InSite, Summer 2017

InSite

SUMMER 2017

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The Global Journal for Clinical Research Sites

eConsent

Five Key Areas of Preparation

Empathetic Communication How Clinical Research Teams Interact With Children and Their Families

MySCRS.org

Patient Perspective The Role of Patient Navigators

SCRS Leadership Council Christine Pierre

President Society for Clinical Research Sites

Thomas Apostle, DO

Founder & Principal Investigator Apostle Clinical Trials

Deena Bernstein

Vice President Site Services QCare

Christophe Berthoux, DVM, MBA

Chief Executive Officer Synexus

Steven Geller, MD

Medical Director Centennial Medical Group

Dalvir Gill, PhD

Chief Executive Officer TransCelerate BioPharma Inc. Member at Large

SCRS Community Chairs Editorial

Donna Benson, BSc, MA The Medical Arts Health Research Group

Education & Standards Lucy Wright Pelletier Beyer Research

Membership Reg Blynn QCare

Mentorship

Steve Satek Great Lakes Clinical Trials

Public Policy

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

Global Site Solutions Summit Chris Hoyle Elite Research Network

Clare Grace, PhD

Vice President, Site and Patient Access INC Research

Mark S. Hanley

Chief Executive Officer Clinical Research Advantage

Hans Christian Hoeck, MD, PhD Chief Executive Officer CCBR Clinical Research

Jackie Kent

Senior Director, Clinical Development Information & Operation Lilly

Michael J. Koren, MD

Chief Executive Officer and Clinical Research Investigator Jacksonville Center for Clinical Research

Mary D’Rozario, MSCR, MBA, CCRP, RAC, CCRA Director of Communications Society for Clinical Research Sites Editor-in-Chief, InSite

Doug J. Peddicord, PhD

Executive Director ACRO Member at Large

Jeff Rosen, MD

Medical Director Clinical Research of South Florida

Fabian Sandoval, MD

CEO & Medical Director Emerson Clinical Research Institute

William Smith, MD

Founder, President & Principal Investigator Volunteer Research Group/New Orleans Center for Clinical Research

Vivienne van de Walle, MD, PhD, CPI Director & Owner PT&R

David Vulcano, LCSW, MBA, CIP, RAC

AVP & Responsible Executive for Clinical Research Clinical Services Group Hospital Corporation of America

10326-B Baltimore National PIke • Ellicott City, MD 21042 For more information, visit MySCRS.org

2 | InSite - Summer 2017

InSite

™

The Global Journal for Clinical Research Sites SUMMER 2017

Table of Contents 4 5 8

JOIN US IN BOCA RATON FOR THE 2017

GLOBAL SITE SOLUTIONS

SUMMIT OCTOBER

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WALDORF ASTORIA

BOCA RATON SiteSolutionsSummit.com

From the President TransCelerate Update TransCelerate’s Patient Technology Initiative – Part of Improving the Patient Experience

Empathetic Communication

How Clinical Research Teams Interact with Children and Their Families

10 eConsent: Five Key Areas of Preparation 12 SCRS Connects Two Perspectives on the Legal Landscape

14 SCRS Current 15 A Principal Investigator Speaks Flux or Stasis?

16 Patient Perspective The Role of Patient Navigators

18 Clinical Trial Diversity

Diversity of Religious Identification and Practices

19 Metrics that Matter

SCRS Site Landscape Survey

20 Five Ways Sites Can Prepare for Implementation of the 21st Century Cures Act 22 Association of Clinical Research Organizations (ACRO) ACRO Releases “Right to Try” Policy Statement

23 Ask the Auditor

Clinical Care Versus Clinical Research

24 Global Site Solutions Summit Reflection Quick Tips for Better Relationships with Sponsors

26 White Paper Highlight

Looking Toward the eSource Revolution

28 How Can the Right RTSM Solution Solve Problems Commonly Faced by Sites?

30 Clinical Trials Transformation Initiative (CTTI) Reflecting on 2016: A Year of Action at CTTI

31 SCRS Ambassador Program 32 Webinar Spotlight

Tackling Common Research Red Flags at the Site Level

33 Legal Lines

Understanding the Medicare Secondary Payer Rule

34 HR Solutions

Don’t Underestimate Labor Costs in Your Budgets

35 Book Review

The Billion-Dollar Molecule

MySCRS.org | 3

From the President Christine Pierre President Society for Clinical Research Sites

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S WE COME UPON THE MIDYEAR MARK, it’s natural to reflect on what has been accomplished as we look forward toward all that remains in our paths to complete. None of these accomplishments would have happened without our dedicated site members and extraordinary industry partners. I am filled with gratitude for the incredible relationship we have all forged for the common goal of getting new medicines to patients faster.

While SCRS has launched a few surveys this year, we are quite selective in what we ask of you. Each survey is specifically tethered to an issue you have identified for us to work on or an initiative SCRS is involved in – all to benefit the sites. Most surveys result in white papers that are specifically aimed at positioning sites for success and educating the industry at large. All SCRS white papers are complimentary on the SCRS website and can be accessed here: http://myscrs.org/learningcampus/white-papers/.

But it doesn’t stop when the white paper is written. SCRS is tirelessly advocating for adoption by industry on these various projects.

That takes time. But we are not going anywhere and will continue to bang the drum and move forward, one partner at a time.

SCRS has also launched an exciting new diversity initiative focused on what sites contribute to meeting clinical trial enrollment diversity expectations. In clinical research, sites are the closest to the patient, and it is their patient relationships that are key to study success. This initiative is supported by our GIPs, other industry partners, and the FDA. During the Global Site Solutions Summit, you will learn more about how to mobilize your site to meet this expectation.

Despite all of the frustrations sites share on the SCRS discussion forums, we also see incredible support and mentoring among the sites. The forums are a hidden gem. Many times, participants have stated, “this alone is worth belonging to SCRS.” Know that we don’t just listen to the frustrations shared between sites, we identify themes and share anonymized feedback with our GIP partners – it’s called The Buzz.

Often, reading The Buzz is the first time industry partners have an opportunity to learn about operational hurdles or process bottlenecks sites face. Our industry partners actively await The Buzz and eagerly review the comments sites have shared. This connection with the sites is important for their own process improvements and business success. Sites should know that SCRS is ensuring the sites’ voice is being heard.

If you aren’t already a member of an SCRS discussion forum, please email Michael Jay at Michael.Jay@myscrs.org and he will help you join the right forum for you. These forums are at the heart of what SCRS does – mentoring, unifying the site voice, and communicating with industry.

All of us are not only clinical research professionals but may also be patients or have loved ones who are patients. We are all living in communities whose dedication is to ensure patients receive the new medicines they need through the hard work done by all of you!

I am grateful for the impact SCRS has made to help that goal become a reality by supporting the sites and the collaborations with our other stakeholders. You are all amazing people doing important work- sometimes I think we fail to stop and realize the impact we’re having. Take a moment today to talk with your staff about the importance of their individual and collective role in this process and send them a special big thanks from SCRS! Stay in touch – CKP

Christine Pierre 4 | InSite - Summer 2017

TransCelerate Update TransCelerate’s Patient Technology Initiative – Part of Improving the Patient Experience

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INCE 2012, TRANSCELERATE HAS WORKED to improve the health of people around the world by simplifying and accelerating the research and development of innovative new therapies. An important part of that work involves one of TransCelerate’s five strategic priorities – Improving the Patient Experience. To this end, several of TransCelerate’s patient-focused initiatives center around creating a more informed and aware patient, decreasing patient burden, promoting new technologies, and improving study participation and engagement.

teams to improve patient participation and experience, and facilitate technology development that can reduce burden and innovate data capture in trials.

As the Patient Technology team is embarking on their journey, they are looking for input from site investigators to

The team looks forward to getting site feedback on the needs related to technology for patients.

The Patient Technology initiative is aimed at facilitating the adoption of patient-facing technologies in clinical trials. The team’s goal is to conduct research and to develop tools that will help implement technology that can improve patient experience and enable richer data collection in clinical trials. To do this effectively, other key stakeholders will be consulted to ensure a wide lens

better understand the site experiences and perspectives on patient-facing technology. As a stakeholder in this field, the Patient Technology initiative has created a quick survey to capture your experiences.

The team looks forward to getting site feedback on the needs related to technology for patients. Additionally, the team looks forward to opportunities to share their latest developments as they meet with site investigators in the coming months, including discussions within the TransCelerate Experience at the SCRS Global Summit in October.

The Patient Technology initiative is aimed at facilitating the adoption of patient-facing technologies in clinical trials. and holistic understanding of the challenges faced in implementing technology in trials is understood. These stakeholders include patients, regulators, sponsors, technology innovators and sites. The initiative also works closely with the Patient Experience initiative and together, will help the industry understand, evaluate, and improve the patient’s clinical trial journey – better enabling study

The survey consists of multiple choice and short answer questions, and results will be kept anonymous. http://bit.ly/2sBV0YE. Thank you in advance.

MySCRS.org | 5

SCRS Thanks Our Corporate Partners Committed to Site Relationships CIRCLE OF INNOVATION

SITE VOICE SITE ENGAGEMENT The Global Enrollment & Retention Specialist

GLOBAL IMPACT

nimblify

6 | InSite - Summer 2017

JOIN US IN OCTOBER!

2017 GLOBAL SITE SOLUTIONS SUMMIT

OCTOBER 5-8, 2017 – BOCA RATON, FL MySCRS.org | 7

Empathetic Communication

How Clinical Research Teams Interact with Children and

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NROLLING CHILDREN IN CLINICAL TRIALS ENGAGES MULTIPLE STAKEHOLDERS beyond just the primary participant- this includes clinical staff, the child’s physician, and the child’s family.

By definition, a child is too developmentally immature and without the legal agency to independently decide to enroll in a clinical trial. Her parents or guardians must provide informed consent. The child’s parents should be comfortable with the research team and feel empowered to ask any and all questions about the trial and their child’s participation in it. In fact, parents have the legal right and responsibility to speak up.

