Clinical Trials Weakened by Poor Diversity Outreach

Lea H. Becker, Department of Emergency Medicine at the University of Virgnia Health System

Clinical trials underserve the public health and, in some cases, limit the value of the data amassed from a pool of subjects, say a number of experts in the field and officials at the U.S. Food and Drug Administration (FDA). Too often “minorities are underserved and it may impede their health,” suggests Lea H. Becker, senior clinical research coordinator with the Department of Emergency Medicine at the University of Virginia Health System.

On the positive side, Becker is encouraged by a survey she recently conducted that looked at 500 consent conversations in an emergency room environment. It suggested that the recruitment gap has closed tight between minority and white patient populations. “I was really happy about it,” Becker says, “I believe it reflects a concerted effort” at her facility bolstered by outside community outreach. She does note that conditions in an emergency room are “very different” than in others settings. Regardless, she advocates the adoption of what she calls “thinking tools” to help other facilities close that recruitment gap.

Looking for ideas on how to improve clinical trial diversity? Sign up for this upcoming ACRP Webinar, Conditions Impacting Consent for Clinical Research, featuring Lea H. Becker, senior clinical research coordinator with the Department of Emergency at the University of Virginia Health System.

“Be clear on who you are approaching, and how much they need to know about a study in advance,” advises Becker. Conversely, ask yourself why are not approaching a particular group. Do you believe, based on anecdotal evidence or your own perceptions, that some groups simply don’t follow up and are too much of a hassle to recruit? “That’s not fair,” Becker says.

By applying thinking tools, it is easier to draw disparate populations into a clinical trial, Becker adds. She allows that egregious lapses in clinical trial ethics that have been brought to light over the years have sometimes highlighted racism as an issue in research that might have made industry professionals overly cautious in their outreach to underrepresented groups. Sensitivities related to clinical trials remain an important factor in some minority populations.

Meanwhile, FDA is co-hosting a seminar in September on improving clinical research in the age of precision medicine.

Speakers include FDA Commissioner Dr. Robert Califf and FDA Assistant Commissioner for Minority Health Dr. Jonca Bull. “The symposium is a unique opportunity to engage with clinical researchers on the front lines in academia and industry to make the case the importance of diversity in clinical trials to advance medical product development that represents the many faces of our country,” says Bull. Look for a full interview with her in the October issue of Clinical Researcher.

FDA, Industry Must Partner to Increase Minority Representation in Clinical Trials

Jonca Bull, MD, director of FDA’s Office of Minority Health

The Food and Drug Administration’s (FDA) initiatives to promote clinical trial diversity are likely to help increase the participation of underserved minority groups, say FDA officials and industry practitioners.

“We’re actively involved in communication strategies to ensure that information about FDA-regulated products is getting to minority communities, including those with limited English proficiency,” says Jonca Bull, MD, director of FDA’s Office of Minority Health.

Dr. Fabian Sandoval, whose Washington, D.C.-area practice includes a large portion of Hispanic and African-American patients, says efforts like the FDA’s are a good start, but aren’t enough on their own. “Federal backing is incredibly important,” he says, “but we need more funding and someone has to step forward to be the steward of those funds.”

However, that effort cannot come directly and overtly from the pharmaceutical industry, Sandoval believes, because of the perception that it is “just trying to push drugs. It can’t be someone like Pfizer alone.” Pfizer’s efforts are collected in a Supplier Diversity Program. Pharmaceutical Research and Manufacturers Association’s (PhRMA’s) “I’m In” campaign is also working to increase minority subject recruitment.

“This effort can’t be done one-on-one,” Sandoval says. Instead, it must be on a larger national scale akin to First Lady Nancy Reagan’s “Just Say No” campaign in the 1980s aimed at educating the public about the dangers of illegal drug use.

Sandoval also stresses that a “one size fits all” approach won’t do much to advance subject diversity in clinical trials.

For example, the immigrant Hispanic population tends to be unaware of clinical trials and reacts with skepticism when told they will get free drugs and even be paid to participate. “They think it is too good to be true,” Sandoval said. In that instance, it is critical to explain to potential subjects how their contributions will advance medical science. “They need to understand they could be helping themselves, or someone like them, or even their children,” Sandoval adds.

