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Use of electronic clinical trial portals has increased in recent years to assist with sponsor-investigator communication, safety reporting, and clinical trial management. Electronic portals can help reduce time and costs associated with processing paperwork and add security measures; however, there is a lack of information on clinical trial investigative staff’s perceived challenges and benefits of using portals.
The Clinical Trials Transformation Initiative (CTTI) sought to (1) identify challenges to investigator receipt and management of investigational new drug (IND) safety reports at oncologic investigative sites and coordinating centers and (2) facilitate adoption of best practices for communicating and managing IND safety reports using electronic portals.
CTTI, a public-private partnership to improve the conduct of clinical trials, distributed surveys and conducted interviews in an opinion-gathering effort to record investigator and research staff views on electronic portals in the context of the new safety reporting requirements described in the US Food and Drug Administration’s final rule (Code of Federal Regulations Title 21 Section 312). The project focused on receipt, management, and review of safety reports as opposed to the reporting of adverse events.
The top challenge investigators and staff identified in using individual sponsor portals was remembering several complex individual passwords to access each site. Also, certain tasks are time-consuming (eg, downloading reports) due to slow sites or difficulties associated with particular operating systems or software. To improve user experiences, respondents suggested that portals function independently of browsers and operating systems, have intuitive interfaces with easy navigation, and incorporate additional features that would allow users to filter, search, and batch safety reports.
Results indicate that an ideal system for sharing expedited IND safety information is through a central portal used by all sponsors. Until this is feasible, electronic reporting portals should at least have consistent functionality. CTTI has issued recommendations to improve the quality and use of electronic portals.
Safety reporting is a necessary element of clinical trials to help ensure patient safety during the investigation of a new drug or medical device. With advances in technology, safety reporting, along with other clinical trial data reporting, is moving to electronic formats from being largely paper-based. To encourage electronic submissions and integration of other technological capabilities into trial document management, the US Food and Drug Administration (FDA) has previously released guidance on electronic submissions and source data [
Aligned with this progress is the increased use of electronic portals to facilitate communication between sponsors and the investigative staff during clinical trials. Few publications in the scholarly literature have focused on portals; however, it is acknowledged within the clinical research field that use of portals is proliferating. Typically, clinical trial portals are developed by sponsors or contract research organizations (CRO) to provide a centralized location for trial-specific documents and information (eg, regulatory and safety documents, protocols, investigator brochures). Using clinical trial portals can reduce the time and cost associated with processing paperwork, among other advantages. The portal also provides increased security with document management and communication through the use of log-in identification and password protection. Once the portals are developed, investigators are given access to the portal through specific log-in credentials. Investigators can access trial-specific documents provided by the sponsor or CRO. Throughout the trial, investigators periodically log in to review safety reports.
The Clinical Trials Transformation Initiative (CTTI) is a public-private partnership whose mission is to develop and drive adoption of practices that will increase the quality and efficiency of clinical trials. CTTI initiated the investigation new drug (IND) Safety Advancement Project to investigate barriers to implementation of the FDA final rule on expedited IND safety reporting (Code of Federal Regulations [CFR] Title 21 Part 312) and propose solutions to address identified barriers, from the perspective of both investigators and sponsors. The project focused specifically on oncology research, where these issues tend to be most acute.
Evidence gathered during the project indicated that investigators have difficulty using clinical trial portals and that portals may contribute to confusion and burden investigators’ experience related to the IND safety reporting system. Therefore, the CTTI project team sought to identify best practices for managing IND safety reports using electronic portals and formulated recommendations based on data collected through evidence-gathering activities.
The IND Safety Advancement Project team included 20 individuals representing a wide range of stakeholders, including industry, academic institutions, institutional review board (IRB), regulatory, patient advocate, and other perspectives; all groups were considered equal partners. The primary focus of the project was to investigate barriers related to the lack of implementation of the final rule (21 CFR 312) and provide recommendations for better compliance; however, a portion of this project was specifically devoted to addressing the use of clinical trial portals. The team employed 3 main research strategies to gather evidence: surveys, expert interviews, and an expert meeting.