Older, more mature children can sometimes make the decision to participate in a trial and provide informed assent. However, for younger subjects, parents may need to decide on their behalf. Ideally, the decision to enroll should be made jointly between parent and child. In each case, an empathic and experienced research team member must listen, provide information, and above all, encourage the family to ask questions.

last, how long the treatment has been studied in other children, and the credentials of the principal investigator.

The research team should continually remind and encourage parents and children to keep asking questionsif they don’t understand, they should ask again. It should be stressed that no question is insignificant, and families should feel comfortable asking simple things such as where to park, if childcare is available, and if meals are provided. While seemingly mundane, these issues significantly impact the child’s and family’s participation experience. Ensuring realistic and accurate expectations for the child and family is key to retaining patient participants.

Having a child in a pediatric trial can become a family activity. Parents often are tasked with keeping medication diaries or records of side effects. This can be a challenge when the parents are dealing with their own anxiety and uncertainty about their child’s diagnosis and prognosis.

Additionally, parents of an in-study child frequently have to miss work or arrange for childcare for their other children, adding to their baseline stress level and increasing the obstacles to clinical trial participation.

In each case, an empathic and experienced research team member must listen, provide information, and above all, encourage the family to ask questions.

The research nurse is often the first and primary resource for these questions as families consider enrollment.

Questions in this phase of study participation typically revolve around whether the study is appropriate for a child, even though he may not directly benefit from participation (as in the case of a placebo-controlled randomized clinical trial). Parents need to understand the fundamental objectives of the clinical trial – to generate knowledge about the safety and efficacy of the investigational treatment on their child’s condition – and that there may or may not be a direct or immediate benefit to their child from participating. Ensuring the child and his parents understand this information is critical to the integrity of informed consent.

Once the decision to participate is made, the family may have questions that are tactical in nature, such as: what should I do if my child spits out the study drug, or, should I still administer the dose if my child seems sick? Other questions may have to do with the logistics of the trial protocol – the number of tests, particularly blood draws, the frequency of site visits, and the degree of risk represented by the investigational therapeutic intervention. Parents want to know how long the study will 8 | InSite - Summer 2017

A child’s participation in a clinical trial not only affects the child’s parents but also impacts their siblings. This can be a particular concern when the child has a chronic condition and requires considerably more attention over a long period of time.

Other siblings may feel neglected, which can introduce tension and complicate family dynamics in an already stressful and difficult situation.

While some pediatric studies can be very short and place few demands on the child and her family, other studies can go on for years and require monthly or weekly site visits or even extended inpatient stays for various assessments. These longer studies can put quite a burden on the parents and family.

Awareness of these “meta-study” issues and close communication between research teams and families are critical elements for the successful participation of children in clinical research. This communication works best when built on a foundation of understanding, empathy, comfort, and trust.

Judith Ng-Cashin, MD Chief Scientific Officer INC Research SCRS Circle of Innovation Partner

Their Families

Parents want to know how long the study will last, how long the treatment has been studied in other children, and the credentials of the principal investigator.

MySCRS.org | 9

eConsent

Five Key Areas of Preparation

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HE SITE’S RECRUITMENT AND RETENTION of an adequate study population remains a major determinant of the success of a clinical trial. Low rates of recruitment and retention result in longer study durations and delayed completion, not to mention higher costs. Over 40% of studies face challenges in meeting predefined enrollment goals, leaving sponsors and sites struggling to effectively conduct trials. Furthermore, 85% of clinical trials fail to retain enough patients, with the average dropout rate being as high as 30%.1

However, like the introduction of any technology, adoption is slow and there is still considerable work to be done in preparing study sites for the change.

A recent survey was undertaken to gather opinions on informed consent related to participant understanding, subject recruitment, and retention from 105 respondents across site-based roles.2 The survey sought to understand the impact of the consent process on the clinical trial.

Electronic informed consent, or eConsent, is one of the technological advancements introduced to clinical trials that has recently gained traction. eConsent offers the potential to address some of the challenges associated with patient recruitment and retention.

Its benefits are helping re-shape interaction with patients, yielding streamlined workflows and higher patient satisfaction for faster product approval.

In today’s increasingly challenging climate, eConsent may bring benefits to patients and to all aspects of industry.

Although most respondents had no experience with eConsent, 85% felt the technology would be useful in their roles, and 61% felt that eConsent would enable them to recruit more subjects.

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eConsent offers the potential to address some of the challenges associated with patient recruitment and retention.

When asked if subjects were unable to finish paper consent forms in a reasonable time frame, 12% of survey respondents indicated that 50% of the subjects they had encountered had this difficulty, while more than one in five respondents spent more than 30 minutes discussing questions with subjects. Perhaps most troublingly, 25% of respondents found that subjects still had questions about the purpose of a study even after reading the informed consent form (ICF).

Although most respondents had no experience with eConsent, 85% felt the technology would be useful in their roles, and 61% felt that eConsent would enable them to recruit more subjects. Respondents also thought that reminders to participants during the trial, and the ability to indicate questions when going through the form electronically, will have the biggest impact on reducing drop out rates.

Site personnel expecting to use eConsent in a study should consider five key areas of preparation: 1. BUSINESS PROCESSES: The introduction of eConsent technology will have a major impact on many site processes. Sites need to first look at their workflows and understand how they currently undertake study startup activities related to informed consent and work with ethics committees. Sites also need to assess how they may need to change how they conduct and document informed consent, how they schedule patients, and how they perform the informed consent process in relation to eConsent. Once these processes are understood, sites can make clear decisions about how eConsent can be best integrated into existing workflows.

2. DOCUMENTATION: Many eConsent technologies document information that traditionally would have been documented on paper, such as whether the patient had any questions and if these had been adequately answered. In addition, some ICF systems enable sites to store source document notes, while others do not offer this functionality. Sites need to build an understanding of what information a solution can automate versus what will still need to be documented manually, and develop plans for how this will be managed. Not every eConsent solution is the same, and

a research site should assess the capabilities of a system before enrollment starts to be sure they have clear expectations of use.

3. TRAINING: Sites will need to ensure provisions are in place to train study staff and patients on the use of eConsent technology. It might initially be that the sponsor or eConsent vendor will provide the training for site personnel. Conversations and planning around training need to begin early to avoid any delays in use or unexpected issues.

4. INSPECTION READINESS: Sites should plan how they would be able to provide direct access to the eConsent system if requested by the regulatory authorities. Sites need to have access to the patient data and the eConsent journal of the participants’ experiences.

Source documentation and record retention requirements still apply to eConsent.

5. DATA SECURITY: Sites will also want to build an awareness of how an eConsent system will protect patients’ private health and personal information. This is a regulatory requirement most often directed by sites, so they need to ensure protection of private information and that the system they use satisfies the privacy laws in their region.

The survey data indicated that sites are interested in the development of eConsent. It is vital that they aren’t bystanders in the move towards its use. Being at the table and being proactive regarding study startup, controls, audit readiness, and communication will allow sites to develop an eConsent process that benefits all stakeholders in research.

1 Lopienski K. Retention in Clinical Trials – Keeping Patients on Protocols. June 1, 2015.

Accessed May 2017 from: https://forteresearch.com/news/infographic-retention-inclinical-trials-keeping-patients-on-protocols/ 2 CRF Health. Electronic Informed Consent: 2017 Industry Survey Results. Accessed May 2017 from: http://resources.crfhealth.com/electronic-informed-consent/electronicinformed-consent-2017-industry-survey-results

Sam Sather Regulatory & Quality, TrialConsent™ CRF Health

MySCRS.org | 11

SCRS Connects Two Perspectives on the Legal Landscape Molly Huggins founded a boutique law firm.

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olly Huggins didn’t know she was going to end up being a life sciences lawyer. She happened to be in college during early attempts at healthcare reform and ended up writing her political science thesis on the topic. When she graduated, her first job was in healthcare administration, which led to a Masters of Healthcare Administration.

developed an expensive medical issue. With the lifting of lifetime insurance caps under the Affordable Care Act, that changed and sites became more willing to allow insurance to be charged first for subject injury, with sponsors covering anything that insurance would not cover. If contemplated healthcare reforms include the return of lifetime insurance caps, the language will have to revert to protecting patients from running up their lifetime limit.

The biggest advice Ms. Huggins has for sites is to

A few years later interest in the legal side of healthcare led her to law school, and she then be aware of their risks. ended up in a general healthcare practice Ms. Huggins also sees continued evolution in Medicare at a large firm. When she was assigned to a clinical billing rules and enforcement for clinical research. research project, she kept coming back to it as the most “Medicare billing enforcement is a ripe area for interesting matter she could work on. Eventually, she compliance actions,” she warned. “We want clients to developed a book of business around clinical research, understand that compliance with billing rules and fraud and in 2015 she formed Huggins & Zuiker, LLP with law and abuse laws applies equally within and outside a partner Erin Zuiker. clinical trial.”

Ms. Huggins and Ms. Zuiker have been frequent contributors to the SCRS education program on webinars, at the Global Site Solutions Summit, and with a column in the quarterly SCRS InSite Journal.

Ms. Huggins says that she likes clinical research work because, “for a lawyer, it is very immediate. It’s very satisfying. Physicians want to get these studies started.”

She explained that often law moves very slowly. “But FDA regulation and life sciences law isn’t like that,” she continued. “It is current, it is fast-paced, and it evolves quickly.”

The biggest advice Ms. Huggins has for sites is to be aware of their risks. She sees sites that don’t have compliance as part of their infrastructure. Ms. Huggins explained, “By compliance I mean a person at the site— they don’t have to be lawyer—who is responsible for overseeing fraud and abuse compliance, for Medicare billing compliance, and for privacy compliance. For a very small site this person probably won’t be a lawyer, but this is the part of the site infrastructure that frequently interacts with the outside lawyer.”

Some sites don’t give a lot of concern to legal issues because of the perception that lawsuits are very rare. Ms. Huggins notes that subject injury lawsuits are relatively rare, but warns, “Compliance cases are very common. And not only are they not rare, they carry the risk of criminal prosecution.” Ms. Huggins advises that risk is a business decision, but a business must be aware of exactly what risks they are taking. “It can be a perfectly reasonable business decision to accept a wide variation of risk from different studies. My concern is that a lot of sites don’t know what risks they are taking.”

