Zöllner 2008.

Methods	Trial Design: multicentre randomised, parallel group trial Location: 10 countries Number of centres: 19 Recruitment period: not stated Funding source: sponsor
Participants	Inclusion criteria: patients missing teeth in premolar and molar areas allowing the placement of 8 mm long and 4.1 mm large single implant Exclusion criteria: post‐extractive implants (at least 4 months healing was required), lack of primary implant stability, opposing fixed dentition, smoking > 10 cigarettes per day, severe bruxism/clenching, and any systemic diseases likely to compromise implant surgery Age at baseline: 46.3 ± 12.8 years Gender: not stated Number randomised: 266 Number evaluated: unclear. Possibly 5 withdrawals from the immediately loaded group (3 subjects withdrew consent and 2 could not be located) and 1 from the early loaded group (withdrew consent) at 5 months (it is unclear whether patients were lost prior to or after implant placement) and unknown number of withdrawals at 1 year
Interventions	Comparison: Immediate versus early loading Gp A (n = 138) Immediate loading: temporary acrylic restoration out of occlusal contact, placed on the day of surgery, with permanent occluding restoration (either single crown or 2‐4 unit fixed prosthesis cemented or screw‐retained restorations made of porcelain, acrylic resin or gold) placed 20‐23 weeks after surgery Gp B (n = 128) Early loading: temporary acrylic restoration out of occlusal contact, placed 28‐34 days after surgery, with permanent occluding restoration (either single crown or 2‐4 unit fixed prosthesis cemented or screw‐retained restorations made of porcelain, acrylic resin or gold) placed 20‐23 weeks after surgery ITI® SLA active (Institut Straumann AG, Waldenburg, Switzerland) solid sand‐blasted large‐grit acid‐etched titanium grade 4 screws, 3 standard plus implants were also used Duration of follow‐up: 1 year (interim analysis)
Outcomes	Prosthesis/implant failures, marginal bone level changes on standardised intraoral radiographs 1‐year data used
Notes	Sample size calculation: reported that 35 patients per group would be required to detect a difference of 0.3 mm in bone loss
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Reported in the first article: "This is an ongoing prospective randomized study in which patients receive between one and four implants in the posterior maxilla or mandible.... Patients were randomized into immediate or early loading arms" Reported in the second article: "The randomization list was generated for each center by an independent statistician using block sizes of 10; randomization numbers were sequential, and each group (immediate or early) had an equal number in each block" Author replied that: "Patients were randomized into two loading arms according to a master randomization list to receive a temporary restoration (single crown or 2‐4 unit fixed partial denture) out of occlusal contact. A randomization list defined which patient is treated within the immediate or early loading arms. The randomization list was generated by an independent statistician for each of the 19 centers using 2 block sizes of 10 for each center, with each center having its own unique center number and sequential randomization number, and an equal number (i.e. 5 each) within each block randomized to either group immediate or early"
Allocation concealment (selection bias)	High risk	Nothing reported in the first article Reported in the second article: "The sequential randomization was placed in sealed envelopes for each center, which were opened before surgery after obtaining signed informed consent from the patient" Author replied that: "The sequential randomization for each center was placed in a sealed envelope, which the investigator was allowed to open at least one to 5 days prior to the planned surgery and only after signed informed consent from the patient had been obtained. Patients were consecutively enrolled into the study and had the sealed treatment code envelope that corresponded to their time of entry, patient 1 received envelope 1, the 2nd patient received envelope 2 and so on for each center. Master copies of the randomization lists were held by the sponsor and the organization who performed the randomization" Comment: as the group allocation was known prior to surgery we have assessed this as high risk bias.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Nothing reported in the article Author replied that: "The analysis of bone level change was performed by an independent expert who was blinded to the allocation of the treatment group. Secondary objective were to evaluate the effectiveness in terms of implant survival, implant success and patient satisfaction at month 5. Secondary parameters were assessed by each clinician. They were not blinded in respect of treatment groups"
Incomplete outcome data (attrition bias) All outcomes	High risk	Possibly 5 withdrawals from the immediately loaded group (3 subjects withdrew consent and 2 could not be located) and 1 from the early loaded group (withdrew consent) at 5 months (it is unclear whether patients were lost prior to or after implant placement) and unknown number of withdrawals at 1 year
Selective reporting (reporting bias)	Low risk	All outcomes appear to be presented
Other bias	Low risk	None detected