Welcome to the July issue of InFocus, where we provide insights and solutions to help sites and other stakeholders ensure site sustainability.
- SCRSConnects: Exclusive interviews with industry leaders. This month: Dr. John Whyte
- MetricsThatMatter: Unique and current metrics supporting your success.
- TransCelerateUpdate: Insights from influential industry stakeholders.
- SiteSpotlight: Site stories of innovation and success. This month: Arizona Research Center
Engagement, communication, transparency: these are three words that represent Dr. John Whyte’s clinical research passion and journey. It is not uncommon for me to feel inspired by the folks I interview, and Dr. Whyte is no exception. Plus, who wouldn’t want to have a conversation with someone who once developed programming for the Discovery Channel? “The first question I usually get is ‘Did you meet Oprah?’, Whyte joked.
My first questions in that regard were, how did your experience working for the Discovery Channel uniquely prepare you for your current work with the FDA? And, what did you do there? Whyte has always had a keen interest in health policy, and he kindly reminded me that he had worked in Medicare/Medicaid prior to the Discovery Channel and is an internist by training who still sees patients. After spending several years in Medicare/Medicaid, Whyte was approached by what was then called the Discovery Health Channel (now called the Oprah Winfrey Network). They wanted to hire a physician to help plan and run their medical programming. Seeing it as an opportunity to translate research into practice and create awareness of various health conditions among a large audience, Whyte accepted. Over a period of almost nine years spent creating hundreds of documentaries, thousands of digital shorts, and a variety of other programming, Whyte decided to shift directions again. He returned to work more directly related to health policy and joined the Federal Drug Administration (FDA) as the director of professional affairs and stakeholder engagement (PASE) in 2013.
His experience engaging with a large audience with varying degrees of awareness about health policy and clinical research taught him the importance of communication. He brought this with him to the FDA: “I’m trying to take introverts and turn them into extroverts. Though we care very much about patient care, most of our staff came to the FDA to interact with data, not patients,” Whyte said. “My goal isn’t to completely alter the course of the ship but to change its course by a few degrees so that the way the FDA engages with patients allows them to be recognized as experts.”
One of Whyte’s biggest FDA project to date has been the creation of Drug Trials Snapshots. This program is part of an overall effort to increase clinical trial transparency, providing consumers and health professionals with information about who participates in clinical trials broken down by sex, race and age. 2017’s Drug Trials Snapshots Summary Report can be found here.
In addition to the creation of Drug Trials Snapshots, Whyte helps the FDA address the challenge of transparency by publishing data within 30 days of approval for all new molecular entities and biologics, including who participated in the clinical trial by sex, race, age and US vs. non-US. This enables the FDA to look into whether there is a difference in safety and efficacy based on these factors.
However, Whyte believes more research is needed into whether responses to a drug differ and based on what factors. “We’re examining sex, race and age because that’s what Congress requires, but I’m not sure this is what really matters,” Whyte shared. “In many cases the sponsors’ default is that there is no difference based on these factors, while advocacy groups tend to believe that there is a difference. That’s where the tension exists. Who’s right? We haven’t conducted adequate research yet to answer that question.”
This is where the importance of talking to patients comes in. “We need to have a better grasp on whether we’re demonstrating clinical trial bias without even realizing it,” Whyte said. “Is it that blacks aren’t being referred for heart disease trials because there’s a misguided belief that they may not be compliant? Or were they asked and they decided not to participate? These are bold and important questions we should be asking, documenting and evaluating.”
The Drug Trials Snapshots document several important factors, but Dr. Whyte believes we need to move beyond this and ask ourselves: what’s accurate, and what’s actually happening? This level of transparency is only possible via communication. And communication can only happen if we engage with patients and clinical research stakeholders to come to new and more complete answers.
This is Your Auditor Calling
FDA audits have been a hot topic of conversation in the SCRS online community forum in 2018, with member sites utilizing the forum to help prepare for audits, mitigate risk factors, and revamp clinical trial practices in preparation for future potential audits. SCRS recently polled member sites about their experience with FDA audits. As shown in Figure 1, 72% of the SCRS member sites who responded indicated that they have received an FDA audit in the past 10 years.
“Routine” inspections make up more than 80% of FDA inspections, with “for cause” inspections accounting for the remaining <20%1. Several factors can increase a site’s likelihood of being selected for an audit, including:
- Conducting a large volume of clinical trials;
- Conducting clinical trials outside of your site’s field of specialty;
- Reporting results that differ from those of other sites with clinical trials investigating the same drug;
- Appearing to have access to more patients with a specific disease than can be reasonably expected within a site’s particular location;
- Complaints from patients, sponsors or site staff1.
