In Touch
by Mary Sgammato
June 2007
Despite a few obstacles limiting their widespread deployment, electronic patient-reported outcomes are evolving into a practical, reliable and efficient means of gathering clinical research data.
In some areas of clinical research, the most important data can be reported only by the patients themselves. Patient-reported outcomes (PROs) are the sole means for physicians to discover certain expressions of symptoms and specific quality-of-life measures.
PROs traditionally have been obtained through structured interviews with trial subjects, observation by investigators, or written questionnaires and diaries completed by the patients. Over the past several years, however, technology has played a growing role in capturing PROs. Electronic diaries and other tools are portable, fast and intuitive, which gives them a distinct advantage over traditional paper-and-pencil reporting. Although there still are concerns to be addressed—particularly regarding source data integrity and security—and barriers to overcome, most notably a high up-front investment, electronic patient-reported outcomes (ePRO) have the potential to enhance subject protocol compliance and reduce both trial subject sample size and the cost of bringing new drugs to market.
Anytime Assessment
Electronic platforms for collecting patient-reported outcomes can yield more precise and complete data than paper-based reports, says Stephen Joel Coons, Ph.D., professor of pharmacy and public health at the University of Arizona, in Tucson, Ariz., USA. “Patient-reported outcomes are the best and in some cases the only means for capturing data related to certain conditions,” he says. “People are much more likely to consistently report in electronic diaries than on paper-based tools, which is a major plus in terms of adherence to protocols.” The mobility of a personal digital assistant or comparable tool can significantly reduce recall bias, which can compromise data validity and reliability, he says. “The closer to an event that data gets recorded, the better.”
Although the speed at which outcome data is gathered in ePROs is a major benefit, it must be balanced against the practical and regulatory contingencies of conducting a paperless trial. Maintaining the integrity of source data for the purposes of meeting regulatory requirements is an area of concern, says Laurie Beth Burke, director of study endpoints and label development in the Center for Drug Evaluation and Research at the U.S. Food and Drug Administration (FDA), in Silver Spring, Md., USA. “We need to be able to clearly see who touched the data and when,” she says.
Current regulations require trial investigators to maintain source documents for review by the FDA as part of the approval process. “Each type of ePRO tool is different with regard to data management, and investigators—regardless of the technology used—must be able to review and authorize the legitimacy of source data,” Burke says.
However, if sponsors using ePRO technology access ongoing trial data too often, the integrity of the trial potentially could be undermined. Interim assessments of trial data usually are built into the study design at pre-defined intervals, but when using ePROs, sponsors may have the ability to review data at any point in the trial process. “There could be bias arising from multiple looks at the data that could lead to conclusions that are not statistically supported,” Burke says. Should an investigator reach a conclusion using preliminary, incomplete data, study bias potentially could interfere with the whole point of the trial—to provide better patient care.
Quality and Consistency
One major advantage of ePROs is that they enable investigators to use responses to improve the care of patients, says Christine Getter, outcomes research senior associate at Pfizer, in New London, Conn., USA. “Real-time data access enables investigators to identify quality-of-life measures of concern,” she says. For example, in a study of patients with depression, an indication of suicidal tendencies can present an opportunity to intervene that might otherwise be missed.
Despite the advantages of ePROs, there will always be a role for paper-based questionnaires in certain trials, and there are certain patient populations for whom electronic diaries are not appropriate, Getter says. “You would still want to use interview-based protocols with low-vision populations, persons in late stages of a disease and persons with compromised motor skills,” she says. The data could still be captured electronically through interactive voice response or call centers, but trial coordinators can’t expect patients to manually enter data into hand-held devices in such cases, she says.
Making Adjustments
Determining the proper method to capture patient outcomes for a specific trial requires continuous evaluation of the multiple ePRO tools and vendors, Getter says. “It’s an evolving technology, and the up-front investment is high,” she says. Furthermore, the globalization of clinical research places new demands on sponsors using ePRO tools in clinical trials, since data transfer and other challenges will need to be addressed.
“Translations of electronic questionnaires can change screen views to accommodate additional characters, reducing the number of questions per screen,” Getter says. “There is still work to be done to ensure validity and reliability of data across global trial sites.” Despite these growing pains, ePRO is a promising trend, primarily due to its reduction of recall bias, Getter says. The statistical accuracy and reliability derived from real-time patient outcome reporting can significantly reduce sample size and lower the costs of conducting clinical trials, she says.
Due to the rapid advances in available technology and increased guidance from regulatory agencies on acceptable data source standards, the presence of ePRO tools in clinical research is certain to grow. “It’s a whole new environment,” Burke says, “and very exciting.”
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