infocusjan22

An excerpt from a white paper developed by MRN  The Covid19 pandemic has clearly highlighted challenges of “traditional”, site-centric clinical trial designs. More than ever, people are talking about direct to patient, decentralized or community-based clinical trials, buzzwords that have appeared in our vocabularies only just recently, but as the organization that pioneered these kinds of studies, over 15 years ago, we know that it isn’t an easy process. This isn’t about taking the complex and making it simple, it’s about making the complex happen efficiently and safely for patients.  Ensuring patients are safe, cared for and comfortable during treatment isn’t simple; making sure data is collected on schedule and accurately, so that the study either proves the efficacy of a treatment or disproves it quickly isn’t simple; coordinating medical professionals, patients, investigational medicinal product to a single point in time and location isn’t simple; managing sample collection, on site processing and shipping to central laboratories from multiple, domestic, locations isn’t simple. Pulling this all together across multiple patients, locations and visits is very complex. Our operational teams bring together the best in the industry to coordinate each and every study touchpoint and ensure your clinical trial can be run in the patient’s communities in an efficient and safe manner; but it isn’t simple.    What do you need to consider? Here are some of the points you should consider if looking to run community-based clinical trials:   What does the protocol entail?   What can be done within the protocol in a home/ work/school environment? Which visits should happen outside of the site? Is the protocol very visit intensive –frequent visits or intensive assessments? What patient centric recommendations can be made to best fit the recruitment, enrollment and retention for the study?   Who are your patients?  Consider your target population; where are they, who are they, what is the prevalence of the disease and how close are those patients likely to be to the sites? “Currently, 70% of potential clinical trial patients live more than two hours from a study center…” (Parexel, 2019)  If regular, in-person interaction between the patient and their physician is required, then visits to the site make sense for a patient relatively close to site. If those patients aren’t near to a site, they are going to struggle to meet the visit demands of the protocol and they’ll either not enroll or not be retained for the full duration of the trial.   Developing the protocol with the patient in mind is absolutely key. Speak to patient advocacy groups for the disease state, they know what it’s like from the patient perspective to take part in a clinical trial, they know how onerous it can be and understand the difficulties of the disease state that they’re trying to manage.   Family often have to take the patients to their visits so that should also be considered. Location is key to reduce the burden on the patient and their caregivers or families. Patients shouldn’t be expected to travel hundreds of miles to see a physician for every trial visit if some can be done at home.   If you are looking at using technology to facilitate virtual visits you must consider the age of the patient population. Will they know how to use a heart rate monitor or a tablet?   To be applying technology to a protocol you need to consider the infrastructure of the countries that you will be working in; how good is the WIFI, the broadband? Will 5G be supported? Do the patients have a WIFI network that can be used?  Who or what do you need?   A lot of detail is required around the actual scope of what needs to be delivered. Nurses conducting visits have a higher success rate if trained properly. What training and equipment is required for the research activities required? What experience do the nursing professionals require to deliver the research assessments? How do you ensure all research nurses are vetted appropriately? What training materials and support must be created to ensure all activities can be undertaken correctly?  Are there country-specific regulations that need to be considered? There may be country-specific regulations that may complicate the running of clinical trials in the community. For instance, in some countries, we know the administration of certain drug types is forbidden outside of a clinic or hospital environment, or it may require a physician rather than a nurse to perform either the assessments or the administration. It’s not just the clinical research regulations that you need to familiarize yourself with, you need to broaden your understanding of the healthcare landscape in all countries that are being used for the study. As well as regulatory differences from country to country, there are also cultural differences to consider as well. In some countries, it isn’t polite for patients to invite professionals other than their physician into their home and that would extend to nurses. Many people will hear the word “decentralized” and think of technology, such as telemedicine or wearables, but it’s so much more than that.  Performing a clinical visit outside of a site requires a trained healthcare professional, a delegate of the PI, to care for the patient and understand clinical research and the protocol. We know from experience that utilizing decentralized solutions isn’t a one size fits all solution. . The right solution should be determined by what is right for the patient.  When you use the right tools, decentralized trials can be successful for all stakeholders.    Download the Full Whitepaper from MRN