Over the last five to ten years one of the biggest evolutions has been a focus on patient privacy.

Over the last five to ten years one of the biggest evolutions has been a focus on patient privacy. “Privacy isn’t just about study data, but about patient data accessed at the site and proper consent,” Ms. Huggins explained. “Additionally, there is more sophistication about the fact that practitioners working on clinical trials answer not only to the FDA but to all the other agencies that regulate healthcare.”

When asked to forecast possible future changes, Ms. Huggins noted that sites used to have to ensure that sponsors paid for subject injury. This was because lifetime insurance caps meant that any use of insurance could cause unforeseeable harms later if the patient

12 | InSite - Summer 2017

These are risks Ms. Huggins understands well not only as a lawyer but as an entrepreneur herself. “I really enjoy working with sites because of the entrepreneurial spirit in research. Celebrating the Type A people who sit in the front of the class is part of why I’ve made my career in research.”

Rick Teague envisions an industrialized approach to site contracts.

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ith his analytics background and position at a legal company, a conversation with Rick Teague risked being a bit dry. It wasn’t. Mr. Teague, the Head of Innovation at Axiom, is focused on the clinical trial contracting process because it’s a high-energy space with lots of room for improvement.

First, the model is broken. That doesn’t sound like a good thing but Mr. Teague explains, “If, for example, pharmaceutical companies were happy and sites were unhappy, I’d probably conclude there was a power imbalance, a really complex problem to solve. But in a

into improvements in business performance. For instance, shaving months from the contracting process can bring a new drug to market faster, significantly increasing profits and improving (even saving) lives.

“Each trial is unique. Each compound has its own risk profile, and then each study phase has its own risk profile; each protocol too,” Mr. Teague explained. “We use a comprehensive model that describes negotiating positions to take these nuances into account and tailors negotiation strategies to each trial and the characteristics of a site. This approach eliminates a lot of back-and-forth.”

“For example,” Mr. Teague continued, “if a state-sponsored institution is prohibited from indemnifying a sponsor, it doesn’t make much sense to send a first draft that includes that Axiom, a legal services provider, sees legal process provision. And what is important regarding publication rights might problems as an opportunity for technology solutions, vary significantly between a Phase I especially where high volumes of contracts are involved. and a Phase III trial.” broken model everyone is unhappy and everyone is ready for solutions.” Mr. Teague also finds the mission focus of healthcare energizing. “Everyone wants to serve the patient.

Everyone involved wants to solve this problem,” he said.

“Our technology enables us to work with a sponsor to quickly develop historical outcome data and a playbook.

Armed with these tools, negotiators and lawyers can come to agreement quickly. We can dramatically reduce the percentage of negotiations that need to be escalated back to the sponsor’s legal department, eliminating unnecessary handoffs that take time,” Mr. Teague said.

Axiom, a legal services provider, sees legal process problems as an opportunity for technology solutions, especially where high volumes of contracts are involved.

He went on to explain that it’s also really important to Instead of scaling up the traditional “artisanal” model understand and accommodate the negotiation and of contract negotiation, they are implementing an approval processes at sites. “I’m not talking about the “industrialized” model. “We’re marrying technology contract language,” Mr. Teague clarified. “I’m talking and contract data with specific legal skills,” Mr. Teague about work processes.” explained. “Combined with a repeatable data architecture, this dramatically Axiom focused on pharmaceutical site contracting after their analysis of streamlines several industries found this is a space where improving the contracting and shortens the negotiation process directly translates into improvements in business performance. cycle. A wealth of knowledge can be gleaned from previously executed contracts to The need to truly understand the sites prompted Mr. Teague improve negotiations. Essentially, the past should inform the to bring Axiom to SCRS as a Global Impact Partner (GIP), future.” the first legal services provider to join the program. As a GIP, Axiom will be involved in SCRS initiatives, including those Axiom focused on pharmaceutical site contracting after aimed at resolving site contract issues. their analysis of several industries found this is a space where improving the contracting process directly translates

MySCRS.org | 13

SCRS Current

News and Updates from SCRS

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N THE LAST QUARTER, SCRS HAS RELEASED SEVERAL WHITE PAPERS with significant information for industry, and SCRS executives have attended industry conferences to share key findings from this new research. Just as this newsletter is going to press, SCRS is at the DIA global meeting building relationships with industry stakeholders and advocating for sites.

SCRS white papers published this year include:

•

In collaboration with Clinical Ink: Why is Clinical Source Data Still Collected on Paper? Despite widespread use of electronic medical records, clinical research is frequently recorded on paper. In this white paper, the expense of this practice was calculated, and the risk to quality discussed. An article in this Journal discusses the paper further.

•

In collaboration with Greenphire: Site Payments and Patient Reimbursements: A Global Perspective. In this white paper, for the first time, global data on how industry payment practices affect sites is presented.

•

Sponsored by Acurian: Meeting Clinical Trial Site Needs with Patient Recruitment Agency Services. Patient recruitment is a serious challenge not just to site sustainability, but to the sustainability of the entire clinical research enterprise. This paper discusses difficulties with patient recruitment innovation at the site level and how they can be overcome.

SCRS is extremely grateful to all of the Entries for the popular Site Patient Enrollment Innovation Global Impact Partners (GIPs) that Award (SPRIA) and Site Tank are now open. support research and advocacy that benefit the sites. The partners named above supported these individual white papers, and all of our GIPs provide input to the surveys and research that SCRS carries out throughout the year.

In addition to the white papers, SCRS has launched an innovative new program: Site Awareness and Best Practices for Inclusion of Diverse Patients in Research. The program is aimed at developing a better understanding of the knowledge, expertise, and best practices at clinical research sites to meet the needs of an increasingly diverse United States population and to provide knowledge and solutions to aid sites in more successfully including diverse patients in clinical research. Keep an eye out for more from this program.

Entries for the popular Site Patient Enrollment Innovation Award (SPRIA) and Site Tank are now open. Both of these competitions provide an opportunity for sites to showcase their innovative ideas.

Last year the finalist for Site Tank immediately received industry support to further develop their idea. Go to the Global Site Solutions Summit website to find out more about these competitions under the “Agenda” tab.

SCRS continues to work to provide a wide variety of educational offerings for members. Check the website for the latest listing of webinars, and register for the Global Site Solutions Summit if you haven’t already.

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Complimentary copies of these white papers and more can be found here.

A Principal Investigator Speaks Flux or Stasis?

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BOUT 2,500 YEARS AGO IN ANCIENT GREECE, there One response is that the regulatory environment is what were two philosophers with contractionary views. stands in the way. These new e-tools are not validated to the Parmenides had a vision that nothing really changed, requirements of the regulatory bodies. The regulatory bodies but only our view of reality changed. Heraclitus stated that want to see certificates to prove you are capable of working everything is constantly changing; even wading through a with that equipment. And so the finger-pointing continues. little river is never the same, as new water flows around your Now let’s have a look at these arguments. Do the regulatory feet. And so you can divide the world into those who thrive bodies really want a certificate that I can handle an on consistency (the stasis of Parmenides) and those who EKG machine, in the sense that I know where the on/off thrive on change (the flux of Heraclitus). button is, can transmit data, and know how to replace Those who thrive on stasis the paper? I have taken will try to avoid changes training programs where Who is keeping us from moving forward, and prevent them in that is the testing the and is the innovation gap between drug sponsor provided for the whatever way possible in order to continue tradition. certification on their EKG development and the rest of the world If necessary, they will equipment- not whether getting increasingly larger? use social pressure and I could recognize a the power of laws and deviation in the EKG that is regulations to maintain considered an exclusion. It conventional standards and values. On the opposite side is unlikely that this sponsor requirement was truly a regulatory are those who thrive in the world of Heraclitus, wanting a body requirement. society in which experiments and innovation are the norm, Sites are not as rejecting of technology as they might first even if this might result in disrupting the traditional way of appear. Sites often have their own technology and portals doing things. implemented that work fine for them. But sites don’t like This was the opening by the president of Dutch Association technologies that don’t work. We had a case in which of Pharmaceutical Medicines in the Netherlands at a onea patient used a blood pressure device for a 24-hour day conference on innovation. We live in a time when measurement. The cuff ruptured, and we were not allowed everything seems to be changing quickly. The financial, to repeat the measurement since the protocol stated that commerce, transportation and entertainment industries rescreening was not allowed. So our very committed patient, constantly adapt to all the new technologies as our day-towho had already completed a two-week washout to enter day environment consisting of bricks and clicks becomes the trial, was lost to the study. more virtual.

Is it really one party that is withholding the innovation? Or And yet drug development is taking longer, timelines are are we stuck in our ways and perhaps even scared to do it extending, costs are going up, and somehow innovations another way? No one involved in clinical trials wants issues aren’t happening at the same rate. Why is this? Who isn’t too during inspections or audits. Sites don’t want to have these keen on innovations? Is it the sponsors, the CROs, the sites? battles on individual studies where they risk losing that Are we scared of the regulatory bodies? Who is keeping us sponsor or CRO for the next trial. from moving forward, and is the innovation gap between Let’s face it- technology is here to stay. A steady beat of drug development and the rest of the world getting technology has been adopted over the last 30 years: IVRS, increasingly larger?

EDC, CTMS, etc. Even those stand-alone e-diaries were I hear people say that sites are “old fashioned.” We don’t at one time a disruptive innovation. Implementation is by embrace technologies; we stick to paper for a lot of things, far not going at the same speed as technology in the rest don’t like e-diaries, portals, etc. We want face-to-face rather of our society. But not adapting because we are scared, than online investigator meetings. At the same time, sites or blaming the other for withholding progress has never claim the industry is very conservative, as the technologies worked. So I think we should join hands and go for it. Let’s used in clinical trials are outdated, and don’t function all find some Heraclitus in ourselves and innovate together properly considering the options that are now available. constructively. We all can only benefit from it.

And sponsors and CROs request sites to maintain paper logs and print things that are available in portals.

