Sack 1997.

Study characteristics
Methods	Design: Randomized controlled trial (individually randomized) Trial dates and duration: Dates not given, 21 days follow‐up
Participants	Number of participants: 50 in outpatient study (a smaller inpatient study is also reported but included no outcomes relevant to this review) Inclusion criteria: Age 18 to 50 years, healthy, willing to participate, informed consent Exclusion criteria: chronic illness, immunosuppressive condition, abnormal stool pattern, significant abnormality in screening laboratory hematology and chemistry tests, HIV +ve, hepatitis B surface antigen +ve, pregnancy, travel to a cholera endemic area within 5 years, receipt of cholera vaccine, history of cholera infection or vaccination, previous participation in a cholera or ETEC vaccine trial, use of antibiotics within 7 days of vaccination, food handlers or close contact with children under age 5
Interventions	Vaccine 1: Full dose Peru 15 ‐ a live attenuated strain of V. cholerae 01 El Tor Inaba 2 x 109 CFU plus buffer Vaccine 2: Reduced dose Peru 15 ‐ a live attenuated strain of V. cholerae 01 El Tor Inaba (AVANT Immunotherapeutics Inc, US) 2 x 108 CFU plus buffer Placebo: Buffer only
Outcomes	Included in the review: Adverse events: reported up to 7 days after vaccination (using a self reported symptom diary) Not included in the review: Immunological outcomes: Geometric mean titres of vibriocidal antibody and IgG antitoxin on days 0, 10 and 21, and proportion who developed ≥2 and ≥4‐fold rises from baseline after one dose
Notes	Location: USA Setting: Students or employee volunteers at John Hopkins University and Hospital Source of funding: National Institute Health, Virus Research Institute
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Comment: Described as 'Randomized'. No further details given.
Allocation concealment (selection bias)	Unclear risk	Comment: None described
Blinding (performance bias and detection bias) Efficacy outcomes	Unclear risk	Not applicable as efficacy not reported
Blinding (performance bias and detection bias) Safety outcomes	Low risk	Quote: 'Volunteers were randomized to receive either a 109 or 108 CFU or a placebo in a double‐masked manner', 'To protect the masked code, some volunteers were assigned to 1 or 0.1 mL of placebo'.
Incomplete outcome data (attrition bias) Efficacy outcomes	Unclear risk	Not applicable as efficacy not reported
Incomplete outcome data (attrition bias) Safety outcomes	Low risk	Comment: No losses are described during the adverse event monitoring.
Selective reporting (reporting bias)	Low risk	No evidence of selective reporting
Other bias	Low risk	No evidence of other bias