Changes brought on by the pandemic have encouraged the industry to adapt quickly, especially when it comes to adoption of new technologies. Many sites pivoted to hybrid decentralized trials, meaning some patient visits were conducted virtually instead of on-site. However, some sites have still expressed hesitation with decentralized visits for various reasons. In the SCRS Member Community, sites discussed subcontracting concerns as one reason for declining decentralized trial opportunities.  One site shared, “We have been approached about participating in a decentralized trial.  We think it may be good to get some experience in such a trial since there seems to be an interest by sponsors in moving in this direction.   Recruiting and many of the visits will be done remotely by another agency the sponsor contracts with. We have been asked to sign a delegation log listing the third-party company on the delegation log, not the specific personnel.  We do not know the staff who will be working on their behalf.  The staff may be in several different states. This makes us a little nervous as our PI is supposed to be responsible for the conduct of the trial and we really do not know the qualifications of any of the people working for this third party. Is this usual and customary?”  This language is not necessarily common, but some CROs may do it more than others. Sites, understandably, are apprehensive to agree to these terms. Many have declined studies because of this language alone.   To clarify, the CRO is responsible for the behavior of its vendors chosen – not the site. This should be stated in the CTA as an indemnification of the site. Additionally, CROs should allow sites the authority to change the vendor or people they work with at the vendor organization as needed.  If the site agrees to this liability, they should have a say in who they work with. Additionally, sites should validate any vendors’ business insurance to limit their liability if they plan to sign a contract with this language.  SCRS Honorary President David Vulcano shared, “I have had conversations with FDA on this via an ACRP Fellows task force, and they don’t like it when the Sponsor/CRO picks the personnel and do not give the investigator any control. It’s fine for them to pay directly for the service, but unless the home visits are set up as a different site under a different PI (i.e. two site/PIs handing the subjects back and forth), you and your PI must be In control.”  If this language is included in your CTA, SCRS encourages sites to have a further conversation with the CRO. Liability should not be solely on the site, and at a minimum there needs to be indemnification language to ensure minimal liability for the site on behalf of the other organization. Sponsors and CROs can be proactive in contracts to provide sites with options for who they would like to work with and reduce the burden of liability for things the site cannot control. The best option, however, would be to separate the two organizations altogether in the CTA. The FDA may release guidance on this topic in the near future, but we recommend sites communicate their needs and concerns to improve industry partnerships for all. 

In November, we reconvened for Sites NOW to discuss the 2021 SCRS Global Site Solutions Summit and some of the highlights from popular sessions. Lindsey Morales of Labcorp Drug Development, Ana Marquez of Clinical Site Partners, and Karin Gulbrandsen of Janssen joined us to share lessons learned and hot topics of discussion in each session.  It’s Not You, It’s Me: How to Manage Long Term Partnerships As the pipeline of clinical trial work evolves and changes over time, the importance of quality relationships between sites and sponsors and CROs will increase. Sponsors and CROs will engage sites that align with current and mid-term projected opportunities and remaining in contact over the long-term will become even more important. Attendees gained insight into navigating clinical trial evolution to position their sites for success. Chris Hoyle of Elite Research Network facilitated the session with panelists Silvina Baudino of Teckro, Lindsey Morales of Labcorp Drug Development, Robyn Schmidtke of Merck.  Fundamentally, this session focused on communication. As we know, partnerships of any type are all about communicating with and learning about one another. But, what does it mean to communicate? What does it mean to be honest and build trust with one another?    Sites, speak up! Sponsors and CROs want sites to share information and challenges because “if they don’t know about it, they can’t help you with it.” Keep conversations going about training as the industry looks for solutions to minimize the amount of training needed for new technologies and reduce overall technology burden for sites. Be open and candid and transparent about the things we’re learning with each other.   One popular point of discussion sites shared was that CRO databases seem to be places where information just goes into a black hole. Industry is incorporating site feedback and working on better databases to keep everything in one place and reduce redundancies, so please continue providing feedback.   We also shared how crucial it is for our industry to attend meetings and conferences to take communication to a new level by putting a face to a name and building a personal connection.  Industry conferences, virtual meetings, site advocacy or focus groups, and community forums are a great place to foster relationships and provide value to one another throughout the year. Continue reaching out to sponsors and CROs to find people you can partner with and who will be an advocate for your site. They want to know you and help you as much as they can, so don’t be afraid to ask for assistance or contacts if needed.  Hybrid Decentralized Trials: Critical Considerations   It’s no secret that digital innovations are here to stay, especially in the form of decentralized trials. While there are important considerations to be made from an administrative and process perspective, it is equally critical that we consider how patients will be affected. This session discussed how decentralized trials affect patient interaction so we can ensure patients’ needs are addressed.  Facilitated by Todd Albin of Cedar Health Research, panelists included Deena Bernstein of Datacubed Health, Nicole Latimer of Medrio, Scott Connor of Signant Health, and Karin Gulbrandsen of Janssen.  Understandably, sites remain concerned about building and maintaining patient relationships when using DCTs. However, the intent of decentralized clinical trials (DCTs) is to engage patients where they are and increase retention. Many opportunities remain to build relationships with trial subjects in different ways and may be nourished through a combination of phone calls, video calls, texts, and in-person visits.  