Example More Than One LLT Selected There is no single MedDRA term for “metastatic gingival cancer”. Therefore, the options are: Select LLT Gingival cancer OR LLT Metastatic carcinoma Select LLT Gingival cancer AND LLT Metastatic carcinoma Check the Hierarchy When considering selecting an LLT, check the hierarchy above the LLT (PT level and further up the hierarchy to HLT, HLGT and SOC) to ensure the placement accurately reflects the meaning of the reported term. Select Terms for All Reported Information, Do Not Add Information Select terms for every AR/AE reported, regardless of causal association. In addition, select terms for device-related events, product quality issues, medication errors, medical history, social history, investigations, and indications as appropriate. If a diagnosis is reported with characteristic and symptoms, the preferred option is to select a term for the diagnosis only (see Section 3.1 for details and examples). When selecting terms, no reported information should be excluded from the term selection process; similarly, do not add information by selecting a term for a diagnosis if only signs or symptoms are reported. Example Reported LLT Selected Comment Abdominal pain, increased serum amylase, and increased serum lipase Abdominal pain It is inappropriate to assign an LLT for diagnosis of “pancreatitis” Serum amylase increased Lipase increased TERM SELECTION POINTS Definitive and Provisional Diagnoses with or without Signs and Symptoms The table below provides term selection options for definitive and provisional diagnoses with or without signs/symptoms reported. Examples are listed below the table. A provisional diagnosis may be described as “suspicion of”, “probable”, “presumed”, likely”, “rule out”, “questionable”, “differential”, etc.
The preferred option for a single or multiple provisional diagnosis(es) is to select a term(s) for the diagnosis(es) and terms for reported signs and symptoms. This is because a provisional diagnosis may change while signs/symptoms do not. SUMMARY OF PREFERRED AND ALTERNATE OPTIONS SINGLE DIAGNOSIS DEFINITIVE DIAGNOSIS PROVISIONAL DIAGNOSIS Single definitive diagnosis without signs/symptoms Diagnosis (only possible option) Single provisional diagnosis without signs/symptoms Provisional diagnosis (only possible option) Single definitive diagnosis with signs/symptoms Preferred: Diagnosis only Alternate: Diagnosis and signs/symptoms Note: Always include signs/symptoms not associated with diagnosis SEE EXAMPLE 1 Single provisional diagnosis with signs/symptoms Preferred: Provisional diagnosis and signs/symptoms Alternate: Signs/symptoms only Note: Always include signs/symptoms not associated with diagnosis SEE EXAMPLE 2 MULTIPLE DIAGNOSES DEFINITIVE DIAGNOSES PROVISIONAL DIAGNOSES Multiple definitive diagnoses without signs/symptoms Multiple diagnoses (only possible option) Multiple provisional diagnoses without signs/symptoms Multiple provisional diagnoses (only possible option)
Pulmonary embolism, myocardial infarction, and congestive heart failure with chest pain, cyanosis, shortness of breath, and blood pressure decreased Congestive heart failure Pulmonary embolism Myocardial infarction Congestive heart failure Chest pain Cyanosis Shortness of breath Blood pressure decreased 4 Chest pain, cyanosis, shortness of breath, and blood pressure decreased. Differential diagnosis includes pulmonary embolism, myocardial infarction, and congestive heart failure. Pulmonary embolism Myocardial infarction Congestive heart failure pain Cyanosis Shortness of breath Blood pressure decreased Chest pain Cyanosis Shortness of breath Blood pressure decreased Always include signs/ symptoms not associated with diagnosis Myocardial infarction, pain, dyspnoea, diaphoresis, ECG changes and jaundice Myocardial infarction Jaundice (note that jaundice is not typically associated with myocardial infarction)
of 1.6 mEq/L is a low result, not high) Ambiguous information Example Reported LLT Selected Comment GU pain Pain Effort should be made to obtain clarification of the meaning of "GU" from the source so that more specific term selection may be possible. “GU” could be either “genito-urinary” or “gastric ulcer”. If additional information is not available, then select a term to reflect the information that is known, i.e., LLT Pain Vague information For information that is attempt to obtain clarification. If clarification cannot be achieved, select an LLT that reflects the vague nature of the reported event. Example Reported LLT Selected Comment Turned green Unevaluable event “Turned green” reported alone is vague; this could refer to a patient condition or even to a product (e.g., pills) Patient had a medical problem of unclear type Ill-defined disorder Since it is known that there is some form of a medical disorder, LLT
Exposures during Pregnancy and Breast Feeding To select the most appropriate exposure term (or terms), first determine if the subject/patient who experienced the event is the mother or the child/foetus. Events in the mother Pregnant patient exposed to medication with clinical consequences If a pregnancy exposure is reported with clinical consequences, select terms for both the pregnancy exposure and the clinical consequences. Example Reported LLT Selected Pregnant patient receiving drug X experienced a pruritic rash Maternal exposure during pregnancy Pruritic rash Pregnant patient exposed to medication without clinical consequences If a pregnancy exposure report specifically states that there were no clinical consequences, the preferred option is to select only a term for the pregnancy exposure. Alternatively, a term for the pregnancy exposure and the additional LLT No adverse effect can be selected (see Section 3.21). Example Reported LLT Selected Preferred Option Patient received drug X while pregnant (no adverse effect) Maternal exposure during pregnancy Maternal exposure during pregnancy No adverse effect Events in the child or foetus Select terms for both the type of exposure and any adverse event(s). Example Setting/Patient Reported LLT Selected Foetus with AE; exposed in utero; mother took product Pregnant woman taking drug X; foetal tachycardia noted on routine examination Drug exposure in utero Foetal tachycardia
