cadth 2015 a6 cadth symposium final
TRANSCRIPT
Drug Class Reviews: Bridging Evidence, Values and Health Policy
Panel DiscussionCADTH 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
4
Researchers and Policy-makers: Perspectives
Researchers Policy Makers
End-Goal(s) PublicationPromotion
Policy DecisionsAvoid 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
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
7
The ODPRN Structure
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
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
• Systematic ReviewsDrug 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)
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
ODPRN’s Comprehensive
Approach to Drug Class
Reviews
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 ReviewsCompleted
• 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
21
• The Ontario Drug Policy Research Network• Drug Class Review
• Systematic Review Team• April 13, 2015
Systematic Review Team
Testosterone in the Treatment of Androgen Deficiency
OVERVIEW OF KEY ACTIVITIES
MethodsTwo 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
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
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?
27
PICO StatementPopulation 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
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
30
Scre
enin
gIn
clud
edEl
igib
ility
Iden
tifica
tion
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 = 17Not low T = 190Did not evaluate TRT = 59 Study design = 208Non-HC TRT = 64No original data = 51Less than 10 participants = 30Less than 3 mo = 70Non-English = 57Other = 39No 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
Records identified through database searching
(n = 9,149)
Additional records identified through other sources
(n = 0)
31
Treatments EvaluatedDose 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
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 FractureQuality of life Myocardial infarction Activities of daily livingErectile dysfunction Stroke Newly diagnosed diabetesLibido Newly diagnosed prostate
cancerNewly diagnosed heart disease
Depression Serious adverse events ErythrocytosisSkin reactions
34
EFFICACY OUTCOMES: NETWORK META-ANALYSIS
Overview
35
NMA - Total testosterone level, 3 months
36
NMA - Total testosterone level, 3 months (vs placebo)
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
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/d2. Androgel 1%, gel 50 mg/d3. Androgel 1%, gel 100 mg/d4. Testim 1% gel, 50 to 150 mg/d + sildenafil5. Testim 1%, gel 50 mg6. Testosterone, gel, 7.5 g/d7. Andriol, oral, 120 mg/d8. Delatestryl, IM, 200 mg/2wk9. Testosterone enanthate, IM, 100mg/wk10. Testosterone enanthate, IM, 200mg/2wk11. Testosterone cypionate, IM, 200mg/2wk
38
NMA - Quality of life
39
NMA - Erectile dysfunction
40
NMA - Libido
41
NMA - Depression
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
43
SAFETY OUTCOMES:META-ANALYSIS
Brief Overview
44
MA - Serious adverse events, any TRT vs placebo
Study or Subgroup
Simon 2001Shores 2009Basaria 2010Spitzer 2012
Total (95% CI)
Total eventsHeterogeneity: Chi² = 2.86, df = 2 (P = 0.24); I² = 30%Test for overall effect: Z = 1.25 (P = 0.21)
Events
10
162
19
Total
617
10670
199
Events
0084
12
Total
616
10370
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
2001200920102012
TRT Placebo Peto Odds Ratio Peto Odds RatioPeto, Fixed, 95% CI
0.01 0.1 1 10 100Placebo TRT
45
MA - Cardiovascular death, any TRT vs placebo
Study or Subgroup
Brockenbrough 2006Boyanov 2003Amory 2004Shores 2009Basaria 2010
Total (95% CI)
Total eventsHeterogeneity: Chi² = 0.01, df = 1 (P = 0.92); I² = 0%Test for overall effect: Z = 2.11 (P = 0.03)
Events
30001
4
Total
19242417
106
190
Events
00000
0
Total
21242416
103
188
Weight
74.0%
26.0%
100.0%
Peto, Fixed, 95% CI
9.20 [0.90, 94.21]Not estimableNot estimableNot estimable
7.18 [0.14, 362.14]
8.62 [1.17, 63.77]
Year
2003200420092010
TRT Placebo Peto Odds Ratio Peto Odds RatioPeto, Fixed, 95% CI
0.01 0.1 1 10 100Placebo TRT
46
MA - Cardiovascular death, T-gel vs placebo
Study or Subgroup
Brockenbrough 2006Shores 2009Basaria 2010
Total (95% CI)
Total eventsHeterogeneity: Chi² = 0.01, df = 1 (P = 0.92); I² = 0%Test for overall effect: Z = 2.11 (P = 0.03)
Events
301
4
Total
1917
106
142
Events
000
0
Total
2116
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
200620092010
1% Testosterone Gel Placebo Peto Odds Ratio Peto Odds RatioPeto, Fixed, 95% CI
0.01 0.1 1 10 100Favours 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.
48
Skin reactions
• 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
• 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 SAFETYSummary
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.
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
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
56
Questions or Thoughts …
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
YEAR PATIENTS <65 YEARS*
PATIENTS ≥65 YEARS**
ACTUAL 2013 $3,408,108 $4,856,167ESTIMATED 2014 $3,905,533 $5,620,231
2015 $4,520,105 $6,262,7042016 $5,230,554 $6,979,470
* Exponential Model** Power Model
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%)
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%)
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%)
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
• “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
Environmental Scan:Listing of TRTs in CanadaDrug BC AB SK/ MB ON QC NB/
PEI/ NLNS 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
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+
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
Num
ber o
f tes
tost
eron
e us
ers
(per
100
,000
elig
ible
pop
ulati
on)
Num
ber o
f tes
tost
eron
e us
ers
(per
100
,000
elig
ible
pop
ulati
on)
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 criteriaLU Criteria CommentDocumented 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
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 optionsPotential Listing Accessibility Budget
impactOther 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
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 2Option 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
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
Implementation
Feasibility of Options
Impacts on Other Drug
Benefits
Impacts on Other Areas of
Ministry
Communication – Education /
Outreach
Financial Considerations
Future Considerations
Discussion
89