You have a patient with cancer who is participating in a clinical trial. The patient has just been told that the trial has been placed on a clinical hold. What does that mean? What should you say to your patient?
A clinical hold is an order issued by the U.S. Food and Drug Administration (FDA) to the sponsor of an investigational new drug (IND) application to delay a proposed clinical investigation or to suspend an ongoing clinical trial. The reason for a clinical hold is concern for the safety of clinical trial participants.
A complete clinical hold is the delay or suspension of all clinical work requested under the IND, whereas a partial clinical hold is a delay or suspension of only part of the clinical work requested under the IND (i.e., a specific protocol is not allowed to proceed but other protocols under the IND are allowed). A hold could also mean that no new participants may be recruited to the study. Complete and partial clinical holds can be placed on any IND, including expanded access INDs.
INDs are placed on hold to further assess the quality of the investigational product to ensure the safety of trial participants. If an application is placed on hold, it means that significant safety reasons are involved. The most commonly cited deficiencies leading to clinical holds were product quality issues, followed by clinical and toxicology issues.
Many diseases may be serious or life-threatening and may lack any approved products available for treatment, which is often the case in oncology. Delays for any reason can cause considerable concerns for patients and families for whom an IND is a glimmer of hope. The FDA aims to work with drug sponsors to move drug development forward but not to expose trial participants receiving the treatments to unnecessary and avoidable serious risks.
The sponsor will initially be notified of the hold by telephone or another means of rapid communication. The clinical hold order, with an explanation of the basis for the hold, will be provided to the sponsor no more than 30 days after imposition of the clinical hold. A clinical trial may resume only after the sponsor has addressed all deficiencies and submits a complete response in writing to the FDA and the FDA has notified the sponsor that the trial may proceed.
The placement of a hold on a clinical trial indicates that the FDA is doing its job of protecting clinical trial participants by stopping a trial when there’s an indication of a serious problem. It means the FDA officials saw a reason to be concerned and halted the clinical trial until they can ensure that potential benefits exceed potential risks.