Nathan M. Lee

	Capturing the Patient’s Voice and Protecting Their Rights

	Technology’s role in clinical trial management is not new. However, that role continues to evolve as more ways are found to make processes simpler, quicker, and more secure in this digital age. At the same time, technology’s status in this area is quickly being upgraded from facilitator to influencer when it comes to approval of pharmaceutical products. What was first introduced as a revolutionary way to reduce human error and increase efficiency–while responding to the call for a louder patient “voice” in outcome reporting–is now often the make-or-break factor in the approval of marketing applications and in reimbursement decisions for many drugs and devices.

	Not only has this factor, called ePRO (for electronic Patient Reported Outcomes), impacted the way in which companies collect patient-reported data, but the technology that is taking the place of traditional paper and pen assessments is changing the way Institutional Review Boards (IRBs) evaluate protocol packages, and thus the strategy for actually getting the approval to begin a research trial. That’s because adding a technology aspect to the PRO element of a study introduces an additional complexity to navigate within the often-subjective area of patient advocacy that IRBs are in place to ensure. 

	“Patient reported outcomes involve a new set of conditions that, for some therapy areas, were previously relegated to post-approval or marketing trials,” says Karen Briegs, Vice President for 

result, an ePRO provider and specialty CRO focused on facilitating the electronic collection of clinical outcomes assessments by patients, clinicians, and observers. “Selection of the right PRO Measure is the first step and can be a speed bump in any trial’s initiation process because it opens up discussion among team members and other gatekeepers about validity, patient burden, and integration of perceptive data with other biometric measures. Add in migration to one of the legacy electronic methods of data collection and it becomes even more challenging although the payoff in terms of clean and complete data is certainly a compelling driver.”

	As Briegs points out, “Because of the greater demand for patient representation, [this] is something that has to quickly become mainstream–and addressing the details is a valid concern for many sponsors.”

	Clearly, the way in which ePRO is executed as part of a study will play a critical role in clearing the marketing approval hurdle. And it’s not just about whether or not a country’s governing regulatory agency approves (for instance, the FDA in the United States); IRBs are in that group of “gatekeepers” that Briegs describes. In carrying out its important role of ensuring patient rights are protected in human research during its review of research trial designs and materials, an IRB has the power to approve, deny or insist upon changes to studies to this end. In this way, it plays a vital role in satisfying the needs of the industry–by facilitating good research, and those of the public–by ensuring patients are not unduly harmed or burdened along the way. Toward the latter objective, an IRB works to ensure that if ePRO is to be included as part of a study, it is done so thoughtfully and with purpose.

	This brings to light the importance of crafting a research trial that not only offers promising results, but facilitates, and also does not hinder (because these are two different things), patient participation in the process. According to Nathan M. Lee, Vice Chairperson of Schulman IRB, an independent IRB, “The Board evaluates each study on a case by case basis…[but] there could be instances where an electronic device might not be appropriate for the subject population–for example, possibly an Alzheimer’s study.” 

	In the Alzheimer’s study example, a diligent IRB might easily conclude that providing patients with data-capturing technology that may be completely foreign to them, compounded by the difficulty of providing training on that technology for that very reason–along with the memory and comprehension challenges that characterize the condition itself, would prove inefficient and burdensome in terms of mental strain for the patient. Researchers must take precautions when deciding how to involve technology-facilitated patient outcome data in their studies, because ePRO represents the future of clinical research and should be implemented properly for maximum impact. The good news is that with some simple foresight and planning, this can be achieved. 

“The IRB is looking at the content more than the delivery method," says Lee. “That said, there may be unique circumstances when because of the subject population, it may be better to use one method over the other.” With any ePRO choice, there would be concern about striking a fair balance between the burden placed on a patient to report his or her own assessments and the severity of their illness. For example, self-assessment would likely be less taxing on an allergy patient than an oncology or HIV patient, so the number or length of the assessments required should be altered to fit the capabilities of the patient population. There is generally no preference by an IRB on the use of paper vs an electronic device, but Lee does point out that evaluation is typically done on a case-by-case basis and “in the context of the study and subject population.”

	Whereas IRBs are largely concerned with the quantity (and sometimes the frequency) of information a patient is being asked to provide, the usability burden of the device may also be called into question. If, for example, a visually-impaired population is expected to complete their assessment on a handheld device with a small screen, the IRB might intervene and request that the sponsors show prior evidence that the assessment can be successfully completed in this fashion. Schulman itself does not typically go as far as review usability results, but they do require screen shots of all patient-facing material to help them in their review. In addition to the actual data input interface(s), this also includes any log-in screens, help screens, and/or supplementary materials available on the device.

