Kristopher Sarajian

Too often, clinical trials are delayed while waiting for technology implementations, which can significantly increase cost, timelines, and frustration for study teams, sites. And the stakes are high: in the US alone, biopharmaceutical companies spent about $1 billion to bring each of their new drugs to market between 2009 and 2018, according to a 2020 JAMA report 2020.

Sponsors and CROs can help their clinical trial technology providers improve study delivery times if they adopt the following three best practices.

Finalize the protocol before building the trial

Align development and procurements teams before kickoff

Maintain ongoing communication and engagement among and within teams

Technology providers always want to be brought into the protocol drafting process early. This is especially the case when the provider has scientific and clinical experts who can advise on best practices for the patient experience, quality of life possibilities, and sometimes even recommend specific scales. That said, all work on actually configuring the systems should be held until after the protocol is finalized. Too often, technology providers are asked to program their systems on a draft version of the protocol, ostensibly to save time; unfortunately, the opposite can happen.

When implementation work begins early, each inevitable change to the protocol may require performing duplicate work and can create significant downstream effects. Whatever the task is—programming an eDiary, writing informed consent, or creating source documents—it will mean extra time repeating processes, potential re-validation exercises, and re-submitting to the IRB for approval. It also drains resources and keeps the technology team doing redundant work instead of moving on to other strategic items.

One of the most important success factors is to make sure the sponsor’s procurement team and study team are in sync from the beginning.

Studies go sideways because the procurement team decides to proceed with the technology provider, but they don’t bring in the study team until the 11th hour. Maybe the study team lost the questionnaires, or they're not ready to proceed because another project is pending. Or they're just not clear on exactly what type of services the technology provider offers. These issues slow the process and can derail timelines.

Sponsors should bring their project team into procurement discussions very early in the process. This sets the expectation that there will be one checklist of questions the study team needs to be prepared to answer, and that checklist will be shared with the procurement team as part of that process.

Having an engaged team on the sponsor side is critically important. At each kickoff meeting, technology providers should include a slide which presents a clear and concise list of what they will commit to in their timelines, and also what they need the customer to commit to for shared success.

This level of transparency and accountability establishes a partnership up front. It can help ensure teams to stay on track not just because people show up to meetings, but because they’re achieving their own milestones. When one team hits the tennis ball onto the other side of the net, the other team hits it right back.

The end goal is to determine how to best capture the data for the trial—for example, with electronic diaries—and then get that data back to inform the study’s endpoints.

It doesn't matter if the customer is a Top 10 pharma or a bootstrap startup, a sponsor or a CRO. If they adopt these three best practices, they can make higher on-time trial delivery a reality.

Estimated Research and Development Investment Needed to Bring a New Medicine to Market, 2009-2018, Olivier J. Wouters, PhD1; Martin McKee, MD, DSc2; Jeroen Luyten, PhD3

Articles

Finalizing protocols, aligning teams, and staying engaged headline best practices. 

Improving Clinical Trial Delivery Times: Best Practices

Given everything else patients have going on in their lives, it can be an unsurmountable burden for people living with a chronic illness, such as elderly cardiovascular patients, to comply consistently with self-administered medication protocols.

While most clinical trials spend millions of dollars or more on clinical systems to improve data management, very few provide any meaningful support for patients at home to help them stay active and compliant.

Why aren’t more companies using these cost-effective and easy-to-implement solutions? Let’s take a look at one that did.

The importance of consistent medication adherence for studies with self-dosing requirements cannot be overstated. As has been reported in Applied Clinical Trials, poor compliance has an exponential impact on the number of patients needed to reach the same statistical outcome, shown in Table 1 below.

Research shows 40% of patients become non-compliant at 5 months on study.

 This means an average Phase III trial will require an additional 460 patients at an estimated cost of $12 million.

Costs will be even higher for certain programs such as lengthy cardiovascular studies and complex oncology trials.

Even an incremental improvement can make a significant difference in time and on the study budget. The Phase III trial referenced above would yield $335k in cost savings for each 1% increase in adherence.