For example, we still hand out stand-alone e-diaries on old Vivienne van de Walle, MD, PhD, CPI technology, rather than using apps installed on the patient’s Director & Owner phone. The clinical trial applications that we use still don’t PT&R communicate with each other, and require numerous logins SCRS Leadership Council Member and multiple portals, even for the same study.

MySCRS.org | 15

Patient Perspective

The Role of Patient Navigators

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he clinical trial experience is one I have become intimately familiar with, thanks to a Stage IV melanoma diagnosis nearly five years ago. Having communicated with hundreds of other patients, primarily in the cancer world, there are multitudes of reasons for the lack of participation in clinical trials. Reasons include the negative perception of being a guinea pig, missed opportunities like “I couldn’t find a trial” or “I was shut out” due to pre-existing conditions, prior treatment history, or a filled cohort.

How patients perceive the clinical trial experience may affect their willingness to consider trials as a treatment option and, ultimately, increase trial participation. Stagnant trial participation numbers1 indicate that longtime stigmas and lackluster physician promotion and patient acceptance continues. While there are many efforts to increase awareness, simply being more effective in helping patients during the critical diagnosis phase could bring a

“lay navigators,” nurses who were not involved in clinical research, who engaged with the patient during the treatment selection process and clinical trial activities. They provided support and helped steer trial-eligible patients through the trial landscape.

This strategy, supported by the National Cancer Institute and the American Society of Clinical Oncology,3 aligns with many of the issues patients present to their peers online. A significant portion of the interactions inside online support groups I am familiar with revolves around more experienced patients sharing their insights with those who are starting down a similar path and staring down similar daunting obstacles to recovery. Veterans helping newbies: this model is organically replicated across nearly every demographic and population where peers influence and interact with one another in professional, social, and personal settings.

Having been on trials at two vastly different research sites, I can attest that clinical trials navigation is an arduous process when done in conjunction with competing initiatives – understanding diagnoses, dealing with the emotions of fear and uncertainty, and juggling health, work, family, bills, and the many details of life that are not stopping because you may be unwell. Few have the background on a specific disease and an understanding of the trial options and processes prior to their first diagnosis. Patients are jumping into an unknown ocean, and while those currents may look calm from the shore, they can quickly engulf and overwhelm.

The limited research into patient navigation supports the notion that assistance in trial understanding promotes greater trial participation. larger slice of the existing population into clinical trials.

The limited research into patient navigation supports the notion that assistance in trial understanding promotes greater trial participation. One study involved using patient navigators to assist in walking through the trial before deciding on treatment options.2 These navigators were

T.J.’s experience with melanoma studies has inspired initiatives at SCRS. View our video to find out more.

16 | InSite - Summer 2017

How can you bring navigation into your site? What are you doing to promote more than just awareness, but assistance that truly helps patients become engaged in clinical research? A poster is nice, a listing of open trials certainly helps, but are you making the right efforts to proactively reach the targeted constituents? Are you offering your patients (and potential patients) more than just marketing and informational materials?

You, the site, are often the first or second interaction a person will have post-diagnosis. There is significant opportunity to positively influence the comprehension of a clinical trial and what it means to the patient.

Having been on trials at two vastly different research sites, I can attest that clinical trials navigation is an arduous process when done in conjunction with competing initiatives – understanding diagnoses, dealing with the emotions of fear and uncertainty, and juggling health, work, family, bills, and the many details of life that are not stopping because you may be unwell.

Regardless of the ultimate treatment decision, aiding them in understanding those choices will continue to catapult clinical trials into more treatment conversations with more patients.

Patients can, and will, find other patients to discuss trial and treatment options, particularly in our online and social media-connected world. If those patients are at your site, and they are considering your trial, doesn’t it make sense to give them the decision support that they are going to seek out regardless? Helping the patient get a clear understanding of their options, and what each of them involves, is what “we” do with each other online. Replicate

that trusted, knowledgeable, and empathetic environment on site and you will be taking a big step towards navigating patients to trials when it is their best option.

1 Memorial Sloan Kettering Cancer Center. Despite pressing need, survey finds most Americans unlikely to enroll in clinical trials. Published May 23, 2016. Accessed May 2017 from: https://www.mskcc.org/press-releases/despite-pressing-need-survey-finds-mostamericans-unlikely-enroll-clinical-trials.

Cartmell KB, Bonilha HS, Matson T, et al. Patient participation in cancer clinical trials: A pilot test of lay navigation. Contemporary Clinical Trials Communications. 2016;3:86-93.

2

3 Denicoff AM, McCaskill-Stevens W, Grubbs SS, et al. The National Cancer InstituteAmerican Society of Clinical Oncology Cancer Trial Accrual Symposium: summary and recommendations. J Oncol Pract. 2013;9(6):267-76.

MySCRS.org | 17

CLINICAL TRIAL

DIVERSITY

Diversity of Religious Identification and Practices

A

s the period of Ramadan draws to a close, when Muslim people fast from dawn to sunset, the issue of how religious diversity affects health and clinical studies is brought to the forefront. This month also saw new research about how religious thoughts affect blood sugar control in Type II Diabetics. Religious beliefs and practices’ effect on diabetes is one example that illustrates why clinical research sites need to be aware of religious diversity.

For Muslim diabetics, Ramadan poses a particular challenge. Omid Safi, director of the Islamic Studies Center at Duke University tried to fast during Ramadan, but then he passed out. He now eats during the day during Ramadan, but he reports experiencing some emotional distress.1

Obviously these religious considerations would affect enrollment and compliance in a diabetes study and would likely affect outcomes. At the very least, a clinical research professional should ask about fasting practices where relevant.

Religious beliefs and practices’ effect on diabetes is one example that illustrates why clinical research sites need to be aware of religious diversity.

Despite advice from religious scholars and medical professionals that fasting is not required for diabetics, a 2015 study reported that 94% of Muslim Type II Diabetics fasted for more than 15 days of Ramadan.2 Others select ad hoc fasting regimens, such as fasting for a shorted period of time every day. Likewise, Christian discussion forums include numerous discussions as people with diabetes develop their own ad hoc fasting regimens for Lent.

Aware of the challenges of Muslim diabetics, in 2016 the International Diabetes Federation partnered with the Diabetes and Ramadan International Alliance and produced a free guide for health care professionals caring for Muslim diabetics.3 This guide provides information on determining the risk level of fasting for a particular patient, as well as information on educating the patient about managing fasting. The United States Conference of Catholic Bishops also mentions diabetes in their “Questions and Answers about Lent and Lenten Practices.”4 In June of 2017, research on how religious coping strategies in couples affect a spouse with Type II Diabetes was published.5 Couples were recruited from southern California clinics and faith-based organizations. This research found that shared management of diabetes between both spouses resulted in better blood sugar control. This shared management and improved blood sugar control was associated with positive religious coping strategies in the nondiabetic spouse. Negative religious coping strategies in the diabetic spouse were associated with worse blood sugar control.

Negative religious coping involves thoughts such as a being abandoned by God. Despite these effects of religious thoughts and experiences on patient health, a survey of psychologists found that religious coping is discussed with less than 30% of patients.6 Would one expect that endocrinologists are any more likely 18 | InSite - Summer 2017

to explore religious coping than psychologists?

Other research suggests that religion may be associated with an individual’s likelihood to be willing to participate in a clinical trial, particularly in specific intersections of religion and ethnicity such as with Catholic Hispanic people in the United States.7 Diversity awareness has many facets and is a continual process of becoming increasingly informed about the heterogeneity of the clinical trial population. In the United States alone, there are at least 300 distinct religious identifications and only two have been discussed in this article. Awareness of religious diversity is just one facet to explore to help all patients become aware of their clinical trial options and to understand how study participation interacts with a patient’s particular religious beliefs and practices.

Thank you to SCRS member Mohammad A. Millwala, CEO of DM Clinical Research, for input on this article.

Khan A. In Ramadan, Muslim diabetes toe a fine line. Religion News Service. 21 June 2017.

Accessed from: http://religionnews.com/2017/06/21/in-ramadan-muslim-diabetics-toe-afine-line/

1

Babineaux SM et al. Multi-country retrospective observational study of the management and outcomes of patients with type 2 diabetes during Ramada in 2010 (CREED). Diabetes Medicine. June 2015;32(6):819-28.

2

International Diabetes Federation and Diabetes and Ramadan International Alliance.

Diabetes and Ramadan: Practical Guidelines. 13 April 2016. Accessed from: https://issuu. com/int._diabetes_federation/docs/idf-dar_guidelines_april_2016_low_r

3

United States Conference of Catholic Bishops. Questions and answers about Lent and Lenten practices. Accessed from: http://www.usccb.org/prayer-and-worship/liturgical-year/ lent/questions-and-answers-about-lent.cfm

4

Fincham FD, et al. Religious coping and glycemic control in couples with type 2 diabetes.

Journal of Marital Family Therapy. 7 June 2017. Accessed from: http://onlinelibrary.wiley.com/ doi/10.1111/jmft.12241/full

5

Hathaway WL, Scott SY, Garver SA. Assessing religious/spiritual functioning: A neglected domain in clinical practice? Professional Psychology: Research and Practice. February 2004;35(1):97-104

6

Daverio-Zanetti S, et al. Is religiosity related to attitudes toward clinical trials participation?

Journal of Cancer Education. June 2015;30(2)220-4.

7

METRICS THAT MATTER

SCRS SITE LANDSCAPE SURVEY

T

HE ANNUAL SCRS SITE LANDSCAPE SURVEY revealed that 66% of sites have less than three months’ worth of operating cash. This is up from the 65% of sites reported in 2014. All the way up to the site category of up to $2.1 million in annual site revenue, more than half of sites have less than three months’ worth of operating cash.

Site Revenue & Less Than 3 Mos. Operating Cash

Considering that sites also reported a drop in profit margin from 20% in 2011 to 13% in 2016, there is increasing pressure on cash flow. Adding to this, sites report that 58% of U.S. study contracts and 37% of contracts outside of the U.S. have a holdback, meaning that a percentage of the study revenue isn’t received until the end of the study, possibly not until months after the study ends.

These core site sustainability issues are just part of the reason SCRS advocates for monthly site payments.

