This study was not powered to detect non-inferiority of the shorter protocol versus the standard approach; therefore, further research is needed to confirm the efficacy of the 12 hour modified acetylcysteine regimen. Furthermore, during the course of the trial, changes to treatment guidelines were introduced by the MHRA that lowered the threshold for acetylcysteine treatment for paracetamol overdose. Whether this change affected the efficacy of the modified acetylcysteine regimen for prevention of adverse effects is unclear and will need to be addressed in future studies.