Reducing the Reporting Burden: Guidelines for Improving the Protection of Trial Subjects

by Glenn Veit, JD, CIP, Copernicus Group IRB Chairperson

To safeguard the rights, safety and welfare of human subjects, clinical research is a shared responsibility among sponsors, investigators, contract research organizations (CROs) and institutional review boards (IRBs). Central to this shared obligation is the meaningful review and communication of new safety information developed during the clinical trial.

Many federal guidance documents pertaining to reporting have been issued in the past few years. Their intent is to assist the research community in interpreting reporting regulations, and to respond to concerns that the overwhelming volume of reports were inhibiting rather than enhancing the protection of human subjects.

A Change in the Reporting Process

But until the reporting process itself changes—among sponsors, CROs and investigative sites—these federal guidance documents will remain largely academic. For reporting to be both effective and sustainable, the reporting burden on all parties must be reduced. Only then will the bar be raised on providing substantive protections for the subjects participating in clinical trials.

Safety reporting is inherently a complicated process. The stakeholders in the research industry all share responsibility for protection of human subjects, but each performs a different function, with different reporting responsibilities and different methods of handling reports. Loose federal regulatory jargon compounds the issue. For example, the investigational new drug (IND) regulations alone use terms such as adverse effect, adverse experience, adverse event and unanticipated problem seemingly interchangeably.

The Role of the Institutional Review Board

Helpful at this point is insight into the role of the IRB—and the negative effect that non-essential reporting has on the review process.

Upon receiving safety-related information, regardless of source, the IRB is obligated to report the following information to its own board members, the institutional official and the Food and Drug Administration (FDA):

  • Any unanticipated problems involving risks to human subjects or others
  • Any instance of serious or continuing non-compliance with these regulations or the requirements of the IRB
  • Any suspension or termination of the IRB approval

An Institutional Review Board must consider action when the potential arises for new or increased risks to humans subjects. Specifically, we look for:

  • Modifications to the informed consent document
  • Changes to the conduct of the study
  • Stopping the study or suspending enrollment until safeguards have been put in place
  • Serious or continuing non-compliance, generally at an investigative site

Corrective action plans can include retraining of staff, re-consenting of subjects, or even suspension of enrollment or approval.

When Is an Event Truly Reportable?

Safety reporting to an Institutional Review Board carries an implicit understanding: That the information is important enough that every party is required to be aware of it, and potentially, to take action on it. This understanding is the crux of the entire issue, because it dictates—or rather, should dictate—what is reported to the IRB and when.

At the very least, information delivered to the IRB should warrant the possibility that some action has to be considered. Action may be in response to any of the three types of information required to be reported by the IRB:

  • Risks to subjects
  • Serious or continuing non-compliance
  • Suspensions or terminations of approval

Keep in mind that taming the reporting burden—reducing the amount of non-critical or non-essential information being reviewed—is central to everyone’s ultimate goal of safeguarding and improving the rights and welfare of trials’ subjects. And so the fundamental question becomes clear: When is an event reportable?

An event is reportable when it meets all of the following criteria:

  • Is related or possibly related to the research
  • Is unexpected in terms of its nature, severity or frequency
  • Suggests that the research places subjects or others at a new or increased risk of harm

Generally, to be reportable, an event should be previously unknown to the IRB and require at least consideration of action to minimize the risk to subjects or others (e.g., a safety-related change to the protocol, or disclosure of risk information in the consent document or investigator’s brochure).

By this definition, most adverse events will not meet reporting requirements. The FDA itself has acknowledged that submission of reports that fail to meet the definition of an “unanticipated problem” do not yield useful information about adverse events—and thus add unnecessarily to the reporting burden, hindering the IRB’s ongoing ability to ensure the protection of human subjects.

This is especially true of most IND safety reports, all of which have already been reported to the same regulatory authority to which the IRB must report—the FDA. In a multisite trial, for example, IND safety reports should be fully assessed and submitted to the IRB by the sponsor or delegated CRO, not by individual investigators—if they are reported at all. As the FDA has noted, the sponsor is in the best position to analyze the significance of the information. Put simply, unless an individual safety report contains information previously unknown to the IRB, and it requires IRB action, then it should not be reported.

Of course, nothing is black-and-white—particularly regulated processes that involve so many different parties. Many of our own clients, for example, have SOPs that require reporting of any event. In such cases, the best practice should become to submit these reports to the IRB in batches, with a narrative explaining the sponsor’s analysis—and the clear indication that no change to the conduct of the study is required.

What Must Be Reported?

In our experience, routine safety events are over-reported to the IRB. This results in many wasted hours receiving, analyzing and responding to meaningless information. If the event doesn’t require the IRB to even consider taking an action, there is no reason to report it.

So what must be reported to the IRB? The answer is straightforward—any risk that was previously unknown or unexpected in type, severity or frequency of occurrence. The IRB should be provided with sufficient information to assess what action is needed to address mitigation of the new risk.

When your safety reporting policy meets these guidelines, the downstream effect will be a dramatically reduced burden of reporting on sponsors, CROs and investigators. The end result will be increased time and attention—for everyone in the process—to attend to the truly important task of assuring the safety of the people who participate in clinical trials.