Expert Insight Into ePRO Industry Trends
By Rob Wright
As technologically savvy as we think we have become, there are still plenty of studies being conducted via pen and paper. In a recent conversation, an executive explained to me how they recently received patient diaries with much of the information being unreadable due to poor handwriting. Electronic patient reported outcomes (ePRO) are not yet the perfect solution, but have a significant number of advantages. For example, use of ePRO can gather data more quickly, which could be very important when reacting to a patient reporting a severe adverse event (SAE). In an effort to gain some additional insights into ePRO, Clinical Leader posed a series of questions to three ePRO experts.
Toshio Kimura is as associate director in Biostatistics at Boehringer Ingelheim Pharmaceuticals. He has worked extensively with PROs and ePROs and has interacted with FDA divisions including the Study Endpoint and Label Development. In his most recent NDA (new drug application) submission, ePRO was used to collect the primary endpoint. Joanne Zuck is a project data manager and a member of the ePRO committee at Boehringer Ingelheim Pharmaceuticals. She has been involved in the implementation of ePRO systems in clinical development leading to Phase 3 studies conducted in 14 countries across Europe and North America. These studies have made extensive use of ePRO measures and devices. Anne Zielinski is VP ofalliances, for Medidata, where she promotes interoperability of the Medidata platform with other technologies. She oversees Medidata’s Developer Central and Technology Partner programs.
Clinical Leader (CL): What is your opinion on the knowledge level around ePRO, its value/benefits?
Toshio Kimura and Joanne Zuck, Boehringer-Ingelheim: Knowledge and adoption specifically around ePRO is trailing behind other eClinical technology such as EDC, although it is quickly gaining momentum. Knowledge around ePRO tends to be siloed by therapeutic areas. In areas where PROs are commonplace, knowledge around ePRO is high. Conversely, in areas where PROs are not commonplace, knowledge around ePRO is low.
Anne Zielinski, Medidata: Sponsors and CROs clearly understand the benefits of gathering data directly from patients that is time- and date-stamped and electronically attributable.
CL: What are some of the trends presently taking place with ePRO and what do you foresee as some of the future possibilities for ePRO?
Kimura & Zuck: ePRO is becoming the standard when collecting nonclinic–visit-based data from patients.
Patients, investigators, researchers, and sponsors are becoming more technology orientated; therefore, the movement toward ePRO, will be the inevitable next step. Scale developers may create digital standards of their scales, and eventually they will develop digitally native scales. The C-Path ePRO Consortium initiatives to qualify ePRO instruments will greatly accelerate ePRO adoption. Other ambulatory measurement devices may also become more ubiquitous and integrate with ePRO devices.
Zielinski: The increase in post-marketing studies requiring ePRO provides a substantial opportunity for use of web-based ePRO that subjects can access from their existing computers or web devices. I expect to see introduction and adoption of web-based ePRO options in the coming year.
CL: What do you see as the driving factor behind the recent 25 to 30% annual adoption of ePRO?
Kimura & Zuck: Scientific and operational rationale (e.g. system enforced adherence to ALOCA principles), regulatory guidance and precedence, earlier involvement of groups such as HEOR during clinical development, and experience of sponsors and KOLs using ePRO are some of the drivers for increased ePRO adoption.
Zielinski: Electronically captured clinical trial data is now the norm; the adoption curve EDC/CDM systems experienced is now being reflected in the ePRO market.
CL: What is your opinion with regard to companies being pressured to incorporate more patient reported outcomes into clinical trial protocols?
Kimura & Zuck: The rationale for the use of any measure in a clinical trial must be based on science. If a PRO (or ePRO) instrument is deemed as the most scientifically appropriate measure, then that particular PRO should be used. The pressure should come from the scientific community.
Zielinski: I believe this reflects an emphasis on real-world assessments of treatments that are difficult to fully capture with investigator-reported data.
CL: What are some of the common mistakes with “first-time” companies/organizations implementing ePRO?
Kimura & Zuck: Mistakes include not starting early enough and not understanding technical specifications. Teams often underestimate lead time required to properly specify, develop, test, and deploy ePRO. Teams must fully understand technical specifications to avoid ePRO solutions that fail to meet trial needs and expectations.
CL: What kind of impact will increased outsourcing to CROs have on ePRO providers?
Kimura & Zuck: CROs and ePRO providers will have to form synergistic strategic partnerships. Sponsors will demand a seamless suite of services, and bids from partnerships with documented past success will undoubtedly be reviewed more favorably. New roles, responsibilities, interactions, decision making, and communication processes need to be clearly established amongst all stakeholders.
Zielinski: The Medidata Partner Program provides a blueprint for outsourcing success as CRO use increases. While obvious, it bears repeating that all vendors working on a trial must have a clear mutual understanding of the implementation and operational processes of the technology, jointly defined requirements and regular communication commencing as soon as the project begins.
CL: To what degree is data integration a key for ePRO providers (and EDC providers/CROs) and more efficient clinical trials?
Kimura & Zuck: The degree of data integration will depend on trial needs. Adaptive design trials, trials with interim analyses that assess ePRO data (early stopping, sample size re-estimation, etc.), or other designs will require earlier access to data, and thus, demand a greater degree of data integration.
Zielinski: Trials using EDC and ePRO should have the systems integrated to provide more efficient management of subjects, unified data management, and integrated reporting. Integrations using web services application programming interfaces (APIs) allow separate applications to act as one, for optimal user experience. I anticipate an increase in the number of integrations with ePRO this year.
CL: What are some of challenges still facing ePRO adoption?
Kimura & Zuck: One challenge is the lack of readily available standard ePRO tools. In the same way that traditional PRO instruments are validated, standardized, and set in stone (or rather inked on paper), ePRO instruments should also have validated, standardized implementation. This minimizes variability between ePRO implementation and reduces development and validation efforts. These are among the goals of initiatives such as C-Path ePRO Consortium and FDA’s guidance on qualification of drug development tools.
Zielinski: The cost and effort involved in acquiring and managing handheld devices has limited the adoption of ePRO. I am excited about the opportunities that web-based ePRO will provide, and expect it to drive a leap in adoption.
CL: What advice would you give sponsors about the benefits/value of ePRO?
Kimura & Zuck: The benefits realized through EDC implementation can also be realized through ePRO implementation. While ePRO certainly has advantages, sponsors should perform due diligence in considering ePRO solution alternatives. Science should be the primary driver in deciding the tool and modality used within clinical research.
Zielinski: To gain the maximum benefit of eClinical systems including ePRO, we encourage sponsors to take advantage of web services’ APIs so that the systems work together, increasing both operational efficiency and data quality.