Medrio Blog

It’s no secret that getting new drugs or biological products approved by the FDA is a challenging task. The low rates at which drugs make it all the way through the research process is a favorite topic of blogs and journalistic outlets alike. Some drugs fall by the wayside due to unfavorable efficacy or underpowered data in the middle and later phases. Many others, though, fall victim to administrative or technical challenges that arise as early as the nascent stages of phase I.  What steps can sponsors and CROs take to position their early-stage studies for success and expedite their final market approval? In this article, we’ll explore three obstacles that researchers face early in phase I studies, as well as some insight into how the right eClinical suite can overcome those challenges. Challenge #1: Phase I Recruitment Across all phases of research, challenges in patient recruitment are often accounted for by a lack of awareness and skepticism of the tested compound’s efficacy compared to existing treatments. Recruitment challenges in phase I, however, have their own additional causes.The most notorious of these is the “guinea pig” fear: as the drug’s safety and tolerability profiles have not yet been established, potential subjects often worry it may pose a danger to their wellbeing.1 Clear and concise communication between patients and clinicians is critical in phase I to dispel any fears and discuss what is expected during the trial. Yet, unclear or incomplete physician communication during the enrollment process of phase I trials is a leading source of patient dropout. Nearly 30% of phase I trial participants reported that their clinician did not fully address the impact that the trial could have on their quality of life.2 When phase I participants were able to discuss their fears and concerns about participating in research with a healthcare provider, it was shown to increase their comfortability and autonomy with decisions about their enrollment.2  Creating opportunities for patients to engage with their healthcare team is critical to not only answer their questions, but also to build confidence, trust, and appreciation. Lack of motivation is another common factor, as most phase I trials involve healthy volunteers with no medical necessity for the tested compound. The exception to this, of course, is phase I oncology trials, which enroll sick patients. But even here, patients with an advanced condition and limited time are often reluctant to try a treatment with undetermined efficacy. To combat this, healthcare teams should find ways to show appreciation for the role patients play in the success of early-stage studies.  Challenge #2: Site Negotiations Before dosing begins in a clinical trial, there is a period of negotiation dedicated to hammering out details related to administrative matters like site payments. Most sponsors aim to complete site negotiations within 20 days, but due to the unpredictable nature of negotiations, 23% of discussions extend beyond 60 days.3   The time spent on negotiations with clinical research sites tends to decrease as research moves from one clinical phase to the next. This is due to the fact that as research progresses, the protocol becomes better established and there are fewer unknowns in the budgeting process. Therefore, it follows that the negotiation period tends to be longest in phase I. In fact, phase I site negotiations often last more than twice as long as other phases3. These lengthy negotiation periods threaten to derail timelines even before research has begun. To combat this challenge, sponsors should aim to build scalable processes that sprint their early-stage negotiations: Challenge #3: Protocol Uncertainties As phase I oncology trials enroll sick patients instead of healthy volunteers, eligibility criteria can be strict and dropout rates are notoriously high. This places the protocols of these trials at particularly high risk of unexpected changes.  A study by the Tufts Center for the Study of Drug Development found patient recruitment struggles to be a common cause of protocol amendments, with many amendments aiming to change patient eligibility criteria.4 Additionally, 57% of protocols had at least one amendment, and nearly all amendments were deemed as “avoidable”.  Outside of oncology, there is another risk: the Tufts study reported that 40% of protocol amendments take place before patient enrollment begins, and therefore create delays in the nascent stages of a trial that may be difficult to recover from as research progresses.4 Although some mid-study changes are unavoidable, there are steps sponsors can take to minimize their impact on early-stage study budget and timelines: An eClinical Solution to Overcome These Obstacles With these challenges lying in wait, researchers can benefit from entering their phase I trials equipped with the tools necessary to address them. The right eClinical solution can provide both mitigate and streamline early phase I challenges.  Medrio’s EDC makes it easy to perform mid-study changes, a feature that eases complications arising from protocol amendments. And our drag-and-drop interface enables researchers to build studies in weeks instead of months, creating time savings that can offset any delays stemming from patient recruitment or site negotiations. Best of all, our integrated eSuite empowers sponsors across all phases of clinical research to accelerate their studies while maintaining control and reducing costs.  The outcomes of phase I trials set the tone for the rest of the research process. The value of a strong start is impossible to overstate. While these trials face considerable challenges in their early stages, a robust and intuitive eClinical like Medrio is available to mitigate those challenges. References:

