Table 1 Some limitations of randomized controlled trials

Patient selection limited by inclusion and exclusion criteria

Short time frame, as long-term clinical trials are ethically or logistically not possible

Differential drop-out patterns between arms of the trial

Statistically significant results might not necessarily be clinically significant, and vice versa

Surrogate markers such as joint tenderness might be suboptimal indicators of prevention of severe long-term outcomes such as radiographic destruction and work disability

Chance (bad luck) can lead to unbalanced groups

Inflexible dosage schedules

'Dose creep' from trial to clinic, rendering trial obsolete

Inability to identify rare adverse events

Hawthorne effect: patients in a study alter their behavior when they are told to be in the study

Design bias: randomized controlled trials might be designed to maximize the probability of a particular outcome, namely the superiority of the new drug