Citation	Groups Studied and Intervention	Results and Findings	Conclusions
[@64073]	Literature search performed on PubMed, ClinicalTrials.gov, Cochrane library, and FDA website produced 6 clinical trials included in the study. The quality of the clinical trials was assessed using the Cochrane Collaboration risk-of-bias tool. Meta-analysis was performed, and the primary endpoint was the calculated standard mean difference (SMD). Other endpoints were the calculated weighted mean difference (WMD), risk ratio (RR) and number needed to treat (NNT), and number needed to harm (NNH) as applicable.	Five of the six studies had a low risk of bias, and one had an unclear risk of bias due to a lack of methodological information. Results confirmed efficacy of valbenazine for TD with SMD =-0.58, WMD = -2.07, RR = 3.05, NNT = 5. No increased risk of AEs over placebo was noted in the meta-analysis of safety data from the pooled trials.	Valbenazine is more effective than placebo at treating TD, and has no increased risk of AEs.
[@64076]	A review and synthesis of all available clinical data from PubMed, US ClinicalTrials.gov, and EMBASE, as well as slides requested from the manufacturers (Neurocrine Biosciences) and the product prescribing information label. NNT and NNH comparing valbenazine and placebo were calculated as applicable.	From the pooled subject data, this review found that the NNT for valbenazine vs. placebo was 5, the NNH for all pooled TEAEs was 76, and the likelihood to be helped or harmed (LHH) was (NNH/ NNT or 76/5) 15.2. Additionally, no clinically significant cardiac AEs or changes to EKG were noted in the pooled subject data.	Valbenazine is significantly more efficacious than placebo in the treatment of tardive dyskinesia and is well-tolerated across pooled data from several clinical trials.
[@64072]	Data from the KINECT, KINECT 2, and KINECT 3 6-week trials, as well as the 42 week extension period of the KINECT 3 trial, were pooled (400 subjects total) and the incidence of cardiac TEAEs analyzed by aggregating the MedDRA terms cardiac failure, chest pain, ECG QT prolonged, myocardial infarction, sudden death, syncope, and torsades de pointes/QT prolongation from all studies. Additionally, the incidence of orthostatic hypotension and hypotension TEAEs were aggregated using the terms blood pressure decreased, dizziness, dizziness postural, fall, hypotension, orthostatic hypotension, orthostatic intolerance, presyncope, and syncope.	11.8% of subjects had an existing cardiac disorder before being enrolled in one of the studies, and 74.3% of the pooled study populations took a concomitant medication known to prolong QTc. No statistically significant difference between the incidence of cardiac TEAEs was found between the groups receiving valbenazine and placebo. At week 6, there was no statistically significant difference in QTc prolongation between either active drug arm and placebo in any of the studies.	There is a minimal increased risk of cardiac TEAEs due to treatment with valbenazine. It is unlikely to prolong QTc, even in patients taking concomitant medications known to prolong QTc.
[@64068]	Two studies of healthy adult male volunteers (56 pooled subjects) not taking any other medications were analyzed to determine the safety, tolerability, and pharmacokinetics (PK) of valbenazine. PK parameters were analyzed using liquid chromatography to determine plasma concentrations, and standard noncompartmental methods and WinNonlin Professional v 5.2 were used to calculate the parameters.	There were no cardiac TEAEs, or QTc prolongation were noted in either study. The most common TEAEs were fatigue, headache, insomnia, and disturbance in attention. PK parameters were stable, predictable, and provide low peak-to-trough variability on a once-daily dosing regimen. A steady state was achieved in 8 days.	Valbenazine is generally well tolerated and has predictable PK parameters that allow for easy once-daily dosing.