CADTH 2015 Symposium

1. Drug Class Reviews: Bridging Evidence,
Values and Health Policy
Panel Discussion
CADTH Symposium
April 13th, 2015
www.odprn.ca

2. Agenda Items
• Introduction to the ODPRN
• ODPRN Drug Class Review
– Traditional components of drug class reviews
– Novel components of ODPRN drug class review
• Drug class reviews to inform drug policy
• Discussion

3. Considering the End-User: The Policy-Maker

4. 4
Researchers and Policy-makers: Perspectives
Researchers Policy Makers
End-Goal(s) Publication
Promotion
Policy Decisions
Avoid media
Enhance Public Image
Research Question Well-Defined Obscure
Timeliness Research takes time –
months to years
‘NOW’:
days / weeks
Level of precision As precise as possible ‘Ballpark’
Metrics of Value ‘Academic’: relative risks ‘Pragmatic’: absolute risks,
temporal trends
Level of Complexity Maximal Minimal

5. Ontario Health Policy Research
• Ontario’s Healthcare Data
– Ontario has ‘universal’ healthcare coverage
– Databases record healthcare transactions for administrative
purposes
– Data related to healthcare stored in separate but linkable datasets:
physician claims, hospitalizations, drug utilization, emergency
department visits
• Institute for Clinical Evaluative Sciences
– ICES is a non-profit research organization established in 1992
– Funded by the Ontario Ministry of Health and granting agencies
– Over 250 faculty and staff
– Stores many of Ontario’s healthcare administrative databases for
research purposes: databases are linked

6. The ODPRN
• Ontario-wide, independent drug policy research group
established in 2008
• Primary Objective
– Provide high quality, relevant drug research to OPDP in a
timely manner on an as-needed basis
• Funded by grants from the Ontario Ministry of Health and
Long-Term Care
Goal:
Bridge clinical researchers with drug policy decision-makers
to advance evidence-informed decision making

7. 7
The ODPRN Structure

8. Objectives of Drug Class Reviews
• Pragmatic formulary modernization research to
provide the Ministry of Health and Long-Term
Care with recommendations for evidence-
informed drug policies.
• Core Principles:
– Scientific rigor
– Timeliness
– Policy relevance

9. Principles of Drug Class Reviews
• Conduct reviews that address the needs of patients,
health-care providers and policy-makers
• Provide basis for evidence-informed policies that
incorporate societal values and beliefs
• May lead to recommendations regarding:
– Expansion of access to drugs on the formulary
– Revision or restriction of access to drugs
– No change to current listing status
– Alternative drug reimbursement models
– Education of prescribers regarding appropriate prescribing

10. Existing DCR Frameworks
•Systematic Reviews
Drug Effectiveness Review
Project (USA)
•Systematic Reviews
•Original research using healthcare administrative databases
Agency for Healthcare
Research and Quality (AHRQ)
(USA)
•Systematic Reviews
•Economic Analyses
•Patient Impact Statements
CADTH Therapeutic Reviews
(Canada)
•Systematic Reviews
•Economic Analyses
•Local and historical contextualizing factors
•Environmental Scans
•Barriers to Implementation and Health Equity
NHS Centre for Reviews and
Dissemination
(UK)

11. ODPRN
Formulary
Modernization
Environmental
Scan/Local
and historical
context
Patient and
healthcare
perspectives
Cost and
utilization
trends
Rapid reviews
and network
meta-analysis
Reimbursement
-based
economics
Stakeholder
feedback

12. 12
ODPRN’s
Comprehensive
Approach to
Drug Class
Reviews

13. Who are our stakeholders?
• Policymakers
• Patients and caregivers
• Individual patients and patient advocacy groups
• Public
• Clinicians
• Individual clinicians and professional organizations
• Governing bodies (e.g., CPSO, OCP)
• Manufacturers

14. ODPRN Stakeholder Engagement
One-on-one interviews
Committee Membership
Input on Comprehensive Research Plan
Evidence Submission Package
Input on Draft Report
Input on Recommendations
Dissemination of Report