As the following case study below shows, a technology-based dosing manager can help patients, even in the challenging elderly patient demographic, achieve compliance rates up to 98% at 18 months on study.

A leading pharmaceutical company sponsored a cardiology trial that required elderly patients to self-administer cardiometabolic medication in tablet form 2x/day in a chronic fashion over multiple years. Published data for average medication adherence in cardiometabolic disease is 56% over 12 months. Twice-daily dosing has even lower adherence.

For this Phase III trial the study team deployed a technology-based dosing mechanism. It helped improve medication adherence by using interactive SMS messages on patients' personal phones. The dosing manager solution sent protocol-specific automated text messages that prompted patients to take their medication at the scheduled time.

The system prompted patients twice daily with an SMS message that enabled them to quickly and easily confirm they had taken their dose—i.e., the patient would hit the Number one to confirm they took their medicine on time. In addition to ensuring compliance, easily access dosing records mitigated the risk of patients over-medicating because they forgot they had already taken a dose.

This simple process removed burden for elderly patients who (counter-intuitively) typically have higher technology compliance than younger people, in part because they have more spare time and stronger relationships with their care teams.

Sites received weekly compliance reports which allowed them to identify patients who would benefit from additional support and follow-up.

In addition to a dosing manager, technology solutions which kept patients engaged during this trial included:

Patients consistently demonstrated 2x/daily medication adherence at 70% and above throughout the duration of the trial. Patients treated at several major academic research centers reached as high as 98% adherence at 18 months on study, with an overall average compliance rate of 86.5%. A few of the research centers along with their patient adherence percentages can be found in Table 2 below.

Technology providers should evolve their technology and service delivery best practices to ensure continual improvement in patient compliance.

This trial faced unique challenges and presented lessons learned technology providers can incorporate into future clinical trials, including…

Make site participation mandatory—Keeping it optional means fewer patients will receive benefit from a dosing manager.

Focus on supporting ex-U.S. sites—While most eClinical technology is inherently global, some countries may have specific deliverability issues a technology provider can solve with a telecommunications partner should challenges arise. It is important to monitor compliance at ex-U.S. sites to identify and resolve issues proactively.

Follow up with non-compliant sites—This ensures sites are reviewing reports and discussing the importance of consistent dosing with low-adhering patients. It is especially important for sites with significant staff and study coordinator turnover.

Patients trust us to provide the best possible care and clinical trial experience for them. As an industry, we must shift to prioritize technology and tools that make it easier for patients to participate throughout the study’s duration. Even using a simple interactive SMS dosing manager can significantly increase compliance, improve safety, and reduce cost and risk. So, let’s work together to help patients, their caregivers, and their families succeed in our clinical trial.

Adherence to medications: insights arising from studies on the unreliable link between prescribed and actual drug dosing histories. Blaschke TF1, Osterberg L, Vrijens B, Urquhart J., Annu Rev Pharmacol Toxicol. 2012

Smith, Dorothy PharmD, Patient Nonadherence in Clinical Trials: Could There Be a Link to Post Marketing Patient Safety?, Consumer Health Information Corporation, October 2011

Improving Medication Adherence in Cardiometabolic Disease, Journal of the American College of Cardiology, 2017

Elderly patients achieved up to 98% compliance at 18 months on Phase III study.

Increasing Adherence With Dosing Reminders

	Aside from patients, there is no greater resource than sites themselves for running a successful clinical trial, and it’s amazing what can be achieved when we treat them well. This article discusses best practices and benefits of keeping a trial top of mind at global sites, and measuring some of the qualitative and quantitative impacts it can have on a trial. In this time of increasing competition for site attention, site engagement is an absolute necessity for sponsors to make their trial activities jump to the top of sites' priority list.

	Let’s explore some of the possibilities of a well-executed site engagement program. Put simply, ask yourself what you want your sites to do-then imagine them doing it better. That’s site engagement at a high level.

