TRM-SLE information for clinicians and researchers

Challenges of current clinical trial outcome measures

Systemic lupus erythematosus (SLE):

  • A disease of high unmet therapeutic need.
  • Challenging to accurately measure clinically meaningful responses to treatment.
  • Few positive outcomes in SLE trials, impeding new drug approvals.
  • Phase 2 trial results that fail to be replicated in Phase 3.
  • Phase 3 trials with identical study protocols producing conflicting results.
  • Discrepancies between the trial outcomes and other efficacy data.

Current primary efficacy endpoints used in SLE trials:

  • Are based on legacy disease activity measures.
  • Not developed according to contemporary recommendations for clinical outcome assessments.
  • Lack patient input in determining which concepts are important to be measured.
  • Discrete thresholds introducing floor and ceiling effects are used.
  • Numerical thresholds defining improvement and manifestation weightings are not based on empirical evidence of meaningful within-patient change.
  • Developed using post-hoc analysis of trial data, risking bias to specific drug mechanisms or specific study design.
  • Some manifestations are poorly defined and/or rarely appear in clinical trials.
  • Adoption prior to extensive testing of measurement properties.
  • Can be complex and non-intuitive to complete and interpret.

Outcome measures used in current SLE trial primary endpoints do not meet contemporary measurement standards, which in combination with their history of unreliable performance, underpins the major need for new instruments.

Overcoming these challenges

The Treatment Response Measure for SLE (TRM-SLE) project is developing a new clinical outcome assessment suitable for implementation in a primary efficacy endpoint in SLE clinical trials. We specifically seek to avoid replicating the liabilities of legacy measures and will follow modern recommendations for instrument development, including guidance documents published by regulatory bodies such as the United States Food and Drug Administration (FDA) and European Medicines Agency (EMA).

Contact us

To express interest in being involved in the TRM-SLE project or for any general enquiries related to the TRM-SLE project, please contact us.