Medrio Blog

Imagine, for a moment, you’re a data manager overseeing a Phase I study. Your endpoints are set, your database built and deployed, and your data collected. Now it’s time to cross your fingers, unblind your database, and hope for favorable tolerability results for the dosage you established.  To your dismay, you discover you’ve overestimated the maximum tolerated dosage. What’s worse, had you been able to access the database during the study, you could have discovered this shortly after deployment and made protocol modifications that would have saved you time, money, and energy that has now been spent in vain. It’s an outcome that would be a shame to repeat.  You resolve to empower yourself to make those modifications by taking an adaptive approach to trial design for future studies — and to invest in the tools that make adaptive trials possible. Adaptive Trials and Electronic Data Capture (EDC) A traditionally designed clinical trial is, by nature, a roll of the dice. Once a database is deployed, researchers can’t make many changes until the end of the study. In adaptive trials, however, databases can be unblinded while the study is in progress so that researchers can make changes to certain endpoints as needed, creating the potential for substantial time and monetary savings.  But while more researchers than ever before are investing in Electronic Data Capture (EDC) software to enhance the efficiency of their research, many EDC companies aren’t effective in accommodating adaptive designs and are thus limited in offering the efficiency those designs make possible.  Some EDCs, for example, when a mid-study discovery in an adaptive trial calls for a modification of the study’s endpoints, require researchers to take the entire database offline, perform complex modifications upon it, and ultimately push it live again. The time and resources spent on such an endeavor negate much or all of the efficiency of an adaptive design. Adaptive trials are most common in Phase I, but some pharma experts see increasing adoption of the approach in Phases II and III.(1) As the trend spreads across the clinical research landscape, the EDC companies best positioned to serve the needs of the industry will be those that are capable of managing adaptive trials with efficiency.  Researchers taking an adaptive approach to trial design will benefit from seeking out an EDC that provides them with the ability not only to make mid-study changes but to do so in a surgical and non-disruptive manner.  Medrio allows users to make select changes to select forms while a study is in progress, as opposed to the wholesale redesign of a study database that is required elsewhere.  Users can also test their changes in a development environment separate from the ongoing study, instead of taking the entire study offline until the changes are finalized and deployed. The ability to make mid-study changes is one thing; the ability to do so without delaying the study or, even worse, starting from scratch will allow researchers to conduct adaptive clinical trials without paying for it in lost efficiency.  Download Our eBook: What Small Teams Need in a Strategic CDMS/EDC Partner Why Phase I? Given the long-term impact that study design can have on a treatment’s success, the degree to which an EDC company can accommodate adaptive trials is an important consideration. There are, after all, reasons why adaptive designs are particularly prevalent in Phase I trials.  According to adaptive trial experts, one of those reasons is that the ability to optimize the results of a Phase I trial significantly increases the chances of success in the next phases of a drug’s development.(2) Modifying certain aspects of a study database as needed during an adaptive trial is one of the most effective ways of achieving that optimization. The question, therefore, of whether an EDC is robust at accommodating adaptive trial designs is one that can have reverberations from Phase I all the way to FDA submission. Researchers would be wise to consider this question thoroughly before making an EDC selection. References:

Statistics suggest that Phase I clinical trials, while by no means free of challenges, are more manageable than later phases. They tend to take less time and cost less money; the drugs they test have a comfortable 70% chance of moving on to the next phase.(1) These figures are a reprieve from some of the realities that make Phase I trials, in some respects, uniquely stressful. The absence of a safety profile for the drug being tested can make subject recruitment particularly challenging. And any errors or delays in Phase I can set the tone for the rest of the drug development process. But what if the statistics that ease these pressures — the shorter timelines, lower price tags, and high success rates — are changing? A blogger at Bracken Data, a company providing analysis of clinical trial data, recently noted that the size of the average Phase I clinical trial seems to be increasing. Based on searches on ClinicalTrials.gov, the average Phase I enrollment increased 14% between 2013 and 2015, from 50 to 57. More patients could mean more sites, more forms, and more data, adding time and, consequently, expenses to these trials. This could be exacerbated by other trends adding complexity to Phase I, such as higher rates of outsourcing to CROs and study designs that integrate single ascending dose (SAD) and multiple ascending dose (MAD) approaches. If the years ahead bring larger, more complex Phase I clinical trials, what can researchers do to stunt the spikes in timeline and expense that may come as a result? Simple tools for complex data management As drug development becomes more complex and expensive in Phase I and beyond, Electronic Data Capture (EDC) has become almost synonymous with quick study build and data management. And as demand for EDC increases, the industry has been a venue of intense competition, with vendors racing to develop the next big thing. But when it comes to creating efficiencies that keep timelines and costs down, truly elite eClinical software depends on more than the sleekest and savviest new product or feature; just as important is whether the software is actually user-friendly. When evaluating EDC vendors, researchers should analyze not only the capabilities of a given software but the quality of its interface. How feasible it is to minimize timelines in increasingly large and complex Phase I studies depends in large part on the answers to these questions: This is a reality Medrio has kept in mind while developing our software. While we regularly release products, features, and upgrades that create new successes for users, one of the most popular qualities of the software is its basic user-friendliness. Its ease of navigation and intuitive interface has earned Medrio a reputation as an ideal software for efficient study build and data management. This, in fact, sets us apart from some of the biggest names in EDC, who may have all the bells and whistles a researcher could ask for but still generate complaints about inefficient or overly complicated navigation. They may require users to scroll from one visit page to the next in order to access an eCRF instead of displaying all eCRFs in one easily accessible location; they may continue to display variables and forms that previously entered data has rendered irrelevant. Cases like these show that no matter how far-reaching the capabilities of an EDC software may be, users will still struggle if the software lacks efficient, sensible design. Phase I clinical trials are already notoriously time-sensitive. If the analysis from Bracken Data and the current interest in integrating SAD and MAD approaches do indeed foreshadow a trend toward larger Phase I trials with more complex protocols, they will become even more so. Without the efficiencies made possible by an intuitive and user-friendly eClinical software, such a shift could cause timelines and budgets to spiral out of control. References:

Anyone with an involvement or interest in clinical research is likely to be aware of the challenges in clinical trials, and in getting their compounds approved by the FDA. The low rates at which drugs make it all the way through the research process is a favorite topic of blogs and journalistic outlets covering clinical research. Many of the drugs that fall by the wayside suffer that fate because of unfavorable efficacy data in the middle and later phases. Many others, though, fall victim to administrative or technical challenges — and these issues often arise not as a compound nears the finish line, but as early as the nascent stages of Phase I. Here are three obstacles that researchers commonly face early in Phase I, as well as some insight into how the right eClinical software can nip some of those obstacles in the bud. 1. Patient Recruitment Across all phases of research, challenges in patient recruitment are often accounted for by a lack of awareness of clinical trials and skepticism of the tested compound’s efficacy compared to existing treatments. Recruitment challenges in Phase I, however, have their own additional causes. Perhaps 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. A 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. 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. As we discussed in a post last year, the time spent on negotiations with clinical research sites tends to decrease as research moves from one clinical phase to the next. It follows, then, that the negotiation period tends to be the longest in Phase I. In fact, Phase I site negotiations often last more than twice as long as many sponsors prefer. These lengthy negotiation periods threaten to derail timelines even before research has begun. 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. Indeed, 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. Outside of oncology, there is another risk: the Tufts study reported that most Phase I 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. A Software Solution to 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 software can provide both direct and oblique solutions to 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 the software has a user-friendly drag-and-drop interface that 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. The outcomes of Phase I trials set the tone for the rest of the research process. The value of a strong start, then, is difficult to overstate. While these trials face considerable challenges in their early stages, a robust and intuitive EDC like Medrio is available to mitigate those challenges.

Let’s say you’ve gone through a rigorous selection process to pick your EDC, deployed it, and are ready to train your staff. Your data management team encompasses a wide spectrum of EDC experience — some data managers have used EDC a lot, others very little — and their training needs, therefore, vary as well. But to your dismay, you discover that only one training option is available: in-person training, beginning with EDC basics, on terms and schedule dictated by the vendor. That’s a problem on several levels. For starters, coordinating schedules and finding a venue for the training can be time-consuming and inconvenient. But the bigger issue is that you’re paying for unnecessary training, delaying start times for studies, and tying up the time of your experienced users to attend sessions they don’t need. Long-time EDC users may find this scenario familiar. But at a time when the EDC industry is making great strides to optimize the user experience, it has become easier than ever to avoid. The push to make EDC more user-friendly extends beyond the software itself to include training and support offerings as well. What does this mean at Medrio? What have we learned about EDC training needs through our interactions with users, and what steps have we taken to put users in control of this essential process? Flexible eLearning for a Shorter Time to Competency We’ve spent lots of time in conversation with lots of EDC users, and found that those conversations often turn to frustrations in the training realm. Users are looking for the flexibility to deliver training by sponsor instead of being confined to an EDC-mandated training regimen. They’re finding that once their costly in-person training sessions finish covering the basics, no time remains to go over the specific needs of their studies. These conversations have thoroughly informed the flexibility with which Medrio has approached training. Users can, for example, opt-out of formal EDC training and integrate training with the Study Initiation Visit. But it’s not enough to offer flexibility through policy — just as important to users is the availability of cutting-edge resources. Observers of the EDC market have noticed that eLearning seems to be on the rise in the industry’s training offerings. With Medrio eLearning, an online on-demand training service, we’ve aimed to address common training frustrations by providing users with general competency in the software, so that any necessary subsequent in-person training can focus on their specific needs instead of going over the basics. And it allows platform users to train at their own convenience, rather than on a schedule dictated by a vendor. Individuals can advance their Medrio knowledge through instructional videos and training modules, and earn their certification. Medrio Customer Support and Services The EDC industry’s increasing focus on maximizing user experience is largely driven by technology and simplicity: the flexibility of the cloud, the rapid data entry made possible with eSource, or the ability to build studies without programming. This also ties into the broader shift from paper-based data collection to electronic methods, as discussed in our blog on ePRO vs Paper Strategies in Clinical Trials.  But on the administrative side, it’s often driven more by the notion that EDC users are entitled to a comprehensive support system that better enables them to conduct their important research with speed and ease. Here are a few things we see as essential rights for EDC users: Until recently, competition in the EDC industry was a matter of racing to convert sponsors and CROs from paper-based data management. Now that electronic processes have become the norm, however, the focus has shifted to making solutions exceptional in terms of user-friendliness. From this perspective, there has never been a better time to be an EDC user.