We Are Seeking Columnists Please contact Mary D'Rozario Director of Communications mary.drozario@myscrs.org

| 919.890.5513 MySCRS.org | 19

5

Ways Sites Can Prepare st of the 21 Century T

HE 21ST CENTURY CURES ACT (“THE ACT”), passed by Congress and signed into law December 2016, represents the most significant milestone in many years for the conduct of human research aimed at new drug and medical device development. Parts of this law will go into effect now and other parts will be implemented over the next five years.1

Several sections of the Act affect the ultimate cooperation and work among regulators, sponsors, and clinical trial sites. A major section affecting clinical trial sites is the Guidance for Industry and FDA Staff: Qualification Process for Drug Development Tools.2 This Guidance document sets up a multi-step process for drug and biologics FDA submissions where several different forms of surrogate information may be considered along with the traditional clinical trial data.

The initiatives from the Act will increase the requirements for quality management and expertise of clinical trial facilities, as well as their qualification for studies in all therapeutic areas.

The FDA defines drug development tools (DDT) as a conclusive and specific interpretation and application in drug development and regulatory process using biomarkers, clinical outcomes assessments, and animal models, as well as other non-traditional patient-centric sources of data.2 The initiatives from the Act will increase the requirements for quality management and expertise of clinical trial facilities, as well as their qualification for studies in all therapeutic areas. This DDT approach encourages the supplementation of traditional clinical outcomes assessments (traditional clinical research) using: • Data gathered from real world experience • Patient experience data and patient-focused drug development data • Broader use of novel adaptive rolling clinical trial design and decision making • Collection of biomarker data (blood and other tissue collection) that is treatment-specific

There is now a much broader definition of clinical research, and advances in site management should be a strong consideration for any site participating in twenty-first-century clinical research.

20 | InSite - Summer 2017

for Implementation Cures Act How can clinical trial sites prepare and show sponsors and contract research organizations (CROs) that they are ready and capable of handling this new integrated clinical research model?

1 2 3

Sites can prepare for the impact of this new regulatory process by providing TRAINING ON THE REGULATORY REQUIREMENTS. Training should include the new methods associated with collecting, analyzing, measuring, managing, and reporting on patient experience during the trial.

Sites should consider HIRING A SPECIFIC SUBJECT (PATIENT) ADVOCATE AND COLLECTOR OF PATIENT-SPECIFIC INFORMATION regarding their communications, experiences, and satisfaction. This advocate will administer and evaluate questionnaires and provide patient follow-up (e.g., to determine quality of experience).

EXPECT THE SITE QUALIFICATION PROCESS TO BE MORE PATIENT-CENTRIC and aimed at site knowledge of good clinical practices (GCP), biomarker handling, and adaptive design protocol. More emphasis will be placed on patient volume, practice expertise (per usual), and good understanding of patient diaries, questionnaires, and quality-of life-outcomes, along with biomarker-related health outcomes.

4

Qualified personnel must be TRAINED ON THE HANDLING OF BIOMARKER DATA COLLECTION FOR THERAPEUTIC INTERPRETATION PURPOSES. Medical sites traditionally use the blood draw process during the protocol data collection; however, if the clinical trial is going to use a particular biomarker to track drug performance, the site should have a staff member trained in collection conditions and handling and shipping requirements of these samples per specifications of the sponsor.

TRAIN STAFF TO UNDERSTAND THE DIFFERENCE BETWEEN CLINICAL OUTCOMES ASSESSMENTS AND OTHER TOOLS. These other tools include data gathered from real world experience, patient experience data, patient-focused drug development data, use of novel adaptive clinical trial design, and proof of staff knowledge of collection, handling, and storage of biomarker data (e.g., blood and other tissue collection). These biomarkers are treatment-specific to the goals of the protocol and the needs of the new drug application (NDA) preparation

5

One of the mechanisms associated with speed to market is the encouragement of the use of DDTs. These are meant to allow more information other than traditional clinical outcome assessments to influence the approval process.

These additional tools affect the expectations of sponsors looking to work with qualified sites. There is now a much broader definition of clinical research, and advances in site management should be a strong consideration for any site participating in twenty-first-century clinical research.3

1

114th U.S. Congress, 2nd Session. 21st Century Cures Act, H.R. 34. December 13, 2016.

US Food and Drug Administration. Guidance for Industry and FDA Staff: Qualification Process for Drug Development Tools. January 2014. Accessed April 2017 from: https://www.fda.gov/downloads/drugs/guidances/ucm230597.pdf.

2

3 Touch A. Understanding the 21st Century Cures Act. January 2017. Accessed April 2017 from: http://www.propharmagroup.com/blog/understanding-21st-century-cures-actpart-i.

Dr. Alan Touch Director Product Development Program Management, ProPharma Group

MySCRS.org | 21

Association of Clinical Research Organizations (ACRO) ACRO Releases “Right to Try” Policy Statement Over the past few years, legislation that would give terminally ill patients access to unapproved treatments, known as “Right to Try,” has gained momentum in a number of states and now in the U.S. Congress. In response to this legislation, ACRO has released the following policy statement, which is also available on the ACRO website.1

I

N 2015, ALL BUT 10 OF 1,278 COMPASSIONATE USE REQUESTS (99.2%) were approved by the FDA (Food and Drug Administration). Applicants usually receive responses within four days of applying, and a recently streamlined FDA form takes about 45 minutes to complete.2 Additionally, average response time for emergency use is one day or less. Provisions in the 21st Century Cures Act will further strengthen the FDA’s Expanded Access program by requiring greater clarity on the policies of pharmaceutical companies and enhancing communication.

in clinical research; however, Right to Try places both objectives at risk. Recent federal Right-to-Try proposals would prevent FDA from considering adverse events arising out of the use of a product through the Right-to-

In 2015, all but 10 of 1,278 compassionate use requests (99.2%) were approved by the FDA.

To further improve the accessibility of information about Expanded Access programs for patients and their providers, the Reagan-Udall Foundation plans to introduce an Expanded Access Navigator, a portal of online resources that includes educational content, tools, and a contact directory. The foundation hopes to promote the use of Compassionate Use through this effort.

This portal is expected to launch in June 2017.

Try path. This would undermine patient safety protections not only for the patients accessing the product outside of a clinical trial but also for the patients using the product once it is on the market.

ACRO notes the European Medicines Agency (EMA) has also provided recommendations on Compassionate Use. Similar to FDA’s Compassionate Use policy, the EMA recommendation states that such compassionate access to investigational (non-approved) drugs should only be used when a patient is left without other treatment options. ACRO generally supports policies that conform to Given the FDA’s implementation of its current international norms for patient safety and best practices Compassionate Use policy, it is unclear that Right-to-Try for clinical research. ACRO legislation would provide any believes that any effort added benefit for individual Recent federal Right-to-Try proposals to make investigational patients in terms of access. would prevent FDA from considering therapies available to Such legislation would, adverse events arising out of the use of patients outside of a clinical however, create potentially should include proper significant concerns for patient a product through the Right-to-Try path. trial patient protections and avoid safety. This legislation could also compromising the current FDA lead to ethical challenges for safety and effectiveness review process. For these reasons, future clinical research, weakening the informed consent ACRO does not support Right-to-Try legislation. process by diminishing the safety and risk/benefit data that should be available to every patient.

By circumventing the FDA, Right to Try eliminates utilizing the agency’s objectivity, expertise and knowledge of treatments in various stages of development, in presenting the best options to the patient. Conversely, under Expanded Access, FDA review can require changes to treatment plans that are most beneficial to patients.

The mission of ACRO member companies is to ensure the safety of human subjects and maintain data integrity

22 | InSite - Summer 2017

Association of Clinical Research Organizations. Right to try ACRO policy statement.

Published May 22, 2017. Accessed May 2017 from: http://www.acrohealth.org/right-tryacro-policy-statement/.

1

Lurie P. Exploring a right to try for terminally ill patients. Oral statement at: Committee On Homeland Security and Government Affairs, U.S. Senate; September 22, 2016; Washington, D.C. Accessed May 2017 from: https://www.fda.gov/NewsEvents/Testimony/ ucm522044.htm.

2

Please Follow ACRO on Twitter

@ACROHealth

Ask the Auditor

Actionable Advice from GCP Experts Clinical Care Versus Clinical Research Question:

How can study sites avoid falling into the standard of care trap?

Answer:

Principal investigators (PI) know that they and their site staff are required to follow the investigational plan, even when the study protocol is a departure from the PI’s standard of care.1 Protocol trumps practice every time.

conditions are also familiar with the complications that ordinarily accompany them. A nephrologist, for instance, knows that a patient with end-stage renal disease frequently suffers from bloat. This insight informs the treatment a specialist gives their patient, yet may work against the PI whose study participant complains of GI discomfort. How? Knowing bloat is common for renal patients, a PI may fail to report a stomach ache as an adverse event (AE) because it’s typical

This principle seems clear enough, but complying Years of practicing medicine have reinforced the with it is not always as straightforward as it sounds. way PIs respond to medical situations, yet those Years of practicing medicine have reinforced the way PIs respond to medical situations, esponses might run counter to the investigational yet those responses might run counter to the plan with which the PI agreed to comply. investigational plan with which the PI agreed to comply. PI experience with a disease can color the and expected. “Renal patients tend to get a buildup of fluid interpretation of the protocol and lead a PI to overlook data between dialysis sessions. If I recorded every GI incident, I’d the site should be collecting. Even before a study starts, PIs be recording AEs all day,” the PI might think. At its surface, need to consider how their commitment to the standard of this PI’s argument sounds reasonable, but what if the study care will affect their enrollment decisions or their ability to drug itself is contributing to the participant’s GI discomfort? In conduct the study at all. order to assess the drug’s gastrointestinal effect, the PI must What’s Your Standard of Care? document the frequency and severity of all GI events.

