1. Outcomes of strategies
to improve drug
utilization in British
Columbia
James (Jim) Wright
Managing Director
Therapeutics Initiative

3. Outline
My journey at the university
The Therapeutics Initiative (TI)
Strategies and outcomes
The Pharmaceutical Task Force and Academic
Review of TI
The problem and some potential solutions
Questions.

4. Warning
Information provided here about prescription
drugs that you may be taking could lead to
cognitive dissonance and affect your well being.
Viewer discretion is advised.

5. My journey at UBC
First Phase
1977 Assistant professor in Pharmacology &
Therapeutics and Medicine.
Clinical Pharmacologist – Clinical practice,
research and teaching.
1977-1983, MRC funded research into
mechanisms of adverse drug effects and drug
interactions.

6. My journey at UBC
Second Phase
In 1983 I began doing drug industry funded
clinical drug trials.
Between 1983 and 1994, I was principal
investigator for 15 trials with 15 different drug
companies.

7. My journey at UBC
Third Phase
In 1994 the Therapeutics Initiative was formed
and I was appointed the Clinical Managing
Director.
I stopped all drug industry funded research.
1994 to present -- main activity, Managing
Director of TI and Editor-in-Chief of Therapeutics
Letter.
2001, I was appointed Coordinating Editor of the
Cochrane Hypertension Review Group.

8. Therapeutics Initiative, 1994
(10 individuals)
Mission: To provide physicians and
pharmacists with up-to-date, evidence-based,
practical information on prescription drug
therapy.
First Task: To become expert in assessing
evidence from clinical trials of new drugs in
Canada, and to provide the evidence to
Pharmacare.
First policy decision: No conflicts of interest
were allowed.

9. What happened?
We became expert in critical appraisal and
assessment of evidence from clinical trials.
We got involved in the Cochrane Collaboration
and learned their methodology.
We hired experts in Health Technology
Assessment and Systematic Review.

10. Interventions implemented
Therapeutics Letter 6 times per year posted on
website and mailed to physicians and
pharmacists in BC.
Letters provided the best available evidence
about the benefits and harms of drugs and drug
classes.
Letters provided drug cost information.

11. What did the clinicians
think about the Letter?
Answered by regular surveys

13. What was the impact on
prescribing of the first
20 Letters?
Answered using a randomised controlled trial.

14. Effect of periodic letters on evidence-based
drug therapy on prescribing behaviour: a
randomized trial
Dormuth CR, Maclure M, Bassett K, Jauca C, Whiteside C,
Wright JM (CMAJ 2004; 171(9): 1057-61)
The Therapeutics Initiative is funded by a grant from the Government of British Columbia

15. Methods
Physicians:
-Study population included 499 physicians from 24 local health
areas in British Columbia, Canada
Communities:
-Paired according to the number of physicians.
-One in each pair was randomly assigned to the intervention
group and the other to the control group
Source databases:
-Physician service records and drug claims records from the
British Columbia Ministry of Health

16. Methods
Analyses:
-Incidence of newly treated patients was measured
-For each drug group studied, patients were classified as being newly treated if none of
the drugs in the group were dispensed to them in the previous year.

17. Results
Table: Characteristics of treatment and control physicians
Treatment Control
Characteristic Group (n=258) Group (n=241)
Physicians:
% General Practitioners 89.9 90.4
Average age 45.6 46.2
% Males/Females 89/11 83/17
Patients:
Average age 35.5 (75.2) 35.0 (75.3)
% Males/Females/Unknown 46/52/2 (44/52/4) 46/52/2 (44/52/4)
Avg. no. visits / MD 6402 (1322) 6660 (1340)
Results in brackets are for subset of patient population 65 and older.

18. Source: Dormuth CR, Maclure, et al. CMAJ 2004; 171(9): 1057-61

19. Interpretation
Printed letters distributed as a series regularly from a trusted
source has a modest desirable impact on prescribing to new
patients.
Further work needs to be done to determine the sustainability of
prescribing changes, and to determine what aspects of printed
letters elicit prescribing changes

20. What policies were
implemented?
Outcomes based coverage.
Funding of new drugs was based on the best
available evidence.
A new drug only became a full benefit if it
represented a therapeutic advantage or a cost
advantage over appropriate alternatives.

21. Examples of drug classes
affected by this policy
Non-steroidal anti-inflammatory drugs (Cox-2
selective NSAIDs).
Oral hypoglycemic drugs (glitazones and others).
Cholinesterase inhibitors for Alzheimers Disease.