An online survey was designed to assess challenges related to cancer researcher management of IND safety reporting processes, with a subset of questions about the specific challenges related to use of electronic portals to manage safety reports (
Questions on current issues:
If IND safety reports are distributed via a sponsor safety reporting portal, do you have difficulty accessing the IND safety reporting portal?
Please describe the difficulty you have accessing the IND safety reporting portal.
Questions on suggestions for improvement:
What things about the current IND safety reporting system should be changed?
If you were starting from scratch, what would an ideal IND safety reporting system look like?
A total of 20 in-depth, hour-long interviews were conducted by a professional interviewer as an opinion-gathering effort to more fully understand sponsor and investigative staff perspectives on the management of IND safety reporting processes. Interview participants who were considered experts in the topic were approached by CTTI. Survey respondents were also able to volunteer for interview participation. In January and February 2015, 13 individuals representing investigative staff working on oncology clinical trials and 7 pharmacovigilance leaders from 5 large global pharmaceutical companies were interviewed. Prepared questions were included in an interview guide [
The project, including the surveys and interview guides, was designated as exempt research by the Duke University IRB.
The IND Safety Advancement Project team analyzed survey results and interviews, developed draft recommendations based on responses, and presented this information at a 2-day expert meeting in July 2015 attended by 47 individuals representing a variety of clinical trial stakeholders. Discussion from the meeting was used by the project team to refine the recommendations through iterative, consensus-driven discussion, and they were approved by CTTI’s Executive Committee prior to official release (December 2015) [
The survey had 201 respondents. The majority of the respondent population had academic or community-based research backgrounds with more than 10 years of clinical trial experience. A majority of the respondent-affiliated organizations conducted more than 30 studies concurrently and represented all phases of clinical trial development sponsored by industry and government. Full results of the survey and interviews are being reported concurrently elsewhere [
Responses from investigators and other study staff indicate that 80% (33/41) of investigators and 92% (133/144) of study staff received IND safety reports through portals. Approximately half (21/41, 51%) of investigators and 44% (64/144) of staff reported difficulty accessing sponsors’ IND safety reporting portals. When survey respondents were asked to provide free-text responses specifying difficulties encountered accessing a portal, a common answer was the problem of remembering passwords for numerous individual sponsor portals. Other difficulties voiced by respondents were challenges with operating systems, software compatibility, and differing application versions. Respondents indicated that many interfaces are difficult to navigate and do not incorporate intuitive design elements. Additionally, many portals have slow processing times, and their applications often crash or fail. For these reasons, downloading reports can be time-consuming for the investigative staff. Finally, respondents noted that generic email notifications are not particularly helpful and many choose to block these emails. The top-rated challenges were as follows:
Remembering numerous, complex passwords for individual sponsor portals
Encountering problems related to different operating systems, software compatibility, and application versioning
Navigating through nonintuitive user interfaces and slow sites
Encountering log-in or site issues due to investigative staff turnover
Receiving too many generic email notifications
Time-consuming process of downloading reports
Although distribution of streamlined reports via electronic portals was intended to improve the efficiency of the safety reporting process, interviewees from investigative sites reported that they continue to receive an unmanageable volume of IND safety reports. Active sites described the volume of reports as “staggering.”
Respondents described a number of benefits related to use of portals for safety reporting, including automatic notifications of trends or unexpected adverse events, which help guide treatment decisions for patients. Investigative staff indicated that it was easier to identify risks when reports were submitted through the portal. Summary reporting and the defined attribution and causality available on the portal can help filter the safety information for study staff. With enhanced signal detection, the investigative staff can identify information that may generate important changes to the protocol or consent and help them make determinations on the utility of the study and other risk/benefit assessments. Additionally, electronic reports are more efficient and easier to retain and track.