Modern clinical trials can be sprawling networks of clinics, people, and data. They can span borders and oceans. They utilize various communication channels. And they involve a multitude of interested parties, including patients, researchers, and other staff. In undertaking such complex trials, it can be difficult to provide sufficient oversight to ensure the quality of the most important and fundamental component of clinical research: the data entered. To prevent lapses in data quality, many EDC companies offer edit check functionality, whereby their software recognizes errors and fires queries when they arise. But ensuring data capture quality is only part of the solution; in today’s competitive research environment, in which there’s more pressure than ever for researchers to keep timelines down and stay within budgets, it’s also essential to do so as fast as possible. That’s why the ability to perform real-time edit checks, rather than having to wait until a designated moment to view and address queries, can make or break a study’s chances of success, elevating one of the clinical trials challenges. Indeed, this ability can be hard to come by. Safeguards of data quality in an EDC typically involve an established range of acceptable data for a given data point; the system fires a query when a piece of data falls outside of that range or isn’t entered. But most EDC companies don’t allow access to those queries until after data is submitted. This means that site staff may not recognize data errors on a form until after they’ve completed and saved it. To address the query, users have to reopen the study and backtrack in order to correct the error. They may be forced to consult their source documents again or to scroll through a lengthy form in search of the query. Over the course of the study—especially one involving long and complicated forms—the time this requires can add up. Recognizing the various drawbacks to this system, Medrio allows for real-time edit checks, so that queries fire the moment an erroneous piece of data enters the system. Users can rest assured, as they conduct their research, that no data errors lie waiting to cause headaches once a form is closed. Why Now? Producing sound data has always been important in clinical research, as has the ability to do so with efficiency. But until recent years, achieving these objectives was less of a challenge. The average clinical trial was smaller and more centralized, making it easier to oversee data entry and keeping the chance of error to a manageable level. Today, larger, farther-reaching, and more complex decentralized studies are growing in popularity among sponsors. A typical study now includes numerous sites across numerous countries, as well as large research teams whose members often work remotely from one another. The sheer quantity of data collected in such complex trials can be overwhelming. It also creates a much higher risk of human error during data entry than previous generations of clinical researchers, whose studies were smaller and more centralized, needed to manage. This, combined with recent regulations aimed at ensuring data quality that has arisen as a result, create a market for an EDC feature like real-time edit checks that can guard against data entry errors without allowing them to compound or delay a study. Current market trends make the case for real-time edit checks even more compelling. Not only are trials getting bigger and more complicated, but they’re also getting more competitive, as well. Increased demand for clinical trials has raised the stakes of competition among sponsors, with effects rippling out among CROs, sites, and other involved parties. And as the cost of drug development continues to rise, budget concerns add even more pressure. Researchers today are racing to get their products to the FDA like never before, both to beat the competition to market and to minimize the impact of their studies on their pocketbooks. The time savings created by real-time edit checks make it easier to accomplish these goals. In light of these conditions, clinical research today is ripe for an EDC tool that can not only detect data-entry errors that site staff may have missed but seamlessly integrate that detection into the research process. From increased error risk, new regulatory compliance burdens, and a higher-than-usual premium on efficiency in an already time-sensitive industry, it’s something of a surprise that only a few EDC providers offer such a tool. Medrio’s real-time edit checks functionality is just one of the many features that make the software uniquely simple, intuitive, and, most importantly, well-positioned to help researchers keep data quality up and timelines down in a competitive industry. References:

We comment a lot, on this blog, on the trends influencing the direction of clinical research and the eClinical technology industry. One trend that has become an especially prominent topic of water cooler conversations today is recent acquisitions in the eClinical space. There have been a number of high-profile cases in recent years of technology giants hoping to edge their way into the life science field by acquiring an eClinical software provider. Opinions and reactions abound when it comes to these things. Many will point out the positive effects of such acquisitions: for the acquired company, stock boosts for employees, more stability, and a growth infusion are just some of the benefits people cite. And they’re right to do so. But when the ink dries and the hands are shaken, the customers of those companies – the people on the ground who rely on fast and easy software in their pursuit of life-saving medical breakthroughs – may find themselves in a strange and unfamiliar landscape. All of this raises the important question of how data managers and site staff should react when their provider announces an acquisition. Customers of acquired eClinical providers can take comfort in the validation and stability that such acquisitions bring. But there are certain aspects of recent acquisitions in the eClinical software industry that have some people scratching their heads. 1. The parent company is an outsider In recent cases, the company acquiring an eClinical provider is not, itself, in the eClinical space. This means only a fraction of the parent company’s product development will go toward improving the eClinical platform that users have come to depend upon, leading to a slower and less robust product roadmap, with fewer resources dedicated to ensuring speed and ease of use for eClinical users. 2. Turnover is inevitable An unavoidable byproduct of corporate acquisitions is significant employee turnover. Many of the people who helped build the acquired company and who understand its strengths, weaknesses, and the unique needs of its customers move on, leaving those customers to work with a whole new cast of characters unfamiliar with the nuances of each project. 3. Doing business becomes a chore The bigger a company gets, the harder it can be to connect with support staff who understand and care. Moreover, with acquisitions, customers can find themselves suddenly facing new and more complex pricing structures from the parent company looking to recoup their investment. The bottom line: clinical researchers who are trying to focus on treating disease and saving lives are suddenly mired in financial and logistical headaches. At the end of the day, clinical researchers need an eClinical solution that delivers the ease of use and functionality to get their studies up and running quickly and create a smooth path to database lock. Along the way, they need to know that they won’t get bogged down by unnecessary complexity, out-of-reach support resources, or opaque cost structures. Adding uncertainty and a diminished customer focus only makes the situation worse. After all, lives are at stake – there’s little time to waste on logistics. While the eClinical acquisitions making headlines in recent years do offer some reason for excitement, the customers of acquired companies should consider what the impact could be on their ability to answer the call of public health.

“We’re faced with an unprecedented challenge in the time of COVID-19, but our collective determination and expertise enabled us to execute. Detecting sepsis early is imperative for effective treatment and would enable the clinical team to ensure that the right patient receives the right level of care at a time when resources are stretched and every moment counts. Achieving FPI in only seven days is a huge feat, and all parties involved should be extremely proud of their efforts,” said Ajay Shah, Ph.D., Co-founder, and CEO of Cytovale. A typical study with Medirio can get FPI within 6 weeks compared to the industry average of 12 weeks, due to the programming free drag and drop interface of our EDC system. Speed coupled with a flexible system puts you in the driver’s seat allowing changes on your timeline without coding or extra fees. From ICH/GCP and 21 CFR to GDPR and HIPAA, our customers are equipped with easy-to-use tools allowing them to focus on the trial with complete confidence that their data is compliant and secure. As organizations transition to more virtual operations, our hybrid and decentralized solutions are ready to help you meet accelerated timelines and changes when you need them.