Silent Partners: How Virtual Clinical Trials Affect the Investigator Site

By Nathan Morton, Director and Co-Owner of the Coastal Carolina Research Center, with Claire Sears, Director of Investigator Engagement, DrugDev

Technology and innovation are changing the clinical landscape for both investigators and sites. This is creating both opportunities and challenges for sites regarding their partnering approach with sponsors and CROs. As that landscape continues to change, opportunities to improve the implementation of these technologies will, in turn, help to improve the clinical trial experience for patients.

This article examines some of these issues and is adapted from an original InvestigatorView webinar, a series of unfiltered opinions directly from leading sites hosted by DrugDev. Learn more at www.drugdev.com

Complexity in Clinical Trials

Since I’ve been involved with clinical trials there has been a gradual shift away from entirely sponsor-controlled clinical trial infrastructures to a more diverse set of companies with which a site interacts. To give you an example, in a study we did in a particular indication in fall 2004, our site interacted with four vendors.  Fast-forward 10 years to fall 2014, and for a study in the same indication we interacted with 15 different vendors.

To a large extent these changes have served their purpose by managing complicated clinical trials better by improving and standardizing data quality, streamlining data collection processes, and providing many ancillary R&D services to sponsors. 

And sites are reacting and adapting to these changes – yet our brick and mortar environment remains the same. We are dealing with more complicated trials, more difficult inclusion/exclusion criteria, more vendor relationships, and the need to collect more data. 

Implementation of New Technologies and Processes

As an investigative research site, we’ve encountered many new technologies being integrated into our clinical trials: electronic patient diaries, electronic data collection, and many more.  However, while these new technologies have created efficiencies and cost savings at the sponsor and CRO levels, these benefits are not passing down to sites. The impact we are seeing is a major upsurge of information and communication needs from all directions, plus significantly more burdensome training requirements. If you're a high volume site like ours, managing over 50 different user names or passwords at one time is not uncommon.

We’re a site that embraces new technology, and we’re well equipped to deal with many of the changes that are being introduced into clinical trial operations.  However, it’s a real issue now that technology and the related vendors are part of the site’s everyday life. What happens when the technology fails? I'll cite four examples: 

eDiaries That Don’t Work – Our site has conducted eight overactive bladder (OAB) trials within the past six years. All but 15 patients we enrolled into one particular study had participated in previous OAB trials, and this new study included eDiaries. Every patient but one had to come back to us during the run-in stage and replace their eDiary. There were no paper diaries as potential backups. To their credit, the sponsor sent a representative to our site to discuss these issues, but while they understood our problem there were no alternatives. The sponsor was a victim of the technology and the process failure as much as we were. And, I question whether these patients will sign up for another research study after this experience. 

Redundant Training – The study training requirements in a trial jeopardized our relationship with contracted investigators, who had to complete the exact same psychiatric rater training for two different trials for the same indication – and had to redo the training every six months.  Over the course of the year, they did the same training four times, and each training session took hours to complete. You can imagine the frustration level of the investigators, who also had other trials that needed their attention as well. 

Changing Electronic Data Capture Guidelines – We screened 360 patients and randomized 170 for a study that started in early 2012. The screening was completed in December 2012. Ninety-eight percent of the study's visits occurred prior to January 2014. As of mid-February 2015 we still had 60 queries pending for this trial, nearly all of which relate to visits which occurred in 2012.  The queries in large part resulted from tweaks in the EDC guidelines, and changes in how and what the sponsor wanted reporting. Not only is the cost of these queries excessive, but the work itself is frustrating for the coordinators. 

Recruiting Problems – We did a Phase IIA dose-ranging Osteoarthritis of the knee trial a couple of years ago. The entry criteria were very difficult and the study-wide screen failure rates were 80%. The sponsor contracted with a central advertising and recruitment vendor. We spent hours onsite going through our screen failures, prescreen failures and other potential obstacles. The vendor offered solutions including signing an agreement with the vendor so they could help us contact 800+ patients.  After their first visit, they contacted us weekly asking our recruiters to complete logs which showed who we prescreened and the results of those prescreens. We expected supplemental recruitment help, but they never contacted our Osteoarthritis population from the list we provided. Two months later another vendor contacted me about the same trial asking the same questions, and wanted to go through the process again. Thankfully, the new recruitment vendor was much more beneficial. 

In all these cases there were good intentions but the technology or the process became a burden to the site, and a problem for the sponsors. Technology is not a solution if it’s implemented incorrectly. How technology strategies are implemented matters. Sponsors and CROs do not have standards for technology adoption, but I hope we can move in that direction. 

Preparing Sites for New Technologies

A new wave of modern technology is being implemented into clinical trials (as one of many examples, DrugDev sponsors an Innovation Lab which is a technology incubator to accelerate emerging solutions in clinical trial automation.)  This started as a way to meet consumer demands for real time fitness metrics with devices like smart watches and wristbands which now are being considered, validated, and implemented in study designs. At Coastal Carolina Research, we’re currently involved in a Smartphone application validation trial for Osteoarthritis, and also a trial that is studying new drug adherence solutions for multiple sclerosis. 

We’re really excited by some of the new drug adherence solutions – smartcaps, smart pills, breath analyzers– because they have much better potential for monitoring compliance than traditional drug accountability methods.

The good news is that using these new solutions could finally allow sites to reduce the overhead costs of conducting clinical trials. My site is preparing to launch new trials utilizing these new technologies. I expect them to become part of the standard research process the way EDC systems did back in 2005-2006. But given how technology has added complexity at the site level over the past 10 years we need to adopt these solutions with care. 

I would ask all sponsors and CROs to answer one question before they bring new technology solutions into clinical trials: Will these technologies make the life of the study coordinator and the patient more, or less, burdensome? 