	Specifically, clients tell us they have seen sites elevate performance in key metrics such as patient enrollment, patient retention, protocol compliance, data query resolution and overall study conduct efficiency (activation timelines, collaboration, transparency, etc.). These benefits and more are realized through three main strategies:

	1.     Creating a sense of ownership among global sites to get them invested from the beginning

	2.     Inspiring friendly competition and recognizing achievements to keep momentum going

	3.     Equipping sites with the information and tools they need to make their jobs easier so they can spend more time working directly with patients

	As the name implies, site engagement keeps sites invested in the outcome of your trial in an effort to improve performance across the board. In short, it helps get the most out of your sites. It possibilities and reach are only limited by how it is used and what it is asked to do.

	The younger generation of site staff who have come into their professional lives as seasoned technology users no doubt are frustrated and perplexed that something as important to our society as clinical research still relies on antiquated communication methods. Understandably, it must be challenging for them in these days of Facebook, Twitter, Instagram and so many more apps that make instant connections a breeze to stay engaged with an abstract sponsor running a trial that sends study information in a newsletter mailed once every few months. The information they receive is wildly out of date, unusable, not personalized to them, and is quickly forgotten.

	By now, we likely all acknowledge that the days of quarterly newsletters being an effective method of communication are long behind us. In many areas clinical technology has a long way to go to catch up with other industries and certainly with the consumer technologies available on mobile phones study coordinators use daily in their personal lives. Fortunately, communication is one area where the clinical technology exists and is ready to serve when called upon. To be successful, a site communication solution should:

	·      Provide usable, personalized data relevant to each site recipient

	·      Be easy to access (ideally from emails) and intuitive to use

	·      Create a real sense of ownership and community-building

	·      Stay current with frequent content updates to bring people back regularly

	·      Feature Google-like search capabilities throughout the portal

	·      Include other valuable solutions in one place (e.g. documents, training modules, contacts, visit guides, etc.)

	The goals of using an online communication platform go far beyond sending out required information. When properly implemented with a consistent and appropriate sending schedule, you can ensure sites read your messages, enable your monitors to follow up with sites that don’t, and create a consistent contact program that keeps your trial top of mind so sites prioritize your study activities above all others.

	At its core, a communication platform needs to send required information to sites, such as an announcement of a protocol amendment being released, drug resupply instructions, or updated hours of study team availability. While important for relaying information, this type of logistical email does not create meaningful mindshare at sites.

	Some DrugDev customers have successfully inspired sites by running campaigns that promote awareness activity and team building. For example, one Top-10 pharma company used the platform to promote a “Wear Orange” campaign in support of Melanoma Monday. Sites were encouraged (but not required) to take team photos of their staff wearing orange and post them to the network, where they were shared with other sites involved in the trial. In addition to showing patients at the clinic that day how much the staff cares about their condition, it creates a bond between the site and the study sponsor as they are working together to combat the same enemy. This type of awareness spreads word of mouth within study sites and increases their sense of ownership in the outcome of your trial.

	Think Like a Gamer to Improve Clinical Research

	Imagine for a moment you are playing a video game, except it doesn’t show you your score-or maybe it does, but lacks any context of how that compares to other players-and whenever you complete a level there are no bonus points, rewards or fireworks above the castle. You simply move onto the next task or activity without fanfare. This doesn’t sound like a particularly engaging game, so why would you play it? Yet that’s how many sites must feel when they participate in clinical trials.

	Comparing the fun and frivolity of video games to something as serious as clinical research may not be entirely appropriate, but the key concepts definitely apply. Without a proper site engagement program, sites likely have no concept as to how well they are performing on a daily basis when it comes to key measurables such as screening, enrollment, patient retention and data query resolution. Worse, there’s a good chance they only hear from monitors when there’s a problem to discuss.

	Good Natured Rivalry and Recognition Encourage Site Performance

	Applying some of the concepts of gamification in a professional manner can bring fresh life to site energy and activity levels throughout the trial. Some systems use site-specific metrics to show staff how they are doing compared to other sites in their country and across the trial over time.

	These powerful data are presented on leader boards which are regularly updated and emailed to the entire virtual site community. Perhaps unsurprisingly, these emails consistently earn the highest open rates from Principal Investigators in particular, who relish the friendly competition of seeing their site climb the leader boards-and ensure study coordinates receive the same message and goals.