15. Citizen’s Panel
• 15 members of general public
• Provide feedback on policy
recommendations from a societal
perspective related to:
– Acceptability
– Accessibility
– Affordability

16. Drug Class Reviews
Completed
• Triptans
• Testosterone replacement therapy (TRT)
Ongoing
• Respiratory Reviews
• ICS/LABA for COPD
• LAMA for COPD
• ICS/LABA for Asthma
• Antipsychotics in the elderly
• Chronic Hepatitis B
• Cognitive Enhancers
• Drugs for treatment of ADHD
• Drugs for treatment of Overactive Bladder syndrome

17. Testosterone Replacement
Therapies (TRT)

18. Why review TRTs?
• Currently under LU
– Is this the best way to list on the formulary?
• Safety concerns identified (e.g., CV events)
• Lack of large-scale, long-term clinical trials
• Rise in utilization of TRT products in
Ontario, especially topical products in men
65+

19. Piszczek et al. The impact of drug reimbursement policy on rates of
testosterone replacement therapy among older men. PLoS One
2014;9:e98003

20. Evidence review
• Traditional components:
– Efficacy, safety
– Economics
• Novel components of ODPRN drug class
review:
– Patient and healthcare perspectives
– Environmental scan
– Utilization and accessibility
– Policy recommendations

21. The Ontario Drug Policy Research
Network
Drug Class Review
Systematic Review Team
Systematic Review Team
Testosterone in the Treatment of Androgen Deficiency
21

22. OVERVIEW OF KEY ACTIVITIES

23. Methods
Two fundamental steps:
1. A broad systematic review of the available
randomized evidence in the published and grey
literature
2. A pair-wise meta-analysis and network meta-
analysis of the evidence

24. Systematic Review and Network Meta-Analysis Process
NMA?
If appropriate and
possible, NMA is
completed. Network
geometry, heterogeneity,
consistency and
convergence assessed for
each outcome analyzed
Perform NMA
by Outcome
Format Data
Abstraction
Sheets for
NMA
Yes
No
Network Meta-Analysis stage
involving systematic review
team and biostatistician

25. APPLICATION TO:
TESTOSTERONE IN THE TREATMENT OF
ANDROGEN DEFICIENCY

26. Primary Research Question
What is the current evidence for the efficacy and
safety of testosterone replacement therapy in
adult men with androgen deficiency?
26

27. PICO Statement
27
Population Adult men with androgen deficiency (serum total testosterone ≤ 12 nmol/L)
Index Node Placebo
Comparisons Testosterone replacement therapies currently available in Canada: testosterone undecanoate
(Andriol, pms-Testosterone), testosterone cypionate (Depo-Testosterone), testosterone enanthate
(Delatestryl), testosterone (Androderm, Testim, Androgel, Axiron).
 Testosterone replacement therapy (TRT) v. placebo
 TRT v. TRT (same TRT at different dose or different TRT)
 Self-administered or administered by health care provider
 Health Canada–approved daily doses
 All routes of administration
Outcomes:
Efficacy
 Serum testosterone level
 Quality of life
 Resolution of symptoms:
 Erectile dysfunction
 Libido improvement
 Depression
 Fractures
 Activities of daily living
Outcomes:
Safety
 Cardiovascular death
 Myocardial infarction
 Stroke
 Erythrocytosis
 Serious adverse events
 Newly diagnosed disease (diabetes/heart disease/prostate cancer)
 Skin or site reactions

28. SYSTEMATIC REVIEW

29. Search Strategy
• Strategies were developed and tested by an experienced
medical information specialist
• Database searches
• Ovid MEDLINE®, Ovid MEDLINE® In-Process & Other Non-Indexed Citations, and Embase
Classic+Embase.
• Cochrane Database of Systematic Reviews and CENTRAL
• Combination of controlled vocabulary and keywords
(vocabulary and syntax adjusted across databases)
• Filter for RCTs and restricted results to the English language.
• Hand-searching the bibliographies of relevant items.
• We also undertook a grey literature search using Google
Scholar and the clinical trial sites listed in CADTH’s Grey Matters

