Table 133, Philips checklist for chronic antibiotic agents - Cystic Fibrosis

Section	Pass/fail	Comments
Structure
Statement of decision problem / objective	P	Decision problem stated clearly in title, and clarified in ‘comparisons’ section
Justification of modelling approach	P	Justified with reference to published literature on the same topic
Statement of scope / perspective	P	Comparisons’ section clearly delineates scope, and perspective explicitly described as being ‘Reference Case’ in section relating to model structure.
Structural assumptions	P	Assumptions justified in section ‘Model structure’, and clinical relevance confirmed with Guideline committee. Biggest assumption (of relationship between short and long-term treatment) described in relevant section
Strategies / Comparators	P	Very nonstandard approach to transition probabilities, but otherwise structure is highly consistent with other similar models in the area
Model type	P	Strategies selected with reference to available literature, especially pre-existing TAs. Choice of cut-offs for FEV states well justified as model is intended to match some of the work of prior economists in the area
Time horizon	P	Choice of Markov Model straightforward and well justified. Use of ‘fully incremental’ analysis slightly unusual, but well justified in the text with reference to heterogeneity of studies
Health states/disease pathways	P	Lifetime time horizon, in keeping with Reference Case
Cycle Length	P	Health states carefully considered and modelled to represent only critical transitions within disease pathway.
Parsimony	P	Cycle length unusual (first cycle is 28 days, subsequent cycles 24 weeks) but justified with reference to literature and committee consensus
Data
Data Identification	P	Systematic review of published literature
Data Synthesis	N/A	Unclear if any synthesis was appropriate
Discounting	P	3.5% as specified in Reference Case
Analysis of trial data	P	Data analysed at most appropriate level
Treatment effects	P	Odds ratios derived from trials and superimposed on population baseline risks
Transition probabilities	P	Derivation of transitions probabilities not standard as model attempts to map a continuous process onto a discrete-state model. Nevertheless the methodology employed here is well-described, and validated by NICE TSU
Mortality	P	Discussion of mortality in model write-up; CF has a very poor prognosis and so life tables not appropriate. Data from Vertex used to calculate ‘all cause CF’ mortality, and lung-transplant specific mortality appended to this
Extrapolation	P	Significant extrapolation, but well justified in text with reference to committee expert opinion. Not possible to validate with reference to literature, as such literature does not exist
Risk factors	P	Evidence of nonlinear effect of risk factors on mortality sought and incorporated into model, for example by considering lung transplant as a separate state
Utilities	P	Utilities described in section on health related quality of life, and justified with reference to literature
Charges and costs	P	Charges and costs described in section on resource and cost use, and come from standard sources such as NHS Reference Costs and PSSRU
Adjustment over time / between countries	P	Costs inflated from historic values using HCHS index
Half-cycle correction	F	Half-cycle correction unlikely to be necessary as cycle length much shorter than time horizon of model
Data incorporation	P	Choice of data to incorporate and how the data are used is clear and well-justified
Uncertainty
General statement regarding sensitivity analysis	P	Described in sections on the method and results of sensitivity analysis
Structural	P	Model structure based on published and validated model, and deviating from this model would be methodologically unsound
Methodological	P	Although discount rate not varied as per Philips (2004), substantial methodological variation examined and discussed
Parameter	P	PSA undertaken for aztreonam comparison. Exclusion of other comparisons justified with reference to relative certainty of parametrisation for these comparisons (they have TAs from NICE which cannot be challenged)
Consistency
Internal	P	Model is highly robust to ‘stress testing’ such as putting extreme values into cells. Model behaves in an intuitive way, for example recommending treatments to which a substantial discount has been applied
External	P	Face validity confirmed with reference to Guideline committee. Additionally, values appear congruent with general clinical practice.
Between-model	P	Results consistent with literature on the topic
Predictive	N/A	Model not intended to be used predictively, and such predictive work would be well outside NICE methods manual

Section

Pass/fail

Comments

Structure

Statement of decision problem / objective

Decision problem stated clearly in title, and clarified in ‘comparisons’ section

Justification of modelling approach

Justified with reference to published literature on the same topic

Statement of scope / perspective

Comparisons’ section clearly delineates scope, and perspective explicitly described as being ‘Reference Case’ in section relating to model structure.