The hurdles are significant, FDA and others allow. For example, there is a distrust among some minorities based on past abuses. An infamous example are the Tuskegee experiments, in which health officials recruited poor black sharecroppers to study the natural progress of syphilis without informing them they had the disease or offering the penicillin that could have cured them, Bull notes.

Bull also points out practical issues that need to be addressed. “Lower income people may have transportation problems and less flexible jobs,” she says. “There are concerns that commercial clinical trial sponsors don’t work aggressively to recruit minorities because of the perception that special needs will slow down recruitment and participation.”

Prediction: Fewer Study Visits Will be Conducted at Clinical Research Sites

This is the eighth installment in the series (Change is in the Air) on changes coming to the clinical research enterprise that John Neal, CEO of PCRS Network, began in April 2016, with the prediction that “major changes are coming that will be disruptive, displacing many people currently working in the industry.”

Prediction 8: Fewer study visits will be conducted at research sites.

John Neal, CEO of PCRS Network

In Part III of this series I touched on some issues related to this prediction in stating that “As individual patients are identified, prescreened, and in many cases ‘assigned’ to a site, the dynamics behind where study visits occur, and who should conduct them will begin to change.“ Here I want to elaborate, because where, when, and who collects study data is going to radically change study conduct as we know it today.

The changes I see coming that will cause a decrease in the number of study visits conducted at study sites will result not from a single factor but from a combination of many factors. Each will contribute slightly to the changes, but together, they represent a major change to the industry.

In no particular order, the primary factors I see coming together include, but are not limited to,

• increased use of “in-home” visits
• adoption of remote visits (visits conducted at locations other than the Principal Investigator’s (PI) location), and
• virtual visits

My definition of Home visits (HV) are and study visits conducted by a clinical trial professional who goes to where the study volunteer is located, as opposed to the volunteer traveling to the research site. This is not a new idea. In fact, many such visits are already occurring. For the most part, these types of visits have been limited to volunteers who are non-ambulatory. In order to attract volunteers who otherwise would not volunteer to participate in a study because of the inconvenience of traveling to the research site, I believe an increasing number of studies will allow for HVs for ambulatory people.

My definition of remote visits (RM) may vary slightly than others. I define them as those research visits where the visit is conducted at a medical facility location other than that of the PI. These are visits requiring the attention of a medical professional, but that do not necessarily require the PI to be present. This is a departure from the conventional model, and could represent an avenue to access additional volunteers from the patients of Primary Care Physicians (PCP) and Specialists who do not otherwise conduct research.

While speaking with Dr. Janet Woodcock, Director of the Center for Drug Evaluation and Research (CDER) recently, she told me:

My theory is that, for some studies, we could relax a little bit and allow community doctors to complete some of the study visits at their office rather than the PI’s office. It would be better for the patients and would probably increase the speed of enrollment.

Such flexibility by the FDA to modify where and by whom certain study visits occur could open avenues to access volunteers that has been virtually untapped to date.

RVs can be supported by “mobile” research staff, such as having a CRC travel to the PCP or Specialists office for the conduct of the visit. In some respects, that is commonly employed in some Site Management Organization (SMO) models today, although they typically establish the PCP or Specialist as the PI for the studies conducted at their location. In that model, the SMO provides all research related staff and infrastructure, so the PI does not have the burden of adding and managing staff.

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Don’t Let Sponsors Dictate Billing Payment Schedule and Terms

Nikki Couturier, BSRT, CCRC, budget and contract specialist with IACT Health

Clinical trial site managers do themselves a disservice if they don’t press sponsors to consider monthly payments as opposed to the industry standard quarterly schedule, says Nikki Couturier, BSRT, CCRC, a budget and contract specialist with IACT Health.

“Sponsors are showing more willingness to work with sites on payment frequency,” Couturier says. In the past, payment schedule terms tended to be very strict, she adds.

That said, Couturier has observed something of a shift of late; sponsors have become more open to negotiating other payment terms if a site pushes back. “Don’t accept their payment rate at face value,” she suggests. A site’s price tag should reflect its own financial statement in terms of real costs in a specific situation.

Sites should also be skeptical when a sponsor says it is offering what other sites get, Couturier says. “That’s not [always] true.” While it makes sense to ask a sponsor how much time a given task or project might take, use that figure only as a starting point for your own calculations.

