Concept: Use and Identification of Specific Drugs in Clinical Research

Introduction

When working with a specific set of drugs or a specific clinical condition you must be sure that all of the appropriate drugs have been identified. This typically will involve at least one, and often more, people with a clinical or pharmacological background. The process tends to be iterative and input and clarification at several steps along the way.

Identification of the condition or group of drugs that you are studying is typically done starting with Anatomical Therapeutic Chemical (ATC) Classification codes (e.g. A10A) or Generic Drug names (e.g. INSULIN). In some cases clinicians will provide product names or even a sample of DINs (e.g. 00446572, 00513644, 00586714, 00587737, …). Usually you need to draw a larger sample based on the starting point and refine this as necessary with input from the clinician or pharmacist. If the drug is being used as a marker of a specific condition then you should also ask if the drug can be used for other conditions. In some cases the specific route or form will be applicable to the condition.

Required Information

1. One of the following: ATC, Generic Names, Product Names or specific DINs (Drug Identification Numbers);
   
2. Access to the MCHP Master Formulary (MF) files;
   
3. Access to the Drug Program Information Network (DPIN) DIN Master files;
   
4. Access to the Health Canada Drug Product Database (DPD);
   
5. A clinician or pharmacist familiar with the drugs or conditions you want to study.

Process

1. Identify broadly drugs and/or condition. If you are using a diagnosis or condition then identify a set of drugs that are used primarily for that condition.
   
2. Identify generic drug name and/or ATC codes for the drugs of interest. Remember ATC codes and indication for drugs can change over time.
   
3. Pull records from the MCHP Master Formulary(s) based on generic name and/or ATC.
   
   
   1. Note prefix if necessary for salt formulations (e.g. AntiBiotic: sodium fusidate, Fusidic acid, Fucidin Ointment)
   
   
4. Re-pull records from DIN Master based on generic or actual product names identified from the Master Formulary.
   
   
   1. Provides complete picture but not always required
   
   
5. Save DINs into a separate file for review with a pharmacist or clinician.
   
   
   1. Include ATC, Generic Name, Product Name, Route(s), Form(s), Dose, Strength.
      
   2. Add information from Health Canada Drug Product Database if not in Master Formulary
   
   
6. Provide file to researcher and/or clinician
   
7. Update information based on input. Generally this involves excluding drugs that have been caught in the "broad sweep" or adding some drugs that were missed and starting again from the top.

Issues

• Change in drug names
• Change in ATC codes
• Coverage by Manitoba Health
• Change in indication for specific drugs
• Use of a single generic drug for multiple conditions. It may be possible to distinguish by route, form, or strength

NOTE: Changes occur regularly in drug names, ATC codes and the list of drugs prescribed for specific conditions. For any research, a review of the drugs used in the study should be done prior to the start of any analysis.

Examples

The following chronic disease examples were taken from the definitions used in the Defining and Validating Chronic Diseases: An Administrative Data Approach deliverable (Lix et al. 2006).

Example 1: Identification of Drugs for Diabetic Definition


• Identification of Diabetics in MCHP Administrative data including the use of Insulin or oral Anti-Diabetic drugs.
  
• ATC code: A10 (DRUGS USED IN DIABETES)
  
• Extract DINs from Master Formularies (1995-2003)
  
  • Number of DINs: 111
    
  • Number of Generic drug Names: 10
  
  
• Merge with DIN Master by Generic
  
  • Additional DINs: 82
    
    Note: Only 5 rarely used actually found in data.
  
  
• Stop Here - pull data from DPIN based on DINs from MF

SAS Code: see Diabetic Drugs in Clinical Research - SAS Code below - (internal access only)

Example 2: Identification of Drugs for Hypertension



• Identification of individuals with Hypertension.
  
  • Note: some drugs are not specific to hypertension definition must be a hybrid of diagnoses and drugs.
  
  
• Extract DINs from MF based on ATC Codes:
  
  • C02 ANTIHYPERTENSIVES
    
  • C03 DIURETICS
    
  • C07 BETA BLOCKING AGENTS
    
  • C08 CALCIUM CHANNEL BLOCKERS
    
  • C09 AGENTS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM
  
  
• Exclude Several drugs not used in Hypertension
  
  • C03BA08, C07AA07, C07AG02
    
  • C03CA01 where route=034 (liquids) inj. and solu.
  
  
• Add new drug based
  
  • Generic Product Name TRANDOLAPRIL or Product Name MAVIK. ATC C09AA10.
  
  
• Number of DINs: 561
  
  
• Using Generic Product Names extract additional drugs from DIN Master.
  
  • Number of generic products from MF: 62
    
  • Number of additional DINs: 272
  
  
• Merge Additional DINs from DIN Master to DPD (Drug Product Database) to obtain ATC, Route(s), Forms
  
  
• Combine MF DINs and Additions.
  
  
• Save file and provide to researcher to review specific drugs and drug groups.

SAS Code: see Hypertension Drugs in Clinical Research - SAS Code below - (internal access only)

Example 3: Identification of Drugs for Asthma



• Identification of individuals with Asthma.
  
  • Note some drugs are not specific to Asthma definition must be a hybrid of diagnoses and drugs.
    
  • Definition may be age specific (e.g. under 7 years).
  
  
• Basic Definitions:
  
  • ATC Codes: R03A, R03B, R03C, R03D (DRUGS FOR OBSTRUCTIVE AIRWAY DISEASES) OR
    
  • Use Asthma Drugs as defined by Anita K.
  
  
• ATC Definition
  
  • Delete Generic Products: PHENOBARBITONE, EPHEDRINE, L-EPHEDRINE, BECLOMETHASONE DIP NASAL SPRAY, BECLOMETHASONE DIP NAS SP
    
  • Delete dosage: 'CRM','CRM-TOP','Cr','INJ','Inj Susp-5mL', 'LOT','Lot','NAS INH','NAS SP', 'NAS SP-80 D', 'NAS-SOL', 'Nas Aero-200','ONT','ONT-ORAL TOP', 'OPH SOL','OPH SOL','P', 'PWR','STP','AEM-F','AEM-SUS', '0.0','0.1'
    
  • Delete Forms (Keep inhaled/Oral): '09' (cream),'20' (enema),'36' (lotion), '43' (ointment), '52' (paste),'55' (powder)
    
  • DINs Remaining: 403
  
  
• Anita Kozyrskyj Definition
  
  • 2+ prescriptions for inhaled or oral beta-agonists (using 2+ important for ages 5+, while 1+ may suffice for age 7+) OR
    
  • 1+ prescriptions for all other asthma drugs, i.e., inhaled corticosteroids (beclomethasone, budesonide, fluticasone) OR chromones OR
    
  • ketotifen with an inhaled or oral beta-agonist (salbutamol, fenoterol). Note: there is a new ophthalmic Ketotifen product in 2004 which will need to be excluded. (Anita Kozyrskyj)
    
  • DINs: 358

SAS Code: see Asthma Drugs in Clinical Research - SAS Code below - (internal access only)