Clinical study report data did not substantially alter point estimates but improved precision in a nephrology systematic review

Abstract

Objectives

To investigate the effect of adding clinical study report (CSR) data to publication and author data on data completeness and meta-analytical results.

Study Design and Setting

Case report of a systematic review with meta-analysis of randomized controlled trials on icodextrin compared to glucose solutions in peritoneal dialysis including 19 clinical trials. We considered the outcomes mortality, peritoneal dialysis technique failure, quality of life, net peritoneal ultrafiltration (at 3–6 months, and 1–2 years), serious adverse events (SAE), peritonitis, and uncontrolled fluid overload. The results for these outcomes were reanalyzed using (a) publication and author data only, then compared with (b) publication and author data with added CSR data. At outcome level, we compared the number of included trials, pooled point estimates (ie, regarding effect direction), and 95% confidence intervals (CIs; ie, regarding overlap and width) between the two groups of trials (a and b). We illustrated the results of our meta-analyses in forest plots and narratively summarized them.

Results

Except for two of the eight assessed outcomes (quality of life and net peritoneal ultrafiltration [1–2 years]), more complete data was available when adding CSRs to publication and author data. Point estimates were not statistically significantly different for publication and author data, compared to publication, author, and CSR data, for any outcome. For peritonitis, point estimates were on opposite sides of the line of no effect but remained statistically nonsignificant when adding CSR data. For SAE and net peritoneal ultrafiltration (3–6 months), the width of the 95% CI was narrower when adding CSR data and for net peritoneal ultrafiltration (3–6 months), in addition, the point estimate statistically significantly favored icodextrin when adding CSR data.

Conclusion

The fraction of publications reporting results varied substantially by outcome, with SAE most under-reported in publications. While the integration of CSR data did not substantially alter meta-analytical results, it enhanced data completeness and precision in effect estimates. Our findings underscore the importance of accessing CSR data to optimize evidence syntheses and inform clinical decision-making.

Plain Language Summary

When researchers want to understand how well a treatment works, they often combine results from several clinical studies in a process called a meta-analysis. Usually, these analyses rely on data published in scientific journals. However, published articles don't always include all the important results. Additional information can sometimes be found in clinical study reports (CSRs), which are detailed documents submitted by pharmaceutical companies to regulatory agencies. In this study, we looked at how including CSR data might affect the results of a meta-analysis. We focused on 19 clinical trials that compared two types of interventions used in peritoneal dialysis for patients with kidney disease: solutions based on icodextrin, a sugar polymer, or on a sugar called glucose. We analyzed several health outcomes such as survival, quality of life, peritoneal ultrafiltration, and complications like infections or kidney function, and serious side effects. First, we analyzed the results using only published articles and information provided by study authors. Then we repeated the analysis, this time adding data from CSRs where available. We compared the number of studies included, the size and direction of treatment effects, and the precision of the results. We found that adding CSRs often provided more complete information, especially for outcomes like serious side effects that were not always reported in journal articles. The overall direction of the results—whether icodextrin was better, worse, or the same—did not change much when CSR data was added. However, the results became more precise in two cases (serious side effects and peritoneal ultrafiltration). In one case, adding CSR data made the benefit of icodextrin statistically significant (peritoneal ultrafiltration). In summary, although adding CSR data did not substantially change the main conclusions, it improved the completeness and accuracy of the results. This shows that using CSRs in research summaries can provide a more reliable basis for making clinical decisions.