Safe Clinical Trials Demand Aggressive Risk Analysis

Assessing risk in advance is the key to running a safe, successful clinical trial, says Peggy Fay, PhD, RN, CCRC, a clinical research consultant with Clinical Research Facilitators in Buford, Ga.


Peggy Fay, PhD, RN, CCRC, Consultant, Clinical Research Facilitators

The stakes are high. She recently worked on a trial where the sponsor and team did everything right—except consider the possibility the product wouldn’t be manufactured in time. In the case of that troubled trial, all sites were open and everything else was ready to roll.

“You’ve got to try to identify anything that could possibly go wrong and come up with a plan to manage it,” Fay stresses. While the unavailability of a supply of an investigational product is an admittedly rare occurrence, proactive risk assessment is also critical in a more common problem area: lagging trial enrollment. A proactive response plan would prepare staff with information showing early indicators that not enough people were being screened or matching trial criteria.

In such as case, the sponsor and team might ultimately decide to delay the trial. However, they might be able to salvage it if they’ve put a response plan in place. For example, they should have a contingency program that helps the contract research organization (CRO) advertise the trial locally. Often, that late public relations push can keep the trial moving forward. However, coming up with that plan after the shortage has been detected has far lower odds of success, Fay says.

With release of a U.S. Food and Drug Administration guidance document in 2013, sponsors were encouraged to adopt risk-based management and monitoring strategies and plans for investigational studies. That’s the good news. The bad? “Although it opened the door to alternative methods for trial management, there was little guidance on how to implement an effective program,” Fay notes.

Today, the challenge is to be able to integrate data streams into reliable intelligence that allows sponsors, CROs, study teams, and monitors to make more informed and intelligent decisions when risks arise.

Fay, who’s delivering a session at the ACRP 2016 Meeting & Expo, says she’ll walk attendees through a case study where a trial face unanticipated, costly risks and other assorted challenges. “It will take them through metric indicators, mitigation strategies, and tools that sponsors used to detect and manage the risks and associated costs of implementing options and mitigation strategies,” she adds.

Learn more about Fay’s presentation, Insights, Implications, Impact and Implementation of Risk Management in Clinical Trial Conduct.

Tiny Regulatory Wrinkles Can Create Big Problems for Clinical Trials

Beware the 234,812-word federal regulation bearing gifts. Even if a new law wasn’t intended to cover clinical research, it can still sneak up and impact the way sites do business, says David Vulcano, LCSW, MBA, CIP, RAC, with HCA (Hospital Corporation of America) in Nashville, Tenn.


David Vulcano, LCSW, MBA, CIP, RAC, Hospital Corporation of America

“Sometimes, the word ‘research’ isn’t even in a federal regulation,” he says. Don’t let that fool you. As an example, the Affordable Care Act (ACA), which clocks in at a Harry Potter-book size with more than 234,000 words, impacts subject recruitment in ways many probably didn’t anticipate, Vulcano notes. For example, because the Act provides access to insurance to millions, it also changed the dynamic for many potential trial participants. In some instances, subjects elect to participate in a trial because they have no other insurance. However, by adding people to the insurance rolls, the Act may have inadvertently impacted trial recruitment, Vulcano says.

Conversely, subjects with individual insurance may be more likely to participate in oncology trials and others with a standard-of-care arm, he notes. The ACA also changed the deductibles charged by many insurance carriers. Generally, they went up. “Have a frank discussion with your subject about their deductibles,” Vulcano says. In some cases, it might make more sense to enroll the trial subject in June, after a deductible is met, rather than the early part of the year. It stands to reason that recruitment and retention numbers will rise if a patient’s deductible is addressed beforehand.

Unfortunately, most clinical trial professionals don’t have the time to wade through long regulations. In some instances, they don’t even know which ones to focus on, Vulcano says.

The ACA has been around since 2009 and continues to engender uncertainty. Regardless of that fact, Vulcano adds, “Lately people are not so much asking what the ACA will bring in the next few years, but what happens to the research industry if it goes away,” as many presidential candidates polling very well are those who are calling for a complete repeal. “Another reshuffling of the insurance card deck?” he muses. “Well, with a complete repeal, yes, it would, among changing many other things, eliminate the Sunshine Act.”

