needed to develop and execute a research study:

1) Define the question you want to answer. As simple as this seems, the research question guides the entire research project. It must clearly describe the issue needing an answer. While this seems easy, it requires careful thought about a number of matters, such as these:

• What information is already available?
• What is the gap between the available information and what you need to answer your question?
• Is your question too wide or not wide enough to garner the data you need?
• Is it even possible to research your issue? (Is it ethical? Do methods exist? etc.)

2) Select the best method for conducting the research. Identify an appropriate study design and write a research protocol. A research protocol clearly lays out how to conduct the study to the detail that investigators can follow it to get the required data. Research protocols generally include:

• An introductory statement giving the rationale for the study
• The study question & hypothesis
• The study design
• The methods of statistical analysis
• Data collection methods & instruments
• Description of the study population & subject selection criteria

3) Execute the study and collect the data.
4) Analyze the data and interpret the findings.
5) Report the results.

The mundane day-to-day requirements of running a study are behind the scenes.  They include developing data collection instruments, data collection, data entry, data quality monitoring and more. CROs may employ clinical research associates to liaise with study sites, data collectors, data monitors, statisticians, technicians, clinicians and others to accomplish all of the tasks with a research study.

Selecting The Right CRO
CROs can be large or small and usually offer a “menu” of services. Once you’ve reviewed your research needs, you’ll want to select and “qualify” a CRO.

Ideally, you’ll want to visit the CRO’s facility and meet with members of management, scientists, clinical and data services, and quality assurance. You can use these criteria as a baseline for evaluating a potential CRO, but certainly adjust them to meet your particular needs. 

• Policies and Procedures: Make a comprehensive review of organizational structure, accreditation status, and compliance with regulatory and legal mandates for clinical research.
• Personnel Management: Review or discuss CRO staff expertise and experience, staffing levels, job descriptions and training records.
• Facilities: Inspect physical structures and equipment used for housing animals or for clinical visits for quality, stability and compliance.
• Security: Confidentiality from the CRO is critical. Evaluate procedures for security of data and correspondence, and for ensuring employee confidentiality.
• Crisis Management: Review the crisis management plan to make sure it covers all potential circumstances and ensures effective communication with you, the sponsor.

Other Criteria To Consider
Aside from these, there are “softer” criteria that bear attention. Researchers Glass and Beaudry identified five criteria users of CROs thought crucial in the selection of CROs (see Table 1).

1) The first they called team chemistry. A positive sponsor-CRO relationship is more likely in cases where both parties share the same values, work ethics and general approaches. If something rubs you wrong after meeting with a CRO, go with your gut feeling.
2) The second criterion is satisfaction that the CRO project management team is wholly devoted to the project. If you get a sense that your project will not receive adequate attention, it’s time to bail.
3 & 4) Most employers, when interviewing potential staff members, list experience as important. This also applies when looking for a CRO that will meet your needs.
5) The final criterion is more nebulous. Team member background is actually an amalgam of expertise, experience and charisma. This is the time to determine how you feel about working with the team, considering interpersonal relationships between the team and between the team and sponsor.

Make sure you put your best foot forward when you plan and implement a clinical trial. Think through the above questions with your team, realizing your strengths and weaknesses.

A well-managed clinical trial is a significant investment in money and time and often critical to success of a nutraceutical product. 

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Gregory Stephens
Windrose Partners

Greg Stephens is president of Windrose Partners, a company serving clients in the the dietary supplement, functional food and natural product industries. Formerly vice president of strategic consulting with The Natural Marketing Institute (NMI) and vice president of sales and marketing for Nurture, Inc (OatVantage), he has 25 years of specialized expertise in the nutritional and pharmaceutical industries. His prior experience includes a progressive series of senior management positions with Abbott Nutrition (Ross Products Division of Abbott Laboratories), including development of global nutrition strategies for disease-specific growth platforms and business development for Abbott’s medical foods portfolio. He can be reached at 267-432-2696; E-mail: gregstephens@windrosepartners.com.

Sheila Campbell
Sheila Campbell, PhD, RD, has practiced in the field of clinical nutrition for more than 30 years, including 17 years with Ross Products Division of Abbott Laboratories. She has authored more than 70 publications on scientific, clinical and medical topics and has presented 60 domestic and international lectures on health-related topics. She can be reached at smcampbellphdrd@gmail.com.