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Objective. To assess the minimal clinically important difference (MCID) in joint damage on hand and foot radiographs of patients with early rheumatoid arthritis (RA) as assessed with the Sharp/van der Heijde and Larsen/Scott methods, and to study how the smallest detectable difference (SDD) relates to the MCID for each method.Methods. The judgments of an international panel of experts on the clinical relevance of progression of joint damage as seen on sets of radiographs obtained at 1-year intervals in 4 clinical settings (early versus late RA and mild versus high disease activity) were used as the external criterion, which was compared with the progression scores as determined by the 2 scoring methods. Progression scores with the highest combined sensitivity and specificity for detecting clinically relevant progression represented the MCID. Subsequently, the sensitivity and specificity of the scoring methods were determined when using the SDD as the threshold for relevant progression, and these were compared with the sensitivity and specificity of the MCID.Results. The panel judged changes in joint damage around the level of the SDD (5.0) of the Sharp/van der Heijde method as minimal clinically important, resulting in satisfactory sensitivity (mean 79%) and specificity (mean 84%) for detecting clinically important progression in the 4 clinical settings when using the SDD as the threshold value. The MCID (mean 2.3) of the Larsen/Scott method was much smaller than its SDD (5.8), and the sensitivity for detecting clinically important progression by applying the SDD as threshold was consequently low (mean 51%), accompanied by high specificity (mean 99%).Conclusion. This study suggests that the SDD of the Sharp/van der Heijde method can be used as the MCID, i.e., as the threshold level for individual response criteria. The SDD of the Larsen/Scott method, however, turned out to be too insensitive to use as the threshold for individual clinically relevant change.

Controlling healthcare budgets is a major priority for all healthcare systems. In the UK, recommendations for the role of specific treatments and disease management guidelines are produced by organisations such as the National Institute of Clinical Excellence (NICE). These recommendations are usually based on cost-effectiveness (utility) analysis that compares therapies based on a combination of outcomes. These include: clinical outcomes (resolution of infection, observed mortality, projected mortality based on age and disease of patients alive), economic outcomes (such as overall treatment costs, including drug acquisition costs, costs due to adverse events, length of stay (LOS) and treatment switches) and humanistic outcomes (quality of life or utility scores). In practice, little if any direct cost-effectiveness analysis exists to support such decisions.Our paper focuses on an economic evaluation of antifungal drugs. The economic burden of fungal infections AbstractObjective: To evaluate the cost-effectiveness of caspofungin vs. liposomal amphotericin B in the treatment of suspected fungal infections in the UK. Methods: The cost-effectiveness of caspofungin vs. liposomal amphotericin B was evaluated using a decision-tree model. The decision tree was populated using both data and clinical definitions from published clinical studies. Model outcomes included success in terms of resolution of fever, baseline infection, absence of breakthrough infection, survival and quality adjusted life years (QALYs) saved. Discontinuation due to nephrotoxicity or other adverse events were included in the model. Efficacy and safety data were based on additional analyses of a randomised, double blind, multinational trial of caspofungin compared with liposomal amphotericin B. Information on life expectancy, quality of life, medical resource consumption and costs were obtained from peer-reviewed published data. Results: The caspofungin mean total treatment cost was £9762 (95% uncertainty interval 6955-12 577), which was £2033 ()2489; 6779) less than liposomal amphotericin B. Treatment with caspofungin resulted in 0.40 ()0.12; 0.94) additional QALYs saved in comparison with liposomal amphotericin B. Probabilistic sensitivity analysis found a 95% probability of the incremental cost per QALY saved being within the generally accepted threshold for cost-effectiveness (£30 000). Additional analyses with varying dose of caspofungin and liposomal amphotericin B confirmed these findings. Conclusion: Given the underlying assumptions, caspofungin is cost-effective compared with liposomal amphotericin B in the treatment of suspected fungal infections in the UK.

Objectives: To investigate whether plain radiographs can show changes in joint damage due to rheumatoid arthritis (RA) within 3 months. Methods: 188 film pairs taken with a 3 month interval were evaluated. They were scored with (chronological) and without (paired) knowledge of the sequence of the films according to the Sharp/van der Heijde method. Changes in joint damage were analysed on a group and an individual level for different subsets of patients. Sample sizes required to detect statistically and clinically significant differences were estimated based on the percentages of patients with progression larger than the smallest detectable change (SDC). Results: Changes in joint damage were seen by both the chronological and the paired scoring method. The percentage of patients with progression of joint damage larger than the corresponding SDCs (1.7 and 2.4) varied in the subsets from 18% to 64% if based on the chronological change-scores and from 9% to 36% using paired change-scores. Acceptable sample size estimates were seen in several subsets, depending on (a) how the investigated drug would reduce the individual risk of progression of joint damage (by an absolute or a relative risk reduction model); (b) how damage was scored (chronological or paired); (c) the baseline risk; and (d) whether a two sided or one sided test would be used. Conclusions: Changes in joint damage due to RA can be detected reliably already within 3 months. This finding can be used to plan short term, randomised controlled trials with radiographic progression as primary outcome.

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