If any discrepancies are discovered by the inspector, the site will be issued FDA Form 483. This document is not publicly available, and it is up to the discretion of the site to determine which findings to address. A warning letter is usually issued when major compliance discrepancies noted in Form 483 are not addressed. This letter should be taken very seriously (as should Form 483, in SCRS’ opinion).
Figure 2 indicates that approximately 40% of SCRS member sites have received Form 483 in response to their FDA audit, and about 37% did not. Of the sites who received and addressed the findings in Form 483, all indicated that no findings were reporting in subsequent audits. This demonstrates the importance of addressing these findings regardless of “requirement.” Several sites stated that the incidents reported in Form 483 were minor and thus easy to remedy. A small handful of sites indicated that their records were not comprehensively examined or that the inspector appeared to have a very specific agenda, and as a result the findings in Form 483 were inaccurate and unsubstantiated. Others indicated significant financial burden resulting from the fees associated with responding to Form 483.
All respondents who have been audited in the last 10 years indicated that they have not received a warning letter (see Figure 3). While SCRS would love to claim bragging rights for our incredible members, it is more likely that this indicates two things: 1) warning letters are received by sites infrequently, and 2) when Form 483 is addressed sufficiently, it is very rarely (dare I say never – the operative word being addressed sufficiently) followed by a warning letter.
Several respondents shared that when they were not told which study was being audited, it more often than not ended up being a bioequivalence study.
The primary grievances shared by sites were:
- Disruption of staff time: The visits required a lot of preparation, and dedicated staff needed to shift their schedules to be with the inspector throughout the duration of the inpection.
- Lack of adequate notice: Some sites shared that they were told an inspector would be onsite the next day and had to drop everything to prepare for the inspector’s arrival. Others stated that inspectors came on weekends or during hours the site was not open, requiring site staff to be present outside of work hours.
- Financial burden: Sites realized financial loss from paying attorney fees to prepare for an audit and/or resolving 483 findings.
- Time burden: Site staff time had to be repurposed to the audit when their schedules were already full, leaving studies unattended.
- Study delay: Studies received less attention than needed to keep them moving forward.
While many of the above outlined burdens are entirely dependant on the particular audit, site and inspector, these are not factors that should be ignored. SCRS suggests that all sides of industry take a closer look at how audits are managed.
Sites also shared positive experiences in almost equal abundance. Many sites stated that their inspector was thorough, helpful and organized. Others share that their site is better as a result of their audit. In general, SCRS member sites seem to feel that the process is improving and that addressing findings thoroughly improves the audit experience the next time around. It also contributes positively to the function and compliance of the site in general. In addition, the SCRS online community forum has proved to be a valuable resource for member sites, with several respondents sharing that they received helpful guidance to prepare for upcoming audits.
The Shared Investigator Platform: An Update on Expansion, Use and Adoption
In 2014, TransCelerate set out to make clinical trials more efficient for sites, sponsors and patients by creating the Shared Investigator Platform (SIP). The SIP was conceptualized as a multi-tenant, multi-vendor platform, highlighting solutions intended to make the life of a site investigator easier when conducting clinical studies. Today that concept is a reality.
Currently, investigator site staff face the difficult task of running studies through various systems, each of which is unique to each sponsor. They must enter the same information and complete the same questionnaires for every system, which creates unnecessary duplicated work. The SIP offers a one-stop, single sign-on solution where users can enter their information once and run multiple studies across multiple participating sponsors. And that’s just the beginning.
Another challenge of delivering new medicines is the bureaucracy of running clinical trials – there is a lot of paperwork and investigative site staff are often left with little time for their patients. The process has become very paper-heavy. It is cumbersome to manually obtain necessary documents, forms and training and to complete them repeatedly for each study and sponsor in a process that includes routing them for signatures, tracking people who need to sign them and then returning the documents to the sponsor of the study. Through the SIP, this process is simplified.
The SIP has grown at an exponential rate since the platform was launched in 2016. It is currently used by 4 TransCelerate BioPharma Member Companies (with another 3 joining by the end of 2018) and has more than 5,000 registered site users across 67 countries. By the end of 2018, more than 25,000 invitations will be sent to site users around the globe. In addition, through collaboration and data sharing with the Investigator Registry, 12 TransCelerate Member Companies have access to principal investigator and site information that will assist in assessing site feasibility and selection activities.
Sponsors have utilized the platform for operational activities for more than 80 trials. More than 1,200 investigators have realized value and benefits as they have participated in more than one study, allowing them to re-use data and reduce data entry across various study activities. Further, some users have been simultaneously conducting trials for more than one sponsor within the SIP.
