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Evidence tables Hans de Beer, Ton Kuijpers, Craig Whittington, Magali Remy-Stockinger, Robin Harbour, Rob Cook, Sara Twaddle, Andreas Gerber Why work on evidence Scottish Charity No: SC034047 Scottish Charity No: SC034047 tables? Need for


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Evidence tables

Hans de Beer, Ton Kuijpers, Craig Whittington, Magali Remy-Stockinger, Robin Harbour, Rob Cook, Sara Twaddle, Andreas Gerber

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Scottish Charity No: SC034047 Scottish Charity No: SC034047

Why work on evidence tables?

  • Need for a common definition
  • Provides a real opportunity for joint working

between guideline agencies and between G-I- N and other international groups

  • Potentially could save significant duplication of

effort across all guideline development agencies

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Work so far…

  • 1. WG agreed definition of ETs at Lyon Conference

2005

– Evidence tables are methodological and outcome summaries that present data from a number of related studies. These answer a well defined question in a consistent format and aim to demonstrate overall trends in the evidence and enable the process of making recommendations.

  • 2. Development of a minimum data set for

summarising studies that evaluate an intervention and a definitive template for describing them

– Presented in a workshop at the Toronto conference in August 2007. – Now accepted for publication by Quality & Safety in Health Care

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Work so far…

  • 3. Development of a template for

summarising studies addressing a diagnostic question and a definitive template for describing them

– The results of the evaluation study were presented at the Helsinki Conference in October 2008

  • 4. Development of draft templates for

summarising prognostic and economic evaluation studies

– Discussed at the Chicago Conference 2010

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Work so far…

  • 5. Agreement of the specification for the registry of

summarised studies to enable G-I-N members to share their work with others

– GINDER: G-I-N Data Extraction Resource (Accessible through the G-I-N website) – Provides an online collaborative working space, which contains a registry of data extracted from individual studies, based on templates developed by the ETWG. – Summaries can be linked with guidelines in the G-I-N library

  • 6. Launch of GINDER

– Launched 29 August 2011 – Roll out:

  • Diagnostic studies -> as soon as testing is complete
  • Intervention studies -> later this year
  • Prognostic studies -> once template finalised
  • Economic evaluation studies -> once template finalised.

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What we are doing now…

  • Developing a definite template

for:

– summarising prognostic studies. – summarising economic evaluation studies

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Members of the Core Group 2010-11

  • Sara Twaddle
  • Craig Whittington
  • Hans de Beer
  • Magali Remy Stockinger
  • Ton Kuijpers
  • Rob Cook
  • Markos Dintsios
  • Andreas Gerber
  • Robin Harbour
  • Kelvin Hill

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Other members of the ETWG

  • Samar Aboulsoud-

Hassona

  • Lorne Becker
  • Bernard Burnand
  • Michel Laurence
  • Thomas Kaiser
  • Eeva Ketola
  • Regina Kunz
  • Jorma Komulainen
  • Stefan Lange
  • Alric Ruether
  • Rick Shiffman
  • Sheamini Sivasampu
  • Jean Slutsky
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Second draft template for prognostic studies

Ton Kuijpers Hans de Beer

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Introduction

  • Prognosis: foreseeing, predicting, or

estimating the probability or risk of future conditions

  • In medicine, prognosis commonly relates

to the probability or risk of an individual developing a particular state of health (an

  • utcome) over a specific time, based on

his or her clinical and non-clinical profile

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Introduction

  • Outcomes are often specific events,

such as death or complications, but they may also be quantities, such as disease progression, (changes in) pain, or quality of life

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Introduction

Prognostic course studies

  • Studies investigating the most likely course of a

disease or complaints Prognostic factor studies

  • Studies investigating whether a single variable

(such as a tumour or other biomarker) may be prognostic. Outcome prediction studies

  • Studies aimed at predicting outcomes from

multiple variables.

