1. Dr. Ilona Große-Michaelis for the CIOMS MLG Exploratory Team
The Elephant in the Room: Meaningful Communication of Near Synonyms as Suspected Adverse Reactions MedDRA Labeling Groupings (MLGs): Practical Examples Underscore Feasibility  Session #282 Tuesday, 25 June 2019, 4:15-5:30 pm, Room 6D
Dr. Ilona Große-Michaelis for the CIOMS MLG Exploratory Team
Senior Medical Dictionary Expert
Bayer AG

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5. MLGs: Practical Examples Underscore Feasibility
Is it feasible to create MLGs considering all the different interests???
YES, we will demonstrate one option used in one institution for MLG creation as the CIOMS MLG WG has just started to work
Stepwise procedure for creation of an MLG
Interdisciplinary approach/ builds on consensus
Creation only if needed
Product independent
Voluntary usage
Principles in a guidance paper available e.g. important principles: - one PT can be in one MLG only (frequency calculation) - only PTs with identical (or very similar degree of ) severity are grouped together

6. MLGs: Practical Examples Underscore Feasibility
AIM for the creation of an MLG: transfer the medical concept into MedDRA language, catch all relevant MedDRA PTs (do not expect a 1:1 translation) The following example for the unique medical concept “headache” illustrates usage of the MedDRA terminology and hierarchy and some of the associated limitations.

7. MLGs: Practical Examples Underscore Feasibility
Starts with Definition of medical condition:
Headache is defined as “pain in the head” [1]. It is synonymously called cephalgia, cephalalgia or cephalodynia [1].
As “pain” is defined as a more or less localized sensation of discomfort, distress, or agony, resulting from the stimulation of specialized nerve endings [1], also head discomfort is included in this MLG.
[1] Dorland's Illustrated Medical Dictionary for Healthcare Consumers, 32nd edition, 2012, Philadelphia, Saunders .

8. MLGs: Practical Examples Underscore Feasibility
Followed by translation into MedDRA and identification of relevant PTs according to the MLG principles Search for relevant MedDRA PTs to identify inclusion (and exclusion) of PTs for headache
Caveat: do not limit by hierarchical MedDRA structure
Hits for this MedDRA search: approx. 25 different hits/ MedDRA PT terms for headache in different hierarchical structures (different HLTs, HLGTs, SOCs) .

9. MLGs: Practical Examples Underscore Feasibility
Identification of relevant PTs according to the principles

10. MLGs: Practical Examples Underscore Feasibility
PT inclusion for headache (alphabetical order): 1) PT Drug withdrawal headache
2) PT Exertional headache
3) PT Headache
4) PT Head discomfort
5) PT Medication overuse headache
6) PT New daily persistent headache
7) PT Primary headache associated with sexual activity
8) PT Sinus headache
9) PT Tension headache
10) PT Vascular headache

11. MLGs: Practical Examples Underscore Feasibility
PT exclusion for headache: 1) PTs representing migraine, e.g., PT Ophthalmoplegic migraine, PTs under HLT Migraine headaches
2) PTs representing syndromes with the potential symptom of headache, e.g., PTs Craniocervical syndrome, Eagle’s syndrome, SUNCT syndrome
3) PTs representing diagnoses with the potential symptom of headache, e.g., PTs Temporal arteritis, Paranasal sinus discomfort, Sinus pain
4) PTs representing headache with specific underlying causes or diseases, of different etiology, e.g., PTs Cold-stimulus headache, Postictal headache, Post-traumatic headache, Post lumbar puncture syndrome, Procedural headache, Premenstrual headache, Primary cough headache, Cervicogenic headache
5) PTs representing different degree of severity, e.g., PTs Thunderclap headache, PT Cluster headache

12. MLGs: Practical Examples Underscore Feasibility
MLG creation principles
Identify all possible MedDRA PTs fitting to the medical concept, independently of MedDRA hierarchy (limitations due to different concepts)
Define inclusion and exclusion criteria for PTs precisely according to the principles
Create and use transparent documentation

13. MLGs: Practical Examples Underscore Feasibility
The approach to developing and simplifying RSI is not harmonized, despite existing regulatory guidance
CIOMS MLG WG is developing principles how MLGs may facilitate simplification of RSI by grouping similar MedDRA terms to communicate meaningful and important medical concepts when not appropriately supported by the established MedDRA hierarchy
MLGs would also facilitate calculation of frequencies of suspected ADRs from clinical trials and for comparison of frequencies between products (and, perhaps, across indications, populations, or posology).
Feasibility of consensus principles will be assessed in more depth by CIOMS, but current status gives a positive answer about feasibility already now!

14. Thank You and looking forward to a fruitful discussion
Dr. Ilona Große-Michaelis for the CIOMS MLG Exploratory Team
Senior Medical Dictionary Expert
Bayer AG

15. Back up slides

16. MLGs: Practical Examples Underscore Feasibility
Example “abdominal pain”, PT inclusion (alphabetical order):
1) PT Abdominal discomfort
2) PT Abdominal pain
3) PT Abdominal pain lower
4) PT Abdominal pain upper
5) PT Abdominal tenderness
6) PT Gastrointestinal pain

17. MLGs: Practical Examples Underscore Feasibility
Example “abdominal pain”, PT exclusion: 1) PTs for abdominal pain forms of great severity, e.g. PT Abdominal rebound tenderness, PT Abdominal rigidity
2) PTs for colic terms, e.g. PT Infantile colic, PT Biliary colic
3) PT Flatulence with LLT Gas pain
4) PT Visceral pain
5) PTs represented in MLG Dyspepsia, e.g. PT Epigastric discomfort, PT Dyspepsia
6) PTs for oral, pharyngeal, oesophageal, rectal pain
7) PTs representing pain in specific abdominal organs, e.g. PT Hepatic pain, PT Gallbladder pain
8) PTs represented in MLG Pelvic pain, e.g. PT Pelvic discomfort, PT Pelvic pain