30. ScreeningIncludedEligibilityIdentification
Records after duplicates removed
(n = 6,140)
Records screened
(n = 6,140)
Records excluded
(n = 5272)
Full-text articles assessed
for eligibility
(n = 868)
Full-text articles excluded
(n = 788)
Women or children = 17
Not low T = 190
Did not evaluate TRT = 59
Study design = 208
Non-HC TRT = 64
No original data = 51
Less than 10 participants = 30
Less than 3 mo = 70
Non-English = 57
Other = 39
No full text = 3
Included
• RCTs: n = 55 reports
(n = 39 unique RCTs)
• NRS: n = 25 reports
(n = 24 unique studies
Search
Results:
PRISMA
Flow
Diagram
30
Records identified through
database searching
(n = 9,149)
Additional records identified
through other sources
(n = 0)

31. Treatments Evaluated
31
Dose and routes of administration of testosterone replacement therapy
TRT product Included doses Route
Brand specified
Andriol 20 mg/d, 40 mg/d, 120–160 mg/d Oral
Depo-Testosterone No studies Intramuscular injection
Delatestryl 125 mg/wk, 150 mg/2 wk, 200 mg/2 wk Intramuscular injection
Androderm 5 mg/d Patch
Testim 1% 50–150 mg/d Topical gel
Androgel 1% 5 mg/d, 25–100 mg/d Topical gel
Axiron No studies Topical solution
Brand not specified
Testosterone gel 125 mg/d Topical gel
Testosterone enanthate 100 mg/wk, 200 mg/2wk, 50–400 mg/1–2
wk, 250 mg/3wk, 300 mg/3wk
Intramuscular injection
Testosterone undecanoate 160 mg/d Oral
Testosterone cypionate 200 mg/2wk Intramuscular injection

32. RCT Characteristics
32
Summary of randomized controlled trial characteristics
Trial characteristic Category No. of included studies
Publication status Literature sources 55
Unique RCTs 39
Country Canada 1
US 20
Multi-national 2
Study design Parallel 34
Factorial 3
Cross-over 2
Sponsors Pharmaceutical 6
Non-Pharmaceutical 11
Mixed 7
Not reported 15
Publication year -- 1992 to 2014
No. randomized -- 10 to 406

33. Outcomes Evaluated
Network
Meta-Analysis
Meta-Analysis No Analysis
Testosterone level, 3 mo Cardiovascular death Fracture
Quality of life Myocardial infarction Activities of daily living
Erectile dysfunction Stroke Newly diagnosed diabetes
Libido Newly diagnosed prostate
cancer
Newly diagnosed heart disease
Depression Serious adverse events Erythrocytosis
Skin reactions
33

34. EFFICACY OUTCOMES:
NETWORK META-ANALYSIS
Overview
34

35. NMA - Total testosterone level, 3 months
35

36. NMA - Total testosterone level, 3 months
(vs placebo)
36
Treatment
Mean difference (SD)
Serum testosterone level,
3 mo
Androderm, patch, 5 mg/d 5.35 (2.52)*
Androgel 1%, gel, 50 mg/d 10.34 (2.72)*
Androgel 1%, gel, 100 mg/d 18.46 (3.41)*
Testim 1%, gel, 50–150 mg/d + sildenafil 10.21 (2.81)*
Testim 1%, gel, 50 mg/d 2.26 (2.77)
Androgel 1%, gel, 75 mg/d 7.56 (3.51)*
Andriol, oral, 120 mg/d –4.34 (2.68)
Delatestryl, IM, 200 mg/2wk 15.66 (3.88)*
Testosterone enanthate, IM, 100 mg/wk 6.30 (3.17)
Testosterone enanthate, IM, 200 mg/2wk 8.66 (2.91)*
Testosterone cypionate, IM, 200 mg/2wk –0.16 (3.26)
*Statistically significant (p < 0.05).

