DISCUSSION Alex Sutton Centre for Biostatistics & Genetic Epidemiology, University of Leicester

DEFINING “RELEVANT” EVIDENCE Driven by pre-specified model structure? –Or should model be malleable to available evidence? – What evidence should be used to define structure Necessarily a dynamic process? –e.g. look for lower grades of evidence if higher grades are not found? –How much evidence is sufficient? Bias precision trade-off? Utilising related evidence –e.g. different population groups / time periods –e.g. indirect comparisons Would guidance / rules be helpful? –Rulebook helpful / fair?

IDENTIFYING “RELEVANT” EVIDENCE Should we always be systematic? Should we always be exhaustive? –or do we need to be more pragmatic for some model parameters? –role of expert? Need to be explicit about what has been done? –Document search strategies Develop standardised search strategies for different parameter types / model structure? Use of Google ?!? Required data may not be primary focus of paper

ASSESSING QUALITY OF EVIDENCE Are hierarchies of evidence useful / correct? –do we need to empirically validate them? Assessing quality of individual studies –scores / checklists difficult across study designs? really assessing quality of reporting?

INCORPORATING QUALITY OF EVIDENCE Incorporation of quality into synthesis / model? –Experience from meta-analysis of RCTs suggests very difficult problem –Options: Define inclusion threshold Use to adjust weighting given to studies Adjust point estimates Cross design synthesis modelling Sensitivity analysis –Problem: little relationship between quality and magnitude of estimate Has anyone ever said evidence not good enough?

HOW TO SYNTHESISE THE DATA Use meta-analysis when multiple sources? Complications: –Data reported in different formats e.g. mean / median survival –Checking for consistency heterogeneity data logically “adding up” –Little developed for costs / utilities Many extensions of meta-analysis / multi parameter evidence synthesis in development –WinBUGS – “realistically complex models”

OTHER ISSUES When is it worth trying to obtain individual patient data? –When relevant info not reported in paper? e.g. side effects / population groups / uncertainty estimate etc. –To increase precision? exploration of individual level characteristics? Publication / outcome reporting bias What data is the responsibility of the companies? Set threshold levels of evidence – fairness?? What have I missed??

“CASE STUDY” Model to evaluate optimum method for diagnosing DVT Several (5+) tests available –Approx 500 studies Diagnostic test studies notoriously poor –Poorly reported –Unclear population groups etc

INDIVIDUAL STUDIES OF D-DIMER Substantial heterogeneity! Publication bias? Reduce to the best studies??

OUTPUTS FROM TODAY Put presentations on website (with speakers’ permission) Write up and distribute discussion to attendees Consensus paper following both workshops? Identification of future empirical / methodological research required –Empirical comparisons of thorough with quick

NEXT WORKSHOP “ Appropriate methodology for identifying & combining the evidence for use in decision analytical models ” Monday 26 th September 2005 (Room G20, Department of Health Sciences, University of Leicester) Suggestions for format / talks?