By Ed Miseta, Chief Editor, Clinical Leader
Follow Me On Twitter @EdClinical
Two of the biggest challenges sponsors face when it comes to clinical trials are bringing down the cost of studies and patient recruitment/retention. One aspect of trials that truly has the potential to impact both is the latest advances in technology. The Internet, social media, electronic data collection, and mobile technologies can reduce the time, effort, and cost of gathering data and significantly improve the experience for trial participants.
Unfortunately, the pharma industry is not known for its rapid acceptance of new technologies. Even technologies that are proven to work and are given the green light by the FDA can be slow to make their way into sponsor firms. We pulled together four pharma executives with a strong background in data and technology to get their thoughts on where we stand with technology adoption, and what new advancements have the best potential to transform the way we conduct trials. The participants in our roundtable are:
What technology-related trend do you feel will have the biggest impact on clinical trials in the coming years?
ABBE STEEL: When Apple recently launched ResearchKit, unleashing the open-source platform and allowing the makers of apps and wearable devices to tap into the capabilities of the iPhone’s wide range of inherent sensors, they opened the door for wearable devices to have a greater impact on clinical trials. The ability to gather data passively, only requiring the patient to wear the device, will mean a greater capacity for insight. At the same time, recruitment and retention should be boosted significantly by the convenience and unobtrusive nature of this type of data collection.
The trend toward instant access to real-time data could have a far-reaching impact on clinical trials over the next few years. Studies that incorporate some type of wearable technology that provides a constant data stream may result in faster analysis and data elements we don’t currently collect.
JOE KIM: There’s no question that patient enrollment in clinical trials is one of the top industry-wide challenges. As Abbe mentioned, technologies that help improve awareness of clinical trials and connectivity between patients and clinical trials are on the rise, and I’m hopeful that they will ultimately enable patients to enroll in clinical trials more efficiently. We’re specifically looking at engaging ePatients, or patients who are well-informed and empowered by digital technology and see themselves as equal partners with their doctors and healthcare providers. We are evaluating what ePatients need and want from their digital experience in order to improve clinical research in forums such as clinical trial matching services and online communities/ social media. Ultimately, ePatients are on their way to becoming more of the norm rather than the exception, and by mobilizing this community, we can empower ePatients to have a significant impact on enrollment, study participation, design, and more.
DAVE BORBAS: Tablets, data integration between systems, and smartphone technology. Tablets and smartphones are common devices across the world and are extremely familiar to users. That means patients, research center teams, and physicians are comfortable with these technologies and will expect good performance from them. Training that is generalized will be a diminishing need, and training will only be needed on the study applications. These technologies have Wi-Fi and cellular connectivity built in and will enable a wide-area use for research protocols.
On the database back end, integration between systems means that once data is entered it will be available in multiple systems. This decreases the need to reconcile data between them and provides the users common data for basic subject information like demographics, ID numbers, and other types of test results like labs, questionnaires, and ECGs. This means more correct data shared across systems, and it will be more quickly available.
TIM DAVIS: I certainly agree with all of what has already been said. Mobile solutions are ideally placed to address the challenges that today’s clinical studies pose and are now being implemented as a means of communicating directly with patients across broad demographics and multiple widespread geographic locations in clinical trials. From enhancing adherence and retention through to the collection of time-stamped and authenticated PRO (Patient Reported Outcomes) data, mobile solutions enable each trial to be designed to include a relevant, standardized, and tailored communication plan. Patients can therefore be prompted to take medication, record data, and attend site visits. Additionally, through the inclusion of timely and relevant educational and motivational messages, they can be better engaged throughout the duration of the study.
"The biggest breakthrough in clinical development will be the increase in patient-centric studies."
What are the most important factors that should be considered when deciding on the use of mobile health technology for a clinical study?
