By Ed Miseta, Chief Editor, Clinical Leader
Follow Me On Twitter @EdClinical
Advancements in technology will continue to propel efficiencies in clinical trials in 2016 and beyond. That is the main takeaway from four experts I interviewed who shared their insights on trends expected in the clinical arena. Companies are continuing to turn to risk-based monitoring (RBM) to identify risk and leverage source data verification (SDV) where and when appropriate. Sponsors and CROs are increasingly turning to electronic health records (EHRs) and electronic medical records (EMRs) to identify potential patients for inclusion in clinical trials. It also seems 2016 and 2017 may well be the years that more companies finally begin to routinely incorporate mobile technologies into their trials. Any way you look at it, technology is quickly moving front and center in the effort to simplify, shorten, and bring down the cost of clinical trials.
To gather industry insights for this article, I spoke with the following individuals:
TRANSCELERATE DRIVES RBM ADOPTION
RBM IS NOT NEW, but based on the amount of coverage it has received in the last 18 to 24 months, you would think it is currently the hottest trend in clinical trials. Although the idea for RBM was introduced in concept papers and guidance by the FDA and EMA (European Medicines Agency) years ago, it wasn’t until TransCelerate released its own recommendations that the industry began to take notice.
“Across the industry, we are now seeing a significant number of studies that are using RBM,” says Zung. “We are finally starting to see it become embedded within the industry, and I believe 2016 will be the year we see RBM become a routine part of clinical trials. That is good news for the industry as a whole because it means we can move on from the days of companies sending CRAs (clinical research associates) to sites to perform 100 percent SDV. Going forward we will be using a lot more predictive analytics and data analytics to look at the data in near real time and in a more risk-based fashion, thereby mitigating the number of CRA visits.”
Sanders, who also serves as vice chair of the board for TransCelerate, agrees. “This is a concept that has been around for many years, but for it to really gain traction and start moving, we needed alignment at the industry level,” she says. “Without that, it would have had a low chance of working.”
While RBM may be a blessing for companies and sites, proper change management will be required to get all employees on board. You may already have heard stories about CRAs concerned about how their roles will change or potentially be eliminated as a result of RBM implementations. Zung believes those concerns are unfounded as he sees this as a natural evolution of the CRA role.
“If you look at the companies that are managing this transition well, you’ll see they are not getting rid of people in those roles; they are simply changing processes and evolving roles. Many job functions performed by CRAs are different today than they were 15 years ago and will be even more different in the clinical trials of the future. Rather than eliminating head count, many companies are taking employees and simply repositioning them to other areas where there is a need.”
Implementing RBM will require companies to perform some activities they may not be currently performing, such as more centralized monitoring and more predictive data analytics. Companies that are implementing RBM and doing it well have put focused change-management plans in place and have generally spent several years preparing for the RBM implementation. “If done right, this change should not come to employees as a surprise,” adds Zung. “It should be done as a gradual change that everyone is aware of and prepared to undertake.”
CAN EHRS SOLVE THE PATIENT RECRUITMENT DILEMMA?
TWENTY YEARS AGO patient recruitment was an issue for pharma. It still is today and will likely continue to be an issue in the future. But one change that many would agree is here to stay is that the old paradigm for recruiting patients is coming to an end. It used to be a sponsor could hire a CRO, the CRO would find sites that would promise a certain number of patients, and you would hold your breath hoping the sites would deliver.
Today, technology has enabled patients to get more involved in their treatments, which has enabled companies to recruit via patient advocacy groups, social media, mobile devices, and the Internet. Increasingly, more and more companies will also be making use of EHRs and EMRs.
“Technology proliferation, especially the growth of EHRs, EMRs, and PHRs [personal health records] has been huge,” notes Gillespie. “It all starts with EMRs located within a given institution. Some of these institutions have millions of records. We are also seeing growth in EHRs, which are records exchanged between two or more institutions. Finally, we are seeing growth in the number of health information exchanges. I believe all of these will increasingly be used for clinical trial recruitment.”
"There is still a technology gap between countries that we will also have to overcome in the future."
