Transcript Drug Class Reviews: Bridging Evidence, Values, and

Drug Class Reviews: Bridging Evidence,
Values and Health Policy
Panel Discussion
CADTH Symposium
April 13th, 2015
www.odprn.ca
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
Considering the End-User: The Policy-Maker
Researchers and Policy-makers: Perspectives
Researchers
Policy Makers
Publication
Promotion
Policy Decisions
Avoid media
Enhance Public Image
Well-Defined
Obscure
Timeliness
Research takes time –
months to years
‘NOW’:
days / weeks
Level of precision
As precise as possible
‘Ballpark’
‘Academic’: relative risks
‘Pragmatic’: absolute risks,
temporal trends
Maximal
Minimal
End-Goal(s)
Research Question
Metrics of Value
Level of Complexity
4
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
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
The ODPRN Structure
7
Objectives of Drug Class Reviews
• Pragmatic formulary modernization research to
provide the Ministry of Health and Long-Term
Care with recommendations for evidenceinformed drug policies.
• Core Principles:
– Scientific rigor
– Timeliness
– Policy relevance
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
Existing DCR Frameworks
Drug Effectiveness Review
Project (USA)
• Systematic Reviews
Agency for Healthcare
• Systematic Reviews
Research and Quality (AHRQ) • Original research using healthcare administrative databases
(USA)
CADTH Therapeutic Reviews
(Canada)
NHS Centre for Reviews and
Dissemination
(UK)
• Systematic Reviews
• Economic Analyses
• Patient Impact Statements
• Systematic Reviews
• Economic Analyses
• Local and historical contextualizing factors
• Environmental Scans
• Barriers to Implementation and Health Equity
Environmental
Scan/Local
and historical
context
Patient and
healthcare
perspectives
Stakeholder
feedback
ODPRN
Formulary
Modernization
Cost and
utilization
trends
Reimbursement
-based
economics
Rapid reviews
and network
meta-analysis
ODPRN’s
Comprehensive
Approach to
Drug Class
Reviews
12
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
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
Citizen’s Panel
• 15 members of general public
• Provide feedback on policy
recommendations from a societal
perspective related to:
– Acceptability
– Accessibility
– Affordability
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
Testosterone Replacement
Therapies (TRT)
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+
Piszczek et al. The impact of drug reimbursement policy on rates of
testosterone replacement therapy among older men. PLoS One
2014;9:e98003
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
Systematic Review Team
Testosterone in the Treatment of Androgen Deficiency
The Ontario Drug Policy Research
Network
Drug Class Review
Systematic Review Team
21
OVERVIEW OF KEY ACTIVITIES
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 metaanalysis of the evidence
Systematic Review and Network Meta-Analysis Process
NMA?
Format Data
Abstraction
Sheets for
NMA
Perform NMA
by Outcome
If appropriate and
possible, NMA is
completed. Network
geometry, heterogeneity,
consistency and
convergence assessed for
each outcome analyzed
Network Meta-Analysis stage
involving systematic review
team and biostatistician
Yes
No
APPLICATION TO:
TESTOSTERONE IN THE TREATMENT OF
ANDROGEN DEFICIENCY
Primary Research Question
What is the current evidence for the efficacy and
safety of testosterone replacement therapy in
adult men with androgen deficiency?
26
PICO Statement
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
27
SYSTEMATIC REVIEW
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
Identification
Additional records identified
through other sources
(n = 0)
Eligibility
Screening
Records after duplicates removed
(n = 6,140)
Included
Search
Results:
PRISMA
Flow
Diagram
Records identified through
database searching
(n = 9,149)
Records screened
(n = 6,140)
Full-text articles assessed
for eligibility
(n = 868)
Included
• RCTs: n = 55 reports
(n = 39 unique RCTs)
• NRS: n = 25 reports
(n = 24 unique studies
Records excluded
(n = 5272)
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
30
Treatments Evaluated
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
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
Brand not specified
31
RCT Characteristics
Summary of randomized controlled trial characteristics
Trial characteristic
Publication status
Category
No. of included studies
Literature sources
55
Unique RCTs
39
Canada
1
US
20
Multi-national
2
Parallel
34
Factorial
3
Cross-over
2
Pharmaceutical
6
Non-Pharmaceutical
11
Mixed
7
Not reported
15
Publication year
--
1992 to 2014
No. randomized
--
10 to 406
Country
Study design
Sponsors
32
Outcomes Evaluated
Network
Meta-Analysis
Meta-Analysis
No Analysis
Testosterone level, 3 mo
Cardiovascular death
Fracture
Quality of life
Erectile dysfunction
Libido
Myocardial infarction
Stroke
Newly diagnosed prostate
cancer
Serious adverse events
Activities of daily living
Newly diagnosed diabetes
Newly diagnosed heart disease
Depression
Erythrocytosis
Skin reactions
33
Overview
EFFICACY OUTCOMES:
NETWORK META-ANALYSIS
34
NMA - Total testosterone level, 3 months
35
NMA - Total testosterone level, 3 months
(vs placebo)
Mean difference (SD)
Treatment
Androderm, patch, 5 mg/d
Serum testosterone level,
3 mo
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).