The skill set of our coordinator staff will have to be reassessed in this new environment. The importance of nursing experience will likely diminish and teaching skills will become more prominent. Mobile technology may allow for faster integration into eClinical systems, but most study coordinators are not technology savvy enough to troubleshoot and manage these systems when there are data collection problems.

We had a study coordinator with 25 years of experience, and when she retired last year we had a brief exit interview. I'll never forget what she said: she had never worked as hard as a study coordinator as she had over the past three years. Despite her many years of experience, her skill set no longer matched the needs of the industry or the studies she worked on. I suspect sponsors and CROs will have the same issues with monitors. The skill set requirements will necessarily change with the implementation of these new technologies. 

Give the Patient Flexibility and Options

When it comes to adding technology and drug adherence solutions, patient ease of use is the key. Will it make participating convenient or a burden? The last thing you want patients to do is to decide not to participate in or drop a trial because of problems with technology, as in my earlier example from the OAB study. 

We need to make it easier for patients to participate in the research process. I have a “glass-half-full” outlook and am cautiously optimistic about the promise of virtual trials.  The key is to put the welfare of the patient first and foremost.  And we have to make our trials more accessible – for example it was shown that 10 minutes of additional travel time produced an 11% reduction in participation in a NCI cancer trial.  

When it comes to using technology, make it entertaining and easy to use. People love to be engaged. For example, I've seen some attractive electronic consent solutions from a number of vendors. 

We often hear the phrase “patient choice” in healthcare. Surely we ought to extend that to clinical trials. Let’s consider letting patients chose what devices they use for some of the data entry systems. When it’s possible allow patients to use the technologies they currently own. That makes it more convenient for patients and less expensive for sponsors. If you have the software available in a cloud-based platform, patients can access it with their own PCs, tablets or smartphones. Make it easy for patients to integrate the trial into their everyday lives.

And let’s not be so rigid and use a one-size-fits-all approach. Plenty of drugs have been approved and been brought to market based on paper diaries, so we can have contingencies in place. Technology is great, but ultimately you need the data. If the technology is too cumbersome to collect the data it serves no purpose. If the patient prefers paper over a device, make that an option.

My simple definition of “patient-centric clinical trials” is the following: If there is a patient who is eligible and wants to participate in a trial, we need to bring the trial to the patient and make it happen, supported by new technology and new processes.

My checklist for increasing patient access:

• Increase patient engagement and expand geographic scope
• Co-operate with and empower patient advocacy groups
• Incorporate telemedicine, video visits, increase telephone visits
• Increase home visits
• Potentially utilize and access existing medical infrastructure
• Eliminate barriers and provide access for new investigators
• Develop real world, evidence based clinical trials (ie: GSK Salford Lung Cancer trial in UK)

Suggestions for the New Age of Clinical Trials

We can develop real-world, evidence-based, technologically driven clinical trials. However, investigators and sites do need more support and I’d offer the following suggestions to help drive us into the new age. 

• We should be doing more to provide access into the clinical research for new investigators, or maybe even consider creating a new class of investigators who can simply help screen for trials, this could speed recruitment and increase efficiency and help reduce or mitigate site screen failure costs.
• Let’s relax the inclusion/exclusion criteria, or at least not add to it. Over the past couple of years these criteria have expanded by about 14%. If this trend continues we will have a hard time finding anyone who can qualify for a trial.
• If we can go paperless sites can improve our workflow solutions at every level and develop our infrastructure around this new model (ie: eConsents, eSource, improve workflow based solutions, cloud-based TMF and content management). 
• When sponsors bring in new technologies, sites should be part of the validation process to help new technologies be accepted more by IRBs and regulatory agencies. 
• We all know drug compliance is a problem. If we look to the government or regulators to figure this out for us, we'll wait a long time. It has to start with sites. We can drive the innovation if we have a collective voice, looking at new drug adherence solutions (breath based, smart pill, smart caps)
• Let’s take another look at investigational product delivery.  Currently my site and others serve as overpriced warehouses for an investigational product, which we monitor constantly at a considerable cost. It's IP that no one is actually using at the moment. We potentially could use existing medical infrastructure better in the delivery system.  
• Consider more non-traditional study designs (ie: adaptive designs, Master Protocols)
• Explore potential laboratory alternatives (eg: Theranos Lab)
• Reduce the research site footprint (ie: home based coordinators, reduced sub-I’s, lower overhead)

Make Sites Partners in Clinical Research

The clinical trial process in its current form is not sustainable long-term, and sites feel a lack of control.  The level of mergers and acquisitions is indicative of this fact. Sites can be innovation drivers, but we need a seat at the table with sponsors and CROs to replace the top-down approach that has occurred with previous implementations of emerging technologies.  It is my feeling that innovation of the clinical trial process requires much more than adding more technology.

If new technologies are implemented in the years ahead and we’re still running on the same clinical trial infrastructure model, it won’t work because sites can’t afford it. Study coordinators at my site spend 35%-40% of their days with patients. The rest of their day they sit at their desks – and like many others, I’m paying for seven empty exam rooms.   

Our goal is to partner with sponsors and CROs to enable virtual clinical trials to improve patient access, reduce costs, with ultimately be able to do more trials and bring more good quality medicines to more patients. 

About the Authors

Nathan Morton has overseen more than 350 clinical trials in a broad spectrum of therapeutic areas. Prior to joining the pharmaceutical industry Nathan was a cryptologist for the United States Navy and served in several business development and management roles within the healthcare industry.  Nathan can be reached at nmorton@coastalcarolinaresearch.com. 

 

Claire Sears, PhD, is Director of Investigator Engagement at DrugDev. She firmly believes closer relationships between investigators, sites and industry can bring great benefits to the clinical trials process. Claire can be reached at Claire.sears@drugdev.com