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Introduction

Example of a prognostic course study

  • Estimate incidence and course of severity-

graded low back pain episodes in adults. Example of a prognostic factor study

  • To identify individual, psychosocial, and

workplace risk factors associated with the transition from acute to chronic

  • ccupational back pain.

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Introduction

Examples of outcome prediction studies

  • Development and validation of a

prediction rule that estimates the probability of complaints persisting for at least 6 months in patients presenting with non-specific neck pain in primary care

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Introduction

Consecutive phases in outcome prediction studies

  • Development studies
  • Validation studies
  • Impact studies

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Introduction

Outcome prediction studies: development studies

  • Development of a multivariable prognostic

model, including – identification of the important predictors, – assigning relative weights to each predictor, and – estimating the model’s predictive performance

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Introduction

Outcome prediction studies: validation studies

  • Validating or testing the model’s predictive

performance in new study participants. Outcome prediction studies: impact studies

  • Quantifying whether the use of a prognostic model

by practising doctors truly improves their decision making and ultimately patient outcomes

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Introduction

References

  • Moons KG, Royston P, Vergouwe Y, Grobbee DE,

Altman DG. Prognosis and prognostic research: what, why, and how? BMJ 2009;338:b375.

  • Royston P, Moons KG, Altman DG, Vergouwe Y.

Prognosis and prognostic research: Developing a prognostic model. BMJ 2009;338:b604..

  • Altman DG, Vergouwe Y, Royston P, Moons KG.

Prognosis and prognostic research: validating a prognostic model. BMJ 2009;338:b605.

  • Moons KG, Altman DG, Vergouwe Y, Royston P.

Prognosis and prognostic research: application and impact of prognostic models in clinical practice. BMJ 2009;338:b606.

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Evaluation study of draft prognostic template

  • Objectives
  • Methods
  • Results
  • Third draft

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Evaluation study of draft prognostic template

Objectives To assess:

  • the relevance of the items proposed in the

template

  • the clarity of the instructions for completing

these items

  • the validity of the data collection
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Evaluation study of draft prognostic template

Methods

  • G-I-N members were invited to participate in the

study

  • They were requested to complete a

questionnaire on the relevance/clarity of items and ease of completion, and

  • To deliver copies of four study summaries

according to the draft prognostic template and instructions given.

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Evaluated draft template

HEADINGS DESCRIPTION

Bibliographic citation

Use Vancouver st yle (Authors. Title. Journal name. Publication Date; Volume (Issue):Page Numbers) Insert the link to the publication.

Sources of funding and competing interest

Report:

  •  The source of funding cited in the paper: give name(s) of
  • rganisation or corporation.

Specify if possible the source type (public research funds, NGO, government, Academic/university healthcare industry or other)

  •  Competing interests: Write “Stated” or “Not Stated” and

specify if any

Setting

Multicenter, Location/Country(ies), Healthcare se tting,

Objective(s) of the study

Report, as cited by author(s), the objective(s) of the study including both primary and secondary aims, if applicable.

Type of prognostic study

Specify whether the study is a prognostic course study, a prognostic factor (Explanatory) study, or an outcome prediction (Risk group) study)

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Evaluated draft template

M ETHO D S

Study design (cited b y a uthor or actual)

Sp ecify the stud y d esign : cross sectiona l stud y, (p rosp ective) coh ort stud y, ca se control stud y, other (give d eta ils). Precise if it’s the d esign cited b y a uthor(s).

Eligib ility criteria

D escrib e the:

  •  Eligibility criteria i.e . inclusion -exclusion criteria ,
  •  M ethod s of selection of p a rticip a nts, e .g . c onven ience sa m p le,

consecutive p a tients etc.