While all of these records will help find patients to participate in studies, Gillespie believes they will help with retention as well. Analytics, when properly used with these records, can help identify those patients who are also most likely to stay in a trial, which is just as important as the recruiting. But Gillespie also cautions individuals to not discount PHRs. “They are going to play into this as well,” he states. “Efforts in this space by Microsoft [HealthVault, launched in 2007] and Google [Google Health, launched in 2008] have not really caused a lot of excitement in consumers. While many thought PHRs would take off, it just hasn’t happened yet. But over time I think this will catch on and eventually we will be using those to recruit patients as well. There are still a few privacy and interoperability issues we need to work through, but all three types of electronic records will be the future of clinical trial recruitment.”
CREATE EFFICIENCIES IN TRIALS
IN ADDITION TO INCREASING RECRUITMENT AND RETENTION, EHRs have the potential to reduce the time and cost of clinical trials. According to Zung, work is under way to take data that has been collected by the physician in their EMR and move it directly into an EDC (electronic data capture) system. This will eliminate duplicate data entry.
White agrees. “That is the real future we hope to achieve from EHRs because this whole effort of collecting data, validating data, transferring it, and getting the source documents verified is a huge resource drain for both the sites and for pharma. We will eventually get there; the question is how quickly we can make all of these technologies searchable.”
Zung notes UCB will be running some pilot studies in 2016 to better understand how to move data from an EHR into an EDC. Although EHRs have been used to perform site feasibility and better understand where patients and doctors are located, he believes in 2016 and 2017 more companies will leverage the vast information that exists in EHRs and how to better capture and use that data.
White adds that an additional problem the industry will have to solve is the interoperability of proprietary platforms. For that reason, technology issues will prevent some of these records from being as searchable as soon as many might hope. But inevitably, she believes technology will get to the point where it will be able to search those records no matter what software platform it resides on.
According to White, a third-party company with proper authorization and patient approval will be able to go into those records and match up patients with available clinical trials. To better facilitate the process, getting patient approval from the outset should become a priority for physicians and clinics.
“Patients could sign a form indicating they want their records to be searchable for any available trials,” she says. “Patients could opt in when they see their doctor, and I believe physicians would be supportive. A recent survey by DrugDev reported that 75 percent of sites would be very amenable to having their records searched for a potential trial matchup.”
White admits things can get a bit more interesting when sites have to refer patients to a different location to be part of a study. But for that reason, she also predicts we will see growth in the ability of patients to participate in a trial from their home through digital devices.
"When you look at what companies mean by patient advocacy, the definitions can be pretty disparate."
James J. Gillespie
CROs will have a role to play as well. “They should try to figure out how they can help identify those patients via EHRs,” notes White. “In addition, if they identify solutions that could help sponsors pull that data from EHRs without having the additional interim step of data collection, this would be transformational for the entire clinical trial industry.”
As you might expect, EHRs will not be the same across countries, creating an additional hurdle the industry may have to overcome. Sanders adds, “You can have a very generic electronic health record that might then be tailored by each country to what they need. There are also language barriers that will need to be overcome to facilitate searches.”
Still, the advantages will be worth the effort. For example, Sanders says looking at biomarkers will be an efficient way of ensuring companies do not enroll more patients than are needed and give companies considerably more control over the recruitment effort. “If a sponsor is conducting a biomarker-driven study, there may be a database already available you can use,” she adds. “That will give companies a good indication of how many patients they might expect to see and where those patients are located.”
PATIENT-CENTRICITY WILL REMAIN A PRIORITY
ALL OF THE EXPERTS INTERVIEWED indicated patient-centricity will remain a high priority for pharma companies in 2016. For most companies, this will involve working with patients and patient groups to get their perspectives integrated into the trial-planning process.
Gillespie refers to the whole movement as empowering engaged patients. This movement has been happening throughout the healthcare system and is now crossing over into clinical trials. The primary factor driving the trend is actionable information becoming available to patients. There is more information available to patients regarding doctors, diseases, support groups, and of course clinical trials. Along with the additional information comes improved decision making on the part of patients, who now have a greater influence in the process.
“This is a major reason why we are seeing CROs and sponsors creating chief patient officer positions and including them on the executive team,” he says. “A review of the media sources covering clinical trials will reveal numerous articles on making patients a part of the planning process. Even consultants are jumping on board with it, and I think that movement is sure to continue into 2016.”
Still, for all the discussion about patientcentricity, many companies are hiring a patient advocacy officer for the first time. As a result, there is still a lot of discussion about what the term patient-centric actually means and how companies can best bring the patient voice in house.