The growth of the platform is only part of the story: users of the SIP are seeing real results in alleviating administrative burden while conducting trials. Assets from the TransCelerate Site Qualification & Training Initiative (SQT) form the basis of SIP Profiles and have been automated within the platform. The Site Profile form is a 1:1 match of the Facility Profile. This form can be completed offline and uploaded directly into the SIP. The User Profile is also a 1:1 match of the CV template, allowing users to enter their information one time and simply push a button to generate their CV using the TransCelerate CV template.
In addition, to accommodate the GCP Mutually Recognized Training (MRT) Program, all courses listed on the TransCelerate website (more than 900 global courses) are available for selection in the SIP, allowing users to upload their certification to their profile only once and providing sponsors with the ability to view and approve the certificate. The integration of the SQT assets within the SIP saves critical hours previously spent on non-value-added, duplicative administrative tasks and repurposes this time into more meaningful activities, like more time with patients.
Looking ahead, users can expect to see continued benefits and growth of the platform. The TransCelerate SIP team and its partners have actively worked with SCRS and its Site Advocacy Group (SAG) to solicit user feedback from site members. This feedback helps TransCelerate develop future features of the SIP including:
- Centralized workflows aligning with the business processes of Site Management Organizations, Academic Research Organizations and Site Networks;
- Addition of Investigator Payment functionality;
- Continuous improvement of workflows including the registration process (e.g. bulk invitations sent directly by site users).
Want to know more about the SIP or learn how to register yourself or your facility? Email SIPHelp@Cognizant.com.
Look for us October 12-14, 2018 at the SCRS Global Site Solutions Summit in Boca Raton, FL, where experts from TransCelerate Member Companies will be inside the TransCelerate Experience to answer your questions about the SIP and many other TransCelerate initiatives.
Learn more about TransCelerate and view recent videos about the Shared Investigator Platform at www.transceleratebiopharmainc.com and follow us on LinkedIn and Twitter (@transcelerate).
After developing and operating an 8-physician orthopedic practice, Dr. Joseph Gimbel stopped performing surgeries in 1997 and entered the research arena. One of the first trials he conducted was a Pfizer Celebrex study, where Arizona Research Center became the top enrolling site through excellent recruitment effort and physician involvement. As a result, Dr. Gimbel was asked to be the lead author of his first article of a peer-reviewed medical journal which was subsequently instrumental in helping to obtain the necessary approval by the FDA. Since then, Dr. Gimbel and his staff have participated in close to 1,000 clinical trials and he has authored over 75 articles in peer-reviewed medical journals.
Arizona Research Center continues to grow. With a staff of nearly 50, we have recently added a full-time, board-certified neurologist, Dr. Stephen Hempelman, to complement Dr. Louise Taber, our board-certified internal medicine physician. Dr. Taber is considered an outstanding and accomplished principal investigator and is the recipient of multiple national awards in the field of research. With Dr. Hempelman, Arizona Research Center will be expanding into the field of neurology. The site was recently chosen for an Alzheimer’s trial and, in the future, we will be adding Parkinson’s, Multiple Sclerosis and Epilepsy trials to our list of indications.
Having just purchased a 40,000 square-foot building and creating a 24,000 square-foot facility within, boasting 15 exam rooms, 22 private rooms and 2 operating rooms, Arizona Research Center is well positioned to expand and move forward. 13,500 square feet of the space is currently earmarked for a potential Phase 1 Unit.
As we move forward this year, Arizona Research Center has a significant potential pipeline of business. We are in line to start multiple studies such as bunion post-op pain, acne, hot flash, psoriasis, two additional knee replacement post-op pain studies with different medications, a knee injection study, shoulder tendonitis, ankle fusion, and several anti-nerve growth factor studies for chronic low back pain, hip and knee arthritis.
Arizona Research Center is considered a premier site on a national level and has received recognition internationally year after year. Our model works much differently than the typical site. We collaborate with over 100 physicians in Arizona Research Center’s community, incorporating them into our studies. This enables our partnering physicians the opportunity to enroll patients, perform study procedures, and have access to emerging new treatments. As a result, we have created an entire community of clinical researchers; working together to make advances in medicine and improve the quality and quantity of healthcare options in Phoenix and beyond.
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Founded in 2012, SCRS is a global trade organization that unifies the voice of the clinical research site community to create greater site sustainability. Representing over 9,000 sites in 47 countries, SCRS membership provides sites with a community dedicated to advocacy, education, connectivity and mentorship. SCRS is an influential voice for sites and an active partner in industry-wide initiatives and dialogues focused on improving the clinical research enterprise. Our Voice. Our Community. Your Success. Join the community.