Making matters more challenging, there are any number of new pieces of legislation that bear watching. One example: “Right to Try” legislation allows Americans to try a drug or device that has passed Phase I of the Food and Drug Administration’s approval process, yet hasn’t reached a local pharmacy because it is still working its way through the regulatory labyrinth. As of January 2016, such legislation had already passed in at least 24 states.

How should sites prepare for it? “It can be a real dilemma,” Vulcano says. He’ll be addressing it and other important regulations on the horizon during his session at the ACRP 2016 Meeting & Expo in Atlanta, Ga., in April.

Learn more about his session, 2016 Update: U.S. Healthcare Changes and How They Affect the Clinical Research Industry.

CRA Job Landscape: Fewer, Tougher Jobs


Jeff Kasher, president of Patients Can’t Wait LLC

Today’s clinical research associates (CRAs) have some justification if they feel like superstar college athletes nailing down big signing bonuses. They should enjoy it while they can. The job landscape of the future could be quite a bit different, says Jeff Kasher, president of Patients Can’t Wait LLC.

Thanks to risk-based monitoring (RBM) (see the October 2015 Clinical Researcher) and recruitment technology such as the Apple ResearchKit™ (see the June 2015 Clinical Researcher), the job market for CRAs could shrink in half over the next five to 10 years, he says. However, the remaining jobs will be tougher and demand more experience.

His advice? Seek out new skill sets, for instance by focusing on project management or specializing in a particular therapeutic area. Tomorrow’s CRAs will be expected to understand the big picture “connectivity of actions” in a clinical trial, Kasher says. That includes resource management and being able to drill down to face tough questions from sponsors or physicians.

Centralized monitoring also demands strong data analytics skills and the ability to spot red flags in data remotely. There will be fewer onsite visits in the clinical trial landscape of the future, Kasher says. The upside: less travel. The downside: CRAs will need a deeper understanding of trial protocols so they can identify study issues that cannot be addressed from afar and merit an onsite visit.

In terms of a career path, Kasher suggests following the areas with the largest unmet medical needs. For example, while there already many good medicines out there for diabetes and cardiovascular issues, there are needs for large advances and improved outcomes in cancer treatment, autoimmune diseases, and neurological conditions such as Alzheimer’s, among others. In other words, the demand for clinical trials will be stronger in the latter cluster of diseases.

ACRP Announces Initiative to Promote, Validate Harmonized Competence for Clinical Research Professionals

The Association of Clinical Research Professionals (ACRP) today announces a major initiative to promote and validate competence in clinical research.

Starting in 2017, ACRP’s industry-leading certification programs will be harmonized with the core competency framework developed by the Joint Task Force (JTF) for Clinical Trial Competency, whose contributors and collaborators include leading organizations representing clinical research sponsors, contract research organizations, sites, and academia.

By aligning its certification programs through exam content with the JTF competencies, ACRP will promote and validate competence in the clinical research workforce.

“Helping develop a competent clinical research workforce is a priority for ACRP and helps advance our mission to promote excellence in clinical research,” says Jim Kremidas, ACRP Executive Director. “Our goal is to provide the training and assessment of competencies needed by the individuals and organizations our association represents. By aligning our certification programs with a widely accepted and industry-defined set of core competencies, ACRP will continue to proactively deliver solutions to the challenges faced by clinical research professionals and organizations.”

Today’s announcement follows completion of a job analysis study, which included a comprehensive survey of more than 2,100 clinical research professionals, designed to collect descriptive information about the tasks performed and the knowledge, skills, or abilities requisite to job competence in clinical research. The JTF competencies framework was used as the foundation for the content-specific questions included in the survey. Results from the extensive survey lead to clearly delineated domains and tasks that characterize proficient performance and were therefore used to define the test specifications for the CCRA, CCRC, and CPI examinations.