In the past, “we had no idea how to evaluate our costs,” Couturier says, but she worked with her team and other personnel to change that. She uses her own experiences as a Certified Clinical Research Coordinator (CCRC) to help gauge how much time a project will take. When some aspect of the work is out of her realm of experience, she goes straight to clinical staff who have a track record in that arena. Ultimately, they base their charges on a real-world hourly assessment, instead of charging by task.

Couturier has also had some success with a new wrinkle—a tiered budget. Describing it as a “huge breakthrough,” IACT has been able to negotiate deals where the site agrees to two sets of contract budget terms. Couturier explains that the second set only kicks in and allows them to charge more if they exceed enrollment goals (for example in one recent trial, $5,000 per patient), “once we’ve proved we can do it ourselves our own way.”

Couturier cautions, though, that the enrollment goals should not be forced in-house as a pressure-filled incentive, but rather more as a goal.

Resources

For additional considerations and tips for developing and building site budgets, check out Mastering Budgeting at Your Site: Building and Negotiating Clinical Trial Budgets that Make Sense.

FDA Inspections Shift Focus to CAPAs, Could Come at Any Time

Dr. DeAnn Cary, director of research with Sharp Healthcare in San Diego, CA

While matters related to how informed consent is obtained at study sites remain at or near the top of most U.S. Food and Drug Administration (FDA) inspectors’ checklists, they’ve also shown an increasing interest in corrective and preventive action (CAPA) programs, says Dr. DeAnn Cary, director of research with Sharp Healthcare in San Diego, Calif.

Cary’s employer has more than 200 trials in process at any given time, she says. Part of her job involves overseeing Sharp’s local institutional review board staff.

Though it isn’t common, FDA inspectors can show up in your waiting room unannounced, Cary says. Typically, however, you’ll have some notice that they plan to come calling. Regardless, it can be a nerve-wracking experience.

“The prospect of a regulatory inspection can be anxiety provoking for sponsors and contract research organizations, and for clinical investigators and their site teams,” notes Terri Hinkley, RN, BScN, MBA, CCRC, deputy executive director of the Association of Clinical Research Professionals.

At Sharp, a community-based health system with seven hospitals and trials running the gamut from neonatal to Alzheimer’s, successful, relatively stress-free FDA inspections are about preparation and keeping the prospect of an inspection in mind every day. It doesn’t have to be an all-consuming fear, of course, Cary stresses.

There are any number of ways to work smart and prepare for an FDA inspection. “There’s no reason you can’t be prepared,” Hinkley says.

For example, Sharp works closely with her team of investigators.  Every quarter, six investigators are tapped to write nine-page self-assessments to ensure they are inspection ready at all times.

“It’s not to catch them out as deficient,” Cary says. “It’s a tool to make sure they have what they need.” The exercise gives everyone peace of mind, she adds. “If the FDA comes knocking at the door, we can feel comfortable handing over our regulatory document binder.”

Resources

To learn more about CAPA, and preparing for and handling FDA inspections, check out:

• Inspection Readiness: Best Practices for Managing Clinical Trial Inspections
• Building Quality Management Systems for Sites and Sponsors: Root Cause and CAPA

Site Quality Devils are in the Daily (and Weekly and Monthly) Details

Katrina Quidley, regulatory manager with IACT Health

Dogged dedication to reviewing documents and keeping training on the cutting edge at study sites are keys to an effective quality assurance (QA) program, says Katrina Quidley, regulatory manager with IACT Health in Columbus, Ga.

“We review every interim monitoring visit letter as it comes in,” Quidley says of her efficient shop. Letters are sorted by reviewer so that trends, such as dosing errors, can be caught early in the cycle, she adds. IACT takes a hard look at letters as a group each week, in order to catch patterns and trends that might spell trouble down the line.

Training and communication are equally important components of a strong site QA program, Quidley says. While IACT formally updates its training manual annually, managers review its components every six months, and have regular informal meetings and communications to consider new tools and tactics gathered at events such as the Association of Clinical Research Professionals’ annual Meeting & Expo.

IACT also conducts full-scale quarterly meetings, plus informal gatherings and e-mail communication on an ongoing basis, to best share new ideas and incorporate those into training sessions.

Among other benefits, such diligence helps give clinical research coordinators at sites better understanding of and more input on the reasons behind, and development of, standard operating procedures, Quidley says.