Study dura tion

Rep ort p eriod s of recruitm ent, exp osure , a nd follow -up m om ents

O utcom e events

D escrib e the outcom e e vents id entified b y a utho r(s), b oth p rim a ry a nd second a ry one s. In ca se of a p rognostic fa ctor stud y : D escrib e the p otentia l p rognostic fa ctors. In ca se of a centra l p rognostic fa ctor, d escrib e the central p rognostic fa ctor a nd a ll p otential confound ers a nd effect m od ifiers

Prognostic factors a nd p otentia l confounders

(a pplies to a prognostic fac tor study, or an outc om e predic tion study)

In ca se of a n outcom e p red iction stud y : D escrib e a ll p otentia l p rognostic fa ctors

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Evaluated draft template

RESULTS N um b ers

Rep ort num b ers of ind ivid ua ls a t ea ch sta ge of stud y:

  •  num b ers p otentially eligib le, exa m ined for eligib ility, c onfirm ed

eligib le, includ ed in the stud y, com p leting follow -up , a nd a na lysed

  •  N um b e r of p a tients exclud ed a nd rea son s (i.e . give rea sons for

non-p a rticip ation a t ea ch sta ge) Pa tients characteristics D escrib e the a ctua l p opula tion involved in the stud y:

  •  G ive cha ra cteristics of stud y p a rticip ants (e .g . d e m ogra p hic,

clinical, socia l) a nd info rm a tion on exp osures a n d p otential confo und ers

  •  Indica te num b er of p a rticip a nts w ith m issing d ata for ea ch

va ria b le of interest

  •  Rep ort Follow -up tim e: a vera ge/ m e d ia n a nd ra nge if

a p p lica ble O utcom e events da ta Rep ort num b ers of o utcom e events or sum m a ry m ea sure s Rep ort a ll a va ila b le figures w ith 95% confid ence interva ls or other m ea sures of d isp ersion such a s sta nd a rd errors (if c onfid ence interva ls a ren’t rep orted ) In ca se of a p rognostic fa ctor stud y: Rep ort a ll a va ila b le figures w ith 95% confid ence interva ls or other m ea sures of d isp ersion such a s sta nd a rd errors (if c onfid ence interva ls a ren’t rep orted ):

  •  Rep ort una d justed univa ria b le estim ates a nd their p recision
  •  Rep ort a d justed m ultiva ria b le estim ates a nd their p recision

Sp ecify ca tegory b o und a ries w hen continuous va ria b les w ere ca tegorized Effect size - p rognostic fa ctors (a pplies to a prognostic fac tor study, or an outc om e predic tion study.) In ca se of a n outcom e p red iction stud y:

  • d evelop m ent of the m o d el
  •  Rep ort una d justed univa ria b le estim a tes a nd their p recision
  •  Rep ort a d justed m ultiva ria b le estim ates a nd their p recision
  •  Rep ort p erform a nce sta tistics of the m od el (AU C , exp ected /
  • b served p rob a b ility p lots, H osm er-Lem e show go od ness-of-fit H -
  • r ? -sta tistics, nega tive / p ositive p red icted va lues.
  • va lid ation of the m od el
  •  Rep ort p erform a nce sta tistics of the m od el (e .g . A UC , exp ected

/ ob served p rob a b ility p lots, H osm e r-Lem e show good ne ss-of-fit H - or ? -sta tistics, nega tive / p ositive p red icted va lues.

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C RITIC A L A PPRA ISA L O F THE STUDY Q UA LITY

Authors conclusion

Report the authors’ conc lusion

Validity of results

D iscuss the validity of the results and potential bias present:

  •  Internal validity: stud y de sign appropriateness, sources of

potential bias, use of ina ppropriate statistical analysis, interpretation of the results (taking into account the study hypotheses), m ultiplicity of analyse s, com m ent on patients lost to follow -up (if applicable), etc.

  •  External validity: disc uss the generalisability of the study re sults

(e .g . setting, population involved , test used , h ow (over)optim istic the m odel perform ance is in predicting outcom es etc.) G eneral com m ents, including ow n conclusion of the review er, if possible .

