Table 1 Issues that potentially affect external validity adapted to Rothwell (10).

Setting of the trial

Healthcare system

Country

Recruitment from primary, secondary, or tertiary care

Selection of participating centers

Selection of participating clinicians

Selection of patients

Eligibility criteria

Exclusion criteria

Random ratio

Patients declining randomization

Characteristics of randomized patients

Baseline clinical characteristics

Severity of disease

Comorbidity

Differences between trial protocol and routine praxis

Trial intervention

Therapeutic or diagnostic advances since the trial was completed

Outcome measures and follow-up

Who measured outcome

Frequency of follow-up

Adequate length of follow-up

Adverse effects of treatment

Completeness of reporting

Selection of trial centers/clinicians

Intensity of trial safety procedures