Multiple definitive diagnoses with Preferred: Multiple diagnoses only Alternate: Diagnoses and signs/symptoms Note: Always include signs/symptoms not associated with diagnosis SEE EXAMPLE 3 Multiple provisional diagnoses with signs/symptoms Preferred: Multiple provisional diagnoses and signs/symptoms Alternate: Signs/symptoms only Note: Always include not associated with diagnosis SEE EXAMPLE 4 EXAMPLES Example Reported LLT Selected Preferred Option 1 Anaphylactic reaction, rash dyspnoea, hypotension, and laryngospasm Anaphylactic reaction Anaphylactic reaction Rash Dyspnoea Hypotension Laryngospasm 2 Possible myocardial infarction with chest pain, dyspnoea, diaphoresis Myocardial infarction Chest pain Dyspnoea Diaphoresis Chest pain Dyspnoea Diaphoresis 3 Pulmonary embolism Myocardial infarction
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 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 Chest 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, chest pain, dyspnoea, diaphoresis, ECG changes and jaundice Myocardial infarction Jaundice (note that jaundice is not typically associated with myocardial infarction)
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 disorder can be selected Combination Terms A combination term in MedDRA is a single medical concept combined with additional medical wording that provides important information on pathophysiology or aetiology. A combination term is an internationally recognised, distinct and robust medical concept as illustrated in the examples below. Example MedDRA Combination Terms PT Diabetic retinopathy PT Hypertensive cardiomegaly PT Eosinophilic pneumonia A combination term may be selected for certain reported ARs/AEs (e.g., a condition “due to” another condition), keeping the following points in mind (Note: medical judgment should be applied): Diagnosis and sign/symptom If a diagnosis and its characteristic or symptoms are reported, select a term for the diagnosis (see Section 3.1). A MedDRA combination term is not needed in this instance. Example Reported LLT Selected pain due to myocardial infarction Myocardial infarction One reported condition is more specific than the other If two conditions are reported in combination, and one is more specific than the other, select a term for the more specific condition. defined
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 taking drug X; foetal tachycardia noted on routine examination Drug exposure in utero Foetal tachycardia
Concept Intentional? By Whom? Therapeutic Use? Additional Sections in this Document Misuse Yes Patient/consumer Yes* 3.16.1 Abuse Yes Patient/consumer No 3.16.2 Addiction Yes Patient/consumer No 3.16.3 Medication error No Patient/consumer or healthcare professional Yes 3.15 Off label use Yes Healthcare professional Yes 3.27 * Definitions of misuse may not always include the concept of therapeutic use; misuse may be similar to the concept of abuse in some regions. Select the most specific term available and always check the MedDRA hierarchy above the selected term to be sure it is appropriate for the reported information. In some cases, it may be appropriate to select more than one MedDRA LLT to represent the reported information. Misuse For the purposes of term selection and analysis of MedDRA-coded data, misuse is the intentional use for a therapeutic purpose by a patient or consumer of a product – or prescription – other than as prescribed or not in accordance with the authorised product information. Example Reported LLT Selected Patient deliberately took the medication daily instead of once daily Intentional misuse in dosing frequency Abuse For the purposes of term selection and analysis of MedDRA-coded data, abuse is the intentional, non-therapeutic use by a patient or consumer of a product – over-the counter or prescription – for a perceived reward or desired non-therapeutic effect including, but not limited to, “getting high”(euphoria). Abuse may occur with a single use, sporadic use or persistent use of the product. Example Reported LLT Selected Comment
Immunosuppression Immunosuppression Unclear if the purpose is to induce or to treat immunosuppression Complex indications Term selection for some indications (e.g., in regulated product information) may be complex and require selection of more than one LLT to represent the information completely, depending on the circumstances. Reported LLT Selected Comment Treatment of aggression in autism Aggression The products do not treat the underlying autism, thalassaemia, or myocardial infarction, but they do address the associated signs/symptoms (aggression, chronic iron overload, atherothrombosis). It may be necessary to select LLT Autism, LLT Thalassaemia major, or LLT Myocardial infarction based on regional regulatory requirements. Treatment of chronic iron overload in thalassaemia major Chronic iron overload Prevention of atherothrombotic events in patients with myocardial infarction Atherothrombosis prophylaxis Indications with genetic markers or abnormalities For indications that describe a genetic marker or abnormality associated with a medical condition, select a term for both the medical condition and the genetic marker or abnormality. Example Reported LLT Selected Non small cell lung cancer with K-ras mutation cell lung cancer K-ras gene mutation 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
Explanations of the interpretations and uses of certain product quality issue terms (e.g., “Product coating incomplete”) are found in the MedDRA Introductory Guide (Appendix B, MedDRA Concept Descriptions). Product quality issue reported with clinical consequences If a product quality results in clinical consequences, term(s) for the product quality issue and the clinical consequences should be selected. Example Reported LLT Selected Comment New bottle of drug tablets have unusual chemical smell that made me nauseous Product abnormal Nauseous I switched from one brand to another of my blood pressure medication, and I developed smelly breath Product substitution brand to brand Smelly breath Consumer noted that the toothpaste they had purchased caused a stinging sensation in the mouth. Subsequent investigation of the product lot number revealed that the toothpaste was a counterfeit product. Product counterfeit Stinging mouth Patient reported severe burning in his nose after using nasal drops that had a cloudy appearance. An investigation by the manufacturer revealed that impurities were found in the batch of nasal drops and that these had been introduced by a faulty piece of equipment. Nasal burning Product appearance cloudy Product impurities Manufacturing equipment Specific product defects and issues with manufacturing systems may be reported subsequently as part of a root cause analysis Product quality issue reported without clinical consequences It is important to capture the occurrence of product quality issues even in the absence of clinical consequences.
Ministry of Health, Labour and Welfare/Pharmaceuticals and Medical Devices Agency Miki Ohta Daisuke Sato Yasuko Inokuma Kiyomi Ueno Pharmaceutical Research and Manufacturers of America Milbhor US Food and Drug Administration Sonja Brajovic# Christopher Breder World Health Organization Daisuke Tanaka * Current Rapporteur # Regulatory Chair † Former Rapporteur Former members of the ICH Points to Consider Working Group Affiliation Member Commission of the European Communities Dolores Montero; Carmen Kreft-Jais; Morell David; Sarah Vaughan European Federation of Pharmaceutical Industries and Associations Barry Hammond†; Reinhard Fescharek† Health Canada Alison Bennett; Valérie Bergeron; Heather Morrison;Polina Ostrovsky; Michelle Séguin; Heather Sutcliffe; Bill Wilson Japanese Maintenance Organization Handa; Akemi Ishikawa; Yasuo Sakurai; Yuki Tada; Reiji Tezuka Japan Pharmaceutical Manufacturers Association Takayoshi Ichikawa; Akemi Ishikawa; Satoru Mori; Yasuo Sakurai; Kunikazu Yokoi MedDRA MSSO JoAnn Medbery; Patricia Mozzicato