OVA‐301 2010.

Methods	Phase III multicentre RCT (21 countries); recruited from April 2005 to May 2007. Participants were followed up every 8 weeks.
Participants	672 women with PR ROC (PFI < 6 months) and women with PS ROC (PFI ≥ 6 months), excluding platinum refractory patients. Planned enrolment was 650 women. Included if measurable disease was present (defined by RECIST); only 1 prior platinum‐based regimen received; ECOG PS 0,1 or 2; PFI based on radiological evaluation; no other major medical conditions.
Interventions	Arm 1: Dexamethasone (IVI 20 mg) + PLD (30 mg/m²) IVI for 90 min +TBD (1.1 mg/m²) IVI for 3‐hours, every 21 days Arm 2: PLD (50 mg/m²) IVI for 90 min every 28 days
Outcomes	Primary: PFS Secondary: OS, ORR, duration of response, SAE (NCI‐CTCAE v3.0) Tertiary: QoL
Notes	Growth factor was necessary in 42% arm 1 versus 17% arm 2 to treat neutropenia (precise figures were not given). There were more withdrawals in the TBD arm than the PLD alone arm due to patient choice or adverse events (126 versus 89 participants). Dexamethasone was given to the TBD group only to reduce hepatic toxicity (personal communication). When results were subgrouped by platinum sensitivity, only women in the PS ROC group experienced significantly longer PFS with arm 1; i.e. TBD + PLD offered no significant additional benefit over PLD alone for women with PR ROC. Similarly for OS, only the PPS ROC subgroup of arm 1 had a statistically significantly longer OS than the arm 2 subgroup (HR 0.59; 95% CI 0.42 to 0.82; P value 0.0015).
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Central block randomisation (1:1) with stratification by platinum sensitivity and ECOG PS.
Allocation concealment (selection bias)	Unclear risk	Not described.
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open‐label.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Independent radiological assessment and oncologist review.
Incomplete outcome data (attrition bias) All outcomes	Low risk	All expected outcomes were reported, although missing data was >20% for QoL outcomes.
Selective reporting (reporting bias)	Unclear risk	The reduced rate of PLD toxicity reported in the TBD + PLD arm could have been due to the premedication drug dexamethasone (and not TBD) that was given to the experimental group, or due to the lower dose of PLD used. This was not mentioned in any of the trial publications.
Other bias	Unclear risk	Women in arm 2 had a significantly longer PFI than arm 1 (P value 0.009) which may have biased the survival data in the direction of PLD alone. When the investigators adjusted OS results for the PFI and other prognostic factors in ad hoc exploratory analyses, the adjusted OS produced a statistically significant result in favour of arm 1 (HR = 0.82; 95% CI 0.69 to 0.98; P value 0.0285).