37. NMA - Head-to-head comparisons of TRTs
on serum total testosterone level at 3 months
37
1 2 3 4 5 6 7 8 9 10 11
1
2
3
4
5
6
7
8
9
10
11
• Green block indicates
that the ‘row’ treatment
is significantly better
than the ‘column’
treatment
• Red block indicates that
the ‘row’ treatment is
significantly worse than
the ‘column’ treatment
• Grey block indicates that
there is no significant
difference between the
‘row’ and ‘column’
treatment.
1. Androderm patch 5 mg/d
2. Androgel 1%, gel 50 mg/d
3. Androgel 1%, gel 100 mg/d
4. Testim 1% gel, 50 to 150 mg/d + sildenafil
5. Testim 1%, gel 50 mg
6. Testosterone, gel, 7.5 g/d
7. Andriol, oral, 120 mg/d
8. Delatestryl, IM, 200 mg/2wk
9. Testosterone enanthate, IM, 100mg/wk
10. Testosterone enanthate, IM, 200mg/2wk
11. Testosterone cypionate, IM, 200mg/2wk

38. NMA - Quality of life
38

39. NMA - Erectile dysfunction
39

40. NMA - Libido
40

41. NMA - Depression
41

42. Summary: Quality of Life, Erectile
Dysfunction, Libido, Depression
• Vs Placebo:
– No significant effects in quality of life, erectile dysfunction, libido,
or depression were identified
• In head-to-head comparisons:
– Few significant differences among the TRTs for quality of life,
erectile dysfunction, libido, and depression
42

43. SAFETY OUTCOMES:
META-ANALYSIS
Brief Overview
43

44. MA - Serious adverse events, any TRT
vs placebo
44
Study or Subgroup
Simon 2001
Shores 2009
Basaria 2010
Spitzer 2012
Total (95% CI)
Total events
Heterogeneity: Chi² = 2.86, df = 2 (P = 0.24); I² = 30%
Test for overall effect: Z = 1.25 (P = 0.21)
Events
1
0
16
2
19
Total
6
17
106
70
199
Events
0
0
8
4
12
Total
6
16
103
70
195
Weight
3.6%
75.9%
20.6%
100.0%
Peto, Fixed, 95% CI
7.39 [0.15, 372.38]
Not estimable
2.05 [0.88, 4.79]
0.50 [0.10, 2.56]
1.61 [0.77, 3.36]
Year
2001
2009
2010
2012
TRT Placebo Peto Odds Ratio Peto Odds Ratio
Peto, Fixed, 95% CI
0.01 0.1 1 10 100
Placebo TRT

45. MA - Cardiovascular death, any TRT
vs placebo
45
Study or Subgroup
Brockenbrough 2006
Boyanov 2003
Amory 2004
Shores 2009
Basaria 2010
Total (95% CI)
Total events
Heterogeneity: Chi² = 0.01, df = 1 (P = 0.92); I² = 0%
Test for overall effect: Z = 2.11 (P = 0.03)
Events
3
0
0
0
1
4
Total
19
24
24
17
106
190
Events
0
0
0
0
0
0
Total
21
24
24
16
103
188
Weight
74.0%
26.0%
100.0%
Peto, Fixed, 95% CI
9.20 [0.90, 94.21]
Not estimable
Not estimable
Not estimable
7.18 [0.14, 362.14]
8.62 [1.17, 63.77]
Year
2003
2004
2009
2010
TRT Placebo Peto Odds Ratio Peto Odds Ratio
Peto, Fixed, 95% CI
0.01 0.1 1 10 100
Placebo TRT

46. MA - Cardiovascular death, T-gel vs
placebo
46
Study or Subgroup
Brockenbrough 2006
Shores 2009
Basaria 2010
Total (95% CI)
Total events
Heterogeneity: Chi² = 0.01, df = 1 (P = 0.92); I² = 0%
Test for overall effect: Z = 2.11 (P = 0.03)
Events
3
0
1
4
Total
19
17
106
142
Events
0
0
0
0
Total
21
16
103
140
Weight
74.0%
26.0%
100.0%
Peto, Fixed, 95% CI
9.20 [0.90, 94.21]
Not estimable
7.18 [0.14, 362.14]
8.62 [1.17, 63.77]
Year
2006
2009
2010
1% Testosterone Gel Placebo Peto Odds Ratio Peto Odds Ratio
Peto, Fixed, 95% CI
0.01 0.1 1 10 100
Favours 1% T gel Favours placebo

