Table 1

Recommendations by North American and European regulatory authorities for determining the need for an IDMC in clinical trials3 9

ConsiderationsFDA3ConsiderationsEMEA/EMA9
Emergency settings with no informed consentRequired
Risk to clinical trial participant, that is,
  • High safety concerns.

  • Highly favourable or unfavourable study endpoint.

  • Particular safety concerns (eg, particularly invasive procedure).

  • Possible serious toxicity with study treatment.

  • Potentially fragile or vulnerable populations.*

  • Study participants with elevated risk of death or other serious outcomes.

  • A large, multicentre clinical trial of long duration.

RecommendedRisk to clinical trial participant, that is,
  • Life-threatening diseases (regardless of whether the study treatment reduces morbidity or mortality, or relieves the patient’s situation).

  • Types of patient population (eg, paediatric or mentally disabled patients).

  • Possible ability of study treatment to harm the patient.

Recommended
Practicality of IDMC, that is,Practicality of IDMC, that is,
  • Clinical trial of short duration.

May be impractical
  • Clinical trial of short duration and the study drugs are well characterised and known to not harm the patient.

May be impractical
  • Short-term trials with high risks (ie, important safety concerns).

Consider
Ensuring scientific validity and perception of the trial, that is,
  • Trials with appreciable duration.†

  • Compelling new external information that may impact on the trial.

  • Accumulating trial data that may indicate the need for modifications to be made.

ConsiderEnsuring scientific validity and perception of the trial, that is,
  • Long-term trials (even if non-life threatening disease).

  • Study design with preplanned interim analyses for early stopping.

  • Accumulating trial data that may indicate the need for modifications to be made.

May be indicated
Clinical trial examining lesser outcomes (eg, symptom relief)‡Generally not needed
  • *For example, study participants who may be children, or pregnant women, or very elderly, or terminally ill, or have diminished mental capacity.

  • †Trials that are conducted over a long period of time may be affected by changes over time (ie, changes in the standard of treatment, or in the understanding of the disease, etc). These external changes may prompt an interest in modifying some aspects of the trial as it progresses.

  • ‡Unless there is an elevated risks of more severe outcomes.

  • EMA, European Medicines Agency; EMEA, European Medicines Evaluation Agency; FDA, Food and Drug Administration; IDMC, independent data monitoring committee.