Impact of trial attrition rates on treatment effect estimates in chronic inflammatory diseases: A meta‐epidemiological study

Author:

Overgaard Silja H.123ORCID,Moos Caroline M.4ORCID,Ioannidis John P. A.56789ORCID,Luta George101112ORCID,Berg Johannes I.2,Nielsen Sabrina M.213ORCID,Andersen Vibeke131415ORCID,Christensen Robin213ORCID

Affiliation:

1. The Molecular Diagnostics and Clinical Research Unit, Institute of Regional Health Research University of Southern Denmark Denmark

2. Section for Biostatistics and Evidence‐Based Research, The Parker Institute Bispebjerg and Frederiksberg Hospital Copenhagen Denmark

3. Department of Internal Medicine University Hospital of Southern Denmark Aabenraa Denmark

4. Department of Clinical Research University Hospital of Southern Denmark Aabenraa Denmark

5. Meta‐Research Innovation Center at Stanford (METRICS) Stanford University Stanford California USA

6. Stanford Prevention Research Center, Department of Medicine Stanford University School of Medicine Stanford California USA

7. Department of Epidemiology and Population Health Stanford University School of Medicine Stanford California USA

8. Department of Biomedical Data Science Stanford University School of Medicine Stanford California USA

9. Department of Statistics Stanford University School of Humanities and Sciences Stanford California USA

10. Department of Biostatistics, Bioinformatics and Biomathematics Georgetown University Washington DC USA

11. Department of Clinical Epidemiology Aarhus University Aarhus Denmark

12. Clinical Research Unit, The Parker Institute, Bispebjerg and Frederiksberg Hospital Copenhagen Denmark

13. Research Unit of Rheumatology, Department of Clinical Research University of Southern Denmark, Odense University Hospital Denmark

14. Institute of Molecular Medicine University of Southern Denmark Odense Denmark

15. OPEN Explorative Network University of Southern Denmark Odense Denmark

Abstract

AbstractThe objective of this meta‐epidemiological study was to explore the impact of attrition rates on treatment effect estimates in randomised trials of chronic inflammatory diseases (CID) treated with biological and targeted synthetic disease‐modifying drugs. We sampled trials from Cochrane reviews. Attrition rates and primary endpoint results were retrieved from trial publications; Odds ratios (ORs) were calculated from the odds of withdrawing in the experimental intervention compared to the control comparison groups (i.e., differential attrition), as well as the odds of achieving a clinical response (i.e., the trial outcome). Trials were combined using random effects restricted maximum likelihood meta‐regression models and associations between estimates of treatment effects and attrition rates were analysed. From 37 meta‐analyses, 179 trials were included, and 163 were analysed (301 randomised comparisons; n = 62,220 patients). Overall, the odds of withdrawal were lower in the experimental compared to control groups (random effects summary OR = 0.45, 95% CI, 0.41–0.50). The corresponding overall treatment effects were large (random effects summary OR = 4.43, 95% CI 3.92–4.99) with considerable heterogeneity across interventions and clinical specialties (I2 = 85.7%). The ORs estimating treatment effect showed larger treatment benefits when the differential attrition was more prominent with more attrition in the control group (OR = 0.73, 95% CI 0.55–0.96). Higher attrition rates from the control arm are associated with larger estimated benefits of treatments with biological or targeted synthetic disease‐modifying drugs in CID trials; differential attrition may affect estimates of treatment benefit in randomised trials.

Funder

Oak Foundation

Knud og Edith Eriksens Mindefond

Region Syddanmark

Publisher

Wiley

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