Plapler 2016.

Methods	RCT; double‐blind, randomised, double‐dummy clinical trial (non‐inferiority) Computer‐generated randomisation Follow‐up time: 10 days (maximum treatment duration 5 days). Outcome measurements at baseline, 60 minutes, 2 days, 4 days, 10 days
Participants	Population: 83 participants, 216 women, 155 men. Mean age (SD): 36 (10.59) years Setting: outpatient clinics of 2 research centres in Brazil Inclusion criteria: diagnosed with moderate or severe acute LBP (VAS > 40 mm), aged 18 to 65 years, able to give written informed consent; women of childbearing age had to agree to use contraceptive methods throughout the study Exclusion criteria: weight < 50 kg; severe congestive heart failure; current alcoholism or illegal drug use; presence of fever or signs of infection; kidney disease; fracture; fibromyalgia; cancer; neuropsychiatric disease; rheumatologic disease; history of peptic ulcer disease; gastrointestinal bleeding or hemorrhagic diathesis; cerebrovascular disease; haemostatic disorders or use of anticoagulants; pregnancy; lactation; postoperative people at high risk of bleeding; history of hypersensitivity to NSAIDs; nasal polyps and asthma. No participation in another experimental study 6 months prior to study entry.
Interventions	NSAID (i): ketorolac‐trometamol sublingual 10 mg t.i.d.; 5 days (N = 66) NSAID (ii): naproxen oral 250 mg, t.i.d.; 5 days (N = 67) From 2nd to 5th day, if participant had VAS > 40 mm, an increased dose of four times per day was allowed.
Outcomes	VAS‐scores are not mentioned separately, only combined scores are mentioned and focus on pain relief by comparing VAS scores 1 hour before and after medication. Relevant outcomes (VAS‐scores) at day 4 are not mentioned. No significant differences mentioned. Adverse events: (i) 42 adverse events (1 withdrew); (ii) 35 adverse events (0 withdrew)
Funding	EMS Sigma Pharma is a domestic pharmaceutical company in Brazil. This study was funded by EMS and they were involved in study design, protocol development, obtaining the data, and evaluating the data together with the authors. The manuscript was written by the authors, together with EMS medical writing services. All authors received grants and consulting fees from EMS Industry.
Notes	83 people were screened, none of them were excluded, despite the strict exclusion criteria.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated lottery, randomly assigned.,
Allocation concealment (selection bias)	Unclear risk	Each participant received a numbered kit in order of arrival. The trial design says double‐dummy and double‐blind assignments; but NSAID (i) was administered sublingually and NSAID (ii) was administered orally, therefore, this seems not possible. It was not mentioned if both tested and reference medication looked identical.
Blinding of participants and personnel (performance bias) All outcomes ‐ participants	Unclear risk	It was written that both medical staff and participants were blinded to treatment assignments; but different way of administering the medication and no details were mentioned.
Blinding of participants and personnel (performance bias) All outcomes ‐ careproviders	Unclear risk	It was written that both medical staff and participants were blinded to treatment assignments; but different way of administering the medication and no details were mentioned.
Blinding of outcome assessment (detection bias) All outcomes ‐ outcome assessors	Unclear risk	Not mentioned
Incomplete outcome data (attrition bias) All outcomes ‐ dropouts	High risk	High dropout rate: 24% (20/83 lost to follow‐up/withdrew)
Incomplete outcome data (attrition bias) All outcomes ‐ ITT analysis	High risk	ITT analysis performed for adverse events only; PP analysis for effect
Selective reporting (reporting bias)	Unclear risk	Trial was registered at local ethical committee. (inter)national trial registry not mentioned. Not mentioned if pain outcome measure (RPR) was registered like this.
Similarity at baseline characteristics	Low risk	Baseline characteristics similar, except for weight
Co‐interventions avoided or similar	Unclear risk	Not mentioned
Compliance acceptable	Unclear risk	Not mentioned
Timing outcome assessments similar	Low risk	Timing similar
Other bias	Low risk	None