Methods	Prospective randomised comparison of 3 drug regimens.
Participants	169 women with singleton pregnancies in first trimester presenting to their obstetrical provider with nausea and/or vomiting
Interventions	3 “commonly prescribed pharmaceutical regimens in the outpatient management of nausea and vomiting in pregnancy”, to “mirror local practices” Group A: 50 mg intramuscular injection of pyridoxine, with metoclopramide 10 mg orally every 6 hours as needed Group B: prochlorperazine as needed 25 mg rectal suppositories every 12 hours or 10 mg tablets orally every 6 hours as needed Group C: promethazine 25 mg orally every 6 hours as needed.
Outcomes	Change in symptoms: scores 1-5 on a scale which comprised: much worse, worse, same, better, much better; recorded by participants on third day of treatment. Responses then divided into 2 subgroups:-those who answered 1-3 (same-worse) and those who answered 4-5 (better) Women also recorded the number of emesis episodes the day before and on the third day of treatment; dry heaves (retching) were counted as nausea, but not vomiting episodes Worsening of symptoms was evaluated and patient admission for hydration or inpatient management was considered on an individual basis Hospitalisation for the specific management of nausea or vomiting was noted Patients also recorded their “medication compliance”.
Notes
Risk of bias
Item	Authors’ judgement	Description
Adequate sequence generation?	Yes	Patients were divided into 3 groups based on a computer-generated randomisation
Allocation concealment?	Unclear	Not described.
Blinding? Change in grade of nausea or vomiting at second visit compared to first	No	Not blinded. The authors raise the possibility of the “placebo effect” of the intramuscular route. The authors conclude that it would have been ideal to randomise the patients in a double blind fashion and possibly to establish a placebo group
Incomplete outcome data addressed? Change in grade of nausea or vomiting at second visit compared to first	Yes	12 patients lost to follow up (3, 5 and 4 from groups A, B and C respectively). 1 patient from Group A withdrew from the study with side effects (acute dystonic reactions, thought to be secondary to metoclopramide)
Free of selective reporting?	No	Results for “subjective response” presented only in graphical format; not usable Emesis frequency only reported. States that “drug usage and compliance was comparable between all three groups”, but no description of amount of each drug used (most were on an “as required” basis)
Free of other bias?	No	2 drugs were given to Group A; this treatment was found to be most effective; it is not possible to identify whether 1 or both agents were effective. The authors note that combining 2 agents that may also both work independently may raise questions of fairness - this was done to mirror local practices Unclear who and where drugs were administered (e.g. IM injections on an “as required” basis). Study was done in out-patient setting