36
NMA - Head-to-head comparisons of TRTs
on serum total testosterone level at 3 months
1
2
3
4
5
6
7
8
1
2
3
4
5
6
9
10
11
• Green block indicates
that the ‘row’ treatment
is significantly better
than the ‘column’
treatment
7
8
9
10
11
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
Androderm patch 5 mg/d
Androgel 1%, gel 50 mg/d
Androgel 1%, gel 100 mg/d
Testim 1% gel, 50 to 150 mg/d + sildenafil
Testim 1%, gel 50 mg
Testosterone, gel, 7.5 g/d
Andriol, oral, 120 mg/d
Delatestryl, IM, 200 mg/2wk
Testosterone enanthate, IM, 100mg/wk
Testosterone enanthate, IM, 200mg/2wk
Testosterone cypionate, IM, 200mg/2wk
• 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.
37
NMA - Quality of life
38
NMA - Erectile dysfunction
39
NMA - Libido
40
NMA - Depression
41
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
Brief Overview
SAFETY OUTCOMES:
META-ANALYSIS
43
MA - Serious adverse events, any TRT
vs placebo
TRT
Study or Subgroup
Placebo
Peto Odds Ratio
Events Total Events Total Weight
Peto, Fixed, 95% CI Year
Simon 2001
1
6
0
6
Shores 2009
0
17
0
16
Basaria 2010
16
106
8
103
75.9%
2.05 [0.88, 4.79] 2010
Spitzer 2012
2
70
4
70
20.6%
0.50 [0.10, 2.56] 2012
Total (95% CI)
Total events
199
19
Peto, Fixed, 95% CI
7.39 [0.15, 372.38] 2001
Not estimable 2009
195 100.0%
1.61 [0.77, 3.36]
12
Heterogeneity: Chi² = 2.86, df = 2 (P = 0.24); I² = 30%
Test for overall effect: Z = 1.25 (P = 0.21)
3.6%
Peto Odds Ratio
0.01
0.1
1
10
100
Placebo TRT
44
MA - Cardiovascular death, any TRT
vs placebo
TRT
Study or Subgroup
Placebo
Peto Odds Ratio
Events Total Events Total Weight
Peto, Fixed, 95% CI Year
Brockenbrough 2006
3
19
0
21
Boyanov 2003
0
24
0
24
Not estimable 2003
Amory 2004
0
24
0
24
Not estimable 2004
Shores 2009
0
17
0
16
Basaria 2010
1
106
0
103
Total (95% CI)
Total events
190
4
Peto, Fixed, 95% CI
9.20 [0.90, 94.21]
Not estimable 2009
26.0%
188 100.0%
7.18 [0.14, 362.14] 2010
8.62 [1.17, 63.77]
0
Heterogeneity: Chi² = 0.01, df = 1 (P = 0.92); I² = 0%
Test for overall effect: Z = 2.11 (P = 0.03)
74.0%
Peto Odds Ratio
0.01
0.1
1
Placebo TRT
10
100
45
MA - Cardiovascular death, T-gel vs
placebo
1% Testosterone Gel
Study or Subgroup
Events
Brockenbrough 2006
3
Shores 2009
Basaria 2010
Peto Odds Ratio
Total Events Total Weight
19
0
0
17
0
16
1
106
0
103
Total (95% CI)
Total events
Placebo
142
4
Heterogeneity: Chi² = 0.01, df = 1 (P = 0.92); I² = 0%
Test for overall effect: Z = 2.11 (P = 0.03)
21
Peto Odds Ratio
Peto, Fixed, 95% CI Year
74.0%
9.20 [0.90, 94.21] 2006
26.0%
7.18 [0.14, 362.14] 2010
Peto, Fixed, 95% CI
Not estimable 2009
140 100.0%
8.62 [1.17, 63.77]
0
0.01
0.1
1
10
100
Favours 1% T gel Favours placebo
46
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
Skin reactions
• 10 studies
• Mild skin irritation, rashes, allergic contact
dermatitis, moderate skin erythema, intense
edema, blistering
• Most commonly associated with topical
preparations
48
Non-randomized studies safety outcomes
• 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
49
Summary
EFFICACY AND SAFETY
50
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
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
•
•
•
•
•
Skin reactions ranged from mild irritation to intense edema and
blistering; were primarily associated with topical preparations
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.