47. Summary: Myocardial Infarction, Stroke,
Prostate Cancer, Heart Disease
• Meta-analysis:
• MI - 2 events in T gel group and 1 in placebo.
• Stroke – 1 event in T gel group and 1 in the placebo.
• Prostate cancer - 2 cases in T gel group and 1 in placebo; 4 in
testosterone IM and 5 in placebo.
• Heart disease (1 study) – 2 cases in testosterone and 4 in
placebo.
47

48. Skin reactions
48
• 10 studies
• Mild skin irritation, rashes, allergic contact
dermatitis, moderate skin erythema, intense
edema, blistering
• Most commonly associated with topical
preparations

49. Non-randomized studies -
safety outcomes
49
• 24 unique non-randomized studies
• 16 had no outcomes of interest
• Prostate cancer was reported by 6 studies, but
reporting was poor and meta-analysis was not
possible

50. EFFICACY AND SAFETY
Summary
50

51. Some high level thoughts on
results of the NMA analysis
• Several of the testosterone replacement therapies were associated
with a substantive increase in serum testosterone levels at 3 months.
• No significant effects in quality of life, erectile dysfunction, libido, or
depression were identified.
• In head-to-head comparisons:
– Androgel 1% (100 mg/d) was associated with more favourable
serum testosterone levels at 3 months than the other TRTs.
– Andriol (120 mg/d) was associated with less favourable serum
testosterone levels at 3 months than the other TRTs.
– Few significant differences among the TRTs for quality of life,
erectile dysfunction, libido, and depression.
51

52. Some high level thoughts on
results of the NMA analysis
• Serious adverse events – T gel (199) v. placebo (195): OR 1.61
(95% CI 0.77–3.36).
• Other safety data were limited:
• CV death – 4 deaths in T gel group and zero in placebo.
• MI - 2 events in T gel group and 1 in placebo.
• Stroke – 1 event in T gel group and 1 in the placebo.
• Prostate cancer - 2 cases in T gel group and 1 in placebo; 4 in
testosterone IM and 5 in placebo.
• Heart disease (1 study) – 2 cases in testosterone and 4 in
placebo.
• Skin reactions ranged from mild irritation to intense edema and
blistering; were primarily associated with topical preparations
52

53. OPPORTUNITIES AND GOING
FORWARD

54. Opportunities
• NMA methods are evolving, so methods develop working on practical
problems
• Provides training for young researchers and research assistants within an
experienced team
• Publishing results of policy relevant questions
• Opportunities to integrate work within other activities to extend work to a
broader context then the ministry directive
• To meet, review and appreciate perspectives of the other ODPRN program
teams (qualitative, pharmacoepidemiology, pharmacoeconomics)
• Working with and sharing process and procedures with the other systematic
review team
• To better appreciate drug issues from perspective of the ministry
• Setting stage to expand beyond the HC doses

55. Going Forward
• Improve automation and increase efficiency of SR process
• Topic scoping
• Software (DISTILLER SR)
• Internal retreat for meeting deadlines of ODPRN and other agencies
• Increase frequency of local review team meetings
• Status/Delays
• Troubleshooting
• Local clinical expertise for SR/NMA-specific advice
• Automated NMA procedures
• Analysis code
• Output directly to tables
• Figures and diagrams

56. Questions or Thoughts …
56

57. Pharmacoeconomics Unit
Testosterone Replacement Therapy
Doug Coyle, Karen M. Lee, Kelley-Anne Sabarre, Kylie Tingley

58. Pharmacoeconomic Unit within
ODPRN
• Coordinated by researchers based at the
University of Ottawa and CADTH
– Potential for involvement of researchers
outside of core group
• Objective
– To generate applied, policy-oriented
pharmacoeconomic models