O ther /Addendum

O ptional Further calculations m ade by the review er

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Evaluation study of draft prognostic template

Results

  • People willing to participate; N=16
  • Response; N=13
  • Professions:

– Clinical nurse specialist (n=1) – Medical specialist (n=3) – Researcher (n=4) – Pharmacist (n=1) – Technical analyst (n=1) – Information officer (n=1) – Systematic reviewer (n=1) – Epidemiologist (n=1)

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Results

  • 100% of the respondents had already

done critical reviews of the literature?

  • Average time to read a paper and

complete a summary was 130 min.

  • 69% thought that completing the template

for the 2nd, 3rd & 4th study was less difficult?

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Evaluation study of draft prognostic template

R ele va n cy 1 = stron g ly d isag ree 9 = stron g ly ag ree U n d ersta n d a b ility 1 = stron g ly d isag ree 9 = stron g ly ag ree D ifficu lty in com p letin g P erce n ta g e N o an sw ers B ibliographic citation 8.5 8.8 92% S ource of funding and com peting interest 8.6 8.6 92% S etting 8.4 7.8 64% O bjectives(s) of the study 8.8 8.8 92% Type of prognostic stud y 7.5 6.6 46% S tudy design 8.2 7.8 77% Eligibility criteria 8.7 8.3 75% S tudy duration 8.4 8.0 83% O utcom e events 7.9 7.8 100% Progn ostic factors and p otential confounders 8.4 7.5 77% N um bers 8.4 8.3 75% Patient characteristics 8.2 8.4 50% O utcom e events data 8.5 8.5 77% Effect size – prognostic factors 8.5 6.5 40% C ritical A ppraisal 7.5 8.2

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Evaluation study of draft prognostic template

W ere in stru ctio n s cle ar an d /or h elp fu l in o rd er to com p lete tem plate ? Percentage Yes answ ers H elpful? C lear? Bibliographic citation 100 92 Source of funding and com peting interest 100 83 Setting 92 92 O bjectives(s) of the study 100 100 Type of prognostic stud y 75 50 Study design 83 58 Eligibility criteria 100 100 Study duration 100 92 O utcom e events 100 100 Progn ostic factors and p otential confounders 100 83 N um bers 100 100 Patient characteristics 92 83 O utcom e events data 100 83 Effect size – prognostic factors 92 75

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Evaluation study of draft prognostic template

Suggestions for additional items

  • Appropriateness of statistics performed
  • How were missing data handled
  • Overall comment
  • Level of quality of the evidence
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Proposed final template

H E AD IN G S Instructions Bibliographic citation

U se Vancouver style (Authors. T itle. Journal nam e. Publication D ate; Volum e (Issue):Page N um bers)  Journal titles are abbreviated (to decipher abbrev iations see: PubM ed Journals D atabase <http://w w w .ncbi.nlm .nih.gov/entrez/query.fcgi?db=journals>)  O nly first words of article title and words that norm ally begin w ith a capital letter are capitalised.  First 6 authors are listed; thereafter add an et al. after the sixth author. Exam ple: G ao SR , M cG arry M , Ferrier T L, P allante B, G asparrini B, Fletcher JR , et al. Effect of cell confluence on production of cloned m ice using an inbred em bryonic stem cell line. Biol R eprod. 2003;68(2):595 -603. Insert the link to the publication. Exam ple: http://w w w .ncbi.nlm .nih.gov/pubm ed/12533424 Sources of funding R eport the source of funding cited in the paper:  give nam e(s) of organisation or corporation.  Specify if possible the source type (public research funds, N G O , governm ent, Academ ic/university healthcare industry or other) Com peting interest C om peting interests: W rite “Stated” or “N ot Stated” and specify if any Setting M ulticenter, Location/C ountry(ies), H ealthcare setting (prim ary, secondary, tertiary), workplace setting O bjective(s) of the study R eport, as cited b y author(s), the objective(s) of the study including both prim ary and secondary aim s, if applicable Type of prognostic study Specify w hether the study is a prognostic course study, a prognostic factor (explanatory) stud y, or an outcom e prediction (R isk group) stud y). T he addendum at the end of docum ent explains and illustrates the types of prognostic studies