“The job analysis survey is a critical component in maintaining the relevancy and industry-leading quality of ACRP’s certification exams,” says Susan Warne, LVN, CCRC, Chair, Academy of Clinical Research Professionals (the Academy), the independent affiliate of ACRP responsible for administering ACRP’s certification programs. “In addition to keeping ACRP certification programs in compliance with standards of the National Commission for Certifying Agencies (NCCA), this job analysis survey equips The Academy with the tools necessary to provide industry with a benchmark for measuring the knowledge, skills, and abilities of clinical research professionals.”

ACRP conducts a comprehensive job analysis survey every 5 years, in accordance with the National Commission for Certifying Agencies (NCCA) Standards for accredited programs to validate the content of its Certified Clinical Research Associate (CCRA), Certified Clinical Research Coordinator (CCRC), and Certified Principal Investigator (CPI) exams. ACRP’s CCRA, CCRC, and CPI certification programs remain the only clinical research-specific certification programs accredited by the NCCA, meaning they meet the highest standards for development, administration, and governance of certification and testing programs.

In addition to alignment with the JTF competencies, ACRP’s certification programs will see the following changes in 2017:

  • Realigned eligibility requirements which accept a current ACRP certification as evidence toward meeting some of the eligibility criteria.
  • Updated Detailed Content Outlines (DCOs) for examinations, reflecting the knowledge and tasks defined by the recent Job Analysis study and content for exams administered as of March 2017
  • Maintenance of Certification continuing education topics will be expanded to align with those of the DCOs

For an Executive Summary of the Job Analysis Survey, please click here or visit:

About ACRP

ACRP supports clinical research professionals through membership, training and development, and certification. Founded in 1976, ACRP is a Washington, DC-based nonprofit organization with more than 13,000 members who work in clinical research in more than 70 countries. ACRP’s vision is that clinical research is performed ethically, responsibly, and professionally everywhere in the world. ACRP’s mission is to promote excellence in clinical research.

About the Academy

The Academy of Clinical Research Professionals is an independent affiliate of ACRP. The Academy, a nonprofit 501(c)6, is solely responsible for the governance, development and administration of ACRP’s certification programs. Its mission is to promote and maintain high standards and best practices of clinical research by recognizing those professionals who demonstrate a well-defined competency through valid and reliable credentialing programs. Academy trustees are elected by individuals holding the CCRA, CCRC, or CPI designation. To date, more than 29,500 individuals in 60 countries have achieved certification through the Academy.

Don’t Overlook the Human Factor When Addressing Consent Issues

There’s been lots of talk about how the clinical research enterprise will need to address new informed consent challenges raised in relation to eConsent, genomics, vulnerable populations, and more. Each issue requires new ways of guaranteeing everyone’s eyes are wide open during the conduct of informed consent.


Claudia Christy, Independent Nurse Consultant

Ultimately, however, it’s still the human factor that decides whether an informed consent program is up to standard, says Claudia Christy, an independent nurse consultant based in North Carolina. It takes time to build the relationships that are the foundation of properly performed informed consent, she says.

New hires and even relatively seasoned clinical research coordinators (CRCs) don’t always understand the why of what they’re being asked to do, Christy says. That’s problematic because it can result in sloppy work.

For example, Christy was a potential subject in a large study with no serious potential of danger. She was vetted by a young summer hire, a medical student probably looking for something good to put on his resume, she says, adding, “He told me to sign the form and then take it home and read it.”

Obviously, it should be the other way around, but the youngster didn’t know that was an issue. He treated the form as more of a pro forma. Another mistake: He didn’t read it closely and missed that the trial required a follow-up a year later.

Because of how easily misunderstandings and mistakes can occur, Christy urges clinical researchers to make sure a potential subject really understands what he or she is signing up for. Specifically, she recommends:

  • Asking the subject to tell you how they’ll describe the trial to their family.
  • Using short quizzes to double-check understanding.
  • Ask the subject if they understand the basics of eConsent, if appropriate.

There’s another important human factor to consider, says Glenn Veit, JD, CIP, executive chair with the WIRB-Copernicus Group. “We need to make informed consent forms easier to read,” he says.

