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Sample size estimates are critical to the planning and interpretation of clinical studies, whether they are descriptive or analytical. Too small a sample size will result in imprecise estimates in a descriptive study and failure to achieve 'statistical significance' in an analytic or comparative study. Here we discuss what both researchers and readers should understand about the reasons for sample size estimates, how they are done and how achieving or not achieving the desired sample size can affect the interpretation of the outcomes.

Introduction: Recurrent pulmonary exacerbations lead to progressive lung damage in cystic fibrosis (CF). Inhaled medications (mucoactive agents and antibiotics) help prevent exacerbations, but objectively measured adherence is low. We investigated whether a multi-component (complex) self-management intervention to support adherence would reduce exacerbation rates over 12 months.Methods: Between October 2017 and May 2018, adults with CF (aged ≥16 years; 19 UK centres) were randomised to the intervention (data-logging nebulisers, a digital platform and behavioural change sessions with trained clinical interventionists) or usual care (data-logging nebulisers). Outcomes included pulmonary exacerbations (primary outcome), objectively measured adherence, body mass index (BMI), lung function (FEV1) and Cystic Fibrosis Questionnaire-Revised (CFQ-R). Analyses were by intent to treat over 12 months.Results: Among intervention (n=304) and usual care (n=303) participants (51% female, median age 31 years), 88% completed 12-month follow-up. Mean exacerbation rate was 1.63/year with intervention and 1.77/year with usual care (adjusted ratio 0.96; 95% CI 0.83 to 1.12; p=0.64). Adjusted mean differences (95% CI) were in favour of the intervention versus usual care for objectively measured adherence (9.5% (8.6% to 10.4%)) and BMI (0.3 (0.1 to 0.6) kg/m2), with no difference for %FEV1 (1.4 (-0.2 to 3.0)). Seven CFQ-R subscales showed no between-group difference, but treatment burden reduced for the intervention (3.9 (1.2 to 6.7) points). No intervention-related serious adverse events occurred.Conclusions: While pulmonary exacerbations and FEV1 did not show statistically significant differences, the intervention achieved higher objectively measured adherence versus usual care. The adherence difference might be inadequate to influence exacerbations, though higher BMI and lower perceived CF treatment burden were observed. [ABSTRACT FROM AUTHOR]

Rationale, aims, and objective: We previously demonstrated that annual review %FEV1 underestimates lung health of adults with CF compared with %FEV1 captured during periods of clinical stability. This has implications in the comparisons against registries with encounter‐based FEV1, such as the United States. It is uncertain whether this bias affects between‐centre comparison within the United Kingdom. Previous funnel plot analyses have identified variation in annual review %FEV1 according to centre size; hence, we investigated whether paired differences between annual review and best %FEV1 also vary according to centre size. Methods: This registry analysis included 18 adult CF centres in the United Kingdom with ≥80% completeness for best FEV1 data in 2014. Mean discrepancy between annual review and best %FEV1 is a surrogate for the extent by which annual review %FEV1 underestimates lung health, and was plotted against centre size. A local polynomial regression (LOESS) curve was used to explore the relationship between the two variables. An appropriate model is fitted based on the LOESS curve to determine the strength of relationship between discrepancies in %FEV1 and centre size. Results: There is an inverted U‐shaped relationship between mean discrepancies in %FEV1 and centre size. A regression of the paired mean difference in %FEV1 against centre size showed a significant improvement in the goodness of fit for a quadratic model (R2 = 23.8% for a quadratic model compared with 0.4% for a linear one; P = 0.048 for the quadratic term). Conclusions: Annual review %FEV1 underestimated lung health of adults from small and large centres in the United Kingdom to a greater extent compared with medium‐sized centres. A plot of %FEV1 against centre size (eg, funnel plot comparison) would be affected by systematic bias in annual review %FEV1. Therefore, annual review %FEV1 is an unreliable metric to compare health outcomes of adult CF centres within the United Kingdom. [ABSTRACT FROM AUTHOR]

Abstract: Rationale, aims and objective: Cross‐country comparisons of cystic fibrosis (CF) outcomes can potentially identify variation in care but are dependent on data quality. An important assumption is that the UK annual review FEV1 is only collected during periods of clinical stability. If this assumption does not hold, results of FEV1 comparisons may be biased in favour of registries with encounter‐based FEV1. We aimed to test the assumption that CF annual reviews in the UK are only performed during periods of clinical stability. Method: Prospective encounter‐based data collected in Sheffield (n = 174) was used to establish whether annual review FEV1 were always collected during periods of clinical stability and to determine the group‐level discrepancy between annual review vs best FEV1. We then went on to quantify the group‐level discrepancy between annual review and best annual FEV1 readings within the UK registry (n = 2995) to determine if the differences observed in Sheffield also apply to the wider UK data. Results: Sheffield results showed a group‐level discrepancy between best and annual review FEV1 of −2.5% (95% CI −3.95% to −1.2%) for annual reviews performed during periods of clinical stability (n = 50). The group‐level discrepancy is larger at −8.0% (95% CI −11.2% to −4.9%) among annual reviews performed during periods of clinical instability (n = 13). Therefore, the magnitude of this group‐level discrepancy is a surrogate for the proportion of clinically stable annual reviews—smaller discrepancy indicates a higher proportion of clinically stable annual reviews and vice versa. The overall group‐level discrepancy in the UK registry (−5.6%, 95% CI −5.9 to −5.4%) was similar to Sheffield (−6.1%, 95% CI −7.1 to −5.1%). Around 20% of the clinician reviewed, annual reviews in Sheffield were performed during periods of clinically instability. Conclusions: Annual review FEV1 underestimates lung health of adults with CF in the UK and may bias cross‐country comparisons. [ABSTRACT FROM AUTHOR]

The paper by Body et al is concerned with the evaluation of decision aids, which can be used to identify potential acute coronary syndromes (ACS) in the ED. The authors previously developed the Manchester Acute Coronary Syndromes model (MACS) decision aid, which uses several clinical variables and two biomarkers to 'rule in' and 'rule out' ACS. However, one of the two biomarkers (heart-type fatty acid bindingprotein, H-FABP) is not widely used so a revised decision aid has been developed (Troponin-only Manchester Acute Coronary Syndromes, T-MACS), which include a single biomarker hs-cTnT. In this issue, the authors show how they derive a revised decision aid and describe its performance in a number of independent diagnostic cohort studies. Decision aids (as well as other types of 'diagnostic tests') are often evaluated in terms of diagnostic testing parameters such as the area under the receiver operating characteristic (ROC) curve, sensitivity and specificity. In this article, we explain how the ROC analysis is conducted and why it is an essential step towards developing a test with the desirable levels of sensitivity and specificity. [ABSTRACT FROM AUTHOR]

Among adults with cystic fibrosis (CF), medication adherence is low and reasons for low adherence are poorly understood. Our previous exploratory study showed that stronger 'habit' (ie, automatically experiencing an urge to use a nebuliser) was associated with higher nebuliser adherence. We performed a secondary analysis of pilot trial data (n=61) to replicate the earlier study and determine whether habit-adherence association exists in other cohorts of adults with CF. In this study, high adherers also reported stronger habit compared with low adherers. Habit may be a promising target for self-management interventions. TRIAL REGISTRATION NUMBER: ACtiF pilot, ISRCTN13076797. [ABSTRACT FROM AUTHOR]