The evolution of the smartphone has extended the reach of individuals–not just for nice-to-haves such as remote control over appliances and household devices from outside the home, but more significantly in terms of access to a nearly limitless breadth and depth of information without the constraints of time or geography. Savvy researchers may soon be looking to leverage this evolution for enhancements to patients’ ePRO devices that provide direct access to media and/or resources on the internet–such as useful targeted articles or videos related to their condition. Asserts Lee, “The Board would need to review any [access] that would be presented to the subject.” However, he also notes that most devices Schulman have evaluated so far only offer “stripped down” access to the PRO components. 

	Another “reach technology” that researchers will surely seek permission to leverage more frequently is the geolocation/GPS capability. This technology has been a game-changer for everything from targeted consumer advertising and marketing research strategies to the dissemination of emergency alerts. An organization doing research may find it appealing to employ geolocation to improve the patient experience. For example, to provide patients with updated alerts about traffic, detours, and other route information on the day of their visit to a study site. 

	For any such organization approaching an IRB with a geolocation element in its research design, the question of privacy would likely come up as quickly as the topic itself. “While there is no standard template language yet established for this type of situation because it’s still rare in studies we see, information around the use of geo-location should definitely be detailed in the informed consent,” says Lee. “And because it’s a privacy-related topic, we would require far more detail to be convinced that patient privacy would be respected and protected.”

Between more stringent global industry regulations–along with the additional precautions needed to satisfy them–and the shrinking space of time between product launch and patent expiration, profits from the sale of a drug aren’t always what they used to be. This means that successful research organizations must be much more prudent in discovering market differentiators (and thus new ways to prove the value of their products and extend the shelf life of their market share) as well as developing strategies to manage development costs. Migrating from paper to electronic data collection has huge potential in both of these areas.

	For one thing, including ePRO assessments can expand the focus of a study beyond the mere treatment of a patient’s disease. With this holistic approach, the goal would become improving the quality of life for the patient as well as others impacted by the disease. For example, the impact of side effects on a patient or the burden of multiple treatments per week on a caregiver. This is a more meaningful outcome that competitors would not be able to duplicate as easily.

	Further, researchers can achieve cost savings with ePRO through gained efficiencies in the data collection and analysis phases of their development process. By reducing the number of handoff points, and thus the potential for human error, data quality is improved. This in turn significantly minimizes (if not altogether eliminates) data queries and responses along with their associated costs. Further, because the data is controlled during the collection process rather than cleaned post hoc, analysis during study closure is greatly accelerated. All in all, these results speak to a significant reduction in manual effort. And like most businesses, research organizations are painfully aware of a very familiar equation: Time = Money.

	The use of ePRO is still emerging and it is safe to say that organizations wishing to gain a competitive advantage through their research model should incorporate electronic patient-reported assessments (where appropriate) into their studies sooner rather than later. At the same time, as with most new ways of operating, everyone is still trying to figure out how to “do” ePRO properly. Thus, it’s clear that its use can actually hinder the research process if not implemented correctly. With that said, researchers should seek guidance from one or more ePRO expert sources to ensure the ePRO model is designed properly for the study, patients, and circumstances.

	The information in this article serves as a good start by providing factors to keep in mind if your organization is considering adopting ePRO. However, as mentioned, appropriateness of ePRO often varies by study and is evaluated individually. As the research landscape continues to shift, being prepared for what’s ahead will help ensure a successful IRB review of your study and facilitate a smoother research process overall. 

Nathan M. Lee is the Vice Chairperson at Schulman IRB and can be contacted with questions about the IRB review and approval process via Stephanie Pyle at 

with questions about ePRO technology. Gail K. Smith-McCarthy, P.M.P., specializes in process design & remodeling, process documentation, and project planning & management.

Articles

The information in this article serves as a good start by providing factors to keep in mind if your organization is considering adopting ePRO. Appropriateness of ePRO often varies by study and is evaluated individually. As the research landscape continues to shift, being prepared will help ensure a successful IRB review of your study and facilitate a smoother research process overall.

Nathan M. Lee

Articles

An IRB’s Perspective on ePRO