“When you look at what companies mean by patient advocacy, the definitions can be pretty disparate,” notes Gillespie. “For some, any process, procedure, or change that makes a clinical trial process more patient-friendly is patient-centricity. It’s almost like achieving quality by design (QbD) on the patient side. But for others, that is not patient-centricity at all. For them, patient-centricity might mean actively speaking to, and receiving feedback from, a patient. That feedback can relate to the design of trial protocols and the conduct of each phase of the trial process.”
According to White, the patient-centricity movement will benefit patients but will also play a key role in helping pharma companies to get their medicines to market faster. With the problem of low patient participation expected to continue in 2016 and beyond, this effort will be a key step in increasing enrollment rates.
“When we have a new protocol design, especially one in a new disease state, we model it at an investigative site before it is finalized,” she says. “Patients and coordinators can then walk through the protocol to make sure it is feasible. It’s a great way to make protocols simpler and eliminate unnecessary burdens on patients. If you don’t perform that step, you may not find out until the trial is under way that patients are unable to fit the requirements into their schedule. If you lose them at that point, it is counterproductive to both the patients and the trial.”
White agrees true patient-centricity means getting patients more involved in trial design. Aside from patients themselves, she believes the person who is best able to tell you what is doable at the site level is the study coordinator. Reaching out to those individuals for input, as well as patients, is one of the best ways to create patient-friendly protocols.
“This input must be received at the study-design level,” notes White. “If you start incorporating it after the protocol is finalized, you will have to go through the amendment process, which is cumbersome. If you want even better feedback, have patients read your protocol and provide input into whether or not it is doable. This feedback is especially valuable when it comes from patients who are knowledgeable about clinical trials or have participated in one in the past. I have found many patients to be quite helpful and savvy. These patients will provide great advice on how to make sure you can answer the research questions while not unduly burdening patients.”
Sanders defines patient-centricity as working with patients to understand what their burden will be and then acting to properly address those concerns. This can take place from the trial planning process right up through the conduct of the trials themselves. Sanders believes the industry working together, in a manner similar to what TransCelerate is doing in other areas, is the best solution. By sharing experiences and coming up with some common practices for how companies can make patient participation in trials less cumbersome, as well as guidance on how to best implement them, companies can move the process along much faster and make a bigger impact in the lives of patients. We may also be able to engage patients who otherwise would not have considered participating in burdensome clinical trials. Finally, patients can provide invaluable input to protocol development and operational design.
MOBILE TECHNOLOGIES ARE READY FOR ADOPTION
ALL OF THE EXPERTS I INTERVIEWED were upbeat about the prospect of mobile technologies finally making a big push into clinical trials next year. “I think these technologies will play a big role in keeping patients involved in trials,” says Sanders. “However, I believe that to be truly successful, the treating physicians must gain a greater level of comfort with these technologies.”
Gillespie concurs that physician adoption will be an issue and sees it as a generational problem. “Younger physicians will tell you they love the new technologies, they love emailing their patients, and they like it when patients come in with their mobile devices. You do not see that level of enthusiasm in the older doctors,” he states.
Zung adds that these technologies have great potential, especially when it comes to eliminating paper. “Mobile technologies enable patients and sites to collect more data off a tablet or smartphone versus paper,” he says. “During the next few years more mobile technologies will be used and less paper will be used in trials.”
Today it is difficult to predict what mobile and wearable devices will look like in the future, but Zung predicts that in three to five years a significant number of devices will routinely be deployed in clinical trials to collect data and then move the information from the patient collecting it right into a data system. “There will be a direct link so we no longer have to go through different systems to collect that data,” he adds.
Direct data entry is also a hot topic at Lilly. White notes doctors and nurses having the ability to walk around with their tablet will greatly simplify the data collection process. Although this trend is gaining traction in the U.S. and Western Europe, in other areas of the world it is still rare to find sites with tablets or even computers in every room.
“There is still a technology gap between countries that we will also have to overcome in the future,” she says. The good news is that EHR adoption might step up to fill that gap. EHR adoption will be pretty far along in many countries, because having electronic records is just a very basic way of running a health network. If that’s the case, we can jump past some of these intermediate data entry solutions and get directly to the benefits of EHRs. That would truly be a good vision to have."