cadth 2015 a6 cadth symposium final

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