Lupus trials and tribulations: are outcome measures the problem?

Many randomised clinical trials in systemic lupus erythematosus have failed, and the manner in which they have failed is of concern. In lupus, phase III trials have a higher risk of failing than phase II trials-going against the expected gradient and against logic, because phase III trials are preferentially based on successful rather than on failed phase II trials. In addition, there have been puzzling discrepancies between different outcomes within individual trials as well as between the same outcomes in different trials. Therefore, it has been suggested that outcome measures are to blame for the difficulties in achieving trial successes in lupus. Additional concerns regarding clinical trial outcomes deal with their complexity and lack of clinical applicability; and the most widely used trial outcomes, SRI-4 (systemic lupus response index [based on four points improvement]) and BICLA (British Isles Lupus Assessment Group-Based Composite Lupus Assessment), are at odds with current therapeutic thinking, which is less concerned with change and more with the disease state that is achieved (treating to target). A number of suggestions have been made, and concrete initiatives launched, to address these issues, and these may change the way in which clinical trials will be done in the future. Meanwhile, it is worth mentioning that a large number of phase III trials are currently underway; their outcomes may yet again change the way we approach clinical trial outcomes in lupus.