	It's only natural the inherent satisfaction of being told “job well done” keeps people motivated to continue performing well. Site engagement should be used to allow study teams to centrally manage (and automate the distribution of) reward badges for individual staff profiles when certain milestones are achieved. For example, a Silver badge may be sent when the site completes activation requirements, and a Gold badge when the site enrolls the first patient in country.

	It’s extremely refreshing for site staff to receive positive feedback, especially when badges are accompanied by personal notes from the study team, thanking them for their hard work and accomplishments. Receiving a badge rewards behavior you want from sites, and inspires them to work hard to earn more. It's also a source of pride-in fact, sponsors tell us they have often seen badges printed and displayed in site offices!

	Infinity Pharmaceuticals is among DrugDev clients that have combined news, leader boards and badges into awareness campaigns aimed at specific goals. In this case, Infinity was behind enrollment goals heading into year-end holidays and decided to implement a 30-day challenge using the DrugDev Spark™ unified clinical suite.

	The concept was simple and highly effective. Infinity developed badges where certain achievements like screening a patient, enrolling a patient, etc. were worth a set number of points. Leader boards were sent at least weekly, and at the end of the 30 days Infinity made a donation to a relevant patient advocacy group on behalf of the site with the most points.

	The response was tremendous. Enrollment rates more than tripled over the prior month and remained elevated for the following months as well. It worked so well Infinity repeated the challenge again later in the trial with similarly impressive results. It’s just one example of the power and ability of site engagement techniques that inspire sites to improve performance for critical objectives.

	Of course, a site engagement program is only effective if sites actually use it. Ensuring adoption hinges on many factors including several mentioned earlier such as valuable content and intuitive usability. Sites do not want “yet another system” to log into. Rather, they want to log in directly from an email, ideally with single sign-on, and get real value from what they find there. It needs to become a habit as they start their day, and a trusted resource they turn to when they have a question about the trial-and only a few minutes free to get the answer and act on it.

	Modern Technology Platforms Makes the Site’s Life Easier

	That’s why the best site engagement portals aren’t site engagement portals at all. They are clinical trial optimization systems or unified clinical operations suites or whatever you want to call them. The important part isn’t the name; it’s the utility that matters.

	What makes today’s unified clinical suites stand out is they do much more than site engagement, as important as that is. They are document exchange repositories, learning management systems, site payments platforms, eConsent solutions, site activation systems and more. They are a unified one-stop-shop for sites to get everything they need to run the trial efficiently in one centralized and convenient location.

	And they can be even more than that by providing sites with support tools that make it easy for them to run the trial, such as visit guides, scheduling and dosing calculators, FAQs, contact directories and more. Site collaboration also can be improved with tools for study teams including dynamic eTrackers that monitor and analyze incoming data from other systems (CTMS, EDC, IVR, labs) to proactively solve key challenges like enrollment diversity, patient retention and closeout visit scheduling.

	By enhancing their value with complementary features that make site lives easier, these platforms are transformed from traditional portals into comprehensive clinical trial solutions sites and study teams alike want to use every day.

	Communicate, Motivate, and Inspire Your Sites

	Sites are the shared resource upon which all sponsors, CROs and studies rely. We have a collective responsibility to make their lives easier while treating them as partners, not employees, and to inspire the best performance from them. In this time of protocol complexity and increased competition it’s no longer acceptable to continue doing things the same old ways. The industry must come together to ensure proper communication, motivation and inspiration, and support for sites using modern technology. I hope you agree that not only is it the right thing to do, but it also can pay real dividends by improving key metrics for global clinical trials.

This article discusses best practices and benefits of keeping a trial top of mind at global sites, and measuring some of the qualitative and quantitative impacts it can have on a trial.

Kristopher Sarajian

Articles

Improving Clinical Trial Delivery Times: Best Practices

Increasing Adherence With Dosing Reminders

Site Engagement: The Key to Running a Successful Clinical Trial