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Yes. This is an adverse event because the injury was sustained while he is a subject in your study (i.e. the injury has a temporal association with your study).

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While you can probably take the subject’s word and attribute the injury to a clumsy bump on the head, you still need to rule out other causes, for example:

• Potential side effects of the study drug
  • Antihistamines can cause blurred vision, drowsiness and reduced co-ordination. ⁽⁸⁾ Supplement X may have unknown side effects such as postural hypotension (a cause of dizziness).
    
    
• Symptoms of the disease / health condition that is under investigation (i.e. allergic rhinitis).
  • The subject’s symptoms could have worsened to the extent that they are now affecting his sleep, leading to tiredness / fatigue; he might have conjunctivitis that causes watery and itchy eyes. ⁽⁹⁾
    
    
• Other triggers of falls / accidents
  • For example, the subject could have been drunk (but was too embarrassed to admit it), or the study drug could have worsened the effect of alcohol.

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While it is difficult to prevent accidents from happening, you could:

• Educate subjects about known side effects of the study drugs. Warn them if there could be any increase in risks of accidents (e.g. to avoid operating heavy machineries if the drug can cause drowsiness, or to avoid taking alcohol with the drug).
  
  
• Follow-up subjects regularly to find out if their symptoms have improved or worsened, and where indicated, conduct interim analyses on the safety and effectiveness of the study drug.

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You identified this AE by direct observation during a follow-up visit. Suppose the bruise has gone down by the time you see him, or you are in fact following-up via a phone call (and so cannot observe for physical symptoms), you could still pick it up if you: ^(10,11)

• Ask a routine set of prompt questions during follow-ups, checking if there have been any illnesses, accidents, unusual symptoms, doctor visits, changes in medications, etc.
  
  
• Ask subjects to use a diary to record any of the above, so that they would not have forgotten about them by the time they attend a follow-up. You may also review the diary.
  
  
• Establish effective means of communication with subjects (by telling them how, where and between what times they can find you), and respond to any correspondence from subjects promptly. 
  
  
• Make sure that all study personnel who conduct follow-ups know what sort of incidents should be regarded as adverse events. They also need to have a clear idea of how they should act if they detect an adverse event.    

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If you are a doctor, you may want to:

• Obtain a full history of the incident to ascertain the cause of the AE.
  • You may consider the length of time it usually takes for subjects to experience side effects after taking the study drug, and see whether it corresponds to the timing of injury. ⁽¹⁰⁾
• Perform physical examination and investigations to detect other signs or injuries.
• Provide simple treatment for pain relief.
• Inform him about warning symptoms and ask him to let you know in case he develops any symptoms later.
• Follow him up more frequently where necessary.

Otherwise, you should refer the subject to a doctor who can assess and treat him properly. Ideally, a referral pathway should have been established in your research protocol.  

You may also want to check whether coming in for follow-up visits is imposing too much burden on him, and whether the follow-up schedule or method can be changed to suit him better. You should provide adequate compensation for travel and inconvenience (perhaps he can get a taxi instead of a bus).

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As in the first scenario, you should document the incident properly in the subject’s case report form as well as in an AE logbook. By consistently compiling a record of all AEs, you can monitor for any emerging trends of AEs. Minor AEs that are occurring repeatedly either in the same subject or other subjects would warrant further attention.

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You should have found out, before you start the trial, whether the study’s sponsor, ethics committee and regulatory authorities would want to know about minor AEs such as this. You may only be required to report non-serious AEs periodically (e.g. every few months) rather than as soon as they arise. You should always check if you are unsure.  

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