Sites are also apprehensive about PI oversight specific to DCTs due to lack of understanding of regulations. PIs still need to make sure they are delivering quality expected from in-person visits, while industry needs to provide guidance for investigators as they navigate these new expectations.   It was also shared that sponsors and CROs need better understanding of financial liabilities for sites regarding implementation of new technology. Sites expressed that budgets are often poor with DCTs, yet add a lot of work for the site.  Additionally, many digital platforms ask for specs, then other sponsors or studies ask the same information again. Communicating these challenges can help industry to create a uniform way for sites to provide technical authentication pieces in the future. It’s important to remember that adding new technologies to trials is not one-and-done; as we implement different elements, we need to continue to get the feedback on what’s working and what’s not. It’s an ongoing learning process that will only be successful if sites and industry work together to find solutions that benefit all.  FDA Audits: Yes, That Really Happened!  FDA audits are an inevitable reality that all sites should be prepared for before they are audited. This session included perspectives from those who have experienced FDA inspections to share how they prepared for the audit and what measures they have implemented to ensure future inspection-readiness.   Ana Marquez of Clinical Research Partners facilitated the session with panelists Shivani Shah of DM Clinical Research, David Vulcano of HCA Healthcare, Rick Arlow of Complion, and Lisa Kodis of Illingsworth Research Group.  This session discussed recent FDA audit need changes and what the FDA is looking for, such as informed consent issues and delegation log issues. How do sites prepare for audits? Panelists noted that it is critical to prepare site staff by discussing specific steps to take after being notified of an audit. Sites should identify a key team for inspection and minimize involvement of too many people as much as possible. One option may be to hire an expert to assist you with the process, especially if you have been issued a 483. Investing in the proper individual to guide you through it can make it a much easier process for your site.  It’s also important to note that sites can set limits in their contracts when it comes to FDA inspections regarding communications protocols,  such as only notifying the sponsors whose trials will be affected by an audit.   SCRS will continue to host workshops, webinars, and provide resources for sites to self-monitor and be as prepared as possible for FDA inspection. FDA also offers an audit manual online that industry can pull which shares every question to anticipate the auditor asking.  The meeting then separated into breakout sessions to discuss  takeaways from these sessions and the 2021 Global Site Solutions Summit. We hope you will join us for the next Site Solutions Summit and encourage you to get your tickets as early as possible to secure the lowest rate! For the full November 2021 Sites NOW discussion, watch the Sites NOW meeting recording here. 

Ready or not, patient-centric trials fueled by technology and new best practices are here to stay, says David Vulcano, LCSW, MBA, CIP, RAC, vice president for Research Compliance & Integrity with HCA Healthcare. “We’re building the plane while it’s flying,” he notes.  The COVID-19 pandemic has forever changed the way clinical trials are going to be conducted, Vulcano believes, beginning with greater usage of decentralized clinical trial (DCT) tools and technology. “Patients are demanding the infrastructure be built around them” after technology demonstrated it could bring many aspects of clinical trials to a patient, rather than forcing them to come to a brick-and-mortar site every step of the way, he says.  Trials in a post-COVID-19 world will be increasingly patient- and not site-centric, Vulcano says. “Patients will want to keep much of that choice,” he notes, especially the ability to use FaceTime and other remote technologies to communicate with clinical trial professionals and other healthcare workers.  With privacy and security regulations relaxed during the pandemic to help maintain critical trials and care, Vulcano thinks patients won’t want to lose those new ways of participating in studies. “When the [pandemic] is declared over, will [regulators] tighten those regulations again?” Vulcano asks. “Patients will want to keep” the convenience and option of remote communication, he believes.  Regulators will need to work with industry to find effective ways to ensure patient safety and data integrity when using remote tools, Vulcano says. “There are privacy and security concerns, and we have to think about how principal investigator oversight and adverse events are handled, among other issues,” he adds.   Ready…Fire!…Aim. How We Got Through the Pandemic and What’s Next  Join Vulcano at ACRP 2022 on Saturday, April 23 as he gives an overview of how the pandemic forced many sites into decentralizing their studies and the effects on site cash flow, workforce safety, and increased flexibility. Examine how we can all help each other through these challenges, and how we as a workforce can maintain compliance while working in a remote environment.  The clinical trial industry is moving from the “Blockbuster to the Netflix model,” Vulcano says. In the old days, going to a brick-and-mortar site was about the only way to rent certain kinds of new entertainment content, but Netflix and others adapted that model to offer consumers different ways to get what they wanted without leaving their homes. “I can still get a DVD in the mail or Redbox or Walmart or other places, but I can also get it streamed to my phone while I’m home or traveling,” Vulcano says.  While he’s optimistic about this future, he notes it will put new demands on the clinical trial workforce, too. For example, it will require greater familiarity with using technology and remote tools, he says. “We’re also going to see new technology and new technology partners” become a more important part of the clinical trial delivery ecosystem, he explains.  “I can’t imagine us going back” to the way clinical trials operated before COVID-19, he says. “These trends were already here—COVID-19 just accelerated them.”  Originally published on ACRP by Michael Causey