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Proposed final template

M ETHO DS Study design Specify w hat you think is the actual study design: cross sectional study, (prospective) cohort study, case control study, other (give details) O ptional: If you think the actual study design differs from the one cited by the author(s), you could m ention this Sam pling m ethod M ethods of selecting study participants, e.g. convenience sam ple, consecutive patients etc. Eligibility criteria D escribe the Eligibility criteria i.e. inclusion -exclusion criteria, Follow-up m om ents R eport periods of recruitm ent and follow-up m om ents O utcom e m easures D escribe the outcom e m easures identified by author(s), both prim ary and secondary ones. Exam ple (see also study of Schellingerhout et al in addendum ): O utcom e m easure is global perceived recovery, dichotom ized into “recovered or m uch im proved” and “persistent com plaints”.) In case of a prognostic factor study: D escribe potential prognostic factors m e ntioned in the paper. In case of a central prognostic factor, describe the central prognostic factor, all potential confounders and effect m odifiers m entioned in the paper Prognostic factors and potential confounders (applies to

a prognostic factor study,

  • r an outcom e prediction

study.) In case of an outcom e prediction study: D escribe all potential prognostic factors m entioned in the paper

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RESULTS Num bers R eport num bers of individuals:  num bers potentially eligible,  included in the study,  com pleting follow-up O ptional: If available copy and paste flowchart from the paper Patients characteristics D escribe the actual population involved in the study by giving characteristics of study participants:  dem ographic characteristics (age, sex, ethnicity, socio -econom ic status) and  relevant context-sensitive (e.g. stage of disease) cha racteristics O utcom e m easures data R eport outcom es m easures data and include all av ailable figures w ith 95% confidence intervals or other m ea sures of dispersion such as standard errors (if confidence intervals aren‟t reported) Exam ple (see also study of Schellingerhout et al in addendum ): Persistent com plaints w ere reported by 43% of th e patients in the developm ent population after 6 m onths of follow -up In case of a prognostic factor study: R eport all available figures w ith 95% confidence intervals or other m easures of dispersion such as standard errors (if confidence intervals aren‟t reported):  R eport statistically significant unadjusted univariable estim ates and their precision  R eport statistically significant adjusted m ultivariable estim ates and their precision Specify category boundaries when continuous variables were categorized Effect size of prognostic factors

(applies to a prognostic factor study, or an

  • utcom e prediction study.)

In case of an outcom e prediction study:

  • developm ent of the m odel

 R eport statistically significant unadjusted univariable estim ates and their precision  R eport statistically significant adjusted m ultivariable estim ates and their precision  R eport perform ance statistics of the m odel (see addendum for relevant statistics)

  • validation of the m odel

 R eport perform ance statistics of the m odel (s ee addendum for relevant statistics) Authors conclusion R eport the authors‟ conclusion

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Proposed final template

CRITIC AL AP PR AIS AL O F THE STUDY Q U A LITY Validity of results D iscuss the validity of the results and potential bias present. R elevant issues are for instance:  how representative is the sam ple of patients?  w as patient follow -up sufficiently long and com plete?  w ere outcom e criteria either objective or applied in a „blind‟ fashion? If subgroups w ith different prognoses are identified, did adjustm ent for im portant prognostic factors take place?  how w ere m issing data handled?  how precise are the prognostic factors estim ated?  appropriateness of statistics perform ed? 

  • verall com m ent

(see for instance w w w .cebm .net) Addendum (optional) Further calculations m ade by the reviewer

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Evaluation study of draft prognostic template

  • Specific items to be discussed

– Type of prognostic study: useful item? – Prognostic factors and potential confounders: is it useful to mention all potential prognostic factors that have been investigated, or should we confine ourselves to mentioning statistically significant prognostic factors – Numbers: numbers potentially eligible; numbers included in the study; numbers completed follow-up. More numbers needed?