Resources

Learn more about effective quality assurance programs and site quality management:

• Site Quality Management Tools: SOPs, Metrics, and Training
• Building Quality Management Systems for Sites and Sponsors: Root Cause and CAPA
• Keys Skills for Ensuring Quality Control through Risk-Based Decision Making
• Quality Essentials: Monitoring Visit Report Review Plans
• Quality by Design: The Value of CRF Mapping
• CAPA Isn’t Just a Compliance Tool: Maximizing Site Performance Applying CAPA Principles
• Reverse Engineering 483s and Warning Letters to Improve Your QA Program

Are Clinical Trial Sites Leaving Billable Items on the Table?

Bonnie Segal, vice president of Segal Institute for Clinical Research

A growing number of billable items are not automatically included in contract agreements between study sites and sponsors, says Bonnie Segal, vice president of Segal Institute for Clinical Research. The upshot? Sites often leave money for a number of billable activities on the negotiating table, she says.

“When it comes to negotiating a contract on behalf of a site, there’s no room anymore for someone who is not on their game,” Segal says. Her Florida-based organization is an 18-year-old group of six sites with some 70 full-time research staff on board.

Example: Subject transportation. After trying to rely on subjects making their way to the site via public transportation or their own cars, Segal saw retention rates go through the roof when she hired drivers and a van service to handle much of the travel services. However, many sites don’t think to get that cost in the billing agreement, and sponsors certainly won’t suggest it themselves. Instead, Segal’s team negotiates upfront for the sponsor to cover that cost. “We get it back about 90% of the time,” she says. “You’ll never get it back if you don’t ask.”

Another example: Psychiatry and neurological trials. It’s become more and more common for a rater training company to be involved in a clinical trial, she says. Sites should also address the costs of certification before they sign anything, she says.

Technological tools also represent an overlooked billing arena. Segal suggests building in some sponsor funds to cover things like glitches (e.g., a patient using an iPad remotely says it has crashed). “You’re going to have to pay some kind of tech support and hour or so every time something like that happens,” she says. Historically, sponsors have not covered some of those costs. Again, you have zero chance of getting reimbursed for that if you don’t ask.

Additional Resources

For more information, check out the October 2015 issue of ACRP’s Clinical Researcher journal, which includes a variety of articles on topics tied to clinical trial billing.

To learn more tips for building and negotiating trial budgets, check out Mastering Budgeting at Your Site: Building and Negotiating Trial Budgets that Make Sense.

Clinical Trial Site QA Management Programs Prevent Operational Pain Down the Road

David Morin, director of research at The Holston Medical Group

It’s easy for overwhelmed sites to get off-track and overlook critical gaps in their quality training programs, says David Morin, director of research at The Holston Medical Group in Kingsport, Tenn. “We’re all so busy and resources are so tight,” he acknowledges. That said, high-quality, proactive training is key to better site management and bolstering quality assurance (QA) performance throughout a site.

Some sites look at QA in too narrow a manner, Morin adds. “Many use it to focus on a review of a single problem or a way to be proactive” about a specific task or situation, he says. That’s all well and good, of course, yet it fails to recognize that QA should apply to operations across the board, he adds.

Adequate QA programs should include strong training, hiring, and ongoing competency verification methodologies, Morin says. He advocates using mentors to help clinical research coordinators (CRCs) and others perform their tasks adequately. He also strongly believes in establishing other ways to ensure that an employee continues to grow in the job and learn new skills to address new challenges as their position evolves (e.g, internal testing with clear explanations of roles and responsibilities).

“Explain why something is done a certain way,” he suggests. “Make certain they understand the concept behind it.” Give them a stake in site operations, too. Synchronize root cause analysis and corrective and preventive action (CAPA) responsibilities with clear job descriptions, Morin adds.

“Errors tend to happen early” in the process, he notes. Vigilant, well-designed, site quality management programs can make all the difference.

Learn More

To learn more about site quality management, check out Site Quality Management Tools: SOPs, Metrics, and Training.

And check out ACRP’s CRC ‘Boot Camp’ if you need to rapidly develop competent and effective early-stage CRCs. This immersive and experiential one-week training program puts CRCs through a mix of didactic learning and practical simulations of real-life scenarios to aid learning retention and immediately develop the competencies required of high-quality, early-stage CRCs.

