July 2004
Issues Surrounding the Collection, Reporting, and Maintenance of Electronic Data
The past five years has seen an increase in the adoption of electronic data capture (EDC) to collect clinical trial data. The largest area of growth has been in the use of hand-held diaries and devices used to collect patient reported outcomes (PROs). PROs provide information about the benefit of a treatment from the patient's perspective, such as improved quality of life, and have become increasingly recognized as important by regulatory bodies when assessing new medications. Collecting PRO data electronically offers many advantages over traditional paper methods including superior data quality, shorter trial cycle time, and reduced data management costs.
It was this increasing interest in PROs and EDC that prompted a recent 2-part DIA-sponsored event. This conference aimed to bring together investigators, sponsors and the US Food and Drug Administration (FDA) to discuss issues surrounding EDC in the healthcare research environment. To this end, this well-attended conference set out to explore the pros and cons of new technologies available to clinical trials, gain feedback from investigative sites, and to discuss the regulatory perspective on current practices for collecting and retaining e-data.
PART 1 Technology at the Investigative Sites: Planning and implementing e-Clinical Trial Solutions to Improve Performance
Investigators took the lead in presenting current concerns, challenges, and future perspectives in EDC at the site level. Of primary importance was the shift in site based DM responsibilities from the sponsor and the associated burden placed on the investigational site, often exacerbated by a lack of adequate training and compensation.
Experienced EDC study centers can manage upwards of seven different collection systems, all with unique passwords, platforms, and user capabilities. From the site perspective, streamlining the collection process across the industry will provide higher quality data, shorten study timelines, and thereby reduce sponsor costs at the site level.
The FDA also expressed an interest in the standardization of EDC collection methods across the industry. From their perspective, a move to standardize the EDC process should result in increased reliability of EDC data provided by the sponsor in support of regulatory filings.
An ePRO working group has been organized to continue the discussions that began at the "Technology at Investigative Sites" workshop. Interested DIA members from all areas of industry are encouraged to join the planned monthly telecom being initiated by current members of the e-Clinical DIA SIAC (Special Interest Area Committee). EDC standards, technologies and adaptation are ranked in the top three topics identified by the eClinical needs assessment survey conducted last summer. DIA members can view the complete survey results at www.diahome.org.
PART 2 Electronic Patient-Reported Outcomes (ePRO) and the Regulatory Process: What's going on?
The second part of the conference focused on the regulatory perspective, with lively debate provoked by a wide variety of oral and poster presentations. Much of this debate stemmed from the first presentation by Rebecca Kush, President of the Clinical Data Interchange Standards Consortium (CDISC), revealing that while technology use in clinical trials has increased, adoption remains relatively slow compared to other industries. Although cost was an important g g factor, the most frequently cited reason for adoption delay given by pharmaceutical companies completing surveys of EDC use was regulatory concerns. Although guidance in this area is currently outlined in the FDA's 21 CFR 11, there are many issues that remain unclear. Of particular concern is the issue of data security and whether e-data can be considered source data when an ePRO provider, employed by the sponsor, collects the data rather than the Investigator. Currently this 'trusted third party' has no regulatory standing with the FDA, with the Investigator being solely responsible. Whilst there are many measures that may be employed to ensure the source data remains secure and unchanged, such as hash functionality and encryption, confusion still remains as to what is acceptable to the FDA.
Another issue raised in this section was the potential of ePRO EDC to raise the hurdle when approaching regulators for approval. Electronic diaries can accurately capture additional information to that of paper diaries, such as compliance rates via electronic time & date stamping. This type of data is not expected of trials employing paper diaries, but with an increasing use of ePRO EDC, such data may become mandatory. Finally, the issue of validation was discussed; both in terms of validating the systems employing ePRO EDC, and also as to whether the validity of instruments developed in paper format persists when transferred to electronic format. Studies suggest this to be the case, but additional validation of questionnaires may be necessary when collecting the data electronically. Currently there are no guidelines covering this area, but the FDA expects to issue a guidance document in the near future, although it is not expected that validation process will have to start from scratch.
To conclude, this was a very interesting and interactive conference bringing representatives from industry and regulatory agencies together for the first time on a large scale to discuss EDC issues. Clearly this is an evolving area, with the FDA continuing to work towards explicit guidelines to clarify current uncertainties about the use of this technology. In the meantime, it was recommended that companies considering employing EDC in their trials approach the FDA early in the planning process for guidance.
Christine Getter
Outcomes Research, Pfizer Global Pharmaceuticals, US
Lucy Abraham
Outcomes Research, Pfizer Global Pharmaceuticals, UK