Table 1.

Why can clinical trials of truly efficacious treatments fail to show their efficacy?

1. Chance

2. Placebo group patients improved “too much”

3. The optimal patients and phenotypes were not studied

4. Existing outcome measures have limited responsiveness to treatment effects

5. Temporal changes in characteristics of patients enrolling in trials

6. Temporal changes in types of clinical sites conducting trials

7. Research subject misbehaviour

8. Research site unintentional bias and misconduct

9. Inadequate sample sizes