When deciding whether or not to conduct a particular Lab values that are either above or below normal range clinical study, a PI needs to determine whether the protocol are also prime candidates for AE underreporting. “Of is aligned with practice norms. An early phase trial might course the participant’s liver enzyme is high – we’re testing exclude a medication that is part of a practice’s routine a cholesterol drug.” therapy. Studies that are placebo-controlled, feature a specific comparator drug, or include a washout period may Summarizing Care versus Research be similarly unsuitable. Perhaps the protocol is a good match Any GCP (good clinical practice) course worth its registration for some patients but incompatible with a PI’s standard of fee will discuss the distinction between standard of care and care for others. The PI will need to clearly communicate this the study protocol. In practice, the distinction is not always to the study coordinator and factor it into the enrollment as obvious as training sessions might suggest. When providing estimates provided to sponsors. clinical care, the PI’s experience informs the type of patient data they typically record. They’re used to doing what’s The Road to Deviation is Paved with Good Intentions best for each of their patients, so following every protocol Therapeutic misconception – a well-documented procedure for every study participant can feel unnatural. phenomenon in clinical research – occurs when a study The protocol may limit the number of patients a PI feels participant “fails to appreciate the distinction between the comfortable enrolling. A PI may even decide to decline a 2 imperatives of clinical research and of ordinary treatment.” study outright if it doesn’t meet the standard of care that their Participants are not alone in this. Researchers blur the patients have come to expect. distinction themselves when they conduct procedures that are consistent with clinical care but deviate from the study Food and Drug Administration. FDA Investigational New Drug Application, 21 CFR 312.60. protocol. This may be particularly true for PIs who recruit Accessed May 2017 from: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/ CFRSearch.cfm?fr=312.60 participants from their own practices. An endocrinologist Lidz CW, Appelbaum PS. The therapeutic misconception: problems and solutions. Med might ordinarily reduce dosage for a particularly diminutive Care. 2002; 40(9 Suppl): V55-V63. patient. A pulmonologist would skip a scheduled chest x-ray she felt wasn’t needed to avoid exposing her patient to unnecessary radiation. An orthopedic surgeon may Lauren Kelley, CCRP decide his patient needs an additional day of recovery Associate Director of GCP Compliance before attempting her first walk. In a clinical care setting, Polaris Compliance Consultants these decisions may be sound and made in an individual patient’s best interest. In a clinical trial, if they differ from the investigational plan, they’re protocol deviations.

Laurie Meehan 1

2

Par for the Course, But Still an Adverse Event Specialists who have experience treating particular

Social Media Manager Polaris Compliance Consultants

MySCRS.org | 23

Global Site Solutions Summit

REFLECTIONS

Quick Tips for Better Relationships with Sponsors

I

had the privilege of leading a master workshop at the last Global Site Solutions Summit titled “Sites and Sponsors: Working Together to Define and Achieve Common Goals.” With half attendees from sites, and the other half from sponsors/CROs, the diversity of the group made for insightful discussion on what sites want sponsors to know about their challenges and vice versa. Several key themes emerged with actionable takeaways for sites to improve their relationships with sponsors and CROs.

Accurately Predicting Enrollment

Defining targets and estimating realistic enrollment numbers is a challenge, with most trials needing to double their original timelines to meet enrollment goals, and 48% of sites under-enrolling participants.1 To make better estimates, sites can:

•

Showcase past enrollment performance. Track metrics and share how your site has done on similar studies.

•

Don’t just tell the sponsor what you think they want to hear. Be honest about competing studies and don’t inflate enrollment estimates so you will be selected.

Give a thoughtful answer and be conservative in your estimate. With almost a fifth of studies closed or terminated due to unsuccessful or insufficient accrual,2 sponsors and CROs would rather have sites underestimate enrollment than overestimate. Being honest will help your chances of being selected for future studies.

•

Update enrollment estimates once you have more information. Often the initial enrollment estimate is based on preliminary abstracts and not a final protocol with full inclusion/exclusion criteria. Similarly, the most frequent changes stemming from amendments are associated with modifications and revisions to participant demographics and eligibility criteria. This substantially lowers the actual number of patients screened and enrolled relative to the plan as compared to protocols without any amendments.3 Update your estimates upon receiving new information so the sponsor can plan accordingly.

•

Pick up the phone and talk to the sponsor. Find ways to thoughtfully explain what you need and why you need it, in order to understand the true priorities and requested information, and how your requests will ultimately fulfill the sponsor’s goals.

•

Do a reverse feasibility questionnaire. Flip around the traditional approach of completing a lengthy questionnaire and instead proactively ask sponsors and CROs for the information you need to know whether the study is a good fit. Be vocal and decisive about what you need.

•

Know your deal breakers and when to walk away.

Identify the “must-haves” and “nice-to-haves” needed from the sponsor/CRO upfront during feasibility that impact whether you move forward with a study, then communicate and stick to them. Serial trial openers end up competing against themselves. Smart sites know when to decline a study, communicating their rationale to the sponsor to keep the relationship in good spirits for future opportunities.

Evaluating Protocol Complexity As protocols become increasingly complicated, sites have to be cautious when deciding if they can realistically take on any given trial. To have a clear picture of what conducting the trial will entail, sites must:

•

Identify staff bandwidth and required resources.

Determine who is needed for the study and make sure they will be flexible enough to provide continuity throughout the trial and any possible delays. After all, 57% of all protocols have at least one substantial global amendment, each of which causes the study to take three months longer than expected.3 Make sure you are fundamentally well-suited and prepared.

Do a break-even analysis, considering the scientific, financial, and resource (both physical and staff) perspectives.

•

Practice walking through the motions. Take a patient through the first few visits in advance to work out the kinks before scaling patient enrollment. Of course, tell the sponsor what you are doing and why. If this isn’t possible, it could be mocked with staff to do an analysis of communication flow, use of technology, procedures, and scheduling.

•

Evaluate if the study went according to plan. Look back and see if expectations were met and identify where inaccurate estimates and prolonged activities

Improving Feasibility Assessments Feasibility questionnaires aren’t always the most effective vehicle to determine which sites will truly be successful on a protocol. To prevent a lot of work from going into study startup only to realize there is incompatibility down the road, sites should:

24 | InSite - Summer 2017

Get the Most From Your SCRS Membership Profile your site on the SCRS Site Directory occurred in the process. Give feedback to the sponsor and use this information to decide which trials to take on in the future.

The biggest issues sponsors and sites face when working together involve communication. By having open and honest conversations, being proactive and aligning expectations upfront, sites can finish trials on time and in good spirits with their sponsor and CRO counterparts.

1 Tufts Center for the Study of Drug Development. 89% of trials meet enrollment, but timelines slip, half of sites under-enroll. Impact Report. 2013;15(1). Accessed June 2017 from: http:// csdd.tufts.edu/files/uploads/jan-feb_2013_ir_summary.pdf.

2 Carlisle B, Kimmelman J, Ramsay T, MacKinnon N. Unsuccessful trial accrual and human subjects protections: An empirical analysis of recently closed trials. Clinical Trials.

2015;12(1):77-83.

3 Tufts Center for the Study of Drug Development. Amendments reduce number of patients, but at high cost, longer study times. Impact Report. 2016;18(1). Accessed June 2017 from: http://csdd.tufts.edu/files/uploads/Summary-JanFebIR2016_.pdf.

Laura Hilty Vice President, Product Management and Operations Nimblify SCRS Global Impact Partner

Access the SCRS Trial Opportunity Platform (TOP™) Join webinars & receive up to 36 contact hour credits Monthly Webinars Good Clinical Practices (GCP) Good Business Practices (GBP™) Good Technology Practices (GTP™) Multi-Week Webinars Inspection Readiness™ The Hidden Cost of Conducting Clinical Research™ Research Administration 101 Complete Good Clinical Practice training recognized by TransCelerate members Communicate with SCRS peers through an SCRS online forum Contribute to the industry dialogue through an SCRS Site Advocacy Group (SAG™) Receive SCRS’ global journal, InSite™ Access SCRS’ white papers and position papers Attend Site Solutions Summits™ at an exclusive membership discount Proudly display the SCRS logo on your company material

For more information members@myscrs.org 410.696.5080 press 2

MySCRS.org | 25

White Paper Highlight Looking Toward the eSource Revolution

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N MAY, SCRS IN COLLABORATION WITH CLINICAL INK Data from the survey indicated that 64% of sites published Why is Clinical Source Data Still Collected use an EMR system, but 96% of sites still collect on Paper? Building on data from the Research Site clinical research data on paper.

Source Survey, this white paper reports that paper source document creation is a task completed at One reason is that EMRs themselves frequently contain many sites at significant expense and risk to quality. This errors which also introduce risk. For example, inclusion task continues despite widespread adoption of electronic criteria are often difficult to determine only from the medical records (EMRs) and the development of a EMR without querying further about the accuracy of the regulatory framework for eSource. In this white paper, the information recorded, such as whether a patient did, in task of paper source document creation and transcription fact, take a contraindicated medication discussed in was explored and the total cost calculated. the record. The second reason is that despite regulations Data from the survey indicated that 64% of sites use an EMR being developed for the use of eSource, where data system, but 96% of sites still collect clinical research data recorded for the medical record are automatically used on paper. Even academic medical centers, with an EMR as study data, eSource has not yet been widely adopted adoption rate of 87%, use paper source for research at 79% by the industry. of centers. Oncology studies, where study procedures and The opportunity to implement eSource offers significant existing EMR configurations are well matched, are likely to cost savings while freeing up site staff to focus on their account for a large part of the 21% of academic medical patients. When sites were asked if it could be helpful to centers that reported using electronic records for research. electronically record study data in eSource during the Creation of paper forms to collect clinical research data patient visit instead of transcribing it into EDC after the visit, is a significant Estimated Resource Capital Expenditure on Creating Source Forms expense at clinical research sites, taking both financial and study coordinator resources away from other tasks. Study coordinators at 34% of sites took more than 33 hours per study to * Based on an average annual salary of $60,000; assumes 1.5 coordinator time for project manager/PI review and approval of source create source forms. document *** Salary based on median between $45,000 and $75,000 for research and nurse coordinator average salaries.8 forms, with an ** Lower estimates are the hourly rate in the first column, weighted by the percentage of sites in the survey reporting that time expenditure category. Upper estimates include a 25% increase to the lower estimate in order to accommodate sites that take more time. expense of up to $1,423 per study. The average clinical research site spends $14 to 79% answered that it would be helpful or extremely helpful. $17 thousand per year creating source document forms.