52
OPPORTUNITIES AND GOING
FORWARD
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
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
Questions or Thoughts …
56
Pharmacoeconomics Unit
Testosterone Replacement Therapy
Doug Coyle, Karen M. Lee, Kelley-Anne Sabarre, Kylie Tingley
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
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
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
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.
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
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
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
Results – Estimated TRT Expenditure
ACTUAL
ESTIMATED
* Exponential Model
** Power Model
YEAR
PATIENTS <65
YEARS*
PATIENTS ≥65
YEARS**
2013
2014
2015
2016
$3,408,108
$3,905,533
$4,520,105
$5,230,554
$4,856,167
$5,620,231
$6,262,704
$6,979,470
Results – Budget Impact
REIMBURSEMENT
SCENARIOS
Move all products (all
dosage forms) to EAP
UNDER 65
YEARS
$3,329,354
Move only topical forms
to EAP
$3,765,913
Move both topical and
oral forms to EAP
$4,365,919
65 YEARS
TOTAL
NET BUDGET
AND OVER
IMPACT
$3,639,447 $6,968,801 -$5,241,223
(-42.9%)
$4,556,654 $8,322,567 -$3,887,457
(-31.8%)
$5,407,006 $9,772,925 -$2,437,099
(-20.0%)
Results – Number of Users
REIMBURSEMENT
SCENARIOS
Status Quo
TOTAL
CHANGE IN AVERAGE NUMBER
OF USERS PER QUARTER
16,069
All to EAP
8,749
Oral/Topical to EAP
13,711
Topical to EAP
15,016
-7,320
(-45.6%)
-2,358
(-14.7%)
-1,053
(-6.6%)
Results – Budget Impact:
Sensitivity Analysis
REIMBURSEMENT
SCENARIO
Status Quo
-
75% OF
TESTS ARE
+VE
-
All to EAP
-$5,241,223
(-42.9%)
-$3,887,457
(-31.8%)
-$2,437,099
(-20.0%)
-$6,837,672
(-56.0%)
-$4,797,769
(-39.3%)
-$3,207,962
(-26.3%)
Oral/Topical to
EAP
Topical to EAP
BASE CASE
50% OF NONTESTED WILL
BE TESTED
-
NO
SWITCHING
WITH EAP
-
USE AS PER
OTHER
PROVINCES*
-
-$4,832,153
(-39.6%)
-$4,058,749
(-33.2%)
-$2,548,106
(-20.9%)
-$4,832,153
(-39.6%)
-$4,638,952
(-38.0%)
-$2,974,195
(-24.4%)
-$6,529,735
(-53.5%)
-$9,018,936
(-73.9%)
-$7,211,086
(-59.1%)
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.
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%
Patient and healthcare perspectives:
Key findings
Diagnosis of
hypogonadism can
be complex
• “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
Multiple factors
influence
formulation choices
• “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
Access to TRT
products
• “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
Environmental Scan:
Listing of TRTs in Canada
Drug
BC
AB
SK/ MB
ON
QC
NB/
PEI/ NL
NS
NIHB/
YK
No
Res
Ben
Pas
Ben
Res
Ben
Ben
Testosterone cypionate
Res
Ben
Ben
Pas
Ben
Ben
Ben
Ben
Testosterone enanthate
Res
Ben
Ben
Pas
Ben
Ben
Ben
Ben
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
Oral
Testosterone undecanoate
Long-acting injectable
Topical
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
Pharmacoepidemiology:
Total utilization of TRT dispensed in Canada
Rate of testosterone use among public drug
plan beneficiaries in 2012
Provincial rate of topical TRT use among
public drug plan beneficiaries 65+
Number of testosterone users
(per 100,000 eligible population)
Rate of testosterone use among public drug plan beneficiaries less than 65 in Ontario
Number of testosterone users
(per 100,000 eligible population)
Rate of testosterone use among public drug plan beneficiaries aged 65 and older in Ontario
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
Current LU criteria
LU Criteria
Documented diagnosis of
hypogonadism
Comment
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
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
Potential Policy Options
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.
ODPRN Citizens’ Panel
• 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
Option C: EAP for oral and topical, LU for
Final ranking Pre-meeting
ranking
1
1
injectable
Option B: EAP for all TRT products
2
2
3
1
4*
4
Option D: EAP for topical, LU for injectable
and oral
Option A: Limited Use for all TRT products
*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
Suggested Policy
Recommendations
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%)
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%)
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%)
Drug Class Reviews: Bridging Evidence, Values and Health Policy
Feasibility of
Options
Impacts on
Other Drug
Benefits
Future
Considerations
Implementation
Impacts on
Other Areas of
Ministry
Financial
Considerations
Communication
– Education /
Outreach
Discussion
89