1. The Use of the World Health Organization’s Defined Daily Dose in Drug Cost & Utilization Analyses Elena Lungu Senior Economist 2008 CADTH Symposium Edmonton, Alberta April 29 th, 2008

2. 2  Established in September 2001 by F/P/T Ministers of Health  Responsibilities of PMPRB established by the Minister of Health, pursuant to Section 90 of the Patent Act  Purpose: to facilitate informed administration of public drug plans in Canada by providing:  Timely, standardized and comparative prescription drug information from participating public drug plans in response the priorities identified by the F/P/T Steering Committee  Critical analyses of price, utilization and cost trends  Collaborative initiative between CIHI and the PMPRB National Prescription Drug Utilization Information System NPDUIS

3. 3 Purpose of the Study  Reliable quantity measures are the foundation of drug utilization studies  There is a need to transform the physical units into treatment units  The Defined Daily Dose (DDD) widely utilized by researchers  As it converts the physical quantities into a standards unit of measure: ‘day’  NPDUIS has applied the DDD methodology to drug utilization studies & gained a strong understanding of the advantages & limitations to applying DDD in the context of Canadian administrative databases, & identified:  Concerns regarding results interpretation that limit the applicability of DDD methodology  The need to consider other quantity measures (e.g. the reported Day Supply)

4. 4 WHO ATC/DDD System – Background  The World Health Organization (WHO) developed & maintains the Anatomical Therapeutic Chemical / Defined Daily Dose (ATC / DDD) system  DDD assigned by WHO Collaborating Centre for Drug Statistics Methodology in collaboration with WHO International Working Group for Drug Statistic Methodology  DDD Methodology: transforms the physical quantities of drugs into a standard unit of measure  DDD Purpose: to serve as a tool for drug utilization research in order to improve quality of drug use  ATC/DDD system widely utilized worldwide by researchers to report on drug utilization statistics

5. 5 DDD Definition UnitsTotal DDDs 58M 45M90M 18M73M 2M18M 123M240M Assumed average maintenance dose per day for a drug used for its main indication in adults Initial dose not captured (if different than maintenance) Average of two or more commonly used dose sizes + 95% Based on a review of the available information including doses used in various countries when this information is available Other indications not captured Children dose not captured, except in drugs prescribed only to children Ingredient & form Example: Atorvastatin DDD = 10mg StrengthDDDs 10mg1 20mg2 40mg4 80mg8 ODB, 2005/06 TOTAL

6. 6 DDD in Canadian Administrative Databases Advantages Limitations Maintained & updated by WHO Integration in Canadian Administrative Databases Interpretation of Canadian Utilization Readily available, inexpensive & easy to use Allows integration with other databases Valuable comparative measure of drug exposure Applicability in Cost Analyses Applicability in Policy Decisions

7. 7 DDD – Integration in Canadian Admin. Databases  Overwhelming majority of drug utilization is for drugs with ATC assigned  Significant utilization for drugs without DDD:  10% of Cost, 12 % of Rx in NPDUIS Selected Public Plans: NS, NB, MB & SK  d  DDD methodology relies on reported units:  Canadian data may be reported in unit measure different than the ATC/DDD system – Unit conversion required  Even for the same DIN, the reported unit of measure may differ – Unit standardization required  Inaccurate unit reporting may occur link AdmR ATC/DDD system Form Canadian Admin. Databases

8. 8 DDD – Interpretation of Canadian Utilization Apply ATC/DDD methodology & interpret with caution  Technical Drug Use Metric – “rarely if ever prescribed” WHO  May not be reflective of the avg. daily dose in Canada, due to differences in:  May not mirror the drug utilization of selected segments of population (demographic or therapeutic skewing)  Purely a comparative measure of drug exposure  DDD not appropriate in making assumptions on treatment lengths Demographics Approved indications Disease prevalence Reimbursement policies Prescribing practices Etc.

9. 9 DDD – Interpretation of Canadian Utilization 99% Example: Atorvastatin in ODB – DDD 10mg 2001/02 StrengthDDDs Units Total DDDs 10mg1 34M 20mg2 21M 42M 40mg4 7M 28M 80mg8 - - TOTAL 62M 104M 2005/06 StrengthDDDs Units Total DDDs 10mg1 58M 20mg2 45M 90M 40mg4 18M 73M 80mg8 2M 18M TOTAL 123M 240M Higher Drug Exposure 130%

10. 10 DDD – Applicability in Cost Analyses “It is usually not valid to use this metric to compare costs of different drugs or drug groups” WHO DDD Misuses in Cost Analyses:  Simple average cost at DDD level across drugs  Comparison of actual or % difference in avg. cost at DDD level not appropriate  Cost decomposition  Contribution of individual effects distorted  Cost per illness, cost-benefit, cost-effectiveness & cost utility analyses  Budget Impact Analyses

11. 11 DDD – Applicability in Cost Analyses (Cont’d) 2001/02 StrengthDDDs Units Total DDD Avg. Cost/Unit Avg. Cost/DDD 10mg1 34M $1.60 20mg2 21M 42M $2.00 $1.00 40mg4 7M 28M $2.15 $0.54 80mg8 - - - - TOTAL 62M 104M $1.80 $1.07 2005/06 StrengthDDDs Units Total DDD Avg. Cost/Unit Avg. Cost/DDD 10mg1 58M $1.62 20mg2 45M 90M $2.03 $1.02 40mg4 18M 73M $2.18 $0.55 80mg8 2M 18M $2.18 $0.27 TOTAL 123M 240M $1.87 $0.96 4% -10% Example: Atorvastatin in ODB – DDD 10mg 99% 130%

12. 12 DDD – Applicability in Cost Analyses (Cont’d) DDD in Cost Drivers Analysis Main ingredients: Price & Quantity If quantity expressed in DDDs, then:  Price Effect: accurate if calculated at DIN level  As it represents the price differential as opposed to actual price  Volume Effect: may be overstated or understated  As it represents the drug exposure as opposed to actual treatment units  Therapeutic-Mix: may be inaccurate  As it is based on average cost / DDD Example

13. 13 Therapeutic-Mix: Serum Lipid Reducing Agents Rosuvastatin DDD = 10mg StrengthDDDs Units Total DDDs Avg. Cost/Unit Avg. Cost/DDD 10mg1 18M $1.36 20mg2 4M 8M $1.70 $0.85 40mg4 1M 3M $1.99 $0.50 -- - - - - TOTAL 23M 29M $1.44 $1.14 Atorvastatin DDD = 10mg StrengthDDDs Units Total DDDs Avg. Cost/Unit Avg. Cost/DDD 10mg1 58M $1.62 20mg2 45M 90M $2.03 $1.02 40mg4 18M 73M $2.18 $0.55 80mg8 2M 18M $2.18 $0.27 TOTAL 123M 240M $1.87 $0.96 19% -23% Example: ODB – 2005/06

14. 14 DDD – Applicability in Policy Decision Misuses of ATC/DDD in Policy Decisions:  Cost analyses based on DDD methodology in support of policy decisions  Determining therapeutic equivalence  Reimbursement decisions  Therapeutic group reference pricing decisions & other pricing decisions  Price comparisons

15. 15 Conclusions – DDD Methodology  A valuable comparative measure of drug exposure  Regional (interprovincial, international, etc.) & trend analyses  Best applied to specific classes of drugs  Comprehensive studies may not be all that comprehensive  DDD may align better with actual daily dose in some classes/drugs than other  Integration process may be eased  Best applied at population level, as opposed to specific population segments  DDD – generally not appropriate in a broad array of Cost Analyses on multiple drugs  Caution required when applying the DDD methodology in analyses in support of policy decisions

16. 16 Unavailable in some administrative databases Day Supply Information Field in Canadian Administrative Databases Already integrated in some drug plan administrative databases Possible misreporting Difficult to interpret in non-daily treatments Claim specific Actual drug utilization Advantages Limitations

17. 17  Scope:  2005/06 fiscal year, NPDUIS selected drug plans: PEI, NS, NB, ON & NIHB  Methods: Avg. Daily Supply (Units/Days) & Avg. Rx Length (Days/Rx)  Results – for the above scope:  Avg. Daily Supply at drug & strength level comparable across plans  Avg. Rx Length at plan level comparable across drugs Day Supply information field quality assurance is a prerequisite Day Supply Information Field Preliminary Quality Investigation Agents Acting on Renin-Angiotensin System Serum Lipid Reducing Agents Drugs for Acid-Related Disorders Psychoanaleptics Similar utilization patterns Oral solids Conclusion: When available & for specific classes of drugs, Day Supply is a valuable information field & may be used in drug utilization & cost analyses

18. 18  Understand the research question & its scope  Know the data availability & quality  Know the advantages & limitations of the available quantity measures given the context  Decide on the most appropriate quantity measure to report on  Recognize that these quantity measures may capture partial drug utilization (unavailable DDD, unreliable Day Supply, etc.) Take away: – It depends…What’s the best quantity measure? If the actual daily dose were to differ than the DDD, would the findings change?