Ensuring The Patient's Voice Is Heard: Advances In PRO And ePRO Data Collection

By Sara Gambrill

By all accounts, the collection of patient-reported outcomes (PRO) through electronic means has been continually increasing and will be for the foreseeable future. One of the reasons for this is biopharma’s drive to “hear” the patient’s voice clearly and accurately.

“We as an industry are increasingly interested in hearing the voice of the patient; ePRO [electronic patient-reported outcomes] is the vehicle for us to capture that voice,” said Craig Lipset, senior director of clinical research and venture partner with Pfizer Venture Investments.

The PRO landscape has changed considerably in the past few years. The FDA drafted a guidance for industry regarding PRO measures that became finalized in December 2009. Also in 2009, the ISPOR (International Society for Pharmacoeconomics and Outcomes Research) ePRO task force issued its ePRO Good Research Practices Report. And, at the end of 2008, the Critical Path Institute, in cooperation with the FDA and industry, formed the PRO Consortium, which has 25 members, comprising mostly Big Pharma and eight working groups categorized by therapeutic area.

The goal of the PRO Consortium is to develop PRO instruments, such as questionnaires and assessments, for specific contexts of use (i.e. for specific diseases and certain populations within those diseases). These instruments would only concern primary, coprimary, or secondary endpoints that would end up being in the label as an endpoint. The ultimate goal is to get these PRO instruments qualified by the FDA and make them publicly available.

To make the PRO instruments coming out of the Consortium as widely available as possible, they will need to be usable in all available data capture modes, including a wide array of electronic modes of data capture. “We want the PRO instruments to be as broadly used as possible, so they become a standard,” said Stephen Joel Coons, Ph.D., executive director, PRO Consortium, Critical Path Institute. “Once a PRO instrument is qualified by the FDA as fit for purpose within a specific target population, it is likely to become the standard clinical trial endpoint measure.”

ePRO Evolution Offers Opportunity for “Mixed Modalities”
When most people think of ePRO, they often think of patients using handheld PDA-type devices to collect data. While these handheld devices are still prevalent in the world of ePRO, there are more ways that PRO data — not only diaries but also questionnaires and assessments — is being collected electronically, depending on study complexity, patient population, and geographical reach of the study. And, these methodologies are gaining traction.

“The patient-centric clinical trial is becoming more and more important for sponsors and regulators, and patient self-report data — whether it be diaries or assessments — needs to be collected in a format that not only improves data accuracy and integrity but also has a positive effect on retention and compliance. For this reason, other ePRO methodologies such as interactive voice response (IVR) systems, digital pen technology, Web-based solutions, and cell phone solutions are all under consideration by sponsors to improve the process,” said Tim Davis, CEO and cofounder of Exco InTouch. “There is not one platform or one type of technology that works for every type of patient population in every clinical study in every corner or the globe, but the choices to assist all stakeholders in the study — sponsors, sites, and patients — have never been better.”

As sponsors become more aware of their ePRO options and which ones are best suited for an e-diary versus an assessment or questionnaire in certain parts of the world for certain kinds of clinical trials, implementation is not as simple as asking the ePRO vendor to use their choice of electronic mode of data collection. Sponsors and ePRO vendors alike come up against such hurdles as the need for “measurement equivalence,” which ensures that, as a PRO instrument migrates from paper to electronic device or from one device to another, there is sufficient data comparability. Measurement equivalence is necessary to keep response bias from being introduced; it would also allow data from a clinical trial implementing “mixed modalities” or various electronic modes of data capture to be pooled and compared.

The need for measurement equivalence is becoming greater as clinical trials are conducted globally. “Being able to provide a client with any kind of methodology within a study or within a program where you have different methodologies is becoming more important,” said Wilhelm Muehlhausen, senior director ePRO Solutions atERT. “We have more requests to mix and match two methodologies, especially large studies that go into remote areas to find more patients where you can’t always assume that technology is as good or infrastructure is as developed as it is in the United States or in Western Europe.”

ePRO Consortium
After the PRO Consortium was established, ePRO vendors sought to become involved. Coons believes that forming an ePRO Consortium would best serve the purpose of advancing the science of electronic data capture to ensure that data submitted to the FDA captured electronically during clinical trials is valid and reliable, no matter what the original form or version of the instrument migrated from or new data capture device migrated to. “There are a lot of questions to be answered. Better to do it collectively in a precompetitive, neutral, nonprofit environment so that it becomes publicly available,” Coons said.

Consortia within the Critical Path Institute support the Critical Path Initiative that the FDA put forth in 2004. One of the goals of the institute is to foster the development of the types of tools and processes that enhance the speed with which all medical products’ safety and efficacy can be tested; thus the ePRO Consortium dovetails with the Institute’s overall objectives. The ePRO Consortium’s kickoff meeting was held in May in conjunction with the ISPOR Meeting in Baltimore.

Coons envisions a collaboration between the PRO Consortium and the ePRO Consortium to ensure that PRO instruments are effectively migrated to all existing, appropriate data capture devices and systems.“We need to get a better level of standardization. If one company has done a conversion from any paper instrument into an electronic version, another sponsor should be able to use it. The other sponsor shouldn’t have to pay another vendor again for the same conversion,” Muehlhausen said.

The main objective of the ePRO Consortium will be to create standardized specifications for migrating a PRO instrument from paper to all types of electronic devices as well as from one ePRO device to another so that measurement equivalence is achieved. These standardized specifications would allow sponsors to collect patient-reported outcomes data from patients regardless of where they live.

“It would really empower the sponsors to allow them to choose what technology would be most appropriate to their clinical trial and to their patient demographic,” Davis said. “The PRO data is getting more important because the patient perspective is incredibly valuable and more and more often being requested by regulators to help prove safety, efficacy, and labeling claims. Often it’s those kinds of insights you get while patients are in their homes or out living their lives as normal that will really identify whether a drug is effective or not. Sponsors are increasingly looking to solutions that make it easy for the patient to give them the data they need and not disrupting their lives in the process.”

The Future of ePRO
While it is impossible to imagine all the electronic modes of data capture the future will bring, the plans to make them work within the context of a clinical trial have been laid down. Some in the clinical research community discuss ePRO’s next frontier as the healthcare setting, especially as the concept of “mobile health,” also called “mhealth,” gains momentum. The day when doctors can have their patients use their own cell phones in myriad ways to help track their health status and medication compliance is on the horizon.

Lipset is one who clearly sees this opportunity. “When you look at the types of health and wellness applications that consumers are downloading, many of them are self-tracking. They’re self-tracking their diet, activity, fitness, and, if they have a condition or disease, they’re self-tracking aspects of those,” Lipset said. “Ultimately, ePRO is a great common ground for enabling the convergence between healthcare and clinical research.”