Reported LLT Selected Comment The patient’s liver enzymes were measured every six months instead of the recommended monthly schedule Drug monitoring procedure incorrectly performed The monthly monitoring schedule is in the for this drug. This is an example of incorrect monitoring of laboratory tests recommended in the use of a drug. Patient taking lithium-based drug did not have his lithium levels measured Therapeutic drug monitoring analysis not performed This is an example of not monitoring the therapeutic drug level to ensure that it is within the therapeutic range as recommended in the label for this drug. If the label describes known effects when the product is co-administered with specific drugs, with specific foods, or to patients with specific disease states, and if the report does not indicate that this is intentional misuse or intentional off label use, then select a medication error term for the type of interaction, such as those listed below: Medication Error Terms – Labelled Interactions Labelled drug-drug interaction medication error Labelled drug-food interaction medication error Labelled drug-disease interaction medication error Documented hypersensitivity to administered product Example Reported LLT Selected Comment Patient became pregnant whilst taking an antifungal drug and an oral contraceptive Labelled drug-drug interaction medication error Pregnancy on oral contraceptive Product is labelled for this drug-drug interaction (see also Section 3.20)
Patient drank grapefruit juice whilst taking a calcium channel blocker Labelled drug-food interaction medication error Product is labelled for this drug-food interaction with grapefruit juice Patient with renal failure is accidentally prescribed a drug that is contraindicated in renal failure Labelled drug-disease interaction medication error Contraindicated drug prescribed Product is labelled for this drug-disease interaction. LLT Contraindicated drug prescribed provides additional information about the nature of the labelled interaction medication error and the stage at which the error occurred Patient with sulfa allergy is administered a sulfonamide-based drug and experienced wheezing Documented hypersensitivity to administered drug Wheezing See Concept Description in Appendix B of the MedDRA Introductory Guide. This medication error refers to the situation when a patient is administered a drug that is documented in the patient's medical file to cause a hypersensitivity reaction in the patient. Do not a medication error Do not infer that a medication error has occurred unless specific information is provided. This includes inferring that extra dosing, overdose, or underdose has occurred (see Section 3.18) Example Reported LLT Selected Comment Patient took only half the prescribed dose Underdose on this report, it is not known whether the underdose is intentional or accidental. If
Physical therapist developed a photosensitivity rash on after exposure to an NSAID-containing pain relief cream that she applied to a patient Occupational exposure to drug Exposure via skin contact Photosensitive rash Pathologist chronically exposed to formaldehyde developed nasopharyngeal carcinoma Occupational exposure to toxic agent Nasopharyngeal carcinoma Exposure to formaldehyde is a known risk factor for this type of malignancy Nurse splashed injectable drug in her own eye resulting in excessive tearing Inadvertent exposure to drug Excess tears An additional term for occupational exposure – e.g., LLT Occupational exposure to drug – could also be selected, if applicable to regional requirements Misuse, Abuse and Addiction The concepts of misuse, and addiction are closely related and can pose challenges for term selection since the terms may overlap to some extent; the specific circumstances of each case/reported event may help in consideration for term selection of these concepts. Medical judgment and regional regulatory considerations need to be applied. It may also be useful to consider these concepts as shown in the table below: Concept Intentional? By Whom? Therapeutic Use? Additional Sections in
Prevention and prophylaxis When an indication for prevention or prophylaxis is reported, select the specific MedDRA term, if it exists (Note: the words “prevention” and “prophylaxis” are synonymous in the context of MedDRA). Example Reported LLT Selected Prophylaxis of arrhythmia Arrhythmia prophylaxis Prevention of migraine Migraine prophylaxis If there is no MedDRA term containing “prevention” or “prophylaxis”, choose one of the following options. The preferred option is to select a general prevention/ prophylaxis term and a term for the condition. Alternatively, select a term for the condition alone or a prevention/prophylaxis term alone. Example Reported LLT Selected Preferred Option Comment Prevention of hepatotoxicity Prevention Hepatotoxicity Represents both the prevention/prophylaxis concept and the condition Hepatotoxicity Represents the condition Prevention Represents the prevention/prophylaxis concept Procedures and diagnostic tests as indications Select the appropriate term if the product is indicated for performing a procedure or a diagnostic test. Example Reported LLT Selected Induction of anaesthesia Induction of anaesthesia Contrast agent for angiogram Angiogram Contrast agent for coronary angiogram Coronary angiogram
MSSO’s Recommendations for MedDRA Implementation and Versioning for Clinical Trials Transition Date for the Next MedDRA Version * Requires user ID and password to access Membership of the ICH Points to Consider Working Group Current members of the ICH Points to Consider Working Affiliation Member Commission of the European Communities Luisa Casini Kavita Chadda European Federation of Pharmaceutical Industries and Associations Hilary Vass* Christina Winter† Health Canada Pritchett Lynn Macdonald Japanese Maintenance Organization Yutaka Kazuyuki Sekiguchi Mitsuru Takano Tomoko Narita Pharmaceutical Manufacturers Association Yo Tanaka Hitomi Takeshita Miyako Shionoiri MedDRA MSSO Judy Harrison Ministry of Health, Labour and Welfare/Pharmaceuticals and Medical Devices Agency Daisuke Miki Ohta Daisuke Sato Yasuko Inokuma Kiyomi Ueno Pharmaceutical Research and Manufacturers of America Milbhor D’Silva
Manabu Yamamoto; Nobuhiro Yamamoto Pharmaceutical Research and Manufacturers of America David Goldsmith; Sidney Kahn; Anna-Lisa Kleckner; Susan M. Lorenski; JoAnn Medbery; Margaret M. Westland† US Food and Drug Administration Miles Braun; Andrea Feight; John (Jake) Kelsey†; Brad Leissa; Toni Piazza-Hepp † Former Rapporteur