22. What was the impact of
the outcome based
coverage policy?

23. Canadian Rx atlas 2007
Non-steroidal anti-inflammatory
drugs

24. Canadian Rx atlas 2007
Oral diabetes drugs

25. Canadian Rx Atlas 2007
Cholinesterase inhibitors

26. What other policies were
implemented?
Reference based pricing of equivalent drugs
within a drug class.
Restricted access based on special authority
criteria.
Therapeutic substitution

27. Reference based pricing
January 1, 1997 least expensive ACE inhibitors
fully covered (captopril, quinapril, ramipril).
More expensive ACE inhibitors covered up to a
maximum of $27 per month (benazepril,
cilazapril, enalapril, fosinopril, lisinopril).
Patients on more expensive ACEI could pay the
difference or switch.

28. Outcomes of reference
pricing for angiotensin-
converting-enzyme inhibitors
Schneeweiss S, Walker AM, Glynn RJ, Maclure M,
Dormuth C, Soumerai SB.
N Engl J Med 2002;346:822-9

29. No increase in Emergency
Hospitalizations due to RP
Schneeweiss et al. N Engl J Med 2002

30. Pharmacysavings
inprevalentACEIusers
$0
$10
$20
$30
$40
$50
$60
Apr-96
May-96
Jun-96
Jul-96
Aug-96
Sep-96
Oct-96
Nov-96
Dec-96
Jan-97
Feb-97
Mar-97
Apr-97
May-97
Jun-97
Jul-97
Aug-97
Sep-97
Oct-97
Nov-97
Dec-97
Jan-98
Feb-98
Mar-98
Apr-98
Month
Average monthly anti-hypertensives
ingredient expenditures per patient
Projectedpre-
policytrend
12monthsavings:
$6,700,000
Schneeweissetal.JCanMedAssoc,2002

31. Reference pricing for ACEI
conclusions
18% of patients switched to lower cost
alternative.
Not associated with changes in physician visits,
hospitalizations or mortality.
Cost savings to drug funder of approximately $6
million per year.

32. What policies were
implemented?
Reference based pricing of equivalent drugs
within a drug class.
Restricted access based on special authority
criteria.
Therapeutic substitution

33. PPI therapeutic substitution

34. Results:1)50%ofPPIusersswitchedtopreferredPPI
0
5
10
15
20
25
30
35
40
45
Jan-02
Feb-02
Mar-02
Apr-02
May-02
Jun-02
Jul-02
Aug-02
Sep-02
Oct-02
Nov-02
Dec-02
Jan-03
Feb-03
Mar-03
Apr-03
May-03
Jun-03
Jul-03
Aug-03
Sep-03
Oct-03
Nov-03
Dec-03
Jan-04
Feb-04
Mar-04
Apr-04
May-04
Jun-04
Daily doses (* 1000) dispensed per 10,000 seniors .
AllPPI
Non-preferredPPIs
PreferredPPI:rabeprazole
Esomeprazole
Fair
PharmaCare*
PPIrestrictionExtrapolated
trend
Rabeprazole
$35/month
$61-$90

35. Results: 4) No increase in adverse GI effects 3) Short-term
increase in visits
0
2
4
6
8
10
12
14
16
18
Jan-02
Feb-02
Mar-02
Apr-02
May-02
Jun-02
Jul-02
Aug-02
Sep-02
Oct-02
Nov-02
Dec-02
Jan-03
Feb-03
Mar-03
Apr-03
May-03
Jun-03
Jul-03
Aug-03
Sep-03
Oct-03
Nov-03
Dec-03
Jan-04
Feb-04
Month
Hospitalizationrateper10,000.
-10
10
30
50
70
90
110
130
150
Officevisitrateper10,000.
Hospitalization: Complicated PUD
Hospitalization: GI hemorrhage
Office visits (GERD, PUD, gastritis)
PPI restrictionFair
PharmaCare†

36. Cost impact
Savings of approximately $3 million in the
first 6 months.

37. Why were the policies
successful?
The TI did not allow any conflicts of interest.
Establishing questions for review was an iterative
process.
Drug Assessment Working Group (DAWG)
followed Cochrane methodology.
DAWG improved critical appraisal skills and
assessing risk of bias over time.

38. Why were the policies
successful?
Researchers were contracted to independently
evaluate the impact on drug utilization and health
outcomes.
Ministry of Health personnel remained committed
to outcomes based coverage despite political
pressures.