59. Roles within each class review
• Clarifying and refining study questions
• Drafting of Health Economics Proposal
• Review of economic literature
• Development of economic model and
population with clinical review data
• Modeling of alternate reimbursement
strategies
– Reimbursement Based Economics

60. Reimbursement Based Economics
• Novel, pragmatic approach to pharmacoeconomics
• Identify the optimal reimbursement model considering
budget impact and cost effectiveness as criteria.
– e.g. bundling strategies, price caps, risk-sharing, CED.
• Comprehensive budget impact analysis plus traditional
pharmacoeconomic models where relevant .
– Incorporate market dynamics of different drug policy scenarios.
• Market expansion, cannibalization, and companion drug utilization effects

61. Research Questions: Testosterone
Replacement Therapy
1) What is the current evidence for the
cost-effectiveness of testosterone replacement therapy
(TRT) in all clinical areas where it is indicated?
2) What is the economic impact of alternative policies for
reimbursing testosterone replacement therapies?
# Given the broad nature of the decision question, a de novo economic
evaluation to assess the value for money for testosterone replacement
therapy in all clinical areas where it is indicated was not feasible.

62. Methods
• Systematic Review of Published Literature
– Focused on strength and quality of evidence, and
generalizability of the reports to OPDP
• Reimbursement Based Economic Assessment
– Developed an applied, policy-oriented economic model
– Estimated TRT expenditure for next three years
– Identified alternative approaches to reimbursement of
TRT
– Estimated TRT expenditure for each reimbursement
scenario

63. Reimbursement Strategies
• Considered three possible strategies
– Move all products (all dosage forms) to EAP
– Move only topical forms to EAP
– Move both topical and oral forms to EAP
• Assumptions
– All tests are positive, so if tested, then patients will be eligible under EAP.
– There will be no extra testing with EAP.
– Overall rates for selective moving of products to EAP based on provinces
with similar listing status.
– The relative use between products not moved to EAP will remain as is.
• Sensitivity analyses conducted to test impact of assumptions

64. Results - Review of Literature
• 1 study included in review; linked to industry
(Arver et al. (2014)
• Study favored industry’s product
• Limitations
– Efficacy data based on assumption of 100% response
– Treatment considered (testosterone undecanoate) not
available in Canada

65. Results – Estimated TRT Expenditure
YEAR PATIENTS <65
YEARS*
PATIENTS ≥65
YEARS**
ACTUAL 2013 $3,408,108 $4,856,167
ESTIMATED 2014 $3,905,533 $5,620,231
2015 $4,520,105 $6,262,704
2016 $5,230,554 $6,979,470
* Exponential Model
** Power Model

66. Results – Budget Impact
REIMBURSEMENT
SCENARIOS
UNDER 65
YEARS
65 YEARS
AND OVER
TOTAL NET BUDGET
IMPACT
Move all products (all
dosage forms) to EAP
$3,329,354 $3,639,447 $6,968,801 -$5,241,223
(-42.9%)
Move only topical forms
to EAP
$3,765,913 $4,556,654 $8,322,567 -$3,887,457
(-31.8%)
Move both topical and
oral forms to EAP
$4,365,919 $5,407,006 $9,772,925 -$2,437,099
(-20.0%)

67. Results – Number of Users
REIMBURSEMENT
SCENARIOS
TOTAL CHANGE IN AVERAGE NUMBER
OF USERS PER QUARTER
Status Quo 16,069
All to EAP 8,749 -7,320
(-45.6%)
Oral/Topical to EAP 13,711 -2,358
(-14.7%)
Topical to EAP 15,016 -1,053
(-6.6%)