DAVIS: As patient-centricity is now seen as vital to pharmaceutical R&D success, the simplification of methods to capture and report patient data obtained during a clinical trial is critical, helping to facilitate continuous patient engagement for the duration of the study. Therefore, putting the patients and their needs at the center of each solution should be the prime consideration when deciding on the use of mobile technology in clinical studies. Giving particular consideration to the needs of the study population up front can ensure that the technology used to capture and disseminate clinical assessments is both practical and effective in addressing protocol requirements, and is also engaging and convenient for study participants.
The main factor is whether the data is being collected for the primary or secondary endpoints. This will determine how much validation and programming is needed and what type of technologies to use. For example, collecting primary efficacy data that is critical to the success or failure of the analysis of the study means that you need to exercise great care when selecting the technology used and manage the programming and validation very well so that you can withstand the audit questions that will follow. If you are using a visual analog scale that needs to have a precise screen display, then using a Web interface will not provide the control that is needed.
If your data collected has less strict requirements or only uses text displays, then it may be possible to use a variety of consumer-type devices instead of a locked-down or purpose-built device. This is a brief description of the decision area that you have to be concerned about. If you have more critical and strict requirements, your time and cost will increase to match the risk of the project and importance of the data.
STEEL: There are a number of factors that I think need to be considered. At a minimum, I believe any technology should be patient-friendly, applicable to the protocol, a fit for the patient population under consideration, and able to perform remote monitoring. Additionally, it should have the ability to report adverse events to a live person and customized to the country it will be used in.
"We are seeing an increased demand for speed and targeted enrollment of the best patients."
KIM: Well, there’s mobile health and then there’s mobile health. If we are talking about new ways to measure a primary endpoint using mobile tech or a wearable device — which in simple, but exciting terms is about moving a traditional endpoint away from an “asking” perspective to one of “measuring” — a body of evidence and credible scientists will need to support this shift. While this could mean more expensive trials, it also could translate into smaller, faster trials. The challenge for a clinical trial team will be to consider how to deploy mobile health technologies for use in clinical trials without any additional challenges than it already takes to manage a study. I do recommend we find a way to practice use of any new technologies before using them in an actual clinical trial, as a way to learn and create best practices.
Patient recruitment and retention has been a challenge in trials for years. What advancements do you see having the biggest impact on patients?
KIM: There are several factors to consider as we strive to advance the development and implementation of clinical studies. In general, we would look to industry to improve raising awareness, increasing Web traffic, using technology, and creating patient-friendly trial designs. In addition, regulations in transparency will be incredibly important to help better educate potential study participants about clinical research. Embracing notions of transparency and turning it into a way to delight our volunteers has the potential to empower individuals to become research advocates. We want to create a community so that those living with a disease and their loved ones not only have a support system, but have information at their fingertips so they can participate in applicable clinical trials. New technology is not necessarily the answer to fix the challenges associated with patient recruitment. Instead, industry needs to work to continue to raise awareness of clinical trial opportunities in addition to telling the story of the value of clinical trial participation in a way that resonates with patients.
STEEL: As technology becomes more sophisticated, and pharmaceutical companies become more engaged with patients and recognize them as key stakeholders in the design process, mobile health technology will impact patients not only during the trial but before the protocol is even designed.
For example, our partnership with StoryVine to create the Patient Experience via a mobile app has led to capturing insights from patients, in their own words, regarding potential study designs and eliciting their feedback regarding potential hurdles to patient-centricity that might prevent them from joining a study or cause them to drop out at a later date.
The Patient Experience provides researchers with a way to see and hear patients who may be halfway around the world, sitting in their own home. At the same time, patients are empowered by this technology. The firsthand input provided by people who are living with disease is having a measurable impact on study design, which ultimately benefits patient recruitment and retention programs.
BORBAS: eRecruiting methods include Web, mobile, and social media. We are moving toward these methods as a primary source of information. Websites are also a good way to interact with patients. We are seeing an increased demand for speed and targeted enrollment of the best patients. These methods will better meet those demands than more traditional methods.
