Table 4 Methodological considerations relevant to determination of the molecular profile of tumors.
From: Mucoepidermoid carcinoma (MEC) and adenosquamous carcinoma (ASC), the same or different entities?
A. Application of an adequate study design | |||
Study design | Outcome measures | Pros | Cons |
Diagnostic randomized controlled trials: adequately controlled with hypotheses stated in advance and evaluated according to a standardized protocol | Sensitivity, specificity, likelihood ratios, accuracy | Properly conducted, randomized controlled trials are the gold standard to determine accuracy, safety and effectiveness of diagnostic tests. Permit analysis by “intention-to-test” and control of biases, such as context and clinical review bias | Needs more resources, sample size is relevant, and interdisciplinary teamwork required. |
Diagnostic cohort studies: allow assessment of the characteristics of a diagnostic test, with control group | Sensitivity and specificity, PPV and NPV, likelihood ratios, diagnostic odd ratios and accuracy can be calculated | Relatively inexpensive, simple to perform, well accepted among the medical research community. | Not directly tied to patient outcomes, risk of bias inherent to study design and difficult to control for confounders and interactions. |
Prospective case series: large, consecutive selected, prospective case series | Inexpensive, simple to perform, well accepted among clinical community. | Allows only weak inferences and high likelihood of bias associated. | |
B. Potential confounders to take into account during the statistical analysis | |||
Related to | To be taken into account for adjustment | ||
Determination of the molecular alteration: laboratory methods and technics | Heterogeneity in techniques, different cut offs, variation in measurements, not comparable values provided, geographical differences in determination methods, fast advancing technology with differences over time in determinations | ||
Study population: method of ample selection and sample size | Potential study participants with confounders known to influence experimental test accuracy excluded from study | ||
Test performance: indeterminate tests/Not performed test | Performance of a diagnostic test may vary in different settings (each setting, different mix of patients) | ||
C. Main biases to avoid | |||
Type of bias | Step in research in which bias control can be applied | ||
Selection bias | Study design | ||
Reporting bias | Analysis and dissemination | ||
Context bias: | Study design | ||
Clinical review bias: | Study design | ||
