Discussion
acne
ACNE
This economic study finds a high degree of uncertainty about whether spironolactone is likely to be cost-effective. Our economic evaluation provides a range of estimates for the cost-effectiveness of spironolactone used alongside routine topical treatment. The base-case analysis, where the comparator is no active systemic treatment plus routine topical treatment, and the delivery of the intervention is costed as via primary care, spironolactone was not estimated to be cost-effective in the unadjusted and adjusted complete case analyses. However, in the adjusted analysis, using MI, the ICER was estimated to be just under the £30 000 per QALY threshold. This divergence in conclusion between the complete case and MI analysis demonstrates the impact of missing data (attrition bias) and suggests more weight ought to be placed on the MI analysis.This economic evaluation followed a HEAP finalised before data were received for analysis, reducing bias in the results from selective reporting or cherry-picked analyses.First, ideally economic evaluations should compare an active treatment to current usual care. The funder for this trial preferred the placebo comparator to current usual care.Second, in practice, clinicians are unlikely to send women away with no active treatment if they consulted with acne persisting beyond 6 months. As advised by the trial clinicians, the clinically important comparator may be another systemic treatment rather than no active systemic treatment. To address this, a sensitivity analysis assuming, for cost purposes, all women in the no active systemic treatment group received an oral antibiotic (in addition to topical treatments) for 24 weeks was planned. This analysis assumed that incremental QALYs remain the same as in the base-case analysis, which we acknowledge is unlikely. There is limited economic evidence comparing oral antibiotics in combination with routine topical treatment compared with routine topical treatment alone.Third, the uncertainty highlighted by this study may be impacted, in part, by the method of measuring utility, an area where further research would be valuable. The conclusion reached about cost-effectiveness was sensitive to the estimates of QALYs generated from EQ-5D-5L, despite 46% in the intervention group and 43% in the control group reporting perfect health (EQ-5D-5L health state 11111) at baseline. For these participants, the EQ-5D-5L had no potential to measure improvements in health-related quality of life. This likely contributes to the wide 95% CIs around the incremental QALY estimates in this study, which means we cannot be certain spironolactone improves QALYs rather than have no difference or worsen QALYs. At design stage, there was discussion about the possible use of other instruments; however, the limited published evidence supported the use of the EQ-5D for acne.Fourth, we acknowledge that the analysis was conducted for a 24-week timeframe and that were a longer timeframe taken the cost-effectiveness of spironolactone may improve if, for instance, there is a sustained effect once treatment stops. We sought to collect resource use and utility data up to 52 weeks, but due to reduced data completion at 52 weeks (see supplementary material for details), it was not feasible to analyse results to a longer time horizon.Finally, a CCA was specified in the HEAP as the base-case analysis (with MI as a sensitivity analysis) reflecting a desire to be consistent with the approach undertaken in the Statistical Analysis Plan for the clinical primary outcome. With the benefit of hindsight primary concern ought to have been around the level of missing economic data, which is known to often be greater than that for clinical outcomes. However, both complete case and MI analyses are reported, as planned, so that the impact of missing data on the results can be clearly seen.Our study provides estimates of the cost-effectiveness of spironolactone in women with persistent acne using the trial data and a range of scenarios. It highlights that there is considerable uncertainty about whether spironolactone is cost-effective and the need for further research with comparators more akin to clinical practice. The CCA estimated ICERs in excess of the upper NICE threshold of £30 000 per QALY, but this analysis took a conservative approach since it may be that incremental QALYs for spironolactone would have been greater had we been able to control for any placebo effect and had more complete data beyond 24 weeks. When taking into account missing data, the ICER was below the upper NICE threshold, suggesting spironolactone may be considered cost-effective. However, all analyses show a high degree of uncertainty suggestive of a need for further research to allow conclusions to be drawn.