As part of its single technology appraisal (STA) process, the National Institute 
for Health and Care Excellence (NICE) invited the manufacturer (Bristol-Myers 
Squibb) of nivolumab (Opdivo®) to submit evidence of its clinical and cost 
effectiveness for metastatic or unresectable urothelial cancer. Kleijnen 
Systematic Reviews Ltd, in collaboration with Maastricht University Medical 
Centre+, was commissioned to act as the independent Evidence Review Group (ERG), 
which produced a detailed review of the evidence for the clinical and cost 
effectiveness of the technology, based on the company's submission to NICE. 
Nivolumab was compared with docetaxel, paclitaxel, best supportive care and 
retreatment with platinum-based chemotherapy (cisplatin plus gemcitabine, but 
only for patients whose disease has had an adequate response in first-line 
treatment). Two ongoing, phase I/II, single-arm studies for nivolumab were 
identified, but no studies directly compared nivolumab with any specified 
comparator. Evidence from directly examining the single arms of the trial data 
indicated little difference between the outcomes measured from the nivolumab and 
comparator studies. A simulated treatment comparison (STC) analysis was used in 
an attempt to reduce the bias induced by naïve comparison, but there was no 
clear evidence that risk of bias was reduced. Multiple limitations in the STC 
were identified and remained. The effect of an analysis based on different 
combinations of covariates in the prediction model remains unknown. The ERG's 
concerns regarding the economic analysis included the use of a non-established 
response-based survival analysis method, which introduced additional 
uncertainty. The use of time-dependent hazard ratios produced overfitting and 
was not represented in the probabilistic sensitivity analysis. The use of a 
treatment stopping rule to cap treatment cost left treatment effectiveness 
unaltered. A relevant comparator was excluded from the base-case analysis. The 
revised ERG deterministic base-case incremental cost-effectiveness ratios based 
on the company's Appraisal Consultation Document response were £58,791, £78,869 
and £62,352 per quality-adjusted life-year gained versus paclitaxel, docetaxel 
and best supportive care, respectively. Nivolumab was dominated by cisplatin 
plus gemcitabine in the ERG base case. Substantial uncertainties about the 
relative treatment effectiveness comparing nivolumab against all comparators 
remained. NICE did not recommend nivolumab, within its marketing authorisation, 
as an option for treating locally advanced, unresectable or metastatic 
urothelial carcinoma in adults who have had platinum-containing therapy, and 
considered that nivolumab was not suitable for use within the Cancer Drugs Fund.