Developing Evidence-Based Best Practices for the Prescribing and Use of Proton Pump Inhibitors in Canada

Presented by: Sumeet R. Singh, COMPUS

April 4, 2006

Background

COMPUS Objective:

•To identify and promote the implementation of evidence-based and cost-effective best practices in the prescribing and use of medicines in key therapeutic areas

•First project: Proton-pump inhibitors (PPIs)

Background

Rationale:

• PPI prescriptions dispensed increased from 10.8 million to 12.4 million between 2003 and 2004, an increase of 15%*

• Rising expenditures on PPIs

*Source: IMS Health Canada

Background

0

200

400

600

800

1000

1200

2000 2001 2002 2003 2004

Mill

ions

of D

olla

rs

91% increase

Estimated total PPI retail pharmacy sales in Canada*:

Year

* Source: IMS Health Canada

Background

Approved Indications for PPIs in Canada:

•Gastroesophageal reflux disease•Reflux esophagitis•Barrett’s esophagus

•Dyspepsia

•Peptic ulcer disease•NSAID-associated ulcer•Helicobacter pylori eradication

•Zollinger-Ellison syndrome

GERD

Dyspepsia

PUD

ZES

Background

PPIs available in Canada:

• Omeprazole (Losec, Apo-omeprazole)• Lansoprazole (Prevacid)• Pantoprazole (Pantoloc)• Esomeprazole (Nexium)• Rabeprazole (Pariet)

Cost:$1.20 - $4.40/day depending upon agent, brand, indication, dose

Methodology

COMPUS Framework for Identifying Best Practices:

1) Identify and summarize existing recommendations regarding the use of PPIs for the approved indications.Sources: Clinical Practice Guidelines (CPGs) and Consensus Documents (CDs)

2) Identify, evaluate, and summarize the available clinical and economic evidence pertaining to these recommendations.Sources: CPGs and CDs, stakeholders’ input, literature search

3) Determine the final content and phrasing of COMPUS Best Practice Recommendations for the Prescribing and Use of PPIs: expert panel.

Rationale for using CPGs and CDs:

• Source of recommendations based on available evidence and clinical experience.

• Have a significant influence on patterns of drug prescribing and use.

Methodology

1) Identify and summarize existing recommendations regarding the use of PPIs for the approved indications.

1a) Collection of CPGs and CDs*.

1b) Extraction of recommendations on PPIs.

1c) Grouping of similar recommendations into a Synopsis of Existing Recommendations (SERs).

* Stakeholders also consulted.

Methodology

2) Identify, evaluate, and summarize the available clinical and economic evidence pertaining to these recommendations.

2a) Identification, selection, and evaluation of CPG/CD-cited evidence for each SER.

2b) Identification, selection, and evaluation of relevant new evidence (published after CPGs/CDs) from SRs and RCTs*.

2c) Identification and evaluation of relevant Canadian economic studies*.

* Stakeholders also consulted.

Methodology

1a) Collection of CPGs and CDs:

Search Strategy:• MEDLINE®, BIOSIS Previews®, EMBASE® and PASCAL,

PubMed, Cochrane Library and CINAHL• Internet-based collections of guidelines: CMA Infobase,

AHRQ's National Guidelines Clearinghouse, the NHS National Electronic Library of Health Guidelines Finder, and the Guidelines International Network web site

• Grey literature: selected web sites using the Google™ and Yahoo! ® search engines and specific websites of gastroenterology associations

Methodology

1a) cont’d

Selection Criteria:

•CPGs and CDs containing recommendations on the use of PPIs for the approved indications in Canada

•Produced by professional groups or bodies in Canada, USA, Western Europe, Australia, and New Zealand

Methodology

1b) Extraction of recommendations1c) Synopsis of similar recommendations

Example:

Guideline 1: Canadian H. pylori Consensus Conference: “All H. pylori-positive patients with duodenal or gastric ulcer… should receive eradication treatment.”

Guideline 2: New Zealand Guidelines Group: “H. pylori eradication is effective in healing peptic ulcers and also very significantly reduces ulcer recurrence (rare) and complications.”

Guideline 3: NICE (UK): “Offer H. pylori eradication therapy to H. pylori-positive patients who have peptic ulcer disease.”

Synopsis of Existing Recommendations: H. pylori eradication therapy is recommended for patients diagnosed with gastric or duodenal ulcer who are infected with H. pylori.