Structural assumptions

Assumptions justified in section ‘Model structure’, and clinical relevance confirmed with Guideline committee. Biggest assumption (of relationship between short and long-term treatment) described in relevant section

Strategies / Comparators

Very nonstandard approach to transition probabilities, but otherwise structure is highly consistent with other similar models in the area

Model type

Strategies selected with reference to available literature, especially pre-existing TAs. Choice of cut-offs for FEV states well justified as model is intended to match some of the work of prior economists in the area

Time horizon

Choice of Markov Model straightforward and well justified. Use of ‘fully incremental’ analysis slightly unusual, but well justified in the text with reference to heterogeneity of studies

Health states/disease pathways

Lifetime time horizon, in keeping with Reference Case

Cycle Length

Health states carefully considered and modelled to represent only critical transitions within disease pathway.

Parsimony

Cycle length unusual (first cycle is 28 days, subsequent cycles 24 weeks) but justified with reference to literature and committee consensus

Data

Data Identification

Systematic review of published literature

Data Synthesis

N/A

Unclear if any synthesis was appropriate

Discounting

3.5% as specified in Reference Case

Analysis of trial data

Data analysed at most appropriate level

Treatment effects

Odds ratios derived from trials and superimposed on population baseline risks

Transition probabilities

Derivation of transitions probabilities not standard as model attempts to map a continuous process onto a discrete-state model. Nevertheless the methodology employed here is well-described, and validated by NICE TSU

Mortality

Discussion of mortality in model write-up; CF has a very poor prognosis and so life tables not appropriate. Data from Vertex used to calculate ‘all cause CF’ mortality, and lung-transplant specific mortality appended to this

Extrapolation

Significant extrapolation, but well justified in text with reference to committee expert opinion. Not possible to validate with reference to literature, as such literature does not exist

Risk factors

Evidence of nonlinear effect of risk factors on mortality sought and incorporated into model, for example by considering lung transplant as a separate state

Utilities

Utilities described in section on health related quality of life, and justified with reference to literature

Charges and costs

Charges and costs described in section on resource and cost use, and come from standard sources such as NHS Reference Costs and PSSRU

Adjustment over time / between countries

Costs inflated from historic values using HCHS index

Half-cycle correction

Half-cycle correction unlikely to be necessary as cycle length much shorter than time horizon of model

Data incorporation

Choice of data to incorporate and how the data are used is clear and well-justified

Uncertainty

General statement regarding sensitivity analysis

Described in sections on the method and results of sensitivity analysis

Structural

Model structure based on published and validated model, and deviating from this model would be methodologically unsound

Methodological

Although discount rate not varied as per Philips (2004), substantial methodological variation examined and discussed

Parameter

PSA undertaken for aztreonam comparison. Exclusion of other comparisons justified with reference to relative certainty of parametrisation for these comparisons (they have TAs from NICE which cannot be challenged)

Consistency

Internal

Model is highly robust to ‘stress testing’ such as putting extreme values into cells. Model behaves in an intuitive way, for example recommending treatments to which a substantial discount has been applied

External

Face validity confirmed with reference to Guideline committee. Additionally, values appear congruent with general clinical practice.

Between-model

Results consistent with literature on the topic

Predictive

N/A

Model not intended to be used predictively, and such predictive work would be well outside NICE methods manual

From: Appendix K, Health Economics

Cystic Fibrosis: Diagnosis and management.

NICE Guideline, No. 78.

National Guideline Alliance (UK).

London: National Institute for Health and Care Excellence (NICE); 2017 Oct 25.

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

Table 133Philips checklist for chronic antibiotic agents