Table A5:

Risk of BiasAmong Randomized Controlled Trials (Cochrane Risk-of-Bias Tool)

Author, Year	Allocation Concealment	Blinding of Participants and Personnel	Incomplete Outcome Data	Selective Reporting	Other Bias
Greden et al, 201957	Low	Highb	Unclear riskc	Highd,e	Highf
Winner et al, 201365	Lowa	Highg	Low	Low	Highf,v
Perez et al, 201762	Low	Highh	Low	Low/highi	Highf
Han et al, 201860	Low	Highj	Highk	Low	Highf,w,u
Singh et al, 201564	Lowa	Highl	Low	Low	Highf,m
Bradley et al, 201858	Lowa	Highn	Lowo	Highp,q	Highf
Perlis et al, 202061	Lowa	Highn	Low	Low	Highf
Shan et al, 201963	Low	Highr	High risks	Low	Hight

^aAllocation concealment was not described in detail. Assessment based on clear randomization process was described.

^bTreating clinicians were not blinded and were involved in recruitment of patients. Patients and raters were blinded.

^cIn overall cohort, loss to follow-up by 8 weeks was considered high (31% pharmacogenic-guided treatment, 25% for treatment as usual). Reasons for discontinuation were not reported in detail; however, baseline characteristics were similar between groups among those who completed 8-week follow-up. No formal intention-to-treat analysis was performed to account for lost patients.

^dProtocol planned for all outcomes to also be analyzed at 12 weeks but none of these results were reported because of unplanned potential unblinding of clinicians before 12 weeks. Not all secondary outcomes were reported in manuscript (e.g., outcomes based on Clinical Global Impressions Scale).

^ePost-hoc, unplanned analyses conducted on the Greden et al data (Thase et al, 2019⁶⁸; Dunlop et al, 2019⁶⁶; Forester et al, 2020⁶⁷) were assessed at high risk of bias owing to selective reporting.

^fStudy received funding from manufacturer or included authors working for manufacturer.

^gTreating clinicians were not blinded and were involved in recruitment of patients. Patients (exception of 4 patients receiving treatment as usual who did not have test) and raters were blinded.

^hTreating clinicians were not blinded and were the assessors for most outcomes; clinicians were also involved in recruitment of patients. Patients and telephone assessors for Patient Global Impression of Improvement; were blinded.

ⁱSeveral analyses were assessed to be at higher risk of bias based on post-hoc evaluations including response and remission with HAM-D17 scale and analysis of 1–3 failed medications. All other outcomes were assessed as low risk of bias for this domain. Results from Menchon et al were all post-hoc analyses and assessed at high risk of bias.

^jTreating clinician and assessors were not blinded. Only patients were blinded. Clinicians were also involved in recruitment of patients.

^kLoss to follow-up was high and not balanced between groups (25% pharmacogenic-guided treatment, 37.5 treatment as usual) with more losses from adverse events with treatment as usual.

Intention-to-treat analysis with last observation carried forward was performed; however, this might not account for potential risk of bias. Many patients were not included in original publication and subsequently reported in a corrigendum, increasing uncertainty about completeness of outcome data.

^lTreating clinicians were not blinded and were involved in recruitment of patients. Only patients and HAM-D assessors were blinded.

(Notes continued on the next page)

^mHow patients were identified or recruited for study was unclear.

ⁿTreating clinicians were not blinded and were involved in recruitment of patients. Patients and all raters were blinded

^oNumber of dropouts was not substantive, with similar numbers in each group, but no information on reasons for drop out or from which patient population (i.e., depression or anxiety) was supplied.

^pData were presented only for a subset of the population. No data were reported on patients with mild depression, and only remission data were reported for severe depression. Definition of moderate depression varied from methods to results.

^qProtocol on clinicaltrials.gov reported change in HAM-D17 scores as an outcome but was not reported in publication.

^rTreating clinicians and patients were not blinded. Rater for assessment scales was blinded.

^sLoss to follow-up was high (37% for pharmacogenetic-guided testing, 32% for treatment as usual), and reasons for losses were not provided. Authors did do both per-protocol and intention-to-treat analyses; however, this might not address potential risk of bias.

^tA single psychiatrist treated all patients. It is unclear if this psychiatrist was originally treating the patients before enrollment.

^uParticipantss were prohibited from using any combination of other new antidepressant, antipsychotic, mood stabilizer, or central nervous system stimulant and anti-addiction agents throughout study period. Discontinuation criteria were said to be established in protocol, but no details were provided.

^vSignificantly more women were randomized to the treatment as usual arm than to the pharmacogenomic-guided treatment arm.

^wCorrigendum published 2 years after study completion identified substantial errors in original publication related to statistical analyses, inclusion of covariates, and missing patient data. It is unclear if version presented in corrigendum was peer reviewed.