68. Results – Budget Impact:
Sensitivity Analysis
REIMBURSEMENT
SCENARIO
BASE CASE 75% OF
TESTS ARE
+VE
50% OF NON-
TESTED WILL
BE TESTED
NO
SWITCHING
WITH EAP
USE AS PER
OTHER
PROVINCES*
Status Quo - - - - -
All to EAP -$5,241,223
(-42.9%)
-$6,837,672
(-56.0%)
-$4,832,153
(-39.6%)
-$4,832,153
(-39.6%)
-$6,529,735
(-53.5%)
Oral/Topical to
EAP
-$3,887,457
(-31.8%)
-$4,797,769
(-39.3%)
-$4,058,749
(-33.2%)
-$4,638,952
(-38.0%)
-$9,018,936
(-73.9%)
Topical to EAP -$2,437,099
(-20.0%)
-$3,207,962
(-26.3%)
-$2,548,106
(-20.9%)
-$2,974,195
(-24.4%)
-$7,211,086
(-59.1%)

69. Conclusions (1)
• Given the lack of evidence and concerns with
the methodological quality of the available study,
no inferences over the cost effectiveness of
testosterone replacement therapy can be made.
• As a result, the reimbursement based economic
assessment focussed solely on the budget
impact of alternative reimbursement scenarios
for testosterone replacement therapy.

70. Conclusions (2)
• In 2013, total OPDP expenditure on TRT
was $8.3 million.
• Without any change in reimbursement in
TRT, TRT expenditure is expected to
surpass $12 million by 2016 ($5 million for
patients <65 years and $7 million for
patients ≥ 65 years).
• Moving products to EAP will reduce TRT
expenditure by between 20% and 43%

71. Patient and healthcare perspectives:
Key findings
•“While we are potentially trying to increase access for
patients who truly need it, we gotta think, if we flood the
market with this product, what are the long term
consequences? We really have no idea, there is no study
that is over 3 years of testosterone supplement.”- Urologist
Diagnosis of
hypogonadism can
be complex
•“One of the important issues is cost. Some of them are very
expensive [especially if] he requires large amounts of
testosterone, others are less expensive. Most of them are
covered by plans but sometimes you have patients who are
not covered by any plan”- Urologist
Multiple factors
influence
formulation choices
• “I know when I was talking to another friend of
mine, when he wanted it I think he got it without
the test, but that’s because he put up a big stink
about it.”- Patient
Access to TRT
products

72. Environmental Scan:
Listing of TRTs in Canada
Drug BC AB SK/ MB ON QC NB/
PEI/ NL
NS NIHB/
YK
Oral
Testosterone undecanoate No Res Ben Pas Ben Res Ben Ben
Long-acting injectable
Testosterone cypionate Res Ben Ben Pas Ben Ben Ben Ben
Testosterone enanthate Res Ben Ben Pas Ben Ben Ben Ben
Topical
Testosterone transdermal
patch (Androderm)
No Res No Pas Ben Res Res No
Testosterone 1% topical gel
(Testim)
No No No Pas Ben Res Res No
Testosterone 1% gel foil packet
(Androgel)
No No No Pas Ben Res Res No
Testosterone 2% topical
solution (Axiron)
No No No No Ben No No No

73. Listing of TRTs in Ontario
• LU listing (Code 397):
For male patients with confirmed low morning serum
testosterone levels associated with documented,
symptomatic hypothalamic, pituitary or testicular
disease, or in HIV-infected patients.
Note: Older males with nonspecific symptoms of
fatigue, malaise, depression who have a low normal
random testosterone level do not satisfy these criteria.
– LU Authorization Period: 1 year

74. Pharmacoepidemiology:
Total utilization of TRT dispensed in Canada

75. Rate of testosterone use among public drug
plan beneficiaries in 2012

76. Provincial rate of topical TRT use among
public drug plan beneficiaries 65+

77. Rate of testosterone use among public drug plan beneficiaries less than 65 in Ontario
Rate of testosterone use among public drug plan beneficiaries aged 65 and older in Ontario
Numberoftestosteroneusers
(per100,000eligiblepopulation)
Numberoftestosteroneusers
(per100,000eligiblepopulation)

78. TRT use in Ontario men (2012)
<65 65+
Total number of users 6,216 8,460
Diagnosis of hypogonadism (past 3
years)
804 (12.9%) 1,230 (14.5%)
HIV prior to cohort entry 435 (7.0%) 69 (0.8%)
Testosterone test prior to initiation of
therapy
NA 3,177* (66.2%)
*new users filling more than one prescription = 4,797

