Definitions and difference in PVG terms: Designated medical event (DME), Important medical events (IMEs), WHO critical terms and AESIs

Definitions and difference in PVG terms: Designated medical event (DME), Important medical events (IMEs), WHO critical terms and Adverse event of special interest (AESI)

Its important to understand these key definitions and more importantly their differences.. Lets just dive in…

Designated medical event (DME):

• Adverse events considered rare, serious, and associated with a high drug-attributable risk and which constitute an alarm with as few as one to three reports

Examples of DMEs include:

• Stevens-Johnson syndrome

• Toxic epidermal necrolysis

• Hepatic failure

• Anaphylaxis

• Aplastic anaemia

• Torsade de pointes

• According to the EMA, the list of so-called designated medical events contains “serious medical concepts often causally associated with drugs across multiple pharmacological/therapeutic classes.”

• A list of standardized terms describing medical events it says will be used by the agency and other European regulators to identify suspected adverse events.

• EMA has developed a list of designated medical events containing medical conditions that are inherently serious and often medicine-related

• It does not address product specific issues or medical conditions with high prevalence in the general population

• DME list serves as a safety net in signal detection

• EMA and Member States use it to focus on reports of suspected adverse reactions that deserve special attention, irrespective of statistical criteria used to prioritize safety reviews

• In short, a regulatory safety net (to avoid missing signals due to MAH subjectivity)- a list with rare, inherently and most often (than not) events likely to be causes by drugs (across classes!)

So DMEs (things to remember):

• Used by regulators

• Events by nature, more likely to occur due to medications than not

• Events can occur due to/across multiple classes of medications (e.g. SJS/TEN)

• Even two cases may lead to a signal

• More severe by design (SJS)

• Signal detection uses DMEs

• Useful for risk analysis

• List available on EMA site

• Regulatory safety net to avoid missing a signal due to MAH subjectivity

Important medical event (IME):

• The EudraVigilance Expert Working Group has coordinated the development of an important medical event (IME) terms list based on the Medical Dictionary for Regulatory Activities (MedDRA).

• This IME list aims to facilitate

1- The classification of suspected adverse reactions

2- The analysis of aggregated data

3- Assessment of ICSRs in the framework of the day-to-day pharmacovigilance activities.

The IME list is intended for guidance purposes only and is available on the EMA website to stakeholders who wish to use it for their pharmacovigilance activities. It is regularly updated in line with the latest version of MedDRA.

Difference between DME and IME:

• DMEs are adverse events considered rare, serious, and associated with a high drug-attributable risk

• DMEs constitute an alarm with as few as one to three reports

• Used by EMA and EU regulators to identify suspected AEs (SAEs)

• IME- IME list prepared by EudraVigilance working group based on MEDDRA

• Intended for guidance MAH can use

• This IME list aims to facilitate:

1- The classification of suspected adverse reactions

2- The analysis of aggregated data

3- Assessment of ICSRs in the framework of the day-to-day pharmacovigilance activities.

DMEs vs IMEs in a nutshell:

• So basically, DMEs are used in signal detection

• If identified → Even 2–3 cases can lead to signal

• More serious and binding

• Used by EU regulators themselves

• These events by nature are more likely to be caused by drugs

• Whereas, IMEs are for MAH guidance, more voluntary and can be used in ICSR and aggregate reports

• IME is more of a list for housekeeping and not alerting

• More for MAH guidance than regulator use

  • DMEs would lead to signal even if 2–3 events, not IMEs

Critical terms:

• The WHO marked some terms as ‘Critical Terms’

• Critical terms are found in WHO directory à WHO ART

• These terms either refer to or might be indicative of serious disease states and warrant special attention, because of their possible association with the risk of serious illness that may lead to more decisive action than reports on other terms

• The WHO list of Critical Terms may serve as a basis for medical judgment of AEs, i.e. to assess whether AEs should be considered serious due to their medical importance

  • Examples: Death, anaphylactic shock, convulsions, erythema multiforme

Adverse event of special interest (AESI):

• An adverse event of special interest (serious or non-serious) is one of scientific and medical concern specific to the sponsor’s product or program

• Ongoing monitoring and rapid communication by the investigator to the sponsor may be appropriate

• Such events may require further investigation in order to characterize and understand them

• Depending on the nature of the event, rapid communication by the trial sponsor to other parties may also be needed (e.g., regulators)

It was a straightforward, technical article, a bit to-the point.. Please let me know what you think in the comments :)

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🏳️‍🌈 Aditi Sheth 🏳️‍🌈

🏳️‍🌈📚 Bookworm fueled by curiosity | 750+ Certificates | PBRER | Aggregate reports | Artificial Intelligence | Trained Psychologist | Introvert | ISFJ |MBBS