The attributes displayed in
Overall system functionality:
Cross-browser compatibility; portal works seamlessly with all commonly used browsers
Operating system independent
Mobile-friendly
Quick report download time (ie, externally hosted, cloud-based)
Simplified security management system (eg, end-user control over password management, biometric identification in lieu of passwords, and/or ability to integrate with various identity access applications)
User interface:
Intuitive, easy-to-navigate interface requiring few clicks to access safety reports directly or via hyperlink contained in an email notification
Flexibility within the portal for use with varied institutional processes
Report management and analysis:
Print reports or download multiple reports with one click to a compact disc, computer, or electronic investigator site file
Filter reports by event so follow-up safety reports do not appear as new events
Search and display safety reports using custom dates, by country of origin and/or event name
Export single reports as well as aggregated data
Drill down to access single reports and write-ups
Reports remain visible for the life of the trial
Report notification, acknowledgment, and verification:
Ability to batch safety report notifications (per day/week) per investigative site user’s preference
Ability for principal investigator to delegate the task of accessing safety reports via portal to another person at the site
Easy acknowledgement of safety reports by investigative site staff (eg, click on a link to the report, check a box, or check-all option)
Ability to send and record acknowledgement of a safety report only once across multiple trials for the same investigational product yet still show the report under each trial
End-to-end audit trail that can be printed and saved or stored for future reference by both the sponsor and investigative site
Ability of the sponsor to document delivery of reports within the portal if an alternative means of reporting is required (ie, the sponsor cannot access the portal and requires hard copy)
Two-way communication between the investigative site and sponsor regarding safety reports
As described elsewhere [
Survey results indicated that an ideal system for sharing expedited IND safety information with investigative sites is through a central portal used by all sponsors in order to improve efficiency and reduce paperwork burden (recognizing that electronic systems may not be feasible for all study sponsors). This approach may reduce the number of passwords and avoid technological issues (eg, software incompatibility) by standardizing the use of a central portal. While literature describing clinical trial portal use is limited, some reports validate survey respondents’ perceived obstacles, indicating that investigative staff and investigators struggle to recall 7 to 15 passwords per individual user [
The attributes listed in
Browser and operating system independence so that all users can access the portal regardless of software preferences
An intuitive interface that is clearly labeled and provides easy navigation
Ability to filter and search reports to quickly access only the relevant documents needed at the time
Increased functionality to batch reports so that all files can be downloaded simultaneously
Ability to acknowledge receipt quickly with a check-box option and to update this acknowledgement across multiple trials for the same product
Portal features to more accurately track audit trails can be particularly helpful, as reports can be categorized or searched by date, number, compound, trial number, upload/availability date, download/access date, identity of users who accessed the report, and any actions (eg, downloading, printing, saving) conducted by a specific user. As indicated in
To support appropriate use of the portal, CTTI also recommends that there be improved education for investigative sites including guidance not only on portal functionality but also regarding best practices for incorporating portal management into site report management processes. Finally, we recommend usability testing for portal-related educational material.
The main limitation of the study that should be acknowledged is the small sample size that was selected by convenience, which may be susceptible to bias. Additionally, survey response rate was not able to be determined. CTTI acknowledges these shortcomings and that this research is exploratory and qualitative in nature and not statistically measureable. However, change often begins with small steps, and it is our hope that this research sparks a broader discussion across the industry. CTTI encourages additional research on this topic. The perspectives described in this manuscript are descriptive; in order to be conclusive, an appropriately powered study would need to be conducted. CTTI and other independent organizations cannot require that sponsors adopt recommendations nor mandate inclusion or standardization of portal features, which is why we urge portal developers to consider the perspectives of the portal users to drive change.
Industry technology companies are investing in integrating sponsor trial portals with enhanced capabilities including interactive voice response, electronic data capture, clinical trial management systems, and investigator databases [
The suggestions provided in this manuscript have been released as CTTI recommendations [
Code of Federal Regulations
contract research organization
Clinical Trials Transformation Initiative
Food and Drug Administration
investigational new drug
institutional review board
The authors wish to acknowledge the contributions of the CTTI IND Safety Advancement Project team and those individuals who participated in the surveys and interviews. Writing assistance was provided by Kelly Kilibarda, PhD, in affiliation with Whitsell Innovations Inc.
Funding for this manuscript was made possible by the FDA through grant R18FD005292. Views expressed in this publication do not necessarily reflect the official policies of the US Department of Health and Human Services nor does any mention of trade names, commercial practices, or organizations imply endorsement by the US government. Partial funding was also provided by pooled membership fees from CTTI’s member organizations.
None declared.