79. Current LU criteria
LU Criteria Comment
Documented diagnosis of
hypogonadism
10-17% of patients had
diagnosis of hypogonadism
(testicular dysfunction or
pituitary gland disorder) OR
HIV-infected
Testosterone level prior to
initiating therapy
1/3 new TRT users (over age
65) had NO lab tests in year
prior to 1st prescription

80. Limitations
• NPDUIS holdings not available for Quebec,
Newfoundland & Labrador or the Territories
• Hypogonadism is not well captured in administrative data
– Therefore sensitivity and specificity are unknown
– Definition was based on:
1. Physician visit with testicular dysfunction indicated in past 3
years (specific definition)
2. Physician visit with testicular dysfunction or pituitary gland
disorders indicated in past 3 years (broader definition)
3. Lab test for testosterone levels in the past year among new
users

81. Potential Policy Options

82. Assessment of options
Potential Listing Accessibility Budget
impact
Other Considerations
Option A:
LU (status quo)
≈14,000 pts
(status quo)
NA • Possible ↑CV events; LU listing exposes
greatest # pts to TRT
• Indication creep (e.g., andropause)
• Alignment with QC
Option B:
EAP for all products
≈7,700 pts
(↓46%)
43%↓ • EAP process (# applications?)
• Alignment with BC†
Option C:
EAP for topical/ oral;
LU injectable
≈11,900 pts
(↓15%)
32%↓ • EAP process (# applications?)
• Alignment with PEI, NL, NB
• Indication creep (e.g., andropause)
Option D:
EAP for topical; LU
injectable/ oral
≈13,000 pts
(↓7%)
20%↓ • EAP process (# applications?)
• Alignment with NIHB††, YK††, MB††,
SK††
• Indication creep (e.g., andropause)
†BC does not provide coverage for oral or topical products; injectable products are available under Special Authorization.
††These jurisdictions do NOT provide coverage for topical products; oral and injectable are listed as general benefits.

83. ODPRN Citizens’ Panel
Final ranking Pre-meeting
ranking
Option C: EAP for oral and topical, LU for
injectable
1 1
Option B: EAP for all TRT products 2 2
Option D: EAP for topical, LU for injectable
and oral
3 1
Option A: Limited Use for all TRT products 4* 4
• ODPRN Citizen’s Panel rated each of the policy options on factors
related to acceptability, accessibility and affordability and ranked
options from most to least preferable from a societal viewpoint
• One teleconference meeting and two rounds of an online survey
*Note that the most consensus was reached with regard to Option A (LU for all products),
where all Citizens’ Panel member respondents ranked this option as the least acceptable
option

84. Suggested Policy
Recommendations

85. EAP for all TRT products
• Restrict use to patients
fulfilling EAP criteria
• Includes all formulations
currently listed on ODB
formulary
Budget Impact:
↓$5.2 million (↓43%)
Accessibility:
≈7,700 pts (↓46%)

86. EAP for topical and oral;
LU injectable
• Restrict use to patients
fulfilling EAP/LU criteria
• EAP/LU criteria would be
the same
• Includes all formulations
currently listed on ODB
formulary
Budget Impact:
↓ $3.9 million (↓32%)
Accessibility:
≈11,900 pts (↓15%)

87. EAP for topical;
LU injectable and oral
• Restrict use to patients
fulfilling EAP/LU criteria
• EAP/LU criteria would be
the same
• Includes all formulations
currently listed on ODB
formulary
Budget Impact:
↓ $2.4 million (↓20%)
Accessibility:
≈13,000 pts (↓7%)

88. Drug Class Reviews: Bridging Evidence, Values and Health Policy
Implementation
Feasibility of
Options
Impacts on
Other Drug
Benefits
Impacts on
Other Areas of
Ministry
Communication
– Education /
Outreach
Financial
Considerations
Future
Considerations

89. Discussion
89