While the new reality might be 60-page forms mandated by legal and other departments, there are still opportunities to improve how that information is presented to prospective test subjects. Veit offers two practical suggestions:

  • Simplify the language. “I’ve always thought a big pharma sponsor should bring in a 6th grade English teacher to vet the forms,” Veit says. The U.S. Food and Drug Administration mandates that consent forms be written at no higher than the 8th grade level. However, that’s often not the case.
  • More white space. “Think of how USA Today changed the way we look at newspapers,” Veit explains as he calls for creative, user-friendly layouts.


 Gain additional insights into the informed consent process at these ACRP 2016 Meeting & Expo sessions: 

Explore more at


Accountability in Clinical Research “Two Way Street”

imgDavid-Morin“If we hold our employees accountable, we have to hold ourselves accountable,” says industry pathfinder David Morin, MD, RPh, FACP, CPI. As Director of Clinical Research at Holston Medical Group, he’s worked hard with his team to come up with a robust accountability program designed to improve overall performance — not to point fingers.

Working to articulate the difference between “explanation and excuse,” Morin’s three keys to creating accountability stress:

  1. Thorough standard operating procedure (SOP) documents.
  2. Clear delineations of job descriptions.
  3. Computer-verified training of all staff (mentors also play an important role).

Morin, a past winner of ACRP’s “Outstanding Physician Leadership in the Profession Award,” says he devoted 600 hours to training over a two-year period. While it was obviously a heavy time commitment, Morin says it was well worth it. “We have a sponsor audit every month or two,” he explains. “We’ve had sponsors tell us we have the best SOPs they’ve ever seen.” That kind of strong documentation inspires a high level of confidence with sponsors. “Our site visits go well” as a result, Morin adds.

Nearly six years into his program, Morin notes that employee error is the culprit in audit findings “about 95% of the time.” However, he says his aggressive and neutral accountability system finds systemic flaws now and then, because “there might be some wrinkle in a new regulation we missed.” In that instance, training is immediately updated.

Morin’s two-way accountability system leverages handouts, checklists, and decision trees to help employees and management quickly identify and remediate problematic issues. The accountability system is further bolstered by a mentor program–a designated supervisor who ensures and documents that an employee receives the appropriate training. It helps avoid the “no one told me to do that” or “I wasn’t trained for that” excuses, he says.

Morin will be speaking with his colleague, Nichole Skirvin, BA, CCRP, Clinical Research Manager, at the ACRP 2016 Meeting & Expo in Atlanta, Ga., in April.

Learn more about their session, Creating Accountability: A Step by Step Approach.

Communication Key to Successful Risk-Based Monitoring

Left floundering in a communications vacuum, any risk-based monitoring program simply won’t ever get off the ground, says Mike Caswell, vice president for clinical evaluation at the Consumer Product Testing Company. It’s critical to seek out and incorporate comments from “different stakeholders,” including sponsors, principal investigators, research staff, and financial officers.

Without a clear understanding of RBM, you “won’t get buy-in from sites and RBM won’t work,” Caswell stresses.

However, open communication is only half the solution. You’ve also got to know the right questions to ask. When risk-based monitoring is employed, gone are the days of simple questions such as “paper or electronic CRFs?” or “frequency of monitoring visits?” to plan site and sponsor workload, anticipated timelines, and projected costs.

Risk-based monitoring requires a team-based approach that tends to be more loosely structured – providing opportunities for efficiencies, but also exposure to inefficiencies.

For example, if an in-house clinical research associate (CRA) is deemed the primary point of contact, but the data management team members and/or medical monitors reach out to site personnel without looping in the in-house CRA, they can all end up asking the site the same question about the severity of an adverse event that appears “off” compared to the other data. As a result, potentially three people have spent time on the same task; the site staff is bombarded about the same thing three times and can easily become frustrated about the triplication of work required. Efficient? No. Cost-Effective? No. Communication in check? No.

So what can be done to prevent these issues? What should every study team member involved in reporting and monitoring trial data be thinking about when planning the study?