DAVIS: The clinical research industry is increasingly adopting a more patient-centric approach that recognizes that if patients are supported throughout a study, higher levels of compliance and retention can be achieved. Listening to the patient during drug development and partnering throughout their clinical trial experience, as well as the simplification of methods to capture and report patient data obtained during the trial, is now seen as vital to pharmaceutical R&D success. Sponsors and CROs have demonstrated a growing desire to simplify clinical data collection by implementing innovative solutions that provide greater access (in real time) to better quality data, in a more cost-effective way — while in parallel helping to facilitate continuous patient engagement for the duration of the study.
A recent study seemed to show that recruitment via texting may have significant advantages over email. Are there any downsides, and do you expect the use of texting to increase in the future?
BORBAS: I think that despite the impersonal nature of texting, people seem to be comfortable with it, and it is a good way to communicate. You have some limitations with texting (the size of the message and the content) that are easily surpassed by an HTML email. However, this is still a good way to make an initial connection that can then deepen over time. In addition, technology can support this with text-based reminders when a patient is on a protocol. In both situations, privacy will likely be the greatest concern.
STEEL: As we become more dependent on technology as a society, and more comfortable with the ways in which it permeates our lives, the idea of recruiting via text message becomes more appealing. While texting may provide a greater level of convenience and immediacy, it also has several potential pitfalls. Autocorrect, for example, can completely change the sender’s intended message. Errors that are commonplace and socially accepted in casual texting can have disastrous results in the context of clinical trial recruitment where accuracy is imperative.
While most cellphone plans include unlimited free texting, some people still pay for texts, especially outside the U.S., and may not appreciate a recruitment screening model driven through back and forth text messaging. However, given the convenience and widespread use of texting, the trend of using it as a recruitment tool is likely to grow.
"The idea of central or remote monitoring has a huge potential to decrease costs."
KIM: According to Pew Research Center, among cellphone owners across 32 countries, 76 percent use text messaging via their phones. This is similar to the 83 percent of cell owners in the U.S. who text. Since the invention of the cellphone, the comfort with which we text each other has skyrocketed globally because of bigger screens and how text threads are organized. Data also shows that texting is exploding across all age groups, even those older than 65 years of age. My mother, who is 70, is even using a video instant message app, and she just got her first smartphone this year. The upsides to texting are numerous — the user dictates the cadence, content is short, enduring (enough), and today it’s quite normal for threads to go on for days and weeks. Responding to a call to action via text allows potential volunteers to easily weave their engagement into their busy lives. In a previous life, I saw more than one-third of research volunteers responding via a text modality. Contrast that with call centers, where patients are in for an unknown time commitment, or visiting new websites, which have their own learning curves.
Cutting the cost of trials is a concern for most pharma executives. What trends in technology and data collection do you feel will have the biggest impact in this area?
DAVIS: The opportunities mobile solutions hold for the clinical industry are vast, with the potential to reduce the major financial burdens as a result of increasing pressure to progress drugs through clinical trials faster. With trials now commonly being conducted on a global scale, increasing efficiencies in data management is critical, and a “device inclusive” approach (enabling the use of any connected device during studies) can deliver return on investment through a number of avenues. Additionally, the use of a familiar and engaging method of capturing data can reduce missing data points and hence increase quality. This, combined with greater retention of patients, can reduce the need to “pad” the sample size. In large events-driven outcomes trials, by retaining the maximum pool of patients in which to observe events, studies can be brought to an earlier close, reducing their overall cost and duration.
KIM: The idea of central or remote monitoring has a huge potential to decrease costs, given that the lion’s share of costs is related to monitoring. In order to do this, the industry needs to explore going digital with its activities, which is of course easier said than done. But, maybe the more challenging thing is to make sure local regulations allow for this approach, for all study-related activities. If you’ve created conditions for 99 percent of the data to be remotely monitored, that remaining 1 percent will still create the need for a monitoring visit by a human.
STEEL: Most definitely, the biggest breakthrough in clinical development will be the increase in patient-centric studies. These studies are built around the patient, reducing the burden on sites and patients. Today, there are a tremendous number of channels with which to communicate with patients. The Internet has not only facilitated increased patients’ access to information, but it has also enabled new pathways for patients to find and access research. As we get the patient voice more involved in the design of trials, I think we will see better data and better retention, which will help to reduce the costs. Incorporate that feedback into bring your own device (BYOD) models, study-specific mobile apps, and disease-specific medical devices (i.e., wireless glucometers), and our industry will certainly see a reduction in overall trial costs.
