Some pragmatic and intrinsic limitations of randomised controlled clinical trials in rheumatoid arthritis
| Pragmatic limitations |
| Relatively short observation period in most clinical trials in chronic diseases |
| Inclusion and exclusion criteria in clinical trials often restrict eligibility to a small minority of patients who will receive the intervention |
| Inflexible dosage schedules and concomitant drug therapies may limit the apparent efficacy of certain drugs such as methotrexate |
| Surrogate markers used in clinical trials are reversible measures of inflammatory activity, which may be suboptimal indicators of long term irreversible damage and poor outcomes—for example, tender joints may be poor predictors of joint deformity and work disability |
| Statistically significant results are not necessarily clinically important and vice versa |
| Rare adverse events cannot be captured in clinical trials of fewer than 10 000 subjects |
| Intrinsic limitations |
| The design of a clinical trial may greatly influence the results, despite inclusion of a control group |
| Clinical trial reports generally ignore individual variation in responses to treatments |
| Interpretation of results and adverse events is not standardised and may introduce bias into the reporting of the results of any clinical trial |
| The format of a clinical trial may distort the “placebo effect” in either direction by informing patients that they are to receive one of several regimens rather than the “best” therapy |