Communication is obviously key, but so is knowing the right questions to ask.


  • What are the possible risks to the study?
  • How are potential risks mitigated, and by whom and when?
  • Who will look at what data point and when?
  • How would a delayed data entry by a site impact this review?
  • Who is the primary point of contact (sponsor/CRO to site and site to sponsor/CRO)?

Knowing the right questions to ask when planning for risk-based monitoring, and actually asking them, is critical to development of a successful monitoring plan and can improve trial efficiencies, reduce costs, and keep trials on time.


img-RBM-QuestionnaireLearn more questions that should be asked of all study team members during start-up/planning by downloading this FREE Risk-Based Monitoring Questionnaire.


This reference sheet is from ACRP’s eLearning Course, Risk-Based Monitoring: The Essentials for CRAs, available for $99 to ACRP Members ($149 for Nonmembers).

Competency Task Force Asks Clinical Researchers to Help Shape Recommendations

The Joint Task Force (JTF) for Clinical Trial Competency Framework will share important feedback from more than 2,500 survey respondents at the ACRP 2016 Meeting & Expo, according to JTF Co-Chair Stephen Sonstein, PhD, director of Clinical Research Administration at Eastern Michigan University in Fort Myers, Fla.

“We’ll talk about definitions and perceptions of core competencies and their relevance,” Sonstein explains. The Task Force has also made an attempt to standardize role descriptions. An extensive review of those suggested competencies can be found in the June 2014 issue of Clinical Researcher.

It’s only an important start, Sonstein stresses. “Not all members of the clinical research team require the highest level competency in all of the areas,” he and coauthors write. However, “these harmonized core competencies can provide a basis for development of specific statements of knowledge, skills, and attitudes required by clinical research professionals in focused environments.”

Sonstein also emphasized that without industry feedback he’s concerned the Task Force could end up operating in a “vacuum.” He’s hoping ACRP conference attendees will provide validation and other input. The conference is a “unique opportunity to share ideas and get down to specifics when assessing core competencies,” Sonstein says.

For more on Sonstein’s ACRP 2016 Meeting & Expo Session, click here.

FDA Inspectors Demand CAPA Documentation

Clinical researchers who fail to adequately document corrective and preventive action (CAPA) programs are missing out on a number of important benefits to save time and money, says Beth D. Harper, MBA, president of Clinical Performance Partners, Inc.

“It’s not just a compliance tool,” she stresses. Instead, CAPA can be leveraged to dig deeper and identify root causes. Think of it as an opportunity to critically examine how you do things and look for ways to improve them. “Why do we devote time to it only in panic mode?”

CAPA capabilities are often the first thing a U.S. Food and Drug Administration (FDA) expert will examine when onsite. Deficiency in this area is usually the most cited issue in Warning Letters across all aspects of industry, including medical devices, pharmaceuticals, and clinical trials. In a recent Warning Letter to a clinical researcher, FDA acknowledged the firm said it had addressed shortcomings and taken corrective action, including:

The research coordinator who falsified data was terminated; All investigators and staff must attest that they have read and will adhere to the department’s Standard Operation Procedures when conducting research; The department will conduct comprehensive standardized training and competency validation for all new research coordinators; The Department of Medicine research manager and staff will perform continuous internal monitoring of studies; Study-specific enrollment criteria for all studies will be reviewed at weekly department research meetings, and investigators will be required to sign eligibility checklists.

However, FDA rejected the response because the clinical researcher failed to adequately document the changes. “We have to think differently about CAPA,” Harper stresses. A good plan isn’t always enough.

A defensible, documented CAPA program can also give a clinical researcher valuable confidence, notes Glenda Guest, CCRA, RQAP-GCP, TIACR and Vice President at NCRA. “If you understand the flexibility of [many] FDA requirements, you can be assertive and defend” the way you operate, she says.

Harper and Guest will present separate sessions sharing the latest CAPA tools and tactics at the ACRP 2016 Meeting & Expo, April 16-19, in Atlanta. Ga. For more information, visit: