The Use of the World Health Organization’sDefined Daily Dose in Drug Cost & Utilization Analyses

Elena LunguSenior Economist

2008 CADTH Symposium Edmonton, AlbertaApril 29th, 2008

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 SystemNPDUIS

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)

5

DDD Definition

Units Total DDDs58M 58M45M 90M18M 73M

2M 18M123M 240M

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

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: AtorvastatinDDD = 10mg

Strength DDDs10mg 120mg 240mg 480mg 8ODB, 2005/06

TOTAL

6

DDD in Canadian Administrative Databases

Advantages Limitations

Maintained & updated by WHO Integration in Canadian Administrative Databases

Interpretation of Canadian UtilizationReadily available, inexpensive &

easy to use

Allows integrationwith other databases

Valuable comparative measureof drug exposure

Applicability in Cost Analyses

Applicability in Policy Decisions

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

linkAdmR ATC/DDD system

Form Canadian Admin. Databases

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

DDD – Interpretation of Canadian Utilization

99%

Units Distribution

55%

34%

11%

2%

15%

36%

47%

0%

10%

20%

30%

40%

50%

60%

10mg 20mg 40mg 80mg

2001/02 2005/06

Example: Atorvastatin in ODB – DDD 10mg

2001/02

Strength DDDs Units Total DDDs

10mg 1 34M 34M

20mg 2 21M 42M

40mg 4 7M 28M

80mg 8 - -

TOTAL 62M 104M

2005/06

Strength DDDs Units Total DDDs

10mg 1 58M 58M

20mg 2 45M 90M

40mg 4 18M 73M

80mg 8 2M 18M

TOTAL 123M 240M

Higher Drug Exposure 130%

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

DDD – Applicability in Cost Analyses (Cont’d)

2001/02

Strength DDDs Units Total DDD Avg. Cost/Unit Avg. Cost/DDD

10mg 1 34M 34M $1.60 $1.60

20mg 2 21M 42M $2.00 $1.00

40mg 4 7M 28M $2.15 $0.54

80mg 8 - - - -TOTAL 62M 104M $1.80 $1.07

2005/06

Strength DDDs Units Total DDD Avg. Cost/Unit Avg. Cost/DDD

10mg 1 58M 58M $1.62 $1.62

20mg 2 45M 90M $2.03 $1.02

40mg 4 18M 73M $2.18 $0.55

80mg 8 2M 18M $2.18 $0.27TOTAL 123M 240M $1.87 $0.96

4% -10%

Example: Atorvastatin in ODB – DDD 10mg

99% 130%

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 / DDDExample

13

Therapeutic-Mix: Serum Lipid Reducing Agents

Rosuvastatin DDD = 10mg

Strength DDDs Units Total DDDs Avg. Cost/Unit Avg. Cost/DDD

10mg 1 18M 18M $1.36 $1.36

20mg 2 4M 8M $1.70 $0.85

40mg 4 1M 3M $1.99 $0.50

- - - - - -TOTAL 23M 29M $1.44 $1.14

AtorvastatinDDD = 10mg

Strength DDDs Units Total DDDs Avg. Cost/Unit Avg. Cost/DDD

10mg 1 58M 58M $1.62 $1.62

20mg 2 45M 90M $2.03 $1.02

40mg 4 18M 73M $2.18 $0.55

80mg 8 2M 18M $2.18 $0.27TOTAL 123M 240M $1.87 $0.96

19% -23%

Example: ODB – 2005/06

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

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

Unavailable in some administrative databases

Day Supply Information Fieldin Canadian Administrative Databases

Already integrated in some drug plan administrative databases

Possible misreporting

Difficult to interpret in non-daily treatmentsClaim specific

Actual drug utilization

Advantages Limitations

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 FieldPreliminary 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

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?