CTTI has published its findings on remaining barriers and potential solutions to full implementation of the FDA final rule on IND safety reporting by investigators, clinical research staff, and sponsors.

In 2010, the FDA final rule established new reporting requirements for serious and unexpected suspected adverse events occurring in clinical trials conducted under an IND. Follow-up FDA guidance clarified sponsors’ role and that they should not submit expedited safety reports for individual cases of serious adverse events for which it does not appear the drug caused the event. It was anticipated that these changes could increase the interpretability of safety reports while decreasing the volume and burden of reporting.

Through a series of surveys and interviews, the results of which were published in the journal Clinical Trials, CTTI discovered that while all groups agreed on the intention of the final rule in increasing early communication of safety signals, they also indicated that the rule was not being strictly implemented. Interviewees reported that the major challenges included lack of global harmonization in reporting rules, difficulties determining causality, and fear of regulatory repercussions, some of which could be improved with increased interaction with the FDA itself.

These findings, which resulted from CTTI’s IND Safety Reporting Project, support recommendations developed by CTTI and underpin educational materials created for sponsors to increase compliance with the final rule, and to facilitate discussion between sponsors, investigators, and FDA representatives. CTTI gathered input on these findings and their impact in a multi-stakeholder expert meeting (a meeting summary is available for additional context) and hosted a webinar to provide guidance on handling a variety of safety reporting situations.

CTTI would like to thank the interview participants and project team members who contributed to this work.

CTTI’s latest research indicates that a single, internet-based portal for investigator reporting of expedited IND safety information to sponsors would be better than the current system of each sponsor having a separate portal. However, until use of a central portal is feasible, the recently published findings and CTTI recommendations provide desired attributes that can promote consistent functionality across electronic portals, improving the quality and use of these systems.

Electronic portals can increase efficiency and lower costs associated with processing safety reports in clinical trials, as well as add an element of security. However, there can be challenges associated with use of these systems that prevent successful adoption. CTTI’s IND Safety Advancement Project sought to identify obstacles and to create recommendations for best practices for following FDA requirements and guidance on expedited safety reporting. Electronic portals are one method sites and sponsors can implement to help adhere to FDA requirements and improve the quality of safety reports.

The recommendations for electronic portals for IND safety reporting are based on results from interviews with research staff, along with multi-stakeholder input on how to address the challenges raised. For example, CTTI found that many research staff report difficulties in tracking multiple passwords and managing different interfaces for various sponsor portals. These research staff views helped to inform strategies that could decrease the burden of IND safety reporting in clinical trials.

For those in the clinical trials enterprise seeking to streamline IND safety reporting, additional recommendations are available from CTTI to improve IND safety assessment and communication.

Are you confused about how best to comply with the FDA final rule on IND safety reporting? Would you like to hear more about how to handle common, yet challenging, safety reporting situations? Do you know someone who is interested?

CTTI invites you to participate in a webinar hosted by the IND Safety Advancement Project Team. This webinar is the first in a CTTI-hosted series designed to explore challenging safety reporting scenarios using case studies. We encourage you to share this invitation to others who may be interested in learning more about IND safety reporting.

Topic: Case Studies on Expedited IND Safety Reporting

Date: Thursday, April 21, 2016

Time: 12:00 p.m. – 1:00 p.m. EST

Presenters:

• Patrick Archdeacon, Senior Clinical Advisor, Office of Medical Policy, Food and Drug Administration, Center for Drug Evaluation and Research
• Annemarie Forrest, Associate Director of Projects, CTTI
• Nina Stuccio, Head, Medical Safety Review, Global Clinical Safety & Pharmacovigilance, Merck, Inc.

WebEx Link
Meeting number: 735 340 171
Meeting password: ctti

After you connect to meeting website, please follow step-by-step instructions for connecting to the audio. If you prefer to connect to audio only, you can join by phone at:
1-855-244-8681 Call-in toll-free number (US/Canada)
1-650-479-3207 Call-in toll number (US/Canada)
Access code: 735 340 171

 

The FDA issued a draft guidance in December 2015 on Safety Assessment for IND Safety Reporting. This guidance was developed as a follow-on to the 2010 guidance for Safety Reporting Requirements for INDs and BA/BE Studies and provides recommendations to help sponsors meet their obligations under 21 CFR 312.32. The FDA provides recommendations on the composition and role of a safety assessment committee, aggregate analyses for comparison of adverse event rates across treatment groups, planned unblinding of safety data, reporting thresholds for IND safety reporting, and development of a safety surveillance plan.

Page 4 of the guidance references CTTI work conducted by the IND Safety Project Team. (Recommendations developed during this project are available here.) The FDA addressed an observation that emerged during the IND Safety Project’s analysis of the evidence from surveys and multi-stakeholder expert meetings: sponsors have concerns about protecting trial integrity when reviewing serious adverse data from ongoing trials. To maintain trial integrity while assessing safety signals, the FDA recommends that sponsors use a safety assessment committee and develop a safety surveillance plan.

Comments on this draft guidance will be accepted until February 16, 2016.

CTTI continues to work in this area: the IND Safety Advancement Project is a follow-on to the IND Safety Project. This follow-on project seeks to promote full implementation of the FDA’s final rule by addressing particular challenges in oncology trials and generalizing solutions to other therapeutic areas.