It is likely that the acceptance and implementation of The total amount spent on creating source documents for eSource will continue to rise as sponsors and CROs seek clinical research is more than $18 million per year, just in the new avenues to reduce cost and risk. SCRS will continue to United States. represent the voice of the site as eSource and other new Transcribing the data collected on those forms back to case technologies are introduced into the research environment. report forms costs an average of $459 per patient per study, Go here to download your complimentary copy of resulting in a total cost to the clinical research enterprise of this new white paper, Why Is Clinical Source Data Still more than $55 million per year in the U.S. This transcription Collected on Paper? process generates additional monitoring expenses and introduces risk in the form of transcription errors.

Paper source documents are used despite the expense and risk for two primary reasons.

26 | InSite - Summer 2017

The average clinical research site spends $14 to $17 thousand per year creating source document forms.

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How Can the

RIGHT RTSM SOLUTION Solve Problems Commonly Faced by Sites?

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S CLINICAL TRIAL INFORMATION SYSTEMS become more interrelated, problems that once took many steps for site and sponsor personnel to solve are now solved automatically.

While this automation is appreciated by everyone, it can move processes into a “black box” that can sometimes leave users confused. Questions like why is the system telling me that the subject cannot be dispensed medication when there is sufficient medication on the shelf? In addition, it is not uncommon for sites to have to record data into multiple systems. Keeping track of the systems and the corresponding login information can be frustrating. This can lead to more confusion, data entry errors, and data reconciliation issues.

additional paperwork and approvals can greatly enhance the user experience for site personnel. No more making phone calls and waiting for a reply while the subject is waiting on site. No more faxing or emailing accountability spreadsheets back and forth trying to figure out what is going on.

Consider a scenario where data has been incorrectly recorded - perhaps a drug kit was errantly pulled from the shelf or the data that determines stratification was misentered. Mistakes happen, and with multiple pieces of data being captured daily, most sites have had this experience at least once.

Sites can advocate for RTSM solutions that deliver on the promise of a site-centric approach. Site personnel benefit from these key features:

Consider another situation where the site entered incorrect vitals/weight/other information, and the system doesn’t allow the subject to be randomized.

Or the site is not able to dispense medication to a subject because a shipment is not received in the system, although the medication is present on the shelf. These are common scenarios that most sites have faced.

In this age of rapidly evolving technology, with so much happening so fast, the challenge that sponsors and CROs face is the selection and use of the right technology that fits the needs of the clinical trials sites and users.

With the right Randomization and Trial Supply Management (RTSM) solution, these problems can be solved immediately, especially while the subject is on site. Consider the improvement in trial conduct if the RTSM system provides immediate feedback regarding the reason for the randomization error or the unable to dispense error.

There are existing solutions that allow for simplified data correction mechanisms. Site awareness of the capabilities of these systems allows sites to advocate for systems that meet site needs and solve site problems. An RTSM solution that enables data corrections to be made quickly without mounds of

The key is to look for RTSM solutions that simplify the user experience, increase efficiency, and provide a simple and unified source of data entry and an easy process of data correction. Implementing such a solution at the site allows site personnel more time to focus on trial management, quality data entry, and patient recruitment. It allows sites to focus on meeting primary endpoints in this age of increasing clinical trials complexity.

• Single source of data, minimizing duplicate data entry and data entry errors

• Single login, reducing the frustration of logging into multiple systems to synchronize data

• Reduction in training due to the simplified user experience

With the right RTSM solution the following can be achieved:

• Less confusion around data entry • Quicker identification and correction of data anomalies

• Easy data reconciliation and reporting • More time to manage site-patient relations and issue resolution

• Increased site efficiency • Greater dedication to the patient • Improved outcomes Electronic solutions do not have to be “black boxes.”

Solutions that are transparent to the user are easier for site personnel to use and contribute to quality in clinical trials.

Wade Wirta Managing Director Medidata Solutions SCRS Site Voice Partner

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Clinical Trials Transformation Initiative Update Reflecting on 2016: A Year of Action at CTTI

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S WE TRANSITION FROM SPRING TO SUMMER, we are confronted with a sense of renewal and excitement for opportunities that lie ahead, this is a great time to take stock of what we have accomplished. The Clinical Trials Transformation Initiative (CTTI) recently released its 2016 annual report, which describes the recommendations and resources we have made available to sites and other stakeholders to improve clinical trials. The report also provides examples of CTTI’s work being used to successfully confront leading challenges.

Here are some highlights on how we made a difference in clinical trials:

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We released tools to help organizations integrate recruitment planning throughout all stages of a clinical trial and to better engage all stakeholders, including investigators and coordinators, which can lead to increased clinical trial enrollment.

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We delivered actionable recommendations for how to organize and conduct data monitoring committees to enhance the quality of clinical trial oversight.

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To support organizations in adopting our early enrollment strategy for more feasible HABP/VABP trials, we enrolled >5,750 patients in a study to provide realworld evidence for this approach.

We have made important strides in creating more efficient and qualit- driven trials. As reflected in our mission statement, our work does not end when we issue recommendations.

Our commitment to actively drive adoption of improved practices will continue. In the annual report, you can read about how our work has been implemented at a variety of organizations across the clinical trial spectrum, including the Cystic Fibrosis Foundation, Eli Lilly, FasterCures, and UCB Pharmaceuticals.

Looking to the rest of 2017, CTTI will be sharing new strategies to curb the epidemic of investigators leaving clinical research, best practices for conducting clinical trials for regulatory purposes within registries, and actionable recommendations to support the use of mobile technology in regulatory submission trials, to name a few.

We hope you will be involved with us as an innovator and apply our evidence-based tools and recommendations to improve your clinical trials.

You can access our 2016 annual report, our tools and recommendations, and all the latest news about CTTI at ctti-clinicaltrials.org.

Pamela Tenaerts, MD, MBA Executive Director

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United Kingdom

“Clinical research in the UK has special opportunities and challenges which bring a unique perspective to the global community of sites.

Engaging UK investigators and site managers in the global community at SCRS supports site sustainability in the UK and around the globe.”

Christine Pierre, SCRS President Professor Martin Gibson of the National Institute for Health Research Clinical Research Network (NIHR CRN) is the SCRS Ambassador for the United Kingdom. The first SCRS research symposium in the UK is being held as this Journal goes to press in June 2017.

The role of the SCRS Ambassador is to support awareness and growth of SCRS in the local region, embodying the SCRS mission to “unify the voice of the global clinical research site community for

United Kingdom Fast Facts Population: 65.5 million Life Expectancy: 80.77 years Median Age: 40.1 years Literacy Rate: 99% at age 15 and above

greater site sustainability.”

“The NIHR Clinical Research Network (CRN) is delighted to be associated with the SCRS. This new relationship will provide broader access and integration with a global network of clinical research sites and further strengthens the reach and capability of both the NIHR networks and SCRS.” Professor Martin Gibson, Clinical Lead for Business Development, NIHR CRN MySCRS.org | 31

SCRS Webinar Spotlight Tackling Common Research Red Flags at the Site Level

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NA MARQUEZ, CEO OF MARQUEZ CLINICAL SITE PARTNERS, LLC and Sonya Robinson, Quality Control Manager at Florida Pulmonary Research Institute, LLC provided a webinar titled “Tackling Common Research Red Flags at the Site Level.” The objectives of this webinar were to identify red flags for audits and implement measures to avoid the most common audit findings.

Three of the most common audit findings are improper delegation of authority, inadequate drug accountability, and protocol nonadherence. The presentation focused on these three topics.

Conversely, if drug compliance is nothing more than accountability, something is missing. The reason the patient missed doses should be documented, as well as anything that was done to help the patient improve their dosing compliance.

On the topic of protocol compliance, Ms. Marquez and Ms. Robinson focused on inclusion/exclusion compliance.

They recommended creating a source document that is not merely a yes/no checklist but requires answering the question posed by the compliance item. For example, if the patient must weigh less than 160 kg, the source document should require writing the weight of the patient. Sometimes these questions are more complicated, using “and” or “or” qualifiers, which should be highlighted.

Ms. Marquez and Ms. Robinson encouraged sites to remember that the principal investigator is ultimately responsible for the delegation log. Sponsor-provided log templates may not meet all of the regulatory requirements; sites may Three of the most common audit findings want to have a standard operating procedure requiring their own delegation of authority, inadequate drug delegation log.

Issues with delegation logs they have seen include having vital signs and physical exam listed in the same column. These procedures are commonly performed by different people at a site and the individuals recording the vital signs are usually limited to that task by their licensing. Also, some key verbs can cause problems when placed in the same delegation column: collect, assess, evaluate, perform, review and obtain. For example, a nursing assistant may be able to “collect” vital signs, but by their licensure would not be able to “assess” vital signs. These tasks are likely to be delegated to different people; therefore, these verbs should not be in the same column.

and protocol nonadherence.

are improper accountability,

This inclusion/exclusion source document should be reviewed and signed by the principal investigator or delegated subinvestigator at the screening visit and again before randomization.

At each stage of the study, the fact that the subject is properly continuing in the study is documented. Likewise, at each stage of the study, if the subject discontinues this should also be thoroughly documented.

Of course, there are many areas in addition to inclusion/exclusion for protocol compliance to go wrong. Ms. Marquez and Ms. Robinson recommended reviewing the protocol thoroughly and considering where these By thinking ahead, the source document can be designed complications or mistakes could to guide the site users through these situations correctly. happen. By thinking ahead, the source document can be designed to guide the site users through these situations correctly.

Moving on to drug accountability, Ms. Marquez and Ms. Robinson pointed out that problems with drug Careful consideration of these three topics will greatly accountability are commonly generated from a reduce any site’s chances of an audit finding. misunderstanding of the purpose of the task. The final A recording of this webinar is available for SCRS members purpose of drug accountability is drug compliance. If the and GIP employees. drug accountability information cannot fully document drug compliance, something is missing.

32 | InSite - Summer 2017

Legal Lines Understanding the Medicare Secondary Payer Rule

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n our law practice, we frequently notice the same questions coming in from clients. In the past few months one of our most common client questions has been: What is the Medicare secondary payer rule, and how does it affect my contract?

