Individual studies were rated as “good,” “fair” or “poor”:

For Controlled Trials:

Each criterion was give an assessment of yes, no, or unclear.

1. Was the assignment to the treatment groups really random?
   • Adequate approaches to sequence generation:
     • Computer-generated random numbers
     • Random numbers tables
   • Inferior approaches to sequence generation:
     • Use of alternation, case record numbers, birth dates or week days
   • Randomization reported, but method not stated
   • Not clear or not reported
   • Not randomized
2. Was the treatment allocation concealed?
   • Adequate approaches to concealment of randomization:
     • Centralized or pharmacy-controlled randomization (randomization performed without knowledge of patient characteristics).
     • Serially-numbered identical containers
     • On-site computer based system with a randomization sequence that is not readable until allocation
     • Sealed opaque envelopes
   • Inferior approaches to concealment of randomization:
     • Use of alternation, case record numbers, birth dates or week days
     • Open random numbers lists
     • Serially numbered non- opaque envelopes
     • Not clear or not reported
3. Were the groups similar at baseline in terms of prognostic factors?
4. Were the eligibility criteria specified?
5. Were outcome assessors and/or data analysts blinded to the treatment allocation?
6. Was the care provider blinded?
7. Was the patient kept unaware of the treatment received?
8. Did the article include an intention-to-treat analysis, or provide the data needed to calculate it (i.e., number assigned to each group, number of subjects who finished in each group, and their results)?
9. Did the study maintain comparable groups?
10. Did the article report attrition, crossovers, adherence, and contamination?
11. Is there important differential loss to followup or overall high loss to followup?

For Cohort Studies:

Each criterion was give an assessment of yes, no, or unclear.

1. Did the study attempt to enroll all (or a random sample of) patients meeting inclusion criteria, or a random sample (inception cohort)?
2. Were the groups comparable at baseline on key prognostic factors (e.g., by restriction or matching)?
3. Did the study use accurate methods for ascertaining exposures, potential confounders, and outcomes?
4. Were outcome assessors and/or data analysts blinded to treatment?
5. Did the article report attrition?
6. Did the study perform appropriate statistical analyses on potential confounders?
7. Is there important differential loss to followup or overall high loss to followup?
8. Were outcomes pre-specified and defined, and ascertained using accurate methods?