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Evaluation study of draft prognostic template

  • Item descriptions: clear enough?
  • More items needed?
  • Has the template unnecessary items?
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Template for summarising economic evaluations

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Evaluation study

  • Invitation sent widely via G-I-N

newsletter and to ten volunteers

  • Six people expressed interest
  • All sent four papers to extract into the

template

  • Four completed all four papers and

provide 16 completed templates for the study

  • Three people completed the

questionnaire too

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Results

  • Respondents found the following items

difficult to complete:

– Time horizon, discounting and sensitivity analysis – Overall summary measure of benefit. A suggestion was made that this item could ask for cost per effectiveness unit or cost per utility specifically – Two respondents wanted clarification of “method used to value benefit” – One respondent asked that a cost-effectiveness plane and cost-effectiveness acceptability curve be asked for in the results section

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Results 2 - suggestions

  • Respondents asked for a glossary to

describe:

– All types of analysis (CUA etc) – Discounting – Time horizon – Difference between utilities and benefits – Methods used to value benefit

  • One respondent suggested that there is a major

challenge in using economic analyses in other than the study country. An item on transferability

  • r applicability was requested.
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Evaluation study draft

HEADING DESCRIPTION Bibliographic citation Use style (Authors. Title. Journal

  • name. Publication Date; Volume

(Issue):Page (Numbers) Hyperlink to publication Sources of funding and competing interests Quote the source of funding if mentioned in the paper. If possible, specify the source type (public research funds, Government, NGO, academic/university, healthcare industry, other). Note: It is not necessary to report funding or conflicts of any secondary sources used in the analysis. Quote any declared competing interests, or write “None stated”

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METHODS Type of economic evaluation Specify the form of economic evaluation being used (CUA, CEA, CBA, etc). Viewpoint / costing perspective State the viewpoint of the analysis.(eg. health system, payer or societal etc.) Country/Countries List the country/countries for economic evaluation Time horizon State the time horizon for both costs and benefits Population Describe the eligible population and the population used for effect/cost data Interventions Describe the alternatives being compared Primary health outcome measure(s) State the primary health outcome measure(s) Overall summary measure of benefit (if used) State the summary measure of benefit for CUA (eg. QALY or DALY etc.)

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Scottish Charity No: SC034047 Scottish Charity No: SC034047

Source of effectiveness estimates Identify the source (meta analysis, RCT, etc.) Methods used to value benefits Identify the methods used (stated WTP, revealed WTP, conjoint analysis etc.) Utilities and benefits Specify where utilities or benefits came from (literature values, elicited in the study etc.) Source of estimates of quantities of resources used Describe the methods use to identify relevant resource use (survey, lit values, expert consultation, formal consensus methods etc) Methods used to estimate unit costs Describe the methods used to identify relevant unit costs (survey, lit values etc) Include cost year Adjustment for inflation Was adjustment for inflation performed if unit costs stemmed from different years? Discounting Was discounting performed? Were effects and cost discounted with the same rate(s)? Approach to sensitivity analysis Describe the methods used for sensitivity analysis (one way, two way, probabilistic etc) Modelling and analysis Detail any model used (Markov, Decision Tree, Discrete Event Simulation etc) www.g-i-n.net

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Scottish Charity No: SC034047 Scottish Charity No: SC034047

RESULTS Costs and outcomes Presented relevant costs and

  • utcomes in both

disaggregated and aggregated form (with confidence intervals, measures of significance) Subgroup analyses Were subgroup analyses performed? Are the based on the results of RCTs etc.? Incremental analysis results Present the results of IA Sensitivity analysis results Present the results of SA

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CRITICAL APPRAISAL OF STUDY QUALITY Authors conclusion Report authors‟ conclusions verbatim Validity of results Comment on the strengths and weaknesses of the study. If weaknesses were identified were these likely to have made a difference to the results of the economic evaluation? Other / addendum (optional)

GINDER