ࡱ>  ubjbjBrBr 7  J*U%U%U%U%U%i%i%i%8%%i%>2'''''("( (111111136R1U%(((((1U%U%''1)))(RU%'U%'1)(1))V0E1'P@i%*)L0 120>20T6v)"6E16U%E1(()(((((11)(((>2((((6((((((((( $: Checklist Table. Mark ( to indicate that the issue has been addressed satisfactorily, and ( if there is any cause for concern on the item. The Comments column should be used to answer the question (YES, NO, NA: not applicable) and/or to spell out the reasons for any concerns, the need for sensitivity analyses etc. tableItem satisfactory?CommentsA. DEFINITION OF THE DECISION PROBLEM A1. Target population for decisionA1.1Has the target patient population for decision been clearly defined?A2. ComparatorsA2.1Decision Comparator Set: Have all the appropriate treatments in the decision been identified?A2.2Synthesis Comparator Set: Are there additional treatments in the Synthesis Comparator Set, which are not in the Decision Comparator Set? If so, is this adequately justified?A3 Trial inclusion / exclusionA3.1Is the search strategy technically adequate and appropriately reported?A3.2Have all trials involving at least two of the treatments in the Synthesis Comparator Set been included?A3.3 Have all trials reporting relevant outcomes been included? A3.4Have additional trials been included? If so, is this adequately justified?A4 Treatment DefinitionA4.1Are all the treatment options restricted to specific doses and co-treatments, or have different doses and co-treatments been lumped together? If the latter, is it adequately justified?A4.2Are there any additional modelling assumptions?A5 Trial outcomes and scale of measurement chosen for the synthesisA5.1Where alternative outcomes are available, has the choice of outcome measure used in the synthesis been justified?A5.2Have the assumptions behind the choice of scale been justified?A6 Patient population: trials with patients outside the target populationA6.1Do some trials include patients outside the target population? If so, is this adequately justified? A6.2What assumptions are made about the impact, or lack of impact this may have on the relative treatment effects? Are they adequately justified?A6.3Has an adjustment been made to account for these differences? If so, comment on the adequacy of the evidence presented in support of this adjustment, and on the need for a sensitivity analysis.A7 Patient population: heterogeneity within the target populationA7.1Has there been a review of the literature concerning potential modifiers of treatment effect?A7.2Are there apparent or potential differences between trials in their patient populations, albeit within the target population? If so, has this been adequately taken into account?A8 Risk of BiasA8.1Is there a discussion of the biases to which these trials, or this ensemble of trials, are vulnerable?A8.2If a bias risk was identified, was any adjustment made to the analysis and was this adequately justified? A9. Presentation of the dataA9.1Is there a clear table or diagram showing which data have been included in the base-case analysis?A9.2Is there a clear table or diagram showing which data have been excluded and why?B. METHODS OF ANALYSIS AND presentation of RESULTS B1 Meta-analytic methodsB1.1Is the statistical model clearly described?B1.2Has the software implementation been documented?B2. Heterogeneity in the relative treatment effects B2.1Have numerical estimates been provided of the degree of heterogeneity in the relative treatment effects?B2.2Has a justification been given for choice of random or fixed effect models? Should sensitivity analyses be considered?B2.3Has there been adequate response to heterogeneity?B2.4Does the extent of unexplained variation in relative treatment effects threaten the robustness of conclusions?B2.5Has the statistical heterogeneity between baseline arms been discussed? B3 Baseline model for trial outcomesB3.1Are baseline effects and relative effects estimated in the same model? If so, has this been justified?B3.2Has the choice of studies to inform the baseline model been explained?B4 Presentation of results of analyses of trial data B4.1Are the relative treatment effects (relative to a placebo or standard comparator) tabulated, alongside measures of between-study heterogeneity if a RE model is used?B4.2Are the absolute effects on each treatment, as they are used in the CEA, reported?B5 Synthesis in other parts of the natural history modelB5.1Is the choice of data sources to inform the other parameters in the natural history model adequately described and justified? B5.2In the natural history model, can the longer-term differences between treatments be explained by their differences on randomised trial outcomes?  C. ISSUES SPECIFIC TO NETWORK SYNTHESIS C1 Adequacy of information on model specification and software implementationC2. Multi-arm trialsC2.1If there are multi-arm trials, have the correlations between the relative treatment effects been taken into account?C3 Connected and disconnected networksC3.1Is the network of evidence based on randomised trials connected?C4 InconsistencyC4.1How many inconsistencies could there be in the network?C4.2Are there any a priori reasons for concern that inconsistency might exist, due to systematic clinical differences between the patients in trials comparing treatments A and B, and the patients in trials comparing treatments A and C, etc?C4.3Have adequate checks for inconsistency been made?C4.4If inconsistency was detected, what adjustments were made to the analysis, and how was this justified?D EMBEDDING THE SYNTHESIS IN A PROBABILISTIC COST EFFECTIVENESS ANALYSIS D1. Uncertainty PropagationD1.1Has the uncertainty in parameter estimates been propagated through the CEA model?D2 CorrelationsD2.1Are there correlations between parameters? If so, have the correlations been propagated through the CEA model?      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