"Listening to the patient during drug development and partnering throughout their clinical trial experience … is now seen as vital to pharmaceutical R&D success."
BORBAS: Based on my experience, data costs are about 20 to 25 percent of a total study. Therefore, reducing cost is more about qualifying patients and reducing the number of screen failures. The other major cost is time. With data management, the question is whether we can decrease the electronic data capture (EDC) build time and database lock time. If so, we can start sooner and faster. However, this is harder to put into practice than it sounds. We have built EDC systems in six-and-a-half weeks, but doing so requires strong support from the entire project team.
Are companies adopting eConsent in trials? What challenges are holding up adoption, and how can they be overcome?
KIM: While I see more and more companies adopting eConsent, challenges still remain. A major challenge revolves around the debate between provisioning devices versus allowing sites to BYOD. While this obviously drives cost, the ghost of EDC past comes to mind as well — many of us still remember the days when stacks of thick, heavy laptops accumulated at the site, each one provisioned for a separate study. At the time, cloud computing had not caught up with EDC, and so this was arguably a necessity. This may not need to be a constraint today. Another challenge is aligning with the local regulations that dictate rules around consenting and monitoring of that consent. The FDA just released its guidance, Use of Electronic Informed Consent in Clinical Investigations, and while this should help normalize perspectives on this subject, there are many countries where research takes place and the industry has to be careful to stay within the regulations of every country. eConsent providers can consider redirecting marketing resources in order to generate high-quality legal opinions that help the industry better understand these implications around the world.
DAVIS: Currently there are a limited number of organizations that specialize in the adoption of eConsent processing as a commercial opportunity. At present the results from the first industry pilot studies are only just coming to the attention of the broader audience. Additionally, they are typically focused on the English language versions in the first instance (as any language requirements for multinational studies are adding complexity to the mix) and the focus is still very much on the U.S. market. However, eConsent has been gaining momentum in the last couple of years as organizations are becoming more confident in it and as people are starting to make the case for change in their own companies, and it’s set to become more prevalent particularly with the recently released draft guidance on eConsent by FDA.
Which mobile technologies do you believe will have the biggest impact on trials?
STEEL: The trend will be toward trial-specific interactive patient engagement tools. An app that reminds patients to take their study medication and about upcoming appointments, gathers data from wearable devices and provides a knowledge base of information regarding the study in a patient-friendly format will alignimpact the overall patient experience, resulting in increased retention and compliance. Patients who are supported throughout the study with meaningful engagement tools will go on to advocate to others about their positive experience, helping to improve not only retention but recruitment as well.
DAVIS: The rise of electronic patient reported outcome (ePRO) tools, especially those implemented through everyday mobile technology, has transformed how CROs and sponsors approach patient engagement in clinical trials. SMS messaging, emails, and in-app notifications now allow sponsors to incorporate a range of reminder, educational, and motivational interventions within study protocols, where previously patients typically would have been left with no support between site visits. Additionally, research sponsors are able to monitor safety, manage compliance (including visit attendance, medication, correct preparation for procedures, home-based actions, etc.), and more closely ensure patient retention throughout the study period. This has not only made clinical trials an easier and more useful experience for patients but has also enabled researchers to collect and process comprehensive data quickly, accurately, and reliably.
KIM: While I will not comment on the specific research or products of other companies, what I can say is that Lilly is committed to transforming clinical development — for science, for innovation, and for those suffering from disease. Part of this transformation includes thinking about new ways to support patients in their successful participation, developing the right medicines for unmet needs, and measuring their efficacy in ways that are meaningful to regulators, healthcare providers, payers, and, most importantly, patients. We are excited to see how aesthetically pleasing, easy-to-use technology can potentially help play a role in enhancing the way research is conducted.