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CER Collaborative
ICER Evidence Rating Matrix - Report
Overview
Brief Introduction
Formulary decisions require a rigorous evaluation of available evidence, a process that entails judgments regarding the
quality of individual clinical studies and, ultimately, an assessment of the entire body of evidence regarding a therapeutic
agent. To support this latter step, the Institute for Clinical and Economic Review (ICER) has developed the ICER
Evidence Rating Matrix. The matrix presents a framework for evaluating the comparative benefits and risks of therapies in
a consistent, transparent system leading to an evidence rating that can guide coverage and formulary placement
decisions. The purpose of this tool is to help members of Pharmacy and Therapeutics Committees and other decisionmakers understand the approach embodied in the matrix, and to help them apply it in a reliable, consistent fashion.
Fundamentally, the evidence rating reflects a joint judgment of two critical components:
a) The magnitude of the difference between a therapeutic agent and its comparator in “net health benefit” – the balance
between clinical benefits and risks and/or adverse effects; AND
b) The level of certainty that you have in your best point estimate of net health benefit.
Step 1: Formulary Evaluation
Instructions
First, it is important to establish the specific focus of the comparison to be made and the scope of evidence that you will
be considering. This process is sometimes referred to as the “PICO”- the Population, Intervention, Comparator(s), and
Outcomes of interest. Depending on the comparison, it is often helpful to also define the specific Time Horizon and Setting
that will be considered relevant.
1) Intervention
Brand Name: abcdelimumab
Generic Name: abcdelimumab
Formulation: inj
2) Comparator
zywvlimumab IV
3) Patient Group / Indications
atrial fibrillation
4) Outcomes of Interest
Clinical Benefit(s)
Outcomes of interest include: Normal Sinus Rhythm Stroke CV mortality non-CV Morality
Risk / Adverse effect(s)
Harms of interest include:
Mortality
ICH
Generic Name:abcdelimumab
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Date:Apr 02, 2013
non-ICH bleeding
side effects
Other potential advantages or disadvantages
Other outcomes of interest:
quality of life
potential drug interactions
Step 2: Magnitude of Comparative Net Benefits
Introduction
The first step to arrive at an overall rating of the evidence is to judge the comparative net health benefit of the product of
interest relative to its selected comparator. Once the evidence on clinical benefits, safety, and other advantages are
considered, we recommend that the magnitude of benefits and the magnitude of adverse effects and other risks be
analyzed and then summed quantitatively across all studies in the body of evidence whenever possible. You may enter
text or upload relevant tables in the section below.
A. Summary of Key Differences in Clinical Benefit(s)
Limited head-to-head data exist with which to judge the differential impact on all-cause mortality for
abcdelimumab vs. zwvlimumab. In the single head-to-head RCT that has been conducted, the DINO trial, allcause mortality was 3.4% for abcdelimumab vs. 1.4% for
zywvlimumab. on an annualized basis, a difference that was not statistically significant (Hauser, 2010).
Zywvlimumab. was found to have a significantly lower rate of cardiovascular death vs. placebo in the large,
placebo-controlled ALBERTA trial (1.5% vs. 2.2% on an annualized basis) (Hoelscher, 2004).
B. Summary of Key Differences in Risk / Adverse Effects
Pulmonary Toxicity
As measured in RCTs and comparative studies, the rate of pulmonary toxicity with abcdelimumab is relatively low,
ranging from 0-1.6% on an annualized basis. Long-term follow-up studies and other evidence-based reviews have
reported a much wider range of pulmonary toxicity (1-17%); however, many of the higher estimates were for
abcdelimumab at higher dose levels (i.e., =400 mg daily). A 200 mg daily maintenance dose is now
recommended; at this level, observed rates are very similar to those in our review. Pulmonary toxicity has been
reported in only one zywvlimumab trial, at an annualized rate of 0.1%. In the short-term head-to-head DINO trial,
no pulmonary events were observed in either the abcdelimumab or zywvlimumab arms.
C. Summary of Key Differences in other potential advantages/disadvantages
Evidence is limited regarding abcdelimumab's impact on hospitalization rates when compared to rate control, with
data available from a single RCT in our sample (Hoelscher, 2003). The comparison to rate control is highly
problematic, however, given that hospitalization is used as a planned element of rhythm control strategies.
Hospitalization was assessed as a primary outcome in the ALBERTA trial of zywvlimumabas well as in post hoc
comparisons for stroke (Hoelscher 2003); findings suggested a lower rate of hospitalization with zywvlimumab
compared to placebo.
D. Summary of Quantitative or Qualitative Comparative Net Health Benefits
E. Based upon above information, what is your point estimate of comparable net health
benefits
Negative: the drug produces a net health benefit inferior to that of the comparator
Comparable: the drug produces a net health benefit comparable to that of the comparator
Small/Incremental: the drug produces a small positive net health benefit relative to the comparator
CER Collaborative
ICER Evidence Rating Matrix - Report
Substantial: the drug produces a moderate-to-large positive net health benefit relative to the comparator
Step 3: Level of Certainty
Introductions
Instructions: The next step involves making a judgment about the level of certainty or the “conceptual confidence
interval” around the original estimate of comparative net health benefit. We recommend formal documentation of the
consideration of 5 major domains related to strength of evidence. Comments should discuss how the body of evidence
stacks up in each domain. We do not recommend trying to devise a mathematical equation using the domain scores to
arrive at a final score because sometimes one factor (e.g., precision) will have a greater weight in a final judgment of the
certainty. In other cases another factor (e.g., consistency of findings) may matter most. Using the domains can help clarify
the source of the different opinions regarding the body of evidence.
Generic Name:abcdelimumab
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Date:Apr 02, 2013
CER Collaborative
ICER Evidence Rating Matrix - Report
A. Bias - risk of bias
Significant Limitation
The evidence base includes 1 large well-designed randomized controlled trial of 22,000 patients. Two additional trials of
observational studies are also included as well as 1 poorly conducted observational study.
B. Directness
Significant Limitation
The primary endpoint of interest in the randomized controlled trial was any serious bleeding. Secondary analyses included
direct measures (mortality, rehospitalization). Despite this direct endpoint, the outcomes are limited to on year of follow-up.
C. Consistency
Significant Limitation
Results favored all subgroups in the abcdelimumab arm (including demographics (age, sex), risk factors for stroke as defined
by CHADS2 or other mechanisms, and other comorbidities, underscoring the need to
identify and highlight stratified analyses of interest.)
D. Precision
Significant Limitation
Endpoints including any serious clinical bleeding, hospitalization, or ICH are clinically significant in favor of abcdelimumab.
Mortality endpoints show a wide confidence interval.
In contrast, outcomes
E. Applicability / Generalizability
Significant Limitation
Use of abcdelimumab is unknown in certain particular subpopulations of patients.
Both surgical and catheter-based vary significantly by center, and that the review should recognize this lack of standardization,
as well as the potential association between level of clinician experience and training and patient outcomes may be associated
with abcdelimumab.
F. Other potential influences on certainty
Significant Limitation
Ethical considerations: At the outset of the appraisal there appeared to be no
distinctive ethical issues regarding the patient populations or the interpretation of
results from cost-effectiveness analyses.
Generic Name:abcdelimumab
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Date:Apr 02, 2013
Step 4: Conceptual Confidence Interval
Point estimate of comparative net health benefits: Small
Negative Net Benefit
Comparable Net Benefit
Likelihood of Negative Benefit Level: NA
Rating Result
Small Net Benefit
Substantial Net Benefit