More Carrot, Less Stick: How to Effectively Drive Adoption of ‘eResearch’ Methods

Lenis Sosa, MSN, RN, CCRC, Houston Methodist Research Institute

Even the most change averse clinical trial practitioners can warm up to managing clinical trials in new electronic environments if the benefits are demonstrated early and often, says Lenis Sosa, MSN, RN, CCRC with the Houston Methodist Research Institute in Texas. It’s a big challenge because transitioning from paper to electronic files in clinical research not only causes concerns related to subject information and trial data confidentiality, it also creates new challenges related to managing a multitude of systems, Sosa says.

At Houston, Sosa and team have implemented an electronic health records system, EPIC, that has streamlined communications with the clinical side of the operation so his team can readily see which patients are enrolled in research, and efficiently flag what patients invoices are research or clinical in nature.

Nurses, researchers and others conducting the trial in a new electronic environment will be less resistant to change if you can give them a clear visualization of the project’s goal and what that change will ultimately mean for them on a day-to-day basis, he adds. He advocates training sessions planned well in advance. It’s also important to adjust training to different audiences. “I’m a nurse, and we’re taught to do assessments with open-ended questions,” Sosa says. He uses some of that same skillset as he designs educational presentations for his own staff and more broadly across the entire hospital system.

In addition to navigating the all-important human factor, it’s also critical to be well-versed in the latest developments in US and EU regulations and guidance documents covering the management and use of electronic tools in clinical research, experts say.

Ultimately, training should be scheduled well in advance of any implementation, strive to be entertaining, and make it clear to wary users how it will make their job easier and more efficient, Sosa says. “You don’t want to surprise anyone,” he adds.

Learn More

For more tips on managing the transition from paper to electronic files in clinical research, check out eResearch: Managing Clinical Trials in an Electronic Environment.

Clinical Research Training Programs Must be Brought into 21st Century

Clinical trial training programs require a significant overhaul to keep pace with the growing demands of the job, say several members of the Joint Task Force for Clinical Trial Competency (JTF).

“Clinical research has become a profession,” says Stephen Sonstein, PhD, Director of Clinical Research Administration at Eastern Michigan University. “It’s no longer just a task,” he adds. Sonstein is lead author on a paper outlining JTF industry survey results scheduled to be published in the December issue of Clinical Researcher.

Given the increased size, complexity, and demands of trials, “the generally accepted on-the-job training model is not acceptable anymore,” Sonstein says. Bottom-line: Clinical Research Coordinator’s (CRCs) and others in the trial chain must be trained to get a better understanding of their roles in the development of medicines and medical devices.

The limits of current training and competency programs are crystal clear, in part because “so many CRCs don’t have a general grasp of how medicines are developed” or the broader role of study coordinators in the process, says Carolynn Jones, Assistant Professor of clinical nursing at The Ohio State University’s Masters of Applied Clinical and Preclinical Research and an active member of the task force.

Example: While the vast majority of CRCs in today’s workforce are strong in their niche area (e.g., data management, patient recruitment), they often have not gotten adequate training to have at least a cursory understanding of scientific concepts and how protocols are designed, Sonstein says.  This has a potential impact on the collection of endpoints and study outcomes, Jones points out.

In the past, competency-based education and training generally focused on specific roles (e.g., investigator, pharmaceutical physician, or clinical research nurse). The JTF aligned and harmonized competency requirements, as identified by surveys and other industry input, into a single framework of eight domains and 51 associated core competencies. These are designed to define professional competence throughout the clinical research roles, as represented by the JTF Core Competency Framework (CCF).

Core Competency Framework Domains

The JTF CCF’s eight domains are:

• Scientific Concepts and Research Design
• Ethical and Participant Safety Considerations
• Medicines Development and Regulation
• Clinical Trial Operations (Good Clinical Practices)
• Study and Site Management
• Data Management and Informatics
• Leadership and Professionalism
• Communication and Teamwork

One organization that has already adopted the CCF is the Consortium of Academic Programs in Clinical Research (CoAPCR) by using the CCF as the curriculum foundation for their academic programs. The JTF members hope to help others recognize the need for prior academic education followed by continuing specialized training Jones says.

Editor’s Note: This is the first blog in a series examining new training concepts proposed by the Joint Task Force for Clinical Trial Competency based on its core competencies.