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Yes. This is an untoward medical event that has occurred to a subject in your study. Because the subject required emergency resuscitation, this is considered a ‘serious adverse event’ (SAE).

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It may or may not have been caused by the study drug. Some potential causes are:

• Side effect of herbal supplement X or the active control (oral antihistamine)
  
• The effect of other medications, food or environmental chemicals that the subject was exposed to.
  
• Pharmacologic interactions between the study drug and other medications / food that the subject had ingested.
• An overdose of the study drug or other medications that the subject was taking
  
• Expiry, improper storage conditions, contamination, sabotage, or anything that could have affected the quality of the study drug

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While this depends on the cause of the incident, there are some general preventative measures that you can take, for example:

• Screen for high-risk subjects and, where necessary, exclude them from the study. For example, people with severe liver or renal impairment may not be able to metabolise / excrete certain medications properly.
  
  
• Ensure that study personnel who dispense the study drugs have sufficient training in handling the drugs and in providing instructions to subjects. 
  
  
• Ensure that subjects fully understand the method of administration of the study drug, for example, by giving them a leaflet with dosing instructions, or watching them when they take their first dose, especially if the steps are complicated. ⁽⁴⁾
  
  
• Work with the research sponsor to ensure that study drugs are manufactured, transported, stored, labelled and disposed of according to the standards of Good Manufacturing Practices (GMP) Annex 13: Manufacture of investigational medicinal products (2018) and Good Distribution Practices (GDP) (2018).

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The adverse event (AE) was reported from the emergency department. You might have detected it earlier if you:

• Watch subjects take the first dose of the study drug and monitor them for an appropriate amount of time before allowing them to leave. In  high risk Phase 1 trials, subjects may need to be admitted to an observation ward for a few days. ⁽⁵⁾ Research sites should also be well-staffed and well-equipped to deal with any emergencies (e.g. staff should be trained in resuscitation techniques, and the resuscitation trolley should be in good working condition).

• Educate subjects, their family members, guardians or doctors about warning symptoms and possible unknown side effects. Tell them what to do when worrying symptoms occur.
  
  
• Provide subjects with a note containing your emergency contact number and other pertinent study details (such as their participant ID and the study drug names), and remind them to always carry the note with them. ⁽⁴⁾

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• You should work with the emergency doctors to identify the cause of this reaction and ensure that the subject receives all necessary treatment. This can be facilitated by:
  
  
  • Referring to the drug information leaflets or other background literature which provide safety information about the study drugs. You should know where they are kept and have already read them before you start the trial.
  • Following the emergency unblinding procedure according to your protocol if unblinding is deemed necessary to provide the right treatment to the subject.
    
    
• You should also check that other subjects in your study are safe. You may want to:*
  
  
  • Continue the study but make changes to the protocol
  • Suspend the study until further investigation and safety data analyses are done
  • Terminate the study
  • Inform all subjects about the AE and any associated actions that have been taken, and re-consent where necessary.
    
    
• You may or may not cover the subject’s medical expenses, but this should have been communicated to the subject early on during the consent process. Ideally, an insurance policy should be purchased for research subjects in a clinical drug trial such as this.
  
  
• You may need to withdraw this subject from the study.
  
  

* These decisions should be made in consultation with the study sponsor (in a sponsored trial), ethics committee and regulatory authorities unless there is immediate threat to the safety of subjects.

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You should document the incident properly in the subject’s case report form, including the full history, examination findings, investigation findings, working diagnoses and all treatments that have been provided. You should monitor the subject’s progress and make further notes until the event has resolved.

You should also record the AE in a logbook so that you can quickly refer to it if similar incidences occur in the future.

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You may need to make an expedited (i.e. fast) report of this SAE to:

• The study sponsor who should work with you to manage this AE and ensure the safety of all subjects, including those in other research sites (in a multi-centre study). 
  
  
• The research ethics committee who will consider whether it is safe to continue the study and suggest additional safety measures that you can take. ⁽⁶⁾
  
  
• The regulatory authority which is responsible for monitoring the safety of all new or registered drugs (i.e. the NPRA). ⁽⁷⁾
  

In your report, you should present all findings about the incident and indicate:

• The seriousness of the AE
• How likely that it is caused by your study procedures or drugs
• Whether it is expected (e.g. a known side effect) or unexpected

Further guidance on adverse event reporting will be provided in Module 8: Ethics review.