40. What did the TI team
learn?
All drugs with any effect have both benefits and
harms.
Drugs are less effective than what we thought was
true.
Drugs are more harmful than what we thought was
true.
In many instances we were shocked that Health
Canada had approved the drugs for market.
In most instances drugs are marketed without
knowing that the benefits outweigh the harms in
many if not all the clinical settings where they are
used.

41. What did we discover?
A novel way of measuring the net health effect
(benefits minus harms) of drugs in clinical trials.
Total serious adverse events are captured in all
clinical trials and represent a measure of total
mortality and serious morbidity.

43. Who were happy about this
program?
Ministry of Health
Taxpayers
Most doctors
PATIENTS

44. Who was unhappy about
the program?
The elephants.
Some doctors (specialists) who were friends of
the elephants.

45. What should of happened?
Expansion of the reference based program to
new classes of drugs eg. Statins.
Continued development of the international
reputation of BC as a drug policy innovator.
Increased funding to the Therapeutics Intiative to
increase the expertise and ensure the long-term
future.

46. What Happened?
In October 2007 a Pharmaceutical Task Force was
announced by BC Health Minister with the following
objectives:
1. Identify and strengthen patient care and choice;
2. Optimize the decision-making process for what
drugs are covered under PharmaCare;
3. Improve the effectiveness of the Common Drug
Review process;
4. Enhance the effectiveness, transparency and
future role of the Therapeutics Initiative.

47. Nine member
Pharmaceutical task force
Chair, Don Avison,
President of the
University Presidents
Council. Board member
LifeSciences BC.
Robert Sindelar, Dean,
Faculty of
Pharmaceutical
Sciences, UBC. Board
member LifeSciences
BC.
Russell Williams,
president of Canada’s
Research-based
Pharmaceutical
Companies (Rx&D).
Susan Paish, Q.C., chief
executive officer,
Pharmasave Drugs
(National) Ltd.
David M. Hall, chief
compliance officer and
senior vice president of
Community Relations,
Angiotech
Pharmaceuticals.
2 Ministry of Health
members.
2 others.

48. PSF recommendations for TI
April 2008
#4 The Ministry of Health should establish a new
Drug Review Resource Committee to carry out
the drug submission review role currently
performed by the Therapeutics Initiative.
#12 Subject to Recommendation #4, if the
Therapeutics Initiative is maintained, action must
be taken in the following areas: improve the
governance, membership and accountability
standards; renew and revitalize the panel of
expert reviewers;

49. The Minister of Health accepted all the
recommendations of the Pharmaceutical Task Force
and set up a mechanism for their implementation.

51. Academic review of TI
http://www.pharmacology.ubc.ca/
3 member external panel reviewed the TI over 2
days in October 2008.
Validated the roles and activities of the TI in drug
assessment, pharmacoepidemiology and
education.
Stable funding must be ensured. The present
funding is inadequate.
3 new permanent University F-slots should be
established.

52. What has happened?
The implementation of the Task Force
recommendations is nearly complete; it has been
costly for the government and extremely
disruptive for the TI.
In November 2009, Don Avison confirmed that
he was recently appointed as the Canadian
representative on Pfizer Global's International
Advisory Board. He did not respond to an e-mail
asking what he will be paid.
Don Avison received a Leadership award from
LifeSciences BC.

53. What has happened?
The TI’s advisory role to the BC Ministry of
Health is unlikely to continue in any meaningful
way.
The TI’s funding from the BC Ministry of Health is
uncertain.

54. What is wrong with the
prescription drug system?
The elephants (Brand Name drug companies)
are too wealthy and powerful.
Recommended reading: “The Corporation: The
pathological pursuit of profit and power”
“Capitalismo Canibal: La Corporacion, La
busqueda patologica de lucro y poder” by Joel
Bakan.
It is not the fault of the corporations.
Governments established the system that got us
here and must bring in regulations to correct it.

55. Ways to improve the
system.
Continue to educate prescribers and patients
about the benefits and harms of prescription drugs.

56. Definition of Advertising
“The science of arresting the human
intelligence long enough to get money
from it.”
Stephen Leacock

57. First regulatory step to
improve the system.
Ban all advertising, marketing, lobbying and
promotion by drug companies.
Ban must include physicians, pharmacists,
nurses, government officials, politicians and the
public.
This would encourage companies to transfer the
huge amounts of money they spend on
marketing to research and development.

58. Second regulatory step to
improve the system
Mandate that all Phase III and Phase IV clinical
trials be designed, conducted, analysed and
reported by independent academic researchers.
The funding for these trials would come from the
companies, but they would be prevented from
manipulating and biasing the results.

60. Questions???Thank you for your attention.

62. www.ti.ubc.ca