Faculty Collaboration Database

Fragility of randomised controlled trials for systemic lupus erythematosus and lupus nephritis therapies. Lupus Sci Med 2024 Jan 10;11(1)

Date

01/11/2024

Pubmed ID

38199863

Pubmed Central ID

PMC10806519

DOI

10.1136/lupus-2023-001068

Scopus ID

2-s2.0-85183020457 (requires institutional sign-in at Scopus site)

Abstract

OBJECTIVE: We aimed to evaluate the robustness of phase III randomised controlled trials (RCTs) for SLE and lupus nephritis (LN) using the fragility index (FI), the reverse FI (RFI) and the fragility quotient (FQ).

METHODS: We searched for phase III RCTs that included patients with active SLE or LN. Data on primary endpoints, total participants and the number of events for each arm were obtained. We calculated the FI score for RCTs with statistically significant results (number of patients required to change from event to non-event to make the study lose statistical significance), the RFI for RCTs without statistically significant results (number of patients required to change from non-event to event to make study gain statistical significance) and the FQ score for both (FI or RFI score divided by the sample size).

RESULTS: We evaluated 20 RCTs (16 SLE, four LN). The mean FI/RFI score was 13.6 (SD 6.6). There were nine RCTs with statistically significant results (seven SLE, two LN), and the mean FI score was 10.2 (SD 6.2). The lowest FI was for the ILLUMINATE-2 trial (FI=2), and the highest FI was for the BLISS-52 trial (FI=17).Twelve studies had non-statistically significant results (10 SLE, two LN) with a mean RFI score of 15.6 (SD 6.1). The lowest RFI was for the ILLUMINATE-1 trial (RFI=4), and the highest RFI was for the TULIP-1 trial (RFI=27). The lowest FQ scores were found in the ILLUMINATE trials and the highest in the Rituximab trials (EXPLORER and LUNAR), meaning that the last ones were the most robust results after accounting for sample size.

CONCLUSIONS: The evidence of therapies for patients with SLE and LN is derived mostly from fragile RCTs. Clinicians and trialists must be aware of the fragility of these RCTs for clinical decision-making and designing trials for novel therapeutics.

Author List

Figueroa-Parra G, Putman MS, Crowson CS, Duarte-García A

Author

Michael Putman MD Assistant Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Clinical Decision-Making
Humans
Lupus Erythematosus, Systemic
Lupus Nephritis
Randomized Controlled Trials as Topic
Rituximab