Medicare billing rules are complex, but critical to understand.

This may be one of our drier columns but stay with me. When all parties understand the Medicare Secondary Payer law and the obligations it puts on sites and sponsors, it’s easier to find common language for the contract.

Sponsor shall pay for all reasonable and necessary medical expenses incurred by Study subjects for any medical care, including hospitalization, in the diagnosis and treatment of adverse reactions arising from the Study subject’s participation in the Study, to the extent not covered by or billable to a Study subject’s nongovernmental third party insurance.

We also see the Medicare Secondary Payer statute triggered in efforts by sponsors to cover other routine (noninvestigational) costs and services arising for uninsured or under-insured subjects participating in a clinical trial.

Although the Medicare rules allow the provider of the services (the hospital or physician) to waive charges in certain circumstances where the patient meets the requirements of an indigent care policy, they do not allow a sponsor to step in to cover the charges without triggering

The Medicare Secondary Payer law guarantees that Medicare is secondary to any primary payer for the health care costs of a Medicare beneficiary.1 If “payment has been made, or can reasonably be expected to be made” by another payer, whether or not it’s an insurance company, Medicare is prohibited by law to pay for the services. Therefore, if a When all parties understand the Medicare Secondary Payer sponsor of a clinical study elects law and the obligations it puts on sites and sponsors, it’s to pay for the routine costs of any items and services provided to a easier to find common language for the contract. study subject, the sponsor may only do so if the sponsor pays the Medicare Secondary Payer statute. The sponsor may the costs for those same items and services provided to all pay for the routine costs of items and services if the subject Medicare beneficiaries enrolled in the trial. Once a sponsor is covered by private insurance and the private insurance pays for some portion of the routine costs of an enrolled study denies payment, or if the study subject is uninsured, but subject, Medicare no longer has a legal obligation to pay for only if the sponsor also pays for all of the routine costs of those costs, and the sponsor has become the primary payer the items and services provided to Medicare patients in the pursuant to the Medicare Secondary Payer statute. study. Therefore, the sponsor may elect to (1) pay all of the The Medicare Secondary Payer statute most often arises Medicare patient’s costs and (2) the portion of the privately in the context of subject injury. In some cases, a sponsor insured patient’s costs after a denial by the private insurer. agrees to pay the costs of services provided in the diagnosis Compliance with the Medicare Secondary Payer statute and treatment of a study injury. In that case, we don’t need is important to both sponsors and sites. If everyone to worry about the Medicare Secondary Payer statute, understands the requirements of the statute, there is no because we know the sponsor is paying all costs. However, reason for this to be a topic that holds up contracts. if a sponsor has contractually agreed to pay for the costs of routine health care services provided for the diagnosis or treatment of an injury suffered as the result of clinical Social Security Administration. Exclusions from Coverage and Medicare as Secondary trial only to the extent such costs are not Payer. Social Security Act, Sec.1862(b), 42 U.S.C. §1395(y)(b). Accessed May 2017 from: https://www.ssa.gov/OP_Home/ssact/title18/1862.htm covered by a third party insurance payer, the sponsor must pay all the expenses of a Medicare beneficiary arising due to subject injury. In that case, your contract language should specifically address Molly Huggins, JD/MHA Huggins & Zuiker, LLP the coverage for Medicare beneficiaries. Here is typical contract language: 1

Erin Zuiker, JD/MPH Huggins & Zuiker, LLP

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HR Solutions Don’t Underestimate Labor Costs in Your Budgets At some point in time, we have all used this calculation: Labor role (e.g., coordinator)

=

(Hourly rate + benefits)

Pretty straight forward, right? Wrong. This simple undercalculation is the reason sites struggle to afford quality or additional employees, and also retain them.

Sites and sponsors typically underestimate labor costs due to lack of awareness of their real costs and to avoid any suspicion of coercion or influence on the outcome of the trial.1 Legislation, specifically the Sunshine Act, along with vague yet threatening terms like “fair market value” have scared sites away from negotiating the labor section of the clinical trial budgets to reflect the true cost sites incur.

x

Number of hours to do the assessment or visit in the clinical trial

the clinical trial can show their competency and training in that role.4 To be considered a premiere site, the sites must invest in their staff with ongoing training opportunities and, potentially, internal trainers. All of this must be documented.

Training opportunities come with memberships to organizations such as SCRS, ACRP, SoCRA, conferences, webinars, and classes. These all take employee time and money and can be incorporated into your sponsor budgets.

The next logical question is, “How can sites incorporate all of these costs into budgets when the other sites are using the initial (under) calculation?” The answer is justification The most common site burdens that go unaccounted documents that explain your very real costs. No one is for are turnover (it’s inevitable), training, and employee suggesting that sponsors retention. As prevention is take the entire burden of cheaper than treatment, Legislation, specifically the Sunshine Act, along paying for turnover, training, retention is cheaper than or retention; however, it attrition. To retain top talent, with vague yet threatening terms like “fair should not be completely sites need to offer continuing the burden of the site. No market value” have scared sites away from education, opportunities for one will argue that these are career growth, and avoid the requirements to be a negotiating the labor section of the clinical trial overworking staff. Staff quality site, and ineffective burnout and lack of career budgets to reflect the true cost sites incur. sites delay trials and increase growth are often listed as the sponsor costs.1 top two reasons for leaving

clinical research site jobs.2 Offering reimbursement for clinical research certification achievement and maintenance is just one example of a measurable cost to retain your talent.

Despite site management efforts, turnover at sites is common due to sponsors, CROs, and competing sites recruiting away top talent for opportunities in career growth and higher salaries. This can leave the site with vacancies for up to nine months, potentially decreasing the productivity of the remaining staff, while also limiting enrollment and the opening of new clinical trials (all sources of revenue). The site has concrete expenses to recruit talent, interview, hire, and onboard new team members. These expenses can, on average, cost the site six to nine months of the employee’s salary.3 Site administrators need to calculate the average rate of turnover and include these hard costs across labor budgets.

EXAMPLE: Average turnover of 1 coordinator/year = $52,000 Onboarding a new coordinator = $26,000-$39,000 Sponsors and CROs expect to work with competent sites that provide ongoing training and education. This is further supported by the Addendum to ICH Guidance for Industry E6 Good Clinical Practice: Consolidated Guidance, Section 4.2.6, which requires the investigator/institution to demonstrate that all staff delegated to perform tasks on 34 | InSite - Summer 2017

Here are some steps to take to start developing these justification documents. Calculate your annual voluntary turnover rate per role, along with employee time and cost spent training. Then, factor in hard costs, such as certification pay, and a reasonable workload per employee. Consider all of these factors when allocating costs to each clinical trial.

Provide justification on where you got your numbers to help the sponsors understand the real cost of labor at sites (and to protect all parties).

1 Arenz D, Hero B, Eichhorst B, et al. Estimating Site Costs Prior to Conducting Clinical Trials.

Future Science. 2014; 4(3): 227–234.

2 Speicher LA, Fromell G, Avery S, et al. The critical need for academic health centers to assess the training, support, and career development requirements of clinical research coordinators: recommendations from the clinical and translational science award research coordinator taskforce. Clinical and Translational Science. 2012; 5(6): 470–475.

Kantor J. High Turnover Costs Way More Than You Think. Huffington Post. February 11, 2017. Accessed from: http://www.huffingtonpost.com/julie-kantor/high-turnovercosts-way-more-than-you-think_b_9197238.html

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4 International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6(R2). November 9, 2015. Accessed from: http://www.ich.org/fileadmin/Public_ Web_Site/ICH_Products/Guidelines/Efficacy/E6/E6_R2__Step_4.pdf

Molly Downhour, MHA, BSN, NEA-BC, OCN Clinical Research Consultant Medix

The Billion-Dollar Molecule One Company’s Quest for the Perfect Drug

Barry Werth. New York, NY: Simon & Schuster; 1994.

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LINICAL TRIALS COME IN THE MIDDLE OF THE LIFE OF A DRUG. Before the trials, the bench scientists have kept ahead of their budget allotment at a large corporation or ahead of venture capital at a small one.

There’s the New Drug Application and animal testing. Only then do the clinical trials begin. Following the clinical trials, the drug either becomes a marketed product, or it goes into oblivion, perhaps taking the company with it.

The Billion-Dollar Molecule is a window into what happens throughout the life of the drug, focusing largely on the period before clinical trials begin. It is a window into the careers of scientists that are made or lost depending on whether they can continue to fund development and coax overburdened laboratory equipment to complete just one more test. In the book, scientists stay in the lab for days at a time without bathing. One puts off heart surgery to meet publication deadlines.

HIV. Instead of finding these drugs by testing molecules that already exist in the environment, the plan was to bioengineer a molecule that had a specific projected effect on the disease.

Though the book was published in 1994 and the state of the companies and products discussed in the book have moved on, the story is still relevant as an explanation of what happens at biotech startups. The author has written a sequel, The Antidote: Inside the World of New Pharma. This book follows the company as they take their first drug to market.

The people described in the book rival the company and the science for the most compelling plot lines of the story.

As already mentioned, they are extremely driven. Their concepts of the scientific world in which they operate shift as they gain experience, leading to new directions of research as they seek scientific breakthroughs. One, lost in college and loathing his humanities class, had an epiphany at age 19 that the direction of his life lay in organic chemistry.

Little did he know that he would enter a world turned full circle, where the tastes of investors would drive the science.

Throughout the hard-charging tale, the question of how business affects the direction of science always lurks in the background. A paper published at the right time, or a paper from another company that puts a scientific idea in doubt can change the course of history.

The company at the center of the book is Vertex, a pharmaceutical company formed by Josh Boger to engineer an immunosuppressant drug to treat organ transplant rejection and other deadly illnesses. With the immune knowledge from that development program, the company also pursued development of a drug to treat

This messy process shapes the lives of everyone involved in clinical trials- people who work at sites and of course the patients who rely on this drug development process to deliver the medications they need.

This book is a fast-paced and yet also a heavily scientific window into exactly how that process works.

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