Feasibility of using real-world free thyroxine data from the US and Europe to enable fast and efficient transfer of reference intervals from one population to another.

Objectives: The direct approach for determining reference intervals (RIs) is not always practical. This study aimed to generate evidence that a real-world data (RWD) approach could be applied to transfer free thyroxine RIs determined in one population to a second population, presenting an alternative to performing multiple RI determinations. Design and methods: Two datasets (US, n = 10,000; Europe, n = 10,000) were created from existing RWD. Descriptive statistics, density plots and cumulative distributions were produced for each data set and comparisons made. Cumulative probabilities at the lower and upper limits of the RIs were identified using an empirical cumulative distribution function. According to these probabilities, estimated percentiles for each dataset and estimated differences between the two sets of percentiles were obtained by case resampling bootstrapping. The estimated differences were then evaluated against a pre-determined acceptance criterion of ≤7.8% (inter-individual biological variability). The direct approach was used to validate the RWD approach. Results: The RWD approach provided similar descriptive statistics for both populations (mean: US = 16.1 pmol/L, Europe = 16.4 pmol/L; median: US = 15.4 pmol/L, Europe = 15.8 pmol/L). Differences between the estimated percentiles at the upper and lower limits of the RIs fulfilled the pre-determined acceptance criterion and the density plots and cumulative distributions demonstrated population homogeneity. Similar RI distributions were observed using the direct approach. Conclusions: This study provides evidence that a RWD approach can be used to transfer RIs determined in one population to another.

Prevalence of elevated Anti-p53 in Chinese patients with upper gastrointestinal or colorectal cancer.

BACKGROUND: The monitoring of anti-p53 auto-antibodies in the peripheral blood has been used in cancer management; however, their clinical significance alone is limited. This pilot study aimed to describe the prevalence of elevated anti-p53 in newly diagnosed or recurrent upper gastrointestinal cancer or colorectal cancer in Chinese subjects. It also evaluated whether the addition of anti-p53 to a set of established tumor markers would allow for the detection of additional cancer cases than when using these markers alone. METHODS: A total of 573 subjects, including 187 healthy individuals, 169 patients with upper gastrointestinal cancer and 217 patients with colorectal cancer were included in this observational, prospective study. All subjects were required to provide up to 10 mL of blood. The following biomarkers were measured: anti-p53, carcinoembryonic antigen, cancer antigen (CA)19-9, and CA72-4. RESULTS: At the cutoff of 0.02 µg/mL, the sensitivity of anti-p53 in early-stage upper gastrointestinal cancer and colorectal cancer was 8.16% and 26.4%, and in late-stage disease was 7.81 and 28.0%, respectively. The specificity of anti-p53 in the healthy cohort at this cutoff was 98.4%. By adding anti-p53 to other tumor markers, the sensitivities were increased by 8.88%-9.47% in upper gastrointestinal cancer, and by 18.06%-25.00% in colorectal cancer; specificities decreased by 1%-2%. CONCLUSION: The addition of anti-p53 to established tumor markers may improve their diagnostic value for patients with colorectal cancer.