Electronic health records (EHRs) are receiving growing attention as a potential source of real-world data. However, their suitability for evaluating the effectiveness of treatments for diseases with complex activity measures is unclear. A recent study sought to evaluate the use of EHR data for estimating treatment effectiveness in inflammatory bowel disease (IBD), using the drug tofacitinib as a use case.
Real-world evidence and IBD treatment effectiveness
Real-world evidence (RWE) refers to the use of observational data to support the effectiveness of different treatments on diseases. EHRs are receiving particular attention as a source of real-world data. However, EHR data has its limitations, including the data being commonly captured in free text rather than a tabular format. This creates a challenge for the study of diseases whose assessments may be captured in narratives. Such data typically requires the use of text processing, which can achieve high accuracy, but is a laborious process. However, the utility of these data approaches remains unclear because the availability of the data in free text is understudied.
A disease that is currently being assessed by complex measures is inflammatory bowel disease (IBD). IBD is comprised of two subtypes: ulcerative colitis (UC) and Chron’s disease (CD). Immunosuppressants are used to treat IBD until treatment failure due to adverse events or inadequate efficacy, hence why research is underway to find and develop new therapies. In trials, treatment effectiveness is assessed according to the Mayo Score and the Chron’s Disease Activity Index (CDAI).
Assessing tofacitinib treatment effectiveness
Tofacitinib is the first small molecule that has been approved to treat IBD. In clinical trials, tofacitinib was able to induce remission in 18.5% of the 476 UC patients who were treated for 8 weeks. Moreover, remission was maintained in 34.3% of the 197 induction responders assigned to 52 weeks of continued treatment. The effectiveness of tofacitinib on CD patients was also assessed in a phase 2b randomised controlled trial. The results showed that 43% of the 86 patients randomised to the 10 mg arm achieved clinical remission following induction. However, unlike for UC, tofacitinib did not show statistical superiority when compared with the placebo for CD.
In this study, the researchers assessed the utility of EHR to evaluate IBD treatment effectiveness. They used cohort of patients being treated with the approved IBD drug – tofacitinib – as a use case . The team’s primary objective was to assess disease activity data at timepoints that roughly corresponded to the clinical trial endpoints. Meanwhile, their exploratory objective was to estimate tofacitinib effectiveness using EHR data and compare it with the clinical trial data.
Using RWE to assess IBD treatment effectiveness
The researchers queried records from the University of California, San Francisco to identify tofacitinib-treated IBD patients. In total, 86 patients were identified as initiating tofacitinib treatment. Baseline characteristics in the real-world and trial cohorts were similar, except for universal failure of tumour necrosis factor inhibitors in the real-world cohort. Overall, 54% of UC and 62% of CD patients had complete capture of disease activity at baseline, while only 32% of UC and 69% of CD patients had complete follow up data in EHRs. Therefore, the researchers developed an approach for estimating real-world treatment effects, where there is missing data. Their approach used data abstraction protocols and methods for stochastic imputation. This enabled the researchers to estimate the proportion of patients achieving the trial primary endpoints as being similar to the published estimates for both UC (16%) and CD (38%).
Although EHR data contains much of the data needed to assess treatment effectiveness, the researchers found the data to be less accessible and associated with significant missing values at baseline and follow-up. The researchers proposed a method for estimating the real-world treatment effects from the data using abstraction protocols and methods for stochastic imputation of missing data. In this study they assessed the treatment effectiveness of tofacitinib for IBD, but their methods to abstract missing data values can be applied to other real-world studies to assess the effectiveness of treatments in the real-world setting, where not all data is available.
Image credit: Zhanna Hapanovich – Canva