Methodology

2a) Identification, selection, and evaluation of CPG/CD-cited evidence for each SER.

Example:

Guideline 1: Canadian H. pylori Consensus Conference: “All H. pylori-positive patients with duodenal or gastric ulcer… should receive eradication treatment.a,b,c”

Guideline 2: New Zealand Guidelines Group: “H. pylori eradication is effective in healing peptic ulcers and also very significantly reduces ulcer recurrence (rare) and complications.a,d,e”

Guideline 3: NICE (UK): “Offer H. pylori eradication therapy to H. pylori-positive patients who have peptic ulcer disease.a,c,f”

Total evidence base for SER contains 6 studies: a, b, c, d, e, f

Methodology

2a) cont’d

Selection of studies for detailed evaluation was based on a hierarchy of evidence:

Systematic reviews > RCTs > Observational studies > Expert opinion

Methodology

2a) cont’d

Algorithm for selecting studies for detailed assessment:

• All cited SRs

• All RCTs for SERs with no good quality SRs cited, or having a direction of effect opposite to good quality SRs

• All observational studies for SERs with no SRs or RCTs, or having a direction of effect opposite to poor quality SRs or RCTs

• Expert or consensus opinion for SERs with no SRs, RCTs, or observational studies

Methodology

2a) cont’d

Quality assessment of selected evidence:

QA instruments:

• SRs: AMSTAR

• RCTs: Adapted SIGN50 Methodology Checklist for RCTs

• Observational studies: Adapted SIGN50 methodology checklist for cohort and checklist for case-control studies

Methodology

2a) cont’d

Summary of selected evidence: Studies summarized according to PICO principle:

Example:

SER: PPIs are more effective than H2RAs for remission of symptoms and healing in patients with GERD.

+59% with ome vs. 35% with ran (p<0.001)

Heartburn relief at 4 weeks

ran 150mg bid for 4 weeks

Ome 20mg qdfor 4 weeks

268 clinically diagnosed GERD patients

Kaplan-Machlis et al 200035

RCT (good)

DirResultsOutcome Measure

Comparator (C)

Intervention (I)

PopulationStudy Type (QA)

Methodology

2b) Identification of relevant new evidence:

• SRs and RCTs related to PPIs published 2003 onwards

• Same process for selecting and evaluating new evidence

• Selected studies were classified by the existing SERs

• Unclassifiable studies were referred to a clinical expert

Methodology

2c) Identification and evaluation of relevant Canadian economic studies:

•Identified from the selected CPGs/ CDs, and literature search in MEDLINE®, BIOSIS Previews® and EMBASE®

•Extraction of Economic Data

•Linking of each selected studies to the relevant SERs

•Assessment of Economic Studies:- Quality parameters: timeliness, type of study, outcomes,

efficacy/effectiveness, cost, discounting and summary efficiencymeasure

- Relevance parameters: population, intervention, time frame and setting

Results

CPGs and CDs selected: •70 documents addressed PPI use for GERD, PUD, dyspepsia- 69 were identified from the literature search- 1 was identified by stakeholders- no CPGs/CDs addressed ZES

Economic Studies selected:•7 studies - 5 from CPGs/CDs, - 5 from the literature search- 3 overlapped between them

Results

16

3

5

8

No. of SERssupported by good

quality RCTs

9

3

0

6

No. of SERssupported

by poor quality RCTs

or SRs

0612PUD

14

6

2

No. of SERssupported by good

quality SRs

2160Total

1324Dyspepsia

824GERD

No. of SERssupported

only by opinion

Total No. of SERs

Indications

Highest Level of evidence by SER:

Results

33(6 SRs

27 RCTs)

47(13 SRs34 RCTs)

80(19 SRs61 RCTs)

PUD

055(2 SRs3 RCTs)

Dyspepsia

04949(12 SRs37 RCTs)

GERD

Related to new clinical points

Related to current SERs

Selected studies

Indications

Evidence Update results

Results

COMPUS interim report:

“Summary of Findings on the Prescribing and Use of Proton Pump Inhibitors” has been posted on the COMPUS website for stakeholder feedback

www.cadth.ca

Next Steps

•Stakeholder consultation

•Multidisciplinary Review Panel:- gastroenterology - internal medicine - family practice - clinical pharmacy - geriatrics- health economics- methodology

•Panel will determine “Best Practices”, using- PPI interim report information- evidence update - stakeholder feedback

Questions?