Earlier this month, the US Food and Drug Administration (FDA) halted a phase 2 clinical trial conducted by Juno Therapeutics (Juno) after two patients died at the end of June. At the time, the company was treating patients with relapsed or refractory B cell acute lymphoblastic leukaemia.

Days after the trial was suspended, Juno disclosed they had recently added the chemotherapy drug, fludarabine, to its trial regimen, which some believe may have precipitated the deaths of the two patients.

When shares in the company subsequently fell (by more than 30 percent), the future of Juno’s leading pipeline drug was under serious threat.   

However, recently the FDA gave the company the all clear to resume its trial after Juno had agreed to remove fludarabine from its regimen, completing a whirlwind set of events.

But as the dust settles on yet another clinical trial tragedy, the events that unfolded in June serve as a grave reminder of the fine lines sponsor companies operate within to ensure the safety of the patient.

Although it goes without saying, it’s vitally important sponsors take the necessary precautions to protect the well-being of patients. But how do you ensure a patient is ever truly safe?

Well for a start, as the FDA states in their draft guidance, Oversight of Clinical Investigations: A Risk­Based Approach to Monitoring, “[t]he most important tool for ensuring human subject protection … is a well-designed and articulated protocol.”[1]

The importance of a thorough protocol cannot be emphasised enough as, when followed, it can significantly reduce patient fatalities. Therefore, the sponsor must identify potential threats to subject safety before tailoring a protocol that either eliminates or mitigate those risks.[2]

Additionally, there are various steps sponsors should consider to further enhance the safety of patients:

• Ensure the protocol is inspected and approved by an ethics committee
• Set up a data monitoring committee that oversees the conduct of the clinical trial
• Put in place an insurance plan for trial participants
• Establish steps that safeguards the privacy of the patient
• Make sure the patient is made explicitly aware of the benefits and risks of the trial before they agree to take part.[3]

The role monitoring plays in the CT process is another factor that cannot be overstated. Having an onsite monitor to inspect the conduct of the trial not only enhances patient safety, it also helps improve the integrity and quality of data accrued. Additionally, monitors can supervise the investigators, assess their compliance with the protocol, and identify practices that might be deemed ineffective (or take up valuable resources).[4]

Once the trial is underway, in the event of an SAE (serious adverse event), it’s important the sponsor notifies it to the relevant authority. Furthermore, the severity of the SAE (mild, moderate, severe), its seriousness (serious, non-serious), and its relatedness (unrelated, possibly related, probably related) should all be reported within 24 hours.[5]

Additionally, the investigator is responsible for assessing the SAE for its expectedness and causality, filing all the data in the appropriate medical records in accordance with the protocol and SOPs.[6]

While it may not be possible to absolutely guarantee the safety of a patient in a study, remembering these key steps could make all the difference in determining its success or failure.

 

References

(1, 2, 4, 6) Oversight of Clinical Investigations: A Risk­Based Approach to Monitoring – http://www.fda.gov/downloads/ScienceResearch/SpecialTopics/CriticalPathInitiative/UCM277529.pdf

(3) Cancer Research UK – http://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/what-you-should-be-told-about-a-clinical-trial/safety-in-clinical-trials#CyQEvqw03PKy5Rxb.99

(5) Safety monitoring and reporting for clinical trials in Europe –http://www.ema.europa.eu/docs/en_GB/document_library/Presentation/2010/06/WC500093378.pdf

Clinical Trial Oversight – http://www.asgct.org/UserFiles/quayeslidesII.pdf

 

[1] http://www.fda.gov/downloads/ScienceResearch/SpecialTopics/CriticalPathInitiative/UCM277529.pdf [2] See previous [3] Cancer Research UK – http://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/what-you-should-be-told-about-a-clinical-trial/safety-in-clinical-trials#CyQEvqw03PKy5Rxb.99 [4] Oversight of Clinical Investigations: A Risk­Based Approach to Monitoring – http://www.fda.gov/downloads/ScienceResearch/SpecialTopics/CriticalPathInitiative/UCM277529.pdf [5]Safety monitoring and reporting for clinical trials in Europe –http://www.ema.europa.eu/docs/en_GB/document_library/Presentation/2010/06/WC500093378.pdf